ObjectiveTo investigate the effects of metformin on the immune functions of immature dendritic cells （imDCs） and the underlying mechanisms. MethodsMouse bone marrow-derived imDCs were treated with different concentrations of metformin. The working concentration and treatment time of metformin in this study were determined based on the results of cell apoptosis and cell viability assays. The effects of metformin on the phagocytic capacity of imDCs was evaluated using an antigen endocytosis assay. The expression of cluster of differentiation 205 （CD205）， the polymerization of filamentous actin （F-actin）， and the underlying regulatory mechanisms were investigated through flow cytometry， laser confocal fluorescence microscopy， and Western blot. ResultsThe working concentrations of metformin were 1， 2， 4 mmol/L for 24 h determined by the apoptosis and cell viability assays.Metformin significantly suppressed the phagocytic capacity of imDCs， down-regulated the expression of the mannose receptor CD205 on the cell surface， which was closely associated with phagocytic function； metformin inhibited the RhoA-ROCK1-LIMK1-Cofilin signaling pathway， which inhibited the polymerization of F-actin and disturbed its dynamic remodeling of imDCs. ConclusionMetformin can inhibit the expression of CD205 and disrupt the remodeling of F-actin， thereby suppressing the antigen-capturing capacity of imDCs.

As people’s attention to health continues to increase, the market demand for traditional Chinese medicine (TCM) is growing steadily. The quality and safety of Chinese medicinal materials have attracted unprecedented social attention. In particular, the issue of exogenous harmful residue pollution in TCM has become a hot topic of concern for both regulatory authorities and society. The Chinese Pharmacopoeia 2025 Edition further refines the detection methods and limit standards for exogenous harmful residues in TCM. This not only reflects China’s high-level emphasis on the quality and safety of TCM but also demonstrates the continuous progress made by China in the field of TCM safety supervision. Basis on this study, by systematically reviewing the development history of the detection standards for exogenous harmful residues in TCM and analyzing the revisions and updates of these detection standards in the Chinese Pharmacopoeia 2025 Edition, deeply explores the key points of the changes in the monitoring standards for exogenous harmful residues in TCM in the Chinese Pharmacopoeia 2025 Edition. Moreover, it interprets the future development directions of the detection of exogenous residues in TCM, aiming to provide a reference for the formulation of TCM safety supervision policies.

Objective:To investigate the impact of postoperative complications on adverse outcomes following curative-intent resection for gallbladder cancer (GBC).Methods:The multi-center real-world study was conducted. The clinicopathological data of 629 patients with GBC, who were admitted to 14 medical centers including The First Affiliated Hospital of Army Medical University from the national multicenter database of Biliary Surgery Group of Elite Group of Chinese Journal of Digestive Surgery, from April 2020 to April 2024 were collected. There were 225 males and 404 females, aged (64±10)years. Patients underwent open curative-intent resection for GBC. Observation indicators: (1)surgery, postoperative complica-tions and adverse outcomes; (2) analysis of risk factors affecting postoperative adverse outcomes in patients and population attributable fraction (PAF). Missing data in predictor variables were addressed using multiple imputation with chained equations, while cases with missing outcome variables were addressed using the "multiple imputation then deletion (MID)" strategy. The severity of multicollinearity among independent variables was assessed using the variance inflation factor (VIF) test. Multivariable possion regression models with log link and robust error variance were construc-ted incorporating restricted cubic splines (3 knots) to address nonlinear relationships in continuous variables, calculating adjusted relative risk ( RR) with corresponding 95% confidence interval ( CI). Adjusted PAF was calculated for each imputed dataset using the AF package of R software, with subsequent pooling performed according to Rubin's rules. Results:(1) Surgery, postoperative complications and adverse outcomes. All 629 patients underwent curative-intent resection for GBC, of which 143 cases had postoperative complications, including 68 cases of intra-abdominal ascites, 39 cases of pulmonary infection, 21 cases of bile leakage, 12 cases of intra-abdominal hemorrhage, 11 cases of liver failure, 10 cases of pan-creatic fistula, 10 cases of wound infection, 10 cases of gastroparesis, 7 cases of cholangitis, 7 cases of sepsis. The same patient could have more than one kind of complication. Of 629 patients, there were 19 cases of postoperative 90-day death and 11 cases of missing data, 42 cases with post-operative 90-day reoperation and 7 cases with missing data, 44 cases with postoperative 90-day readmission and 3 cases with missing data, 155 cases with prolonged postoperative hospital stay and 3 cases with missing data. (2) Analysis of risk factors affecting the postoperative adverse outcomes in patients and PAF. Results of multivariate analysis showed that pulmonary infection and liver failure were independent risk factors for postoperative 90-day mortality ( RR=3.74, 12.15, 95% CI as 1.18-11.83, 1.98-74.48, P<0.05). Pulmonary infection demons-trated the highest PAF as 4.61% (95% CI as 3.94%-5.28%, P<0.05). Intra-abdominal ascites, pulmonary infection, bile leakage, and intra-abdominal hemorrhage were independent risk factors for post-operative 90-day reoperation ( RR=4.80, 3.62, 3.46, 4.99, 95% CI as 2.49-9.26, 1.42-9.21, 1.34-8.92, 1.55-16.06, P<0.05). Intra-abdominal ascites demonstrated the highest PAF as 8.65% (95% CI as 8.22%-9.08%, P<0.05). Intra-abdominal ascites, bile leakage, and liver failure were independent risk factors for postoperative 90-day readmission ( RR=6.20, 3.33, 14.33, 95% CI as 3.21-11.95, 1.33-8.35, 3.72-55.28, P<0.05). Intra-abdominal ascites demonstrated the highest PAF as 9.11% (95% CI as 8.85%-9.37%, P<0.05). Intra-abdominal ascites, pulmonary infection, bile leakage, liver failure, and wound infection were independent risk factors for prolonged postoperative hospital stay ( RR=2.29, 2.21, 2.26, 2.14, 3.35, 95% CI as 1.63-3.23, 1.41-3.46, 1.32-3.86, 1.11-4.13, 1.70-6.60, P<0.05). Intra-abdominal ascites demonstrated the highest PAF as 6.03% (95% CI as 5.71%-6.35%, P<0.05). Conclusion:Pulmonary infection is the most significant risk factor for postoperative 90-day mortality after curative-intent resection for GBC, while intra-abdominal ascites is the most significant risk factor for postoperative 90-day reoperation, postoperative 90-day readmission, and prolonged postoperative hospital stay.

Objective:To explore the effect of Lactobacillus reuteri on testicular injury in mice exposed to neonicotinoid insec-ticides(NNI).Methods:Fifteen C57BL/6 male mice were randomly divided into control group(CTRI.group),exposure group(NNI group)and Lactobacillus intervention group(NNI-L group).The mice in CTRL group were given 0.02ml/g of 0.5％carboxym-ethyl cellulose sodium solution by gavage for 14 days.The mice in NNI group were given 0.02 ml/g of NNI mixture by gavage for 14 days.The mice in NNI-L group were given 0.02 ml/g of NNI mixture by gavage and 5 × 108cfu/ml of Lactobacillus reuteri powder so-lution for 14 days.Then,the histomorphology and function of testicle were evaluated by hematoxylin-eosin staining,immunofluores-cence staining and RNA sequencing.Results:Compared with CTRL group,the thickness of testicular seminiferous epithelium in the NNI group was significantly thinner.And the decline in the number of spermatogenic cells and sperm was observed.And the expression of spermatogonial stem cell marker UCHL1 was down-regulated which was significantly improved in NNI-L group compared with the NNI group.The abnormal expressions of hormone and sperm methylation related genes in testis of NNI group were detected by RNA sequen-cing,with significant down-regulation being found in NPFF and IGF2.While the expression of HSD3B8 was significantly up-regulated.The abnormal expression of these genes could be significantly improved after oral administration of Lactobacillus reuteri.Conclusion:Testicular spermatogenesis and endocrine function can be damaged by NNI exposure.And oral administration of Lactoba-cillus reuteri protects testis from the adverse effects of NNI toxicity.

Aim To explore the therapeutic effect of Shenwuyishen tablets(SWYST)in treating chronic kidney disease(CKD)and the underlying mechanism.Methods The pharmacological action of SWYST was evaluated in folic acid(FA)-induced mouse models by levels of serum creatinine and blood urea nitrogen,in-dexes of tubulointerstitial inflammation and tubular in-jury,and degrees of renal fibrosis.Differential genes from 22 types of cells in kidney tissue of CKD were i-dentified by single-cell and single-nuclei RNA sequen-cing datasets.Network pharmacology was used to pre-dict key ingredients,cells,and targets.The binding mode between the key ingredients and key targets was elucidated using molecular docking and molecular dy-namics simulation.Results Serum creatinine and blood urea nitrogen levels,tubulointerstitial inflamma-tion and tubular injury indexes,and renal fibrosis de-grees were significantly reduced by SWYST administra-tion.Quercetin,kaempferol,luteolin,baicalein and wogonin were considered as key components that main-ly acted through FOS and JUN of endothelial cells,neu-trophils and thick ascending limb cells to ameliorate CKD.Molecular docking and molecular dynamics sim-ulation revealed that quercetin stably occupied the cross pocket of FOS-JUN heterodimers to inhibit the binding between FOS-JUN heterodimers and DNA.Conclusion SWYST inhibits the binding of FOS-JUN heterodimers and DNA of endothelial cells,neutrophils and thick ascending limb cells to ameliorate CKD.

Objective To propose an in vitro cytotoxicity evaluation method for novel iron-based biodegradable mateirals focusing on their degrading characteristics.Methods Half-finished scaffolds of nitrided iron tubes with a higher iron content of over 99％and a nitrogen content of 0.03％to 0.20％were selected as test samples,and based on the treatment mode were divided into an anaerobic treatment group,a non-anaerobic treatment group,a non-anaerobic treatment with removed iron particle group and a non-anaerobic treatment with plate-washing group.The anaerobic treatment group was processed in an anaerobic workstation;the conventional treatment group underwent standard handling in a biosafety cabinet;the conventional treatment with removed iron particle group was subjected to iron particle elimination using a Midimacs Starting Kit manual sorter after conventional treatment;and the conventional treatment with plate-washing group was rinsed with 0.9％sodium chloride injection before tetrazolium salt reagent treatment.Different extraction media(simulated body fluid,cell culture medium,phosphate buffer and 0.9％sodium chloride injection)were used for the immersion treatment of the test samples in each group to compare the effects of the degradation products on the survival rate of L929 cells.Results The anaerobic treatment group and the conventional treatment with removed iron particle group exhibited no detectable cytotoxicity.Trypan blue staining revealed significant cytotoxicity in the conventional treatment group,while false-negative results emerged due to interactions between the tetrazolium salt reagent and degradation products.In the non-anaerobic treatment with washing plate group,the false negative from iron particles was eliminated while potential cytotoxicity was showen,and the result accuracy was affected because some cells were washed out.Conclusion The proposed method can be used for the in vitro cytotoxicity evaluation,and facilitates the safety evaluation of the application of such materials.[Chinese Medical Equipment Journal,2025,46(3):35-41]

Objective To investigate the characteristics of a novel FANCL mutation identified in a patient with premature ovarian insufficiency(POI)and to explore its potential functional impacts in vitro.Methods A novel FANCL heterozygous mutation c.1033G>A(p.Glu345Lys)was screened in a patient with POI using whole exome sequencing(WES),which was found to be inherited from a mother who had undergone early menopause.The authenticity of the mutation was identified by Sanger sequencing and the conserved nature of the mutation site was predicted by software.Overexpressing FANCL mutant and wildtype plasmids were constructed and transiently transfected into HEK293T cell lines,and the effect of the mutation was detected by qPCR,immunofluorescence and Western blot.Results The mutation site of FANCL was located within the Ring domain of FANCL,which was highly conserved across multiple species.The mutant showed no significant change in mRNA expression level,while the protein expression level was significantly down-regulated.In vitro cellular experiments further revealed that the mutation leads to decreased expression levels by reducing protein stability.Conclusion A FANCL c.1033G>A mutation was found and it may cause disease in the POI patient due to decreased protein stability.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective:This study aimed to explore the utility of transcutaneous electrical acupoint stimulation (TEAS) combined with skin sympathetic response (SSR) in assessing the effectiveness of perigastric autonomic nerve preservation during radical gastrectomy.Methods:A retrospective cohort analysis was conducted involving 221 patients who underwent laparoscopic radical gastrectomy at the Department of Gastric Surgery, Taizhou People's Hospital, affiliated with Nanjing Medical University, between June 2022 and September 2024. The cohort comprised 109 patients who underwent laparoscopic radical total gastrectomy without autonomic nerve preservation (total gastrectomy without nerve preservation group). Additionally, 112 patients underwent laparoscopic radical distal gastrectomy, including 34 patients who received autonomic nerve preservation (nerve preservation group) and 78 patients who did not (without nerve preservation group). TEAS was administered at the Zusanli and Tianshu acupoints one day before and one day after surgery, during which SSR latency and voltage amplitudes in the upper and lower extremities were recorded and compared across groups. Differences in SSR latency and voltage amplitude between the nerve preservation and non-nerve preservation groups of the distal gastrectomy cohort were also analyzed. Further, TEAS was applied at the same acupoints for 15 minutes on the 1st, 2nd, and 3rd postoperative days, and changes in intestinal sounds and intestinal functional recovery time were monitored. Surgical parameters, including operative duration, intraoperative blood loss, and harvested lymph node, were documented. Postoperative inflammatory indicators, including interleukin-6 (IL-6), C-reactive protein (CRP), procalcitonin (PCT), and the incidence of anastomotic leakage, were evaluated. At three months postoperatively, gastroscopy was performed to assess residual gastric food and bile reflux. Additionally, the prognostic nutritional index (PNI) was evaluated across all patient groups.Results:Following total gastrectomy, TEAS of Zusanli combined with arms' SSR revealed a latency of (23 59.71±410.55) ms and a voltage amplitude of (0.43±1.67) mV; for the legs, latency was (2 596.88±369.01) ms and voltage amplitude was (0.25±0.08) mV. TEAS of Tianshu combined with arms' SSR demonstrated a latency of (2 746.47±224.37) ms and a voltage amplitude of (0.31±0.14) mV; for the legs, latency was (2 891.90±193.61) ms and voltage amplitude was (0.19±0.72) mV. Postoperative latency was significantly prolonged, and voltage amplitude was markedly reduced (all P < 0.01). In the distal gastrectomy with nerve preservation group, TEAS of Zusanli combined with arms' SSR showed a latency of (1 668.04±261.91) ms and a voltage amplitude of (0.78±0.26) mV; for the legs, latency was (1 568.86±220.09) ms and voltage amplitude was (0.61±0.24) mV. TEAS of Tianshu combined with arms' SSR demonstrated a latency of (1 519.36±206.99) ms and a voltage amplitude of (0.66±0.34) mV; for the legs, latency was (2 004.80±508.53) ms and voltage amplitude was (0.55±0.28) mV. In the distal gastrectomy without nerve preservation group, TEAS of Zusanli combined with arms' SSR revealed a latency of (2 385.95±710.27) ms and a voltage amplitude of (0.23±0.11) mV; for the legs, latency was (2 506.81±779.37) ms and voltage amplitude was (0.26±1.29) mV. TEAS of Tianshu combined with arms' SSR indicated a latency of (2 697.78±385.55) ms and a voltage amplitude of (0.21±0.14) mV; for the legs, latency was (2 949.14±506.61) ms and voltage amplitude was (0.17±0.11) mV. The group without nerve preservation exhibited significantly prolonged latencies and reduced voltage amplitudes (all P<0.01). No statistically significant differences were observed between the groups in operative time, intraoperative bleeding, the number of dissected lymph nodes, inflammatory indicators (IL-6, CRP, PCT) at 3 days postoperatively, or anastomotic leakage rates (all P>0.05). In the group without nerve preservation, bowel sounds on postoperative days 1, 2, and 3 were (0.36±0.58), (1.04±0.97), and (1.74±1.10) times/min, respectively, with bowel function recovery time of (62.24±9.91) hours. The PNI at 3 months postoperatively was (37.42±3.01). Incidences of food residue in the residual stomach and bile reflux were 21.79% (17/78) and 29.49% (23/78), respectively. In the group with nerve preservation, bowel sounds on postoperative days 1, 2, and 3 were (0.76±0.82), (2.03±1.34), and (3.71±1.27) times/min, respectively, with bowel function recovery time of (44.94±8.05) hours. The PNI at 3 months postoperatively was (41.34±3.40). Incidences of food residue and bile reflux were 5.88% (2/34) and 11.76% (4/34), respectively. Statistically significant differences were observed between the groups (all P < 0.05). Conclusion:TEAS of Zusanli and Tianshu combined with SSR provides an objective measure for assessing the preservation of perigastric autonomic nerves during radical gastrectomy.

Objective:This study aimed to explore the utility of transcutaneous electrical acupoint stimulation (TEAS) combined with skin sympathetic response (SSR) in assessing the effectiveness of perigastric autonomic nerve preservation during radical gastrectomy.Methods:A retrospective cohort analysis was conducted involving 221 patients who underwent laparoscopic radical gastrectomy at the Department of Gastric Surgery, Taizhou People's Hospital, affiliated with Nanjing Medical University, between June 2022 and September 2024. The cohort comprised 109 patients who underwent laparoscopic radical total gastrectomy without autonomic nerve preservation (total gastrectomy without nerve preservation group). Additionally, 112 patients underwent laparoscopic radical distal gastrectomy, including 34 patients who received autonomic nerve preservation (nerve preservation group) and 78 patients who did not (without nerve preservation group). TEAS was administered at the Zusanli and Tianshu acupoints one day before and one day after surgery, during which SSR latency and voltage amplitudes in the upper and lower extremities were recorded and compared across groups. Differences in SSR latency and voltage amplitude between the nerve preservation and non-nerve preservation groups of the distal gastrectomy cohort were also analyzed. Further, TEAS was applied at the same acupoints for 15 minutes on the 1st, 2nd, and 3rd postoperative days, and changes in intestinal sounds and intestinal functional recovery time were monitored. Surgical parameters, including operative duration, intraoperative blood loss, and harvested lymph node, were documented. Postoperative inflammatory indicators, including interleukin-6 (IL-6), C-reactive protein (CRP), procalcitonin (PCT), and the incidence of anastomotic leakage, were evaluated. At three months postoperatively, gastroscopy was performed to assess residual gastric food and bile reflux. Additionally, the prognostic nutritional index (PNI) was evaluated across all patient groups.Results:Following total gastrectomy, TEAS of Zusanli combined with arms' SSR revealed a latency of (23 59.71±410.55) ms and a voltage amplitude of (0.43±1.67) mV; for the legs, latency was (2 596.88±369.01) ms and voltage amplitude was (0.25±0.08) mV. TEAS of Tianshu combined with arms' SSR demonstrated a latency of (2 746.47±224.37) ms and a voltage amplitude of (0.31±0.14) mV; for the legs, latency was (2 891.90±193.61) ms and voltage amplitude was (0.19±0.72) mV. Postoperative latency was significantly prolonged, and voltage amplitude was markedly reduced (all P < 0.01). In the distal gastrectomy with nerve preservation group, TEAS of Zusanli combined with arms' SSR showed a latency of (1 668.04±261.91) ms and a voltage amplitude of (0.78±0.26) mV; for the legs, latency was (1 568.86±220.09) ms and voltage amplitude was (0.61±0.24) mV. TEAS of Tianshu combined with arms' SSR demonstrated a latency of (1 519.36±206.99) ms and a voltage amplitude of (0.66±0.34) mV; for the legs, latency was (2 004.80±508.53) ms and voltage amplitude was (0.55±0.28) mV. In the distal gastrectomy without nerve preservation group, TEAS of Zusanli combined with arms' SSR revealed a latency of (2 385.95±710.27) ms and a voltage amplitude of (0.23±0.11) mV; for the legs, latency was (2 506.81±779.37) ms and voltage amplitude was (0.26±1.29) mV. TEAS of Tianshu combined with arms' SSR indicated a latency of (2 697.78±385.55) ms and a voltage amplitude of (0.21±0.14) mV; for the legs, latency was (2 949.14±506.61) ms and voltage amplitude was (0.17±0.11) mV. The group without nerve preservation exhibited significantly prolonged latencies and reduced voltage amplitudes (all P<0.01). No statistically significant differences were observed between the groups in operative time, intraoperative bleeding, the number of dissected lymph nodes, inflammatory indicators (IL-6, CRP, PCT) at 3 days postoperatively, or anastomotic leakage rates (all P>0.05). In the group without nerve preservation, bowel sounds on postoperative days 1, 2, and 3 were (0.36±0.58), (1.04±0.97), and (1.74±1.10) times/min, respectively, with bowel function recovery time of (62.24±9.91) hours. The PNI at 3 months postoperatively was (37.42±3.01). Incidences of food residue in the residual stomach and bile reflux were 21.79% (17/78) and 29.49% (23/78), respectively. In the group with nerve preservation, bowel sounds on postoperative days 1, 2, and 3 were (0.76±0.82), (2.03±1.34), and (3.71±1.27) times/min, respectively, with bowel function recovery time of (44.94±8.05) hours. The PNI at 3 months postoperatively was (41.34±3.40). Incidences of food residue and bile reflux were 5.88% (2/34) and 11.76% (4/34), respectively. Statistically significant differences were observed between the groups (all P < 0.05). Conclusion:TEAS of Zusanli and Tianshu combined with SSR provides an objective measure for assessing the preservation of perigastric autonomic nerves during radical gastrectomy.