ObjectiveDiabetic kidney disease (DKD) is a major microvascular complication of type 2 diabetes mellitus (T2DM), and its early identification is crucial. As a novel endocrine marker, the relationship between sclerostin and DKD, as well as its combined diagnostic value with 25-hydroxyvitamin D (25(OH)VD), remains unclear. This study aims to investigate circulating sclerostin levels in patients with DKD and its combined diagnostic value with 25(OH)VD, providing evidence for early clinical diagnosis.MethodsA total of 308 patients with T2DM were enrolled, including 113 with DKD (DKD group) and 195 without DKD (T2DM group). The DKD group was subdivided into microalbuminuria and macroalbuminuria groups based on UACR. General information and clinical indicators were collected for all patients. Concurrently, blood samples were collected to measure serum sclerostin levels using the ELISA method. Statistical analysis evaluated sclerostin expression differences across groups and its correlations with other indicators. Binary logistic regression analyzed the independent associations of sclerostin and 25(OH)VD with DKD. Receiver operating characteristic (ROC) curves were plotted to assess the predictive efficacy of serum sclerostin and 25(OH)VD levels for T2DM with albuminuria.ResultsCompared to the T2DM group, patients in the DKD group exhibited decreased serum sclerostin and 25(OH)VD levels (P< 0.05). Further subgroup analysis of DKD revealed that serum sclerostin levels were significantly lower in both the microalbuminuria and macroalbuminuria groups compared to the normal albuminuria group (P< 0.05). Serum 25(OH)VD in the massive proteinuria group was significantly lower than in both the normal proteinuria and microalbuminuria groups (P< 0.05). Correlation analysis showed a significant negative correlation between sclerostin and UACR (r = -0.197, P< 0.001) and a significant positive correlation with 25(OH)VD (r = 0.167, P = 0.003). Binary logistic regression analysis demonstrated that serum sclerostin and 25(OH)VD remained independent predictors of DKD even after adjusting for variables. ROC curve analysis showed that the AUC for predicting DKD using serum sclerostin and 25(OH)VD was 0.73, with a sensitivity of 61.1% and specificity of 75%.ConclusionThis study confirms that serum levels of sclerostin and 25(OH)VD are significantly reduced in patients with DKD, and both are independent protective factors for DKD. Their combined assessment demonstrates good predictive value for the early identification of DKD, providing clinical insights into the interaction between bone metabolism and renal pathology.

Objective To investigate the association between the weight-to-waist ratio and total bone mineral density in US adults. Methods This cross-sectional study included 7005 adults from the National Health and Nutrition Examination Survey 2011–2018. The weight-to-waist ratio was calculated as body weight divided by waist circumference, and total bone mineral density was measured using dual-energy X-ray absorptiometry. Survey-weighted multivariable linear regression and restricted cubic spline analyses were conducted to evaluate the association between the weight-to-waist ratio and total bone mineral density after adjustment for demographic, socioeconomic, lifestyle, and clinical covariates. Results A higher weight-to-waist ratio was significantly associated with greater total bone mineral density across all models. In the fully adjusted model, each 1-unit increase in the weight-to-waist ratio was associated with a 0.39 g/cm 2 increase in total bone mineral density (95% confidence interval: 0.35–0.42; P < 0.001). Participants in the highest weight-to-waist ratio quartile had significantly higher total bone mineral density than those in the lowest quartile (β = 0.09, 95% confidence interval: 0.08–0.10; P < 0.001). Restricted cubic spline analysis indicated a significant positive linear association. The association was stronger in men than in women (P for interaction <0.001). Conclusions A higher weight-to-waist ratio was independently associated with greater total bone mineral density in US adults, particularly among men. The weight-to-waist ratio may provide complementary anthropometric information regarding skeletal health, although prospective studies are needed to confirm causality.

BackgroundThe consumption of dairy products has been suggested to be associated with the prevention of obesity, cardiovascular diseases, and type 2 diabetes. However, it is unclear whether dairy consumption has a protective effect on gestational diabetes mellitus (GDM). This study aimed to investigate the prospective associations between pre-pregnancy dairy consumption and risk of GDM among Chinese women.MethodsA total of 1,012 women aged 18–40 years were enrolled from a prospective cohort between 2022 and 2024. Dairy consumption 1 year before pregnancy was collected by food frequency questionnaire. To screen for GDM, participants were scheduled for an oral glucose tolerance test (OGTT) at 24–28 weeks of gestation. Logistic regression and restricted cubic spline analyses were conducted to analyze the associations between dairy consumption and risk of GDM.ResultsDuring the follow-up, 126 (12.5%) were diagnosed with GDM. Compared with non-consumers of room-temperature-storage yogurt, women in the highest tertile of consumption had 2.64-fold higher odds of GDM (OR: 2.64, 95% CI: 1.25–5.38) after adjusting for potential confounders. In subgroup analyses, the positive associations between room-temperature-storage yogurt consumption and risk of GDM were observed in women who were 30 years and older, whose pre-pregnancy BMI was lower than 24.0 kg/m2, and who were multiparas. No significant association was found for consumption of total dairy, whole milk, low-fat milk, refrigerated yogurt, or pregnant milk powder.ConclusionOur results indicated that higher consumption of room-temperature-storage yogurt before pregnancy might be a risk factor for GDM. Further research is warranted to elucidate the underlying associations and mechanisms between dairy consumption and GDM.

AIMS:To estimate the prevalence and incidence of hypoglycaemia and the variations in Chinese type 2 diabetes (T2D) patients. MATERIALS AND METHODS:A multi-centre, non-interventional study was conducted across 103 hospitals in 20 provinces in China between 18 March 2022 and 5 December 2023. The study adopted an integrated 12-week prospective cohort study design, enrolling 15 437 adults with T2D. Hypoglycaemic events were captured through a structured questionnaire and patient diary, including laboratory-confirmed, symptomatic, any, severe and nocturnal hypoglycaemia. Variations in hypoglycaemia burden were examined by socio-demographic factors, health status, treatment regimens, geographic region and hospital level. The endpoints were the prevalence of patients experiencing at least one hypoglycaemic event and the corresponding incidence during the study period. RESULTS:The 15 437 participants who completed the follow-up at Week 12 were included in this study. During this period, 9.0% [95% CI: 8.6, 9.5] of the participants experienced at least one hypoglycaemic event, corresponding to an incidence rate of 79.8 [76.9, 82.8] events per 100 person-years. Hypoglycaemia burden differed markedly according to treatment background. The 12-week prevalence of any hypoglycaemia was 5.5%, 9.7% and 12.2% among participants receiving neither insulin nor secretagogues, secretagogues without insulin and insulin, respectively, with corresponding incidence rates of 48.6, 105.0 and 104.3 events per 100 person-years. Similar treatment-related patterns were observed for laboratory-confirmed, symptomatic and nocturnal hypoglycaemia. Hypoglycaemia burden also varied substantially across age, diabetes duration, body mass index (BMI), HbA1c, geographic region and hospital level. Greater hypoglycaemia burden was generally observed among participants with longer diabetes duration and lower BMI. The prevalence of any hypoglycaemia was highest in the eastern region and tertiary hospitals, whereas its incidence rate was highest in western regions and primary hospitals. CONCLUSIONS:Although the prevalence and incidence of hypoglycaemia among Chinese T2D patients were lower than previous studies, hypoglycaemia still remains a significant clinical concern. These findings highlight the importance of individualized strategies for glycaemic management to minimize hypoglycaemia risk in routine diabetes care. TRIAL REGISTRATION:Chinese Clinical Trial Registry: ChiCTR2100053847.

Objective:To investigate the causal association between Seipin and breast cancer risk using the Mendelian randomization (MR) approach. Methods:Genome-wide association study (GWAS) data for Seipin and breast cancer were analyzed, and genetic variants associated with Seipin were selected as instrumental variables (IVs). Inverse variance weighting (IVW) was used as the primary analytical method, supplemented by MR-Egger, weighted median, simple mode, and weighted mode MR analyses to evaluate the causal relationship between Seipin and breast cancer risk. Furthermore, immunohistochemistry was performed to detect Seipin expression in pathological specimens from patients with breast cancer and those with mammary hyperplasia, and the correlation between Seipin expression and clinicopathological characteristics was analyzed. Results:MR analyses indicated that Seipin was inversely associated with breast cancer risk (IVW: OR = 0.89, 95% CI: 0.83-0.96, P < 0.05). Consistent with this, immunohistochemical results showed lower Seipin expression in breast cancer tissues than in mammary hyperplasia tissues, and its low expression was correlated with adverse clinicopathological features. Further independent validation using the TCGA-BRCA cohort recapitulated reduced BSCL2 expression in tumor versus adjacent normal tissues (P = 9.58 × 10-3). Conclusion:MR combined with immunohistochemistry and independent public database validation suggests that Seipin may serve as a potential protective factor closely related to the occurrence and progression of breast cancer. Further functional studies are needed to elucidate the underlying mechanisms.

ObjectiveThis study aims to investigate the association between serum calcium and asprosin levels in community-dwelling elderly patients with type 2 diabetes mellitus (T2D). It seeks to clarify the relationship between serum calcium and other metabolic indicators, as well as identify independent factors influencing serum calcium levels. The findings are intended to provide a foundation for elucidating the interactive mechanisms between calcium metabolism and adipokines.MethodsA total of 321 elderly T2D patients aged ≥65 years were enrolled from November 2019 to July 2021 at the Zhuoma Community Health Service Station and Chengbei Xijie Community Health Service Center in Changzhi City, Shanxi Province. General information including age, duration of diabetes, body mass index (BMI), etc., was collected. Fasting plasma glucose (FPG), glycated hemoglobin A1c (HbA1c), creatinine (CRE), high-density lipoprotein cholesterol (HDL-C), uric acid (UA), and other biochemical indicators were measured. Serum asprosin levels were determined using enzyme-linked immunosorbent assay (ELISA) while serum calcium levels were assessed with an automatic biochemical analyzer. Pearson/Spearman correlation analysis was employed to evaluate associations between serum calcium and various indicators; multiple linear regression analysis was utilized to identify independent factors affecting serum calcium levels.ResultsSerum asprosin levels increased progressively across serum calcium tertiles. Correlation analyses demonstrated statistically significant associations between serum calcium and HDL-C (r = 0.123), uric acid (r = 0.132), asprosin (r = 0.124), and creatinine (r = −0.113). In multivariable linear regression analysis, creatinine (standardized β = −0.179, p = 0.003) and asprosin (standardized β = 0.187, p = 0.002) remained independently associated with serum calcium levels. Pearson correlation analysis demonstrated a significant positive association between serum asprosin and total calcium (r = 0.214, P < 0.001). A similar positive correlation was observed between asprosin and albumin-corrected calcium (r = 0.170, P = 0.002).ConclusionSerum asprosin was independently associated with serum calcium levels in elderly patients with T2D, suggesting a potential link between calcium homeostasis and adipokine regulation. Further longitudinal and mechanistic studies may help elucidate the clinical and biological implications of this relationship.

Objective To probe the serum asprosin levels in community-dwelling individuals diagnosed with type 2 diabetes mellitus (T2DM) and to verify their association with blood pressure. Methods From November 2019 to July 2021, detailed information was systematically collected from 498 patients diagnosed with type 2 diabetes mellitus at a community health service station located in southeastern Shanxi Province. Blood pressure measurements taken on the same day, laboratory indices, and serum asprosin concentrations were recorded. The systematization of participants was based on their blood pressure measurements, categorized into two groups: normotensive and hypertensive. The variance in indices between these two sets was analyzed through the application of t-tests, χ2 tests, and non-parametric tests. The association between asprosin and elevated blood pressure was subsequently examined via logistic regression analysis. Results The group with elevated blood pressure demonstrated significantly higher levels of asprosin in comparison to the normotensive group (P < 0.01). Multivariate logistic regression analysis indicated that, after tertile stratification and using the T1 group as the reference, the risk of hypertension was significantly increased in both the T2 and T3 groups in the unadjusted model (Model 1: P < 0.003). Following stepwise adjustment for age, gender, BMI, metabolic parameters, and the use of antihypertensive and antidiabetic medications, the associations persisted as statistically significant in Model 2 (P < 0.009) and Model 3(P < 0.015). Conclusions Elevated serum asprosin levels are correlated with a heightened risk of hypertension among community-dwelling individuals with T2DM.

ObjectiveThis article aimed to explore the clinical presentation, genetic underpinnings, and therapeutic approach to Gitelman syndrome (GS) in pediatric patients.MethodsThis article presents a detailed case report of a child with persistent hypokalemia, incorporating clinical evaluations, laboratory testing, treatment strategy, and whole-exome sequencing. A literature review was conducted to contextualize the findings.ResultsThe patient was found to carry compound heterozygous mutations in the SLC12A3 gene, with each inherited from a different parent. These mutations were identified as the primary cause of the child's refractory hypokalemia and impaired growth.ConclusionHypokalemia is a hallmark manifestation of pediatric GS. Genetic testing is instrumental for accurate diagnosis and differentiation from other hypokalemic conditions. The non-specific clinical phenotype of GS can lead to a missed or delayed diagnosis. In addition, co-occurrence of the p.T60M and p.T649M mutations is extremely rare in China. The presentation of this case underscores the need for heightened awareness of GS among pediatricians to enable early diagnosis and therapy, thereby optimizing the long-term quality of life of affected children.

Background: Acute intermittent porphyria (AIP) is the most common and severe form of acute hepatic porphyria, caused by heterozygous mutations in the HMBS gene. Due to its non-specific clinical manifestations and low clinical awareness among clinicians, AIP is frequently misdiagnosed, leading to significant diagnostic delays and potentially fatal complications. Case presentation: We report a 20-year-old female patient who presented with a 9-month history of recurrent abdominal pain, paralytic ileus, unexplained liver injury, and hyponatremia, followed by progressive limb weakness. She was initially misdiagnosed with Guillain-Barré syndrome (GBS) and received intravenous immunoglobulin and systemic glucocorticoids. However, her condition deteriorated, and she developed life-threatening respiratory muscle paralysis requiring invasive mechanical ventilation. The diagnosis of AIP was confirmed by positive urinary porphobilinogen (PBG) testing and identification of the heterozygous HMBS c.517C>T pathogenic variant. The patient was treated with high-dose carbohydrate loading therapy and comprehensive supportive care, resulting in gradual clinical improvement. Discussion and Conclusions: This case exemplifies the substantial diagnostic challenges associated with AIP, especially when it manifests with peripheral neuropathy that closely mimics GBS. The triad of absent albuminocytologic dissociation in cerebrospinal fluid, preceding visceral symptoms, and inadequate response to standard first-line GBS therapy should immediately raise clinical suspicion for AIP. Enhanced clinical awareness of this rare disorder and timely implementation of urinary PBG screening are of paramount importance to prevent irreversible neurological complications and optimize long-term patient outcomes.

Background:Multiple myeloma (MM) presents a growing public health challenge in Asia, yet evidence on its epidemiology and risk factors in transitioning economies like China is limited. This study aimed to compare the disease burden, risk factors, and future trends of multiple myeloma between China and the High-Income Asia Pacific (HIC AP) region. Methods:We conducted an integrated analysis combining data from the Global Burden of Disease (GBD) study 2023 (1993-2023) with a matched case-control study at a tertiary cancer center in China (2021-2025). The case-control component included 235 newly diagnosed MM cases and 235 healthy controls. Exposures of interest were sex, age, body mass index (BMI), and income level. Main outcomes included age-standardized incidence (ASIR), mortality (ASMR), and disability-adjusted life years (DALYs) rates (ASDR); individual-level risk associations; and Bayesian projections to 2040. Results:From 1993 to 2023, China's ASIR increased by 175% (from 0.34 to 0.94 per 100 000), while its ASMR plateaued after 2,000. The HIC AP region maintained high but stable ASIRs (2.00 to 2.13 per 100 000) alongside declining ASMRs. In the case-control study, older age (50-69 years: adjusted odds ratio [aOR], 6.69; 95% confidence interval [CI], 4.08-10.99; ≥70 years: aOR, 6.10; 95% CI, 3.30-11.27) and male sex (aOR, 1.59; 95% CI, 1.06-2.37) were significant risk factors. Sex-stratified analysis revealed that higher BMI (24-27.9 kg/m2) was associated with increased risk in males (aOR, 2.14; 95% CI, 1.19-3.85) but not in females (aOR, 0.86; 95% CI, 0.45-1.64). Income level showed no significant association. Projections indicate China's ASIR will continue rising to 2.55 per 100 000 by 2,040 with declining ASMR, while the HIC AP burden remains high and stable. Conclusion:China exhibits transitional MM epidemiology characterized by rapidly rising incidence and plateauing mortality, driven by aging and improved healthcare access. The identified sex-specific association between BMI and myeloma risk highlights population heterogeneity. These findings underscore the need for tailored prevention and control strategies for Asia's evolving disease landscape.

POU3F2, a member of the Pit-Oct-Unc (POU) domain transcription factor family, is widely expressed in the central nervous system and essential for the development and maturation of brain. POU3F2 deletion results in impaired hypothalamus and neocortex development, and most mice die between postnatal days 0 and 10. Recently, emerging evidences have demonstrated that POU3F2 is involved in neuropsychiatric disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, bipolar disorder, schizophrenia, and autism spectrum disorder, albeit still with some limitations in current studies. Besides, POU3F2 also plays a vital role in the reprogramming of somatic cells into neuronal lineages, which provides new ideas and directions for the treatment of neuropsychiatric disorders. This review aims to systematically summarize and analyze the diverse roles of POU3F2 in brain development, neuropsychiatric disorders, and neuronal reprogramming. Furthermore, the potential of POU3F2-targeted therapies for neuropsychiatric disorders and proposed key questions for future research are also emphasized. POU3F2 plays a pivotal role in brain development, the pathogenesis of neurological and psychiatric disorders, and the reprogramming of neural cells. A more comprehensive and systematic understanding of its molecular mechanism might provide novel therapeutic approaches for neuropsychiatric disorders.

Atherosclerosis (AS) lacks the therapy of targeting and inhibiting foam cells. In this study, a biomimetic delivery system was designed utilizing monocytes as vehicles to transport reactive oxygen species (ROS)-responsive nanovehicles containing M2 macrophage secretion and ATV, thus generating reinfusion of functional monocytes (MAMS) after remodeling to treat atherosclerosis. MAMS utilized active transportation to specifically target and regulate immune responses at the focus. The findings demonstrated that MAMS effectively induced the polarization of M2 macrophages and maintained their optimal activity. MAMS exhibited significant scavenging capacity against ROS, effectively inhibited foam cell formation and promoted the efflux of lipids in vitro. Furthermore, MAMS promoted the conversion of monocytes into M2 macrophages and their migration towards foam cells. In murine models of AS, MAMS displayed significant lipid-lowering efficacy, regulated relevant enzymes, reduced foam cells and fibers, induced M2 macrophages, and regulated the proliferation of smooth muscle. The integration of this ROS-responsive material and the reinfusion of functional monocytes has resulted in a novel cell shipping administration method that exhibits a multi-faceted effect on AS treatment, including lipid reduction, inflammation resistance, antioxidant activity, targeted delivery, microenvironment modification, and immune repair. This innovative approach is poised to revolutionize the management of AS.

Background: Type 2 diabetes mellitus (T2DM) is a metabolic disorder that significantly impacts women's reproductive health. Therefore, this study utilizes the latest Global Burden of Disease (GBD) data to comprehensively assess the burden of T2DM among women of reproductive age (WRA) worldwide from 1990 to 2021. Methods: Data on T2DM incidence, prevalence, disability-adjusted life years (DALYs), and mortality among WRA were extracted from the GBD database for 1990–2021. Global, regional, and age-specific trends were analyzed using percentage changes and estimated annual percentage changes. The Spearman correlation test examined the relationship between the Social Development Index (SDI) and disease burden indicators. Future trends were projected using Bayesian Age-PeriodCohort and Nordpred models. Results: From 1990 to 2021, the global burden of T2DM among WRA rose substantially, with incidence, prevalence, DALYs, and deaths increasing by 201%, 251%, 181%, and 90%, respectively. Age-standardized incidence rates (ASIR), prevalence rates (ASPR), and mortality rates (ASDR) also exhibited significant upward trends. Low-SDI regions experienced the highest growth in absolute numbers, while high-SDI regions saw the greatest increases in ASIR, ASPR, and ASDR. Agestratified analysis indicated a pronounced rise in burden with advancing age. Projections suggest a continued increase in the global T2DM burden among WRA by 2040. Conclusions: The global burden of T2DM among WRA has increased significantly from 1990 to 2021, with this trend expected to further worsen in the coming years. It is imperative to strengthen relevant management measures to address this severe health challenge.

AimsAsprosin is a newly discovered adipokine, it is associated with the insulin resistance, lipid metabolism disorder, diabetes and obesity. However, there have been no reports on the relationship between asprosin and type 2 diabetic patients with obesity. This study aims to investigate the relationship between serum asprosin and type 2 diabetic patients with obesity in the community.Materials and methodsA total of 491 patients with Type 2 Diabetes Mellitus (T2DM) were recruited from Zhuoma Community Care Station and Chengbei West Street Community Care Service Center in Changzhi City of Shanxi Province from November 2019 to July 2021. Patients were divided into the Normal group (n= 145), Overweight group (n=201) and Obesity group (n= 145). The t-test, Mann–Whitney U test, and χ² test were used to compare indicators between the Normal group, Overweight group and Obesity group. Pearson or Spearman correlation analysis was adopted to evaluate the correlation between serum asprosin and other clinical data. Multivariate logistic regression analysis was applied to analyze the influencing factors on obesity. In addition, the diagnostic ability of asprosin to detect type 2 diabetic patients with obesity was tested using receiver operating characteristic (ROC) curve analysis.ResultsCompared with patients with normal weight, the circulating level of asprosin was significantly higher in the obese group than in the normal weight and overweight group (P <0.05). Asprosin was positively correlated with Systolic Blood Pressure(SBP), Body Mass Index (BMI), Waistline, serum uric acid (SUA), aspartate transaminase (AST), creatinine(CRE), and negatively correlated with alanine aminotransferase(ALT). In addition, serum asprosin was significantly correlated with BMI even after adjusting for age, sex, SBP and ALT, SUA, glycosylated hemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) and glomerular filtration rate (eGFR) ((P < 0.05). Compared with the patients in the lowest tertile of serum asprosin (<250.7 pg/mL), patients with asprosin between 250.7–314.0 pg/mL [OR (95% CI) is 1.774 (0.978-3.218), P < 0.05] and asprosin >314 pg/mL [OR (95% CI) is 8.406 (4.788-14.758), P < 0.05] have a higher risk of obesity.ConclusionsSerum asprosin was correlated with obesity in community-based type 2 diabetic patients with obesity. Additionally, the risk of obesity was obviously increased with the raise of asprosin. Therefore, we speculate that serum asprosin could be used as a risk predictor of type 2 diabetic patients with obesity.

Background Diabetes, a chronic disease necessitating long-term treatment and self-management, presents significant challenges for patients who spend most of their treatment time outside of hospitals. The potential of digital therapeutics for diabetes has garnered recognition from different organizations. Although some prior studies have demonstrated successful reductions in patients’ blood glucose levels and body weight through digital diabetes programs, many studies were limited by including patients with prediabetes, including patients treated with mostly premixed insulin, or evaluating user engagement outcomes rather than clinical outcomes. Consequently, limited evidence remains regarding the effectiveness of health management mobile apps specifically designed for patients with type 2 diabetes mellitus (T2DM) initiating basal insulin (BI). Based on this, a data-based and artificial intelligence management system named “TRIO” was developed to provide patients with more personalized intervention methods in stages, in groups, and around the clock. TRIO assists doctors and nurses in achieving better blood glucose controls, truly carries out standardized management around patients, and allows them to have a higher quality of life. TRIO represents the 3 essential pillars in comprehensive diabetes management: physician, nurse, and patient. Objective This prospective observational study evaluated the effectiveness and safety of the TRIO optimal health management program for patients with T2DM initiating BI therapy in a real-world setting. Methods Patients aged 18-85 years with inadequate glycemic control (baseline hemoglobin A1c [HbA1c] ≥7%) starting BI therapy were enrolled in outpatient and inpatient settings. The study lasted 3 months, with health education and phone-based follow-up assessments. Data collected included patient characteristics, medical history, baseline diabetes conditions, treatment compliance, glycemic control, and safety indicators. Results A total of 199,431 patients were included, and 118,134 patients completed the 3-month follow-up between December 1, 2019, and December 31, 2021, involving 574 hospitals in China. The mean baseline HbA1c was 9.2%, the mean duration of diabetes was 7.3 years, and 80.4% (1,59,930/1,98,969) of patients were using BI with oral antihyperglycemic drugs. After the intervention, mean HbA1c decreased by –2.59% from baseline, with 55.6% (28,858/51,912) achieving the target HbA1c level of <7%. Patients who set lower fasting plasma glucose goals (<6.1 mmol/L) showed more significant HbA1c reductions (P<.001) and higher target achievement than those with fasting plasma glucose goals of ≥6.1 mmol/L. Factors such as complications, diabetes duration, and baseline HbA1c levels influenced the magnitude of HbA1c reduction. The presence of complications, shorter diabetes duration, and higher baseline HbA1c were significantly associated with increased hypoglycemia incidence risk (all P<.05). Conclusions The TRIO optimal health management program effectively improved glycemic control in patients with T2DM initiating BI therapy. Individualized treatment approaches considering patient characteristics and glycemic goals are vital for optimal outcomes.

Background:Cluster of Differentiation-4(CD4),Cluster of Differentiation-8(CD8), and interleukin-10 (IL-10) have long been considered to be related to cervical cancer, but the exact relationship remains unclear. Few studies investigated the relationship between CD4,CD8,IL-10, and high-risk human papillomavirus (HPV) with risk of cervical intraepithelial neoplasia (CIN). Objective:Our aim is to evaluate the relationship between CD4, CD8, IL-10, and high-risk HPV infection with the risk of CIN, as well as their interactions on CIN. Design:In 2014-2015, a cross-sectional study of screening data was conducted among 2285 women aged 19-65 years who participated in an ongoing community-based cohort of 40,000 women in Shanxi, China. Using categorical and spline analyses to evaluate the relationship between local vaginal fluids of CD4,CD8,CD4/CD8,IL-10, and CIN risk. A total of 1,503 controls were followed up until January 31, 2019. A nested case-control study was used to assess the relationship between vaginal lavage CD4, CD8, CD4/CD8, and IL-10 levels and the risk of CIN progression. Results:After adjusting for possible confounding factors,CD4 and CD8 levels were positively related to CIN risk (the 1st versus 4th quartile CD4,CD8 OR = 0.45[0.34, 0.60] and 0.34[0.26, 0.45] for CIN1, 0.32 [0.21, 0.48] and 0.24 [0.16, 0.38] for CIN2/3). Increased CD4 and CD8 levels were positively related to the occurrence of CIN(P-overall<0.01).CD4/CD8 levels and the risk of CIN1 followed a nonlinear "U-shape" (P-nonlinear <0.01). IL-10 levels and the risk of CIN1 followed a nonlinear "n-shape"(P-nonlinear <0.01).IL-10 levels were inversely related to the occurrence of CIN2/3(OR = 3.87, [2.49, 6.00],P-overall<0.01). The highest risk of CIN was observed in women with high-risk HPV, whose CD4 and CD8 levels were the highest(P-interaction < 0.01).Patients with the lowest IL-10 levels(IL-10 ≤ 53.17pg/ml) who are positive for high-risk HPV infection have the highest risk of CIN2/3(OR = 18.46,[9.33-36.51]). Nested case-control analysis observed a positive relationship between CD4,CD8 levels, and risk of CIN progression (CD4 OR = 0.34,[0.13, 0.94];CD8 OR = 0.27, [0.09, 0.79]),and an opposite relationship between IL-10 levels and risk of CIN progression (OR = 2.92, [1.09, 7.84]). Conclusions:Local vaginal CD4 and CD8 levels were positively correlated with CIN risk, and IL-10 levels were inversely correlated with CIN2/3, whether or not with high-risk HPV infection in Chinese women.

Purpose:To investigate Henagliflozin's effect on high-molecular-weight (HMW) adiponectin in serum and saliva of type 2 diabetes mellitus (T2DM) patients. Patients and Methods:This study included 66 patients with T2DM consecutively recruited from two community health service stations in southeastern Shanxi Province between December 2023 and November 2024, along with 66 healthy individuals as the normal control group. T2DM patients with glycated hemoglobin A1c (HbA1c) >7% and without drug treatment received henagliflozin (10 mg once daily) for 12 weeks. The general data of the two groups before and after treatment were collected and the clinical indicators were detected, including body mass index (BMI), waist circumference, fasting plasma glucose (FPG), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), etc. At the same time, the blood and salivary samples of the two groups were collected before and after treatment, and the levels of HMW adiponectin in serum and saliva were detected by ELISA. Statistical comparisons were performed using paired or unpaired t-tests for normally distributed variables and the Mann-Whitney U test for non-normally distributed ones. The correlation between serum and saliva HMW adiponectin levels was assessed using Spearman's rank correlation. Furthermore, stepwise linear regression was employed to identify factors affecting HMW adiponectin levels in serum and saliva. Results:Compared with the healthy control group, the serum and salivary levels of HMW adiponectin were decreased in T2DM patients (4.10 (2.30,6.80) VS 3.70 (1.55,5.65), 2.35 (0.87,5.80) VS 1.80 (0.72,4.53), P < 0.05). T2DM patients treated with henggliflozin for 12 weeks exhibited significant increases in both serum and salivary HMW adiponectin levels (3.70 (1.55,5.65) VS 4.70 (2.65,8.60), 1.80 (0.72,4.53) VS 3.85 (1.88,10.33), p < 0.05). Furthermore, significant improvements were observed in multiple metabolic parameters, including reductions in DBP, BMI, TC and TG (p < 0.05). A weak but statistically significant correlation was found between serum and salivary adiponectin levels (r = 0.210, R² = 0.044; p < 0.05). In order to reveal the influence factors of adiponectin in serum and saliva, linear stepwise regression analysis showed that waist circumference was an independent risk factor for adiponectin in serum (95% CI: -0.087, -0.015; P < 0.05), and gender was an independent risk factor for adiponectin in saliva (95% CI: -4.663, -0.529; P < 0.05). Conclusion:In our study, serum and salivary HMW adiponectin levels were decreased in patients with T2DM, and Sodium-glucose co-transporter-2 (SGLT2) inhibitors could improve serum and salivary HMW adiponectin levels after treatment, which is expected to be a major target for diabetes treatment.

Few epidemiological evidence is available on genetic hypoparathyroidism (HP) in adult-onset non-surgical hypoparathyroidism (ns-HP). This study aimed to investigate the spectrum of genotypes and clinical phenotypes of genetic HP in a single-center large sample of Chinese adult-onset ns-HP cohort. A systemic screening of HP-causing genes and clinical studies were conducted in adult-onset (age > 18 years old) ns-HP patients. Targeted next-generation sequencing/whole exome sequencing (T-NGS/WES) and multiplex ligation-dependent probe amplification (MLPA) of the TBX1 gene were performed to identify rare variants of 20 HP-causative genes. The fluorescence imaging of intracellular ionized calcium (Ca2+) experiments were conducted to identify the function of CASR with variants of uncertain significance. Clinical data were collected retrospectively and compared between patients with pathogenic/likely pathogenic (P/LP) variants and idiopathic HP (IHP). A total of 97 adult-onset ns-HP patients were enrolled in the study. The detection rate of P/LP variants was 5.2