OBJECTIVE To explore the dynamic changes and development trend of quantitative pharmacology in recent years based on the publications of Chinese institutions from 2017 to 2022. METHODS Quantitative pharmacology papers published by China institutions were systematically searched from six databases， namely PubMed， Web of Science， Scopus， China National Knowledge Infrastructure （CNKI）， VIP and Wanfang Medicine. Bibliometric methods were applied for extracting number of published papers， number of citations， research areas， authors and institutions. Moreover cooperation across institutions and other information were examined through social network diagram. RESULTS From 2017 to 2022， 395 institutions published 483 Chinese and 900 English papers， including 859 Science Citation Index （SCI） papers， of which 14 papers were cited over 30 times in SCI and 35 institutions published over 10 papers. The total number of first and corresponding authors was 1 912. Government regulatory agencies and research institutes have witnessed the fastest growth in the number of publications. In addition to population pharmacokinetics/pharmacodynamics， physiologically based pharmacokinetics， model-based meta-analysis and quantitative system pharmacology spiked yearly. Inter-agency cooperation became more frequent. CONCLUSION In the past 6 years， the number of pharmacometric studys in China has jumped rapidly. Both research fields and contents are continuously broadening and deepening. Researchers are growing with deeper cooperation and exchange across institutions. Pharmacomety plays a vital role in model-informed drug development and model-informed precision dosing.
OBJECTIVE To explore the effects and mechanisms of norwogonin （Now） in ameliorating brain tissue injury induced by acute hypobaric hypoxia （AHH） in mice. METHODS A total of 78 male BALB/c mice were randomized into six groups of normal control， HH， rutin （200 mg·kg–1）， low-dose （50 mg·kg–1）， medium-dose （100 mg·kg–1） and high-dose （200 mg·kg–1） norwogonin. Drugs were administered by an intraperitoneal injection in normal control group. HH groups received saline intraperitoneally. Mice were exposed to a low-oxygen chamber at a simulated altitude of 8 000 m for 24 h for modeling of AHH-induced brain tissue injury. Hematoxylin eosin （HE） stain was utilized for assessing pathological changes. The levels of hydrogen peroxide （H2O2）， malondialdehyde （MDA）， superoxide dismutase （SOD） and glutathione （GSH） in brain tissues were measured for assessing the state of oxidative stress. Enzyme-linked immunosorbent assay （ELISA） was employed for detecting the levels of interleukin-1β （IL-1β）， tumor necrosis factor-alpha （TNF-α） and interleukin-6 （IL-6） in brain tissues for assessing inflammatory responses. Western blot was utilized for quantifying the expression levels of hypoxia-related proteins ［hypoxia-inducible factor-1α （HIF-1α） & vascular endothelial growth factor （VEGF）］， antioxidative stress-related proteins ［nuclear factor erythroid 2-related factor 2 （Nrf2） & heme oxygenase 1 （HO-1）］， inflammation-related proteins ［nuclear factor kappa-B （NF-κB） & TNF-α］ and apoptosis-related proteins ［Bcl-2-associated X protein （Bax） & B cell lymphoma 2 （Bcl-2） & cleaved caspase-3］. RESULTS As compared with control group， brain tissues of HH group showed some pathological changes. The levels of H2O2， MDA， IL-1β， TNF-α and IL-6 rose markedly while the levels of SOD and GSH declined significantly. Also the expressions of VEGF， Nrf2， HO-1， NF-κB， TNF-α， Bax and cleaved caspase-3 were elevated， the expression of Bcl-2 dropped and the ratio of Bax/Bcl-2 spiked. Norwogonin pretreatment reversed these changes. CONCLUSION Norwogonin alleviates AHH-induced brain tissue injury in mice through suppressing oxidative stress， inflammatory responses and apoptosis.
OBJECTIVE To examine the sponsoring overviews and hotspots of clinical pharmacology projects supported by National Natural Science Foundation of China （NSFC） and provide references for fund application. METHODS For the related projects of clinical pharmacology from 2016 to 2022 （application code settings： H3111 for 2016–2020， H3511 for 2021–2022）， the relevant items were thoroughly retrieved from the NSFC official website， LetPub Inquiry System and ZCOOL database. Approval year， project name， sponsoring type， supporting institution and funding amount were statistically analyzed and visualized with Excel and CiteSpace software. RESULTS An aggregate of 89.34 million was allocated to 225 projects of clinical pharmacology. Both quantity and number of sponsored projects exhibited an erratic rising trend. Two major categories of support were Youth Foundation and General Program. There was an unequal regional distribution and Beijing， Jiangsu and Shanghai were three key areas. Central South University， Peking University and Zhejiang University were the most prominent. Molecular mechanisms， especially of tumor progression and drug resistance， became a major focus of investigation. Personalized medication and adverse reactions were important study areas as well. Signal transduction pathway， genetic polymorphism， biomarker， PK/PD and multi-omics technologies were among other study hotspots. CONCLUSION NSFC provides strong research supports for clinical pharmacology. With deepening applications and researches of novel technologies， more breakthroughs are expected in the field of clinical pharmacological researches in the future.
OBJECTIVE To explore the protective mechanism of 1， 8-cineole antagonizing inflammatory injury in human umbilical vein endothelial cells （HUVECs）. METHODS CCK-8 was utilized for detecting different concentrations of 1，8-cineole （0.08， 0.12， 0.31， 0.63， 1.25， 2.50， 5.00， 10.00 μg·L–1） for screening the optimal concentration. HUVECs were exposed to lipopolysaccharide （LPS）. HUVEC cells were assigned into six groups of control， model， low/medium/high-dose 8-cineole and medium-dose8-cineole plus KLA. Cellular viability， apoptosis and migration were detected by CCK-8， flow cytometry and transwell. The contents of malondialdehyde （MDA） and superoxide dismutase （SOD） were detected by kits. The mRNA contents of anti-intercellular adhesion molecule-1 （ICAM-1） and anti-vascular cell adhesion molecule-1 （VCAM-1） were detected by polymerase chain reaction （PCR）. The expression levels of interleukin-6 （IL-6）， tumor necrosis factor-alpha （TNF-α）， Toll-like receptor 4 （TLR4）， cytoplasmic nuclear factor-kappa B p65 （NF-κB p65）， nuclear NF-κB p65 and cleaved caspase-3 protein were detected by Western blot. RESULTS As compared with control group， inhibition rate， apoptotic rate， MDA content， IL-6/TNF-α protein expression， ICAM-1 /CAM-1 mRNA expression， NF-κB p65 nuclear translocation， TLR4， nuclear NF-κB p65 and cleaved caspase-3 protein expression rose obviously in model group （P<0.05） while migration number， SOD and cytoplasmic NF-κB p65 protein expression dropped markedly （P<0.05）. As compared with model group， cellular inhibition rate， apoptotic rate， MDA content， IL-6/TNF- α protein expression， NF-κB p65 nuclear translocation， TLR4， nuclear NF-κB p65 and cleaved Caspase-3 protein expression decreased significantly （P<0.05） while migration number， SOD and cytoplasmic NF-κB p65 protein expression spiked significantly in low/middle/high-dose group （P<0.05）. The mRNA expression of ICAM-1/VCAM-1 declined markedly in middle/high-dose group （P<0.05）. All parameters were worse in medium-dose +KLA group than those in medium-dose group. CONCLUSION Inflammatory injury of vascular endothelial cells induced by LPS may be correlated with nuclear translocation of NF-κB p65 in TLR4/NF-κB pathway. And 1，8-cineole may treat vascular endothelial cell injury through suppressing NF-κB p65 nuclear translocation， blunting inflammatory response， lowering oxidative stress and reducing vascular endothelial cell adhesion.
OBJECTIVE To establish the characteristic chromatogram of Gangmei Qingyan Mixture （GQM） with high performance liquid chromatography （HPLC） and simultaneous content determination of multiple characteristic components. METHODS HPLC was utilized for establishing the characteristic atlas of 10 batches of GQM， evaluating their similarity， determining the common characteristic peaks and assigning the common peaks. Stoichiometric analysis was performed through taking the common peak area of characteristic map as a variable. The differential components were screened out according to the importance projection （VIP） value of variable >1. And the contents of 6 characteristic chemical components were determined simultaneously. RESULTS A total of 21 common characteristic peaks were identified in 10 batches of GQM. The similarity of 10 preparation batches was >0.950 and 11 characteristic peaks were detected when compared with control products. The results of cluster analysis （CA） and principal component analysis （PCA） revealed that 10 batches of samples could be classified into three distinct categories. The results of orthogonal partial least squares discriminant analysis （OPLS-DA） indicated that 10 components were screened out for components with VIP value >1， namely 4 （gallic acid）， 10/9 （caffeic acid）， 13/8 （cryptochlorogenic acid）， 2/3/17 （isochlorogenic acid C）， 15 （isochlorogenic acid A） and 7 （chlorogenic acid）. The contents of gallic acid， chlorogenic acid， cryptochlorogenic acid， caffeic acid， isochlorogenic acid A and isochlorogenic acid C in 10 batches of samples were （0.097-0.591）， （0.055-0.131）， （0.051-0.20）， （0.402–1.171）， （0.019-0.104） and （0.013-0.123） mg·mL–1. CONCLUSION Both stable and feasible， HPLC characteristic mapping may be employed for quality control of GQM.
OBJECTIVE To establish a high performance liquid chromatography （HPLC） method for measuring linezolid in human plasma and create a clinical sampling process based upon a whole blood stability study to enhance the comprehensive investigation of whole blood stability and advance the clinical sampling procedure， offering references for precise linezolid therapeutic drug monitoring （TDM） and personalized drug dosing scheme formulation， as well as fostering the standardization and uniformity of anti-infective drug TDM system. METHODS Plasma samples were treated with an internal standard （cefoperazone） and precipitated with a solution of acetonitrile （0.1% formic acid）. The supernatant was diluted with water （1∶1，V/V） and subsequently loaded. Separation of the components was achieved on a Shim-pack GIST C18 column （4.6 mm×250 mm， 5.0 μm） with a mobile phase consisting of 50 mmol·L–1 potassium dihydrogen phosphate containing 0.05% formic acid-acetonitrile （75∶25，V/V）. Flow rate was set at 1.0 mL·min–1. Detection was performed at a wavelength of 254 nm and a column temperature of 40 ℃. The study examined the stability of linezolid in whole blood and plasma samples under varying temperatures and sampling vessels. Based upon the findings from the analysis of whole blood stability， the development of clinical sampling and testing protocols and the clinical implementation of TDM were implemented. RESULTS The concentration range of linezolid exhibited a strong linear relationship within a range of 0.59–23.40 μg·mL–1 （r2>0.999）. The lower limit of quantization was 0.59 μg·mL–1. The extraction recoveries for low， medium and high concentrations were 95.97%–111.35%. Additionally， intraday and daytime precision RSD values were <8.72%. The linezolid in whole blood samples in heparin sodium collection tubes remained stable within 24 h at room temperature （18–23 ℃） and in a 4 ℃ refrigerator. It was superior to EDTA-K2 collection tubes under the same conditions （stable within 12 h）. Additionally， plasma quality control samples underwent pretreatment and stabilization in an automatic injector at 6 ℃ for 24 h. Plasma samples remained stable when stored at 4 ℃， room temperature （18–23 ℃） for 24 h， frozen at –80 ℃ for 65 days and subjected to freeze-thaw cycles at –80 ℃ for 3 times. CONCLUSION The utilization of the established linezolid TDM method and clinical sampling process can effectively maintain the stability of linezolid and enhance the precision of test outcomes. Furthermore， these practices may offer valuable references for the standardization and harmonization of linezolid TDM procedures.
OBJECTIVE To explore the effect of genistein on metabolism of short-chain fatty acids （SCFAs） in mice with ulcerative colitis （UC） induced by dextran sulfate sodium salt （DSS） using targeted metabolomics. METHODS Twenty-seven specific pathogen free （SPF） male Balb/c mice were randomized into 3 groups. No intervention was applied in control group while UC model was constructed by giving DSS drinking water （5%， W/V） in model and treatment groups. After successful modeling， treatment group received an intragastric injection of genistein （15 mg·kg–1） while model group had the same amount of saline for 7 days. Additionally， disease activity index （DAI） scores were performed. At the end of experiment， pathological observations of colon were made by hematoxylin-eosin （HE） stain and serum levels of interleukin-10 （IL-10）， interleukin-6 （IL-6）， tumor necrosis factor-alpha （TNF-α）， interleukin-1β （IL-1β） and transforming growth factor-beta （TGF-β） were measured by enzyme-linked immunosorbent assay （ELISA）. And the level of SCFAs in intestinal contents were performed by gas chromatography mass spectrometry （GC-MS）. RESULTS Pathological examinations revealed genistein could restore mucosal structure significantly and alleviate inflammatory infiltration. Moreover， model group had lower levels of IL-10 and TGF-β and higher levels of IL-6， TNF-α and IL-1β than normal group （P<0.05）. There were higher levels of IL-10 and TGF-β and lower levels of IL-6， TNF-α and IL-1β in treatment group as compared with model group （P<0.05）. The findings of targeted metabolomic analysis indicated differences in distance between model and normal groups using orthogonal partial least squares discriminant analysis （OPLSDA）. Treatment group approximated normal group. The quantitative data of SCFAs showed a downward trend of acetic acid， butyric acid， and propionic acid and an upward trend of valeric acid in model group as compared with normal group （P<0.05）. Furthermore， as compared with model group， an upward trend was observed in acetic acid， butyric acid and propionic acid along with a downward trend in valeric acid （P<0.05）. CONCLUSION Genistein has been shown to exhibit related efficacy through alleviating mucosal barrier injury， mitigating inflammatory infiltration， reducing the levels of pro-inflammatory factors IL-6， TNF-α and IL-1β， increasing the levels of acetic acid， butyric acid and propionic acid in SCFAs and suppressing the levels of valeric acid in UC model.
OBJECTIVE To establish an inductively coupled plasma mass spectrometer （ICP-MS） method for the determination of 12 metal impurities （Mg， Al， V， Cr， Mn， Co， Ni， Cu， As， Cd， Tl & Pb） in the contents and capsule shell of valsartan capsules and conduct health risk assessments of 4 hazardous elements. METHODS The contents and shell of valsartan capsules were digested by microwave respectively. The contents of 12 metal impurity elements were determined by ICP-MS standard curve with Sc， Ge， In and Bi as internal standards. Moreover， hazard quotient （HQ i ） and hazard index （HI） were utilized for evaluating the health risk of Cr， Ni， Cu and Pb. RESULTS The correlation coefficients of calibration curves of 12 metal impurity elements were all >0.999. The spiked recoveries of the contents ranged from 81.2% to 113.4%， And the spiked recoveries of capsule shells were between 83.2% and 117.4% with RSD <15%. The results of health risk assessment showed that hazard index （HI） of Cr， Ni， Cu and Pb elements in contents and shells were <1. CONCLUSION The established ICP-MS method is simple， rapid and accurate for determining 12 metal impurity elements in the contents and shells of valsartan capsules. And the exposure values of Cr， Ni， Cu and Pb in 16 batches of valsartan capsules have no significant health risk.
OBJECTIVE To evaluate the effects of fistular onion bulb （FOB） extract on oxidative stress and apoptosis in hypoxia/reoxygenated H9c2 cardiomyocytes through regulating HIF-1α/VEGF pathway. METHODS Hypoxia/reoxygenation （H/R） cell model was constructed by H9c2 rat cardiomyocytes with a reoxygenation time of 24 h as determined by cell morphology observation and CCK-8 assay. The cells were assigned into five groups of control， H/R， H/R+FOB， H/R+YC-1 （HIF-1α inhibitor） and H/R+YC-1+FOB. Cell proliferation activity was assessed by CCK-8 while cell apoptosis by flow cytometry. The contents of reactive oxygen species （ROS） were detected by flow cytometry and malondialdehyde （MDA） and level of lactate dehydrogenase （LDH） by biochemical kits. Western blot was utilized for determining the protein expression levels of Bax， Bcl-2， hypoxia-inducible factor-1α （HIF-1α） and vascular endothelial growth factor （VEGF）. RESULTS As compared with control group， cell proliferation activity and apoptotic rate decreased in H/R group （P<0.05） while the contents of ROS， MDA and LDH rose significantly （P<0.05）. Additionally， apoptosis-related protein Bax was up-regulated （P<0.05） while Bcl-2 down-regulated （P<0.05）. Protein expression levels of HIF-1α/VEGF pathway became elevated （P<0.05）. As compared with H/R group， cell proliferation activity spiked obviously in both H/R+FOB and H/R+YC-1 groups （P<0.05） while apoptotic rate decreased （P<0.05）. Furthermore， the contents of ROS， MDA and LDH all declined （P<0.05） while Bcl-2 protein was up-regulated （P<0.05）. The protein expressions of Bax， HIF-1α and VEGF all decreased （P<0.05）. CONCLUSION FOB may suppress the activation of HIF-1α/VEGF pathway， resulting in lower oxidative stress and slower apoptosis within hypoxic/reoxygenated cardiomyocytes， ultimately alleviating cellular injury .
OBJECTIVE To explore the potential hepatotoxic mechanism of Polygoni multiflori caulis （PMC） through network pharmacology and molecular docking techniques. METHODS Based upon the literature data， the relevant databases of TCMSP， TCMID and HIT were searched for identifying the major active ingredients of PMC， as well as target proteins associated with drug-induced liver injury （DILI）. Intersection analysis of PMC/DILI targets was performed for acquiring core intersecting targets. Protein-protein interaction network， KEGG pathway and GO enrichment analyses were performed with information from core intersecting targets. Molecular docking was performed with AutoDock version 1.5.7. And the docking results were visualized with PyMOL software. Finally， the results were preliminarily validated through in vitro experiments， toxicology databases and in vivo experiments. RESULTS Network pharmacology indicated that PMC could interact with targets such as BCL2 and EGFR， leading to DILI through cancer and PI3K-AKT signaling pathways， etc. Important active ingredients included emodin， chrysophanol and chrysophanol-8-O-β-D-glucopyranoside. Molecular docking results showed stable binding affinity between active ingredients and core targets. In vitro validation assays demonstrated cytotoxicity of emodin and physcion-8-O-β-D-glucoside. And in vivo validation assays revealed potential hepatotoxicity of emodin consistent with the screening results of network pharmacology. CONCLUSION Network pharmacology and molecular docking techniques are applied for a preliminary exploration of the components， mechanisms， targets and pathways of PMC-induced liver injury， providing data supports for further clinical application researches and elucidating the underlying mechanisms.
OBJECTIVE To explore the adverse consequences of obesity plus Candida albicans （CA） infection and examine the therapeutic effect of fluconazol （FLC） in combination with piperlonguminine （GBN）. METHODS A model of high-fat diet （HFD） obese mice plus invasive Candida albicans infection was constructed. Different drugs were dosed. Death， organ mass， renal load and renal histopathological morphology were detected. The serum levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein-C （LDL-C） and high-density lipoprotein-C （HDL-C） were measured. And the levels of neutrophil extracellular traps （NETs） in intraperitoneal lavage fluid were quantified， as well as the expressions of inflammatory factors transforming growth factor-beta （TGF-β）， interleukin-6 （IL-6）， monocyte chemotactic protein-1 （MCP-1） and keratinocyte-derived chemokine （KC） in renal tissues. In vitro assays were performed using all-trans retinoic acid （ATRA） for inducing differentiation of HL-60 cells into neutrophil-like granulocytes （dHL-60）. dHL-60 cells were pre-treated with GBN and stimulated by phorbol ester （PMA）. The intracellular levels of reactive oxygen species （ROS） and NETs were detected. RESULTS Obese mice infected with CA had dramatically lower survival， elevated renal load and higher levels of lipids and NETs. FLC in combination with GBN restored survival to 100% in obese infected mice and improved visceral indices， while further reducing renal load， lipids， inflammatory factors and NETs. In vitro results indicated that GBN reduced the levels of reactive oxygen species （ROS） and NETs generated by PMA-stimulated neutrophils. CONCLUSION CA infection in obese mice is associated with higher mortality and severe inflammatory response in vivo. GBN regulates the inflammatory state through suppressing ROS production and NETs release from neutrophils and ameliorates infection in obese mice in combination with FLC.
OBJECTIVE To compare the quality differences between steamed tablets produced from dried and fresh Citrus medica L. var. sarcodactylis Swingle and examine the chemical constituents related to "dryness" of raw product. METHODS Total flavonoid content was determined by ultraviolet （UV） method while the levels of naringin， hesperidin， scopoletin， diosmin， 5，7-dimethoxycoumarin and bergapten were quantified with high performance liquid chromatography （HPLC）. Volatile components were analyzed by gas chromatography-mass spectrometry （GC-MS） and quality differences among various steamed tablets were compared. RESULTS Fresh steamed tablets showed slightly higher levels of total flavonoid content and major components as compared with dried steamed tablets. Specifically， total flavonoids， hesperidin， artemisinin lactone and 5，7-dimethoxycoumarin in fresh steamed tablets and dried steamed tablets were 2.321， 0.061， 6.902， 1.113 mg·g–1 and 2.297， 0.054， 6.452， 1.069 mg·g–1， respectively. As compared with raw tablets， steaming resulted in an elevation of artemisinin lactone content but a decline of 5，7-dimethoxycoumarin level， with no significant change in other components. Ten components in dried steamed tablets and seven in fresh steamed tablets showed lower relative content as compared with raw tablets. Notably， four components of 4，7，7-trimethylbicyclo［4.1.0］hept-2-ene， linalool， （-）-4-terpineol and α-terpineol decreased in both steaming methods. CONCLUSION A higher content of key components in fresh steamed tablets suggests that steaming fresh slices may reduce the need for additional processing steps. The comparison of steamed and raw products indicated that volatile components decrease after steaming. And these volatile constituents may be responsible for "dryness" associated with Citrus medica L. var. sarcodactylis Swingle.
OBJECTIVE To explore the clinical efficacy and safety of rivaroxaban for head and neck venous thromboembolism （VTE）. METHODS From December 2015 to January 2022， for this retrospective cohort study， 291 patients with head and neck VTE were recruited at Nanjing Drum Tower Hospital. Based upon specific anticoagulants， they were assigned into two groups of warfarin and rivaroxaban. Follow-up period was at least 2 years. Baseline profiles， recurrent VTE and bleeding events were recorded for two groups. Inverse probability of treatment weighting （IPTW） was employed for balancing the inter-group differences in baseline profiles. Kaplan-Meier curve and multivariate COX proportional hazard model were utilized for comparing the inter-group differences in recurrent VTE and bleeding events. RESULTS After stable IPTW， there was no significant inter-group difference in baseline profiles. And no statistically significant inter-group difference existed in rates of recurrent VTE， all bleeding events and major bleeding events （HR=0.64， 95%CI： 0.30-1.31； HR=0.47， 95%CI： 0.20-1.11； HR=0.65， 95%CI： 0.23-1.85）. Renal function hinted at significant interaction with treatment group in terms of all bleeding events and major bleeding events （P=0.012； P=0.048）. CONCLUSION Rivaroxaban has similar anticoagulation efficacy and safety to warfarin in patients with head and neck VTE.
OBJECTIVE To evaluate the economics of transdermal donepezil patch （TDP） versus tablets for Alzheimer's disease （AD） from the perspective of the whole society and provide references for the relevant health decision-making. METHODS A Markov model with four states of mild， moderate， severe and death was developed on the basis of disease progression. Cost-effectiveness analysis was performed. Incremental cost-effectiveness ratio （ICER） was utilized as an index for evaluating the economics of TDP as compared with tablets. And the results were analyzed for sensitivity. RESULTS ICER of TDP versus tablets was 590 606.15 yuan/QALY. It was much higher than 3 folds per capita gross domestic product （GDP） in 2022. TDP was not economical. Sensitivity analyses revealed that severe state utility value， cost of TDP and mild state utility value had the greatest impact on the results； with a willingness-to-pay threshold of 3 folds GDP per capita in 2022， the probability of TDP being economical was zero. CONCLUSION From the perspective of the whole society， TDP is not economical as compared with tablets for AD.
OBJECTIVE To explore the influencing factors of prevention failure of chemotherapy-induced nausea and vomiting （CINV） in breast cancer patients and construct its prediction model. METHODS From January 2022 to December 2023， retrospective study was conducted for 450 breast cancer patients on chemotherapy at Fuyang People's Hospital. They were assigned into two groups of failure and control according to whether or not there was prevention failure of CINV. Multivariate logistic regression analysis was performed for examining the influencing factors of prevention failure of CINV. Receiver operating characteristic （ROC） curve was plotted for exploring the value of prediction model for prevention failure of CINV. RESULTS Among them， 130 cases had prevention failure of CINV. Numeric rating scale （NRS）（OR=0.501， 95%CI： 0.350-0.716， P＜0.01）， anxiety status （OR=4.169， 95%CI： 2.175-7.991， P=0.000），high risk of vomiting （OR=68.528， 95%CI：8.807-533.203， P＜0.01）， risk of intermediate vomiting （OR=3.154， 95%CI： 1.686-5.902， P＜0.01）， low risk of vomiting （OR=5.367， 95%CI： 2.280-12.632， P＜0.01）， oral preparation of proprietary Chinese medicine （OR=12.780，95%CI：6.321-25.836， P＜0.01） and serum albumin （OR=0.923， 95%CI： 0.862-0.989， P=0.023） were independent risk factors for prevention failure of CINV. Logit （P1）=0.297–0.692×NRS+1.428×anxiety status +4.227×high risk of vomiting or 1.149×risk of intermediate vomiting or 1.680×low risk of vomiting+2.548×cinobufacini capsule–0.08×serum albumin， the accuracy of internal and external validation sets was 91.67% and 86.67% respectively. CONCLUSION The risk prediction model constructed based upon NRS/anxiety status/high risk of vomiting/risk of intermediate vomiting/low risk of vomiting/cinobufacini capsule/serum albumin has demonstrated an excellent performance.
OBJECTIVE To explore the correlation between early interferon spray intervention and rehospitalization rate due to pneumonia within the first 2 years after discharge from Neonatal Intensive Care Unit （NICU） among preterm infants diagnosed with broncho-pulmonary dysplasia （BPD）. METHODS Preterm infants with a gestational age of <32 weeks and a diagnosis of moderate BPD at discharge in Affiliated Zhongshan Hospital， Xiamen University， between July 2018 and June 2023 were recruited. The observation group consisted of 22 cases subjected to early interferon spray intervention， triggered either when close contacts displayed evident respiratory symptoms or when infants presented with symptoms such as cough， nasal congestion， pharyngeal congestion or fever. The control group comprised 24 cases without early intervention. The study compared the frequency of rehospitalization， duration of each hospitalization and antibiotics use density （AUD） within the initial 2 years post-NICU discharge between two groups. RESULTS In control group， mean frequency of rehospitalization， hospitalization stay and AUD were （6.13±1.54） times， （7.31±1.52） days and 14.26±0.38 vs. （4.00±1.38） times， （6.89±1.30） days， and 11.61±3.63 in observation group. The inter-group differences were statistically significant with P-values of 0.000， 0.029 and 0.001. CONCLUSION In infants with moderate BPD， early interferon spray intervention is associated with a lower rehospitalization rate due to pneumonia， shorter hospitalization stay and lower AUD. These findings offer valuable clinical insights.
OBJECTIVE To explore the relationship between polymorphisms of azathioprine metabolizing enzymes and transporters and the levels of 6-thioguanine nucleotides （6-TGNs） and leukocytes in patients of Crohn's disease （CD）. METHODS A total of 74 Han patients on a treatment of azathioprine for over 3 months at First Affiliated Hospital of Anhui Medical University were recruited. The steady-state trough concentration of 6-TGNs in red blood cells was measured by high performance liquid chromatography （HPLC）. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was utilized for detecting 22 loci of single nucleotide polymorphisms， including TPMT rs1142345. The correlations between genotypes， concentration of 6-TGNs and levels of white blood cells were examined by univariate and multiple linear regression analyses. RESULTS The results of univariate and multivariate regression analyses revealed that the elevations in absolute or relative concentrations of 6-TGNs were associated with mutants of TPMT rs1142345 and ITPA rs1127354. No correlation existed between NUDT15 rs116855232 mutation and the levels of 6-TGNs and white blood cells. However， patients of CT genotype had significantly lower median standard doses as compared with those with wild-type （CC） genotype （P<0.05）. ATIC rs3821353 mutation served as an independent risk factor for predicting lymphocyte reduction in patients on a treatment of azathioprine. CONCLUSION Detecting TPMT rs1142345， ITPA rs1127354， ATIC rs3821353， NUDT15 rs116855232 genotypes， as well as 6-TGNs and leukocyte levels in CD patients before and after azathioprine dosing are vital in lowering the risk of azathioprine-induced leukopenia and improving therapeutic efficacy.
OBJECTIVE To excavate the patterns and characteristics of adverse reactions of PD-1 inhibitors and provide rationales for patient medication safety. METHODS The adverse reactions of PD-1 inhibitor collected by Shandong ADR Monitoring Center from April 2019 to May 2023 were retrieved. Statistical analysis was performed on types of adverse reactions， severity， unintended or not， patient gender， age， outcome and involved organs/systems. RESULTS Among 1 056 reports of adverse reactions related to PD-1 inhibitors， males dominated （74.91%） with age mostly over 65 year （49.53%）. A total of 18 system organ classifications （SOCs） and 1 672 preferred terms （PTs） were involved， with choking sensation as a PT not reported for any of the drugs. And 609 patients with severe ADR occurred， accounting for 57.67%. A comparison of different factors leading to severe adverse drug reaction revealed a significant statistical difference between group with serious adverse drug reactions and group with general adverse drug reaction during off-label drug uses and the previous of adverse drug reaction/event. CONCLUSION Clinicians should pay a high alert for the occurring patterns and characteristics of adverse reactions of PD-1 inhibitors and strengthen the monitoring of adverse drug reactions to ensure the safety of drug dosing.
OBJECTIVE To explore the clinical features， treatments， pathogenic mechanisms and preventive measures of myocarditis due to immune checkpoint inhibitors （ICIs） and provide reference for clinical safe dosing. METHODS Through searching marketed ICIs in combination with "myocarditis"， case reports on immune myocarditis induced by ICIs were retrieved from the databases of China National Knowledge Infrastructure （CNKI）， Wanfang and PubMed. RESULTS A total of 84 articles and 88 cases were collected. Pembrolizumab was the most commonly reported， followed by sintilimab and camrelizumab. Average age was （64.33±9.84） year and elders predominated. There were 63 males （71.6%） with a mortality rate of 21.6%. The most common clinical symptoms were dyspnea or tachypnea （44.3%， 39/88）. Most symptoms occurred after 1-2 cycles of medication （81.8%， 72/88） and over 90% of them exhibited elevated levels of cardiac biomarkers. Among 84 cases （95.5%） on glucocorticoid therapy， the symptoms of 67 cases （79.8%） improved. And treatments with other immunosuppressants， plasma exchange， implanted pacemaker or extracorporeal membrane oxygenation （ECMO） could further improve clinical symptoms. CONCLUSION ICIS-induced immune myocarditis is predominant in elderly males and clinical symptoms are non-specific. Glucocorticoid therapy is effective. And immunosuppressants， plasma exchange， implanted pacemaker and ECMO may improve clinical symptoms and survival rate. The mortality rate of ICIS-induced immune myocarditis remains high so that clinicians should raise a high alert.
OBJECTIVE To explore the feasibility of using tenofovir fumarate and telbivudine for blocking mother-to-child transmission of hepatitis B virus （HBV） during late pregnancy. METHODS From January 2017 to October 2022， 204 pregnant women hospitalized with HBV infection in late pregnancy were selected. They were assigned into two groups of tenofovir fumarate （TDF） and telbivudine （LDT） according to specific medications. General profiles， HBsAg， HBeAg， HBV-DNA， alanine aminotransferase （ALT） and adverse reactions of two groups was compared. RESULTS HBsAg， HBeAg， baseline HBV-DNA and postpartum HBV-DNA levels were lower in LDT group than those in TDF group （P<0.05）. The serum levels of HBV DNA dropped markedly in both groups as compared with pre-treatment values. In TDF group， HBV DNA dropped from （7.4±1.2） to （3.6±1.1） lg copies·mL–1 （P<0.05） versus （7.3±1.1） to （4.1±1.2） lg copies·mL–1 in LDT group （P<0.05）. No statistically significant inter-group difference existed in serum ALT level before or after treatment. A few parturients experienced a slight elevation of ALT after discontinuing drugs. However， all normalized within 3 months. No maternal discontinuation due to adverse reactions occurred in neither groups. TDF group reported a higher incidence of nausea， vomiting， abdominal distension， loss of appetite， diarrhea and gastric pain as compared with LDT group （P<0.05）. Conversely， joint pain and fatigue were more prevalent in LDT group than those in TDF group （P<0.05）. And no significant difference existed in other symptoms （P>0.05）. Additionally， the incidence of neonatal adverse events， including asphyxia， premature birth， low birth weight， macrosomia， pathological jaundice and pneumonia， showed no significant inter-group differences （P>0.05）. CONCLUSION Using TDF or LDT in the third trimester of pregnancy significantly may lower HBV infection rate in neonates， offering theoretical rationales for researches on preventing mother-to-child transmission of HBV.
OBJECTIVE To promote the efficiency of prescription reviews through a homogeneous management of ophthalmic glucocorticoids. METHODS Evidence-based information of 38 ophthalmological diseases was retrieved from the databases of VIP， China National Knowledge Infrastructure （CNKI）， WANFANG DATA， Medlive， DXY， Baidu Library， PubMed， Cochrane Library， Canadian Medical Association： Clinical Practice Guideline and official websites of some ophthalmological societies. Appraisal of Guidelines Research and Evaluation Ⅱ （AGREE Ⅱ） was utilized for evaluating these guidelines and literature items. Detailed rules were formulated for reviewing the prescriptions of ophthalmic glucocorticoids. RESULTS Two reviewers with or without glucocorticoid review experience applied the review rules for 896 prescriptions in 2022. It took 2 and 2.5 hours and reasonable rates were 33.4% and 33.8%. The percentage of prescriptions failing to complete reviews decreased by 24.1%. CONCLUSION Formulating detailed rules is conducive to promoting the development of reviewing ophthalmic glucocorticoid prescriptions.
