The time to pharyngeal polymerase chain reaction (PCR) negativity (TPCRN) in patients with coronavirus disease 2019 (COVID-19) is influenced by multiple factors. This study aimed to investigate the association between clinical symptoms of COVID-19 patients and TPCRN. This retrospective study enrolled 486 participants with COVID-19, aged 18–89 years, who were admitted to Shanghai Lingang Makeshift Hospital between April 10, 2022, and May 20, 2022. Clinical data, including patient demographics, clinical symptoms, and TPCRN, were collected and analyzed. This study enrolled COVID-19 patients with a median age of 38 years, consisting of 66.05

BackgroundUltra-radical cytoreductive surgery is frequently performed for patients with advanced ovarian cancer (OC). However, anastomotic leakage (AL) is a serious complication of such surgeries and the risk factors remain unclear. This study identified early postoperative C-reactive protein (CRP) and albumin were the strongest predictors of leakage.MethodsThis multicenter retrospective study involved 305 patients with ovarian cancer who underwent primary anastomosis following enterectomy, spanning January 2018 to June 2023. Comprehensive clinical and demographic data were used to develop predictive models. Feature selection was performed using LASSO and univariate logistic regression. Machine learning algorithms were subsequently applied, with model interpretability assessed using SHapley Additive explanations (SHAP).ResultsThe study revealed an AL prevalence of 14.1%, with 46.5% of affected patients requiring reoperation. Five predictors were identified, including postoperative CRP, serum albumin levels, Eastern Cooperative Oncology Group score, N stage, and blood urea nitrogen. The Lasso-Logistic model demonstrated the best predictive performance with an area under the curve of 0.828 (0.119). SHAP analysis highlighted early postoperative CRP, albumin, and N stage as major contributing factors. Economic analysis revealed a significant correlation between AL and hospital stay, hospital costs, and time to chemotherapy.DiscussionEarly postoperative inflammatory and nutritional biomarkers, particularly CRP and albumin, demonstrated significant predictive value for anastomotic leakage, providing an early warning for risk stratification and intervention. The investigation also bolstered the evidence supporting the restrictive surgical scope approach advocated in clinical guidelines.

This study examined the effects of exercise on islet fibrosis in mice with type 2 diabetes and investigated the role of irisin in the regulation of islet stellate cell (ISC) activation. Following the 16-week moderate-intensity exercise intervention, db/db mice showed reduced body weight and improved glucose tolerance and insulin sensitivity. This exercise intervention also decreased collagen-I (Col-I), fibronectin (FN), and α-smooth muscle actin (α-SMA); reduced islet fibrosis area (assessed by Masson staining); and lowered the numbers of α-SMA-positive ISCs in the pancreas. Serum irisin was increased after a single bout of moderate-intensity exercise but decreased following the 16-week exercise intervention. In vitro experiments showed that irisin suppressed ISC activation by delaying lipid droplet loss, inhibiting migration, and reducing expression of α-SMA, Col-I, and FN. Irisin also attenuated advanced glycation end products-or transforming growth factor-β (TGF-β)-induced ISC activation and extracellular matrix production and competitively bound to TGF-β receptor 2 (TGFBR2), inhibiting TGF-β/Smad pathway phosphorylation. These findings suggest that exercise may help to alleviate diabetes-related islet fibrosis, in part by suppressing ISC activation via irisin-mediated inhibition of TGF-β/Smad signaling.

Microvascular disease has traditionally been regarded as a defining complication of diabetes, responsible for major clinical outcomes including retinopathy, nephropathy, neuropathy, and limb amputation. Existing frameworks have largely attributed microvascular injury to chronic hyperglycaemia, mediated through pathways such as advanced glycation end product formation, protein kinase C activation, and oxidative stress. While these mechanisms are well established, a predominantly glucose-centric paradigm may incompletely capture the complexity of microvascular pathology. Accumulating evidence indicates that microvascular abnormalities are also prevalent in individuals without diabetes and may arise across a continuum of metabolic dysfunction. Epidemiological studies and clinical trials further suggest that intensive glucose lowering alone does not fully eliminate the risk of microvascular complications, highlighting the importance of non-glycaemic contributors, including hypertension, dyslipidaemia, insulin resistance, adiposity, and chronic inflammation. Notably, these metabolic disturbances may precede overt hyperglycaemia and provide earlier signals of vascular vulnerability. These observations have direct clinical relevance for diabetologists, as they suggest that microvascular injury may develop during prediabetes or earlier stages of metabolic dysfunction, with important implications for early screening and risk stratification in diabetes-oriented clinical practice. In this review, we propose the concept of metabolic microvascular disease (MMD), which reframes microvascular pathology as a systemic consequence of metabolic dysregulation rather than a complication confined to diabetes. We synthesise evidence of microvascular disease across populations with and without diabetes, summarise shared and distinct pathogenic mechanisms, and outline a pragmatic framework to support early clinical recognition and research stratification. Finally, we discuss the clinical and public health implications of adopting a metabolic perspective, emphasising the need for prevention strategies that extend beyond glucose-lowering to include comprehensive metabolic risk management.

Case numbers of metabolic diseases such as diabetes and hyperlipidaemia are increasing worldwide and show geographic heterogeneity, but the role of environmental geography in shaping this pattern is poorly defined. Here we integrate large multi-region cohorts in China (n = 3,648 cross-sectional; n = 1,547 prospective) with high-resolution soil trace-element data to test whether geography shapes levels of dietary ions and risk of metabolic disease. We observe geographic variations in levels of serum and urinary trace elements, with selenium, zinc and chromium linked to metabolic outcomes. Soil selenium was a predictor of serum selenium in participants even after incorporating regional dietary, socioeconomic and air-quality indicators. In a prospective cohort, participants in the highest serum selenium tertile (107.2–162.8 µg l−1) had a 35% higher risk of incident diabetes than those in the lowest tertile (relative risk (RR) = 1.35; 95% confidence interval (CI) = 1.02–1.77) after multivariable and dietary adjustment; the association was significant in men (RR = 1.96; 95% CI = 1.21–3.17), but not in women (RR = 1.10; 95% CI = 0.77–1.58). Globally, an estimated 14% of land area—home to approximately 1 billion people—has high soil selenium, with residents projected to have serum selenium levels above 110 µg l−1, a range in which selenium supplementation could increase diabetes risk. In a prospective multi-centre cohort in China, people living in areas of high soil selenium had a 35% increased risk of incident diabetes over a 3-year study period, with a stronger effect seen for men.

Background: Prediabetes comprises three heterogeneous glucometabolic phenotypes and is associated with an increased risk of metabolic dysfunction-associated fatty liver disease (MAFLD). However, the association of different prediabetes phenotypes with the presence of MAFLD and liver fibrosis remains underexplored. Objectives: To examine the association of different prediabetes phenotypes with MAFLD and liver fibrosis. Design: Population-based cross-sectional study. Methods: Prediabetes was stratified as an isolated defect (impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or impaired hemoglobin A1c (IA1c)), two defects (IFG + IGT, IFG + IA1c, or IGT + IA1c), or all three defects (IFG + IGT + IA1c). Hepatic steatosis and liver fibrosis were assessed by vibration-controlled transient elastography. Multivariate logistic regression analysis was conducted to estimate the odds ratio (OR) and 95% confidence interval (CI) for different prediabetes phenotypes associated with MAFLD and liver fibrosis. Results: A total of 1599 subjects (394 with normal glucose tolerance (NGT) and 1205 with prediabetes) were included. The prevalence of MAFLD and liver fibrosis was higher in prediabetes than in NGT. The odds of MAFLD in prediabetes with two or three glucometabolic defects were increased compared with those with a single glucometabolic defect, with insulin resistance as a possible mediator. Compared with isolated IA1c, isolated IGT had an increased prevalence of MAFLD ( p < 0.05). Moreover, glucose-defined prediabetes had higher odds of MAFLD than HbA1c-defined prediabetes (OR 1.72, 95% CI 1.00–2.96). However, there was no significant difference in the odds of liver fibrosis across different prediabetes phenotypes ( p = 0.58). Conclusion: The odds of MAFLD but not liver fibrosis were increased with the increasing number of glucometabolic defects in participants with prediabetes. Trial registration: Not applicable.

Physical function declines with ageing; however, the changes in the prevalence of impaired physical function during ageing and how the changes would be affected by physical activity are not well investigated. This study aimed to address the issues. We included participants aged ≥ 65 years in the 2008–2010 wave, who were followed-up in the 2012–2014 and the 2016–2018 waves of the Health and Retirement Study. Types of impaired physical function included weak grip strength, slow walking speed, and poor standing balance. Their prevalence in each wave was calculated and their changes over time were estimated using the mixed-effects logistic regression model. A total of 6,537 older adults were included. The prevalence of slow walking speed ranked the highest in all the types of impaired physical function in all the 3 individual waves (all Pcomparison <0.001). During follow-up, participants were increasingly being older and the prevalences of all the types of impaired physical function were gradually increased after multivariate-adjustment (all Ptrend <0.001). These increases were unlikely to be significantly moderated by weight status, drinking history or the presence of diabetes (all Pinteraction ≥0.19). However, the increases in the prevalences of weak grip strength and slow walking speed were nonsignificant in participants with regular physical activity, but was significant in those without (Pinteraction = 0.009 and 0.01, respectively). Despite gradual increases in the prevalence of impaired physical function during ageing, regular physical activity may help to preserve physical function in older adults. Not applicable.

Background:Increased physical activity and reduced sedentary time are associated with lower risks of diabetes. However, their association with diabetic kidney disease (DKD) is unclear. This study aimed to assess this issue in the Chinese adults with diabetes. Methods:This multicenter, cross-sectional study included adults with diabetes from 40 hospitals across 26 diverse Chinese cities. Leisure-time physical activity (LTPA), housework physical activity (HPA), occupational physical activity (OPA), and sedentary time were assessed using a validated questionnaire. DKD was defined according to the NKF-K/DOQI guidelines. Associations between activity domains and DKD were examined using multivariable logistic regression, with subgroup, interaction, and sensitivity analyses to assess robustness. Results:A total of 4,979 patients with diabetes were included. After multivariable adjustment, those meeting the guideline-recommended amount of LTPA had lower odds of DKD (OR 0.79, 95% CI 0.68-0.91 for aerobic exercise; OR 0.69, 95% CI 0.50-0.96 for resistance exercise) compared with those not meeting recommendations. However, heavier HPA and larger OPA were associated with higher odds of DKD (OR 1.51 and 1.66, respectively). Moreover, longer daily sedentary time was associated with increased odds of DKD only in women (OR 2.10), but not in men. Further stratified analysis suggested that the association between LTPA and lower odds of DKD may be modified by HPA, OPA, or sedentary time. Conclusions:Among Chinese adults with diabetes, LTPA was associated with lower odds of DKD, whereas higher occupational and household physical activity showed positive associations, underscoring the differences in domain-specific physical activity in DKD prevention.

INTRODUCTION:Pancreatic stellate cells (PSCs) play a central role in pancreatic physiology and disease, and the transition between their quiescent and activated states influences processes such as fibrosis and regeneration. However, the stem cell-like properties of PSCs remain unclear. This study aims to clarify the stem cell characteristics of PSCs and establish a method to maintain their quiescent state, thereby providing a new perspective on pancreatic regeneration. METHODS:PSCs from Lrat-cre; Rosa26-tdTomato mice were fate-traced, and immunofluorescence was used to assess Lrat, Oct4, and Nanog co-localization. Primary PSCs from C57BL/6 mice were cultured in mesenchymal stem cell (MSC) or DMEM/F12 medium. Lipid droplets, morphology, activation markers (α-SMA, collagen-I, fibronectin), and stemness-associated markers were analysed via qRT-PCR and immunofluorescence. RESULTS:Lrat co-localized with Oct4/Nanog in mice. MSC-cultured PSCs had more lipid droplets, a quiescent morphology, and lower levels of activation markers than DMEM/F12-cultured cells. They also expressed stemness-associated markers (Pdx1, Oct4, Nkx6.1, Ngn3, Sox2, Pax6). DISCUSSION:These results indicate that PSCs possess stemness and can be preserved under specific culture conditions. The ability of MSC medium to maintain PSCs in a quiescent and stem-like state provides a valuable model for studying their biology. CONCLUSION:PSCs exhibit stemness, and MSC medium maintains their quiescence, offering a novel experimental platform to study PSC biology and lineage plasticity.

Emerging evidence implicates cerebellar degeneration-related protein 1 antisense transcript (CDR1as) and alpha-synuclein (α-Syn) in diabetes and cognitive decline, suggesting their potential to serve as biomarkers. This study aimed to evaluate their diagnostic efficacy for type 2 diabetes mellitus-associated mild cognitive impairment (T2DM-MCI) and establish a corresponding diagnostic model using machine learning. T2DM-MCI-associated differentially expressed genes were identified from the hippocampus using the Gene Expression Omnibus and predictive databases. The study involved 529 T2DM patients in two phases (training set = 408, test set = 121). Levels of plasma CDR1as, α-Syn, Aβ1-40/1–42, and ApoE genotype were detected. Three diagnostic models were identified using least absolute shrinkage and selection operator (LASSO) and logistic regression. Their performance was assessed using the area under the curve (AUC), net reclassification index (NRI), and integrated discrimination improvement (IDI). The best-performing model was selected from nine machine learning algorithms. Personalized risk assessment was achieved with the SHapley Additive exPlanations (SHAP). Bio-informatics analysis identified CDR1as and α-Syn as potential biomarkers. Their inclusion in multi-modal panels markedly improved diagnostic accuracy. The Random Forest (RF) model outperformed eight other machine learning classifiers (AUC = 0.975, 95 https://www.xsmartanalysis.com/model/list/predict/model/html?mid=6734 symbol=816GyBh9ag1Wr9367341 ). The study preliminarily identified CDR1as and α-Syn as promising biomarkers for T2DM-MCI. Integrating these markers with conventional blood tests showed potential clinical utility for improving diagnostic precision.

BACKGROUND:Cardiorespiratory fitness (CRF) is inversely associated with the risk of cardiovascular disease, which is related to impaired vascular function. However, its relationship with vascular function remains unknown in patients with type 2 diabetes. AIM:To assess the relationship of CRF with vascular function in type 2 diabetes. METHODS:Patients with type 2 diabetes who were aged ≥ 18 years and underwent an incremental and symptom-limited exercise test were included. Vascular function was assessed by the construction of the vascular health index (VHI), which is defined as a composite score of ankle-brachial index, transcutaneous oxygen pressure, pulse wave velocity, and carotid intima-media thickness. Impaired vascular function is defined as a VHI of < 8 points. Linear and logistic regression analyses were used to assess the associations. RESULTS:We included 343 patients with type 2 diabetes. CRF was positively correlated with VHI (β = 0.10, P = 0.047), particularly with ankle-brachial index and pulse wave velocity. The odds ratio (OR) of impaired vascular function was 0.44 [95% confidence interval (CI): 0.20-0.96] for the highest vs the lowest CRF category. For each one metabolic equivalent increase in CRF, the OR of impaired vascular function was 0.73 (95%CI: 0.57-0.93). CONCLUSION:Higher CRF was associated with better vascular function and lower odds of impaired vascular function in patients with type 2 diabetes.

Objective: Minimally invasive surgery is rapidly developing and widely used, but the difficulty of laparoscopic endoscopic single-site surgery (LESS) poses a challenge to many surgeons. We aim to enrich the study of the learning curve of LESS application in adnexectomy surgery so as to provide more information support for surgeons. Methods: The medical records of 369 patients who underwent LESS of benign adnexal masses from January 2018 to December 2023 were reviewed by a chief physician from Zhongda Hospital affiliated to Southeast University. The medical records of patients who underwent conventional laparoscopic surgery of benign adnexal masses in the same period were collected in a ratio of 1:2. After collecting data according to the standards of waste and discharge, the learning curve of LESS was drawn, and the differences in objective outcomes between LESS and conventional multisite laparoscopy were compared. Results: All 101 patients underwent successful surgery. In the LESS group, the median operation time was 65 (55-80) min, and the median diameter of the tumor was 7 (5-8) cm. The fitting curve equation was y (R-2 = 0.743), the median postoperative hospital stay was 4 (3-5) days, the average postoperative hemoglobin decrease was 18.49 +/- 11.12 g/L, the median postoperative leukocyte increase was 1.04 (-0.04, 2.55) x 10(9)/L, the postoperative ambulation time was 1 day, and the postoperative exhaust time was 2 days. Two groups were compared in 284 patients. The median intraoperative blood loss in the LESS group was 25 (20, 50) ml, which was higher than that in the conventional laparoscopy (CL) group (20 [10, 50] mL, p = 0.03). The median postoperative hemoglobin decrease in the LESS group was 20 (12, 27) g/L, which was also higher than that in the CL group (15 [7, 20] g/L, p = 0.01). The white blood cell count in CL group increased by 0.98 [-0.51, 2.12] x 10(9)/L, which was significantly higher than that in LESS group (-0.99 [-2.04, 0.11] x 10(9)/L, p < 0.05). There was no significant difference in operation time (p = 0.74) and total postoperative hospital stay (p = 0.85). Conclusion: After 57 or more cases of surgical training, the surgeon can cross the learning curve to meet the surgical requirements and be more skilled in performing LESS of adnexal masses. There is no significant difference in overall patient benefits between transumbilical LESS and CL, but the inflammatory response after LESS is lower, and LESS has important advantages in the resection of accessory masses.

The activation of islet stellate cells (ISCs) plays an important role in islet fibrosis, which leads to impaired islet function. While our previous work showed that the expression of the Pdpn gene was significantly increased in activated ISCs, it remains unknown whether Pdpn is responsible for islet fibrosis. This study was aimed at elucidating its function on islet fibrosis, along with the exploration of the underlying mechanisms. Then, diabetic mice were used for in vivo studies, while primary ISCs were used for in vitro experiments. Podoplanin (PDPN) expression was manipulated using gene knockdown and overexpression techniques. Beta-cell function was assessed by insulin secretion and glucose tolerance tests. Islet fibrosis was evaluated by quantifying extracellular matrix deposition and ISCs activation markers using histological staining and immunohistochemistry, respectively. The effects of advanced glycation end products (AGEs) and TGF-β1 on PDPN expression and the corresponding mechanisms of ISCs activation were investigated. Finally, it was found that knocking down PDPN in diabetic mice led to reduced ISCs activation and islet fibrosis, accompanied by improved insulin expression and lower fasting blood glucose. AGEs were found to induce PDPN expression in ISCs. The overexpression of PDPN triggers the activation of ISCs via cell deformation and TGF-β1 secretion. Interestingly, TGF-β1 in turn activates the TGF-β1/SMAD2/3 pathway by binding to TGF-βRI, inducing the expression of PDPN and the activation of ISCs. In summary, PDPN regulates the activation of ISCs through a mechanism involving cell deformation and a PDPN-TGF-β1 autocrine feedback loop, thereby significantly contributing to islet fibrosis in diabetes.

AIMS:Current hypertension guidelines fail to discriminate between fasting and postprandial blood pressure (BP) measurements. Meal ingestion often triggers a marked increase in splanchnic blood flow, potentially inducing a sustained fall in systolic BP of ≥20 mmHg, termed postprandial hypotension (PPH). This study aimed to evaluate BP responses to a 75 g glucose drink and its implications for detecting hypertension and PPH in community-dwelling adults. METHODS AND RESULTS:A stratified multi-stage random sampling method was used to obtain a nationally representative sample of n = 4429 adult residents between April 2020 and January 2021 in China. BP and heart rate (HR) were measured before, and 1 and 2 h after, a 75 g glucose drink. When fasting, 38.4% of the study population had high BP (BP ≥140/90 mmHg). Following the glucose drink, SBP and DBP decreased (SBP by 6.2 [95% CI: 5.8, 6.6] mmHg and 8.1 [7.7, 8.5] mmHg, DBP by 4.7 [4.4, 4.9] mmHg and 6.1 [5.8, 6.4] mmHg), and HR increased (by 4.3 [4.0, 4.5] bpm and 2.6 [2.4, 2.9] bpm) at 1 and 2 h (P < 0.001 for all), with only 30.9% and 27.0% of the study population having high BP at 1 and 2 h, respectively. After adjustment for age and sex distribution, 19.9% of the general population was estimated to have PPH. Postprandial hypotension was associated with an increased risk of combined cardiovascular disease and stroke. CONCLUSION:Ingestion of a 75 g glucose drink often lowers BP, frequently leading to PPH and influencing the detection of hypertension. Accordingly, guidelines for measurements of BP and interpretation of outcomes should consider the potential impact of meal ingestion on BP.

INTRODUCTIVE:Early impairments in post-challenge glucose regulation are not fully captured by fasting measures alone. The postload-fasting gap, defined as the difference between 2-hour postload plasma glucose (2hPG) and fasting plasma glucose (FPG), may reflect dynamic dysregulation, yet its relation with glycaemic deterioration and remission in Chinese populations remains unclear. To characterise the dose-response relation between the postload-fasting gap and four glycaemic outcomes: incident diabetes, incident prediabetes, progression from prediabetes to diabetes, and reversion to normal glucose tolerance in a large multicentre Chinese cohort. RESEARCH DESIGN AND METHODS:We analyzed 3094 adults free of diabetes at baseline with two revisits over a mean follow-up of 3.24 years. Outcomes were ascertained at each visit by oral glucose tolerance test (OGTT) using World Health Organization (WHO) 1999 criteria, with sensitivity analyses using American Diabetes Association (ADA) definitions that include HbA1c. Primary associations were estimated on person-period data using discrete-time hazard models with a complementary log-log link, modeling the postload-fasting gap with restricted cubic splines after adjusting for demographic, clinical, and lifestyle covariates; cluster robust SEs accounted for repeated observations. Spline knots (K=3, 4, or 5) were placed at recommended percentiles and selected by Akaike information criterion, treating delta Akaike information criterion less than or equal to 2 as equivalent and favoring the more parsimonious model. Multiplicity was controlled using the false discovery rate. Internal validation used cluster bootstrap resampling. We further assessed prediction with six nested models (A-F), reporting area under the curve (AUC) with bootstrap CIs, net reclassification improvement and integrated discrimination improvement, and evaluated clinical utility by decision curve analysis. RESULTS:Higher postload-fasting gaps were associated with more adverse metabolic profiles at baseline and with higher risks of incident diabetes, incident pre-diabetes, and progression; lower postload-fasting gaps were associated with reversion to normal glucose tolerance. Dose-response curves showed that for incident diabetes, risk was flat close to a postload-fasting gap of 0 and increased beyond 2 mmol/L; for incident pre-diabetes, risk increased in a generally monotonic fashion; for progression, the increase was steeper; for reversion, risk decreased as postload-fasting gap increased. Findings were robust to alternative covariate sets, knot choices, and diagnostic definitions. In prediction analyses, the model that combined FPG with the postload-fasting gap (model F) provided the greatest incremental value across outcomes. For incident diabetes, the optimism-corrected AUC was 0.686, continuous net reclassification improvement was up to 0.349, and integrated discrimination improvement was 0.005; decision curve analysis indicated a higher net benefit for model F across clinically relevant thresholds. CONCLUSIONS:The postload-fasting gap is an independent and non-linear marker of glycemic risk and remission potential. Incorporating this measure, particularly together with FPG, improves risk stratification and clinical utility, supporting its use as a practical OGTT-derived metric for early identification of people at risk of developing diabetes and targeted prevention.