Diabetic cataract, a prevalent ocular complication of diabetes mellitus, arises from a complex interplay of pathological mechanisms, with oxidative stress and glycation stress playing central roles. Autophagy, a critical cellular self-protection mechanism, sustains intracellular homeostasis by selectively degrading damaged organelles and misfolded proteins, thereby counteracting the detrimental effects of oxidative and glycation stress under hyperglycemic conditions. Emerging evidence indicates a synergistic interaction between glycation stress and oxidative stress, which may exacerbate autophagic dysfunction and accelerate the onset and progression of diabetic cataract. However, the precise molecular mechanisms underlying this relationship remain incompletely understood. This review systematically examines the regulatory role of autophagy inthe pathogenesis of diabetic cataract, with a particular focus on how autophagic impairment influences disease progression under the combined effects of glycation and oxidative stress. By elucidating these mechanisms, the paper aims to provide novel insights into molecular diagnostic approaches and targeted therapeutic strategies for diabetic cataract.

Objective To investigate the role and mechanism of RNA-Specific adenosine deaminase 3 (Adar3) in regulating macrophage polarization during Coxsackievirus B3(CVB3)-induced viral myocarditis (VM). Methods Bone marrow-derived macrophages (BMDM) from mice were cultured in vitro and induced into M1/M2 macrophages using interferon-gamma (IFN-γ)/lipopolysaccharide (LPS) or interleukin 4 (IL-4), respectively. The mRNA expression levels of Adar1, Adar2, and Adar3 in each group of cells were assessed by real-time quantitative PCR (qRT-PCR). Specific siRNAs targeting the Adar3 gene were designed, synthesized, and transiently transfected into M2 macrophages. The mRNA levels of M2 polarization-related marker genes-including arginase 1 (Arg1), chitinase 3-like molecule 3 (YM1/Chi3l3), and resistin-like molecule alpha (RELMα/FIZZ1)-were detected by qRT-PCR. RNA sequencing was performed to analyze the signaling pathways affected by Adar3. The expression levels of Wnt/β-catenin signaling pathway were further validated using qRT-PCR and Western blot. The adeno-associated virus overexpressing Adar3 was designed, synthesized, and injected into mice via tail vein. Three weeks later, a myocarditis mouse model was established. After an additional week, the phenotype and function of cardiac macrophages, as well as multiple indicators of VM (including echocardiography, body weight, histopathology and serology) were examined. Additionally, the protein levels of the Wnt/β-catenin signaling pathway were assessed. Results Compared to M0-type macrophages, the expression level of Adar3 was significantly increased in M2-type macrophages. After transfection of Adar3 siRNA, the mRNA levels of Arg1, YM1 and FIZZ1 in M2 macrophages were downregulated. RNA sequencing revealed 149 upregulated genes and 349 downregulated genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and subsequent validation experiments indicated that Adar3 modulated the Wnt/β-catenin signaling pathway. In vivo experiments demonstrated that Adar3 overexpression alleviated the cardiac dysfunction of VM mice. The proportion of M1 macrophages in the heart decreased, while the proportion of M2 macrophages increased. At the same time, the Adar3 overexpression activated the Wnt/β-catenin signaling pathway. Conclusion Adar3 promotes macrophage polarization toward the M2 phenotype by activating the Wnt/β-catenin signaling pathway, thereby alleviating VM.
Animals ; Adenosine Deaminase/metabolism* ; Macrophages/immunology* ; Wnt Signaling Pathway/genetics* ; Myocarditis/immunology* ; Mice ; Coxsackievirus Infections/metabolism* ; Male ; Mice, Inbred BALB C ; Enterovirus B, Human/physiology* ; beta Catenin/genetics*

Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

Objective: To explore sex difference in the cardiovascular health (CVH) status of 6-8 year old children in Beijing, so as to inform the early intervention of CVH related lifestyles. Methods: Based on the Beijing Children s Growth and Health Cohort (PROC), baseline physical examination, sequential questionnaire survey, and laboratory tests were conducted among 1 914 grade 1 students. Children s CVH and its subscales (health behaviors and health factors) scores were calculated according to the Life s Essential 8 (LE 8) index and categorized into high, moderate, and low CVH. CVH scores were reported as medians and interquartile ranges; sex differences were compared using the Chi square test and Wilcoxon test. Results: Among the 1 914 participants, the percentages of high, moderate, and low CVH were 35.7%, 63.5%, and 0.8%, respectively, and the percentages of high, moderate, and low health behavior scores were 25.9%, 67.5%, and 6.6%, respectively, with no statistically significant differences between sex ( χ 2=2.30, 0.07, P >0.05). The rates of high, moderate, and low health factor scores for boys and girls were 61.1%, 36.0%, 2.9% and 71.1%, 28.4%, 0.5%, respectively, with a statistically significant sex difference ( χ 2=31.88, P < 0.01). The overall CVH score was 76.0(70.0, 83.0), 76.0(69.0, 82.0) for boys, and 77.0(71.0, 83.0) for girls. Among the health behavior metrics, sleep scores were the best and physical activity scores were the worst[100.0(90.0,100.0), 40.0(20.0, 80.0 )]; among the health factor metrics, blood glucose scores were the best and lipid scores were the worst[100.0(100.0,100.0), 60.0(40.0,100.0)]. In respect to health factors, there were significant gender differences in body mass index, blood lipids, blood sugar, and blood pressure scores ( Z =-6.92, 3.01, -6.60, -2.30, <0.05), but there were no significant gender differences in diet, physical activity, nicotine exposure, or sleep scores with regards to health behaviors ( Z =0.99, 0.88, -0.13, 0.36, P > 0.05 ). Compared to boys, girls in the low and moderate CVH groups had high health factor scores despite low health behavior scores. Conclusion Most 6 to 8-year-old children in Beijing were found to have relatively good CVH, and optimization of children s CVH status can be achieved by promoting healthier lifestyles and monitoring health factors, especially among boys.

School is a densely populated place, which can easily lead to tuberculosis clusters, then affect the physical and mental health of students and the normal teaching order of school. Tuberculosis latent infection (LTBI) screening for new students and close contacts of tuberculosis patients has become important parts of school tuberculosis prevention and control strategies. Previous studies have shown that the LTBI rate of Chinese in-school students is about 5.74% to 11.67%, and there are differences in gender, studying phase and urban-rural distributions. Preventive treatment is an effective measure to prevent LTBI from developing into active tuberculosis, but the proportion of LTBI preventive treatment for students in most areas is low. The difficulties in implementing preventive treatment may be attributed to concerns about adverse reactions to medication and sense of shame towards illness among students, and lack of awareness about preventive treatment among medical staff. This review searches the research literature published from 2016 to 2023, and summarizes the prevalence of LTBI in Chinese students and progress on preventive treatment, so as to provide insights into prevention and control of tuberculosis among students.

Objective: To explore the longitudinal association between organophosphate esters (OPEs) exposure and blood pressure in children, so as to provide a reference for identifying the effects of OPEs exposure on child health. Methods: A total of 404 children from the Beijing Child Growth and Health Cohort (PROC) were enrolled using a case cohort study design, baseline physical examination, urine collection, questionnaires survey were administered in 2018 and follow up surveys in 2019-2020 and 2023. Participants were divided into case group ( n =140) and control group ( n =264) according to the observation of new onset of high blood pressure during the follow up period. High performance liquid chromatography tandem mass spectrometry was used to detect diethyl phosphate (DEP)，bis (2-chloroethyl) phosphate (BCEP)，bis (1-chloro-2-propyl) phosphate, (BCIPP), diphenyl phosphate(DPHP), dibutyl phosphate (DnBP), bis (1,3-dichloro-2-propyl) phosphate(BDCIPP), bis(2-butoxyethyl) phosphate(BBOEP), bis (2-butoxyethyl) 2-hydroxyethyl phosphate (BBOEHEP), 4-hydroxyphenyl diphenyl phosphate (4-OH-TPHP). Generalized linear mixed models and Quantile g computation models were developed to analyze the longitudinal associations between OPEs individual/mixed exposure and blood pressure in children. Results: The detection range of 9 OPEs metabolites,including DEP, BCEP, BCIPP, DPHP, DnBP, BDCIPP, BBOEP, BBOEHEP and 4-OH-TPHP at three time points (baseline, first follow up and second follow up) were 27.7%-92.1%, 24.0%-99.3% and 39.2%-90.9% respectively. Without adjustment for covariates such as gender, age, body mass index, Tanner stage, parental education, and monthly household income, and family history of hypertension, the increase of BDCIPP concentration and mixed exposure of OPEs may reduce children s systolic blood pressure( β= -0.85，-2.40，95%CI=-1.69--0.01，-3.30--1.50，P <0.05). After adjusting for the covariates, the longitudinal association of individual OPEs or mixed exposure with pediatric BP was not statistically significant ( P >0.05). Conclusion Children are commonly exposed to OPEs, and although no significant longitudinal associations are observed between exposure to OPEs and blood pressure among school aged children in Beijing, it is recommended that child exposure should be minimized whenever possible.

Purpose To explore the predictive value of nomogram model for invasive breast cancer with axillary lymph node metastasis.Materials and Methods Retrospective analysis was made on 122 patients suspected to be breast cancer in the General Hospital of Ningxia Medical University from September 2020 to March 2022.According to whether there was axillary lymph node metastasis,all subjects were divided into 57 patients in the metastasis group and 65 patients in the non-metastasis group.All lesions were pathologically confirmed by surgery.The two groups received synthesis of magnetic resonance imaging(syMRI),dynamic contrast enhancement magnetic resonance imaging(DCE-MRI)and diffusion weighted imaging(DWI)scans.The syMRI parameters[including T1,T2,proton density(PD)],DCE-MRI time signal intensity curve,apparent diffusion coefficient(ADC)value of breast lesions were measured.Compared the difference of parameters between the two groups,and screened the independent risk factors of invasive breast cancer with axillary lymph node metastasis.Results Logistic regression results showed that Ki-67(OR=2.971,95%CI 1.306-6.762,P=0.009),lesion size(OR=1.652,95%CI 1.067-2.556,P=0.024),ADCratio(OR=1.685,95%CI 1.014-2.801,P=0.044),T2ratio(OR=3.015,95%CI 1.433-6.340,P=0.003),PDratio(OR=2.782,95%CI 1.471-5.262,P=0.002)were independent risk factors for invasive breast cancer with axillary lymph node metastasis.The comparison of the five models showed that the Logistic regression model had the best performance,with the area under curve of 0.729(95%CI 0.621-0.789),the accuracy,specificity and sensitivity were 70.65%,62.79%and 77.55%,respectively.The accuracy of the nomogram model was tested,and C-index=0.844,the accuracy of the nomogram model established was good,cut-off risk was 0.468,and the cut-off score was 143.50,which means that when the total score exceeds 143.50,the risk of axillary lymph node metastasis would be higher than 46.8%.Conclusion Nomogram model has a good predictive ability for invasive breast cancer patients with axillary lymph node metastasis.

OBJECTIVE To clarify the institutional logics of the dilemma of the use of national medical insurance negotiation drugs（referred to as “national negotiation drugs”）， and promote the implementation and use of these drugs in medical institutions. METHODS Based on the complex institutional environment in which medical institutions were situated， the theory of multiple institutional logics was used to construct an analytical framework for the behavioral choices of medical institutions， and reveal the mechanism of the difficulty in the use of national negotiation drugs by clarifying the interaction and conflict of multiple logics in this process， so as to put forward some measures. RESULTS & CONCLUSIONS There were contradictions and coupling among the state logic， market logic， social logic and professional logic in the use of national negotiation drugs. In the game of multiple logics， the market logic and professional logic tended to be risk-averse， the failed “pressure-type system” of state logic， and the social logic was weakened， which caused the lack of action in the use of national negotiation drugs with the goal of completing performance evaluations in the current medical institutions. Thus， it is suggested to unbundle the invisible policy restrictions on the use of national negotiation drugs， form the pressure and motivation of medical institutions by incentive and constraint mechanisms， respond to the clinical demand by establishing a green procurement channel， and construct the supervision mechanism on the use of national negotiation drugs by social force， etc.， so as to enhance the effect of the national negotiation drugs.

Objective To establish an ideal modeling method for diarrhea predominant irritable bowel syndrome(IBS-D)with anxiely and depression in rats,and to provide a basis for the clinical study of IBS-D.Methods 60 rats were used in this study.(1)At first,20 rats were randomly divided into blank,3%acetic acid enema,4%acetic acid enema,and 5%acetic acid enema groups.After the modeling and observation period,the diarrhea status and the degree of colon injury caused by different modeling concentrations were observed by diarrhea related index and colon histopathology.(2)After the optimal modeling concentration was assessed,40 rats were randomly divided into control(a),acetic acid enema(b),acetic acid+binding(c),and acetic acid+binding+tail clip(d)groups and correspondingly treated for 8 days.After the treatments,the general condition,diarrhea-related index,open field test(OFT)score,and colonic histopathology of rats were evaluated.Results(1)Compared with the blank group,the fecal trait score of 4%acetic acid enema group was increased on days 1 to 3 after intervention(P＜0.001),and gradually decreased on days 4 to 7 after intervention.After 1 week,there was no significant difference between the fecal trait score and that of the blank group(P＞0.05).Body weight was lower(P＜0.01),fecal water content was higher(P＜0.001).Compared with blank group,body weight of the 5%acetic acid enema group was decreased(P＜0.001),the fecal trait score and diarrhea index were increased(P＜0.01).No significant difference was found between 3%acetic acid enema and blank groups.The pathological colon tissue showed that,compared with the blank group,the mucosal structure of the 4%acetic acid enema group was complete with a small amount of inflammatory cell infiltration,and the pathological tissue score showed no significant difference(P＞0.05),whereas the 5%acetic acid enema had a medium to large amount of inflammatory cell infiltration,and the pathological tissue score was increased(P＜0.01).(2)Compared with group a,group b had lower body weight(P＜0.001),and higher fecal trait score,fecal water content and diarrhea index(P＜0.01).Compared with a and b groups,the body weight of c and d groups was lower(P＜0.001),the fecal traits score,fecal water content,and diarrhea index were increased(P＜0.01),and the colon running time was decreased(P＜0.01).Compared with group c,Fecal water content in group D was higher(P＜0.001).In the OFT score,compared with a and b groups,the OFT distance,standing times,and upright times in c and d groups were lower(P＜0.05).Compared with c,the OFT distance,standing times,and upright times in d group were lower(P＜0.05).The pathological tissue of colon showed that the mucosal structure of the four groups was complete,and there were different degrees of inflammatory cell infiltration.The pathological tissue scores of groups c and d were higher than those of groups a and b(P＜0.05).Conclusions The 4%acetic acid concentration is appropriate for IBS-D modeling.After superposition and binding,the IBS-D diarrhea and internal hypersensitivity characteristic state can be better simulated.After superposition of a tail clip,the IBS-D model of liver stagnation and spleen deficiency can be established successfully.

Objective To explore the longitudinal trajectories of symptom clusters in patients with rectal cancer within 6 months after laparoscopic anal preservation surgery,and analyze the predictive factors of each trajectory subgroup.Methods A longitudinal survey was conducted to select 128 patients who underwent laparoscopic anal preservation surgery for rectal cancer at the Department of Gastrointestinal Surgery,a tertiary hospital in Nanchong from November 2021 to April 2022.The general information questionnaire,Chinese version of Anderson Symptom Inventory for Gastrointestinal Cancer and Charlson Comorbidity Index were used to conduct follow-up surveys of the selected patients at 2 weeks,1 month,3 months and 6 months after surgeiy.The symptom cluster were extracted by exploratory factor analysis,and the latent category growth model was constructed to identify the trajectory subgroups of each symptom cluster.The predictive factors of each trajectory subgroup were analyzed by Mplus statistical software.Results There were 4 symptom clusters within 6 months after laparoscopic anus preserving surgeiy for rectal cancer,which were named as sickness symptom cluster,psychological-sleep symptom cluster,gastrointestinal symptom cluster,and psychological-treatment-related symptom cluster.The variance contribution rates were 65.173％,66.225％,62.421％,and 60.492％,respectively.The latent class growth model identified that there are 4 to 5 trajectory subgroups in the symptom cluster.Gender,education level,Charles Comorbidity Index,clinical T stage,medical cost burden,and treatment method were the predictors of high-risk trajectory subgroups in the symptom cluster(P＜0.05).Conclusion There are 4 symptom clusters within 6 months after laparoscopic anus preserving surgeiy for rectal cancer.The gastrointestinal symptom cluster is a specific symptom cluster for this type of patients with the heaviest symptom burden.The overall trajectory of each symptom cluster shows a dynamic decline trend,but individual trajectoiy subgroups still have an exacerbation trend.There are differences in predictive factors for different symptom clusters.Clinical medical staff should pay attention to the management of symptom clusters in patients with female patients,low education level,high Charles Comorbidity Index,high clinical T stage,heavy medical cost burden,and patients whose treatment method is chemotherapy plus surgery.High-risk groups should be timely identified;corresponding intervention methods were dynamically adjusted;the quality of precision nursing was improved.