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.

Drug-target interaction (DTI) is fundamental to novel drug research and development (R &D), playing a critical role in elucidating drug mechanisms of action and improving the cost-effectiveness of drug discovery. Although China has seen rapid accumulation of drug-target resources in recent years, the industry still faces challenges such as a shortage of original targets and excessively high target concentration. The rapid advancement of artificial intelligence (AI) has provided an efficient technological pathway for DTI prediction, establishing it as a core tool for accelerating drug discovery. This paper systematically reviews the fundamental data support framework for DTI prediction tasks, elaborating in detail on three core data types— drug characterization, target characterization, and drug-target associations-as well as the classification and application boundaries of mainstream benchmark datasets tailored to different tasks within the field. On this basis, it comprehensively surveys the technological evolution of AI-driven DTI prediction, summarizing the core paradigms and technical advances of traditional machine learning and deep learning methods in a single-modality setting, alongside cutting-edge multimodal approaches that integrate two modalities (cross-subject/within-subject fusion) and three or more modalities for multidimensional information integration. Finally, this paper analyzes the current major challenges in data quality, model generalizability and interpretability, and real-world deployment, while also discussing future trends in standardized dataset construction, generative AI, and large-scale biomedical foundation models, aiming to provide a reference for both research and industrial applications in the AI-driven DTI prediction field.

Objective:To analyze the clinical features and genetic sequencing results of a patient with Kallmann syndrome(KS) carrying digenic mutations who initially presented with osteoporosis, and to enhance awareness of this disease phenotype.Methods:Clinical data were collected, and peripheral blood DNA was extracted for whole-exome sequencing. Relevant literature was reviewed to summarize phenotypes associated with digenic/oligogenic variants involving CHD7.Results:The patient exhibited back pain, delayed development of secondary sexual characteristics, and hyposmia. Laboratory tests revealed reduced sex hormones and gonadotropin levels, while pituitary imaging was unremarkable. Bone mineral density imaging confirmed osteoporosis, and thoracolumbar X-rays showed multiple vertebral compression fractures. Genetic analysis identified a heterozygous splice-site mutation in CHD7(c.2698-1G>T) and a heterozygous missense mutation in WDR11(c.439G>A: p.D147N). According to ACMG criteria, the CHD7 mutation was classified as pathogenic, while the WDR11 variant was defined as a variant of uncertain significance(VUS). Literature review indicated that 40% of KS patients with digenic/oligogenic variants involving CHD7 presented with hearing or ocular abnormalities.Conclusion:This study reports a novel CHD7 mutation and a previously undescribed digenic combination of CHD7 and WDR11 variants in a KS patient. CHD7 variants may be implicated in auditory or ocular involvement in KS cases with digenic/oligogenic inheritances. KS patients may also manifest skeletal abnormalities in addition to hypogonadotropic hypogonadism. Tailored management of sex hormones and osteoporosis therapies across life stages is essential for optimizing bone health in KS.

Objective:To analyze the epidemiological characteristics of severe fever with thrombocytopenia syndrome (SFTS) in Beijing in 2024, to investigate the infection status of reservoir hosts, vector organisms, and baseline human populations, and provide a scientific basis for formulating prevention and control strategies.Methods:Epidemiological surveys were conducted on all confirmed cases. Serum samples from healthy populations and reservoir hosts were collected for SFTSV antibody detection. Questing ticks were monitored using the flagging method. Real-time fluorescent quantitative PCR was employed to detect SFTSV in cases, reservoir hosts, and ticks. Positive samples underwent whole-genome sequencing and genetic evolution analysis.Results:In 2024, Beijing reported 15 locally infected cases with 4 deaths. The age of onset ranged from 50 to 80 years (median: 66 years). Cases showed a certain degree of geographical clustering, with June being the peak month of onset. The affected population was predominantly farmers, with a male-to-female ratio of 3∶2. Animal contact history emerged as a significant risk factor alongside tick bites. Parthenogenetic tick populations were identified in Pinggu district, while SFTSV-carrying ticks were detected in endemic areas (Mentougou, Shijingshan, and Fengtai Districts). Viral presence was also confirmed in ticks or dogs from non-endemic areas. Sequencing and phylogenetic analysis revealed stable clustering of strains into two distinct genotypes (A and B). Antibody-positive individuals were identified in healthy populations from non-endemic areas.Conclusions:The incidence of SFTS in Beijing is increasing, with natural viral circulation already established in non-endemic regions. Enhanced surveillance and adjusted prevention strategies are urgently needed.

Objective To describe the clinical features of patients with primary sclerosing cholangitis(PSC)in China based on a nationwide multicenter patient cohort,and to investigate the risk factors for prognosis.Methods A retrospective cohort study was conducted among the patients with a confirmed diagnosis of PSC based on the electronic medical record system of seven grade A tertiary hospitals across the country,and related data were extracted.The Mann-Whitney U test was used for comparison of continuous data between groups,and the chi-square test was used for comparison of categorical data between groups.The Kaplan-Meier method was used to estimate liver transplant-free survival,and the log-rank test was used for comparison of survival rate between PSC patients with different features.The Cox regression model was used to identify independent risk factors for the prognosis of PSC patients and the interactions between key factors.Results A total of 107 patients were enrolled,among whom 55.6%(55/99)had large-duct PSC and 29.0%(31/107)had comorbidity with inflammatory bowel disease(IBD).The positivity rate of anti-neutrophil cytoplasmic antibody(ANCA)was 32.9%(24/73),and 50.0%(40/80)of the patients had an increase in IgG/IgM.The median symptom-to-diagnosis interval was 1 year(<1-4.0),and 38.3%(41/107)of the patients had progressed to decompensated cirrhosis at the time of diagnosis.The median liver transplant-free survival time was 114 months(95%confidence interval[CI]:62-166),with a 5-year survival rate of 65.7%.The multivariate analysis showed that an increase in total bile acid(TBA)(hazard ratio[HR]=1.006,95%CI:1.002-1.010,P=0.001)and a prolonged symptom-to-diagnosis interval(HR=1.252,95%CI:1.059-1.480,P=0.009)were independent risk factors for prognosis.The interaction analysis showed that compared with the female patients with TBA<50 μmol/L,both male and female patients with TBA≥50 μmol/L had a significant increase in the risk of liver transplantation or death(male:HR=16.563,95%CI:2.103-130.449,P<0.001;female:HR=17.009,95%CI:2.113-136.934,P<0.001),and compared with the patients with an age of<45 years and a TBA level of<50 μmol/L,the patients with an age of≥45 years and a TBA level of≥50 μmol/L had a significant increase in the risk of liver transplantation or death(HR=10.729,95%CI:1.325-86.859,P=0.026).Compared with the female patients with an symptom-to-diagnosis interval of≤2 years,the male patients with a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.825,95%CI:1.725-13.644,P=0.003),and compared with the patients with an age of<45 years and a symptom-to-diagnosis interval of≤2 years,the patients with an age of<45 years and a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.983,95%CI:1.366-18.173,P=0.015).Conclusion Compared with the reports from Western countries,large-duct PSC is also the main type of PSC in China,but with a relatively low proportion,and there is also a relatively low proportion of patients with IBD or positive ANCA.An increase in TBA and a prolonged symptom-to-diagnosis interval are independent risk factors for prognosis,with significant interactions with age and sex.This suggests that early screening and intervention should be enhanced to improve prognosis.

Public hospitals have formed a relatively perfect working foundation in the introduction and training of young talents,but the evaluation system of young talents is not perfect.Based on the requirements of high-quality development,grasp the principle of party management of talents,combine the talents development situation in Jiading District Maternal and Child Health Care Hospital,takes the special training of young talents in administration as the starting point,comprehensively uses the literature method,interview method and Delphi method to establish the index database,uses the exploratory factor analysis meth-od to calculate the index weight,and constructs the evaluation model of young talents in hospital administrative management,so as to help hospitals better screen and evaluate talents and give full play to the value and role of talents as the first resource.

Objective A randomized controlled trial was conducted on colonoscopy inpatient and outpatients to compare the efficacy and safety of water exchange(WE)colonoscopy and CO2 convention insufflation colonoscopy in elderly patients.Methods 340 patients underwent fully sedated colonoscopy were randomly divided into two groups according to colonoscopy with either WE colonoscopy group(WE group)and CO2 insufflation colonoscopy group(CO2 group).The two groups were compared in terms of Boston bowel preparation scale(BBPS),withdrawal time,cecal intubation time,cecal intubation success rate,abdominal compression,willingness to repeat,polypdetectionrate(PDR),adenoma detection rate(ADR),and safety.Results The cecal intubation success rate was significantly higher in WE group(100.0%)compared with CO2 group(96.5%),the difference was statistically significant(P=0.013).The average cecal intubation time of WE group was(10.50±1.79)min,which was longer than that of CO2 group(7.55±1.50)min,and the difference was statistically significant(P<0.01).Comparison of withdrawal time and BBPS between the two groups,the differences were not statistically significant(P>0.05).The abdominal pressure rate was lower in WE group(5.9%)compared with CO2 group(13.5%),the difference was statistically significant(P=0.017).The rate of willingness to re-examination in the WE group was 98.2%,which was significantly higher than the 93.5%in the CO2 group.The PDR in WE group(80.6%)was higher than that in CO2 group(70.6%),the ADR in WE group(67.1%)was higher than that in CO2 group(50.6%),the differences were statistically significant(P<0.05).Multivariate Logistic regression analysis showed that WE group was an effective factor in improving ADR(O＾R=2.027,P<0.01).The overall adverse events were less than 3%,with no difference between the two groups(P=1.000).Conclusion The use of WE colonoscopy has a better improved efficacy in elderly patients,and safety should be ensured by individualized assessment of the patient's co-morbidities,bowel preparation tolerance,and willingness prior to the procedure.

Human commensal microbiota exists in the gastrointestinal tract, oral cavity, ocular surface, and intraocular organs.Gastrointestinal commensal microbiota can cause glaucomatous optic nerve damage through autoimmune injury mechanisms, inflammation, or oxidative stress.The imbalance of intestinal microbiota represented by Helicobacter pylori infection may affect the function of trabecular cells by releasing inflammatory mediators and vasoactive substances.The resulting active metabolites affect the oxidative stress and apoptosis of trabecular cells.Autoimmune activation of glial cells leads to apoptosis of retinal ganglion cells.The imbalance of oral symbiotic microbiota can mediate the activation of microglia in the retina and optic nerve and the loss of retinal ganglion cells through the body's immune response.Bacterial products' toxic effects lead to optic nerve degeneration and induce chronic subclinical systemic inflammatory vascular endothelial cell dysfunction resulting in optic nerve damage.Ocular surface commensal microbiota mainly causes optic nerve damage through immune response, but whether it is related to intraocular diseases such as glaucoma remains to be studied.The imbalance of intraocular symbiotic microbiota is a specific characteristic of glaucoma.The changes in the intraocular immune microenvironment caused by intraocular microbiota may involve the complex effects of multiple inflammatory mediators and multiple molecular pathways.This article reviews the recent research in these areas, the extraocular, ocular surface, and intraocular symbiotic microbiota and their metabolites may directly or indirectly play a specific role in the pathogenesis of glaucoma.The comprehensive study and analysis of the microbiome of each part of the same individual in the future will provide a new angle to explore the cause and pathogenesis of glaucoma and provide new research ideas for the diagnosis and treatment of glaucoma.

Objective: To evaluate the safety and efficacy of preoperative autologous blood donation (PABD) under anesthesia monitoring in elective surgical procedures, and to provide scientific data for promoting its clinical application. Methods: 1) A total of 1 164 patients scheduled for elective surgery and met the criteria for stored autologous blood transfusion in our hospital from March 2022 to September 2023 were enrolled. Prior to surgery, stored autotransfusion was performed under anesthesia monitoring. During the operation, blood pressure (BP), heart rate (HR), blood oxygen saturation (SpO ) and other basic life indicators before and after blood collection were recorded and analyzed. Adverse reactions during blood collection were documented, and potential influencing factors were analyzed. 2) The autologous transfusion group (experimental group, patients receiving intraoperative autologous blood reinfusion) was compared with the allogeneic transfusion group (control group, patients without PABD during the same period) using propensity score matching. The length of hospital stay, transfusion-related costs, perioperative hemoglobin (Hb), hematocrit (Hct), platelet count (Plt) and coagulation function were compared between the two groups after matching. Results: 1) Three patients (0.26%) had adverse reactions during blood collection. Autologous blood transfusion was performed in 443 patients (38.1%) during or after operation, with no adverse reaction during blood transfusion. 2) The systolic blood pressure (SBP) and diastolic blood pressure (DBP) of patients after blood collection were lower than before blood collection, and the SpO was higher than before blood collection, with statistically significant differences (P<0.05); There was no significant difference in heart rate before and after blood collection (P>0.05); Our analysis found that age, gender, blood collection volume, department, or mild-to-moderate circulatory system complications didn’t significantly affect BP, HR and SpO fluctuations (P>0.05). 3) The experimental group had shorter hospital stays and lower transfusion costs than the control group (P<0.05). 4) No significant differences were observed in Hb, Hct, Plt levels or coagulation function (PT, APTT) between the two groups after operation (P>0.05). The hospitalization duration and transfusion related expenses in the experimental group were lower than those in the control group (P<0.05). Conclusion: PABD under anesthesia monitoring is safe and feasible in elective surgeries across diverse patient groups and surgical fields. It reduces the costs and conserves blood resources, which is worthy of further promotion.

OBJECTIVE: To observe the effects of "olfactory three needles" on cognition, learning and memory abilities, as well as hippocampal microglia (MG) phagocytic activity in vascular dementia (VD) rats, and explore the mechanisms of acupuncture in regulating MG activation and improving remyelination, so as to ameliorate VD. METHODS: Among 38 SD rats meeting experimental requirements, 9 rats were randomly assigned to a sham-operation group, and the remaining rats underwent permanent bilateral common carotid artery ligation to establish VD model. Eighteen successfully modeled rats were randomly divided into a model group and an electroacupuncture (EA) group, with 9 rats in each one. In the EA group, EA was performed at "olfactory three needles" ("Yintang" [GV24⁺] and bilateral "Yingxiang" [LI20]), at disperse-dense wave, the frequency of 2 Hz/15 Hz and the current intensity of 1 mA, for 15 min per intervention, once daily. One course was composed of 7 days, and 2 courses were required, with the interval of 2 days. The novel object recognition test was employed to assess the cognition of rats, and the Morris water maze was adopted to observe learning and memory abilities. Luxol fast blue (LFB) staining was performed to evaluate myelin sheath loss in the hippocampus, the Western blot was used to detect the protein expression of triggering receptor expressed on myeloid cells-2 (TREM2) and proteolipid protein (PLP) in the hippocampus; and the immunofluorescence staining was used to detect the positive expression of PLP, sex determining region Y-box 10 (SOX10), ionized calcium binding adaptor molecule 1 (Iba1)⁺ TREM2⁺ and Iba1⁺ lysosome-associated membrane protein 1 (LAMP1)⁺ in the hippocampus. RESULTS: Compared with the sham-operation group, the rats in the model group exhibited the prolonged escape latency on day 3 and 4 (P<0.05, P<0.01), the increase of the total distance traveling (P<0.01) and the decrease of the recognition index (RI) and platform crossing frequency (P<0.01). Compared with the model group, the rats in the EA group showed the shortened escape latency on day 3 and 4 (P<0.05), the decrease of total distance traveling (P<0.01) and the increase of RI and platform crossing frequency (P<0.05, P<0.01). When compared with the sham-operation group, the rats of the model group presented uneven staining, sparse arrangement of myelin sheath fibers, unclear contours, and prominent vacuole-like changes in the hippocampal CA1 region. When compared with the model group, the EA group showed more dense staining, the increase of myelin sheath fibers with more orderly alignment, and fewer vacuolar changes in the hippocampal CA1 region. Compared with the sham-operation group, the model group exhibited the increase of TREM2 protein expression and the decrease of PLP protein expression in the hippocampus (P<0.01), whereas the EA group showed the up-regulation of TREM2 and PLP protein expression when compared with the model group (P<0.01, P<0.05). The positive expression of the hippocampal PLP, SOX10, and Iba1⁺LAMP1⁺ in the model group was reduced in comparison with the sham-operation group (P<0.05, P<0.01), and the positive expression of Iba1⁺ TREM2⁺ was elevated (P<0.05). In the EA group, the positive expression of PLP, SOX10, Iba1⁺TREM2⁺, and Iba1⁺ LAMP1⁺ was higher compared with that in the model group (P<0.05, P<0.01). CONCLUSION "Olfactory three needles" can improve the learning and memory, and cognitive functions of VD rats, and its mechanism may be associated with the up-regulation of TREM2 and LAMP1 to adjust MG phagocytic activity and intracellular degradation, and promote remyelination.
Animals ; Dementia, Vascular/metabolism* ; Rats ; Rats, Sprague-Dawley ; Microglia/metabolism* ; Male ; Acupuncture Therapy/instrumentation* ; Acupuncture Points ; Humans ; Remyelination ; Memory ; Hippocampus/cytology* ; Cognition ; Electroacupuncture ; Needles