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.

Objective: To examine the association between health behaviors and depressive symptoms among junior and senior high school students, so as to provide evidence for combined behavioral interventions targeting adolescent mental health. Methods: From September to November 2023, a stratified cluster random sampling method was used to recruit 104 834 junior and senior high school students from all 13 prefecture level cities (124 districts/counties) in Heilongjiang Province, China. Multivariable Logistic regression models, as well as multiplicative and additive interaction analyses were employed to analyze the associations between health behaviors and depressive symptoms, and Chi-square tests for trend were conducted to explore ,the changing tendency in the risk of depressive symptoms with increasing numbers of health behaviors among junior and senior high school students. Results: Healthy diet ( OR =0.66, 95% CI =0.63-0.68), healthy physical activity ( OR =0.47, 95% CI =0.45-0.49), healthy outdoor activity ( OR =0.55, 95% CI =0.52-0.57), healthy sleep ( OR =0.72, 95% CI =0.69-0.75), and healthy screen use ( OR =0.79, 95% CI =0.76-0.82) were independently associated with lower rates of depressive symptoms (all P <0.01). The risk of depressive symptoms decreased progressively with an increasing cumulative number of health behaviors ( χ 2 trend =996.73, P <0.01). Except for the interaction between healthy diet and healthy sleep, significant additive interactions were observed among the remaining health behaviors( RERI =0.07-0.23,all P <0.05). The probability of depressive symptoms was lower among girls with 2-3 healthy behaviors than among boys ( Z =2.51, 2.65), lower among urban students with 2-3 healthy behaviors than among suburban county students ( Z =-2.36, -2.04), and lower among senior high school students with 2-4 healthy behaviors than among junior high school students ( Z =2.17, 2.10, 2.04) (all P <0.05). Conclusions Health behaviors are significantly associated with depressive symptoms among junior and senior high school students. The probability of depressive symptoms is lower among girls, urban students, and senior high school students who engage in multiple healthy behaviors. Implementing combined interventions targeting multiple health behaviors in these populations may yield greater benefits.

Objective:To investigate the trends in detection, treatment, and outcomes of rifampicin-resistant tuberculosis (TB) in Jiangsu Province from 2013 to 2023, assess the effectiveness of control policies and measures for drug-resistant TB, and provide evidence for better control of drug-resistant TB.Methods:Data and indicators related to the screening, diagnosis, treatment, and outcomes of rifampicin-resistant TB in Jiangsu Province from 2013 to 2023 were obtained from the Tuberculosis Management Information System. The Joinpoint regression method was employed to analyze the trends over this period, and annual percent change (APC) and average annual percent change (AAPC) were calculated. A comparative analysis was also conducted to evaluate the changes before and after implementing relevant policies and measures.Results:From 2013 to 2023, the number of registered rifampicin-resistant TB patients in Jiangsu Province showed a consistent upward trend (APC=AAPC=1.45%, P=0.035). The screening rates for drug resistance among new TB patients in high-risk groups and the proportion of molecular biological testing for drug resistance all exhibited increasing trends, with a notable turning point occurring in 2018. The trend of the treatment enrollment rate for rifampicin-resistant TB patients experienced a significant shift in 2020, showing a marked increase from 2013 to 2020 (APC=12.91%, P=0.008). The treatment success rate of rifampicin-resistant TB patients also showed a significant upward trend after a turning point in 2020 (APC=9.94%, P=0.004). Conclusion:From 2013 to 2023, significant progress was seen in preventing and treating rifampicin-resistant TB in Jiangsu Province, with relevant policies and measures proving to be highly effective.

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.

Objective To investigate the effects of open reading frame 1 protein(ORF1p),encoded by long interspersed nuclear element-1(LINE-1),on the proliferation,migration,and invasion of esophageal squamous cell carcinoma(ESCC)cells,and explore the underlying molecular mechanism.Methods① Western blotting was performed to compare the expression of ORF1p between normal esophageal squamous epithelial cells and ESCC cells.② Immunohistochemistry(IHC)assay was used to examine ORF1p expression in ESCC tissues and paired normal tissues adjacent to tumor.③ The effects of ORF1p knockdown and overexpression on malignant behaviors in ESCC cells were determined through functional assays.④ Xenograft tumor model in nude mice was established to evaluate the impact of ORF1p on tumor growth in vivo.⑤ Transcriptome sequencing combined with cell functional rescue experiments were conducted to identify downstream targets regulated by ORF1p.Results ① Western blot analysis demonstrated the expression of ORF1p was significantly higher in the ESCC cell lines than the normal esophageal squamous epithelial cells(P<0.05).② IHC confirmed remarkable up-regulation of ORF1p in ESCC tissues than paired adjacent normal tissues(P<0.000 1).③ Functional assays and experiments on xenograft tumor models revealed that ORF1p substantially enhanced the proliferation,migration,and invasion of ESCC cells,as well as tumorigenic potential in vivo(P<0.05).④ Functional rescue experiments showed that ORF1p facilitated the proliferation,migration,and invasion of ESCC cells by modulating AJUBA expression(P<0.05).Conclusion ORF1p is significantly up-regulated in ESCC and promotes the proliferation,migration,and invasion of ESCC cells by regulating AJUBA expression.

Renal tubular acidosis（RTA）in children is mainly primary，with a low incidence rate and often an insidious onset. It exhibits strong clinical heterogeneity，and the related complications include growth retardation，abnormal bone metabolism，and renal dysfunction，which seriously affect the life quality of children. Currently，clinical attention to RTA remains insufficient，and its genetic mechanisms have not been fully clarified. The metabolic control rate and patient compliance need to be improved. This article reviews important research advances in the field of primary RTA，summarizes progress in classification，etiology，diagnostic and therapeutic strategies，prognosis and long-term disease management. It emphasizes that the precise diagnosis and treatment of children with primary RTA require the integration of molecular genetic technologies，individualized treatment regimens，and long-term monitoring and follow-up. In the future，efforts should focus on enhancing epidemiological studies and establishing evidence-based guidelines，further elucidating the pathogenesis of RTA，developing better-tolerated medications suitable for long-term use，and advancing parallel strategies for the prevention and management of primary RTA.

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

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*