Association between BMI and osteoporotic fractures at different sites in Chinese women: a case-control retrospective study in Changsha.

BACKGROUND: Osteoporotic fractures are a growing problem in an aging society. The association between body mass index (BMI) and osteoporotic fractures varies by fracture site and ethnicity. Limited knowledge exists regarding this association in native Chinese, particularly utilizing local databases as reference sources. OBJECTIVE: To investigate the association between BMI and osteoporotic fractures at different sites in Chinese women. METHODS: Three thousand ninety-eight female patients with radiographic fractures and 3098 age- and sex-matched healthy controls without fractures were included in the study. Both of them underwent assessment using dual-energy X-ray absorptiometry (DXA), with BMD measurements calculated using our own BMD reference database. Participants were classified into underweight (BMI < 18.5 kg/m2), normal weight (18.5 ≤ BMI < 24.0 kg/m2), overweight (24 ≤ BMI < 28 kg/m2) and obese (BMI ≥ 28 kg/m2) according to the Chinese BMI classification standard. RESULTS: There were 2296 (74.1%) vertebral fractures, 374 (12.1%) femoral neck fractures, and 428 (13.8%) other types of fractures in the case group. Bone mineral density (BMD) was almost lower in the fracture groups compared to the control groups (p = 0.048 to < 0.001). Compared with normal weight, underweight had a protective effect on total [odds ratio (OR) = 0.61; 95% confidence interval (CI), 0.49 -0.75; P< 0.001], and lumbar fractures (OR = 0.52; 95% CI, 0.41 - 0.67; P < 0.001), while obesity was associated with an increased risk for total (OR = 2.26; 95% CI, 1.85 - 2.76; P < 0.001), lumbar (OR = 2.17; 95% CI, 1.72 - 2.73; P < 0.001), and femoral neck fractures (OR = 4.08; 95% CI, 2.18 - 7.63; P < 0.001). Non-linear associations were observed between BMI and fractures: A J-curve for total, lumbar, and femoral neck fractures, and no statistical change for other types of fractures. Underweight was found to be a risk factor for other types of fracturess after adjusting for BMD (OR = 2.29; 95% CI, 1.09 - 4.80; P < 0.001). Osteoporosis and osteopenia were identified as risk factors for almost all sites of fracture when compared to normal bone mass. CONCLUSIONS: Underweight has a protective effect on total and lumbar spine fractures in Chinese women, while obesity poses a risk factor for total, lumbar, and femoral neck fractures. The effect of BMI on fractures may be mainly mediated by BMD.

Association of geriatric nutritional risk index with bone mineral density and osteoporosis in postmenopausal elderly women with T2DM.

BACKGROUND AND OBJECTIVES: To investigate the relationship between geriatric nutritional risk index (GNRI) and osteoporosis (OP) in postmenopausal elderly women with type 2 diabetes mellitus (T2DM). METHODS AND STUDY DESIGN: A total of 141 postmenopausal elderly women with T2DM was divided into OP and normal bone mineral density (BMD) groups, the differences in GRNI levels between the two groups were compared. According to the tertile levels of GRNI, T2DM were divided into three groups (T1, T2, T3 groups), and the differences in OP prevalence and levels of BMD among the three groups were compared. RESULTS: Among postmenopausal elderly women with T2DM, GNRI levels were lower in the OP group compared to the nor-mal BMD group [(103±5.46) vs. (105±5.46), p<0.05)]. With elevated GNRI levels, the BMD levels of femoral, total hip, total body, and lumbar vertebrae (L) were gradually increased, which were higher in the T3 group than in the T1 group (all p< 0.05). GNRI levels were positively correlated with the BMD levels of femoral, spine, total hip, total body, L1, L2, L3, L4, and L1-L4. GNRI was an independent influencing factor for the occurrence of OP (OR=0.887, 95%CI [0.795,0.988]). The ROC curve showed that the GNRI combined with serum ALP and P levels had a high predictive value for OP, with an area under the curve of 0.725 (p<0.01). CONCLUSIONS: In postmenopausal elderly women with T2DM, GNRI was independently and positively correlated with BMD levels. GNRI may be a predictor development of OP.

Association of C-peptide level with bone mineral density in type 2 diabetes mellitus.

This study revealed that there was no significant linear relationship between fasting C-peptide (FCP) level and bone mineral density (BMD) or fracture risk in type 2 diabetes mellitus (T2DM) patients. However, in the FCP ≤ 1.14 ng/ml group, FCP is positively correlated with whole body (WB), lumbar spine (LS), and femoral neck (FN) BMD and negatively correlated with fracture risk. PURPOSE: To explore the relationship between C-peptide and BMD and fracture risk in T2DM patients. METHODS: 530 T2DM patients were enrolled and divided into three groups by FCP tertiles, and the clinical data were collected. BMD was measured by dual-energy X-ray absorptiometry (DXA). The 10-year probability of major osteoporotic fractures (MOFs) and hip fractures (HFs) was evaluated by adjusted fracture risk assessment tool (FRAX). RESULTS: In the FCP ≤ 1.14 ng/ml group, FCP level was positively correlated with WB, LS, and FN BMD, while FCP was negatively correlated with fracture risk and osteoporotic fracture history. However, FCP was not correlated with BMD and fracture risk and osteoporotic fracture history in the 1.14 < FCP ≤ 1.73 ng/ml and FCP > 1.73 ng/ml groups. The study has shown that FCP was an independent factor influencing BMD and fracture risk in the FCP ≤ 1.14 ng/ml group. CONCLUSIONS: There is no significant linear relationship between FCP level and BMD or fracture risk in T2DM patients. In the FCP ≤ 1.14 ng/ml group, FCP is positively correlated with WB, LS, and FN BMD and negatively correlated with fracture risk, and FCP is an independent influencing factor of BMD and fracture risk. The findings suggest that FCP may predict the risk of osteoporosis or fracture in some T2DM patients, which has a certain clinical value.

Heat waves accelerate the spread of infectious diseases.

COVID-19 pandemic appeared summer surge in 2022 worldwide and this contradicts its seasonal fluctuations. Even as high temperature and intense ultraviolet radiation can inhibit viral activity, the number of new cases worldwide has increased to >78% in only 1 month since the summer of 2022 under unchanged virus mutation influence and control policies. Using the attribution analysis based on the theoretical infectious diseases model simulation, we found the mechanism of the severe COVID-19 outbreak in the summer of 2022 and identified the amplification effect of heat wave events on its magnitude. The results suggest that approximately 69.3% of COVID-19 cases this summer could have been avoided if there is no heat waves. The collision between the pandemic and the heatwave is not an accident. Climate change is leading to more frequent extreme climate events and an increasing number of infectious diseases, posing an urgent threat to human health and life. Therefore, public health authorities must quickly develop coordinated management plans to deal with the simultaneous occurrence of extreme climate events and infectious diseases.

Association of Insulin-Like Growth Factor-1 With Polycystic Ovarian Syndrome: A Systematic Review and Meta-analysis.

OBJECTIVE: Circulating concentration of insulin-like growth factor (IGF)-1 in patients with polycystic ovary syndrome (PCOS) is still unclear. Therefore, we aimed to investigate the association of IGF-1 with PCOS through this meta-analysis. METHODS: Literature search was conducted through PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure (up to July 2022). A manual search was performed on the references of related original research. Then, we applied the random-effects model to evaluate the overall effect size by calculating the standard mean difference and its 95% CI. Subgroup analyses were used to explore the sources of heterogeneity. In addition, a sensitivity analysis was performed and publication bias was assessed. RESULTS: Twenty studies were included in this meta-analysis involving 657 individuals: 362 patients with PCOS and 295 normal controls. The results of meta-analysis showed that serum IGF-1 levels were significantly higher in patients with PCOS than in controls (standard mean difference, 0.89; 95% CI, 0.34-1.45; P = .002). The final pooled data were determined by the random-effects model because a significant high heterogeneity (I2 = 89%) was found. A subgroup analysis based on body mass index showed that elevated IGF-1 level was associated with normal-weight and overweight patients in the PCOS group, but there was no significant association with obesity. The sensitivity analysis indicated that no individual study significantly affected the overall pooled result and no publishing bias was observed. CONCLUSION: These data suggest that elevated serum IGF-1 levels may not be a major cause of PCOS pathogenesis. Body mass index may be a major determinant of serum IGF-1.

Cardiovascular disease in type 2 diabetes mellitus: progress toward personalized management.

Cardiovascular diseases (CVDs) are the main cause of death among patients with type 2 diabetes mellitus (T2DM), particularly in low- and middle-income countries. To effectively prevent the development of CVDs in T2DM, considerable effort has been made to explore novel preventive approaches, individualized glycemic control and cardiovascular risk management (strict blood pressure and lipid control), together with recently developed glucose-lowering agents and lipid-lowering drugs. This review mainly addresses the important issues affecting the choice of antidiabetic agents and lipid, blood pressure and antiplatelet treatments considering the cardiovascular status of the patient. Finally, we also discuss the changes in therapy principles underlying CVDs in T2DM.

Relationship between prevalence and risk of osteoporosis or osteoporotic fracture with non-alcoholic fatty liver disease: A systematic review and meta-analysis.

The aim of this study was to investigate the relationship between prevalence and risks of osteoporosis or osteoporotic fracture and NAFLD. Patients with NAFLD should be monitored regularly for bone mineral density and bone metabolism indicators to prevent osteoporosis or osteoporotic fractures. OBJECTIVES: The aim of this meta-analysis was to investigate the relationship between prevalence and risks of osteoporosis or osteoporotic fracture and non-alcoholic fatty liver disease (NAFLD). METHODS: Five databases, including PubMed, Web of Science, Embase, Scopus and Cochrane Library, were searched since the conception of these databases until December 2021. The cohort studies, cross-sectional analyses or case-control studies evaluating the relationship between osteoporosis or osteoporotic fracture and NAFLD were retrieved from these databases. Relevant data were extracted from the included studies, and a meta-analysis was performed. RESULTS: A total of seven studies were included. The prevalence of osteoporosis or osteoporotic fractures was higher in the NAFLD group than in the non-NAFLD group [OR = 1.17, 95%CI(1.04,1.31)], while the prevalence of osteoporosis was higher in the NAFLD group than in the non-NAFLD group [OR = 1.46, 95%CI (1.21,1.77) and OR = 1.48, 95%CI (1.31,1.68), respectively] in men and women. The risk of osteoporosis or osteoporotic fractures was higher in the NAFLD group than in the non-NAFLD group [OR = 1.33,95%CI (1.24,1.44) and OR = 1.57,95%CI (1.08,2.29), respectively]. The risk of osteoporosis or osteoporotic fractures was higher in male and female NAFLD groups than that in the non-NAFLD group [OR = 1.29, 95%CI(1.14,1.47) and OR = 1.36, 95%CI (1.25,1.48), respectively]. After parameter adjustment, the risk of osteoporosis or osteoporotic fracture was higher in the male NAFLD group than in the non-NAFLD group [OR = 2.10, 95%CI(1.36,3.25)], while no significant difference was found among women [OR = 1.13, 95%CI (0.86,1.48)]. CONCLUSIONS: The prevalence and risk of osteoporosis or osteoporotic fractures were significantly associated with NAFLD in men and women. TRIAL REGISTRATION: PROSPERO 2022 CRD42022304708.

Relationship between iron metabolism and gestational diabetes mellitus: A systemic review and meta analysis.

BACKGROUND AND OBJECTIVES: To investigate the relationship between serum iron metabolism indexes and gestational diabetes mellitus (GDM) using a meta-analysis. METHODS AND STUDY DESIGN: Databases including PubMed, Web of Science, Embase, and Cochrane Library were searched. Prospective cohort or case-control studies evaluating the relationships between serum iron metabolism indexes and GDM were retrieved from these data-bases. The outcome indicators, such as mean ± standard deviation, relative risk (RR), or odds ratio (OR) were extracted. The RR or OR, standard mean difference (SMD), and 95% confidence interval (CI) were used to calculate the combined effect sizes. RESULTS: A total of 32 studies on the relationships between serum iron metabolic indexes and GDM were included. The serum iron [SMD=0.40 mg/dL, 95% CI (0.16, 0.64), p=0.001], ferritin [SMD=0.58 ng/mL, 95% CI (0.35, 0.81), p˂0.001], hemoglobin [SMD=0.48 g/dL, 95% CI (0.28, 0.67), p˂0.001], transferrin saturation [SMD=0.83%, 95% CI (0.15, 1.52), p=0.000], and hepcidin [SMD=0.63 ng/mL, 95% CI (0.09, 1.18), p=0.023] levels were higher in the GDM group than in the non-GDM group, whereas total iron binding ability [SMD = -0.53 µg/dL, 95% CI (-1.05, -0.02), p=0.001] was lower in the GDM group than in the non-GDM group. High serum ferritin [OR=1.92, 95% CI (1.59, 2.32), p˂0.001] and hemoglobin levels [OR=1.30, 95% CI (1.04,1.63), p=0.023] were associated with GDM risk. CONCLUSIONS: Serum iron, ferritin, transferrin saturation, hepcidin, and hemoglobin levels were higher and total iron binding ability was lower in GDM patients than in those without GDM. High serum ferritin and hemoglobin levels were associated with GDM risk.

Aromatase deficiency caused by mutation of CYP19A1 gene: A case report. / CYP19A1åŸºå› çªå˜è‡´èŠ³é¦™åŒ–é ¶ç¼ºä¹ç—‡1例.

Aromatase deficiency (AD) is a rare autosomal recessive genetic disease caused by loss-of-function mutations in aromatase gene (CYP19A1), leading to congenital estrogen deficiency syndrome. Both mothers of AD patients during pregnancy and female AD fetus show virilization, while male patients are usually diagnosed in adulthood due to continued height increase and metabolic abnormalities. In 2019, a patient with AD was admitted in the Second Xiangya Hospital. The patient was a 37-year-old adult male who continued to grow linearly after adulthood. His estradiol was below the measurable line, the follicle-stimulating hormone (FSH) increased, bone age delayed, epiphysis unfused, and the bone mass reduced. CYP19A1 gene detection showed that c.1093C>T, p.R365W was homozygous mutation. This disease is rare in clinic. Clinicians need to raise awareness of the disease for early diagnosis and treatment to improve the long-term prognosis of patients.

Relationship between bone mineral density and fragility fracture risk: a case-control study in Changsha, China.

BACKGROUND: Fragility fracture is associated with bone mineral density (BMD), and most databases used in related researches are instrument-matched. Little is known about the relationship between BMD and fragility fracture risk of native Chinese, especially using local databases as reference databases. OBJECTIVE: To investigate relationship between BMD and risk of fragility fracture in native China. METHODS: 3,324 cases, including 2,423 women (67.7 ± 8.9 years) and 901 men (68.4 ± 11.6 years) having radiological fragility fractures and 3,324 age- and gender-matched controls participated in the study. We measured BMD at posteroanterior spine and hip using dual-energy X-ray absorptiometry (DXA), calculated BMD measurement parameters based on our own BMD reference database. RESULTS: BMDs and mean T-scores were lower in case group (with clinical fragility) than in control group (without clinical fragility). In patients with fragility fractures, prevalence of lumbar osteoporosis, low bone mass, and normal BMD were 78.9 %, 19.3 %, and 1.8 %, respectively, in women, and 49.5, 44.8 %, and 5.7 %, respectively, in men. In hip, these prevalence rates were 67.2 %, 28.4 %, and 4.4 % in females, and 43.2 %, 45.9 %, and 10.9 % in males, respectively, showing differences between females and males. Multivariate Cox regression analysis showed that after adjusting age, height, weight, and body mass index, fracture hazard ratio (HR) increased by 2.7-2.8 times (95 % CI 2.5-3.1) and 3.6-4.1 times (95 %CI 3.0-5.1) for women and men respectively with decreasing BMD parameters. In both sexes, risk of fragility fracture increased approximately 1.6-1.7 times (95 % CI 1.5-1.8) for every 1 T-score reduction in BMD. CONCLUSIONS: Risk of clinical fragility fracture increases with decreasing BMD measurement parameters and anthropometric indicators in native China, and fracture HR varies from gender and site.

Vitamin D deficiency in diabetes exacerbates longitudinal risk for atherosclerotic cardiovascular disease in Lanzhou, China.

BACKGROUND AND OBJECTIVES: Vitamin D deficiency has been considered a risk factor for atherosclerotic cardiovascular disease (ASCVD). The aim of this study was to investigate the correlation between serum 25(OH)D concentration and the risk of ASCVD in Chinese, especially in Type 2 diabetes mellitus (T2DM) patients. METHODS AND STUDY DESIGN: Based on the "REACTION" study conducted in 2011, some 9,014 Lanzhou residents aged 40-75 years were followed from 2014 to 2016. A total of 7,061 with complete data were analyzed. Baseline population was classified into four groups based on 25(OH)D quartiles. Cox proportional hazard models were used to estimate relations between 25(OH)D concentration and ASCVD. RESULTS: The prevalence of vitamin D deficiency [25(OH)D <20 ng/mL] was 75.1%. Followed-up for 3.3 years, those with the lowest of 25(OH)D concentration had higher rates of ASCVD (HR: 1.748, 95% CI: 1.149-2.660, p<0.01). A 10 ng/mL increase in baseline serum 25(OH)D was accompanied by a 24 % decrease in ASCVD risk (HR: 0.760, 95% CI: 0.590-0.980, p<0.05). For 25(OH)D and ASCVD risk with glycaemic status, low 25(OH)D plus T2DM was highly associated with ASCVD (HR: 2.296, 95% CI: 1.246-4.232, p<0.01). With diabetes, ASCVD risk decreased by 36% when serum 25(OH)D increased by 10 ng/mL (HR: 0.644, 95% CI: 0.440-0.941, p<0.05). CONCLUSIONS: Serum 25(OH)D is independently and inversely associated with the risk of ASCVD in Lanzhou Chinese, especially those with T2DM. Maintaining sufficient levels of vitamin D may be an effective measure in ASCVD prevention.

Correlation of serum vitamin D with lipid profiles in middle-aged and elderly Chinese individuals.

BACKGROUND AND OBJECTIVES: Deficiency of vitamin D has been associated with various health conditions. The purpose of this study was to evaluate the associations between the serum 25OHD concentration and lipid profiles in Chinese individuals. METHODS AND STUDY DESIGN: Serum 25OHD and lipid profiles were obtained for a cross sectional sample of 10100 individuals aged 40-75 years from Lanzhou city, which is located in western China. Linear-by-linear association, partial correlation analysis and multiple logistic regression analysis were used to evaluate associations between serum 25OHD concentration and lipid profiles. RESULTS: 10038 subjects aged 40- 75 years were included in the study. The 25OHD deficient and insufficient groups had higher TC, LDL-C and TG when compared to the optimal group. The dyslipidemia rates of vitamin D deficiency, insufficiency, and sufficiency groups were 45.4%, 41.6%, 38.8%, respectively. The prevalence rates of dyslipidemia, high cholesterol, high LDL-C, hypertriglyceridemia and mixed type hyperlipidemia exhibited decline trend in vitamin D deficiency, insufficiency and sufficiency groups. The correlation coefficients in between TC and 25OHD, LDL-C and 25OHD, TG and 25OHD were -0.033, -0.022, -0.044, respectively. Low 25OHD levels were associated with the risk of onset of dyslipidemia [OR 1.225 (95% CI 1.075-1.397), p=0.002] in the logistical regression analyses. CONCLUSIONS: Deficient serum 25OHD is associated with higher TC, LDL-C, and TG in middle-aged and elderly Chinese individuals. These findings suggest that low 25OHD levels observationally is simply a marker for elevated atherogenic lipoproteins and question a role for vitamin D supplementation in the prevention of cardiovascular disease.

The status of 25-hydroxyvitamin D across the spectrum of glucose tolerance among middle-aged and elderly Chinese individuals.

CONTEXT: Although vitamin D status and its inverse association with diabetes among White people have been recognized, little research on vitamin D status has been well conducted in Chinese individuals based on glucose tolerance. OBJECTIVE: To compare the vitamin D status of Chinese individuals aged 40-75 years based on the glucose tolerance status. DESIGN AND METHODS: Serum 25OHD was measured in a cross-sectional sample of 10 038 individuals aged 40-75 years from Lanzhou city, which is located in western China. RESULTS: People with normal glucose tolerance (NGT, n = 4744), prediabetes (n = 2808) or diabetes (n = 2486) aged 40-75 years were included in the study. The difference in 25OHD concentration between people with NGT and prediabetes was not significant (16·5 vs 16·0 ng/ml, P = 0·773), but the 25OHD concentration of diabetes was higher than that of subjects with NGT (16·5 vs 16·5 ng/ml, P = 0·025) and prediabetes (16·5 vs 16·0 ng/ml, P = 0·032) after adjusting confounders. There was no difference in the prevalence of vitamin D deficiency between people with NGT and diabetes (74·7% vs 74·0%, P = 0·535), but the prevalence of vitamin D deficiency of prediabetes was higher than that of people with NGT (77·0% vs 74·7%, P = 0·024) and diabetes (77·0% vs 74·0%, P = 0·012). CONCLUSIONS: Although vitamin D status was significantly different across the spectrum of glucose tolerance in middle-aged and elderly Chinese individuals, the difference was not clinically significant. The results, however, highlight the very high prevalence of vitamin D deficiency in this population and should raise the awareness of this important public health issue among health-care providers.

Urinary arsenic metabolism in a Western Chinese population exposed to high-dose inorganic arsenic in drinking water: influence of ethnicity and genetic polymorphisms.

To investigate the differences in urinary arsenic metabolism patterns of individuals exposed to a high concentration of inorganic arsenic (iAs) in drinking water, an epidemiological investigation was conducted with 155 individuals living in a village where the arsenic concentration in the drinking water was 969µg/L. Blood and urine samples were collected from 66 individuals including 51 cases with skin lesions and 15 controls without skin lesions. The results showed that monomethylated arsenic (MMA), the percentage of MMA (%MMA) and the ratio of MMA to iAs (MMA/iAs) were significantly increased in patients with skin lesions as compared to controls, while dimethylated arsenic (DMA), the percentage of DMA (%DMA) and the ratio of DMA to MMA (DMA/MMA) were significantly reduced. The percent DMA of individuals with the Ala/Asp genotype of glutathione S-transferase omega 1 (GSTO1) was significantly lower than those with Ala/Ala. The percent MMA of individuals with the A2B/A2B genotype of arsenic (+3 oxidation state) methyltransferase (AS3MT) was significantly lower than those with AB/A2B. The iAs and total arsenic (tAs) content in the urine of a Tibetan population were significantly higher than that of Han and Hui ethnicities, whereas MMA/iAs was significantly lower than that of Han and Hui ethnicities. Our results showed that when exposed to the same arsenic environment, different individuals exhibited different urinary arsenic metabolism patterns. Gender and ethnicity affect these differences and above polymorphisms may be effectors too.

SIRT3: A Potential Target of Different Types of Osteoporosis.

Osteoporosis (OP) is a common age-related disease. OP is mainly a decrease in bone density and mass caused by the destruction of bone microstructure, which leads to an increase in bone fragility. SIRT3 is a mitochondrial deacetylase that plays critical roles in mitochondrial homeostasis, metabolic regulation, gene transcription, stress response, and gene stability. Studies have shown that the higher expression levels of SIRT3 are associated with decreased levels of oxidative stress in the body and may play important roles in the prevention of age-related diseases. SIRTs can enhance the osteogenic potential and osteoblastic activity of bone marrow mesenchymal stromal cells not only by enhancing PGC-1α, FOXO3, SOD2, and oxidative phosphorylation, but also by anti-aging and reducing mitochondrial autophagy. SIRT3 is able to upregulate antioxidant enzymes to exert an inhibitory effect on osteoclasts, however, it has been shown that the inflammatory cascade response can in turn increase SIRT3 and inhibit osteoclast differentiation through the AMPK-PGC-1ß pathway. SIRT3 plays an important role in different types of osteoporosis by affecting osteoblasts, osteoclasts, and bone marrow mesenchymal cells. In this review, we discuss the classification and physiological functions of SIRTs, the effects of SIRT3 on OCs osteoblasts, and BMSCs, and the roles and mechanisms of SIRT3 in different types of OP, such as diabetic OP, glucocorticoid-induced OP, postmenopausal OP, and senile OP.

Low Selenium and Low Protein Exacerbate Myocardial Damage in Keshan Disease by Affecting the PINK1/Parkin-mediated Mitochondrial Autophagy Pathway.

OBJECTIVE: Keshan disease (KD) is a myocardial mitochondrial disease closely related to insufficient selenium (Se) and protein intake. PTEN induced putative kinase 1 (PINK1)/Parkin mediated mitochondrial autophagy regulates various physiological and pathological processes in the body. This study aimed to elucidate the relationship between PINK1/Parkin-regulated mitochondrial autophagy and KD-related myocardial injury. METHODS: A low Se and low protein animal model was established. One hundred Wistar rats were randomly divided into 5 groups (control group, low Se group, low protein group, low Se + low protein group, and corn from KD area group). The JC-1 method was used to detect the mitochondrial membrane potential (MMP). ELISA was used to detect serum creatine kinase MB (CK-MB), cardiac troponin I (cTnI), and mitochondrial-glutamicoxalacetic transaminase (M-GOT) levels. RT-PCR and Western blot analysis were used to detect the expression of PINK1, Parkin, sequestome 1 (P62), and microtubule-associated proteins1A/1B light chain 3B (MAP1LC3B). RESULTS: The MMP was significantly decreased and the activity of CK-MB, cTnI, and M-GOT significantly increased in each experimental group (low Se group, low protein group, low Se + low protein group and corn from KD area group) compared with the control group (P<0.05 for all). The mRNA and protein expression levels of PINK1, Parkin and MAP1LC3B were profoundly increased, and those of P62 markedly decreased in the experimental groups compared with the control group (P<0.05 for all). CONCLUSION: Low Se and low protein levels exacerbate myocardial damage in KD by affecting the PINK1/Parkin-mediated mitochondrial autophagy pathway.

Evaluation of bi-directional causal association between obstructive sleep apnoea syndrome and diabetic microangiopathy: a Mendelian randomization study.

Background: The relationship between obstructive sleep apnea syndrome (OSAS) and diabetic microangiopathy remains controversial. Objective: This study aimed to use bidirectional two-sample Mendelian Randomization (MR) to assess the causal relationship between OSAS and diabetic microangiopathy. Methods: First, we used the Linkage Disequilibrium Score Regression(LDSC) analysis to assess the genetic correlation. Then, the bidirectional two-sample MR study was conducted in two stages: OSAS and lung function-related indicators (forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1)) were investigated as exposures, with diabetic microangiopathy as the outcome in the first stage, and genetic tools were used as proxy variables for OSAS and lung function-related measures in the second step. Genome-wide association study data came from the open GWAS database. We used Inverse-Variance Weighted (IVW), MR-Egger regression, Weighted median, Simple mode, and Weighted mode for effect estimation and pleiotropy testing. We also performed sensitivity analyses to test the robustness of the results. Furthermore, we performed multivariate and mediation MR analyses. Results: In the LDSC analysis, We found a genetic correlation between OSAS, FVC, FEV 1, and diabetic microangiopathy. In the MR analysis, based on IVW analysis, genetically predicted OSAS was positively correlated with the incidence of diabetic retinopathy (DR), diabetic kidney disease (DKD), and diabetic neuropathy (DN). In the subgroup analysis of DR, there was a significant causal relationship between OSAS and background diabetic retinopathy (BDR) and proliferative diabetic retinopathy (PDR). The reverse MR did not show a correlation between the incidence of diabetic microangiopathy and OSAS. Reduced FVC had a potential causal relationship with increased incidence of DR and PDR. Reduced FEV1 had a potential causal relationship with the increased incidence of BDR, PDR, and DKD. Multivariate MR analysis showed that the association between OSAS and diabetic microangiopathy remained significant after adjusting for confounding factors. However, we did not find the significant mediating factors. Conclusion: Our results suggest that OSAS may be a cause of the development of diabetic microangiopathy, and OSAS may also be associated with a high risk of diabetic microangiopathy, providing a reference for a better understanding of the prevention of diabetic microangiopathy.

Roles of Mitochondrial Dysfunction in Diabetic Kidney Disease: New Perspectives from Mechanism to Therapy.

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes and the main cause of end-stage renal disease around the world. Mitochondria are the main organelles responsible for producing energy in cells and are closely involved in maintaining normal organ function. Studies have found that a high-sugar environment can damage glomeruli and tubules and trigger mitochondrial dysfunction. Meanwhile, animal experiments have shown that DKD symptoms are alleviated when mitochondrial damage is targeted, suggesting that mitochondrial dysfunction is inextricably linked to the development of DKD. This article describes the mechanisms of mitochondrial dysfunction and the progression and onset of DKD. The relationship between DKD and mitochondrial dysfunction is discussed. At the same time, the progress of DKD treatment targeting mitochondrial dysfunction is summarized. We hope to provide new insights into the progress and treatment of DKD.

A novel AVPR2 gene mutation in a Chinese pedigree with nephrogenic diabetes insipidus.

Nephrogenic diabetes insipidus (NDI) is a rare genetic disorder primarily associated with mutations in the arginine vasopressin receptor 2 (AVPR2) gene or the aquaporin 2 (AQP2) gene, resulting in impaired water reabsorption in the renal tubules. This report describes a case of a young male patient with NDI from China with a history of polydipsia and polyuria for over 15 years. Laboratory examinations of the proband indicated low urine-specific gravity and osmolality. Urologic ultrasound revealed severe bilateral hydronephrosis in both kidneys, bilateral dilatation of the ureters, roughness of the bladder wall, and the formation of muscle trabeculae. The diagnosis of diabetes insipidus was confirmed by water deprivation tests. The administration of posterior pituitary hormone did not alter urine-specific gravity, and osmolality remained at a low level (<300 mOsm/kg). Based on these findings, and the genetic tests of the proband and his parents were performed. A missense mutation (c.616 G>C) in exon 3 of the AVPR2 gene of the proband was found, caused by the substitution of amino acid valine to leucine at position 206 [p.Val206Leu], which was a hemizygous mutation and consistent with X-chromosome recessive inheritance. The administration of oral hydrochlorothiazide improves the symptoms of polydipsia and polyuria in the proband. This novel AVPR2 gene mutation may be the main cause of NDI in this family, which induces a functional defect in AVPR2, and leads to reduced tubular reabsorption of water.

The BRAFV600E mutation maintains the aggressiveness of papillary thyroid cancers requiring downregulation of primary cilia.

Although disorders of primary cilia (PCs) were first reported in human papillary thyroid cancer (PTC) tissues in 1987, their precise role in PTC remains unclear. PCs sense the thyroid follicle colloid environment and act as a cell signaling hub. The present study investigated whether PCs are needed for BRAFV600E-driven PTC. We assessed whether BRAFV600E protein expression correlates with papillary histological architecture and clinicopathological features of PTC. We found that expression of ciliary intraflagellar transport 88 (IFT88) and PC formation were reduced in BRAFV600E-driven PTCs and that loss of cilia may be associated with lymph node metastasis. In PTC cells, the BRAFV600E mutation maintained the aggressiveness of PTC, which was partially related to loss of PCs. Our work confirms that BRAFV600E mutation-driven PC downregulation contributes to maintaining the aggressiveness of PTCs and that manipulating PC can potentially reduce the adverse incidence of PTC in a range of conditions.