Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

BACKGROUND: Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke. METHODS: This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days. RESULTS: There were 57 and 60 patients finally included in the ANP and placebo groups, respectively for modified intention-to-treat analysis. The median age was 66.0 years, and the median NIHSS score at baseline was 12.0. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: -7.1 mL; interquartile range [IQR]: -18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively ( median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups ( P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P = 0.03). CONCLUSIONS: ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis. TRAIL REGISTRATION Clinicaltrials.gov , No. NCT04475328.
Aged ; Female ; Humans ; Male ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Ischemic Stroke/drug therapy* ; Pilot Projects ; Stroke/drug therapy* ; Treatment Outcome

OBJECTIVES: To evaluate the strategies and outcomes of assisted reproductive technology (ART) for fertility preservation and promotion in women with malignant tumors, and to analyze ART outcomes across different tumor types. METHODS: We conducted a retrospective analysis of female patients who underwent ART for fertility preservation or treatment at the Reproductive Center of the Women's Hospital, Zhejiang University School of Medicine, between January 1, 2018, and December 31, 2023. A total of 163 ART-aided pregnancy patients with malignant tumors were included in the case group, among which 6 patients underwent embryo cryopreservation for fertility preservation before radiotherapy or chemotherapy. Additionally, 11 unmarried women underwent oocyte cryopreservation due to borderline ovarian tumors, ovarian cancer, breast cancer, or hematological malignancies. The control group was selected from women without a history of malignant tumors who received ART treatment during the same period, using propensity score matching at a ratio of 1∶2, resulting in 326 cases. Data were collected through the reproductive medical record system and telephone follow-up (as of October 31, 2024). Baseline characteristics, controlled ovarian hyperstimulation parameters, laboratory indicators, and pregnancy outcomes were compared between case and control groups and among patients with different tumor types, and the tumor recurrence of the patients was followed up. RESULTS: Patients in the case group had significantly lower ovarian reserve (AMH, AFC) and a higher proportion of diminished ovarian reserve compared to the control group (all P<0.01). Regarding the ovulation induction protocol, the proportion of patients using the minimal stimulation protocol in the case group was significantly higher than that in the control group (29.45% vs. 12.88%, P<0.01), and the total dosage of gonadotropins used was lower (P<0.01). In terms of assisted reproductive outcomes, there were no statistically significant differences between the two groups in the number of retrieved oocytes, number of high-quality embryos, fertilization rate, cumulative pregnancy rate, cumulative live birth rate, or miscarriage rate (all P>0.05). However, the number of oocyte retrieval cycles and embryo transfer cycles required to achieve a live birth outcome in the case group were significantly higher than those in the control group (both P<0.05). Subgroup analysis showed that there were no significant differences in cumulative pregnancy rate and live birth rate among patients with different tumor types (thyroid cancer, reproductive system tumors, breast cancer, lung cancer). Nevertheless, lung cancer patients had the lowest ovarian reserve and required the most oocyte retrieval cycles due to their older age; breast cancer patients had a relatively lower fertilization rate partially because some of them were complicated with male factors. A follow-up of 154 tumor patients (with a follow-up rate of 88.5%) revealed that 6 patients (4.20%) had tumor recurrence, and 1 breast cancer patient died due to tumor recurrence. None of the 11 unmarried patients who had undergone oocyte cryopreservation had used the cryopreserved oocytes for assisted pregnancy yet, and 1 patient who had undergone fertility preservation died due to tumor recurrence. CONCLUSIONS Women of reproductive age with malignant tumors are at risk of diminished fertility. ART can effectively preserve and promote fertility, enabling favorable pregnancy and live birth outcomes. It is recommended to initiate a multidisciplinary assessment promptly prior to radiotherapy/chemotherapy and formulate an individualized ART regimen for fertility preservation or promotion, so as to achieve reproductive goals or safeguard future fertility potential.

OBJECTIVES: Cardiovascular disease (CVD) poses a major threat to global health. Evaluating atherosclerosis in asymptomatic individuals can help identify those at high risk of CVD. This study aims to establish an individualized nomogram prediction model to estimate the risk of vascular plaque formation in asymptomatic individuals. METHODS: A total of 5 655 participants who underwent CVD screening at the Health Management Center of The Third Xiangya Hospital, Central South University, between January 2022 and June 2024 we retrospectively enrolled. Using simple random sampling, participants were divided into a training set (n=4 524) and a validation set (n=1 131) in an 8꞉2 ratio. Demographic and clinical data were collected and compared between groups. Multivariate logistic regression analysis was used to identify independent factors associated with vascular plaques and to construct a nomogram prediction model. The predictive performance and clinical utility of the model were evaluated using receiver operating characteristic (ROC) curves, the Hosmer-Lemeshow goodness-of-fit test, calibration plots, and decision curve analysis (DCA). RESULTS: The mean age of participants was 52 years old. There were 3 400 males (60.12%). The overall detection rate of vascular plaque in the screening population was 49.87% (2 820/5 655). No statistically significant differences were observed in clinical indicators between the training and validation sets (all P>0.05). Multivariate Logistic regression analysis identified age, systolic blood pressure, high-density lipoprotein (HDL), low-density lipoprotein (LDL), lipoprotein(a), male sex, smoking history, hypertension history, and diabetes history as independent risk factors for vascular plaque in asymptomatic individuals (all P<0.05). The area under the curve (AUC) of the nomogram model for predicting vascular plaque risk were 0.778 (95% CI 0.765 to 0.791, P<0.001) in the training set and 0.760 (95% CI 0.732 to 0.787, P<0.001) in the validation set. The Hosmer-Lemeshow goodness-of-fit test indicated good model calibration (training set: P=0.628; validation set: P=0.561). The calibration curve plotted using the Bootstrap method demonstrated good agreement between predicted probabilities and actual probabilities. DCA showed that the nomogram provided a clinical net benefit for predicting vascular plaque risk when the threshold probability ranged from 0.02 to 0.99. CONCLUSIONS The nomogram prediction model for vascular plaque risk, constructed using readily available and cost-effective physical examination indicators, exhibited good predictive performance. This model can assist in the early identification and intervention of asymptomatic individuals at high risk for cardiovascular disease.
Humans ; Male ; Middle Aged ; Female ; Nomograms ; Retrospective Studies ; Risk Factors ; Plaque, Atherosclerotic/diagnosis* ; Aged ; Adult ; Physical Examination ; Logistic Models ; Cardiovascular Diseases/epidemiology* ; ROC Curve

OBJECTIVES: Stress urinary incontinence (SUI) is a common condition among women that severely impairs quality of life. Pelvic floor proprioceptive training (PFPT) has attracted increasing attention for its potential to enhance pelvic floor muscle function and alleviate SUI symptoms. This study aims to observe and compare the clinical efficacy of PFPT combined with electroacupuncture, electrical stimulation, and biofeedback therapy versus conventional therapy consisting of electroacupuncture, electrical stimulation, and biofeedback alone in women with SUI, and to explore the role of PFPT in improving symptom and functional outcomes. METHODS: In this randomized controlled trial, 72 women with mild to moderate SUI were recruited from the Department of Rehabilitation Medicine at Third Xiangya Hospital, Central South University, between December 2021 and October 2023. Participants were randomly assigned to an experimental group (n=36) or a control group (n=36). Both groups received health education. The control group underwent electroacupuncture combined with electrical stimulation and biofeedback therapy, while the experimental group additionally received PFPT 3 times per week for 4 weeks. The primary outcome was assessed using the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). Secondary outcomes included pelvic floor muscle strength, bladder neck mobility, and balance ability. The ICIQ-SF was reassessed at 1, 3, 6, and 12 months post-treatment. RESULTS: Both groups showed statistically significant improvements in all parameters after treatment (all P<0.05). However, there were no statistically significant differences between groups in most measures (all P>0.05). The experimental group demonstrated longer single-leg stance duration with eyes closed than the control group (left leg: P=0.026; right leg: P=0.006), with a significant increase from baseline (P<0.001). At 6 months post-treatment, the cure rate in the experimental group was significantly higher than that in the control group (P=0.037). CONCLUSIONS Conventional therapy effectively improves SUI symptoms, but adding PFPT provides notable additional benefits, including enhanced balance ability and sustained mid-term cure rates. These findings suggest that PFPT is a valuable adjunct to standard SUI management strategies.
Humans ; Female ; Urinary Incontinence, Stress/physiopathology* ; Pelvic Floor/physiopathology* ; Middle Aged ; Biofeedback, Psychology ; Adult ; Exercise Therapy/methods* ; Proprioception ; Electroacupuncture/methods* ; Quality of Life ; Electric Stimulation Therapy/methods* ; Treatment Outcome ; Combined Modality Therapy

BACKGROUND AND AIM: Remnant cholesterol (remnant-C) mediates the progression of major adverse cardiovascular events. It is unclear whether remnant-C, and particularly cumulative exposure to remnant-C, is associated with nonalcoholic fatty liver disease (NAFLD). This study aimed to explore whether remnant-C, not only baseline but cumulative exposure, can be used to independently evaluate the risk of NAFLD. METHODS: This study included 1 cohort totaling 21,958 subjects without NAFLD at baseline who underwent at least 2 repeated health checkups and 1 sub-cohort totaling 2,649 subjects restricted to those individuals with at least 4 examinations and no history of NAFLD until Exam 3. Cumulative remnant-C was calculated as a timeweighted model for each examination multiplied by the time between the 2 examinations divided the whole duration. Cox regression models were performed to estimate the association between baseline and cumulative exposure to remnant-C and incident NAFLD. RESULTS: After multivariable adjustment, compared with the quintile 1 of baseline remnant-C, individuals with higher quintiles demonstrated significantly higher risks for NAFLD (hazard ratio [HR] 1.48, 95%CI 1.31-1.67 for quintile 2; HR 2.07, 95%CI 1.85-2.33 for quintile 3; HR 2.55, 95%CI 2.27-2.88 for quintile 4). Similarly, high cumulative remnant-C quintiles were significantly associated with higher risks for NAFLD (HR 3.43, 95%CI 1.95-6.05 for quintile 2; HR 4.25, 95%CI 2.44-7.40 for quintile 3; HR 6.29, 95%CI 3.59-10.99 for quintile 4), compared with the quintile 1. CONCLUSION Elevated levels of baseline and cumulative remnant-C were independently associated with incident NAFLD. Monitoring immediate levels and longitudinal trends of remnant-C may need to be emphasized in adults as part of NAFLD prevention strategy.
Adult ; Humans ; Cohort Studies ; Non-alcoholic Fatty Liver Disease/etiology* ; Cholesterol ; Proportional Hazards Models ; Risk Factors

Objective:Insulin resistance(IR)is closely associated with atherosclerosis and adverse cardiovascular events.The triglyceride-glucose(TyG)index is an effective indicator for assessing IR.This study aims to explore the relationship between the TyG index and the risk of arterial stiffness progression. Methods:This retrospective cohort study included adults who had undergone at least 2 health examinations with arteriosclerosis testing at the Health Management Medical Center of the Third Xiangya Hospital,Central South University,between January 2012 and December 2022.Clinical data were collected.The TyG index was calculated using the formula of ln(triglyceridesxfasting blood glucose/2).The baseline TyG index was assessed as both a continuous variable and as a quartile-based categorical variable.The progression of arteriosclerosis was evaluated by the annual change rate of brachial-ankle pulse wave velocity(baPWV)and the new onset of increased arterial stiffness.Linear regression model and Cox proportional hazard model were used to explore whether the TyG index is an independent risk factor for arterial stiffness progression.Subgroup analyses were performed based on age,gender,body mass index(BMI),and the presence of type 2 diabetes,hypertension,or hyperlipidemia to determine the characteristics of the association between the TyG index and arterial stiffness progression. Results:A total of 4 971 participants were included,with a follow-up period of(3.01±1.98)years.During follow-up,the annual baPWV change rate was(24.94±81.15)cm/s,and 278 cases of new onset of increased aterial stiffness were recorded.After fully adjusting for confounding factors,the baseline TyG index was independently positively correlated with both the annual baPWV change rate(β=17.5,95％CI 9.00 to 25.94,P＜0.001)and the risk of new onset of increased aterial stiffness[hazard ratio(HR)=1.43,95％CI 1.18 to 1.74,P＜0.001]when the TyG index was treated as a continuous variable.When treated as a categorical variable,higher TyG index quartiles were associated with progressively higher baPWV change rates and new onset of increased arterial stiffness(all P＜0.055).In subgroups of participants aged ≥45 years,males,BMI＜28 kg/m2,those with or without hypertension,and those without type 2 diabetes or hyperlipidemia,the baseline TyG index(both continuous and categorical)was significantly associated with new onset of increased arterial stiffness(all P＜0.05),with no significant interactions observed across subgroups(all P＞0.05). Conclusion:The TyG index is independently associated with an increased risk of arterial stiffness progression and may serve as a useful indicator for assessing arterial stiffness progression risk in health check-up populations.