BACKGROUND: The American Heart Association (AHA) introduced the concept of cardiovascular-kidney-metabolic (CKM) health and stage, reflecting the interaction among metabolism, chronic kidney disease (CKD), and the cardiovascular system. However, the association between CKM stage and the long-term risk of cardiovascular disease (CVD) has not been validated. This study aimed to evaluate the long-term CVD risk associated with CKM health metrics and CKM stage using data from a population-based cohort study. METHODS: In total, 5293 CVD-free participants were followed up to around 13 years in the Chinese Multi-provincial Cohort Study (CMCS). Considering the pathophysiologic progression of CKM health metrics abnormalities (comprising obesity, central adiposity, prediabetes, diabetes, hypertriglyceridemia, CKD, and metabolic syndrome), participants were divided into CKM stages 0, 1, and 2. The time-dependent Cox regression models were used to estimate the cardiovascular risk associated with CKM health metrics and stage. Additionally, broader CVD outcomes were examined, with a specific assessment of the impact of stage 3 in 2581 participants from the CMCS-Beijing subcohort. RESULTS: Among participants, 91.2% (4825/5293) had at least one abnormal CKM health metric, 8.8% (468/5293), 13.3% (704/5293), and 77.9% (4121/5293) were in CKM stages 0, 1, and 2, respectively; and 710 incident CVD cases occurred during a median follow-up time of 13.3 years (interquartile range: 12.1 to 13.6 years). Participants with each poor CKM health metric exhibited significantly higher CVD risk. Compared with stage 0, the hazard ratio (HR) (95% confidence interval [CI]) for CVD incidence was 1.31 (0.84-2.04) in stage 1 and 2.27 (1.57-3.28) in stage 2. Significant interactive impacts existed between CKM stage and age or sex, with higher CVD risk related to increased CKM stages in participants aged <60 years or females. CONCLUSION These findings highlight the contribution of CKM health metrics and CKM stage to the long-term risk of CVD, suggesting the importance of multi-component recognition and management of poor CKM health in CVD prevention.
Humans ; Female ; Male ; Cardiovascular Diseases/etiology* ; Middle Aged ; Adult ; Cohort Studies ; Renal Insufficiency, Chronic/metabolism* ; Aged ; Risk Factors ; Metabolic Syndrome/metabolism* ; China ; East Asian People

Objective:To analyze the hearing outcomes of high-risk children of diabetic mothers, especially in the subtypes of pre-pregnancy diabetes and gestational diabetes, in order to provide some reference for clinical practice. Methods:The basic characteristics and hearing levels of children whose mothers had a history of diabetes during pregnancy and underwent audiological diagnosis and evaluation at our hospital's Children's Hearing Diagnosis Center from January 2003 to June 2024 were analyzed. T-tests, Wilcoxon rank-sum tests, and chi-square tests were used for inter-group comparisons, with a significance level set at P<0.05. Results:A total of 285 children（570 ears） of diabetic mothers were included. Hearing loss was found in 310 ears, and the incidence of hearing loss was 54.39%（310/570）. The mean ABR threshold in the pregestational diabetes group was（50.01±29.29） dB HL, while that in the gestational diabetes group was（44.13±26.19） dB HL. The degree of hearing loss in the pregestational diabetes group was more severe than that in the gestational diabetes group（χ²=10.000, P=0.019）. Conclusion:Maternal history of diabetes may be one of the risk factors for hearing loss in their offspring, and the risk of hearing loss in children whose mothers had diabetes before pregnancy may be higher than that in the gestational diabetes group. It is suggested that the clinical practice should pay attention to the monitoring and follow-up management of the hearing status of such children, so as to improve the auditory outcomes of children born to diabetic mothers.
Humans ; Female ; Pregnancy ; Diabetes, Gestational ; Hearing Loss/etiology* ; Child ; Pregnancy in Diabetics ; Risk Factors ; Child, Preschool ; Mothers ; Male

Objective:To summarize and analyze the clinical characteristics of patients with sudden sensorineural hearing loss（SSHL） accompanying diabetes mellitus, to explore whether diabetes affects the treatment outcomes during hospitalization, and to identify the factors influencing the efficacy of SSHL patients with diabetes. Methods:A retrospective analysis was conducted on clinical data from 939 patients with SSHL. The baseline characteristics, and onset conditions of the diabetes group（79 cases） and the non-diabetes group（860 cases） were compared. Propensity score matching（PSM） was applied in a 1︰ 2 ratio to match initial hearing levels with baseline characteristics such as age, sex, and BMI, resulting in 73 diabetes cases and 144 non-diabetes cases for treatment efficacy comparison. For the analysis of prognostic factors, a logistic regression model was established based on the treatment outcomes of 217 patients with SSHL. Results:The proportion of SSHL patients accompanying diabetes was 8.40%（79/939）. Compared to non-diabetic patients, those with diabetes were older（median age of 53 years in the diabetes group and 39 years in the non-diabetes group） and had a higher proportion of hypertension（43.04% vs 12.67%）, with significant difference observed（P<0.05）. After PSM, the treatment efficacy during hospitalization was better in the diabetes group than in the non-diabetes group（58.90% vs 47.92%）, although the difference was not statistically significant（P>0.05）. The prognosis of patients with SSNHL accompanied by diabetes was analyzed using a multivariate logistic regression model that included age, HDL-C, and INR as variables; however, no statistically significant differences were found（P>0.05）. Conclusion:Patients with SSHL accompanying diabetes are generally older with a higher incidence of hypertension. The presence of diabetes does not affect the treatment outcomes during hospitalization.
Humans ; Propensity Score ; Retrospective Studies ; Hearing Loss, Sensorineural/therapy* ; Hearing Loss, Sudden/therapy* ; Middle Aged ; Diabetes Mellitus ; Male ; Female ; Prognosis ; Adult ; Logistic Models ; Diabetes Complications ; Aged ; Treatment Outcome

This study aimed to elucidate the mechanism of action of metformin (MET) in inhibiting the malignant progression of hepatocellular carcinoma (HCC) by regulating the degradation of aldo-keto reductase family 1 member C3 (AKR1C3). The correlation between the sensitivity of different hepatocellular carcinoma cell lines to MET and their basal expression levels of AKR1C3 was firstly evaluated. MET was found to significantly reduce the level and accelerate the degradation rate of AKR1C3 protein by Western blot. The interaction between MET and AKR1C3 protein was confirmed by cellular thermal shift assay (CETSA). Proteasome inhibitor MG132 and the lysosomal inhibitor chloroquine (CQ) were used to screen the degradation pathway, and confirm, in combination with the HBSS starvation-induced autophagy model, that MET mediated the degradation of AKR1C3 through the autophagy lysosome pathway. Ubiquitylation assay showed that MET specifically enhanced the K63-linked polyubiquitylation modification of AKR1C3. Sequestosome 1 (SQSTM1/p62) knockdown, immunoprecipitation, and immunofluorescence co-localization analyses confirmed that the autophagy receptor p62 plays a key role in mediating MET-induced degradation of AKR1C3. The adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) inhibitor compound C was used to demonstrate that the regulatory effect of MET on AKR1C3 is independent of the classical AMPK signaling pathway. The experimental results showed that metformin promoted the ubiquitination modification of AKR1C3 by targeting AKR1C3, enhanced the binding of AKR1C3 to autophagy receptor p62, then degraded the AKR1C3 protein through selective autophagy-like pathway, and ultimately inhibited the malignant phenotypes of hepatocellular carcinoma cells, which is a regulatory mechanism free of the classical AMPK activation pathway of metformin.

Objective:To explore the experience of self-management dilemma ofadults with emerging ankylosing spondylitis, and to provide reference for the construction of self-management intervention strategies for emerging adults with ankylosing spondylitis.Methods:Descriptive phenomenology was used to conduct in-depth interviews with 14 adults with emerging ankylosing spondylitis in the Rheumatology and Immunology Department of Drum Tower Hospital Affiliated to Medical College of Nanjing University from August 2022 to March 2023. The interview data were analyzed by Colaizzi′s seven-step analysis method.Results:A total of 14 patients completed the interview,10 males, 4 females, aged 21-30 years. In adults with emerging ankylosing spondylitis, there were dilemmas of role maladjustment and disease management disorder, including role maladjustment of disease management and social role maladjustment. Barriers to disease management included weak self-management awareness, insufficient support for self-management information, inadequate self-management skills, and poor compliance with self-management behaviors.Conclusions:The role adaptation and self-management ability of adults with emerging ankylosing spondylitis are seriously inadequate. It is urgent to construct health management strategies for adults with emerging ankylosing spondylitis to help them improve the level of role adaptation and disease management.

ObjectiveTo observe the therapeutic effect of Shugan Huazheng prescription on hepatic fibrosis model rats induced by carbon tetrachloride （CCl₄） and explore whether it plays its role through hypoxia-induced factor-1α/vascular endothelial growth factor/transforming growth factor-β₁ （HIF-1α/VEGF/TGF-β₁） pathway. MethodA total of 54 male SPF SD rats were randomly divided into six groups： blank group， model group， colchicine group （0.2 mg·kg^-1）， and high-， medium-， and low-dose groups （29.52， 14.76， and 7.38 g·kg^-1） of Shugan Huazheng prescription， with nine rats in each group. The molding was conducted three times a week for eight weeks. Administration began the day after the first injection， and the drug intervention was once a day for eight weeks. On the day after the last administration， the rats were deprived of food and water， and they were killed the next day， during which the physiological status of each group of rats was dynamically monitored. The pathological changes in the liver were observed by hematoxylin-eosin （HE） staining， and the content of hydroxyproline （HYP） and angiotensin Ⅱ （AngⅡ） in liver tissue were detected by enzyme-related immunosorbent assay （ELISA）. Real-time fluorescent quantitative PCR （Real-time PCR） was used to determine the mRNA expression levels of HIF-1α， VEGF， and TGF-β₁ in liver tissue， and immunohistochemical method （IHC） and Western blot were used to detect the protein expression levels of HIF-1α， VEGF， and TGF-β₁ in liver tissue. ResultCompared with the blank group， the overall condition of rats in the model group decreased significantly. The proliferation of connective tissue and the increase in adipose cells between hepatocytes were obvious. The content of HYP and Ang was increased. The mRNA and protein expressions of HIF-1α， VEGF， and TGF-β₁ were increased to varying degrees （P<0.05）. Compared with the model group， the proliferation of connective tissue and inflammatory cell infiltration in the liver tissue of colchicine and Shugan Huazheng prescription groups were reduced. The content of HYP and Ang was decreased. The mRNA and protein expression levels of HIF-1α， VEGF， and TGF-β₁ were decreased， and the colchicine group and high-dose group of Shugan Huazheng prescription were the most significant （P<0.05）. ConclusionShugan Huazheng prescription has an obvious therapeutic effect on CCl₄-induced hepatic fibrosis model rats. Its therapeutic mechanism may be related to the regulation of the HIF-1α/VEGF/TGF-β₁ signaling pathway and the improvement of hepatic hypoxia， vascular remodeling， and the syndrome of Qi deficiency and blood stasis in hepatic fibrosis.

Objective:To analyze the clinical characteristics, curative effect related factors and follow-up situation of bilateral sudden sensorineural hearing loss (BSSHL).Methods:The clinical data of 169 patients(338 ears) with BSSHL were retrospectively summarized, and the demographic characteristics, predisposing factors, concomitant symptoms and diseases, and audiological characteristics were statistically described. Additionally, influencing factors of curative effect and prognosis were statistically analyzed.Results:Among the 169 patients, 50.9% (86/169) of patients had at least one incentive, with cold and fatigue being the most common incentives(both 23/169). There were high rates of accompanying symptoms including tinnitus (150/169, 88.8%) and dizziness (100/169, 59.2%). Hypertension(49/169, 29.0%)and diabetes(23/169, 13.6%)were the most common concomitant diseases observed. Most cases exhibited all frequencies involvement, with flat type and total deafness type accounting for 83.1%(281/338 ears). The most common degree of hearing loss was total deafness(86/338 ears), with approximately 60.1%(203/338 ears) of the cases being severe or worse. The total effective rate of treatment was only 29.0%, but it increased to 39.5% for patients with course of disease≤14 days, however, when course of disease>30 days, the effective rate decreased sharply to 3.6%, showing a significant difference between these two groups( χ2=13.776,<0.01). Different types of hearing curves showed statistically significant difference in efficiency( χ2=14.782, P<0.01). Comparing the hearing improvements of 28 BSSHL patients from admission to discharge and from discharge to follow-up, it was found that the hearing improvement of the two groups showed statistically significant difference at the frequencies of L-250 Hz, L-500 Hz, R-125 Hz, R-250 Hz and R-500 Hz( Z value was -2.495, -3.083, -3.970, -3.388 and -3.264 respectively, all P<0.05). The proportion of patients with elevated serum IgE was much higher than that of the normal population. Conclusion:BSSHL patients suffer from serious hearing loss, and many also experience tinnitus and vertigo symptoms. Due to the poor efficiency of treatment, it is better for patients to be treated within 30 days of onset. For patients of hearing loss in the low frequency range, hearing improvement is more significant during hospitalization. And the occurrence of BSSHL may involve an immune mechanism.

Objective:To explore the value of 18F-fibroblast activation protein inhibitor (FAPI) PET/CT in the assessment of early-stage graft fibrosis (S1-S2) after liver transplantation (LT). Methods:From November 2021 to April 2022, 17 adult liver transplant recipients (12 males and 5 females; age (52.6±7.9) years) in the Affiliated Hospital of Qingdao University were enrolled retrospectively in this study. All 17 patients received laboratory examinations, FibroScan, 18F-FAPI PET/CT and liver biopsy. According to the Scheuer scoring system, hepatic tissue was divided into no fibrosis (S0) and early fibrosis (S1-S2). Independent-sample t test was used to compare SUV max between two groups, and Mann-Whitney U test was used to compare liver stiffness measurement (LSM). ROC curve analysis was used to evaluate the diagnostic efficacy of LSM and SUV max in the early fibrosis of liver grafts. Delong test was used to compare the difference of AUCs. Results:Among 17 adult LT recipients, 11 were in stage S0, 5 were in stage S1, and 1 was in stage S2. There were significant differences in LSM and SUV max between no fibrosis group and early fibrosis group (LSM: 5.4(4.7, 6.6) vs 12.9(5.6, 19.9) kPa, z=-2.01, P=0.044; SUV max: 1.7±0.8 vs 3.9±1.6, t=-3.14, P=0.019). The threshold value of LSM in predicting early-stage graft fibrosis was 8.2 kPa and the AUC was 0.80 (95% CI: 0.54-0.95), which was 2.0 and 0.92 (95% CI: 0.78-1.00) for SUV max respectively. There was no significant difference in AUC between the two tools ( z=0.80, P=0.421). Conclusion:18F-FAPI PET/CT can precisely evaluate the early fibrosis of allografts, with the similar diagnostic efficacy with FibroScan (LSM), which is expected to be a new non-invasive diagnostic tool for predicting the early-stage of graft liver fibrosis.

College students shoulder the heavy responsibility of the times and are the key to improving the quality of the peo-ple.The strategic goal of"Healthy China"has put forward higher requirements for general education courses in universities.Immunity and Health is a general education course offered by Shandong University for the entire school.While optimizing teaching content in the classroom to achieve knowledge goals,it guides students to think about the emotional value behind knowledge,improve immune intel-ligence,and thus achieve the mission of cultivating talents for the construction of a"Healthy China".This article explores the develop-ment process of the teaching mode of"Immunity and Health",which has important practical significance for enhancing general educa-tion in universities and promoting the purpose of"advocating a healthy and civilized lifestyle,shaping self-discipline and healthy behavior"in China.