OBJECTIVE To optimize the extraction technology of the ancient formula Shangdangshen Ointment （SO）， and to evaluate its effect on mouse immune function. METHODS Independent variables included extraction frequency， the amount of water added， and extraction time， and evaluation parameters included the content of lobetyolin， and the comprehensive score of the ointment yield. The weight coefficient of each evaluation index was determined by the composite entropy weight of analytic hierarchy process （AHP）-index weight determination method （CRITIC）. Box-Behnken response surface method was to identify the optimal extraction technology of SO. An immunosuppressive mouse model was established by intraperitoneal injection of cyclophosphamide， followed by oral gavage of Lentinan and SO for 30 days. The body weight， organ index of immune organs， and serum immune factors （interleukin IL-2， IL-4） were detected， and the intestinal pathology of mice was observed by hematoxylin and eosin （H&E） staining. RESULTS The optimal extraction process for SO was three extractions （1 h， 0.5 h and 0.5 h， respectively） by adding 10-fold， 8-fold and 6-fold， respectively. Compared with the blank group， mouse in the model group had significantly decreased body weight and thymus index， increased spleen index and serum immune factors （all P<0.01）， and seriously damaged structure of small intestine. Model mice treated with SO had significantly increased body weight and thymus index （P<0.01）， and decreased spleen index and serum immune factors （P<0.05）. The impaired structure of small intestinal tissue was significantly alleviated. CONCLUSION Based on the Box-Behnken response surface methodology， the optimized extraction process of SO has the advantages of strong operability， high extraction rate， energy saving and good reproducibility. SO can significantly improve the immune function of immunocompromised mice induced by cyclophosphamide.

OBJECTIVE To investigate the extraction effect of total flavonoids from Epimedium brevicornu （E.brevicornu） by using ultrasonic-assisted deep eutectic solvents （DESs）， and to optimize the extraction parameters. METHODS Using the yield of total flavonoids of E.brevicornu as an indicator， ten DESs were prepared for extracting total flavonoids of E.brevicornu， and that with the highest yield was identified. Then， the response surface methodology was employed to optimize the extraction process based on the univariate experiments ［extraction temperature （℃）， liquid-solid ratio （mL·g^–1） and ultrasonic time （min）］， and obtain the optimal process parameters. Meanwhile， the optimal extraction process was validated by in-vitro hypoglycemic activity evaluation. RESULT 1，3-propanediol/choline chloride （molar ratio 2∶1） containing 40 wt% water was chosen as the optimal extraction solvent， and the optimum extraction parameters were as follow： ultrasonic time （27 min）， liquid-solid ratio （44 mL·g^–1） and extraction temperature （72 ℃）. Under the above extraction condition， the yield of total flavonoids was 8.26%. Total flavonoids showed an IC₅₀ of 0.31 mg·mL^–1 on the hypoglycemic activity， which was superior to the alcohol extraction method. CONCLUSION 1，3-propanediol/choline chloride is a good solvent for extracting total flavonoids from E.brevicornu， which can effectively improve the yield of total flavonoids， and provide the scientific evidence for the resource development and utilization of E.brevicornu.

OBJECTIVE To investigate the mechanism of Danggui Buxue Decoction combined with Ginseng in improving renal interstitial fibrosis （RIF） in rats with unilateral ureteral obstruction （UUO） by regulating the Notch signaling pathway. METHODS A total of 56 Wistar rats in the specific pathogen free （SPF） level were randomly divided into sham operation （Sham） group， UUO group， losartan potassium （RX） group， Danggui Buxue Decoction （DBD） group （3.75 g·kg^–1， 7.5 g·kg^–1）， and Danggui Buxue Decoction combined with Ginseng （GDBD） group （4.4 g·kg^–1， 8.8 g·kg^–1）. Rats in the Sham group were stripped of the ureter without ligation， and those in the remaining groups were subjected to unilateral ureteral ligation to construct a RIF model in rats with UUO. Serum blood urea nitrogen （BUN） and creatinine （Cr） were detected by biochemical analyzer. Serum TGF-β1， TNF-α and α-SMA in rats were detected by Enzyme-linked immunosorbent assay （ELISA）. H&E and Masson’s trichrome staining were used to observe the pathological changes and collagen fiber deposition of the kidney tissue. polymerase chain reaction（PCR） and Western blot were applied to detect the mRNA and protein levels of Notch1， JAG1 and HES1 in rat kidney tissue， respectively. RESULTS Compared with Sham group， rats in the UUO group had abnormal renal function， increased serum levels of kidney injury and fibrosis markers （TGF-β1， TNF-α， α-SMA）， and upregulated mRNA and protein levels of Notch1， JAG1 and HES1. Compared with the UUO group， opposite changing trends were observed in rats with drug administration. There were significant differences in the levels of BUN， Cr， α-SMA， Notch1， JAG1 and HES1 between DBD and GDBD groups. CONCLUSION Ginseng has a synergistic effect on DBD in delaying RIF. GDBD plays an important role in delaying RIF in UUO rats by downregulating TGF-β1 and regulating the Notch signaling pathway.

OBJECTIVE To evaluate accurately the quality of Suanzaoren Decoction （SZRD） based on the ultra-high-performance liquid chromatography （UPLC） fingerprint， network pharmacology and quantitative analysis. METHODS Firstly， the fingerprint of SZRD was established， and similarity evaluation and common peak identification were carried out through the analysis of the 10 batches of SZRD. Then， the pharmacodynamic components of SZRD were predicted by network pharmacology and verified by molecular interconnection. Finally， the content determination method of SZRD was established based on the obtained pharmacodynamic substances to evaluate the quality of SZRD. RESULTS A total of 32 common peaks were obtained through the UPLC fingerprint analysis and 22 chemical constituents were successfully identified. A network of “herbs-active components-targets-disease” was conducted through network pharmacology. Based on the measurability of components and availability of reference substances， the 11 compounds with higher contribution were finally selected as the pharmacodynamic substances for content determination. Molecular docking proved that the 11 compounds had good binding ability with the targets. The methodological validation showed that the 11 compounds exhibited a good linear relationship within the assay range （r²>0.9940）， and their precision， accuracy and stability were good. CONCLUSION The combination approach of UPLC fingerprint， network pharmacology and quantitative analysis is simple， rapid， accurate and reliable for screening pharmacodynamic substances and quality evaluation of SZRD. It also provides ideas for the screening of the active ingredients and quality evaluation of traditional Chinese medicine herbals.

OBJECTIVE To analyze the clinical utilization and changing trends of three commonly used anti-vascular endothelial growth factor （VEGF） drugs in the ophthalmology department before and after the implementation of the “National Medical Insurance Negotiation” policy at Zhengzhou Second Hospital， and to provide valuable insights for policy formulation. METHODS The prices of three commonly used anti-VEGF drugs in the ophthalmology department， including ranibizumab injection， conbercept eye injection， and aflibercept intraocular injection solution， were collected from medical insurance catalog at different years. Descriptive statistical analysis was conducted to examine the price， sales volume， defined daily doses（DDDs）， and defined daily dose cost （defined daily dose cost，DDDc） of the three drugs from 2013 to 2023. RESULTS Following several rounds of the “National Medical Insurance Negotiation” policy， the prices of ranibizumab injection， conbercept eye injection， and aflibercept intraocular injection solution decreased by ¥6 126.5， ¥3 347.2， and ¥1 750 respectively. The three drugs showed a reduction rate of 62.52%， 49.22%， and 29.91%， respectively. Since 2021， conbercept eye injection had the lowest price. Overall usage and sales volume showed significant increases， while DDDc decreased significantly. In particular， the domestic innovative drug conbercept eye injection had significantly higher usage rates and DDDs values in 2020， 2021， and 2023 compared to the other drugs. It has been increasingly used in clinical setting. CONCLUSION The implementation of the “National Medical Insurance Negotiation” policy has reduced the prices of expensive drugs， increased accessibility for patients， alleviated financial burdens on patients， and saved medical insurance funds significantly. The continuous optimization of the “National Medical Insurance Negotiation” policy coupled with ongoing research and development efforts for novel medications and approval of generic drugs for marketing， will have effectively lowered the price of anti-VEGF drugs. The recognition of domestic innovative drugs by doctors and patients is also increasing.

OBJECTIVE To establish a high-performance liquid chromatography （HPLC） method for the determination of Fe（Ⅱ） in ferric maltol capsules， and to verify the method. METHODS The separation was performed on the Ultimate^® LP-C8 column （4.6 mm×250 mm， 5 μm）， and elution was performed with pH 7.0 TRIS-Ferrozine buffer. Acetonitrile： tetrahydrofuran （98.8∶1.0∶0.2）-acetonitrile （80∶20） was used as the mobile phase. The injection volume was 5 μL. The detection wavelength was 561 nm. The column temperature was 30 ℃. The flow rate was 1 mL·min^–1. RESULTS The accuracy and precision met the requirements. The limits of detection and quantification were 0.045 μg·mL^–1 and 0.075 μg·mL^–1， respectively. The linear relationship was good with the range of 0.075-2.55 μg·mL^–1. The results of durability and solution stability （stable within 18.5 h） also met the requirements. CONCLUSION We for the first time suggested that the content of Fe（Ⅱ） in ferric maltol capsules is directly determined by HPLC. The method has high accuracy， precision and sensitivity， and can be used for process development and quality control of iron issue.

OBJECTIVE To explore the pharmacological mechanism of Xiaoban Quzhi Prescription in relieving obesity. METHODS The active ingredients of Xiaoban Quzhi Prescription were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and literature review. Their targets were obtained from the TCMSP and SwissTarget Prediction platform， and annotated in the Uniprot database. Disease targets of obesity were obtained from the Genecards. The interaction between the targets of Xiaoban Quzhi Prescription and obesity was obtained using Venny 2.1.0. The common targets were introduced to the String 11.0 to perform the protein-protein interaction （PPI） analysis， and visualized by the CytoScape 3.9.1. The common targets were subjected to Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses using the Metascape， and then， a drug-component-target network was visualized via the CytoScape 3.9.1. Molecular docking of active ingredients of Xiaoban Quzhi Prescription to the targets was conducted by the Auto Dock Tools 1.5.6. The viability of 3T3-L1 preadipocytes induced with Xiaoban Quzhi Prescription at the concentrations of 10 µg·mL^–1， 20 µg·mL^–1， 40 µg·mL^–1， and 80 µg·mL^–1 was detected by cell counting kit-8 （CCK-8） assay. After 3T3-L1 preadipocytes were induced into mature adipocytes， reverse transcription-quantitative polymerase chain reaction （RT-qPCR） was used to detect the mRNA levels of insulin substrate receptor 1 （IRS-1） and glucose transporter 4 （GLUT-4）. Western blot was used to detect protein expressions of key members in the phosphatidylinositol-3-kinase/protein kinase B （PI3K/Akt） signaling pathway and their phosphorylated levels. RESULTS A total of 235 active ingredients were screened from Xiaoban Quzhi Prescription， with 280 targets. After intersecting disease targets of obesity with those of Xiaoban Quzhi Prescription， 117 intersecting targets were available. The core targets were serine/threonine-protein kinase （AKT1）， tumor necrosis factor （TNF）， interleukin-6 （IL-6）， IL-1B， and tumor protein p53 （TP53）. KEGG enrichment analysis showed that the intersecting targets were mainly enriched in the PI3K/AKT signaling pathway. Active ingredients of Xiaoban Quzhi Prescription included quercetin， kaempferol， and luteolin. Molecular docking showed the docking affinity of quercetin， kaempferol and luteolin with AKT1 was less than -5.0 kcal·mol^–1， showing a good binding activity. In vitro data showed that treatment of 10 µg·mL^–1 and 20 µg·mL^–1 Xiaoban Quzhi Prescription significantly increased the mRNA levels of IRS-1 and GLUT-4 in 3T3-L1 adipocytes （P < 0.01）， and the phosphorylated levels of PI3K and AKT （P < 0.01）. CONCLUSION Xiaoban Quzhi Prescription relieves obesity by upregulating the mRNA levels of GLUT-4 and IRS-1 in adipocytes and activating the PI3K/AKT signaling pathway.

OBJECTIVE To establish a quality control method for the Compound Zhizhuxiang Gel Plaster （CZGP） and a method for the determination of the contents of multiple components. METHODS Thin-layer chromatography （TLC） was used to qualitatively identify hesperidin （HSP）， costunolide （CL） and dehydrocostus lactone （DCL） in the CZGP. Their contents were determined via a quantitative analysis of multi- components with a single-marker （QAMS） using high-performance liquid chromatography （HPLC） with HSP as the internal standard. Meanwhile， CZGP was also examined with the amount of paste contained， heat-resistant properties， content homogeneity and the initial adhesive force. RESULTS In the TLC of each component， the same colour spots at the same position as the control product were clearly visible， with a good separation effect. HSP， CL and DCL respectively in the range of 13.20–1 689.00 µg·mL^–1 （r=0.999 6）， 2.85–365.40 µg·mL^–1 （r=0.999 8）， 4.14–530.40 µg·mL^–1 （r=0.999 9） showed a good linear relationship. Their average sample recovery rate was 97.820%， 101.38%， and 102.19%， respectively. The relative standard deviation （RSD） was 1.62%， 1.36%， and 1.42%， respectively. The measured content was 11.183， 1.707 0 and 1.921 0 mg·g^–1， respectively. QAMS obtained the similar finding as that of the external standard method， suggesting the feasibility of the former. The average paste content of each CZGP was 24.300 g， and the adhesion， heat resistance and content homogeneity were all complied with the requirements of the Chinese Pharmacopoeia （2020 Edition）. CONCLUSION The established quality control method is stable and reliable， and it can effectively control the quality of CZGP.

OBJECTIVE To establish the ultra-high performance liquid chromatography （UPLC） fingerprint of Gardeniae Fructus， and to illustrate its spectral effect of the hypoglycemic effect， thus preliminarily clarifying the material basis of the hypoglycemic effect of Gardeniae Fructus. METHODS A total of 11 batches of Gardeniae Fructus were analyzed by UPLC to establish the UPLC fingerprints. Similarity evaluation was carried out， and the fingerprint data were analyzed by clustering analysis. The ultra-high-performance liquid chromatography- tandem quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS） was used to identify the common feature peaks in the fingerprint. The inhibition rate of α-glucosidase was used as the pharmacodynamic index to analyze the hypoglycemic effect of Gardeniae Fructus. The spectral effect of Gardeniae Fructus was established by grey relational analysis （GRA） and partial least squares （PLS） to study the material basis of its hypoglycemic effect. RESULTS Through the establishment of fingerprints， 14 common peaks were calibrated. The information of each characteristic peak was preliminarily determined by database searching and literature comparison. The inhibition rate of α-glucosidase was determined by the analysis of spectral activity， showing that the hypoglycemic effect of Gardeniae Fructus was the co-result of various components. Among them， isoquercetin， 6″-O-trans-p-cinnamoylgenpin gentiobioside， gardenin， jasminoside Q and genipin-1-O-β-D-gentiobioside contributed greatly. CONCLUSION The 11 batches of Gardeniae Fructus have a good hypoglycemic activity attributed to the synergistic effect of the contained components. The components corresponding to the total peaks 7， 12， 5， 8， 4 are closely related to the hypoglycemic activity， revealing the pharmacodynamic material basis of hypoglycemic effect of Gardeniae Fructus.

OBJECTIVE To investigate the effect of Rubia yunnanensis on heart failure（HF） in mice and the underlying mechanism. METHODS Six wild-type C57 BL/6J mice were taken as the control group， and 18 apoE-knockout （ApoE-/-） mice were randomly divided into the HF group， treatment group， and positive control group for establishing HF model via a high-fat diet. Mice in the treatment group were given 7.5 g·kg^–1 Rubia yunnanensis decoction， and those in the positive control group were given oral gavage of trimetazidine 0.5 mg·kg^–1. Mice in the HF group were given an equal volume of saline by gavage. After feeding for 12 weeks， heart tissues were taken for H&E staining to detect the myocardial tissue changes. Myocardial fibrosis was detected by Masson’s trichrome staining， and type Ⅰ/Ⅲ collagen ratio was detected by Sirius red staining. The positive expression of brain natriuretic peptide （BNP） served as the golden standard for HF， which was measured in mouse heart to validate the success of modeling. Heart tissue was extracted for mRNA sequencing， and differentially expressed genes （DEGs） were subjected to GO and KEGG enrichment analyses. The mRNA expressions of DEGs were verified by real-time reverse transcriptase-polymerase chain reaction （RT-qPCR）. Protein levels of autophagy markers were detected by Western blot. RESULTS Compared with the control group， cell number in the model group was significantly lower （P<0.05）， and the myocardial fibrosis and type Ⅰ/Ⅲ collagen ratio were significantly higher （P<0.05）.Compared with the model group， cell number in the treatment and the positive control groups was significantly higher （P<0.05）， and myocardial fibrosis and type Ⅰ/Ⅲ collagen ratio were significantly lower （P<0.05）. There were 197 DEGs in the treatment group versus the model group， 205 DEGs in the model group versus the control group， and 21 DEGs in their intersection. Among them， expression levels of 13 DEGs were altered by the treatment of Rubia yunnanensis， involving 5 associated with HF： H2-Ab1， Ddit4， Mycn， Myl4， and Nppa. RT-qPCR showed that Rubia yunnanensis could reverse the mRNA expressions of H2-Ab1， Ddit4， Mycn， Myl4， and Nppa in the heart tissue of mice with HF. Western blot results showed that Rubia yunnanensis could downregulate LC3-I， LC3-Ⅱ and P62. CONCLUSION Rubia yunnanensis can improve HF in mice through the cytokine-cytokine receptor interaction， chemokine signaling pathway， and autophagy by regulating H2-Ab1， Ddit4， Mycn， Myl4， Nppa， and BNP.

OBJECTIVE To evaluate the cost-effectiveness of Selumetinib in the treatment of symptomatic and inoperable plexiform neurofibromas （PN） associated with neurofibromatosis type 1 （NF1） in Chinese children aged 3‒18 years. METHODS From the two perspectives of the whole society and Chinese health system， a partitioned survival model （PSM） model was constructed based on the SPRINT phase II clinical trial （NCT01362803） to perform a cost-effectiveness analysis of health outcomes and economic burden of disease in Chinese children aged 3‒18 years with NF1-PN who were treated with Selumetinib versus natural progression （optimal supportive care）. Scenario analysis and sensitivity analysis were performed on key parameters. RESULTS The baseline analysis revealed that， compared with natural progression of NF1-PN， the incremental effects of the Selumetinib were 4.91 quality-adjusted life years （QALYs）， incremental cost of ¥256 567， and incremental cost-effectiveness ratio of 52 223 yuan/QALY from the perspectives of whole society. From the perspectives of Chinese health system， the incremental effects of the Selumetinib were 3.73 QALYs， incremental cost of ¥290 891， and incremental cost-effectiveness ratio of 77 929 yuan/QALY. When taking one time of China’s per capita gross domestic product （GDP） in 2023 as the willingness to pay （WTP）， Selumetinib was cost-effective from the both perspectives. The results of the situational analysis were consistent with the basic analysis. Univariate sensitive analysis from the both perspectives showed that the annual discount rate made the greatest influence on ICER. When the WTP threshold is one time of China’s per capita GDP in 2023， the economic probability of Selumetinib was greater than the natural progression of disease. CONCLUSION For symptomatic and inoperable NF1-PN children aged 3‒18 years in China， Selumetinib is a very economical drug treatment option than the natural progression.

Doxycycline is a semisynthetic derivative of oxytetracycline that belongs to the second generation of tetracycline drugs. With high oral bioavailability， long half-life and wide antibacterial spectrum， doxycycline has a good effect on respiratory diseases and bacterial infections caused by Gram positive and negative bacteria， as well as typhus， malaria and mycoplasma pneumonia， etc. It is mainly used to treat macrolide resistant mycoplasma pneumonia and Rocky Mountain spotted fever in children. Instructions for tetracycline drugs only recommend the use in children at 8 years of age and older. Its safety in the application to younger children has been well concerned. Therefore， this article summarized the safety of doxycycline in the clinical treatment of children through literature review， especially those under 8 years old， thus providing references for a better clinical guidance on the safe use of doxycycline in children.

OBJECTIVE To understand the research progress of economic evaluation of paroxysmal nocturnal hemoglobinuria （PNH） at home and abroad， so as to provide a reference for subsequent research and payment decision-making. METHODS Pharmacoeconomic research of PNH was searched in the databases of CNKI， Wanfang Data， VIP， CBM， PubMed， Web of Science， Cochrane Library， Embase， EBSCO， Scopus and the International Network of Agencies for Health Technology Assessment （INAHTA）. The search time limit was from the establishment of the database to August 31， 2023. RESULTS A total of 342 literatures were obtained from the initial review and 10 were finally included， including 5 pharmacoeconomic evaluations and 5 HTA reports， all of which were model-based cost-utility analyses.The overall quality of the literatures was good. Four treatment options were reported， including supportive care， Eculizumab， Ravulizumab and Pegcetacoplan. For patients with classic PNH， Eculizumab was not economical compared with supportive care. For adult PNH patients， Ravulizumab dominantly superior to Eculizumab. For PNH patients treated with a stable dose of C5 complement inhibitor for more than 3 months but still without improvement in anemia status， Pegcetacoplan dominantly superior to Eculizumab， although its economic advantages compared with Ravulizumab are controversial. CONCLUSION PNH complement inhibitors are expensive and difficult to have economic advantages. In the future， health technology assessments based on the Chinese setting are still needed to provide high-quality evidence for health decision-making， thereby improving the clinical diagnosis and treatment of PNH in China and reducing the economic burden on patients’ families and health systems.

OBJECTIVE To provide a comprehensive description and evaluation of the clinical characteristics and outcomes associated with the use of ceftazidime-avibactam （CAZ-AVI） in the treatment of patients with carbapenem-resistant Gram-negative organisms （CRO） infections. METHODS The relevant data were retrospectively collected from patients who received CAZ-AVI for CRO infection at the First Hospital of Fujian Medical University from September 2020 to December 2023.The basic clinical data were subjected to descriptive analysis. The 30-day mortality rate and the 14-day bacterial clearance rate were employed as clinical indicators to evaluate the prognosis and drug efficacy of CAZ-AVI in treating CRO infections. The factors affecting the efficacy of CAZ-AVI in treating CRO infections were analyzed using univariate and multivariate logistic regression. RESULTS A total of 40 eligible patients were included for data assessment. Of them， 35 patients had carbapenem-resistant Enterobacteriaceae （CRE） as the causative organism， while 5 had carbapenem-resistant Pseudomonas aeruginosa （CRPA）. Pulmonary （72.5%， 29/40） and central nervous system （CNS） infections （10%， 4/40） were the predominant infection sites. No significant differences were observed in the 30-day mortality， 14-day bacterial clearance rates， and 30-day clinical cure rate between the CRE and CRPA groups. Univariate and multivariate logistic analyses indicated that a shortened treatment course with CAZ-AVI was an independent risk factor for a poor prognosis of CRO infections. Furthermore， admission to the ICU was identified as an independent risk factor for the failure of bacterial clearance by CAZ-AVI therapy. A total of three patients developed diarrhea related to CAZ-AVI. CONCLUSION The efficacy and safety of CAZ-AVI in the treatment of CRO infections is superior， while the appropriate prolongation of the treatment course may enhance the efficiency.

OBJECTIVE To provide theoretical basis for selection and safe and rational use of glucagon-like peptide-1 receptor agonist （GLP-1 RA） listed in China in medical institutions. METHODS The pharmaceutical properties， efficacy， safety， economy and other attributes （including medical insurance status， essential drugs status， storage conditions， drug validity， global use and corporate reputation） of GLP-1 RA were comprehensively evaluated using the evaluation method of the Rapid Guideline for Drug Evaluation and Selection in Chinese Medical Institutions （Second edition）. RESULTS The comprehensive evaluation showed the scores as follows： dulaglutide （80 points）， semaglutide （78.7 points）， liraglutide （74 points）， lixisenatide （65.6 points）， exenatide （65.1 points）， losenatide （64.2 points）， and benalutide （56.5 points）. Duraglutide， semaglutide， and liraglutide were strongly recommended. Lixisenatide， exenatide， and losenatide were weakly recommended or not recommended depending on whether there were clinically available alternatives. Benalutide was not recommended. CONCLUSION Duraglutide， semaglutide and liraglutide with cardiac and renal benefits are more advantageous in the selection. The comprehensive clinical evaluation of GLP-1 RA provides a technical support for drug selection in medical institutions and clinical rational drug use in patients.

OBJECTIVE To introduce the experience of establishing a clinical medicine pathway by the Affiliated Hospital of Qingdao University for perioperative pain management， and to provide references for other medical institutions. METHODS This study clarified the definition and characteristics， principles and goals， and drug selection and use of the medicine pathway based on medical evidence. The construction idea， implementation process and effect evaluation were analyzed and discussed， and the role of clinical pharmacists in this process was proposed. RESULTS In the formulation of medicine pathway， clinical pharmacists were responsible for exploring therapeutic drugs and multimodal analgesic strategies based on clinical needs and benchmark departments， thus improving the participation and enthusiasm of clinical departments. The evidence-based clinical medicine pathway was established and continuously modified. It was evaluated by effective parameters. From July 2019 to June 2023， the medicine pathway has been implemented in 46 wards of 22 surgical departments， and clinical pharmacists made monthly discharged case reviews and continuous improvement for existing problems. The medicine pathway has been effectively verified in the department of thoracic and cardiac surgery， ensuring a high pathway implementation rate， pain relief， less usage of postoperative opioid， reduced average drug costs， and decreased incidence of adverse events. CONCLUSION The evidence-based clinical medicine pathway for perioperative pain management has good operability， efficacy and safety， demonstrating pharmacist values， and improving the quality of pharmacy services in the perioperative period.

This paper reported a rare case of rhabdomyolysis （RM） combined with acute kidney injury （AKI） in an 80-year-old patient after using iodixanol injections， and analyzed the relationship between RM combined with AKI and the use of iodixanol injection and the possible mechanism. The prevention and treatment measures of adverse events of iodixanol were further discussed to improve the clinical safety of the drug used by clinicians.

OBJECTIVE To summarize the current status and characteristics of medication use in pregnant women， and to analyze medication factors affecting pregnancy outcomes， thus guiding the work of pharmacy clinics during pregnancy. METHODS Patients attending the pharmacy clinics during pregnancy of Affiliated Maternity and Child Health Care Hospital of Nantong University from January 2021 to August 2022 were taken as the study subjects. Medication risk assessment was carried out and the target population was followed up. Data of medication exposure， pregnancy outcomes， and neonatal conditions were collected. Risk factors influencing the decision to continue the pregnancy among the consultees were analyzed. Additionally， the correlation of the use of contraindicated medications， male partner medication use， and folic acid issueation with adverse pregnancy outcomes was examined. RESULTS A total of 420 counselling cases were collected. 93.98% of pregnant women used medication without knowing that they were pregnant， involving 412 types of medications. The most frequently used drugs were anti-infectives （21.75%）. 36.14% of pregnant women were exposed to 89 prohibited drugs. Among the 359 successfully followed-up cases， 26.46% abandoned the continuation of the pregnancy， 240 cases resulted in successful deliveries， and only 1 newborn exhibited abnormalities. The number of previous pregnancies significantly influenced the decision to continue pregnancy among consultees （OR=0.49， 95% CI： 0.32－0.76， P=0.002）. The study involved 24 cases of male medication users with all 12 live births showing no abnormalities. 66.85% of pregnant women were issueed with folic acid， of which 68.75% started issueation after the first month of pregnancy. CONCLUSION Most of the counsellors used medication without knowing they were pregnant， involving a wide range of drugs， yet no significant association was seen between drug use and offspring malformations in either females or males. The issueation rate of folic acid among consultees was relatively low. It is important to improve the pharmacological literacy of the reproductive-aged population through pharmacy clinics， thus providing references for a scientific clinical decision-making.

Hepatic fibrosis （HF） is a reversible pathological process associated with various chronic liver diseases. If left untreated， it can progress to severe pathological stages like cirrhosis and liver cancer， significantly impacting the health and quality of life. Currently， available clinical treatments for HF demonstrate limited efficacy， highlighting the urgent need for new drugs or active ingredients against HF. The mitogen-activated protein kinase （MAPK） signaling pathway plays a crucial regulatory role in cell proliferation， differentiation， and apoptosis， making it a key target in the modulation of HF development. Research has shown that interfering with the activation of MAPK signaling pathways through active ingredients of traditional Chinese medicine （TCM） herbals can yield positive outcomes in combating HF. This review examined the role of the MAPK signaling pathway in regulating HF and explored the therapeutic potential of active ingredients of TCM herbals targeting this pathway. Our aim is to provide insights that may contribute to the future development of novel drugs against HF.

A patient with pulmonary neuroendocrine carcinoma developed immune-related myocarditis after treatment with serplulimab was reported. After treatment with glucocorticoid， the patient’s condition improved and was discharged. The clinical data of the patient was reviewed and the immune-related myocarditis caused by immune checkpoint inhibitors serplulimab was discussed and analyzed.

Proprotein convertase subtilisin kexin 9 inhibitor （PCSK9i） is a novel lipid-lowering drug that acts on the proprotein convertase subtilisin kexin 9 （PCSK9）. PCSK9 binds to low density lipoprotein receptor （LDLR）， and inhibits its binding to low-density lipoprotein cholesterol （LDL-C）， thus affecting cholesterol metabolism in vivo. PCSK9 inhibitors play a role in regulating blood lipids and reversing atherosclerotic plaques by inhibiting the synthesis of PCSK9 or suppressing its function. This article described the current classification， target and mechanism of action of PCSK9 inhibitors， and briefly summarized their clinical studies. At the same time， we illustrated their role in regulating blood lipids and combating atherosclerosis from the perspective of evidence-based medicine.

OBJECTIVE To investigate and analyze the current situation， demand， driving and hindering factors of prescription circulation in China， thus providing references for promoting prescription circulation. METHODS An online questionnaire survey was conducted on the current situation and demand of prescription circulation by convenient sampling based on the network member hospital of Chinese Medical Economic Information. RESULTS A total of 3 826 questionnaires were collected and 3 823 were valid. 43.81% of the respondents had used prescription circulation. 76.62% of respondents knew the prescription circulation. Most of the respondents used prescription circulation services 1-3 times in the past year （1 168 respondents）； 859 respondents had experienced a drug change at a social pharmacy. The circulating prescriptions were mainly chronic disease drugs. 920 respondents used prescription circulation mode to buy cold medications against fever， cough and analgesia. “Previous usage of a prescription circulation” was the primary way to spread the concept of prescription circulation. Most of the respondents had the demand （2 189 respondents， 57.26%） and willingness （2 469 respondents， 64.58%） of prescription circulation. 3 218 respondents were willing to transfer prescriptions to “social pharmacies designated by medical insurance”. The largest demand （1 465 respondents） was the use of prescription circulation to buy cold medications against fever， cough and analgesia. The most important driving factor was “saving time in hospital queues to pick up drugs”. The main hindering factors to offline prescription circulation was respondents’ concern that the supervision of pharmacies was not as strong as that of hospitals， while the main hindering factors to online prescription circulation was lack of medication guidance services. Occupation （whether it is a medical practitioner） significantly affected the awareness， use， and demand of respondents for prescription circulation. CONCLUSION The awareness rate， utilization rate and demand of prescription circulation in China are increasing. However， there is a gap between the standardization and ability level of pharmaceutical care in social pharmacies and the needs of patients. The payment of medical insurance， the supervision of drugs in the field of circulation and the safety of drug distribution are important factors influencing the development of prescription circulation.

Narrow therapeutic index drugs （NTIDs） are drugs where small alterations in the dose or blood concentration may lead to serious therapeutic failures and/or adverse drug reactions that are life-threatening or persistently or significantly cause disability/incapacity. The rational clinical use of NTIDs helps prevent or avoid ineffective drug therapy， ensuring medication safety and reducing drug-related risks. To enhance the understanding of NTIDs among clinicians， pharmacists， and other healthcare professionals， and to standardize the rational use of these drugs， this consensus aims to improve the safety of NTID clinical applications. This consensus was developed by the Hospital Pharmacy Professional Committee of Chinese Pharmaceutical Association and the Clinical Pharmacy Branch of Chinese Medical Association. It provided guidance on therapeutic drug monitoring （TDM）， pharmacogenetic testing， drug interactions， adverse drug reaction management， overdose management， medication use in special populations， and principles for drug substitution.

OBJECTIVE To investigate the potential mechanisms of Buqi Xiaozhi Formula in the prevention and treatment of high-fat diet-induced non-alcoholic fatty liver disease （NAFLD） and the involvement of the phosphoinositide 3-kinase （PI3K）/protein kinase B （AKT）/mechanistic target of rapamycin （mTOR） signaling pathway and autophagy. METHODS A NAFLD mouse model was created by 16 weeks of high-fat diet. From weeks 13 to 16， oral gavage of Buqi Xiaozhi Formula and polyene phosphatidylcholine （Essentiale forte） was given. Serum liver function， blood lipids， and inflammatory cytokine levels were measured. Hematoxylin and eosin （H&E） and Oil Red O（ORO） staining were used to observe liver tissue morphology. Lipids and lipid peroxidation indicators in liver tissue were also determined. Western blot was used to detect the protein levels of proteins related to fat metabolism， autophagy， and the PI3K/AKT/mTOR pathway. RESULTS Buqi Xiaozhi Formula significantly reduced the activities of liver function enzymes （alanine aminotransferase and aspartate aminotransferase）， blood triglycerides （TG）， total cholesterol （TC）， low-density lipoprotein （LDL） and malondialdehyde （MDA）， but significantly increased activities of superoxide dismutase （SOD） and glutathione peroxidase （GPx） in the NAFLD mice. Buqi Xiaozhi Formula significantly downregulated lipid metabolism-related protein acetyl-CoA carboxylase， fatty acid synthase， autophagy substrate P62 and proteins involved in the PI3K/AKT/mTOR signaling pathway， but significantly upregulated carnitine palmitoyl transferase， and autophagy marker LC3. CONCLUSION Buqi Xiaozhi Formula effectively prevents and treats high-fat diet-induced NAFLD by improving autophagy via inhibiting the PI3K/AKT/mTOR signaling pathway.

OBJECTIVE To explore the hypoglycemic activity of chamomile total flavonoids and its role in improving the physiological indexes of type 2 diabetes mellitus （T2DM）. METHODS The enzyme screening method was used to screen the activities of aldose reductase （AR）， protein tyrosine phosphatase 1B （protein tyrosine phosphatase 1B，PTP1B） and dipeptidyl peptidase Ⅳ （dipeptidyl peptidase Ⅳ ， DPP Ⅳ） influenced by chamomile total flavonoids. Using db/db mice and db/m mice as experimental animals to observe the effects of chamomile total flavonoids on the weight and blood glucose of diabetic mice. Serum total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein-cholesterol（HDL-C）， low-density lipoprotein-cholesterol （LDL-C）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST） and gamma-glutamyl transpeptidase （GSP）were detected. Hepatic steatosis of mice was observed. Malondialdehyde （MDA）， superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px）in liver tissue were detected. Western blot was used to detect the protein levels of aldo-keto reductase family 1 member B1 （AKR1B1）. RESULTS The results of enzyme screening showed that chamomile total flavonoids did not have an inhibitory effect on PTP1B and DPP Ⅳ， but a strong inhibitory effect on AR［IC₅₀=（91.16±1.20） μg·mL^–1］. Compared with normal control group， serum TG， TC，LDL-C， ALT， AST and GSP in the model group significantly increased， while serum HDL-C significantly decreased. The content of MDA in liver tissue significantly increased， and SOD and GSH-PX levels significantly reduced. The results of mouse liver disease slices showed that the liver injury was serious. AKR1B1 protein in the liver tissue was significantly upregulated. Compared with model control group， serum TG， TC， LDL-C， ALT， AST and GSP significantly decreased in all-dose chamomile total flavonoid groups， while serum HDL-C significantly increased. The content of MDA in liver tissue significantly decreased， and SOD and GSH-PX levels significantly increased in all-dose total chamomile flavonoid groups. The steatosis of liver tissue was significantly reduced in each dose group of total chamomile flavonoid. AKR1B1 protein level was significantly down-regulated in all-dose chamomile total flavonoid groups. CONCLUSION Chamomile total flavonoids play a hypoglycemic role by inhibiting the activity of aldose reductase. It can improve the physiological indexes of diabetic mice and delay the development of diabetes.

Taxus L is the generic name of Taxus， which mainly contains taxanes， flavonoids， lignans， phenols and other chemical constituents. Taxus L has many pharmacological effects such as anti-tumor， anti-inflammatory， analgesic， antioxidant and hypoglycemic effects. This study integrated and summarized the chemical composition and pharmacological effects of Taxus chinensis. Based on the theory of quality marker （Q-Marker） of traditional Chinese medicine， the Q-Marker of Taxus chinensis was predicted and analyzed from the aspects of plant phylogeny， the peculiarity of chemical components， testability of chemical components， pharmacodynamics and blood components. Preliminary predictions suggested that paclitaxel， harringtonine， bacatineⅢ， 10-deacetylbacatineⅢ， （+）-taxing， quercetin， kaempferol， sciadopitysin， ginkgo biloba， amentoflavone， and so on may be potential Q-Markers for it. Our findings provide a basis for establishing and improving the quality evaluation of Taxus chinensis.

OBJECTIVE To prepare baicalin-zein nanoparticles （BA-ZNPs） using plant-derived zein as a carrier material and to evaluate their in vitro anti-tumor activity. METHODS BA-ZNPs were synthesized using the phase separation method， and characterized by morphological observation， particle size， zeta potential， encapsulation efficiency and drug loading. The effect of BA-ZNPs on the proliferation of the metastatic human breast cancer cell line MDA-MB-231 was detected by cell counting kit-8 （CCK-8） assay. Cell scratch assay and Transwell assay were used to evaluate the effects of BA-ZNPs on cell migration and invasion， respectively. Flow cytometry was employed to investigate the cell cycle distribution and apoptosis induced by BA-ZNPs. RESULTS BA-ZNPs were spherical in shape， with an average particle size of approximately 110 nm， an encapsulation efficiency of （83.02±1.24）%， and a drug loading capacity of （4.39±0.32）%. The carrier material was non-cytotoxic. Both BA and BA-ZNPs displayed significant inhibitory effects on tumor cell growth. Nanoization significantly enhanced the cytotoxicity of BA. Compared to BA， BA-ZNPs had a significantly stronger inhibitory effect on the healing ability， migration， invasion and cell cycle arrest of tumor cells， which also enhanced the kill effect on tumor cells and induced cell apoptosis. CONCLUSION BA-ZNPs can effectively inhibit the proliferation， migration， and invasion of MDA-MB-231 cells， and then induce apoptosis. This study is expected to provide a theoretical basis for the treatment of metastatic breast cancer.

A patient with systemic lupus erythematosus complicated with antiphospholipid syndrome developed pulmonary embolism and treated with warfarin after catheter thrombolytic therapy was reported. After 20 days of discharge， the patient developed swelling， distension and discomfort in the right lower limb again. Color ultrasound indicated a deep venous thrombosis in the right lower limb. Clinical pharmacists and physicians formulated an anticoagulant regimen and then changed the anticoagulant therapy to rivaroxaban. The therapeutic effect on this case was satisfactory. The use of rivaroxaban in this population remains controversial. Through literature review， we recommended the use of rivaroxaban in patients with systemic lupus erythematosus and secondary antiphospholipid syndrome who are poorly responsive to warfarin， aiming to achieve improved therapeutic outcomes.

OBJECTIVE To investigate the interventional effect of Xuanfei Huazhuo Recipe on lipopolysaccharide （LPS）-induced alveolar epithelial cell injury. METHODS Serum containing Xuanfei Huazhuo Recipe， and blank control serum were prepared. A549 cells were cultured in vitro， and subjected to the LPS-induced alveolar epithelial cell injury model. Optimal conditions for LPS induction were screened by detecting the cell survival rate using the CCK-8 assay. Cells were induced with blank control， LPS， and LPS+low-dose， medium-dose and high-dose Xuanfei Huazhuo Recipe. The apoptosis rate was detected by flow cytometry. The mRNA and protein levels of apoptosis genes were detected by Reverse-transcription PCR （RT-PCR） and Western blot， respectively. RESULTS CCK-8 assay showed that 12.5 µg·mL^–1 LPS induction for 24 h offered the optimal intervention condition. Compared with the control group， cell survival rate significantly decreased after LPS induction， while the apoptosis rate significantly increased （P<0.01）. Compared with LPS-induced cells， those managed by low-dose， medium-dose and high-dose Xuanfei Huazhuo Recipe showed significantly higher survival rate （P<0.05， P<0.01） and lower apoptosis rate （P<0.05， P<0.01）. In cells induced with LPS+low-dose， medium-dose and high-dose Xuanfei Huazhuo Recipe， the protein and mRNA levels of Bax and Caspase-3 were dose-dependently downregulated， and those of Bcl-2 were dose-dependently upregulated. CONCLUSION Xuanfei Huazhuo Recipe inhibits A549 cell apoptosis and improves alveolar epithelial cell injury by up-regulating Bcl-2 and down-regulating Bax and Caspase-3 by regulating the Bax/Bcl-2/Caspase-3 signaling pathway.

OBJECTIVE To investigate the impact of Astragalus membranaeus-Rhizoma curcuma （HQEZ） drug pair on the metabolism， transformation， and targets of capecitabine in gastric cancer cells， and to elucidate the underlying biological mechanisms by which this drug pair synergistically enhances the chemotherapeutic effect of capecitabine. METHODS The influence of HQEZ combined with capecitabine on gastric cell proliferation was evaluated using the CCK-8 assay. High-performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS） was employed to assess the conversion of capecitabine to 5-fluorouracil （5-FU） in gastric cancer cells after co-administration with HQEZ. Real-time fluorescence quantitative PCR （RT-qPCR） and Western blot analyses were conducted to determine the mRNA and protein levels of 5-FU-related enzymes， cytidine deaminase （CDD） and thymidine phosphorylase （TP）， respectively. Protein expressions of membrane drug efflux protein P-glycoprotein （P-gp） and 5-FU target enzyme thymidylate synthase （TS） were also examined by Western blot. RESULTS HQEZ combined with capecitabine significantly enhanced the inhibitory effect of capecitabine alone on the proliferation of SGC7901 cells， which was associated with an increase in the intracellular content of the active metabolite 5-FU derived from capecitabine. At the mRNA and protein levels， HQEZ dose-dependently upregulated metabolic transformation-related enzymes CDD and TP in SGC7901 cells. Furthermore， HQEZ dose-dependently downregulated the protein expressions of drug efflux-related target P-gp， and the key target TS of 5-FU. CONCLUSION HQEZ can enhance the antitumor effect of capecitabine by facilitating its transformation to 5-FU in gastric cancer cells SGC7901 by reducing drug efflux to increase the concentration of 5-FU， and inhibiting the expression of TS.

OBJECTIVE To analyze the components of Biwen Jiedu Granules （BWJD） by UHPLC-Q Exactive Focus MS/MS technology （ultra high performance liquid chromatography coupled with a Thermo Scientific Q Exactive Focus mass spectrometer， capable of performing tandem mass spectrometry）， and to explore its relevant mechanisms and active ingredients in the treatment of respiratory diseases with the syndrome of cold and dampness， heat stagnation and fluid injury in an integrated method of network pharmacology and molecular docking technology. METHODS UHPLC conditions were as follows： Thermo Accucorea Q C₁₈（2.1 mm×150 mm， 2.6 μm）with the mobile phase of acetonitrile（A）-0.1% formic acid aqueous solution（B）for gradient elution， and the components of BWJD were analyzed. Potential active ingredients in BWJD were screened using the SwissADME database， and the targets were retrieved from the Swiss TargetPrediction database. At the same time， the targets of respiratory diseases with the syndrome of cold and dampness， heat stagnation and fluid injury were searched by GeneCards using fever， cough， sore throat， bloating， diarrhea， nausea and vomiting as the main symptoms. Then STRING and DAVID database was used to perform protein-protein interaction network analysis， GO function and KEGG pathway enrichment analysis. The drug-component-target-pathway network was constructed using the Cytoscape software. Furthermore， Autodock software was employed for molecular docking of the components and potential targets. RESULTS A total of 102 components were identified in BWJD， and 40 potential active components were screened. Furthermore， 513 potential targets related to components and 367 targets related to diseases were obtained. Seventy-six intersection targets between components and disease-related targets were selected for GO and KEGG pathway analysis. Significantly enriched signaling pathways mainly included tumor signal pathways， resistance of EGFR tyrosine kinase inhibitors， and AGE-RAGE signal pathway in diabetes complications. The molecular docking results indicated a well binding between the active ingredients and the main targets. CONCLUSION The active components in BWJD， such as luteolin， emodin， wogonin， hesperetin may be the material basis acting on AKT1， EGFR， ESR1 and other targets to regulate the AGE-RAGE， MAPK， PI3K-AKT and other signaling pathways. It serves as the molecular mechanism of BWJD in treating respiratory diseases with the syndrome of cold and dampness， heat stagnation and fluid injury.

OBJECTIVE To establish and validate a liquid chromatography tandem mass spectrometry （LC-MS/MS） method for quantification of nine folate metabolites in biological samples， and to apply it to the preconception and pregnancy cohorts. METHODS The blood samples were pre-processed by antioxidant protection， protein dissociation， and organic solvent protein precipitation. Using the Kinetex F₅ column，0.1% formic acid aqueous solution and methanol as the mobile phase at a flow rate of 300 μL·min^–1 for an 8-minute gradient elution， LC-MS/MS was conducted. Electrospray ionization was in positive ion multiple reaction monitoring mode. A total of 918 blood samples collected from Nantong Maternal and Child Health Hospital from May 2022 to September 2023 were analyzed for the differences in folate metabolites at different stages. Their distribution patterns were summarized. RESULTS Nine folate metabolites， including folic acid （FA）， 5-methyltetrahydrofolate（5-MTHF）， 5-formyltetrahydrofolate（5-FTHF）， homocysteine （Hcy）， S-adenosylmethionine （SAM）， S-adenosylhomocysteine （SAH）， vitamin B₁₂（VB₁₂）， vitamin B₂（VB₂）， vitamin B6（VB₆）， and 5-MTHF in red blood cells， exhibited linear correlations within a defined range， with correlation coefficients≥0.9928. The accuracy was 87.61%–109.72%， and the precision（relative standard deviation ［RSD］）≤ 7.97%. The intra- and inter-batch precision （RSD） was lower than 18.18%. The maximum dilution and instrument residues met relevant requirements， and sample stability was good after 24 hours in the autosampler. As pregnancy progressed， serum and red blood cell levels of 5-MTHF increased， while concentrations of Hcy and VB₁₂ decreased. Additionally， the ratio of SAM to SAH （SAM/SAH） declined. CONCLUSION The LC-MS/MS method is simple to operate， with good accuracy， sensitivity， and repeatability， allowing for simultaneous determination of 9 folate metabolites. Clinical practice evidence validates its effective application to precise supplementation of folates in women during preconception and pregnancy， enabling the establishment of local reference range for folate.

OBJECTIVE To summarize and analyze the refined construction and practical experience of pediatric pharmacy clinic using the medicine referral collaboration model in the Peking University Third Hospital， and to provide references for the similar type of clinics. METHODS The medicine referral collaboration model was constructed to improve the hardware and software conditions of the pediatric pharmacy clinic and the refined pharmacy service model. We collected data from patients attending the clinic， pharmacy outpatient service data， and assessed the effect of inhalation device patient education and service satisfaction. RESULTS One year after the opening of the pediatric pharmacy clinic in our hospital， a total of 700 children and their families visited the clinic， with an average of 58 visits per month. A total of 19 physician conducted referrals. Totally 296 （42.29%） cases completed the charge for pharmacist services. The median duration of visit was 11 minutes， with 13 mins in medical visit with special device education， and 8 minutes without education. Totally 79 （11.83%） cases completed repeated visits. The predominant disease was respiratory， and the most frequent teaching was about the use of inhalation devices. After visiting the pediatric pharmacy clinic， the error rate of using the device was significantly reduced， and the number of teachings on expiration， inhalation and breath-holding was significantly reduced （P<0.05）. Healthcare professionals and families of the children satisfied the services provided by the pediatric pharmacy clinic. CONCLUSION The pediatric pharmacy clinic of our hospital has adopted the collaborative model of medicine referral and constructed a more complete pharmacy service process and refined service content， which is effective and provides a useful reference for the construction of the similar type of clinic. In the future， we will gradually build the service guidelines and pathways of pediatric subspecialty pharmacy clinic， improve the informationization level to ensure the efficiency of consultation， and promote the high-quality development of pediatric pharmacy clinic.

OBJECTIVE To explore the mechanisms underlying antipsychotics （APs） in inducing astrocyte death and the potential intervention strategies. METHODS Human-derived astrocytes were cultured in vitro and treated with 10 μmol·L^–1 olanzapine （OLZ） or quetiapine （QUE） combined with betahistine at different concentrations （10 μmol·L^–1 or 5 μmol·L^–1） for 24 hours. Quantitative real-time PCR， Western blot， immunofluorescence and electron microscopy were used to assess the activation of pyroptosis by OLZ and QUE， as well as the inhibitory effects of betahistine. RESULTS Compared to the control group， OLZ or QUE treatment significantly upregulated mRNA and protein expression levels of key markers in the classical pyroptosis signaling pathway， including Caspase-1， gasdermin D （GSDMD）， NOD-like receptor thermal protein domain associated protein 3 （NLRP3）， interleukin-1beta （IL-1β）， as well as Caspase-4 and Caspase-5 involved in the non-classical signaling pathway in astrocytes （all P<0.05）. Co-treatment of betahistine and OLZ/QUE significantly inhibited the upregulation of mRNA and protein expressions of these pyroptosis-related markers in a dose-dependent manner （all P<0.05）. Further morphological studies revealed that OLZ or QUE treatment significantly induced pyroptosis-like membrane perforations in astrocytes， while co-treatment of betahistine and OLZ/QUE reduced the number of membrane perforations， with cell morphology resembling that of the control group. CONCLUSION OLZ or QUE induces astrocytic pyroptosis through activating both classical Caspase-1-dependent and non-classical Caspase-4/5-dependent pyroptosis signaling pathways. Betahistine inhibits the activation of these pathways， thus reducing pore formation and thereby mitigating OLZ/QUE-induced astrocytic pyroptosis， and providing a neuroprotective effect.

OBJECTIVE To analyze the effects of general anesthesia induction using remimazolam at various doses on stress response during tracheal intubation， hemodynamics， myoclonus and agitation in elderly patients after abdominal surgery. METHODS A total of 90 elderly patients undergoing abdominal surgery in Zibo 148th Hospital between June 2022 and June 2023 were enrolled. According to random number table method， they were randomly divided into group A， group B and group C， with 30 cases in each group. All the three groups were given general anesthesia induction using remimazolam （0.2， 0.3， 0.4 mg·kg^–1）， and the anesthesia methods were the same in the three groups. At T₀ （at the beginning of induction）， T₁ ［the first time of bispectral index （BIS）≤60］， T₂ （after tracheal intubation） and T₃ （30 min after extubation）， stress response indexes ［epinephrine （E）， norepinephrine （NE）， serum cortisol （Cor）］， hemodynamics indexes ［heart rate （HR）， systolic blood pressure （SBP）， diastolic blood pressure （DBP）］ and the occurrence of adverse events （myoclonus， agitation） were compared among the three groups. RESULTS There were significant differences in the time point， inter-group and interaction dimensions of Cor， E and NE among the three groups （P<0.05）. At T₃， Cor， E and NE in group C were significantly lower than those in group A and group B （P<0.05）， and they were significantly lower in group B than group A （P<0.05）. There were no significant differences in the between-group and interaction dimensions of HR， SBP and DBP among the three groups （P>0.05）， but there were significant differences in the time dimension （P<0.05）. There was no significant difference in the incidence of myoclonus among the three groups （P>0.05）. The incidence of agitation was 3.33% in group A and 6.67% in group B， which was significantly lower than that of 23.33% in group C （P<0.05）. CONCLUSION General anesthesia induction using remimazolam at various doses （0.2， 0.3 mg·kg^–1， 0.4 mg·kg^–1） can effectively maintain hemodynamics stability in elderly patients after abdominal surgery. However， intravenous injection of remimazolam at 0.2 and 0.3 mg·kg^–1 can reduce the incidence of agitation， while remimazolam at 0.3 mg·kg^–1 and 0.4 mg·kg^–1 can effectively inhibit stress response during tracheal intubation. Remimazolam at 0.3 mg·kg^–1 is both effective and safe.

This article reported the diagnosis and treatment process of a patient with G4 grade immune-related colitis caused by sintilimab treatment for pulmonary sarcomatoid carcinoma. During the treatment process， an analysis was conducted on the mechanism and clinical manifestations of sintilimab-induced immune-related colitis. From initially considering infectious diarrhea to drug-induced enteritis， the treatment effect was unsatisfactory after anti-infection， regulation of gut microbiota， and correction of electrolyte imbalance. Finally， the patient was improved by methylprednisolone. This case report aims to further enhance the understanding of immune-related adverse events among clinical physicians and pharmacists， and increase the clinical application experience of immune checkpoint inhibitors.

OBJECTIVE The explore the effects of Jianpi-Zishen Formula on differentially expressed serum metabolites and metabolic pathways in MRL/lpr mice with systemic lupus erythematosus mice （SLE）. METHODS Twelve MRL/lpr mice with SLE were randomly divided into model group， and traditional Chinese medicine （TCM） group， and 6 C57BL/6 mice were as the control group. Through LC-MS/MS， differentially expressed serum metabolites of Jianpi-Zishen Formula responsible for treating SLE were identified through the principal component analysis （PCA）， partial least squares discriminant analysis （PLS-DA） and orthogonal partial least squares discriminant analysis （OPLS-DA）， with the criteria of variable importance projection （VIP） >1， P<0.05 in the t test and fold change （FC） ≥ 1.5 or ≤0.5. Online databases， including the HMDB， Massbank， LipidMaps， mzcloud， Kyoto Encyclopedia of Genes and Genomes （KEGG） and the self-built standard library of metabolism （Suzhou Panomix Biomedical Tech Co.， Ltd.） were used for identification. MetaboAnalyst software package was used for functional pathway enrichment and topology analysis of the screened differentially expressed metabolites. The enriched pathways were visualized using the KEGG Mapper tool to display the differentially expressed metabolites and pathways. RESULTS A total of 338 metabolites were detected. Compared with the normal group， there were 33 differentially expressed metabolites between the model group and the normal group， with 22 up-regulated and 11 down-regulated metabolites. A total of 31 differentially expressed metabolites were found between the model group and the TCM group， involving 18 up-regulated and 13 down-regulated metabolites. After treatment with Jianpi-Zishen Formula， the contents of differentially expressed metabolites， including the 3-hydroxy-2-aminobenzoic acid， sphingosine 1-phosphate and myristic acid were significantly up-regulated， and raffinose and ethyl 4-acetylbutyrate were significantly down-regulated. KEGG enrichment analysis showed 49 metabolic pathways with significant differences， and the top five pathways were cell burial， pentose phosphate pathway， melanin production， galactose metabolism， and Fcγ receptor-mediated phagocytosis. CONCLUSION The therapeutic effects of the Jianpi-Zishen Formula in treating SLE may be associated with significant alterations in metabolites like 3-hydroxy-2-aminobenzoic acid， sphingosine-1-phosphate， myristic acid， raffinose， and ethyl 4-acetylbutyrate. These metabolites are involved in the regulation of metabolic pathways， including efferocytosis， the pentose phosphate pathway， melanogenesis， galactose metabolism， and Fcγ receptor-mediated phagocytosis.

OBJECTIVE To understand the occurrence of potentially clinically significant drug-drug interactions （pcsDDIs） in elderly inpatients and the factors affecting them， thus providing an important basis for the clinical drug safety in elderly patients. METHODS Discharged elderly patients （≥65 years old） in the electronic medical records system of Huaibei People’s Hospital from May 1， 2022， to May 20， 2022 were retrieved. The occurrence of pcsDDIs was assessed by the inpatient medical orders based on the International Consensus List of pcsDDIs in Older People. Risk factors for pcsDDIs were analyzed by logistic regression. RESULTS A total of 856 elderly patients with a median age of 74 years were included， of whom 413 （48.2%） had at least 1 pcsDDI. A concomitant use of more than 2 potassium-protecting drugs （24.4%） was the dominant pcsDDI. There were 19 single factors affecting pcsDDIs， and multifactorial logistic regression revealed that history of drug allergy， total number of discharge diagnoses， age-corrected Charlson comorbidity index （aCCI）， comorbid cerebral infarction， comorbid hypertension， comorbid myocardial infarction， comorbid coronary artery disease， comorbid cardiac insufficiency， comorbid atrial fibrillation， number of Western medication varieties， and use of biologics were the risk factors. CONCLUSION The incidence of pcsDDIs in the medication of hospitalized elderly patients is high. The risk of drug interactions should be highlighted to strengthen the monitoring of the rational use of medication in elderly patients， and optimize medical resources.

Chimeric antigen receptor T （CAR-T） cell therapy is a novel cellular immunotherapeutic means that holds great promise in the treatment of hematological malignancies. CAR-T cells， as a kind of “living” drug， have the property of in vivo proliferation and differentiation， as well as special cellular pharmacokinetic （PK） behavior. Previous studies have shown that the in vivo kinetic characteristics of CAR-T cells may be associated with the clinical efficacy and safety of CAR-T therapy. It is important to clarify the kinetic behavior of CAR-T cells to grasp the mechanism of CAR-T cells， thus further guiding the precision therapy of CAR-T. Therefore， this article reviewed the research progress on CAR-T cell pharmacokinetics and its influencing factors in the treatment of hematological malignancies， in order to provide references for the safe and effective treatment of CAR-T cells in clinical practice.

Continuously promoting the rational use of medicines based on the principles of safety， efficacy， economics， and appropriateness is an important approach to improve clinical management of medicines and optimize the allocation of health resources. Pharmacoeconomics aims to integrate the concept of quantifying the value of medicines into healthcare decisions， thus systematically and scientifically comparing and analyzing the economic costs and health returns of pharmaceutical technologies. It facilitates the formulation of the optimal strategy for decision-making and improvement of the overall efficiency of healthcare resource allocation. Focusing on the issue of rational use of drugs， this review explained how pharmacoeconomic evaluation， real-world treatment status research， medication use patterns and disease burden causal analysis based on the guiding principles of basic theories and research methods of pharmacoeconomics assist drug selection， promote standardized use of drugs， and improve the clinical use model of drugs after they are launched on the market. Targeting on current pharmacoeconomics research issues like insufficient data quality and imperfect study design， this review put forward targeted suggestions and solid scientific basis to help the pharmacoeconomics evidence develop in a higher quality direction and provide guidance for the practice of rational drug use.