Safety and benefit of modified mesohepatectomy in the treatment of bilobar involvement congenital biliary dilatation.

BACKGROUND: The diseased bile duct in bilobar congenital biliary dilatation is extensive and often requires major hepatectomy or liver transplantation associated with a higher risk. We aimed to evaluate the safety and benefit of modified mesohepatectomy, in comparison with trisectionectomy, to treat bilobar congenital biliary dilatation. METHODS: This study included 28 patients with type IV and V bilobar congenital biliary dilatation. An innovative mesohepatectomy comprising the hepatectomy technique beyond the P/U point and bile duct shaping was applied to 14 patients to address the extensively diseased bile duct and difficulty in hepaticojejunostomy. Another 14 patients received trisectionectomy. The perioperative and long-term outcomes of these patients were compared. RESULTS: The ratio of residual liver volume to standard liver volume in the mesohepatectomy group was higher (78.68% vs. 40.90%, p = 0.005), while the resection rate of the liver parenchyma was lower (28.25% vs. 63.97%, p = 0.000), than that in trisectionectomy group. The mesohepatectomy group had a lower severe complication (>Clavein III, 0% vs. 57.70%, p = 0.019) and incidence of posthepatectomy liver failure (7.14% vs. 42.86%, p = 0.038). No significant difference was observed in blood loss and bile leakage (p > 0.05). All the patients in the mesohepatectomy group achieved optimal results in the long-term follow-up. CONCLUSIONS: mesohepatectomy provides an efficient treatment option for bilobar congenital biliary dilatation and can achieve radical resection, retain more liver parenchyma, and reduce the difficulty of hepaticojejunostomy, especially for patients that are not eligible for major hepatectomy and liver transplantation.

Community screening for dementia among older adults in China: a machine learning-based strategy.

BACKGROUND: Dementia is a leading cause of disability in people older than 65 years worldwide. However, diagnosing dementia in its earliest symptomatic stages remains challenging. This study combined specific questions from the AD8 scale with comprehensive health-related characteristics, and used machine learning (ML) to construct diagnostic models of cognitive impairment (CI). METHODS: The study was based on the Shenzhen Healthy Ageing Research (SHARE) project, and we recruited 823 participants aged 65 years and older, who completed a comprehensive health assessment and cognitive function assessments. Permutation importance was used to select features. Five ML models using BalanceCascade were applied to predict CI: a support vector machine (SVM), multilayer perceptron (MLP), AdaBoost, gradient boosting decision tree (GBDT), and logistic regression (LR). An AD8 score ≥ 2 was used to define CI as a baseline. SHapley Additive exPlanations (SHAP) values were used to interpret the results of ML models. RESULTS: The first and sixth items of AD8, platelets, waist circumference, body mass index, carcinoembryonic antigens, age, serum uric acid, white blood cells, abnormal electrocardiogram, heart rate, and sex were selected as predictive features. Compared to the baseline (AUC = 0.65), the MLP showed the highest performance (AUC: 0.83 ± 0.04), followed by AdaBoost (AUC: 0.80 ± 0.04), SVM (AUC: 0.78 ± 0.04), GBDT (0.76 ± 0.04). Furthermore, the accuracy, sensitivity and specificity of four ML models were higher than the baseline. SHAP summary plots based on MLP showed the most influential feature on model decision for positive CI prediction was female sex, followed by older age and lower waist circumference. CONCLUSIONS: The diagnostic models of CI applying ML, especially the MLP, were substantially more effective than the traditional AD8 scale with a score of ≥ 2 points. Our findings may provide new ideas for community dementia screening and to promote such screening while minimizing medical and health resources.

Sociodemographic and lifestyle determinants of multimorbidity among community-dwelling older adults: findings from 346,760 SHARE participants.

BACKGROUND: This study aimed to investigate the prevalence of multimorbidity and its associated factors among the older population in China to propose policy recommendations for the management of chronic diseases in older adults. METHODS: This study was conducted based on the 2021 Shenzhen Healthy Ageing Research (SHARE), and involved analysis of 346,760 participants aged 65 or older. Multimorbidity is defined as the presence of two or more clinically diagnosed or non self-reported chronic diseases among the eight chronic diseases surveyed in an individual. The Logistic analysis was adopted to explore the potential associated factors of multimorbidity. RESULTS: The prevalences of obesity, hypertension, diabetes, anemia, chronic kidney disease, hyperuricemia, dyslipidemia and fatty liver disease were 10.41%, 62.09%, 24.21%, 12.78%, 6.14%, 20.52%, 44.32%, and 33.25%, respectively. The prevalence of multimorbidity was 63.46%. The mean count of chronic diseases per participant was 2.14. Logistic regression indicated that gender, age, marriage status, lifestyle (smoking status, drinking status, and physical activity), and socioeconomic status (household registration, education level, payment method of medical expenses) were the common predictors of multimorbidity for older adults, among which, being women, married, or engaged in physical activity was found to be a relative determinant as a protective factor for multimorbidity after the other covariates were controlled. CONCLUSION: Multimorbidity is prevalent among older adults in Chinese. Guideline development, clinical management,and public intervention should target a group of diseases instead of a single condition.

[Prevalence and factors of nonalcoholic fatty liver disease among elderly in Shenzhen City in 2018].

OBJECTIVE: To analyze the prevalence and influence factors of nonalcoholic fatty liver disease(NAFLD) among elderly in Shenzhen City. METHODS: From January to December in 2018, a convenient sampling method was used to select 121 042 survey subjects from Shenzhen community residents aged 65 years and above through questionnaire survey, physical examination, laboratory biochemical examination and b-ultrasound examination, demographic information, lifestyle, height, weight, waist circumference, blood pressure, fasting blood glucose, blood lipids, past history and liver B ultrasound result were collected. A total of 121 042 of the subjects were selected for the study with complete information. The logistic regression analysis were used to analyze the data. RESULTS: There were 33 179 NAFLD patients(27.41%). The variables adjusted by logistic regression analysis revealed that male(OR=0.633, 95%CI 0.612-0.654), illiteracy(OR=0.761, 95%CI 0.720-0.804), primary school education(OR=0.889, 95%CI 0.862-0.916), current smoking(OR=0.719, 95%CI 0.675-0.767), former smoking(OR=0.802, 95%CI 0.749-0.859), low-weight(OR=0.157, 95%CI 0.128-0.193) was negatively correlated with NAFLD(P<0.01).65-79 years old, obesity(OR=4.744, 95%CI 4.511-4.989), overweight(OR=2.421, 95%CI 2.341-2.504), central obesity(OR=1.823, 95%CI 1.764-1.883), hypertension(OR=1.101, 95%CI 1.069-1.134), diabetes(OR=1.578, 95%CI 1.528-1.630) and dyslipidemia(OR=1.685, 95%CI 1.639-1.734) was positive correlation with NAFLD(P<0.01). CONCLUSION: The prevalence of NAFLD among the elderly in Shenzhen City is relatively low compared with the national level, but its absolute value is higher. The prevalence of NAFLD is higher among the elderly who are female, highly educated, overweight, obese, central obese, suffering from hypertension, diabetes and dyslipidemia.

6-Year trends in lipids among adults in Shenzhen, China.

BACKGROUND: There may be a beneficial effect on lipid levels in Shenzhen in recent years. In this study, we aimed to examine trends in serum lipids in population in Shenzhen between 2009 and 2015. METHODS: We enrolled 2210 adults aged 18-70 years from two independent cross-sectional studies conducted in 2009 and 2015. Blood lipid profiles, such as total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), were measured. Chi-square test, t-test and multivariate logistic regression analysis were applied for data analysis. RESULTS: From 2009 to 2015, mean LDL-C declined from 3.05 ± 0.76 mmol/L in 2009 to 2.27 ± 0.75 mmol/L in 2015 (P < 0.001). Similarly, a significant 7.09% decrease in the prevalence of high LDL-C was observed over the same period (P < 0.001). There was an increasing trend in the prevalence of low HDL-C among adults in Shenzhen (P < 0.001). A no-significant increase in prevalence of dyslipidemia was also observed over this 6-year interval (P = 0.139). The prevalence of dyslipidemia was closely related with increasing age, male gender, current smoker, diabetes, obesity and overweight. CONCLUSION: This study shows a favourable downward trend in LDL-C concentration in Shenzhen. However, more intense strategies are needed to control dyslipidemia.

Prevalence, treatment, control of type 2 diabetes and the risk factors among elderly people in Shenzhen: results from the urban Chinese population.

BACKGROUND: Type 2 diabetes is regarded as one of the major public health problems worldwide. We aim to investigate the prevalence, treatment, and control rate in the Chinese urban population aged 65 years or older and also identified associated risk factors. METHODS: One hundred twenty-four thousand seven participants aged 65 years old and older were recruited from January 2018 through December 2018 at local community health service centers in Shenzhen. Fasting plasma glucose, as well as other biochemical indicators, were measured by standard methods. The analysis of multivariate logistic regression was applied to assess associated risk factors of type 2 diabetes. RESULTS: Approximately 22.5% of elderly urban Chinese residents had diabetes. Among people with diabetes, 54.8% received medical treatment. Only 34.4% of those who were treated had their glycemic controlled. The prevalence of T2D increased with increasing age before 80 years old, male, inadequate active physical activity, drinking, previous history of CVD, higher BMI, central obesity, and hypertension. CONCLUSIONS: Our findings suggested that attention should be paid to the prevention and control of T2D in Chinese urban elderly population. The health policy department should develop effective strategies aimed at improving health care management of T2D in elderly adults.

Serum lipids and associated factors of dyslipidemia in the adult population in Shenzhen.

BACKGROUND: Dyslipidemia is one of the most important independent modifiable risk factors for cardiovascular diseases. The objective of this study was to determine the prevalence and risk factors for dyslipidemia in Shenzhen, a special economic zone and large metropolitan area neighboring Hong Kong. METHODS: A cross-sectional survey of 1,995 adults with a mean age of 46.56 years was conducted between February and July 2011 using a multistage stratified cluster random sampling. All the subjects were administered questionnaires regarding socio-demographic characteristics and other possible factors associated with the prevalence of dyslipidemia. Fasting venous blood samples were collected to assess the lipid profile. Weight, height, waist circumference, and blood pressure were measured. RESULTS: The mean concentrations of total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) were 5.11 ± 1.15 mmol/L, 1.59 ± 1.47 mmol/L, 1.42 ± 0.33 mmol/L, and 3.22 ± 0.84 mmol/L, respectively. High values of TC, TG, low HDL-C, and high LDL-C were obtained in 14.49%, 16.14%, 8.82%, and 12.13 % of the 1,995 participants, respectively. The prevalence of dyslipidemia was 34.64%, among which 25.04% of subjects were aware. Presence of dyslipidemia was significantly associated with increasing age, smoking status, hypertension, diabetes, and body mass index. CONCLUSIONS: High prevalence of dyslipidemia with relative low awareness in Shenzhen was found. A comprehensive strategy is required for the prevention, screening, treatment, and control of dyslipidemia in Shenzhen.

Endothelial-to-mesenchymal transition contributes to cardiac fibrosis.

Cardiac fibrosis, associated with a decreased extent of microvasculature and with disruption of normal myocardial structures, results from excessive deposition of extracellular matrix, which is mediated by the recruitment of fibroblasts. The source of these fibroblasts is unclear and specific anti-fibrotic therapies are not currently available. Here we show that cardiac fibrosis is associated with the emergence of fibroblasts originating from endothelial cells, suggesting an endothelial-mesenchymal transition (EndMT) similar to events that occur during formation of the atrioventricular cushion in the embryonic heart. Transforming growth factor-beta1 (TGF-beta1) induced endothelial cells to undergo EndMT, whereas bone morphogenic protein 7 (BMP-7) preserved the endothelial phenotype. The systemic administration of recombinant human BMP-7 (rhBMP-7) significantly inhibited EndMT and the progression of cardiac fibrosis in mouse models of pressure overload and chronic allograft rejection. Our findings show that EndMT contributes to the progression of cardiac fibrosis and that rhBMP-7 can be used to inhibit EndMT and to intervene in the progression of chronic heart disease associated with fibrosis.

[Snacks consumption among residents in Shenzhen City].

OBJECTIVE: To describe the status of snacks consumption among residents in Shenzhen. METHODS: By a multiple stage probability proportionate to size sampling, 12 communities were randomly selected from 8 districts of Shenzhen based on population proportion. In the second stage, 30 households were randomly selected from each community. In each household, 2 years or older were invited to take dietary survey. RESULTS: There were 66.1% residents consuming snacks. More girls ate snacks than boys (chi2 = 11.552, P < 0.01) and more children and adolescents ate snacks than adults (chi2 = 27.207, P < 0.01). The average daily intake of energy, protein, fat, carbohydrate, fiber, vitamin A, vitamin C, vitamin E, calcium, sodium,magnesium, iron and zinc from snacks were 107.8 kcal (451.5 kJ), 1.7 g, 0.8 g, 22.0 g, 1.1 g, 23.1 microg, 8.3 mg, 1.1 mg,17.0 mg, 9.3 mg, 21.0 mg, 0.8 mg and 0.4 mg. Food categories the most frequently consumed as snacks were fruit, pastry, milk and products, beverages and grains. CONCLUSION: It's important to strengthen the diet education among residents in Shenzhen, especially the knowledge how to select snacks correctly and rationally.

Freestanding Nanofiber-Assembled Aptasensor for Precisely and Ultrafast Electrochemical Detection of Alzheimer's Disease Biomarkers.

Amyloid beta-protein (AßAß) is a main hallmark of Alzheimer's disease (AD), and a low amount of Aß protein accumulation appears to be a potential marker for AD. Here, an electrochemical DNA biosensor based on polyamide/polyaniline carbon nanotubes (PA/PANI-CNTs) is developed with the aim of diagnosing AD early using a simple, low-cost, and accessible method to rapidly detect Aß42 in human blood. Electrospun PA nanofibers served as the skeleton for the successive in situ deposition of PANI and CNTs, which contribute both high conductivity and abundant binding sites for the Aß42 aptamers. After the aptamers are immobilized, this aptasensor exhibits precise and specific detection of Aß42 in human blood within only 4 min with an extremely fast response rate, lower detection limit, and excellent linear detection range. These findings make a significant contribution to advancing the development of serum-based detection techniques for Aß42, thereby paving the way for improved diagnostic capabilities in the field of AD.

Associations of low-density lipoprotein cholesterol with all-cause and cause-specific mortality in older adults in China.

CONTEXT: Limited information was available on detailed associations of low-density lipoprotein cholesterol (LDL-C) with all-cause and cause-specific mortality in older adults. METHODS: This prospective cohort study included a representative sample of 211,290 adults aged 65 or older, who participated in Shenzhen Healthy Aging Research 2018-2019. The vital status of the participants by 31 December, 2021 was determined. We estimated the hazard ratios (HR) with 95% confidence intervals for all-cause or cause-specific mortality using multivariable Cox proportional hazards models and Cox models with restricted cubic spline(RCS) . RESULTS: The median follow-up time was 3.08 years. A total of 5,333 participants were confirmed to have died. Among them, 2,303 cardiovascular disease (CVD) deaths and 1,881 cancer deaths occurred. Compared to those with LDL-C of 100-129 mg/dL, the all-cause mortality risk was significantly higher for individuals with LDL-C level that was very low (< 70 mg/dL) or low (70-99 mg/dL). Compared with individuals with the reference LDL-C level, the multivariable-adjusted HR for CVD-specific mortality was 1.327 for those with very low LDL-C level (< 70 mg/dL), 1.437 for those with high LDL-C level (160 mg/dL ≦ LDL-C < 190mg/dL), 1.528 for those with very high LDL-C level (≥ 190 mg/dL). Low LDL-C level (70-99 mg/dL) and very low LDL-C level (< 70 mg/dL) were also associated with increased cancer mortality and other-cause mortality, respectively. The results from RCS curve showed similar results. CONCLUSION: Considering the risk of all-causes mortality and cause-specific mortality, we recommended 100-159 mg/dL as the optimal range of LDL-C among older adults in China.

Integrating multi-task and cost-sensitive learning for predicting mortality risk of chronic diseases in the elderly using real-world data.

BACKGROUND AND OBJECTIVE: Real-world data encompass population diversity, enabling insights into chronic disease mortality risk among the elderly. Deep learning excels on large datasets, offering promise for real-world data. However, current models focus on single diseases, neglecting comorbidities prevalent in patients. Moreover, mortality is infrequent compared to illness, causing extreme class imbalance that impedes reliable prediction. We aim to develop a deep learning framework that accurately forecasts mortality risk from real-world data by addressing comorbidities and class imbalance. METHODS: We integrated multi-task and cost-sensitive learning, developing an enhanced deep neural network architecture that extends multi-task learning to predict mortality risk across multiple chronic diseases. Each patient cohort with a chronic disease was assigned to a separate task, with shared lower-level parameters capturing inter-disease complexities through distinct top-level networks. Cost-sensitive functions were incorporated to ensure learning of positive class characteristics for each task and achieve accurate prediction of the risk of death from multiple chronic diseases. RESULTS: Our study covers 15 prevalent chronic diseases and is experimented with real-world data from 482,145 patients (including 9,516 deaths) in Shenzhen, China. The proposed model is compared with six models including three machine learning models: logistic regression, XGBoost, and CatBoost, and three state-of-the-art deep learning models: 1D-CNN, TabNet, and Saint. The experimental results show that, compared with the other compared algorithms, MTL-CSDNN has better prediction results on the test set (ACC=0.99, REC=0.99, PRAUC=0.97, MCC=0.98, G-means = 0.98). CONCLUSIONS: Our method provides valuable insights into leveraging real-world data for precise multi-disease mortality risk prediction, offering potential applications in optimizing chronic disease management, enhancing well-being, and reducing healthcare costs for the elderly population.

The novel costimulatory programmed death ligand 1/B7.1 pathway is functional in inhibiting alloimmune responses in vivo.

The programmed death ligand 1 (PDL1)/programmed death 1 (PD1) costimulatory pathway plays an important role in the inhibition of alloimmune responses as well as in the induction and maintenance of peripheral tolerance. It has been demonstrated recently that PDL1 also can bind B7.1 to inhibit T cell responses in vitro. Using the bm12 into B6 heart transplant model, we investigated the functional significance of this interaction in alloimmune responses in vivo. PD1 blockade unlike PDL1 blockade failed to accelerate bm12 allograft rejection, suggesting a role for an additional binding partner for PDL1 other than PD1 in transplant rejection. PDL1 blockade was able to accelerate allograft rejection in B7.2-deficient recipients but not B7.1-deficient recipients, indicating that PDL1 interaction with B7.1 was important in inhibiting rejection. Administration of the novel 2H11 anti-PDL1 mAb, which only blocks the PDL1-B7.1 interaction, aggravated chronic injury of bm12 allografts in B6 recipients. Aggravated chronic injury was associated with an increased frequency of alloreactive IFN-γ-, IL-4-, and IL-6-producing splenocytes and a decreased percentage of regulatory T cells in the recipients. Using an in vitro cell culture assay, blockade of the interaction of PDL1 on dendritic cells with B7.1 on T cells increased IFN-γ production from alloreactive CD4(+) T cells, whereas blockade of dendritic cell B7.1 interaction with T cell PDL1 did not. These data indicate that PDL1 interaction with B7.1 plays an important role in the inhibition of alloimmune responses in vivo and suggests a dominant direction for PDL1 and B7.1 interaction.

[Relationship between the body mass index, waist circumference and lipids levels among adults in Shenzhen].

OBJECTIVE: To study the relationship between the body mass index (BMI), waist circumference (WC) and lipids levels, dyslipidemia among adults. METHODS: Totally 12 communities from 8 districts were sampled through stratified randomized sampling, 75 households from each community were sampled by random sampling for questionnaire survey, physical examination and laboratory tests. RESULTS: Within different BMI categories, the triglyceride (TG) in higher BMI group were higher than in lower BMI group, and the high density lipoprotein-c (HDL-c) in higher BMI group were lower than in higher BMI group; Within different WC categories, the TG, total cholesterol (TC), low density lipoprotein-c (LDL-c) in higher WC group were higher than in lower WC group. With the increase of BMI/WC, the levels of TG, TC and LDL-c showed a rising trend (P<0.05), HDL-c showed a falling trend (P<0.05). With the increase of BMI, the odds ratios (ORs) of high TG, high TC, low HDL-c, high LDL-c and dyslipidemia showed a rising trend (P<0.05), and with the increase of WC, the ORs of high TG, high TC, high LDL-c and dyslipidemia showed a rising trend (P<0.05). There were positive partial correlations between BMI/WC and TG, TC, HDL-c, LDL-c. HDL-c had a higher correlation with BMI (P<0.05), TC had a higher correlation with WC (P<0.05). CONCLUSION: BMI and WC were independently associated with blood lipids levels, and high BMI and WC were the risk factors for dyslipidemia.

Comprehensive analysis of cuproptosis-related genes on bladder cancer prognosis, tumor microenvironment invasion, and drug sensitivity.

Cuproptosis, a newly discovered form of programmed cell death, plays a vital role in the occurrence and development of tumors. However, the role of cuproptosis in the bladder cancer tumor microenvironment remains unclear. In this study, we developed a method for predicting the prognostic outcomes and guiding the treatment selection for patients with bladder cancer. We obtained 1001 samples and survival data points from The Cancer Genome Atlas database and Gene Expression Omnibus database. Using cuproptosis-related genes (CRGs) identified in previous studies, we analyzed CRG transcriptional changes and identified two molecular subtypes, namely high- and low-risk patients. The prognostic features of eight genes (PDGFRB, COMP, GREM1, FRRS1, SDHD, RARRES2, CRTAC1, and HMGCS2) were determined. The CRG molecular typing and risk scores were correlated with clinicopathological features, prognosis, tumor microenvironment cell infiltration characteristics, immune checkpoint activation, mutation burden, and chemotherapy drug sensitivity. Additionally, we constructed an accurate nomogram to improve the clinical applicability of the CRG_score. qRT-PCR was used to detect the expression levels of eight genes in bladder cancer tissues, and the results were consistent with the predicted results. These findings may help us to understand the role of cuproptosis in cancer and provide new directions for the design of personalized treatment and prediction of survival outcomes in patients with bladder cancer.

Cathelicidin LL-37 promotes EMT, migration and metastasis of hepatocellular carcinoma cells in vitro and mouse model.

The effect of cathelicidin hCAP18/LL-37 in hepatocellular carcinoma (HCC) metastasis remains unclear. Here, we confirmed that LL-37 expression enhanced endothelial-mesenchymal transition (EMT), migration and invasion in HCC cells. And the HER2/EGFR-MAPK/ERK signal participated in the process above. More frequent lung metastases were observed in an LL-37-overexpressing hematogenous metastasis model. Interestingly, 1,25(OH)2D3 together with si-LL-37 significantly enhanced 1,25(OH)2D3-induced inhibition of migration and invasion in PLC/PRF-5 cells, and also enhanced reversion of the EMT process. Therefore, LL-37 is involved in HCC metastases, and may act as an important factor to attenuate the inhibitory activity of 1,25(OH)2D3 on HCC metastasis. Targeting hCAP18/LL-37 may offer a potential strategy to improve the anticancer activity of 1,25(OH)2D3 in HCC therapy.

Recent Progress on Nanomaterial-Facilitated Electrochemical Strategies for Cancer Diagnosis.

Cancer is a malignant disease that endangers human life, especially owing to its high fatality rate; therefore, rapid and accurate early screening is needed to effectively improve the survival rate. Compared with traditional cancer detection methods, electrochemical biosensors that recognize cancer biomarkers in blood have the advantages of low invasiveness, fast diagnosis, and low cost. However, there is always a trade-off between sensitivity and selectivity, which limits the detection of trace amounts of biomarkers produced in the early stages. To address this issue, an increasing number of nanomaterials with simultaneous improvements in both sensitivity and selectivity have recently been reported. In this review, different categories of state-of-the-art electrochemical biosensors and their operating principles are introduced, and their respective advantages and disadvantages are described. Furthermore, the review discusses the existing detection strategies and performance of nanomaterial-based cancer biosensors for biomarker recognition, providing overall guidance for the material selection of different biomarkers. Finally, the main challenges involving existing electrochemical cancer biosensors are evaluated to present the future development prospects of nanomaterials and detection strategies.

Concordance of Non-Alcoholic Fatty Liver Disease and Associated Factors among Older Married Couples in China.

Background: Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases which affects mainly middle-aged and older adults, resulting in a considerable disease burden. Evidence of concordance on NAFLD and lifestyle factors within older married couples in China is limited. This study aimed to evaluate spousal concordance regarding lifestyle factors and NAFLD among older Chinese couples. Methods: We conducted a cross-sectional study using data from 58,122 married couples aged 65 years and over recruited from Shenzhen, China during 2018−2020. Logistic regression analyses were used to estimate the reciprocal associations in NAFLD within couples after incremental adjustment for potential confounders. Results: There was a marked concordance regarding NAFLD among older married couples in our study. After adjustment for confounders, the odds of having NAFLD were significantly related to the person's spouse also having NAFLD (1.84 times higher in husbands and 1.79 times higher in wives). The spousal concordance of NAFLD was similar, irrespective of gender. Couples with both a higher educational level and abdominal obesity were more likely to have a concordance of NAFLD compared to couples with both a lower educational level and no abdominal obesity, respectively (p < 0.05). Conclusion: Our results indicated that health care professionals should bear in mind the marked spousal concordance with respect to risk factors and NAFLD for the prevention and early detection of the highly prevalent disease in older Chinese adults.

Protocol for Shenzhen Ageing Cohort Study (SZ-ageing): a prospective observational cohort study of elderly disability and cognitive impairment.

INTRODUCTION: The incidence and prevalence of disability and cognitive impairment, which are age-related, increase as China has become an ageing society. This study aims to establish the Shenzhen Ageing Cohort Study (SZ-ageing) to explore the epidemiological situation, risk factors and biomarkers of disability and cognitive impairment among Chinese elderly individuals. METHODS: About 3000 participants aged 65 years and older are to be recruited from communities in Shenzhen by using a multistage sampling method. They will receive a baseline investigation between 2022 and 2024. The comprehensive data on disability and cognitive impairment will be collected by using standardised questionnaires, standardised scale assessments, clinical measurements and clinical laboratory tests. Active follow-up surveys with the same content as the baseline investigation will be conducted every 3 years. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the ethics committee of the Shenzhen Center for Chronic Disease Control (SZCCC-2022-001-01-PJ; 21 February 2022). The research findings will be presented at professional conferences and submitted to peer-reviewed journals. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR2200060055).

TIM-3: a novel regulatory molecule of alloimmune activation.

T cell Ig domain and mucin domain (TIM)-3 has previously been established as a central regulator of Th1 responses and immune tolerance. In this study, we examined its functions in allograft rejection in a murine model of vascularized cardiac transplantation. TIM-3 was constitutively expressed on dendritic cells and natural regulatory T cells (Tregs) but only detected on CD4(+)FoxP3(-) and CD8(+) T cells in acutely rejecting graft recipients. A blocking anti-TIM-3 mAb accelerated allograft rejection only in the presence of host CD4(+) T cells. Accelerated rejection was accompanied by increased frequencies of alloreactive IFN-γ-, IL-6-, and IL-17-producing splenocytes, enhanced CD8(+) cytotoxicity against alloantigen, increased alloantibody production, and a decline in peripheral and intragraft Treg/effector T cell ratio. Enhanced IL-6 production by CD4(+) T cells after TIM-3 blockade plays a central role in acceleration of rejection. Using an established alloreactivity TCR transgenic model, blockade of TIM-3 increased allospecific effector T cells, enhanced Th1 and Th17 polarization, and resulted in a decreased frequency of overall number of allospecific Tregs. The latter is due to inhibition in induction of adaptive Tregs rather than prevention of expansion of allospecific natural Tregs. In vitro, targeting TIM-3 did not inhibit nTreg-mediated suppression of Th1 alloreactive cells but increased IL-17 production by effector T cells. In summary, TIM-3 is a key regulatory molecule of alloimmunity through its ability to broadly modulate CD4(+) T cell differentiation, thus recalibrating the effector and regulatory arms of the alloimmune response.