Purpose: This study aimed to evaluate the safety and efficacy of gemcitabine and cisplatin (GP) regimen in combination with immune checkpoint inhibitor sintilimab as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC) patients and the feasibility of the following selective bladder sparing surgery. Materials and Methods: Patients with histopathologically confirmed urothelial carcinoma without distant metastases (T2-4a, N ≤ 1, M0, American Joint Committee of Cancer 8th) and with adequate organ function will be enrolled. The therapeutic regimen was sintilimab 200 mg once on day 8, gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 once on days 1 and 8, every 21 days for four cycles. The primary endpoint was pathologic complete response (pCR, pT0N0) rate. The secondary end points were ypT < 2 rate, R0 resection rate, event-free survival, and safety. Results: From May 4, 2020, to May 20, 2023, 55 patients were enrolled. Forty-six patients were evaluated for efficacy. Among the 42 patients who underwent surgery, 16 patients (38.0%) achieved pCR. Thirty-three patients (78.6%) achieved pT < 2. With a median follow-up of 15.7 months, the 1-year event-free survival was 91.3%. Notwithstanding the poor pathological baseline characteristic of a high T3-T4a proportion (39.1%), a promising bladder preservation (including 22 patients transurethral resection of bladder tumor, 5 patients partial cystectomy, and 4 surveillances) rate was achieved (67.4%). The most common grade ≥ 3 treatment-related adverse events was neutropenia (n=15, 27.3%), which was related to chemotherapy. There were no grade 3 immune-related adverse events. Conclusion Neoadjuvant GP plus sintilimab is a promising regimen for MIBC patients, with relatively high pT < 2 rate and triggering the emerging roles for the multi-disciplinary team decision-making for bladder sparing surgery.

OBJECTIVES: Neurodegenerative diseases are closely associated with myelin loss, and the proliferation and differentiation of oligodendrocyte precursor cells (OPCs) are crucial to remyelination. However, the regulatory mechanisms involved remain incompletely understood. This study aims to investigate how astrocytes (ASTs) regulate the secretion of chitinase-3-like protein 1 (CHI3L1) via connexin 47 (Cx47)-mediated exosome signaling, and its subsequent effect on OPC proliferation. METHODS: Primary cells were isolated from postnatal day 1 Sprague-Dawley (P1SD) rats to establish 3 culture conditions: OPCs alone (Group O), OPCs in direct contact with ASTs (Group C), and OPCs cultured with AST-conditioned medium (Group A). Cellular morphology and proliferation were assessed using optical microscopy, 5-ethynyl-2'- deoxyuridine (EdU) incorporation, and flow cytometry. RNA sequencing (RNA-Seq) and bioinformatics analysis (BA) were conducted to identify differentially expressed genes (DEGs) among groups. Protein expression and cell cycle distribution were analyzed by Western blotting (WB) and flow cytometry. Exosomes were isolated and purified via differential centrifugation, characterized by nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM), and CHI3L1 expression in exosomes was verified via WB. Cx47 was silenced using small interfering RNA (siRNA) to evaluate its effect on OPC proliferation and exosome secretion. Artificial exosomes were constructed by encapsulating CHI3L1 in single unilamellar vesicles (SUVs), whose structure and size were validated by NTA and TEM. Following Cx47 knockdown, artificial exosomes were added back, and OPC proliferation was assessed via flow cytometry and EdU assay. RESULTS: Direct co-cultured with ASTs (Group C) resulted in significantly enhanced OPC proliferation compared to the Group O and Group A (P<0.05). RNA-Seq and WB analyses revealed that ASTs promote OPC proliferation and exosome secretion enriched in CHI3L1 through Cx47. Cx47 knockdown by siRNA led to significant decreases in OPC proliferation and exosome release (P<0.05). The inhibitory effect of Cx47 silencing on OPC proliferation was partially reversed by supplementation with either isolated exosomes or exogenous CHI3L1. CONCLUSIONS This study reveals a novel mechanism by which ASTs regulate OPC proliferation: Through direct contact, ASTs enhance the secretion of CHI3L1-rich exosomes via Cx47, thereby converting intercellular contact signals into secretory signals that promote OPC proliferation. As a key exosomal molecule, CHI3L1 may play an important role in neural function and remyelination and warrants further investigation.
Animals ; Exosomes/metabolism* ; Cell Proliferation ; Rats, Sprague-Dawley ; Rats ; Connexins/genetics* ; Oligodendrocyte Precursor Cells/metabolism* ; Astrocytes/metabolism* ; Chitinase-3-Like Protein 1/metabolism* ; Cells, Cultured ; Cell Differentiation

Objective:To explore the role and molecular mechanisms of S100A6 protein in neonatal meningitis caused by Streptococcus agalactiae. Methods:Human brain microvascular endothelial cells (HBMECs) were used as an in vitro experimental model, and siRNA was employed to construct S100A6 gene knockdown HBMECs strain. The S100A6 gene overexpression cell line was established by lentiviral transfection method. Western blot was used to detect the expression level of S100A6 protein in HBMECs after Streptococcus agalactiae infection, and the change in intracellular inflammatory cytokine protein levels after S100A6 gene knockdown or overexpression. A neonatal bacterial meningitis model was established by injecting Streptococcus agalactiae suspension into the cisterna magna of neonatal Sprague-Dawley (SD) rats. HE staining was used to observe pathological changes in brain tissue; immunohistochemistry was used to detect the expression and distribution of S100A6 protein in brain tissue; Western blot and ELISA were used to measure S100A6 protein levels in cerebrospinal fluid (CSF). Results:Compared with the control group, the intracellular S100A6 protein level in HBMECs increased significantly following Streptococcus cgalactiae infection. After S100A6 gene knockdown, the invasion rate of Streptococcus agalactiae into the HBMECs was significantly reduced ( P<0.01), while intracellular TNF-α and IL-6 protein levels were elevated markedly ( P<0.01). In contrast, overexpression of S100A6 gene increased the invasion rate ( P<0.01) and notably decreased TNF-α and IL-6 protein levels ( P<0.001). In the neonatal SD rat bacterial meningitis model, HE staining revealed substantial neutrophil infiltration in brain tissue after Streptococcus agalactiae infection. Immunohistochemistry showed extensive deposition of S100A6 protein around the meninges, and significant expression of S100A6 protein was also detected in CSF. Conclusions:S100A6 protein is crucial in mediating neonatal meningitis caused by Streptococcus agalactiae infection. S100A6 gene knockdown promotes the production of intracellular inflammatory cytokines and reduces Streptococcus agalactiae invasion into cells, thereby alleviating bacteria-induced cellular damage. Additionally, the increased expression of S100A6 protein in brain tissue and CSF after Streptococcus agalactiae infection suggests its potential as a diagnostic biomarker for bacterial meningitis.

Objective:To analyze the correlation between mental health status and metabolic syndrome (MetS) in health checkup people.Methods:It was a cross-sectional study, 2 920 participants who received health checkup in the Health Examination Center of Peking University Third Hospital from January 2019 to December 2023 were selected using cluster sampling method. Their general information, physical examination, biochemical indicators, body composition, and self-evaluation scores on the Symptom Checklist-90 (SCL-90) were collected. According to the inclusion and exclusion criteria, a total of 2 813 study subjects were included, and divided into the MetS group and the non-MetS group based on whether they had MetS. The differences in general demographic information, body composition, blood biochemistry, and SCL-90 scores between the two groups were compared. Binary Logistic regression analysis was used to explore the correlation between mental health status and MetS.Results:Of the 2 813 subjects included, 1 576 were males (56.0%) and 1 237 were females (44.0%), with an average age of (41.7±11.0) years, the MetS group had 586 cases (20.8%) and the non-MetS group had 2 227 cases (79.2%). The MetS group had higher levels of age, body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, total cholesterol, triglycerides, low density lipoprotein cholesterol (LDL-C), fasting blood glucose, glycosylated hemoglobin (HbA 1c), free thyroxine(FT4), total triiodothyronine (TT3), free triiodothyronine (FT3), waist-to-hip ratio, visceral fat area, body fat percentage, uric acid/creatinine, homocysteine (Hcy), aspartate aminotransferases (AST), and alanine transaminase (ALT) levels, as well as higher scores for somatization, hostility, paranoia, and other factor compared to the non-MetS group (all P<0.05), while high density lipoprotein cholesterol (HDL-C) and estimated glomerular filtration rate (eGFR) levels were lower than those in the non-MetS group (all P<0.05). The proportion of male, and the positive rates of SCL-90, somatization, interpersonal sensitivity, hostility, paranoia and other factor in the MetS group were higher than those in the non-MetS group (all P<0.05). Multifactorial analysis showed that individuals with a positive SCL-90 assessment had a 1.34 times higher risk of MetS than those with a negative assessment ( OR=1.34, 95% CI: 1.06-1.68; P=0.014). Among them, individuals with positive somatization ( OR=2.02, 95% CI: 1.25-3.28; P=0.004) and hostility ( OR=1.61, 95% CI: 1.02-2.56; P=0.042) had increased risk of MetS. Conclusion:Poor mental health status increases the risk of MetS.

Objective:To explore the correlation between normalized grip strength (NGS) and normal weight obesity (NWO) in the population undergoing health check-ups.Methods:It was a cross-sectional study. A cluster sampling method was adopted to consecutively select 4 104 subjects who completed general health check-ups, body composition tests, and grip strength tests at the Medical Examination Center of Peking University Third Hospital from January 2019 to December 2023. The general information, physical examination results, biochemical indicators, body composition, and grip strength test results were collected. The subjects were grouped by gender and whether they had NWO (male: NWO group 314 cases, normal control group 690 cases; female: NWO group 834 cases, normal control group 2 266 cases). The differences in various indicators between the NWO group and the normal control group were compared by using t-tests, χ 2 tests, or Mann-Whitney U tests. The subjects were divided into four groups with the quartiles of NGS (Q 1-Q 4 groups), and binary logistic regression analysis was used to explore the correlation between the NGS and NWO. The receiver operating characteristic (ROC) curve was used to evaluate the optimal cut-off point of the NGS for diagnosing NWO. Results:Among the 4 104 subjects included in the analysis, 1 148 (28.0%) had NWO. The risk of NWO in both males and females increased with the decrease of NGS. Compared with the Q 4 group, the risk of NWO in the Q 2 and Q 1 groups of males increased by 2.600 times ( OR=2.600, 95% CI:1.556-4.343) and 4.350 times ( OR=4.350, 95% CI: 2.618-7.229), respectively; the risk of NWO in the Q 3, Q 2, and Q 1 groups of females increased by 2.024 times ( OR=2.024, 95% CI: 1.322-3.099), 4.265 times ( OR=4.265, 95% CI: 2.856-6.371), and 7.395 times ( OR=7.395, 95% CI: 4.991-10.956), respectively (all P<0.05). The optimal cut-off point of the NGS for diagnosing NWO in males and females was 0.636 2 and 0.472 2, respectively. Conclusions:The NGS is negatively correlated with the risk of NWO. Evaluation of the NGS can provide a reference for the early diagnosis and prevention of NWO.

Objective:To construct a health management mode for functional community groups and evaluate its health management effect.Methods:This study was a non-randomized controlled trial. A cluster sampling method was adopted to select 3 352 subjects who completed three health examinations at the Physical Examination Center of Peking University Third Hospital from January 2022 to October 2024 and received health management for two consecutive years from a certain functional community (an enterprise) in Beijing as the research subjects. A health management mode for functional community groups was constructed, and a cohort of the population was established. A health management platform was built, and the research subjects were included in the health management system. Comprehensive interventions were carried out using multiple methods, including disease risk assessment, daily monitoring and reminders, exercise and nutrition assessment and intervention, personal health consultation, and health science popularization knowledge push. The subjects were classified and analyzed based on general information such as age and gender. The changes in systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were assessed using One-way Repeated Measures Analysis of Variance before the intervention and at 1 and 2 years after the intervention. The changes in triglycerides were assessed using Generalized Estimating Equations before the intervention and at 1 and 2 years after the intervention.Results:The systolic blood pressure, total cholesterol, and LDL-C levels of the total population showed a linear decreasing trend after the intervention (all P0.001). The HDL-C level showed an overall upward trend after the intervention [(1.45±0.32) vs (1.39±0.30) vs (1.47±0.33) mmol/L, F=12.746, P0.001]. However, there was no linear change trend in diastolic blood pressure, fasting blood glucose, and triglycerides after the intervention (all P0.05). The systolic blood pressure, total cholesterol and LDL-C levels of both men and women showed a linear decreasing trend after the intervention. For men, systolic blood pressure [(128.6±16.1) vs (127.6±16.3) vs (126.5±15.5) mmHg (1 mmHg=0.133 kPa); F=33.488, P0.001], total cholesterol [(5.29±1.02) vs (5.07±1.00) vs (4.94±1.03) mmol/L; F=286.525, P0.001], and LDL-C [(3.45±0.86) vs (3.43±0.84) vs (3.33±0.83) mmol/L; F=55.419, P0.001] all decreased. For women, systolic blood pressure [(118.9±15.6) vs (117.5±15.6) vs (117.2±15.8) mmHg; F=34.188, P0.001], total cholesterol [(5.13±0.94) vs (4.96±0.90) vs (4.85±0.90) mmol/L; F=274.080, P0.001], and LDL-C [(3.13±0.79) vs (3.10±0.76) vs (3.10±0.75) mmol/L; F=6.861, P=0.009] also decreased. The HDL-C level of men showed an overall upward trend after the intervention [(1.30±0.26) vs (1.25±0.25) vs (1.32±0.28) mmol/L; F=6.866, P0.05]. For men and women, diastolic blood pressure, fasting blood glucose and triglyceride levels showed no linear change trend after the intervention (all P0.05). The systolic blood pressure and total cholesterol levels of all age groups showed a linear decreasing trend after the intervention(all P0.001). In the 50-59 age group, diastolic blood pressure showed a linear decreasing trend after intervention [(81.6±11.6) vs (80.1±11.6) vs (79.9±11.6) mmHg; F=7.043, P0.05]. In the 40-49 age group, triglyceride showed an overall decreasing trend after intervention [1.29(0.91-2.01) vs 1.27(0.88-1.91) vs 1.27(0.92-1.89) mmol/L; Wald χ 2=10.062, P0.05]. In the 30-39 age group, LDL-C showed a linear decreasing trend after intervention [(3.23±0.80) vs (3.20±0.79) vs (3.19±0.77) mmol/L; F=7.702, P0.05]. In the 40-49 age group, LDL-C also showed a linear decreasing trend after intervention [(3.39±0.84) vs (3.36±0.82) vs (3.30±0.80) mmol/L; F=22.801, P0.001]. In the 50-59 age group, LDL-C showed a linear decreasing trend after intervention [(3.38±0.92) vs (3.32±0.91) vs (3.15±0.88) mmol/L; F=27.920, P0.001]. In the 30-39 age group, HDL-C showed an overall increasing trend after intervention [(1.46±0.33) vs (1.39±0.31) vs (1.48±0.34) mmol/L; F=10.047, P0.05]. In the 40-49 age group, HDL-C also showed an overall increasing trend after intervention [(1.45±0.30) vs (1.40±0.30) vs (1.47±0.32) mmol/L; F=10.118, P0.05]. However, there was no linear change trend in fasting blood glucose and triglyceride levels in all age groups after intervention ( F=1.169, 2.643, 0.663, 0.001, all P0.05). Conclusion:The functional community group health management mode constructed in this study has a good effect.

Objective To analyze the economic cost of self-monitoring of gestational diabetes mellitus, and provide a basis for measuring the economic burden of gestational diabetes mellitus, and to provide a reference for the formulation of intervention development and the adjustment of resource allocation. Methods The individual economic cost of self-monitoring for gestational diabetes mellitus was measured based on a decision tree model, and the total economic cost of self-monitoring for gestational diabetes mellitus in Beijing was estimated. The uncertainty of the model parameters was analyzed using one-way sensitivity analysis. Results The average individual economic cost of gestational diabetes self-monitoring was 1184 RMB, and the individual cost incurred by choosing different types of blood glucose meters ranged from 403 to 18 000 RMB. The average individual economic cost of finger-stick blood glucose monitoring was 606 RMB and the average individual economic cost of continuous glucose monitoring was 2 374 RMB. The total economic cost of gestational diabetes self-monitoring in Beijing was 23.818 0 million RMB, and the total economic cost incurred by choosing different types of blood glucose meters ranged from 0.292 5 to 9.027 9 million RMB. The proportion of the finger-stick blood glucose monitoring had the greatest impact on the robustness of the results. Conclusion Finger-stick blood glucose monitoring is still the dominant self-monitoring method and is less costly than continuous glucose monitoring. Self-monitoring of pregnant women with gestational diabetes mellitus incurs certain economic cost and causes an economic burden on society.

Coptis chinensis Franch. and Panax ginseng C. A. Mey. are traditional herbal medicines with millennia of documented use and broad therapeutic applications, including anti-diabetic properties. However, the synergistic effect of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng on type 2 diabetes mellitus (T2DM) and its underlying mechanism remain unclear. The research demonstrated that the optimal ratio of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng was 4∶1, exhibiting maximal efficacy in improving insulin resistance and gluconeogenesis in primary mouse hepatocytes. This combination demonstrated significant synergistic effects in improving glucose tolerance, reducing fasting blood glucose (FBG), the weight ratio of epididymal white adipose tissue (eWAT), and the homeostasis model assessment of insulin resistance (HOMA-IR) in leptin receptor-deficient (db/db) mice. Subsequently, a T2DM liver-specific network was constructed based on RNA sequencing (RNA-seq) experiments and public databases by integrating transcriptional properties of disease-associated proteins and protein-protein interactions (PPIs). The network recovery index (NRI) score of the combined treatment group with a 4∶1 ratio exceeded that of groups treated with individual components. The research identified that activated adenosine 5'-monophosphate-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling in the liver played a crucial role in the synergistic treatment of T2DM, as verified by western blot experiment in db/db mice. These findings demonstrate that the 4∶1 combination of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng significantly improves insulin resistance and glucose and lipid metabolism disorders in db/db mice, surpassing the efficacy of individual treatments. The synergistic mechanism correlates with enhanced AMPK/ACC signaling pathway activity.
Animals ; Panax/chemistry* ; Ginsenosides/administration & dosage* ; Diabetes Mellitus, Type 2/metabolism* ; Mice ; Male ; Alkaloids/pharmacology* ; Coptis/chemistry* ; Drug Synergism ; Insulin Resistance ; Mice, Inbred C57BL ; Humans ; Transcriptome/drug effects* ; Blood Glucose/metabolism* ; Hypoglycemic Agents/administration & dosage* ; Drugs, Chinese Herbal/administration & dosage* ; Hepatocytes/metabolism*

Objective: To construct a Family with sequence similarity 50 member A(FAM50A) gene knockout mouse insulinoma pancreatic β-cell line Beta-TC-6 using CRISPR/Cas9 gene editing technology and to prepare polyclonal antibodies specifically recognizing FAM50A. Methods: Two guide RNAs(sgRNAs) targeting the FAM50A gene were designed,and a recombinant plasmid expressing blue fluorescent protein(BFP) was constructed for gene knockout.The successfully constructed plasmid was transfected into Beta-TC-6 cells,and BFP-positive single cells were isolated for clonal expansion.The expanded monoclonal cell lines were genotyped by Sanger sequencing,and FAM50A protein expression was assessed by Western blot.Purified human recombinant FAM50A protein was used to immunize New Zealand rabbits for the preparation of a polyclonal antibody.The specificity of the prepared antibody was then validated using the successfully established FAM50A knockout cell line. Results: A monoclonal cell line with a successful knockout of the FAM50A gene was identified.Sanger sequencing confirmed base deletions at the target site.Western blot analysis showed a complete absence of FAM50A protein expression in this cell line.The prepared polyclonal antibody successfully recognized endogenous murine FAM50A protein in wild-type Beta-TC-6 cells and in hTERT-RPE1 cells overexpressing human FAM50A-GFP fusion protein,while no signal was detected in the FAM50A knockout cells. Conclusion This study successfully established a FAM50A gene knockout Beta-TC-6 cell model and generated a FAM50A polyclonal antibody,providing powerful tools for future research.

Objective To investigate the impact of catheter-associated urinary tract infection(CAUTI)on the prognosis of neurosurgical inpatients with indwelling catheters.Methods Neurosurgical inpatients with indwelling catheters and hospital stays＞2 days from January 2018 to December 2023 were selected as the study subjects.CAUTI during hospitalization was used as the exposure factor.A 1∶2 propensity score matc-hing method was applied to control for confounding factors,subsequently,63 patients were included in the CAUTI group and 121 in the non-CAUTI group.The impact of CAUTI on prognostic indicators in these pa-tients was analyzed.Results A total of 554 neurosurgical inpatients with indwelling catheters were included,among whom 70 developed CAUTI,yielding an infection rate of 12.64％.After propensity score matching,compared with the non-CAUTI group,the CAUTI group showed significantly longer hospital stays and in-dwelling catheter durations,higher total hospitalization costs,and higher out-of-pocket expenses,the differ-ences were statistically significant(P＜0.05).However,there was no significant difference in mortality be-tween the two groups(P＞0.05).Among the various medical cost items,significant differences were observed in medical service fees,diagnostic fees,other treatment fees,Western medicine fees,antibacterial drug fees,traditional Chinese medicine fees,consumable costs,and other expenses(P＜0.05),while no significant differ-ence was found in surgical treatment fees(P＞0.05).Conclusion CAUTI prolongs hospital stays and in-dwelling catheter durations,and increases medical costs.Effective measures should be taken to prevent and control CAUTI,thereby improving patient prognosis,reducing patients' direct financial burden,and enhancing the utilization of medical resources.