AIM:To evaluate the safety and toler-ability of single dose oral BTK inhibitor YZJ-3058 tablets under fasting conditions in healthy adults,as well as the pharmacokinetic and pharmacologi-cal characteristics of YZJ-3058 and its metabolites.METHODS:A total of 22 healthy subjects were en-rolled in this experiment and administered a single dose orally.They were divided into three groups:50 mg,100 mg,and 200 mg.Among them,2 sub-jects were enrolled in the 50 mg dose group,and 10 subjects were enrolled in the 100 mg and 200 mg dose groups,respectively.RESULTS:In healthy subjects,YZJ-3058 tablets were administered orally on an empty stomach at doses of 50,100,and 200 mg,with a median Tmax of 1.25 to 2.00 hours and an average Cmax of 62.85,89.44,and 99.20 ng/mL,re-spectively.The average AUC0-t was 183.87,297.72,and 453.98 h·ng-1·mL,respectively.The average AUC0-∞ was 189.30,321.33,and 551.44 h·ng-1·mL,and the median t1/2 was 1.16,5.06,and 7.97 hours,respectively.After a single oral administration of 50,100,and 200 mg YZJ-3058 tablets,the highest target occupancy rate was achieved at 4 hours.The average BTK occupancy rates at 24 hours after ad-ministration were 88.95％,96.73％,and 99.24％,re-spectively.The average BTK occupancy rates at 48 hours after administration were 75.65％,89.80％,and 96.68％,respectively.No serious adverse events or adverse events leading to withdrawal oc-curred,and all subjects had good tolerability.CON-CLUSION:YZJ-3058 tablets have good safety and tolerability for single oral administration on an empty stomach in healthy subjects within the dose range of 50-200 mg.Cmax and AUC increase with dose,with fast absorption and saturation.The ter-minal elimination rate gradually slows down with dose increase,and it has a significant and sus-tained occupying effect on BTK targets.

Objective:To evaluate a transhiatal tunnel flap designed to reconstruct the cardiac functional structure in proximal gastric cancer patients in our center.Methods:A descriptive case study method was used to select the data of 11 patients undergoing surgery for upper gastric cancer from Jan to Jul 2024. After laparoscopic dissection is completed, the esophagus is transected 2 cm from the upper edge of the tumor and the specimen is removed. The distance from the lower edge of the tumor is 5 cm. The cutting width is 4 cm, and the length of sleeve distal stump stomach is 20 cm. A seromuscular flap tunnel was made with a length of 2 cm and a width of 2 cm, 2 cm away from the top of the remnant stomach. The digestive tract was reconstructed using the Overlap hybridization method.Results:The median operation time was 175 (139-285) minutes. The median muscle flap production time and reconstruction time was 10.5 (5.5-21.0) minutes and 15.0 (11.8-33.6) minutes, respectively. The median blood loss is 50 (20-100) ml. The median postoperative hospitalization was 8 (6-25) days. The median tumor size was 2.5 (1.0-4.0) cm, and 31 (15-52) lymph nodes were dissected. The median follow-up after surgery was 3.5 (0.7-6.0) months, and no tumor recurrence or metastasis was found. Postoperative anastomotic leakage (Clavien-Dindo grade Ⅱ) occurred in one case, and there was no perioperative death. The Visick score of the whole group was 1 point in 8 cases and 2 points in 3 cases, and there was no anastomotic stenosis. Reflux esophagitis (Los Angeles classification grade B) was found in 1 case after gastroscopy, and the symptoms were relieved by conservative treatment.Conclusion:The transhiatal tunnel flap arthroplasty method has high surgical safety, low reconstruction difficulty, and an reliable anti-reflux effect.

Objective: Data on syncopal donation-related vasovagal reaction (DRVR) collected from 74 blood centers between 2020 and 2023 was statistically analyzed to provide a reference for developing preventive strategies against syncopal DRVR. Methods: Data on blood donation adverse reactions and basic information of donors from 2020 to 2023 were collected through the information management system at monitoring sentinel sites. Statistical analysis was performed on the following aspects of syncopal DRVR: characteristics of donors who experienced syncope, reported incidence, triggers, duration, presence and occurrence time of syncope-related trauma, clinical management including outpatient and inpatient treatment, and severity grading. Results: From 2020 to 2023, 45 966 donation-related adverse reactions were recorded. Of these, 1 665 (3.72%) cases were syncopal DRVR. The incidence of syncopal DRVR decreased with age, being the highest in the 18-22 age group. Incidence was significantly higher in female donors than male donors, in first-time donors than repeat donors, and in university and individual donors than group donors (all P<0.05). There was no statistically significant difference among different blood donation locations (P>0.05). The top three triggers were tension, fatigue, and needle phobia or fear of blood. Among syncopal DRVR cases, 60.36% occurred during blood collection, 87.63% lasted for less than 60 seconds, and 5.05% were accompanied by trauma. Notably, 57.14% of these traumas occurred after donor had left the blood collection site. Syncope severity was graded based on required treatment: grade 1 (fully recovered without treatment, 95.50%); grade 2 (recovered after outpatient treatment, 4.02%); and grade 3 (recovered after inpatient treatment, 0.48%). Conclusion: By analyzing the data of syncopal DRVR cases, it is possible to provide a reference for formulating blood donor safety policies.

Shanghai Hospital Development Center has paid high attention to clinical research and the biomedical research translation of municipal hospitals. We conducted a systematic research of the current development status in the Republic of Korea and Australia, focusing on aspects of clinical research, clinical trials, medical quality training, research infrastructures, etc. To align with the actual conditions of Shanghai municipal hospitals, we proposed four main constructive suggestions to enhance the quality of clinical research, accelerate clinical trial efficiency, strengthen policy support and stimulate research motivation, while facilitating clinical research in municipal hospitals and driving high-quality development of the local biopharmaceutical industry.

Objective To summarize the best evidence for diaphragm rehabilitation in mechanically ven-tilated ICU patients with ventilator-associated diaphragm dysfunction based on evidence-based methods.Meth-ods A systematic search was conducted across guideline websites,professional associations,and Chinese/English databases for evidence regarding diaphragm rehabilitation in mechanically ventilated ICU patients.The search timeframe spanned from database inception to December 31,2024.Two researchers independently per-formed quality assessment and synthesized the evidence.Results Twenty articles were included:2 clinical de-cisions,1 guideline,2 evidence summaries,3 systematic reviews,7 randomized controlled trials(RCT),and 5 expert consensuses/opinions.Twenty-seven pieces of evidence were formed across 6 themes:rehabilitation team,rehabilitation assessment,rehabilitation interventions,outcome evaluation,precautions,and education/training.Conclusion This study summarizes the best evidence for diaphragm rehabilitation in ICU mechani-cally ventilated patients.Healthcare professionals should implement diaphragm rehabilitation by integrating this evidence with specific clinical contexts to improve patient outcomes and enhance nursing quality.

Objective To analyze the diversity and composition of gut microbiota in individuals with circadian rhythm disruption and their correlation with cognition.Methods Night shift workers and regular shift workers were subjected from our hospital during August 2022 and October 2024.The participants with circadian rhythm disorders were assigned into an experimental group(n=24),and those with normal circadian rhythms were into a control group(n=24).Their height,weight,age,gender,body mass index(BMI)and fresh fecal samples were collected,and Montreal Cognitive Assessment(MoCA)and Mini-Mental State Examination(MMSE)were used to evaluate their mental status.Metagenomics,Alpha and Beta diversity analyses,Linear Discriminant Analysis Effect Size(LEfSe),and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were employed to investigate the diversity and function characteristics of gut microbiota in the participants.Results There were no statistical differences between the 2 groups in baseline data,such as height,weight,gender,age,and BMI(P>0.05).Alpha diversity analysis indicated that no statistical differences were observed in the ACE,Chao1,Shannon,or Simpson indices between the 2 groups,while beta diversity analysis revealed significant differences(P<0.01),suggesting different structure of gut microbiota between them.In the experimental group,the abundance of Faecalibacterium prausnitzii and Agathobacter rectalis was decreased,while that of Escherichia coli and Phocaeicola vulgaratus was increased,with significant differences when compared with the control group(P<0.05).Additionally,KEGG functional analysis showed that the experimental group had obviously higher expression levels in Th17 cell differentiation and the IL-17 signaling pathway than the control group(P<0.05).Agathobacter rectalis and Faecalibacterium prausnitzii were positively correlated with MoCA score and MMSE score(P<0.05,P<0.01).Agathobacter rectalis was negatively correlated with the IL-17 signaling pathway and Th17 cell differentiation.Conclusion Individuals with circadian rhythm disorders have significant changes in the structure and function of gut microbiota when compared to those with normal circadian rhythms.Agathobacter rectalis may be involved in the regulation of the IL-17 signaling pathway and differentiation of Th17 cells,thereby possibly impacting the increases of cognitive score related to circadian rhythm disorders.

Tibetan sheep,the main domestic animal raised in the Qinghai-Tibet Plateau region,are a source of human plague transmission.In the Qinghai-Tibet Plateau region,Tibetan sheep are considered valuable breeding resources,because of their large body size and high adaptability to high-altitude environments.In recent years,many pastoral areas,particularly those with marmot plague sources,have improved the structure of sheep breeds through pure breeding of Tibetan sheep or hybridization with Tibetan sheep to improve breed quality.The scale of breeding of Tibetan sheep or hybrid sheep is increasing,and their participation in the spread of plague poses a severe challenge to plague prevention and control.This article provides a comprehensive review of the current status of Tibetan sheep plague and related research progress,to provide a theoretical basis for further exploration and research on plague infection and transmission in Tibetan sheep and hybrid sheep.The findings will be critical for conducting risk assessment of Ti-betan sheep plague in marmot plague source areas,enhancing monitoring and early warning capabilities,formulating and implement-ing risk control measures,and strictly preventing the occurrence and spread of human plague.

Tibetan sheep,the main domestic animal raised in the Qinghai-Tibet Plateau region,are a source of human plague transmission.In the Qinghai-Tibet Plateau region,Tibetan sheep are considered valuable breeding resources,because of their large body size and high adaptability to high-altitude environments.In recent years,many pastoral areas,particularly those with marmot plague sources,have improved the structure of sheep breeds through pure breeding of Tibetan sheep or hybridization with Tibetan sheep to improve breed quality.The scale of breeding of Tibetan sheep or hybrid sheep is increasing,and their participation in the spread of plague poses a severe challenge to plague prevention and control.This article provides a comprehensive review of the current status of Tibetan sheep plague and related research progress,to provide a theoretical basis for further exploration and research on plague infection and transmission in Tibetan sheep and hybrid sheep.The findings will be critical for conducting risk assessment of Ti-betan sheep plague in marmot plague source areas,enhancing monitoring and early warning capabilities,formulating and implement-ing risk control measures,and strictly preventing the occurrence and spread of human plague.

Objective:To investigate the detection status of serological markers for hepatitis B virus (HBV) among Tibetan college students and their relationship with HBV- deoxyribonucleic acid (DNA) load.Methods:A cross-sectional study was carried out to retrospectively analyze data from 1 514 Tibetan college students who visited the Affiliated Hospital of Xizang Minzu University for consultations or health examinations between June 1, 2021 and June 1, 2022. The prevalence of HBV infection among these students was analyzed, the primary epidemiological patterns of HBV markers were identified, and their relationship with HBV-DNA load was determined.Results:The positive rate of hepatitis B surface antigen (HBsAg) among the 1 514 Tibetan college students was 6.7% (101/1 514), while the positive rate for Hepatitis B surface antibody (HBsAb) was 42.2% (639/1 514). The primary serological pattern of HBV infection consisted of positive results for HBsAg, HBeAg, and HBcAb, which accounted for 48.5% of cases. This pattern showed significantly higher rates of HBV-DNA positivity and elevated viral load compared with other serological patterns ( χ2 = 8.70, P < 0.05). Conclusions:The HBV infection rate among Tibetan college students is 6.7%. The primary infection pattern is characterized by positive tests for HBsAg, HBeAg, and HBcAb, with an HBV-DNA positivity rate as high as 87.0% and elevated viral loads.

Diaphragmatic dysfunction often occurs in ICU patients with prolonged mechanical ventilation, which seriously affects patients′prognosis. This article reviewed the progress of rehabilitation treatment of diaphragmatic dysfunction in ICU patients with mechanical ventilation, focused on the concept and assessment of diaphragm rehabilitation, the current status, evaluation indexes, emphasized the importance of nurses, analyzed the dilemmas and countermeasures in the application, which aimed to provide a reference for the promotion of diaphragm rehabilitation in clinical practice.