OBJECTIVE To explore clinical characteristics and risk factors of drug-induced hypofibrinogenemia， providing a reference for rational clinical drug use. METHODS Retrospective case analyses literature on drug-induced hypofibrinogenemia were collected from domestic and international databases from their inception to December 31， 2024. The patients’ gender， age， fibrinogen （FIB） levels before and after treatment， drug types， the incidence of drug-induced hypofibrinogenemia， time of occurrence， bleeding rates， clinical manifestations， risk factors， and protective factors were all analyzed. RESULTS A total of 40 retrospective case analysis studies were included， involving 17 313 patients. Patient age ranged from 0.83 to 78.40 years， with males accounting for 16.90%-81.00%. The involved drugs comprised 5 categories and 13 specific agents， including tigecycline， snake venom hemocoagulase， tocilizumab， and alteplase， etc. The incidence of drug-induced hypofibrinogenemia ranged from 0 to 100%， occurring between 2 hours and 9 months after drug administration， and FIB levels rebounded in most patients after drug discontinuation. The bleeding rate varied from 0% to 91.30%， including epistaxis， airway bleeding， gastrointestinal bleeding， and cerebral hemorrhage. Risk factors included high drug dosage， prolonged treatment duration， abdominal infection， advanced age， and low baseline FIB levels. Protective factors were only mentioned in studies on tigecycline， including skin and soft tissue infections and high baseline FIB levels. CONCLUSIONS Drug-induced hypofibrinogenemia is commonly associated with tigecycline， hemocoagulase， and tocilizumab. Its clinical features vary depending on the drug， and risk factors include high drug dosage， prolonged treatment， low baseline FIB levels， and advanced age. For high-risk medications， individualized medication management and monitoring of FIB levels are recommended.

ObjectiveTo investigate the clinical efficacy and potential mechanism of Shengmai Jiuxin decoction in the treatment of acute decompensated heart failure （ADHF） with the traditional Chinese medicine （TCM） pattern of Qi and Yin deficiency， Yang deficiency， and blood stasis. MethodsA total of 68 patients diagnosed with ADHF of Qi and Yin deficiency， Yang deficiency， and blood stasis type were randomly assigned to an observation group （34 cases） and a control group （34 cases）. Both groups received conventional Western medical treatment， while the observation group was additionally administered Shengmai Jiuxin decoction. Parameters compared before and after treatment included： TCM syndrome score， TCM syndrome efficacy， New York Heart Association （NYHA） functional classification， left ventricular ejection fraction （LVEF）， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， six-minute walk distance （6MWD）， hypoxia-inducible factor-1 alpha （HIF-1α）， vascular endothelial growth factor A （VEGF-A）， Caspase-3， and the number of rehospitalizations for heart failure within one month after discharge. ResultsThere were no significant differences in sex， age， vital signs， or underlying diseases between the two groups. Compared with baseline， both groups exhibited significant reductions in TCM syndrome scores， NT-proBNP， and HIF-1α levels （P<0.01）， as well as significant increases in 6MWD， LVEF， VEGF-A， and Caspase-3 levels （P<0.05， P<0.01）. After treatment， the observation group showed significantly greater reductions in TCM syndrome score， NT-proBNP， HIF-1α， and Caspase-3 levels compared with the control group （P<0.05） and significantly greater increases in 6MWD， TCM syndrome efficacy， and VEGF-A levels （P<0.05）. No significant differences were observed between the groups in NYHA functional classification， LVEF， or the number of rehospitalizations for heart failure within one month after discharge. No drug-related adverse events were reported in either group during the treatment period. ConclusionShengmai Jiuxin decoction can improve cardiac function and clinical symptoms in patients with ADHF of Qi and Yin deficiency， Yang deficiency， and blood stasis type. Its mechanisms may be related to the regulation of the HIF-1 signaling pathway by modulating targets such as HIF-1α， VEGF-A， and Caspase-3.

ObjectiveTo investigate the clinical efficacy and potential mechanism of Shengmai Jiuxin decoction in the treatment of acute decompensated heart failure （ADHF） with the traditional Chinese medicine （TCM） pattern of Qi and Yin deficiency， Yang deficiency， and blood stasis. MethodsA total of 68 patients diagnosed with ADHF of Qi and Yin deficiency， Yang deficiency， and blood stasis type were randomly assigned to an observation group （34 cases） and a control group （34 cases）. Both groups received conventional Western medical treatment， while the observation group was additionally administered Shengmai Jiuxin decoction. Parameters compared before and after treatment included： TCM syndrome score， TCM syndrome efficacy， New York Heart Association （NYHA） functional classification， left ventricular ejection fraction （LVEF）， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， six-minute walk distance （6MWD）， hypoxia-inducible factor-1 alpha （HIF-1α）， vascular endothelial growth factor A （VEGF-A）， Caspase-3， and the number of rehospitalizations for heart failure within one month after discharge. ResultsThere were no significant differences in sex， age， vital signs， or underlying diseases between the two groups. Compared with baseline， both groups exhibited significant reductions in TCM syndrome scores， NT-proBNP， and HIF-1α levels （P<0.01）， as well as significant increases in 6MWD， LVEF， VEGF-A， and Caspase-3 levels （P<0.05， P<0.01）. After treatment， the observation group showed significantly greater reductions in TCM syndrome score， NT-proBNP， HIF-1α， and Caspase-3 levels compared with the control group （P<0.05） and significantly greater increases in 6MWD， TCM syndrome efficacy， and VEGF-A levels （P<0.05）. No significant differences were observed between the groups in NYHA functional classification， LVEF， or the number of rehospitalizations for heart failure within one month after discharge. No drug-related adverse events were reported in either group during the treatment period. ConclusionShengmai Jiuxin decoction can improve cardiac function and clinical symptoms in patients with ADHF of Qi and Yin deficiency， Yang deficiency， and blood stasis type. Its mechanisms may be related to the regulation of the HIF-1 signaling pathway by modulating targets such as HIF-1α， VEGF-A， and Caspase-3.

OBJECTIVE To investigate the establishment and promotion of a new standardized management model for anti- osteoporosis medication after fragility fracture surgery by resident clinical pharmacists， and provide references for resident pharmacists to carry out clinical pharmaceutical services. METHODS From July 2023 to March 2024，595 post-brittle fracture surgery patients were enrolled. Using the PDCA （plan-do-check-act） cycle，resident clinical pharmacists identified issues and conducted investigations in clinical practice. Through integrating clinical pharmacist intervention services before， during and after treatment， a medication treatment pathway was developed， thereby establishing a standardized management model for anti- osteoporosis treatment following fragility fracture surgery. Leveraging the National Brittle Fracture Big Data Platform （under the National Clinical Research Center for Orthopedics and Sports Rehabilitation）， a dedicated data module was constructed， providing big data support to evaluate the efficacy of this pharmaceutical care model. RESULTS Continuous PDCA cycle driven improvements significantly increased the proportion of osteoporosis diagnosis （from 9% before intervention to 81%） and proportion of drug treatment （from 4% to 75%）.The proportions of bone density and bone metabolism testing also rose markedly，positively impacting long-term patient outcomes. CONCLUSIONS The establishment of a standardized management model for anti- osteoporosis treatment following fragility fracture surgery by resident clinical pharmacists has enhanced clinicians’ diagnostic and therapeutic capabilities for osteoporosis， ensures rational medication use in osteoporosis patients， and demonstrates significant potential for widespread adoption and application.

Objective To investigate the effects and mechanisms of peimine(PME)on chronic obstructive pulmonary disease(COPD)in mice.Methods The mice were randomly divided into 4 groups(20 mice in each group),control group,PME group,chronic obstructive pulmonary disease group and treatment group.Animal models of COPD were induced in mice by lipopolysaccharide combined with smoke.The effects of PME on COPD model mice was analyzed by HE staining,transmission electron microscopy and the ratio of wet/dry weight of mouse lung tissue.The effects of PME on COPD model mice were analyzed by HE staining,transmission electron microscopy and the ratio of wet/dry weight of mouse lung tissue.The effects of PME on inflammatory factor tumor necrosis factor(TNF)-α,interleukin(IL)-6 and IL-1β in lung tissue were analyzed by ELISA and Western blotting.The effects of PME on oxidative stress in lung tissue were analyzed by dihydroethidium(DHE)staining and Western blotting.The effects of PME on nuclear factor kappa-B(NF-κB)pathway and nuclear factor erythroid 2-related factor 2(Nrf2)pathway were analyzed by protein immunoblotting.Results Compared with the COPD group,PME treatment could significantly improve the lung tissue injury and the number of inflammatory cells in mice,and the wet/dry weight ratio of lung tissue was significantly reduced.Compared with the control group,the levels of TNF-α,IL-6 and IL-1β in the alveolar lavage fluid of COPD mice significantly increased,and the level of TNF-α,IL-6 and IL-1β in the alveolar lavage fluid of mice after PME treatment was significantly reduced.In addition,compared with the control group,the protein expression of TNF-α,IL-6 and IL-1β in the lung tissue of COPD mice significantly increased,and the level of TNF-α,IL-6 and IL-1β in the lung tissue of COPD mice after PME treatment were significantly reduced.Immunohistochemistry and Western blotting showed that the level of superoxide dismutase 2(SOD2)protein in COPD group was significantly lower than that in control group,while PME treatment could improve the level of superoxide dismutase protein.The analysis of MDA content in lung tissue showed that compared with the COPD group,the production of MDA in lung tissue of COPD mice was significantly inhibited after PME treatment.Protein Western blotting showed that PME treatment could prevent the phosphorylation of inhibitor of NF-κB(IκBα)and the transfer of NF-κB p65 to the cell nucleus,and the expression of Nrf2 and its main downstream target heme oxygenase-1(HO-1)in the lung tissue of mice treated with PME significantly increased.Conclusion PME is able to inhibit inflammation and oxidative stress and improve lung tissues damage in the COPD model in vivo and this protection effect might be both the Nrf2 pathway activation and NF-κB pathway inhibition.

Objective To construct reference ranges of cardiac size and morphologic parameters in low-risk fetuses at 28-39 gestational weeks using two-dimensional speckle tracking technique.Methods A prospective collection of 453 low-risk singleton pregnancies with echocardiography at Obstetrics and Gynecology Hospital,Fudan University was used to assess the size(length,width,and area)and morphology(sphericity index,i.e.,the ratio of length to width)of the fetal four-chamber view and two ventricles using two-dimensional speckle tracking technique.Repeated inter-and intra-observer agreement of measurements was assessed using the intraclass correlation coefficients(ICCs).Statistical analysis of cardiac measurement parameters was performed to establish reference ranges of values for cardiac size and morphology in low-risk fetuses.Results The inter-and intra-group ICCs for reproducibility tests of fetal cardiac parameters measurements were 0.691 to 0.980.Fetal four-chamber view and ventricular size increased with gestational week(all P<0.001),the end-diastolic length of the left ventricle was larger than that of the right ventricle,and the end-diastolic diameter was smaller than that of the right ventricle(both P<0.001),while there was no significant difference in the end-diastolic area of the two ventricles(P= 0.050).The spherical index of four-chamber view did not correlate with gestational week(P=0.811).The sphericity index of the basal and intermediate segments of the left ventricle was greater than that of the right ventricle,and the sphericity index of the apical segment was less than that of the right ventricle,the differences were statistically significant(all P<0.01).Conclusion The two-dimensional speckle tracking technique for measuring fetal cardiac parameters has good reproducibility.The reference ranges for cardiac size and morphology in low-risk fetuses developed in this study will be useful for prenatal evaluation of cardiac remodeling.

Objective To investigate the characteristics,clinical indicators and risk factors of levofloxacin-induced arrhythmias in large hospitalized populations.Methods Using the"Adverse Event Active Monitoring and Intelligent Assessment Alert System-Ⅱ"(ADE-ASAS-Ⅱ),the electronic medical record of inpatients using levofloxacin in 2019 was monitored to obtain relevant data for patients with arrhythmias.Patients without arrhythmia were selected by propensity score matching,and the risk factors of levofloxacin-induced arrhythmias were analyzed by univariate and multivariate conditional logistic regression.Results The incidence of levofloxacin-induced arrhythmias was 1.64％in 12 879 people who used levofloxacin.The incidence in people over 65 years was 3.22％.The main manifestations of levofloxacin-induced arrhythmias were extrasystole(0.84％),tachycardia(0.63％),QT interval prolongation(0.44％),and no severe arrhythmias such as torsades de pointes and ventricular fibrillation.Multivariate Logistic regression analysis showed that the course of administration(OR=1.030,95％CI 1.009 to 1.050,P=0.004)and intravenous administration(OR=2.392,95％CI 1.478 to 3.870,P＜0.001)independent risk factors for levofloxacin-induced arrhythmias.Conclusion Arrhythmias caused by levofloxacin are common and have various types,among which the occurrence of QT interval prolongation is occasional.We should pay more attention to elderly patients who receive intravenous levofloxacin and try to avoid long courses of medication.

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Objective To develop the functions and optimize the automatic monitoring module for arrhythmias of the adverse drug event active surveillance and assessment system-Ⅱ,in order to continuously improve the performance,enhance the monitoring efficiency,and explore the ways to optimize the module.Methods Expand and optimize the functions of the module,increase the customized configuration,and determine the optimal setting conditions;compare the optimized test data with the results of the evaluation studies on the automatic monitoring of drug-induced arrhythmias in large samples of medicated population previously,and verify the optimization extent as well as the accuracy of the module.Results In the new module optimized according to the characteristics of the monitoring population,the function of"mandatory medical order keywords"was added,and it was determined that the inclusion of 6 electrocardiogram examination-related medical order keywords with a frequency of not less than 2 occurrences was the optimal configuration condition for the optimization of the module;combining the results of the previous automatic monitoring and evaluation researches,the system functions were verified and compared under the conditions of using the whole drugs and 2 kinds of single drug.While there was no loss of true positive cases,the number of cases with system alarms decreased by 30.75％,80.13％and 90.82％,respectively,compared with that before the optimization of the module,and the positive predictive value was significantly improved.Conclusion After the function expansion and optimization,the automatic monitoring module of drug-induced arrhythmias significantly reduces the labor cost of case evaluation and keeps the accuracy of monitoring results constant;the new module can better adapt to the demands of different automatic monitoring modes and operates stably,which is more generalizable and flexible,and provides a new way of considering for the research and development of automatic monitoring modules.

Objective To obtain the occurrence and clinical characteristics of central nervous system adverse drug reactions(CNS-ADR)associated with three kinds of carbapenems,and to provide reference for clinical drug safety.Methods Based on adverse drug event active surveillance and assessment system-Ⅱ(ADE-ASAS-Ⅱ),retrospective automated monitoring of inpatients using imipenem,meropenem,and biapenem in a tertiary hospital from January 2022 to December 2022 was conducted.The incidence of carbapenem related CNS-ADR was calculated,and the basic conditions,disease conditions,drug use,occurrence time of ADR and symptoms of patients with CNS-ADR were analyzed by descriptive statistics.Results A total of 2 482 patients with 2 709 times of medication were included in this study,and a total of 93 positive cases of CNS-ADR occurred,with an overall incidence of 3.43％for all three medications,3.98％for imipenem,3.51％for meropenem,and 2.78％for biapenem.The indications for the 93 positive cases of CNS-ADR were mainly pulmonary infections(59.13％)and abdominal infections(25.80％);they occurred mostly within 7 days of the administration of the medication;with a variety of clinical manifestations,with anxiety/irritability being the most common,and epilepsy appearing most frequently in severe cases.Co-administration of proton pump inhibitors and cephalosporins accounted for a greater proportion of positive cases,50.54％of positive cases had a history of surgery,and 69.89％of positive cases were associated with electrolyte disturbances.Conclusion Clinical use of carbapenems should be based on the actual situation of the patient to develop an individualised drug regimen,and special attention should be paid to patients with comorbidities of renal disease,electrolyte disorders,and a history of previous surgery and neurological disorders,in order to reduce the risk of the occurrence of CNS-ADR.