Targeting of G protein-coupled receptor 39 alleviates angiotensin II-induced renal damage by reducing ribonucleotide reductase M2.

Renal fibrosis, apoptosis and autophagy are the main pathological manifestations of angiotensin II (Ang II)-induced renal injury. G protein-coupled receptor 39 (GPR39) is highly expressed in various tissues including the kidney, but its role in the kidney is entirely unclear. This study was performed to investigate the underlying mechanism by which knockdown of GPR39 alleviated Ang II-induced renal injury. In vivo, GPR39 knockout (KO) mice were constructed and infused with Ang II for 4 weeks, followed by renal function tests. In vitro, Ang II-induced cells were treated with si-GPR39 for 48 h. Fibrosis, apoptosis and autophagy were detected in both cells and mice. The underlying mechanism was sought by mRNA transcriptome sequencing and validated in vitro. GPR39 was upregulated in renal tissues of mice with Ang II-mediated renal injury. Knockdown of GPR39 ameliorated renal fibrosis, apoptosis, and autophagy, and decreased the expression of ribonucleotide reductase M2 (RRM2). In vitro, knockdown of GPR39 was also identified to improve the Ang II-induced cell fibrosis, apoptosis, and autophagy. mRNA transcriptome results showed that knockout of GPR39 reduced the expression of RRM2 in Ang II-induced kidney tissue. Activation of RRM2 could reverse the therapeutic effect of GPR39 knockout, and the inhibitor of RRM2 could improve the cell fibrosis, apoptosis and autophagy caused by GPR39 agonist. These results indicated that targeting of GPR39 could alleviate Ang II-induced renal fibrosis, apoptosis, and autophagy via reduction of RRM2 expression, and GPR39 may serve as a potential target for Ang II-induced renal injury.

Association between dietary inflammatory index and Stroke in the US population: evidence from NHANES 1999-2018.

BACKGROUND: There is an increasing awareness that diet-related inflammation may have an impact on the stroke. Herein, our goal was to decipher the association of dietary inflammatory index (DII) with stroke in the US general population. METHODS: We collected the cross-sectional data of 44,019 participants of the National Health and Nutrition Examination Survey (NHANES) 1999-2018. The association of DII with stroke was estimated using weighted multivariate logistic regression, with its nonlinearity being examined by restricted cubic spline (RCS) regression. The least absolute shrinkage and selection operator (LASSO) regression was applied for identifying key stroke-related dietary factors, which was then included in the establishment of a risk prediction nomogram model, with the receiver operating characteristic (ROC) curve being built to evaluate its discriminatory power for stroke. RESULTS: After confounder adjustment, the adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for stroke across higher DII quartiles were 1.19 (0.94-1.54), 1.46 (1.16-1.84), and 1.87 (1.53-2.29) compared to the lowest quartile, respectively. The RCS curve showed a nonlinear and positive association between DII and stroke. The nomogram model based on key dietary factors identified by LASSO regression displayed a considerable predicative value for stroke, with an area under the curve (AUC) of 79.8% (78.2-80.1%). CONCLUSIONS: Our study determined a nonlinear and positive association between DII and stroke in the US general population. Given the intrinsic limitations of cross-sectional study design, it is necessary to conduct more research to ensure the causality of such association.

Gender differences in the association between healthy eating index-2015 and hypertension in the US population: evidence from NHANES 1999-2018.

BACKGROUND: Diet has long been recognized as an important modifiable risk factor for hypertension. Herein, our research goal was to decipher the association of healthy eating index-2015 (HEI-2015) with hypertension, and to explore potential gender differences. METHODS: We collected the cross-sectional data of 42,391 participants of the National Health and Nutrition Examination Survey (NHANES) 1999-2018. The association of HEI-2015 with hypertension was estimated using weighted multivariate logistic regression, with restricted cubic spline (RCS) regression being adopted to examine the nonlinearity of this association in both genders, and the stability of the results were examined by sensitivity analysis. We also performed subgroup analysis to detect potential difference in the link between HEI-2015 and hypertension stratified by several confounding factors. RESULTS: After eliminating potential confounding bias, the adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for hypertension across higher HEI-2015 quartiles were 0.93 (0.85-1.03), 0.84 (0.77-0.93), and 0.78 (0.72-0.86) compared to the lowest quartile, respectively. HEI-2015 was nonlinearly and inversely associated with hypertension in all participants. The gender-specific RCS curves presented a U-shaped correlation in males, while showed a linear and inverse correlation in females. Besides, subgroup analyses showed a lower risk of hypertension in participants who were females, younger than 40 years, Whites, obese, and diabetic patients. CONCLUSIONS: We determined a nonlinear and inverse association between HEI-2015 and hypertension in the US general population, and revealed a remarkable gender difference when adhering to a HEI-2015 diet for preventing hypertension.

Lipid metabolism, BMI and the risk of nonalcoholic fatty liver disease in the general population: evidence from a mediation analysis.

BACKGROUND: Body mass index (BMI) and lipid parameters are the most commonly used anthropometric parameters and biomarkers for assessing nonalcoholic fatty liver disease (NAFLD) risk. This study aimed to assess and quantify the mediating role of traditional and non-traditional lipid parameters on the association between BMI and NAFLD. METHOD: Using data from 14,251 subjects from the NAGALA (NAfld in the Gifu Area, Longitudinal Analysis) study, mediation analyses were performed to explore the roles of traditional [total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C)] and non-traditional [non-HDL-C, remnant cholesterol (RC), TC/HDL-C ratio, LDL-C/HDL-C ratio, TG/HDL-C ratio, non-HDL-C/HDL-C ratio, and RC/HDL-C ratio] lipid parameters in the association of BMI with NAFLD and quantify the mediation effect of these lipid parameters on the association of BMI with NAFLD using the percentage of mediation. RESULT: After fully adjusting for confounders, multivariate regression analysis showed that both BMI and lipid parameters were associated with NAFLD (All P-value < 0.001). Mediation analysis showed that both traditional and non-traditional lipid parameters mediated the association between BMI and NAFLD (All P-value of proportion mediate < 0.001), among which non-traditional lipid parameters such as RC, RC/HDL-C ratio, non-HDL-C/HDL-C ratio, and TC/HDL-C ratio accounted for a relatively large proportion, 11.4%, 10.8%, 10.2%, and 10.2%, respectively. Further stratified analysis according to sex, age, and BMI showed that this mediation effect only existed in normal-weight (18.5 kg/m2 ≤ BMI < 25 kg/m2) people and young and middle-aged (30-59 years old) people; moreover, the mediation effects of all lipid parameters except TC accounted for a higher proportion in women than in men. CONCLUSION: The new findings of this study showed that all lipid parameters were involved in and mediated the risk of BMI-related NAFLD, and the contribution of non-traditional lipid parameters to the mediation effect of this association was higher than that of traditional lipid parameters, especially RC, RC/HDL-C ratio, non-HDL-C/HDL-C ratio, and TC/HDL-C ratio. Based on these results, we suggest that we should focus on monitoring non-traditional lipid parameters, especially RC and RC/HDL-C ratio, when BMI intervention is needed in the process of preventing or treating NAFLD.

Association between migraine or severe headache and hypertension among US adults: A cross-sectional study.

BACKGROUND AND AIMS: Epidemiological evidence of the association between migraines, severe headaches, and hypertension is contradictory. Hypertension is a critical risk factor for cardiovascular diseases. Migraine is a common neurological disease and a major cause of disability worldwide. Therefore, we aimed to investigate the relationship between migraine, severe headaches, and hypertension among US adults. METHODS AND RESULTS: Cross-sectional data from 5716 subjects were obtained from the National Health and Nutrition Examination Survey between 1999 and 2004. Weighted logistic regression models investigated the association between migraines, severe headaches, and hypertension. In total, 5716 subjects were enrolled in the present study, of whom 1134 (19.8%) had migraine or severe headaches. Participants with migraine were predominantly younger females and had a higher body mass index (BMI), lower educational level, lower dietary intake of potassium and calcium, lower serum levels of total cholesterol (TC), creatinine, and hemoglobin, as well as a higher estimated glomerular filtration rate (eGFR) (all P < 0.05). After fully adjusting for potential confounders, migraine or severe headaches were positively associated with hypertension (OR 1.25, 95% CI: 1.03-1.53). CONCLUSION: Our study found a positive association between migraine, severe headaches, and hypertension. Further studies are needed to verify the causality of this association and elucidate the underlying mechanisms.

Assessing the longitudinal association between the GGT/HDL-C ratio and NAFLD: a cohort study in a non-obese Chinese population.

BACKGROUND: A cross-sectional association between the combination indicator of high-density lipoprotein cholesterol (HDL-C) and gamma-glutamyl transferase (GGT) and fatty liver has been described in several recent studies, and this study aims to further evaluate the longitudinal relationship between the ratio of GGT to HDL-C (GGT/HDL-C ratio) and nonalcoholic fatty liver disease (NAFLD). METHODS: This cohort study included 12,126 individuals without NAFLD at baseline, followed prospectively for 5 years, and the endpoint of interest was new-onset NAFLD. The relationship of the GGT/HDL-C ratio with new-onset NAFLD and the shape of the association was assessed by Cox regression models and restricted cubic spline (RCS) regression, respectively. Time-dependent receiver operator characteristics (ROC) curves were constructed to evaluate the predictive value of GGT, HDL-C, GGT/HDL-C ratio and BMI for the occurrence of NAFLD at different time points in the future. RESULTS: The prevalence of NAFLD was 72.46/1000 person-years during the 5-year follow-up period. Results of multivariate Cox regression analysis showed a positive association of the GGT/HDL-C ratio with new-onset NAFLD after adequate adjustment of the related confounding factors, and the degree of correlation was slightly higher than that of GGT, and further subgroup analysis found that this association was more significant in the population with elevated systolic blood pressure (SBP). In addition, we also found a nonlinear relationship of the GGT/HDL-C ratio with the risk of new-onset NAFLD using the RCS regression, where the saturation threshold was about 31.79 U/mmol. Time-dependent ROC analysis results showed that the GGT/HDL-C ratio was increasingly valuable in predicting NAFLD over time, and was better than HDL-C in predicting NAFLD in the early stage (1-3 years), but was not superior to BMI and GGT. CONCLUSIONS: In this large longitudinal cohort study based on a Chinese population, our results supported that the GGT/HDL-C ratio was positively and nonlinearly associated with the risk of new-onset NAFLD in a non-obese population. In the assessment of future NAFLD risk, the GGT/HDL-C ratio was slightly better than GGT alone; However, the GGT/HDL-C ratio did not appear to have a significant advantage over GGT and BMI alone in predicting NAFLD.

Abdominal obesity phenotypes are associated with the risk of developing non-alcoholic fatty liver disease: insights from the general population.

BACKGROUND: The diversity of obesity-related metabolic characteristics generates different obesity phenotypes and corresponding metabolic diseases. This study aims to explore the correlation of different abdominal obesity phenotypes with non-alcoholic fatty liver disease (NAFLD). METHODS: The current study included 14,251 subjects, 7411 males and 6840 females. Abdominal obesity was defined as waist circumference ≥ 85 cm in males and ≥ 80 cm in females; according to the diagnostic criteria for metabolic syndrome recommended by the National Cholesterol Education Program Adult Treatment Panel III, having more than one metabolic abnormality (except waist circumference criteria) was defined as metabolically unhealthy. All subjects were divided into 4 abdominal obesity phenotypes based on the presence ( +) or absence (- ) of metabolically healthy/unhealthy (MH) and abdominal obesity (AO) at baseline: metabolically healthy + non-abdominal obesity (MH-AO-); metabolically healthy + abdominal obesity (MH-AO+); metabolically unhealthy + non-abdominal obesity (MH+AO-); metabolically unhealthy + abdominal obesity (MH+AO+). The relationship between each phenotype and NAFLD was analyzed using multivariate logistic regression. RESULTS: A total of 2507 (17.59%) subjects in this study were diagnosed with NAFLD. The prevalence rates of NAFLD in female subjects with MH-AO-, MH-AO+, MH+AO-, and MH+AO+ phenotypes were 1.73%, 24.42%, 7.60%, and 59.35%, respectively. Among male subjects with MH-AO-, MH-AO+, MH+AO-, and MH+AO+ phenotypes, the prevalence rates were 9.93%, 50.54%, 25.49%, and 73.22%, respectively. After fully adjusting for confounding factors, with the MH-AO- phenotype as the reference phenotype, male MH-AO+ and MH+AO+ phenotypes increased the risk of NAFLD by 42% and 47%, respectively (MH-AO+: OR 1.42, 95%CI 1.13,1.78; MH+AO+: OR 1.47, 95%CI 1.08,2.01); the corresponding risks of MH-AO+ and MH+AO+ in females increased by 113% and 134%, respectively (MH-AO+: OR 2.13, 95%CI 1.47,3.09; MH+AO+: OR 2.34, 95%CI 1.32,4.17); by contrast, there was no significant increase in the risk of NAFLD in the MH+AO- phenotype in both sexes. CONCLUSIONS: This first report on the relationship of abdominal obesity phenotypes with NAFLD showed that both MH-AO+ and MH+AO+ phenotypes were associated with a higher risk of NAFLD, especially in the female population. These data provided a new reference for the screening and prevention of NAFLD.

Waist-to-height ratio and non-alcoholic fatty liver disease in adults.

BACKGROUND: The waist-to-height ratio (WHtR) has been recognised as a powerful indicator to evaluate non-alcoholic fatty liver disease (NAFLD) in recent years, but few related studies are available. Thus, clarifying the association between the WHtR and NAFLD may be beneficial to the prevention and treatment of NAFLD. METHODS: The cross-sectional study population was from a large-scale health examination programme called 'human dock' in Japan. In this study, 14,125 participants in this health examination programme were included. To understand the association between the WHtR and NAFLD more intuitively, we grouped the WHtR values into quintiles and used a multivariable logistic regression model to assess WHtR and its quintile with NAFLD risk. Moreover, we used the generalised additive model to model the association between WHtR and NAFLD to explore their non-linear relationship. RESULTS: The prevalence of NAFLD among participants in this study was 17.59%, with an average age of 43.53 ± 8.89 years. After adjusting for all non-collinear covariables, we observed a 66% increase in the NAFLD risk per SD increase in WHtR. Furthermore, in the quintile groups of WHtR, the participants in quintile 2, quintile 3, quintile 4, and quintile 5 had 3.62-fold, 5.98-fold, 9.55-fold, and 11.08-fold increased risks of NAFLD, respectively, compared with those in quintile 1 (Ptrend < 0.0001). Non-linear relationship analysis revealed threshold and saturation effects between WHtR and NAFLD in which a WHtR of approximately 0.4 might be the threshold effect of NAFLD risk, 0.6 might be the saturation effect of NAFLD risk. Additionally, subgroup analysis showed that the interaction between WHtR and BMI was significant. CONCLUSIONS: Our results suggest that in adults, the WHtR is associated with NAFLD, and the association is not purely linear but non-linear, with significant threshold and saturation effects.

The usefulness of obesity and lipid-related indices to predict the presence of Non-alcoholic fatty liver disease.

BACKGROUND: Conicity index, body-shape index, lipid accumulation product (LAP), waist circumference (WC), triglyceride, triglyceride-glucose (TyG) index, hepatic steatosis index (HSI), waist-to-height ratio (WHtR), TyG index-related parameters (TyG-WHtR, TyG-BMI, TyG-WC), body mass index (BMI), visceral adiposity index, triglyceride to high-density lipoprotein cholesterol ratio and body roundness index have been reported as reliable markers of non-alcoholic fatty liver disease (NAFLD). However, there is debate about which of the above obesity and lipid-related indices has the best predictive performance for NAFLD risk. METHODS: This study included 6870 female and 7411 male subjects, and 15 obesity and lipid-related indices were measured and calculated. NAFLD was diagnosed by abdominal ultrasound. The area under the curve (AUC) of 15 obesity and lipid-related indices were calculated by receiver operating characteristic (ROC) analysis. RESULTS: Among the 15 obesity and lipid-related indices, the TyG index-related parameters had the strongest association with NAFLD. ROC analysis showed that except for ABSI, the other 14 parameters had high predictive value in identifying NAFLD, especially in female and young subjects. Most notably, TyG index-related parameters performed better than other parameters in predicting NAFLD in most populations. In the female population, the AUC of TyG-WC for predicting NAFLD was 0.9045, TyG-BMI was 0.9084, and TyG-WHtR was 0.9071. In the male population, the AUC of TyG-WC was 0.8356, TyG-BMI was 0.8428, and TyG-WHtR was 0.8372. In addition, BMI showed good NAFLD prediction performance in most subgroups (AUC>0.8). CONCLUSIONS: Our data suggest that TyG index-related parameters, LAP, HSI, BMI, and WC appear to be good predictors of NAFLD. Of these parameters, TyG index-related parameters showed the best predictive potential.

Clinical outcomes of doubled-suture Nice knot augmented plate fixation in the treatment of comminuted midshaft clavicle fracture.

BACKGROUND: Free bone fragments were difficult to be fixed in many comminuted midshaft clavicle fractures, and the absence of cortical alignment in comminuted fractures had direct influence on the stability of fixation. This survey was performed to assess the efficacy of doubled-suture Nice knot augmented plate fixation in the treatment of comminuted midshaft clavicle fractures. METHODS: Between 2013 and 2018, all patients with comminuted midshaft clavicle fractures treated with doubled-suture Nice knot augmented plate fixation were retrospectively reviewed and included in this research. Demographic data of the patients, characteristics of the fractures, intraoperative parameters and follow-up data of the patients were evaluated and summarized. RESULTS: A total of 56 patients were included in this study. The mean follow-up time was 25.6 months (range, 12-60 months). The number of male patients was 38 (67.9 %) and of the female patients was 18 (32.1 %). The average age of all patients was 47.89 ± 16.5 years. The mean time of surgery was 85.6 ± 24.0 min. The average length of incision was 9.2 ± 1.9 cm. The number of doubled-suture Nice knot applied ranged from 1 to 5 knots. All the patients reached bone union after the treatment. There was no implant failure or neurovascular injury observed. And most of the patients showed good functional outcome. CONCLUSIONS: The doubled-suture Nice knot could provide reliable fixation for small bone fragments in comminuted clavicle fractures. Combination of the doubled-suture Nice knot and plate screws fixation was a safe and effective method in comminuted midshaft clavicle fractures treatment.

TRPV1 signaling of perirenal adipose tissue promotes DOCA-Salt-induced hypertension and kidney injury.

BACKGROUND: Denervation of renal or perirenal adipose tissue (PRAT) can reduce arterial blood pressure in various hypertensive experimental models. Trpv1 (transient receptor potential vanillin 1) channel is highly expressed in the renal sensory nerves and the dorsal root ganglias (DRGs) projected by PRAT. However, it is currently unclear whether Trpv1 in DRGs projected from PRAT can regulate renal hypertension. METHODS: We used resintoxin (RTX) to block the afferent sensory nerves of rat PRAT. We also constructed Trpv1 -/- mice and Trpv1 +/- mice or used the injection of AAV2-retro-shTrpv1 to detect the effects of Trpv1 knockout or knockdown of PRAT-projected DRGs on deoxycorticosterone acetate (DOCA)-Salt-induced hypertension and kidney injury. RESULTS: Blocking the afferent sensory nerves of PRAT with RTX can alleviate DOCA-Salt-induced hypertension and renal injury in rats. And this blockade reduces the expression of Trpv1 in the DRGs projected by PRAT. Injecting AAV2-retro-shTrpv1 into the PRAT of DOCA-Salt mice also achieved the same therapeutic effect. However, DOCA-Salt-induced hypertension and renal injury can be treated in Trpv1 +/- mice but not alleviated or even worsened in Trpv1 -/- mice, possibly because of compensatory increase of Trpv5 in DRG of Trpv1 -/- mice. CONCLUSION: Reducing, rather than eliminating, Trpv1 in DRG from PRAT-projection can reduce blood pressure and kidney damage in DOCA-Salt in rats or mice. Trpv1 in PRAT-DRGs may serve as a therapeutic target for salt-sensitive hypertension and its renal complications.

The role of predicted lean body mass and fat mass in non-alcoholic fatty liver disease in both sexes: Results from a secondary analysis of the NAGALA study.

Objective: High body mass index (BMI) is an important risk factor for non-alcoholic fatty liver disease (NAFLD). However, the association of body composition such as fat mass (FM) and lean body mass (LBM) with NAFLD has not been adequately studied. The purpose of this study was to clarify the contribution of body composition FM and LBM to NAFLD. Methods: We analyzed data from 7,411 men and 6,840 women in the NAGALA cohort study. LBM and FM were estimated for all subjects using validated anthropometric prediction equations previously developed from the National Health and Nutrition Examination Survey (NHANES). Using multiple logistic regression and restricted cubic spline (RCS) to analyze the association and the dose-response curve of predicted LBM and FM with NAFLD in both sexes. Results: The prevalence of NAFLD in man and woman subjects was 27.37 and 6.99%, respectively. Predicted FM was positively and linearly associated with NAFLD in both sexes, with each 1 kg increase in predicted FM associated with a 27 and 40% increased risk of NAFLD in men and women, respectively. In contrast, predicted LBM was negatively associated with NAFLD in both sexes, with each 1 kg increase in predicted LBM reducing the risk of NAFLD by 4 and 19% in men and women, respectively. In addition, according to the RCS curve, the risk of NAFLD did not change in men when the predicted LBM was between 47 and 52 kg, and there seemed to be a saturation effect; further, the threshold value of the saturation effect was calculated to be about 52.08 kg by two-piecewise logistic regression, and the protective effect on NAFLD would be significantly enhanced when the man predicted LBM was greater than 52.08 kg. Conclusion: The current findings suggested that body composition LBM and FM had opposite associations with NAFLD in both sexes, with higher LBM associated with a lower risk of NAFLD and higher FM increasing the risk of NAFLD, especially in women.

Association between MetS-IR and prediabetes risk and sex differences: a cohort study based on the Chinese population.

Objective: The metabolic score for insulin resistance (MetS-IR) is an emerging surrogate marker for insulin resistance (IR). This study aimed to investigate the association and sex differences between MetS-IR and prediabetes risk in a Chinese population. Methods: This cohort study included 100,309 adults with normoglycemia at baseline and had followed longitudinally for 5 years, and with prediabetes, defined according to the 2018 American Diabetes Association (ADA) recommended diagnostic criteria, as the outcome of interest. Multivariate Cox proportional hazards regression and restricted cubic spline (RCS) regression models were used to assess the association between MetS-IR and prediabetes risk. Results: During an observation period of 312,843 person-years, 7,735 (14.84%) men and 4,617 (9.57%) women with pre-diabetes onset were recorded. After fully adjusting for confounders, we found an independent and positive correlation between MetS-IR and the risk of prediabetes in the Chinese population, and the degree of correlation was stronger in women than in men (HR: 1.24 vs 1.16, P-interaction<0.05). Furthermore, using RCS nested in the Cox regression model, we found that there was a nonlinear correlation between MetS-IR and prediabetes risk in both sexes with an obvious saturation effect point, and when the MetS-IR was greater than the value of the saturation effect point, the risk of prediabetes was gradually leveling off. We further calculated the saturation effect points of MetS-IR used to evaluate the risk of prediabetes which in men was 42.82, and in women was 41.78. Conclusion: In this large cohort study, our results supported that MetS-IR was independently and positively associated with the risk of prediabetes in the Chinese population, with the association being stronger in women than in men.

High waist circumference is a risk factor for hypertension in normal-weight or overweight individuals with normal metabolic profiles.

This study aims to investigate the relationship between waist circumference and hypertension risk in normal-weight/overweight individuals with normal cardiometabolic profiles. The authors included 7217 normal-weight and overweight individuals with normal cardiometabolic profiles from the 2001 to 2014 US National Health and Nutrition Examination Survey. The authors summarized demographic characteristics, cardiometabolic profiles, and behavioral factors across waist circumference quartiles. Then, in the logistic regression analysis, the authors observed a positive and significant association between waist circumference (as a continuous variable) and the prevalence of hypertension in all three models (nonadjusted, minimally adjusted, and fully adjusted), with odds ratios (95% confidence intervals) of 1.76 (1.65-1.86), 1.29 (1.20-1.39), and 1.24 (1.09-1.40), respectively. When analyzed as a categorical variable, individuals in the highest waist circumference group had a 1.48-fold increased risk of hypertension than the lowest group in the fully adjusted model. Moreover, the Cox regression analysis revealed a positive and significant association between waist circumference and all-cause mortality in individuals with hypertension in the nonadjusted model (HR, 1.27; 95% CI, 1.10-1.47) and the fully adjusted model (HR, 1.59; 95% CI, 1.22-2.06). In conclusions, our results showed that, even in those with normal metabolic profiles, high waist circumference was significantly associated with the increased prevalence of hypertension. And once hypertension has been established, patients with high waist circumference showed elevated all-cause mortality. Therefore, waist circumference should be routinely measured and controlled regardless of metabolic profiles.

[Differentiation of QY1 bone marrow pluripotential mesenchymal stem cell line cells into cardiomyocytes and vascular endothelial cells in vitro].

OBJECTIVE: To explore the differentiation potential of QY1 bone marrow mesenchymal stem cell (MSCs) line cells into cardiacmyocytes and vascular endothelial cells in vitro, to optimize the suitable conditions of MSCs differentiating into cardiomyocytes in vitro, and to examine the potentials of MSCs differentiating into cardiomyogenesis and vasculogenesis. METHODS: Specifically committed differentiation inductive medium was employed, including 5-azacytidine for cardiomyogenesis and vascular endothelial growth factor for vasculogenesis in culture respectively in vitro. The differentiated cells were identified by immunohistochemistry and molecular biology. RESULTS: MSCs line cells had been cultured in the normal culture medium for 72 hours, then the differentiation inductive medium including 10 micromol/L 5-azacytidine was added into the normal culture dishes for 24 hours only. After that the culture medium was changed back to the normal culture medium. Normal culture medium was changed every 7 days. The second induction was performed after 14 days. The differentiated cells treated with 5-azacytidine could beat spontaneously and formed myotube structures in the optimal induction conditions, and the differentiation rate was (39.47+/-0.56)%. The differentiated cells expressed specific cardiomyocytic proteins identified by the positive immunohistochemistry staining with anti-alpha-sarcomeric antibody and anti-Cx-43 antibody, and also expressed the alpha-myosin heavy chain examined by RT-PCR. The differentiated cells began to appear as the lined up vascular endothelial cells after 48 hour treatment with vascular endothelial growth factor. Some of the differentiated cells connected each other to form vascular endothelial web-like structure after 7 day treatment with vascular endothelial growth factor. On 14 d after treating with vascular endothelial growth factor, the differentiated cells were identified by immunohistochemistry staining. The expressions of both specific surface antibody CD31 and factor VIII for vascular endothelial cells were positive. CONCLUSION: The cells of QY1 bone marrow mesenchymal stem cell line may differentiate into cardiomyocytes or vascular endothelial cells in vitro under specific condition.

[Pluripotential differentiation of QY1 bone marrow mesenchymal stem cell line].

OBJECTIVE: To explore the ability of QY1 bone marrow mesenchymal stem cell (MSCs) line cells to differentiate into adipocytes, chondrocytes, osteoblasts, cardiac myocytes,vascular endothelial cells, and neural cells in vitro. METHODS: The QY1 cells at passage 5 were treated with the adipogenic medium, the chondrogenic medium and the osteogenic medium, 5-azacytidine, vascular endothelial growth factor and neural cell medium (revulsant 1 was 10 mmol/L beta-mercaptoethanol; revulsant 2 was 2%dimethylsulfoxide and 10(-8)mol/L dexamethasone) in culture respectively in vitro. The differentiated cells were identified by staining, immunohistochemistry and RT-PCR. RESULTS: The differentiated cells induced by the adipogenic medium formed adipocytes and contained fat lipid droplets, which were stained positively with Sudan III after 21 days of culture. The differentiated cells induced by the chondrogenic medium formed chondrogenic nodules, which were stained positively by Alcian blue at pH 1.0 after 21 days of culture. The differentiated cells induced by the osteogenic medium formed osteogenic nodules, which were stained positively by Von Kossa staining after 35 days of culture, and the secretion of a calcified extracellular matrix as black nodules was observed. The differentiated cells treated with 10 micromol/L 5-azacytidine could beat spontaneously and formed myotube structures,which were identified by the positive immunohistochemistry staining with anti-alpha-sarcomeric antibody and anti-Cx-43 antibody. The expression of alpha-myosin heavy chain was also observed by RT-PCR. The differentiated cells treated with 50 ng/mL vascular endothelial growth factor could form vascular endothelial cells and vascular endothelial web like structure, which were identified by the positive immunohistochemistry staining with CD31 and Factor VIII. The differentiated cells induced by revulsant 1 were positive in the immunohistochemistry staining with neuron-specific nuclear protein, while the expression of glial fibrillary acidic protein was negative. The differentiated cells induced by revulsant 2 were positive in the immunohistochemistry staining with glial fibrillary acidic protein, while the expression of neuron-specific nuclear protein was negative. CONCLUSION: QY1 bone marrow mesenchymal stem cell line has the ability to differentiate into adipocytes, chondrocytes, osteocytes, cardiomyocytes, vascular endothelial cells, neurons and neural glial cells in vitro. A bone marrow mesenchymal stem cell line cell can at least differentiate into 7 types of cells, which come from mesoderm and ectoderm.

[Effectiveness of cerclage and a figure-of-eight tension band by a single titanium wire in treatment of patellar fracture].

Objective: To estimate the outcome of cerclage followed by a figure-of-eight tension band with a single titanium wire for the treatment of patellar fracture. Methods: A retrospective analysis was made on the clinical data of 46 patients with patellar fractures treated between June 2012 and November 2014. There were 30 males and 16 females, aged 20-86 years (mean, 54 years). The fracture causes included falling in 27 cases, traffic accident in 16 cases, and knock in 3 cases. There were 41 cases of closed fractures and 5 cases of open fracture. The injury located at the left side in 24 cases and the right side in 22 cases. According to AO classification, fracture was rated as type 34-A in 3 cases, as type 34-B in 1 case, as type 34-C1 in 7 cases, as type 34-C2 in 13 cases, and as type 34-C3 in 22 cases. The time between injury and operation ranged 1-12 days (mean, 3.7 days). During operations, a single titanium wire was used to pass around the patellar, followed a figure-of-eight wrapping, to tight and fix at the tension of 35 kg. Results: All incisions healed primarily. The patients were followed up 20.6 months on average (range, 6-24 months). Partial wire loosening was found in 2 cases, irritation of skin or soft tissue in 1 case. The X-ray examination showed bony healing at 3 months after operation, without breakage of titanium wire. The internal fixation was removed in 38 cases at 12 months after operation. According to the Böstman rating score, the mean score was 28.34 (range, 24-30) at 12 months after ope-ration; the results were excellent in 42 cases and good in 4 cases, with an excellent and good rate of 100%. Conclusion: For patellar fracture, cerclage followed by a figure-of-eight tension band with a single titanium wire is able to achieve an effective stability and to allow early motion for patient with less complication.

Mesenchymal stem cells participate in angiogenesis and improve heart function in rat model of myocardial ischemia with reperfusion.

OBJECTIVE: The effect of transplanted mesenchymal stem cells (MSCs) on the left ventricular (LV) function and morphology in a rat myocardial infarct heart with reperfusion model were analyzed. METHODS: One week after 60 min of myocardial ischemia and reperfusion by left anterior descending artery (LAD) occlusion, 1.0x10(7) 6-diamidino-2-phenylindole (DAPI)-labeled MSCs were injected into the infarcted myocardium and compared with controls, and sham-operated rats, in which a cell-free serum medium was injected into the infarcted region or the myocardial wall, respectively. Measurement of vascular endothelial growth factor (VEGF) expression 1 week after MSC injection using Western blot analysis (n=5), and immunohistochemical staining using HE staining and fluorescent microscopy of the DAPI-positive regions from MSC implantation, cTnT immunostaining of potential myocardial-like cells, and SM-actin and CD31 immunostaining demonstrating neovascular transformation of implanted MSCs 1 week, 2 weeks and 4 weeks after transplantation (n=5). Hemodynamic measurements were performed after 4 weeks in vivo. Subsequently, hearts were quickly removed and cut for histological analysis using HE staining with measurement of the infarcted LV-area, the LV-wall thickness within the scar segment compared to non-infarcted scar segments, and the capillary density counting capillary vessels with 400x light microscopy (n=10). RESULTS: Measurement of hemodynamics 4 weeks after transplantation in vivo showed LV function to be significantly greater in MSCs than in the control group. Semi-quantitative histomorphometric examinations showed a significantly lower infract size, a greater LV-wall thickness, and a lower Hochman-Choo expansion index in the MSC-treated group compared to the control group. Immunofluorescence demonstrated that transplanted MSCs were positive for cTnT, suggesting that a small number of transplanted MSCs can differentiate into cardiomyocytes. Other MSCs were positive for CD31 and SM-actin. The transplanted MSCs in MI area had significantly higher expression rates of cTnT, CD31 and SM-actin 2 weeks after transplantation. HE staining showed marked augmentation of neovascularization in the MSC group. Semi-quantitative analysis demonstrated that capillary density was significantly higher in the MSC group than in the control group. CONCLUSION: Implanted MSCs could improve cardiac structure and function through the combined effect of myogenesis and angiogenesis.

[Biological stability analysis of QY1 pluripotential mesenchymal stem cell line from Sprague Dawley rat bone marrow].

OBJECTIVE: To explore the optimal culture conditions in vitro and the biological characterizations of the QY1 pluripotential mesenchymal stem cell (MSC) line from Sprague-Dawley rat bone marrow and to analyze the biological stability of this MSC line so as to provide an ideal cell model for the further differentiation and actual application. METHODS: The methods and technologies of cell biology and stem cell tissue engineering were used to purify MSCs. We determined the effects of morphology of cell proliferation, the time of change medium, growth curves, doubling time, adhesive rates, chromosome, culture conditions, and repeated frost on the biological characterizations of MSCs. RESULTS: The cells had a fibroblastic-like morphology and were well spread out; 80% - 90% cells became confluent between 10 and 12 days in primary culture. The growth curves of Passage 1, 3, 10, and 20 were quite similar (P>0.05). The doubling time of passage 1, 3, 10, and 20 were 34.2, 33.9, 31.8, and 30.6 hours, respectively. The adhesive rates of Passage 1, 3, 10, and 20 were very much similar (P>0.05) and about 89% subcultured cells adhered to the wall in 10 hours. The most appropriate concentration of serum was 20% and the most appropriate concentration of cell number was 8 x 10(4)/mL. The cells of Passage 8 showed light red cytoplasm and heavy blue nuclear stained by Giemsa staining. The chromosomes of Passage 8 and 20 were normal in appearance and their karyotypes were 42, XY. The cells were resuscitable after repeated frozen, and more than 85% cells were alive. The cells had been continuously cultured for more than 10 months so far. CONCLUSION: The QY1 MSCs line from Sprague-Dawley rat bone marrow is a purified cell line, which can maintain its undifferentiation and the stable biological characterizations for the long term.

[Committed hematopoeitic differentiation of embryonic stem cell].

OBJECTIVE: To explore a stable technology for inducing ES cell to committed hematopoietic differentiation. METHODS: The effects of various inductive factors on BLast Colony-Forming Cell (BL-CFC) were investigated. In vitro differentiative system for ES cells was employed in this study. RESULTS: A high linear correlation between the number of D3.5 EB-derived cells plated and the number of blast cell colonies was developed, r = 0.9931. With high frequency of blast colonies observed (1.08-1.2 colonies per 100 cells). 20%-30% D4T conditioned medium (D4T CM) showed the most significant growth potentials of blast colonies. D4T CM, EPO or KL alone had no blast colony growth promoting effect (P > 0.05). But VEGF alone had high significant blast colony growth promoting effect (P < 0.001). However, any two factors combination from above four factors exerted better growth promoting effect than VEGF alone (EPO + D4T CM, P < 0.05; KL + D4T CM, P < 0.01; VEGF + D4T CM, P < 0.001). There were no significant difference among VEGF + KL and EPO + D4T CM or KL + D4T CM, and KL + D4T CM (P > 0.05). While the combination of VEGF + D4T CM was better than KL + D4T CM, VEGF + KL or EPO + D4T CM (P < 0.001). Moreover, the combination of VEGF + KL + D4T CM + EPO, had the highest significant blast colony growth promoting effect (P < 0.001). And the highest frequency of blast colonies was observed (1.5-1.2 colonies per 100 cells). CONCLUSION: VEGF may be the main factor which stimulates the growth of significant numbers of blast cell colonies. D4T CM maybe contains strong cofactors. EPO and KL are the main factors for the induction of BL-CFC to committed hematopoietic differentiation. D3.5 EB-derived cells are more sensitive to various stimulators and have strong blast colony growth promoting effect than that of D3.25 EB-derived cells.