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.

Immobilized enzyme-based enzyme electrode biosensors, characterized by high sensitivity and efficiency, strong specificity, and compact size, demonstrate broad application prospects in life science research, disease diagnosis and monitoring, etc. Immobilization of enzyme is a critical step in determining the performance (stability, sensitivity, and reproducibility) of the biosensors. Random immobilization (physical adsorption, covalent cross-linking, etc.) can easily bring about problems, such as decreased enzyme activity and relatively unstable immobilization. Whereas, directional immobilization utilizing amino acid residue mutation, affinity peptide fusion, or nucleotide-specific binding to restrict the orientation of the enzymes provides new possibilities to solve the problems caused by random immobilization. In this paper, the principles, advantages and disadvantages and the application progress of enzyme electrode biosensors of different directional immobilization strategies for enzyme molecular sensing elements by specific amino acids (lysine, histidine, cysteine, unnatural amino acid) with functional groups introduced based on site-specific mutation, affinity peptides (gold binding peptides, carbon binding peptides, carbohydrate binding domains) fused through genetic engineering, and specific binding between nucleotides and target enzymes (proteins) were reviewed, and the application fields, advantages and limitations of various immobilized enzyme interface characterization techniques were discussed, hoping to provide theoretical and technical guidance for the creation of high-performance enzyme sensing elements and the manufacture of enzyme electrode sensors.

Objective: To establish a prediction model for high-risk cardiovascular disease (CVD) among residents aged 35 to 75 years, so as to provide the basis for improving CVD prevention and control measures. Methods: Permanent residents aged 35 to 75 years were selected from Dongcheng District, Beijing Municipality using the stratified random sampling method from 2018 to 2023. Demographic information, lifestyle, waist circumference and blood biochemical indicators were collected through questionnaire surveys, physical examinations and laboratory tests. Influencing factors for high-risk CVD among residents aged 35 to 75 years were identified using a multivariable logistic regression model, and a prediction model for high-risk CVD was established. The predictive effect was evaluated using the receiver operating characteristic (ROC) curve. Results: A total of 6 968 individuals were surveyed, including 2 821 males (40.49%) and 4 147 females (59.51%), and had a mean age of (59.92±9.33) years. There were 1 155 high-risk CVD population, with a detection rate of 16.58%. Multivariable logistic regression analysis showed that gender, age, smoking, central obesity, systolic blood pressure, fasting blood glucose, triglyceride and low-density lipoprotein cholesterol were influencing factors for high-risk CVD among residents aged 35 to 75 years (all P<0.05). The area under the ROC curve of the established prediction model was 0.849 (95%CI: 0.834-0.863), with a sensitivity of 0.693 and a specificity of 0.863, indicating good discrimination. Conclusion The model constructed by eight factors including demographic characteristics, lifestyle and blood biochemical indicators has good predictive value for high-risk CVD among residents aged 35 to 75 years.

Objective The risk of death in patients undergoing maintenance hemodialysis(MHD)significantly increases if they develop concomitant gastrointestinal bleeding(GIB).This study aims to investigate the clinical characteristics of MHD patients with concomitant GIB,identify risk factors associated with in-hospital mortality among them,and provide a basis for the early clinical identification and optimized clinical management of this specific patient population.Methods The clinical data of MHD patients with GIB admitted to West China Hospital,Sichuan University between July 2019 and May 2024 were collected and a retrospective analysis was conducted accordingly.The patients were divided into a death group and a survival group based on their discharge status.Clinical characteristics,laboratory test results,endoscopic findings,etc.,of the two groups were collected.Oversampling was used to reduce the bias caused by data imbalance between the two groups,and stepwise logistic regression and other methods were used for analysis.Results A total of 212 patients were included,with 40 in the death group and 172 in the survival group.According to the findings of logistic regression,the following were identified as independent risk factors for mortality among the patients:activated partial thromboplastin time(APTT)(odds ratio[OR]=1.014;95%CI,1.002-1.027;P=0.024),Glasgow-Blatchford bleeding score(GBS)(OR=2.348;95%CI,1.686-3.269;P<0.001),and age-corrected Charlson comorbidity index(aCCI)(OR=1.522;95%CI,1.185-1.954;P<0.001),and small intestinal vascular malformation(OR=0.372 2;95%CI,0.161-0.858;P=0.020).Conclusion For MHD patients with concomitant GIB,APTT,GBS,aCCI,and small intestinal vascular malformation are independent risk factors for in-hospital death.

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 discern the association between autism-like behaviors and resilience within the ado-lescent demographic.Methods:A total of 7 063 middle school students were selected to assess ASD-like behaviors and resilience in adolescents using the Autism Spectrum Screening Questionnaire(ASSQ)as well as the Resilience Scale for Chinese Adolescent(RSCA).Subgroups bounded by P5 and P95 of the total ASSQ score,a comparative analysis of the resilience scores between these groups was executed.A correlation evaluation and linear regression a-nalysis was carried out between ASSQ and RSCA scores from all participants.Results:The RSCA scores within the high ASSQ scoring group,were inferior to those in the low scoring group.ASSQ scores were negatively correlated with RSCA scores for the full sample(Ps＜0.01);Social interaction scores on the ASSQ were negatively correlated with the five-factor RSCA scores(β=-0.23,-0.27,-0.11,-0.23,-0.37,Ps＜0.05).Conclusion:There was a negative association between autism spectrum disorder-like behaviors and resilience in adolescents,with more severe social interaction symptoms being associated with poorer resilience.

Objective:To explore the mediating role of dietary health beliefs in the relationship between family functioning and the frequency of sugar-containing food intake among adolescents with dental caries, in order to clarify the underlying mechanism through which dietary health beliefs influence caries-related dietary behaviors via family factors.Methods:Using convenience sampling method, we selected adolescents patients diagnosed with dental caries and their parents who visited the Affiliated Stomatological Hospital of Nanjing Medical University from July to September 2023 as the research subjects. Conducted a cross-sectional survey using a general information questionnaire, Family Functioning Scale, Adolescent Dietary Health Belief Scale, and Sugar-Sweetened Diet Intake Frequency Scale. Mediation analysis was conducted.Results:A total of 475 questionnaires were distributed, and 460 valid responses were obtained, yielding a valid response rate of 96.84%. Among the 460 adolescent patients, 306 were female and 154 were male, with a mean age of (13.42 ± 1.17) years old. The mother's age was (40.28 ± 4.24) years old, and the father's age was (42.12 ± 4.48) years old. The score for the frequency of sugar-containing food intake was 15.95 ± 5.34, the dietary health belief score was 75.57 ± 18.62, and the family functioning score was 174.24 ± 25.39. Family functioning was positively correlated with dietary health beliefs ( r = 0.428, P<0.05), and negatively correlated with the frequency of sugar-containing food intake ( r = -0.225, P<0.05). Dietary health beliefs were negatively correlated with the frequency of sugar-containing food intake ( r = -0.332, P<0.05). The mediating effect of dietary health beliefs on the relationship between family functioning and sugar-containing food intake frequency was -0.332, accounting for 43.92% of the total effect. Conclusions:Dietary health beliefs play a partial mediating role between family function and the frequency of sugary diet intake. It is suggested that family function construction should be strengthened to improve adolescents' health beliefs and reduce the incidence of dental caries.

This review has introduced the Coronary Artery Tree description and Lesion EvaluaTion(CatLet or Hexu)angiographic scoring system,which,based solely on coronary angiography results,has characterized 6 types of right coronary artery,3 types of left descending artery,and 3 types of diagonal size,together resulting in 54 types of coronary circulation pattern.This novel angiographic scoring system can be utilized to account for coronary anatomy in its diversity,severity and complexity of diseased coronary arteries,and their subtended myocardial territories in jeopardy.The CatLet angiographic scoring system is unique in that the importance of a coronary artery is weighted according to its subtended myocardial segments,by which the variability of coronary artery has been accounted for and measured.Researchers at home and abroad have increasingly paid attention to its clinical utilities,which warrant further validation in the context of large sample size,prospective,and randomized controlled trials.The CatLet angiographic scoring system is accessible at www.catletscore.com.

Objective:To explore the mediating role of activity of daily living between social support and cognitive function of rural elderly.Methods:A face-to-face questionnaire survey was conducted from July to August 2019 among 1 626 rural elderly people selected by multi-stage cluster random method in Guiyang City and Qiannan Prefecture, Guizhou Province.The contents include general situation, social support rate scale (SSRS), activity of daily living scale (ADL) and mini-mental state examination (MMSE). Partial correlation analysis and multiple linear regression analysis were used to analyze the relationship among social support, activity of daily living and cognitive function in the elderly by SPSS 23.0 software. AMOS 28.0 software was used to construct structural equation models, and Bootstrap method was used to test the mediating role of activity of daily living.Results:The scores of cognitive function, social support and activity of daily living of the rural elderly were (20.83±5.47), (34.96±6.42) and (16.51±3.29), respectively.There were statistically significant differences in the cognitive function scores among rural elderly with different levels of social support and activity of daily living( F=33.418, t=25.533, P<0.01). The partial correlation analysis showed that the social support score was positively correlated with the cognitive function score ( r=0.161, P<0.01), and the activity of daily living score was negatively correlated with scores of social support and cognitive function ( r=-0.083, -0.453, both P<0.01). Multiple linear stepwise regression analysis showed that social support, objective support dimensions, activity of daily living and instrumental activity of daily living were influencing factors of cognitive function of rural elderly( P<0.001).The results of structural equation model showed that the activity of daily living played a partial mediating role between social support and cognitive function in rural elderly, with the mediating effect of 0.046 (95% CI=0.025-0.075), accounting for 13.18% of total effect (effect value=0.349, 95% CI=0.277-0.415). Conclusion:The activity of daily living of rural elderly plays a partial mediating effect between social support and cognitive functioning.

Objective:This study aims to investigate the predictive performance of serum levels of white blood cell count(WBC),D-dimer(D-D)and N-terminal pro-brain natriuretic peptide(NT-proBNP)for major adverse cardiovascular events(MACE)in elderly patients with acute ST-segment elevation myocardial infarction(ASTE-MI).Methods:A total of 70 elderly patients with ASTEMI treated in Bozhou People's Hospital between April 2020 and May 2023 were prospectively selected as observation group.Incidence of MACE during 1-year follow-up were recorded,another 50 patients with unstable angina pectoris treated in our hospital simultaneously were selected as control group.Serum levels of WBC,D-D and NT-proBNP were compared among above groups.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of serum WBC,D-D and NT-proBNP for MACE in elderly patients with ASTEMI.A nomogram was established,and calibration curve and deci-sion curve analysis(DCA)were used to evaluate the performance of model.Results:A total of 40 cases(59.70％)experienced MACE during one-year follow-up.Compared to those in control group,patients in observation group had significant higher serum WBC[(11.43±1.98)×109/Lvs.(6.30±1.99)× 109/L],D-D[(0.91±0.20)mg/L vs.(0.47±0.18)mg/L]andNT-proBNP[(192.31±63.19)pg/ml vs.(114.05±22.79)pg/ml](P＜0.001 all).Compared to participants without MACE,those with MACE had significantly higher serum WBC[(13.33±1.90)× 109/L vs.(10.27±0.98)× 109/L],D-D[(1.11±0.25)mg/L vs.(0.87±0.21)mg/L]and NT-proBNP[(238.73±50.22)pg/ml vs.(150.70±39.16)pg/ml](P＜0.001 all).ROC analysis showed that the ar-ea under the curve(AUC)of the combined detection of serum WBC(AUC=0.791,95％CI 0.677～0.879),D-D(AUC=0.767,95％CI 0.650～0.859)and NT-proBNP(AUC=0.733,95％CI 0.614～0.832)was 0.916(95％CI 0.825～0.969),which was significantly higher than those of single detections(Z=2.386,4.953,3.190,P=0.017,0.004,＜0.001).The total score of the nomogram model constructed based on the levels of WBC,D-D and NT-proBNP ranged from 70 to 126 points.The predicted incidence was basically consistent with the actual in-cidence.For the internal verification of the model,the AUC of ROC curve of the training set and the validation set was 0.863 and 0.926 respectively.The DCA curve was located above the critical curve,indicating that the model had a net benefit and good clinical effectiveness.Conclusion:Serum WBC,D-D and NT-proBNP significantly el-evated in elderly patients with ASTEMI.The combined detection of serum WBC,D-D and NT-proBNP levels has good predictive value for MACE in these patients.