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 reveal the differences in the transcriptome maps of brain tissues in mice subjected to Flash irradiation and conventional dose rate irradiation with electron beams and to explain the biological effect and mechanisms of Flash irradiation from multiple perspectives.Methods:Following the principle of grouping based on approximate body weights, 36 female C57BL/6J mice were divided into three groups, i. e., the control, conventional dose rate irradiation (CONV), and Flash irradiation (Flash) groups, with 12 mice in each group. Both the CONV and Flash groups received a single 15 Gy whole-brain irradiation with 9 MeV electron beams. At 3 d post-irradiation, the whole-brain tissue specimens were collected for hematoxylin-eosin (HE) staining to observe pathological changes. At 1, 3, and 10 weeks post-irradiation, the motion function, cognitive ability, depression level, and spatial memory capacity of the mice were assessed using ethology. At 1 and 10 weeks after behavioral experiments, brain tissue samples were collected and snap-frozen in liquid nitrogen for reference-based transcriptome sequencing. Accordingly, the differences in the transcriptome maps of radiation-induced brain injury between CONV and Flash groups were analyzed.Results:The HE staining-based pathological result revealed that compared to the CONV group, the Flash group exhibited reduced glial cell hyperplasia and inflammatory cell infiltration in brain tissues. Ethological research result at 1 week post-irradiation showed that the CONV group manifested a significantly decreased total traveled distance compared to the control and Flash groups ( t = 5.51, 2.38, P < 0.05) and a significantly increased immobility time compared to the control group ( t = 3.60, P < 0.05). Ethological research result at 3 weeks post-irradiation indicated that compared to the CONV group, the Flash group displayed significantly alleviated cognitive impairment ( t = 3.35, P < 0.05) and reduced depression levels ( t = 2.39, P < 0.05). Ethological research result at 10 weeks post-irradiation demonstrated that the CONV group showed the worst cognitive performance, significantly differing from the control group ( t = 4.53, P < 0.05). Transcriptome sequencing result revealed that besides immune-related pathways, the Flash group also exhibited multiple upregulated metabolic pathways and fibroblast growth factor (FGF)-related pathways compared to the CONV group. Conclusions:Compared to conventional dose rate irradiation, Flash irradiation can effectively alleviate radiation-induced brain injury in mice. This effect is associated with various metabolic pathways (including amino acid metabolism) and FGF-related pathways besides immune pathways.

Objective:To observe the characteristics of gastrointestinal tract symptoms in patients with Parkinson′s disease (PD) and analyze the characteristics of these symptoms in patients with different PD subtypes.Methods:A total of 297 PD patients who were admitted to the Neurology Department of the Second Affiliated Hospital of Soochow University from November 2022 to March 2024 were enrolled. The gastrointestinal symptoms of PD patients were evaluated using Drooling Severity and Frequency Scale (DSFS), Sialorrhea Clinical Scale for Parkinson′s disease (SCS-PD), Drooling Rating Scale (DRS), Eating Assessment Tool 10 (EAT-10), Gastroparesis Cardinal Symptom Index (GCSI), and Rome Ⅳ diagnostic criteria. The patients were grouped based on the presence or absence of gastrointestinal symptoms. Additionally, they were stratified according to disease duration (≤2 years, 2-5 years, 5-10 years, and>10 years) and motor symptom subtype [tremor-dominant (TD) vs. postural instability and gait difficulty (PIGD)]. One-way ANOVA and logistic regression analysis were applied to examine between-group differences while Spearman correlation analysis was employed to assess correlations between clinical symptoms.Results:The average age of the patients with PD was 67.0 (60.0, 72.0) years, and 161 (54.2%) were male. The incidence of PD combined with gastrointestinal symptoms was, in descending order: constipation (191, 64.3%), salivation (155, 52.2%), gastroparesis (93, 31.3%), and dysphagia (68, 22.9%). Compared with PD patients without gastrointestinal symptoms, those with symptoms had higher scores in the RBD-HK [12.0 (5.0, 21.5) vs. 5.0 (0.0, 9.0), Z=-3.74, P=0.017], ESS [6.0 (2.0, 12.0) vs. 3.0 (0.0, 6.0), Z=-3.20, P=0.023], and MDS-UPDRS Part Ⅰ [9.0 (5.0, 14.0) vs. 5.0 (2.3, 9.0), Z=-3.61, P=0.014]. The severity of sialorrhea and deglutition disorders, along with the incidence of constipation, all increased with longer disease duration. Patients with the PIGD subtype had higher GCSI scores than those with the TD subtype [0.0 (0.0, 1.9) vs. 0.0 (0.0, 0.0), Z=-3.57, P=0.007]. Across the cohort, sialorrhea, deglutition disorders, gastroparesis, and constipation were positively associated with the H-Y stage, MDS-UPDRS Ⅰ, HAMD, NMSQ, and SCOPA-AUT; EAT-10 scores were negatively correlated with MoCA ( r=-0.171, P<0.05); and GCSI scores were negatively correlated with MMSE and MoCA ( r=-0.154, r=-0.169, both P<0.05). Conclusions:Overall, 84.5% of the patients with PD had one or more gastrointestinal symptoms, and the incidence and severity of gastrointestinal symptoms increased with disease duration. The severity of gastroparesis was higher in the PIGD group than in the TD group. The scores of all gastrointestinal symptoms were positively correlated with the H-Y stage and MDS-UPDRS Ⅰ, while the GCSI scores were negatively correlated with the cognitive scores.

Objective:To determine the prevalence of self-reported food allergies among children in the grasslands of North China and to analyze its associated risk factors.Methods:In this study, a cross-sectional epidemiological survey method was used to select children under 14 years old by multi-stage, stratified and random cluster sampling in the grassland ecological area of Zhangbei County, Hebei Province, China from May to July 2018. Face-to-face questionnaires were administered to gather food allergy-related information from the participants. Multivariate logistic regression analysis was used to analyze the risk factors associated with self-reported food allergy.Results:A total of 2 086 children completed the survey. The prevalence of self-reported food allergies was 22.0%(459/2 086). The prevalence of multiple food allergies (≥3 types) was 3.1%(64/2 086) versus 16.3% (341/2 086) for a single food allergy among all children. Mango allergy (6.1%, 127/2 086) was the most common, followed by peach allergy (4.1%, 85/2 086). Children who reported food allergies had a significantly higher prevalence of all 4 atopic disorders (eczema, asthma, allergic rhinitis, and allergic conjunctivitis than those without food allergies(35.73% vs. 20.65%, 5.88% vs. 2.77%, 17.86% vs. 7.38%, 16.78% vs. 10.45%, χ2 =44.663 1, 10.434 3, 45.038 3, 13.728 4, all P<0.001).Significantly associated risk factors of food allergy were found to be pollen allergy ( OR: 2.29; 95% CI: 1.80-2.92) and drug allergy ( OR: 1.53; 95% CI: 1.12-2.09). Conclusions:The prevalence of self-reported food allergies among children in the Zhangbei County area of the North China Grassland was relatively high. Pollen allergy and drug allergy are major risk factors.

Objective To explore the publication trends and future directions in the field of value of MRI for diagnosing uterine fibroids using bibliometrics.Methods Literature related to diagnostic value of MRI for uterine fibroids in CNKI,Wanfang Med Online,SinoMed and WOSCC databases from 2006 to 2024 were retrieved,and 460 Chinese and 166 English articles were included.A bibliometric analysis was conducted to examine annual publication volume,country/region collaborations,journal distribution,core authors,highly cited literatures and keywords related to MRI for diagnosing uterine fibroids.Results From 2006 to 2024,the number of publications showed a fluctuating upward trend,with Chinese literature dominating.Authors from United States led research in this field and had the closest collaboration with those from France.Chinese and English articles were published in 221 and 81 journals,respectively,with several journals demonstrating significant influence.Highly cited articles mainly focused on differential diagnosis in early publications.Keywords analysis indicated that Chinese studies emphasized diagnosis and pathological typing,while English studies were more concerned with technical comparisons and accuracy assessment.Since 2020,research focus shifted toward image analysis technology and MRI-guided therapy.Conclusion The research on value of MRI for diagnosing uterine fibroids has been continuously developing.In the future,application of new technologies could be further explored,and multi-center cooperation and clinical transformation should be strengthened to promote the development and innovation in this field.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

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: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.