ObjectiveTo evaluate the efficacy of Shexiang Baoxinwan in treating stable angina pectoris with Qi stagnation and blood stasis syndrome in patients with coronary artery disease （CAD） complicated with anxiety and depression and explore its underlying mechanisms. MethodsThis study employed a randomized， double-blind， and placebo-controlled clinical trial design. Patients admitted to the hospital were randomly assigned to the observation group and the control group， with 52 patients in each group. Patients in the observation and control groups received Shexiang Baoxinwan and placebo， respectively， both in combination with conventional Western medication. The dose was 45.0 mg， three times daily， for a total duration of eight weeks. The primary outcome was the Seattle Angina Questionnaire （SAQ） scores before and after treatment. Secondary outcomes included changes in traditional Chinese medicine （TCM） syndrome score， the patient health questionnaire-9 （PHQ-9）， generalized anxiety disorder-7 （GAD-7）， inflammatory markers ［interleukin-18 （IL-18）， interleukin-10 （IL-10）， tumor necrosis factor-alpha （TNF-α）， CD40， etc.］， monoamine neurotransmitters ［e.g.， dopamine （DA）］， vascular endothelial function markers ［e.g.， endothelin-1（ET-1）］， adipokines， and ischemia-modified albumin （IMA）. Adverse reactions were also recorded. ResultsA total of 92 patients completed the study， with 44 in the observation group and 48 in the control group. Compared with baseline， both groups showed significant decreases in PHQ-9， GAD-7， and TCM syndrome scores following treatment （P<0.05）， along with a significant increase in SAQ scores （P<0.05）. In the observation group， DA levels were significantly increased （P<0.05）， while levels of IL-18， TNF-α， CD40， ET-1， and IMA were decreased （P<0.05）. In contrast， the control group exhibited significantly increased CD40 levels （P<0.05）. Compared with the control group after treatment， the observation group showed significant improvements in the SAQ dimensions of physical limitation， angina stability， treatment satisfaction， and disease perception， as well as in TCM syndrome score， PHQ-9 score， IL-18， CD40， ET-1， and IMA （P<0.05）. No adverse reactions were observed in either group during treatment. ConclusionShexiang Baoxinwan can improve anxiety and depression， alleviate angina symptoms， and reduce TCM symptoms of Qi stagnation and blood stasis in CAD patients. The mechanism may involve anti-inflammation， improvement of vascular endothelial function， reduction of IMA， and increase of monoamine neurotransmitter levels.

ObjectiveTo evaluate the efficacy of Shexiang Baoxinwan in treating stable angina pectoris with Qi stagnation and blood stasis syndrome in patients with coronary artery disease （CAD） complicated with anxiety and depression and explore its underlying mechanisms. MethodsThis study employed a randomized， double-blind， and placebo-controlled clinical trial design. Patients admitted to the hospital were randomly assigned to the observation group and the control group， with 52 patients in each group. Patients in the observation and control groups received Shexiang Baoxinwan and placebo， respectively， both in combination with conventional Western medication. The dose was 45.0 mg， three times daily， for a total duration of eight weeks. The primary outcome was the Seattle Angina Questionnaire （SAQ） scores before and after treatment. Secondary outcomes included changes in traditional Chinese medicine （TCM） syndrome score， the patient health questionnaire-9 （PHQ-9）， generalized anxiety disorder-7 （GAD-7）， inflammatory markers ［interleukin-18 （IL-18）， interleukin-10 （IL-10）， tumor necrosis factor-alpha （TNF-α）， CD40， etc.］， monoamine neurotransmitters ［e.g.， dopamine （DA）］， vascular endothelial function markers ［e.g.， endothelin-1（ET-1）］， adipokines， and ischemia-modified albumin （IMA）. Adverse reactions were also recorded. ResultsA total of 92 patients completed the study， with 44 in the observation group and 48 in the control group. Compared with baseline， both groups showed significant decreases in PHQ-9， GAD-7， and TCM syndrome scores following treatment （P<0.05）， along with a significant increase in SAQ scores （P<0.05）. In the observation group， DA levels were significantly increased （P<0.05）， while levels of IL-18， TNF-α， CD40， ET-1， and IMA were decreased （P<0.05）. In contrast， the control group exhibited significantly increased CD40 levels （P<0.05）. Compared with the control group after treatment， the observation group showed significant improvements in the SAQ dimensions of physical limitation， angina stability， treatment satisfaction， and disease perception， as well as in TCM syndrome score， PHQ-9 score， IL-18， CD40， ET-1， and IMA （P<0.05）. No adverse reactions were observed in either group during treatment. ConclusionShexiang Baoxinwan can improve anxiety and depression， alleviate angina symptoms， and reduce TCM symptoms of Qi stagnation and blood stasis in CAD patients. The mechanism may involve anti-inflammation， improvement of vascular endothelial function， reduction of IMA， and increase of monoamine neurotransmitter levels.

As a patented characteristic medicine of Yi ethnic minority， Pingxuan capsules have the effects of nourishing the liver and kidney， pacifying the liver， and subduing Yang. With the main indications of dizziness， headache， palpitations， tinnitus， insomnia， dreaminess， waist and knee soreness caused by liver-kidney deficiency and liver Yang upward disturbance， Pingxuan capsules are widely used in the treatment of posterior circulation ischemic vertigo， vestibular migraine， benign paroxysmal positional vertigo. However， the current knowledge is limited regarding the efficacy， syndrome differentiation， and safety of this medicine. On the basis of summarizing the experience of clinicians and the existing evidence， this study invites clinical experts of traditional Chinese and Western medicine， pharmaceutical experts， and methodological experts from relevant fields across China to conduct evidence-based evaluation of Pingxuan capsules. The evaluation follows the Specifications for the Development of Clinical Expert Consensus on Chinese Patent Medicines issued by the Standardization Office of the China Association of Chinese Medicine， and reaches 5 recommendations and 16 consensus suggestions. The consensus clarifies the clinical applications， efficacy， dose， course of treatment， combination of medicines， precautions， and contraindications of Pingxuan capsules in the treatment of vertigo and explains the safety of clinical application. This consensus is applicable to clinicians （traditional Chinese medicine， Western medicine， and integrated traditional Chinese and Western medicine） and pharmacists in tertiary hospitals， secondary hospitals， and community-level medical and health institutions across China， providing a reference for the rational use of Pingxuan capsules in the treatment of vertigo. It is hoped that the promotion of this consensus can facilitate the rational use of drugs in clinical practice， reduce the risk of drug use， and give full play to the advantages of Pingxuan capsules in the treatment of vertigo diseases. This consensus has been reviewed and published by the China Association of Chinese Medicine， with the number GS/CACM330-2023.

Objective To construct a module for drug-induced central nervous system adverse reactions(CNS-ADR)within the Clinical Adverse Drug Event Active Monitoring and Intelligent Assessment Alert System-Ⅱ(ADE-ASAS-Ⅱ),and to conduct a large-scale,real-world active monitoring and evaluation of CNS-ADR specifically related to imipenem/cilastatin.Methods Based on literature review,spontaneous report evaluation,and initial word set of CNS-ADR related descriptions in electronic medical records,text recognition technology was used to construct and optimize the condition settings of the CNS-ADR automatic monitoring module.Hospitalized patients using imipenem/cilastatin were retrospectively monitored from 2017 to 2021,and the positive patients which had CNS-ADR were statistically described in terms of the demographic characteristics,CNS symptoms,and hospital departments.Results Based on a repeated testing optimization using 1 185 manually monitored results,the best setting for the determined module includes 62 sets of keywords,with a positive predictive value(PPV)of 13.63％and a recall rate of 100％.Expanding the monitoring to 8 222 medication users using this module,281 cases of positive causality were identified,with an incidence rate of 3.42％.Among them,patients over 60 years old accounted for 50.17％,and the main manifestations of CNS-ADR were epileptic seizures,headaches,mania,and delirium.Conclusion The CNS-ADR automatic monitoring module established based on ADE-ASAS-Ⅱ provides fast and reliable text data mining support for conducting real-world research on CNS-ADR.

Vascular calcification is a highly regulated process of ectopic calcification in cardiovascular system while no effective intervention can be clinically performed up to date.As vascular calcification undergoes a common regulatory mechanism within bone formation,bone morphogenetic protein 7(BMP-7)main-tains contractile phenotype of vascular smooth muscle cells and further inhibits vascular calcification via promoting the process of osteoblast differentiation,reducing ectopic calcification pressure by increasing bone formation and reducing bone resorption.This work systematically reviews the role of BMP-7 in vascular calcifi-cation and the possible mechanism,and their current clinical application as well.The current proceedings may help develope early diagnostic strategy and therapeutic treatment with BMP-7 as a new molecular marker and potential drug target.The expec-tation could achieve early prevention and intervention of vascular calcification and improve poor prognosis on patients.

Aim To explore the effect of quercetin(Que)on ferroptosis and the potential mechanisms in an Erastin-induced ferroptosis model in chondrocytes.Methods A model of Erastin-induced ferroptosis was established in C28/I2 chondrocytes.Cells were treated with different concentrations of Que.Cell viability and cytotoxicity were assessed by MTT and LDH assays.The expression levels of Prdx6 and ferroptosis-related proteins ACSL4 and GPX4 in chondrocytes were deter-mined by Western blot.Lipid ROS production in chon-drocytes was measured by flow cytometry,while the changes in mitochondrial membrane potential were de-tected by RH123 staining.Prdx6 mRNA expression in chondrocytes was quantified by RT-qPCR.The chan-ges in the expression of the ferroptosis-related proteins ACSL4 and GPX4 were detected by immunofluores-cence staining.Results Compared to the Erastin-in-duced ferroptosis model group,Que significantly im-proved the viability of C28/I2 chondrocytes and re-duced cell cytotoxicity.It decreased the expression of the ferroptosis-related protein ACSL4 and increased the expression of GPX4.Que also inhibited the production of lipid ROS in chondrocytes and strengthened their mitochondrial membrane potential.In addition,the ex-pression of Prdx6 was significantly reduced in the Eras-tin group compared to the control group,while Que treatment upregulated the expression of Prdx6.Mean-while,the inhibitory effect of Que on chondrocyte fer-roptosis was reduced by the use of MJ33,an inhibitor of Prdx6.Conclusion Que can inhibit Erastin-induced ferroptosis of C28/I2 chondrocytes,possibly by upregu-lating Prdx6,and thus play a protective role in chon-drocytes.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

This study investigated the characteristics of gut microbiota imbalance in patients with infectious diarrhea caused by various pathogenic infections,and the role of Bacteroides in maintaining homeostasis in the intestinal environment.The gut microbiota in patients with diarrhea caused by pathogenic infections,such as viral and bacterial infections,was determined through full-length 16S rRNA amplicon sequencing.Patients with diarrhea were grouped and analyzed according to the presence of single bacterial infection,single viral infection,mixed infection,or Clostridioides difficile infection.Bacteroides had the highest absolute number and relative abundance in the gut microbiota in healthy people,whereas patients with infectious diar-rhea showed lower relative abundance of Bacteroides at each phylum/order/family/genus taxonomic level.Alpha diversity anal-ysis indicated no significant differences among groups.NMDS and PCoA indicated formation of distinct clusters in the control group compared with the different infectious diarrhea groups.The diversity of the gut microbiota was higher in the control group than the infectious diarrhea groups.Patients with infec-tious diarrhea caused by different pathogens showed differing predominant gut microbiota.Bifidobacterium predominated in the single viral infection group,Streptococcus predominated in the single bacterial infection group,and Lachnoclostridium predominated in the mixed infection group.Escherichia and Klebsiella were the major gut microbiota in the C.difficile infection group.Meanwhile,the dominant gut microbiota in the healthy population was Bacteroides.COG function prediction revealed that the healthy control group formed a distinct cluster from the different infection groups.The functions of defense mechanisms,cell wall synthesis,protein modification,cellular differentiation,and replication and recombination were signifi-cantly diminished in all infectious diarrhea groups.In general,patients with infectious diarrhea caused by different pathogens showed dysbiosis,with diminished gut microbiota diversity and the emergence of related biomarkers.Our findings indicated that Bacteroides has a key role in maintaining the homeostasis of the human intestinal environment,thus providing new ideas for the subsequent treatment of infectious diarrhea and research in other fields.

Biliary fibrosis (BF) is the result of pathological repair of bile tract injury, characterized by thickening and sclerosis of the bile duct wall and progressive stricture of the lumen, which may ultimately lead to serious adverse outcomes such as biliary obstruction, biliary cirrhosis, liver failure, and hepatobiliary malignancies. Current research describes BF as a pathological feature of certain bile tract diseases, lacking a systematic summary of its etiology, pathophysiology, molecular mechanisms, and treatment. BF is a common but easily neglected disease state in biliary system, which may promote the development and progression of hepatobiliary diseases through abnormal repair mechanism after pathological biliary tract injury. Based on the latest research progress from both domestic and international perspectives, the authors review the concept, clinical manifestation, etiology, pathogenesis, and therapeutic strategies of BF to provide a reference for clinical physicians.

Objective To understand the incidence and characteristics of adverse drug reactions(ADRs)of carbapenems,explore the relevant risk signals,and provide a reference for clinically safe drug use.Methods All spontaneous reports of carbapenem drug-related ADRs from January 2008 to October 2022 in the Adverse Drug Reaction Monitoring Center,PLA General Hospital's ADR database were retrieved,and information such as patients'general conditions,involved systems and organs damage,and the names of ADRs involved were retrospectively analysed.Using the reporting odd ratio method,the proportional reporting ratio method,the Medicines and Healthcare Products Regulatory Agency method,and information component method to obtain risk signals of carbapenem antimicrobial drug-related ADR.Results A total of 2 642 ADR reports of carbapenems were reported,of which 410 serious ADR reports(15.52％)were serious ADR reports,five cabapenem antimirobial drug species were mainly involved.In descending order of composition were imipenem cilastatin(51.28％),meropenem(32.13％),biapenem(8.10％),ertapenem(7.68％),and panipenem(0.79％).The male to female ratio of patients was 1.74:1,with the most age＞60 years(59.69％).A total of 14"drug-ADR name"combinations generated risk signals in all four data mining methods,with meropenem being the most signals,and imipenem cilastatin and ertapenem had a high number of reported ADR in nervous system.Conclusion The results of risk signal mining are basically consistent with the known carbapenem ADR information,during the use of carbapenem antimicrobial drugs in the clinic,it is recommended to monitor patients'liver and kidney functions as well as blood biochemical indexes,so as to strengthen the awareness of vigilance in the clinical use of carbapenem antimicrobial drugs,and timely recognize and deal with ADRs in a timely manner,and to avoid the occurrence of serious ADRs.