To reflect specialty teaching characteristics and levels in clinical standardized training of medical professional degree postgraduates and highlight the thinking of evidence-based medicine culture,in urology rotation training practice,we conducted clinical pathway teaching according to picot principle (PICOT-CP teaching).According to the requirements of the teaching syllabus,the six kinds of major diseases were brought into PICOT-CP teaching.After the screening of pre teacher training,teaching tools and teaching cases,and based on the form of PICOT-CP,we standardized the implementation of clinical teaching of Urology,fully used subject website platform to discuss the interaction between teachers and students,and assessed the effect in combination with the departmental rotation examination and the teaching questionnaire survey of the students and the training teachers.Preliminary practice shows that PICOT-CP teaching helps to stimulate students' interest in learning,improve their overall quality,expand their clinical thinking,and establish their concept of evidence-based medicine.In addition,PICOT-CP teaching is beneficial to the teaching norms of teachers' teaching and can improve teaching level.

Objective To investigate the risk factors for castrate-resistant prostate cancer (CRPC) after prostate cancer treated with androgen deprivation therapy (ADT) within 1 year.Methods One hundred and thirty-one prostate cancer patients treated with ADT in our institute between Jan.2008 and Jan.2011 were selected for this study.Patients were followed up by telephone or in clinic,including serum testosterone,serum PSA,clinical symptoms,imaging studies,digital rectal examination (DRE),survival data,PSA nadir,time to PSA nadir and et al.We mainly studied the CRPC after prostate cancer treated with ADT within 1 year.In the 131 patients,the median age was 70 (ranged from 44-89) years.There were 13 patients (9.9％) less than 60 years,43 patients (32.8％) between 60 and 69 years,62 patients (47.3％) between 70 and 79 years,13 patients (9.9％) more than 80 years.The average body mass index (BMI) was 23.0 (ranged from 14.4-34.4) kg/m2.There were 10 patients less than 18.5 kg/m2,77 patients between 18.5 and 24.0 kg/m2,34 patients between 24.1 and 28.0 kg/m2,and 10 patients more than 28.0 kg/m2.The initial PSA was between 0.3 and 4 707.0 μg/L,there were 19 patients (14.5％) less than 20 μg/L,45 patients (34.4％) between 20 and 99 μg/L,67 patients (51.1％) more than 100 μg/L.One patient (0.7％) was in T1,39 patients (29.8％) in T2,59 patients (45.0％) in T3,32 patients (24.4％) in T4.5 patients (3.8％) were with Gleason score 4,13 patients (9.9％) were with Gleason score 5,24 patients (18.3％) were with Gleason score 6,51 patients (38.9％) were with Gleason score 7,26 patients (19.8％) were with Gleason score 8,9 patients (6.9％) were with Gleason score 9,3 patients (2.3％) were with Gleason score 10.Results There were 32 of 131 patients (24.4％) progressed to CRPC after treated with ADT within 1 year.In the CRPC group,there were 3 patients less than 60 years,15 patients between 60 and 69 years,12 patients between 70 and 79 years,2 patients more than 79 years; 3 patients were less than 18.5 kg/m2,19 patients were between 18.5 and 24.0 kg/m2,7 patients were between 24.0 and 28.0 kg/m2,3 patients were more than 28.0 kg/m2 ; 4 patients were less than 20 μg/L,6 patients were between 20 and 100 μg/L,22 patients were more than 100 μg/L; 4 patients were in T2,13 patients were in T3,15 patients were in T4; 2 patients were with Gleason score 6,11 patients were with Gleason score 7,11 patients were with Gleason score 8,6 patients were with Gleason score 9,2 patients were with Gleason score 10; 29 patients were with metastasis,3 patients without metastasis.Clinical stage (P =0.001),Gleason score (P＜0.001) and metastasis (P=0.011) were statistically significant between the CRPC within 1 year group and the rest group.Conclusions The clinical stage and Gleason score are the risk factors of CRPC treated with ADT within 1 year.The higher of the clinical stage and Gleason score,the greater risk to be the CRPC within 1 year.

Objective:To compare the prevalence of frailty and related factors in middle-aged and elderly people aged ≥45 years in island and mountainous areas of Taizhou, Zhejiang Province.Methods:Based on cross-sectional design, stratified cluster sampling and quota sampling methods were adopted. One administrative district was randomly selected from each of six coastal and three inland administrative districts in Taizhou during July to August, representing two different geographical terrains. In the island area (Jiaojiang District), all residents aged ≥45 years were included by cluster sampling. In the mountainous area (Xianju County), participants were selected through quota sampling, with same gender and age distributions. Data about their demographic characteristics, lifestyle and health-related factors were collected through questionnaire surveys and laboratory examinations. The prevalence of frailty was assessed using the Fried frailty phenotype scale. Hierarchical analysis and multivariate logistic regression analysis were used to compare the influencing factors of frailty.Results:A total of 1 011 local residents were studied, in whom island and mountainous residents accounted for 48.1% (486/1 011) and 51.9% (525/1 011) respectively; men and women accounted for 45.9% (464/1 011) and 54.1% (547/1 011) respectively. Middle-aged (45-49 years), younger elderly (60-74 years), and older elderly (≥75 years) residents accounted for 38.6% (390/1 011), 44.6% (451/1 011), and 16.8% (170/1 011) respectively. The overall prevalence rate of frailty was 3.6% (36/1 011), the prevalence rate was 3.7% (17/464) in men and 3.5% (19/547) in women. The prevalence rates in age groups 45-59,60-74 years and ≥75 years were 0.3% (1/390), 2.2% (10/451), and 14.7% (25/170), respectively. The prevalence rates of frailty and pre-frailty in island area were 6.0% (29/486) and 39.1% (190/486), respectively, which was higher than those in mountainous area (1.3%, 7/525) and (30.9%, 162/525). After adjusting for potential confounding factors, the risk for frailty in island residents was significantly higher than that in mountainous residents (a OR=1.55,95% CI: 1.07-2.25, P=0.019). In island area, older age (60-74 years:a OR=2.52,95% CI: 1.56-4.13; ≥75 years:a OR=11.65,95% CI:5.38-26.70), being women (a OR=1.94,95% CI: 1.20-3.17), suffering from depression (a OR=1.09,95% CI:1.02-1.17) were associated with frailty symptoms. In mountainous area, older age was also associated with an increased risk of frailty symptoms, but the OR value was lower than those in island area (60-74 years: a OR=1.74,95% CI:1.04-2.94;≥75 years: a OR=4.78,95% CI:2.45-9.50). Polydrug use (a OR=2.08,95% CI: 1.14-3.80) and suffering from depression (a OR=1.10,95% CI: 1.02-1.18) had significant positive association with frailty symptoms. Higher education level had significant negative association with frailty symptoms (junior high school: a OR=0.40,95% CI: 0.21-0.75; senior high school and technical secondary school: a OR=0.29,95% CI: 0.15-0.53; college or above:a OR=0.22,95% CI: 0.11-0.42). Conclusions:The prevalence of frailty in middle-aged and elderly community residents was significantly higher in island area than in mountainous area in Taizhou. The frailty-related factors varied with area. The elderly people (≥75 years) and women in island area had higher risk for frailty. Older age and suffering from depression were the independent risk factors for frailty. It is necessary to pay attention to the health risk factors and special environment in island area, and take comprehensive intervention measures to delay the process of debilitation and improve the quality of life of middle-aged and elderly people.

ObjectiveTo analyze the failure of antiretroviral therapy (ART) and drug resistance characteristics among the newly reported HIV-infected patients in Taizhou City from 2020 to 2022. MethodsBlood samples, sociodemographic characteristics and ART information of the newly reported HIV-infected patients who received ART for ≥6 months in Taizhou City from 2020 to 2022 were collected for the detection of recent infections and HIV-1 genotypic drug resistance. Multivariate logistic regression analysis was used to analyze the influencing factors of treatment failure. The gene sequences of cases with failed ART were submitted to the HIV drug resistance database of Stanford University to determine the drug resistance mutation sites and drug resistance characteristics. ResultsAmong the 1 023 newly reported HIV-infected patients receiving ART, the median age （P₂₅，P₇₅） was 47 (33, 58) years, 81.4% were male, 66.4% (679/1 023) were infected through heterosexual transmission, 74.7% had a WHO clinical stage Ⅰ/Ⅱ, 62.2% had a baseline CD4 count of >200 cell·μL^-1, 94.4% (966/1 023) received an immediate ART, and 78.7% were long-term infected. Among the 66 patients with treatment failure (6.5%), the likelihood of treatment failure was lower in those with homosexual transmission (OR=0.39, 95%CI: 0.17‒0.84) and without history of sexually transmitted disease (STD) (OR=0.45, 95%CI: 0.24‒0.92), but higher in those with a baseline CD4 count of ≤200 cell·μL^-1, delayed ART (OR=3.19, 95%CI: 1.24‒7.52), and primary drug resistance (OR=4.69, 95%CI: 1.68‒11.89). Among the 36 HIV-infected patients with virological failure, 27 sequences were successfully amplified, with a successful amplification rate of 75.0% (27/36). The total drug resistance rate was 55.6% (15/27), of which the drug resistance rates of nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) were 37.0% (10/27), 51.9% (14/27) and 3.7% (1/27), respectively. Among the NNRTIs, the degree of resistance to efavirenz and nevirapine was consistent, with a majority (51.9%) of highly drug-resistant. K103N and M184V were the most common mutation sites, but PIs mutations occured less frequently. A total of 8 genotypes of HIV-1 were detected, in which subtype CRF01_AE accounted for 37.0% (10/27), followed by CRF07_BC [14.8% (4/27)], CRF08_BC [14.8% (4/27)] and subtype C [14.8% (4/27)]. ConclusionDuring the period from 2020 to 2022, the newly reported HIV-infected individuals in Taizhou City were predominated by long-term infections. Immediate initiation of ART can reduce the risk of treatment failure in HIV-infected individuals. Virological treatment failures are primarily associated with resistance to NRTIs and NNRTIs. It is recommended to strengthen active detection and promptly initiate ART to minimize the occurrence of ART failure. Simultaneously, there is a need to intensify drug resistance detection targeted for those with treatment failure, so as to provide a scientific guidance for drug replacement.

The skeletal system, which contains bones, joints, tendons, ligaments and other elements, plays a wide variety of roles in body shaping, support and movement, protection of internal organs, production of blood cells and regulation of calcium and phosphate metabolism. The prevalence of skeletal diseases and disorders, such as osteoporosis and bone fracture, osteoarthritis, rheumatoid arthritis, and intervertebral disc degeneration, increases with age, causing pain and loss of mobility and creating a huge social and economic burden globally. Focal adhesions (FAs) are macromolecular assemblies that are composed of the extracellular matrix (ECM), integrins, intracellular cytoskeleton and other proteins, including kindlin, talin, vinculin, paxillin, pinch, Src, focal adhesion kinase (FAK) and integrin-linked protein kinase (ILK) and other proteins. FA acts as a mechanical linkage connecting the ECM and cytoskeleton and plays a key role in mediating cell-environment communications and modulates important processes, such as cell attachment, spreading, migration, differentiation and mechanotransduction, in different cells in skeletal system by impacting distinct outside-in and inside-out signaling pathways. This review aims to integrate the up-to-date knowledge of the roles of FA proteins in the health and disease of skeletal system and focuses on the specific molecular mechanisms and underlying therapeutic targets for skeletal diseases.

Ischemic stroke is the second leading cause of death worldwide with limited medications and neuroinflammation was recognized as a critical player in the progression of stroke, but how to control the overactive neuroinflammation is still a long-standing challenge. Here, we designed a novel SIRT6 activator MDL-811 which remarkably inhibited inflammatory response in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and primary mouse microglia, which were abolished by silencing SIRT6. RNA-seq screening identified the forkhead box C1 (