Idiosyncratic drug-induced liver injury (IDILI) has long posed a challenging and pivotal concern in pharmaceutical research. The complex composition of traditional Chinese medicine (TCM) has introduced a bottleneck in current research, hindering the elucidation of the component basis associated with IDILI in TCM. Using Epimedii Folium (EF) and Psoraleae Fructus (PF) as illustrative examples, this study endeavors to establish an in vitro evaluation model, providing a high-throughput and preliminary assessment method for screening components related to TCM-induced IDILI. A TNF-α-mediated HepG2 susceptible model was first established in this study, with the focus on the index components present in EF and PF. The release of lactate dehydrogenase (LDH) in the cell supernatant served as the detection index. A concentration-toxicity response curve was constructed, and the hepatotoxic components of EF and PF were identified utilizing the synergistic toxicity index. The LDH results unveiled the hepatotoxic effects of bavachin, backuchiol, isobavachin, neobavaisoflavone, psoralidin, isobavachalcone, icarisid I, and icarisid II on both normal and susceptible cells, categorizing these 8 components as both direct hepatotoxicity components and idiosyncratic hepatotoxicity components. Bavachin and neobavaisoflavone exhibited no hepatotoxicity on normal cells but demonstrated significant effects on susceptible cells, designating them as potential idiosyncratic susceptible hepatotoxicity components. The study further delineated that 10 EF components and 3 PF components were direct immune-promoting hepatotoxicity components. Additionally, 14 idiosyncratic immune-promoting hepatotoxicity components were identified, encompassing 10 EF components and 4 PF components, with neobavaisoflavone, bavachinin, and isobavachin being potential idiosyncratic susceptible immune-promoting hepatotoxicity components. Synergistic toxicity index results indicated that 13 idiosyncratic immune-promoting hepatotoxicity components (except anhydroicaritin) combined with bavachin demonstrated synergistic hepatotoxicity on susceptible cells. Notably, 3 idiosyncratic susceptible immune-promoting hepatotoxicity components combined with bavachin exhibited synergistic hepatotoxicity, with neobavaisoflavone displaying the highest synergistic toxicity index and bavachinin the lowest. In summary, this methodology successfully screens hepatotoxic and immune-promoting hepatotoxic components in EF and PF, distinguishing the types of components inducing hepatotoxicity, evaluating the hepatotoxicity degree of each component, and elucidating the synergistic relationships among them. Importantly, these findings align with the characteristics of IDILI. The method provides an effective model tool for the fundamental research of TCM-related IDILI components.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

AIM To evaluate the quality of Beidougen Formula Granules.METHODS Fifteen batches of standard decoctions and three batches of formula granules were prepared,after which paste rate and contents,transfer rates of magnoflorine,daurisoline,dauricine were determined.HPLC specific chromatograms were established,and cluster analysis was adopted in chemical pattern recognition.RESULTS For three batches of formula granules,the paste rates were 15.1%-16.6%,the contents of magnoflorine,daurisoline,dauricine were 18.93-19.39,9.42-9.60,6.79-6.85 mg/g with the transfer rates of 34.42%-35.25%,43.81%-44.65%,27.27%-27.51%from decoction pieces to formula granules,respectively,and there were seven characteristic peaks in the specific chromatograms with the similarities of more than 0.95,which demonstrated good consistence with those of standard decoctions and accorded with related limit requirements.Fifteen batches of standard decoctions were clustered into two types,and the medicinal materials produced from Jilin,Hebei,Shangdong could be used for the preparation of formula granules.CONCLUSION This reasonable and reliable method can provide references for the quality control and clinical application of Beidougen Formula Granules.

Objective To investigate the ameliorative effect of ginsenoside Rf on endometriosis(EMS)and its mechanism.Methods In animal experiments,Wistar female rats were randomly divided into sham group(laparotomy without other treatment),model group(EMS construction),low dose group(1.0 mg·kg-1 ginsenoside Rf),middle dose group(2.0 mg·kg-1 ginsenoside Rf),high dose group(3.0 mg·kg-1 ginsenoside Rf),positive group(0.25 mg·kg-1 pregnrienone capsule).The volume of ectopic lesions and the number of painful twisting were detected;the apoptosis rate in tissues was detected by TdT mediated dUDP nick end labeling(Tunel)assay;the expression of related proteins in each group was detected by Western blot assay.Cell experiment:The isolated primary rat endometrial cells were randomly divided into control group(normal tissue isolation),EMS group(EMS cells),Rf group(20 μmol·L-1 ginsenoside Rf treated EMS cells),combined group(20 μmol·L-1 ginsenoside Rf and 50 μmol·L-1 autophagy inhibitor 3-MA treated EMS cells).Western blot assay was used to detect the expression of related proteins;flow cytometry was used to detect apoptosis.Results Animal experiment:The times of body twisting in sham group,model group,high dose group and positive group were 0,37.10±4.64,14.70±1.90 and 20.20±1.78,respectively;the ectopic lesion volumes were 0,(118.91±19.51),(50.11±9.69)and(37.64±3.56)mm,respectively;the apoptosis rates were(3.43±0.33)％,(3.22±0.27)％,(20.42±1.82)％and(22.92±2.67)％,respectively;Beclin 1 protein expression were 0.32±0.03,0.36±0.04,0.79±0.12,0.35±0.07,respectively;glutathione peroxidase 4(GPX4)protein expression were 1.10±0.07,0.94±0.11,0.53±0.03,0.96±0.16,respectively.The above indexes of the model group were compared with those of the sham group,and the above indexes of the high dose group were compared with those of the model group,and the differences were significant(all P＜0.05).Cell experiment:Beclin1 protein expression in control group,EMS group,Rf group and combined group were 0.22±0.05,0.31±0.03,0.52±0.07 and 0.19±0.03,respectively;GPX4 protein expression were 0.97±0.07,0.81±0.09,0.63±0.05 and 1.05±0.09,respectively;the apoptosis rates were(3.48±0.04)％,(3.42±0.23)％,(21.66±2.95)％and(12.51±1.15)％,respectively;the above indexes in Rf group were compared with those in EMS group,and the above indexes in combined group were compared with those in Rf group,and the differences were significant(all P＜0.05).Conclusion Ginsenoside Rf can improve endometrial lesion,pain sensitivity and apoptosis in EMS rats,which may be related to the regulation of autophagy dependent ferroptosis.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Objective Postoperative delirium(POD)has become a critical challenge with severe consequences and increased incidences as the global population ages.However,the underlying mechanism is yet unknown.Our study aimed to explore the changes in metabolites in three specific brain regions and saliva of older mice with postoperative delirium behavior and to identify potential non-invasive biomarkers. Methods Eighteen-month-old male C57/BL6 mice were randomly assigned to the anesthesia/surgery or control group.Behavioral tests were conducted 24 h before surgery and 6,9,and 24 h after surgery.Complement C3(C3)and S100 calcium-binding protein B protein(S100beta)levels were measured in the hippocampus,and a metabolomics analysis was performed on saliva,hippocampus,cortex,and amygdala samples. Results In total,43,33,38,and 14 differential metabolites were detected in the saliva,hippocampus,cortex,and amygdala,respectively."Pyruvate""alpha-linolenic acid"and"2-oleoyl-1-palmitoy-sn-glycero-3-phosphocholine"are enriched in one common pathway and may be potential non-invasive biomarkers for POD.Common changes were observed in the three brain regions,with the upregulation of 1-methylhistidine and downregulation of D-glutamine. Conclusion Dysfunctions in energy metabolism,oxidative stress,and neurotransmitter dysregulation are implicated in the development of POD.The identification of changes in the level of salivary metabolite biomarkers could aid in the development of noninvasive diagnostic methods for POD.

Purpose Focusing on the characteristics of for-malin fixed paraffin embedded(FFPE)samples,explored nano-magnetic bead nucleic acid extraction solutions with higher qual-ity/yield and continued to improve molecular pathology technolo-gy.Methods Alternative magnetic beads were synthesised in four major categories and 15 sub-categories and we screened to obtain high-quality/yield magnetic beads centred on FFPE samples.Simulated conventional tissues,simulated coarse needle punctures(liver),and simulated fiberoptic bronchoscopy sam-ples(lungs)were sectioned with the same number of serial slices in tubes.The nucleic acids of slices were extracted using the best magnetic beads screened in this study and common com-mercially available kits,and then perform comparison and purifi-cation quality parameters such as total amount and fragment size.The downstream applications of nucleic acids were validated by PCR and Sanger sequencing.Results Screening all homemade nanomagnetic beads centered on the DNA of FFPE samples,the total recoveries of the best performance nanomagnetic beads were obtained to be 58.5％±1.58％,and the total recoveries of five commercially available commercial magnetic beads and three do-mestic kit magnetic beads ranged from 18.68％to 40.71％.The total amount of DNA(ng)extracted from the same amount of tis-sue(serial slices),the nucleic acid yield of this study in simu-lated conventional tissues,simulated coarse needle punctures,and simulated fiberoptic bronchoscopy samples were increased by 39.49％-181.72％compared with those of the commercially a-vailable kits(P＜0.05).The total amount of extracted nucleic acid from simulated fiberoptic bronchoscopy tissue sections can be more than 100 ng for 1 slice(4 μm)and more than 400 ng for 5 slices.Conclusion The DNA purification nanomagnetic beads screened with DNA from FFPE samples have a significant enhancement comparing to the existing commercial bead proto-cols,and provide space for quality assurance,automated testing,and program expansion for clinical molecular pathology testing.

Objective To observe the clinical effect of Dongjing Tiaoshen Comprehensive Therapy combined with computerized cognitive behavioral therapy for insomnia(CCBT-I)in the treatment of chronic insomnia patients with liver depression and spleen deficiency syndrome.Methods A total of 60 patients with chronic insomnia of liver depression and spleen deficiency type were randomly divided into observation group and control group,30 cases in each group.Both groups of patients were treated with CCBT-I as the basic treatment,the observation group was additionally treated with Dongjing Tiaoshen Comprehensive Therapy,i.e.,mind-regulating acupuncture therapy combined with regular aerobic exercises and Dantian Qigong exercises,and the control group was additionally treated with cranial electrotherapy stimulation.The course of treatment for the two groups covered 4 weeks.The changes of Pittsburgh Sleep Quality Index(PSQI)score,Self-rating Anxiety Scale(SAS)score and Self-rating Depression Scale(SDS)score in the two groups were observed before and after treatment,and the clinical efficacy of the two groups was evaluated after treatment.Results(1)After 4 weeks of treatment,the total effective rate of the observation group was 86.67%(26/30),and that of the control group was 70.00%(21/30).The intergroup comparison(tested by rank sum test)showed that the curative effect of the observation group was significantly superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the PSQI scores of the two groups were significantly lower than those before treatment(P＜0.05),and the decrease of PSQI scores in the observation group was significantly superior to that in the control group,the difference being statistically significant(P＜0.05).(3)After treatment,the SAS and SDS scores of the two groups were significantly lower than those before treatment(P＜0.05),and the decrease of SAS and SDS scores in the observation group tended to be superior to that in the control group,but there was no significant difference between the two groups(P＞0.05).Conclusion For the treatment of chronic insomnia of liver depression and spleen deficiency type,the combination of Dongjing Tiaoshen Comprehensive Therapy with CCBT-I can significantly improve the sleep quality,relieve anxiety and depression,and improve the quality of life of the patients,which exerts significant efficacy.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units，and the top five bacteria were Staphylococcus aureus（ n=1 147，36.3%），coagulase-negative Staphylococci（ n=928，29.3%）， Enterococcus faecalis（ n=369，11.7%）， Enterococcus faecium（ n=296，9.4%）and alpha-hemolyticus Streptococci（ n=192，6.1%）. The detection rates of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）were 26.4%（303/1 147）and 66.7%（619/928），respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome，rifampin，compound sulfamethoxazole，linezolid，minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%（2/369），and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions（ χ2=14.578， P=0.002），while the detection rate of MRCNS in northern China was significantly higher than that in other regions（ χ2=15.195， P=0.002）. The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals（ χ2=13.519 and 12.136， P<0.001）. The detection rates of MRSA and MRCNS in economically more advanced regions（per capita GDP≥92 059 Yuan in 2022）were higher than those in economically less advanced regions（per capita GDP<92 059 Yuan）（ χ2=9.969 and 7.606， P=0.002和0.006）. Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China， Staphylococci is the most common while the MRSA incidence decreases continuously with time；the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China，with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.

AIM To investigate the clinical effects of Bushen Quyu Decoction combined with conventional treatment on patients with postmenopausal osteoporosis due to Kidney Deficiency and Blood Stasis.METHODS One hundred and six patients were randomly assigned into control group(53 cases)for 6-month intervention of conventional treatment,and observation group(53 cases)for 6-month intervention of both Bushen Quyu Decoction and conventional treatment.The changes in clinical effects,TCM syndrome scores,bone metabolism indices(β-CTX,PINP,BGP),bone mineral density,oxidative stress indices(SOD,AOPP,MAOA)and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,β-CTX,BGP,AOPP,MAOA(P＜0.05),and increased PINP,bone mineral density,SOD(P＜0.05),especially for the observation group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with postmenopausal osteoporosis due to Kidney Deficiency and Blood Stasis,Bushen Quyu Decoction combined with conventional treatment can safely and effectively improve bone mineral density,bone metabolism indices,and alleviate oxidative stress responses.