Human carboxylesterase 2A (hCES2A) plays pivotal roles in prodrug activation and hydrolytic metabolism of ester-bearing chemicals. Targeted inhibition of intestinal hCES2A represents a feasible strategy to mitigate irinotecan-triggered gut toxicity (ITGT), but the orally active, selective, and efficacious hCES2A inhibitors are rarely reported. Here, a novel drug-like hCES2A inhibitor was developed via three rounds of structure-based drug design (SBDD) and structural optimization. Initially, donepezil was identified as a moderate hCES2A inhibitor from 2000 US Food and Drug Administration (FDA)-approved drugs. Following two rounds of SBDD and structural optimization, a donepezil derivative (B7) was identified as a strong reversible hCES2A inhibitor. Subsequently, nine B7 carbamates were rationally designed, synthesized and biologically assayed. Among all synthesized carbamates, C3 showed the most potent time-dependent inhibition on hCES2A (IC₅₀ = 0.56 nmol/L), excellent specificity and favorable drug-like properties. C3 could covalently modify the catalytic serine of hCES2A with high selectivity, while this agent also showed favorable safety profiles, high intestinal exposure, and impressive effects for ameliorating ITGT in both human intestinal organoids and tumor-bearing mice. Collectively, this study showcases a rational strategy for developing drug-like and serine-targeting covalent inhibitors against target serine hydrolase(s), while C3 emerges as a promising orally active drug candidate for ameliorating ITGT.

Objective:To explore the lifestyle pattern of the physical examination population and analyze its association with metabolic associated fatty liver disease (MAFLD).Methods:This was a cross-sectional study. Based on the data of 196 515 physical examination individuals from the Health Management Center of the Third Xiangya Hospital of Central South University from January 2016 to December 2020, the subjects were grouped and characterized by principal component analysis and cluster analysis. Among them, 137 277 cases with MAFLD diagnosis information were included in the association analysis between lifestyle pattern and MAFLD. The differences in lifestyle pattern choice among different age, sex, education level, marital status, occupational category and medical insurance type and their differences with the risk of MAFLD were analyzed. The generalized linear mixed model was used to control confounding factors and then association analysis was conducted.Results:There were 6 types of lifestyle patterns in the physical examination population, which were respectively: indulgent type-both physical and mental damage, remedial type-excessive diet, giving type-unique intensity, comfortable type-natural health, heavy smoking type-sedentary injury, heavy drinking type-attempting to make up, accounting for 7.29%, 9.62%, 7.43%, 52.16%, 9.77%, 13.73% in the population. Among them, the male lifestyle pattern was mainly the indulgent type, the remedial type, the heavy smoking type and the heavy drinking type, showing the characteristics of unhealthy lifestyle pattern; Women tended to have healthier lifestyle patterns. After association analysis with MAFLD, it was found that the prevalence of MAFLD was more than 50% in the people who belonged to the indulgent type, remedial type, the heavy smoking type and the heavy drinking type (53.62%, 57.06%, 51.25% and 50.50%, respectively), and the prevalence of MAFLD in the giving type group was 40.17%. The risk of MAFLD in comfortable group was relatively low (28.25%), and the difference in risk of MAFLD among all modes was statistically significant after controlling for confounding factors ( P<0.001). Conclusion:According to cluster mining, there are 6 types of lifestyle patterns in the physical examination population, and the healthier lifestyle pattern has a lower risk of MAFLD.

Objective:To gain an in-depth understanding of the career development of male nurses in China, analyze trends, challenges, and opportunities, and provide a basis for policy-making, talent cultivation, and professional development in the nursing field.Methods:A descriptive qualitative research method was adopted. From March 29th to July 30th, 2023, the heads of the male nurses working groups of nursing associations in 26 regions of China were selected by purposive sampling method for semi-structured interviews. Content analysis was used to analyze the data.Results:The current situation of the career development of male nurses in China could be summarized into the following three themes. (1) Current situation: the organizational structure of provincial-level male nurses work was basically complete, but there were obvious differences at the grassroots level; the work was carried out in various forms, and diverse models developed in coordination; (2) Trends: there were obvious stratifications in professional ideology and professional abilities of male nurses among different regions and different-level medical institutions; the gender dividend was gradually decreasing, and male nurses should give play to their advantages in logical thinking ability; (3) Prospects: early intervention was needed to enhance professional identity and organizational support; male nurses should be trained in various aspects through multiple forms such as counterpart assistance, expert databases or online academic forums; interdisciplinary development might be the key to stimulating internal driving force.Conclusions:Significant progress has been made in the career development of male nurses in China, but there are still challenges and issues to address. Further improvements in related policies, enhancement of social recognition and professional status, and increased investment and support in research and education are needed to promote the sustained development of male nursing careers.

Objective:To gain an in-depth understanding of the career development of male nurses in China, analyze trends, challenges, and opportunities, and provide a basis for policy-making, talent cultivation, and professional development in the nursing field.Methods:A descriptive qualitative research method was adopted. From March 29th to July 30th, 2023, the heads of the male nurses working groups of nursing associations in 26 regions of China were selected by purposive sampling method for semi-structured interviews. Content analysis was used to analyze the data.Results:The current situation of the career development of male nurses in China could be summarized into the following three themes. (1) Current situation: the organizational structure of provincial-level male nurses work was basically complete, but there were obvious differences at the grassroots level; the work was carried out in various forms, and diverse models developed in coordination; (2) Trends: there were obvious stratifications in professional ideology and professional abilities of male nurses among different regions and different-level medical institutions; the gender dividend was gradually decreasing, and male nurses should give play to their advantages in logical thinking ability; (3) Prospects: early intervention was needed to enhance professional identity and organizational support; male nurses should be trained in various aspects through multiple forms such as counterpart assistance, expert databases or online academic forums; interdisciplinary development might be the key to stimulating internal driving force.Conclusions:Significant progress has been made in the career development of male nurses in China, but there are still challenges and issues to address. Further improvements in related policies, enhancement of social recognition and professional status, and increased investment and support in research and education are needed to promote the sustained development of male nursing careers.

Objective:To explore the lifestyle pattern of the physical examination population and analyze its association with metabolic associated fatty liver disease (MAFLD).Methods:This was a cross-sectional study. Based on the data of 196 515 physical examination individuals from the Health Management Center of the Third Xiangya Hospital of Central South University from January 2016 to December 2020, the subjects were grouped and characterized by principal component analysis and cluster analysis. Among them, 137 277 cases with MAFLD diagnosis information were included in the association analysis between lifestyle pattern and MAFLD. The differences in lifestyle pattern choice among different age, sex, education level, marital status, occupational category and medical insurance type and their differences with the risk of MAFLD were analyzed. The generalized linear mixed model was used to control confounding factors and then association analysis was conducted.Results:There were 6 types of lifestyle patterns in the physical examination population, which were respectively: indulgent type-both physical and mental damage, remedial type-excessive diet, giving type-unique intensity, comfortable type-natural health, heavy smoking type-sedentary injury, heavy drinking type-attempting to make up, accounting for 7.29%, 9.62%, 7.43%, 52.16%, 9.77%, 13.73% in the population. Among them, the male lifestyle pattern was mainly the indulgent type, the remedial type, the heavy smoking type and the heavy drinking type, showing the characteristics of unhealthy lifestyle pattern; Women tended to have healthier lifestyle patterns. After association analysis with MAFLD, it was found that the prevalence of MAFLD was more than 50% in the people who belonged to the indulgent type, remedial type, the heavy smoking type and the heavy drinking type (53.62%, 57.06%, 51.25% and 50.50%, respectively), and the prevalence of MAFLD in the giving type group was 40.17%. The risk of MAFLD in comfortable group was relatively low (28.25%), and the difference in risk of MAFLD among all modes was statistically significant after controlling for confounding factors ( P<0.001). Conclusion:According to cluster mining, there are 6 types of lifestyle patterns in the physical examination population, and the healthier lifestyle pattern has a lower risk of MAFLD.

Background::Artificial intelligence (AI) technology represented by deep learning has made remarkable achievements in digital pathology, enhancing the accuracy and reliability of diagnosis and prognosis evaluation. The spatial distribution of CD3 + and CD8 + T cells within the tumor microenvironment has been demonstrated to have a significant impact on the prognosis of colorectal cancer (CRC). This study aimed to investigate CD3 CT (CD3 + T cells density in the core of the tumor [CT]) prognostic ability in patients with CRC by using AI technology. Methods::The study involved the enrollment of 492 patients from two distinct medical centers, with 358 patients assigned to the training cohort and an additional 134 patients allocated to the validation cohort. To facilitate tissue segmentation and T-cells quantification in whole-slide images (WSIs), a fully automated workflow based on deep learning was devised. Upon the completion of tissue segmentation and subsequent cell segmentation, a comprehensive analysis was conducted.Results::The evaluation of various positive T cell densities revealed comparable discriminatory ability between CD3 CT and CD3-CD8 (the combination of CD3 + and CD8 + T cells density within the CT and invasive margin) in predicting mortality (C-index in training cohort: 0.65 vs. 0.64; validation cohort: 0.69 vs. 0.69). The CD3 CT was confirmed as an independent prognostic factor, with high CD3 CT density associated with increased overall survival (OS) in the training cohort (hazard ratio [HR] = 0.22, 95% confidence interval [CI]: 0.12–0.38, P <0.001) and validation cohort (HR = 0.21, 95% CI: 0.05–0.92, P = 0.037). Conclusions::We quantify the spatial distribution of CD3 + and CD8 + T cells within tissue regions in WSIs using AI technology. The CD3 CT confirmed as a stage-independent predictor for OS in CRC patients. Moreover, CD3 CT shows promise in simplifying the CD3-CD8 system and facilitating its practical application in clinical settings.

Objective:To explore the effect of nursing based on Roy adaptation model on negative emotions and adverse reactions in patients with multiple myeloma during chemotherapy.Methods:Using the convenient sampling method, a total of 100 patients with multiple myeloma who were admitted to Zhoushan Hospital in Zhejiang Province from July 2017 to August 2019 were selected. They were divided into the control group and the observation group by lottery method, with 50 cases in each group. The control group was given routine nursing measures while the observation group was given nursing based on Roy adaptation model on basis of the control group. And patients in both groups were also given the same chemotherapy intervention.The incidence of negative emotions, chemotherapy compliance, nursing satisfaction and adverse reactions after nursing were compared between the two groups.Results:There were no statistically significant differences in the scores of anxiety and depression before nursing between the two groups ( P>0.05) . The scores of anxiety and depression of the two groups after nursing were lower than those before nursing, and the scores of the observation group after nursing were lower than those of the control group, and the differences were statistically significant ( P<0.01) . The incidence of adverse reactions after nursing in the observation group (12.00%, 6/50) was lower than that of the control group (48.00%, 24/50) , and the difference was statistically significant ( P<0.01) . In the observation group, the proportions of patients with good treatment compliance and nursing satisfaction were respectively 90.00% (45/50) and 96.00% (48/50) , which were higher than 64.00% (32/50) and 80.00% (40/50) in the control group, and the differences were statistically significant ( P<0.05) . Conclusions:Nursing based on Roy adaptation model on the basis of routine nursing can improve the adverse reactions of patients with multiple myeloma during chemotherapy, relieve their negative emotions and improve their compliance and nursing satisfaction, which is worthy of promotion and application.

Objective:To understand the characteristics and associated factors of newly reported HIV/AIDS cases with non-marital or non-commercial heterosexual transmission, in Guangxi Zhuang Autonomous Region (Guangxi), 2015-2018.Methods:Information of newly reported HIV/AIDS cases aged ≥18 years in Guangxi between 2015 and 2018 was collected from the National Comprehensive HIV/AIDS Information System. Unconditional logistic regression model was used to access those factors that were associated with HIV infections through non-marital or non-commercial heterosexual contact.Results:Between 2015 and 2018, a total number of 35 497 HIV/AIDS cases, aged ≥18 years were newly reported in Guangxi. Among them, 32 648 (92.0 %) were infected heterosexually while 10 500 were infected through non-marital or non-commercial heterosexual behavior. Non-marital or non-commercial heterosexual transmission accounted for 29.6 % (10 500/35 497) of the newly reported HIV/AIDS cases, and 32.2 % (10 500/32 648) of those with heterosexual transmission. Males counted for 53.5 % (5 617/10 500) of non-marital or non-commercial heterosexual transmission and males to females ratio was 1.2∶1 (5 617∶4 883). Those married or had regular sexual partners counted for 55.9 % (5 873/10 500). Commercial heterosexual transmission appeared the main mode of HIV transmission for males (64.4 %,16 516/25 633) while main mode for females was non-marital or non-commercial heterosexual transmission and counted for 49.5 % (4 883/9 864). Results from the multivariate logistic regression analysis showed that adjusted OR of female HIV/AIDS infected HIV via non-marital or non-commercial heterosexual transmission, was 3.98 times (95 %CI: 3.78-4.20) hight than that of males. Among the group aged<50 years and the aged 50-59 years, the adjusted ORs were 1.35 times (95 %CI: 1.27-1.44) and 1.13 times (95 %CI: 1.05-1.21) hight than that of aged ≥60 years. Those who were single/divorced/widowed, the adjusted OR was 1.53 times (95 %CI: 1.45-1.61) hight than that of those married/regular partners. Those with junior high school education, high school education and above the adjusted ORs were 1.22 times (95 %CI: 1.16-1.29) and 1.18 times (95 %CI: 1.10-1.27), compared to those only with education levels of primary school or below. Conclusions:The number of HIV/AIDS cases via non-marital or non-commercial heterosexual transmission accounted for nearly 30.0 % of all the routes of HIV transmission in Guangxi, 2015-2018. Female, aged<60 years old, single/divorced/widowed and having had junior and above high school education etc., appeared as risk factors on non-marital or non-commercial heterosexual transmission, among newly reported HIV/AIDS in Guangxi.

Objective: To understand the characteristics of HIV/AIDS epidemic in Guangxi Zhuang Autonomous Region (Guangxi) with a purpose to accurately provide scientific basis for prevention and control measures, 2010-2017. Methods: Data were retrieved from case reporting cards of Guangxi during 2010 to 2017 through National HIV/AIDS Comprehensive Response Information Management System. Data was analyzed using epidemiological methods such number of cases, proportion and rate. χ² test was used for statistical analysis. Results: The HIV positive rate was 12.53 per ten thousand (85 182/67 959 000) in Guangxi during 2010 to 2017. The number of newly diagnosed HIV/AIDS cases and the number of death yearly respectively increased by 22.34%(2 602/11 648) and 32.83% (952/2 900) in 2011 compared with 2010, and both showed a six-year continuous downward trend (the number of newly diagnosed cases respectively 12 229 cases, 10 877 cases, 9 460 cases, 9 190 cases, 8 848 cases, 8 680 cases, and the number of death respectively 3 888 cases, 3 316 cases, 2 914 cases, 2 717 cases, 2 595 cases, 2 600 cases) from 2012 to 2017. But proportion of late discovery remained above 50.00% (50.53%-57.06%) for eight-years continuously. The ratio of male and female was 2.47 ∶ 1 (60 639/24 543). The ratio of males and females aged 50 and over was 2.71∶1 (28 654/10 557). Proportion of the cases in 25-49 years old group and 50 years old group accounting for 47.40%(40 377/85 182) and 46.03% (39 211/85 182) respectively. The occupation was farmers accounting for 68.40% (58 262/85 182), housekeeping, housework and unemployment accounting for 11.21% (9 546/85 182), student accounting for 0.86% (729/85 182). Heterosexual transmission accounted for 90.60% (77 171/85 182, homosexual transmission accounted for 3.13% (2 669/85 182), injection drug use transmission accounted for 4.60%(3 924/85 182) and mother-to-child transmission accounted for 0.73% (619/85 182). Conclusions The number of newly diagnosed cases and the number of death yearly showed a continuous downtrend for six-years from 2012 to 2017. However, proportion of late discovery remained above 50.00% for eight-years. The major route of infection was heterosexual transmission. With the change of HIV/AIDS newly epidemic mode in Guangxi, there are many new challenges for HIV/AIDS prevention and control work. Strategy of targeted intervention modes should be innovated for a new breakthrough.

Objective To investigate the knowledge and attitude of nurses on the prevention and nursing of common complications among bedridden patients in Wuhan City, and provide scientific basis for the implementation of targeted training in improving clinical nursing quality. Methods A total of 748 clinical nurses from 4 hospitals in Wuhan City were selected in November 2016 using convenient sampling method. A self-designed questionnaire was applied to investigate the common complications nursing knowledge and attitude of nurses on bedridden patients. Results The accuracy of nurses' knowledge on the prevention and nursing of common complications among bedridden patients were listed as follows: deep vein thrombosis (DVT) (77.44%), pneumonia (73.88%), urinary tract inflammation (70.63%), and pressure ulcers (61.44%). The scores of nurses' attitude were listed successively: pressure ulcers (88.21%), urinary tract inflammation (86.81%), pneumonia (86.66%), and DVT (85.92%). There were positive correlation between the scores of knowledge and attitude of nurses on four kinds of complications (P< 0.05). Conclusions Nursing administrators should improve the training and update of common complications knowledge on nurses, and promote their positive attitude to the prevention of common complication to increase the quality of nursing.