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 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 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 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 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.
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 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 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 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.
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.
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.
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.
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.
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.
