Crosstalk between skeletal muscle ratio and cholesterol metabolism disorders: a cross-section study.

BACKGROUND: Dysfunction of cholesterol metabolism may be associated with low skeletal muscle mass.  This study aimed to explore the relationship between skeletal muscle mass and cholesterol metabolic disorders in adults. METHODS: The data of a total of 5949 people with complete medical history data, biochemical data and body composition analysis were recruited. According to the serum cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL) and nonHDL, the population was divided into a disorder group and a normal group. Independent sample t tests, chi-square tests, Pearson's correlation analyses and binary logistic regression analyses were used to study the effect of body composition on abnormal cholesterol metabolism. According to BMI and sex, the population was divided into different subgroups, and binary logistic regression analysis was used to study the effect of the skeletal mass ratio on cholesteral metabolic disorders in different subgroups. RESULTS: There were significant differences in sex, alcohol consumption, body weight, BMI, skeletal muscle mass index (SMI) [total skeletal muscle mass (kg)/height 2 (m2)] and skeletal muscle mass ratio (SMR) [total skeletal muscle mass (kg)/weight (kg) *100] between the disorder group (hypercholesterolemia, hyper-LDL, lower-HDL and hyper-nonHDL) and the normal group. Pearson correlation analysis revealed that the SMR was negatively correlated, while the SMI was positively correlated with cholesterol metabolic disorders in both sexes. The overweight group was older and had a greater SMI, abnormal cholesteral metabolism ratio and lower SMR than the normal-weight group. In the normal-weight group, the SMR was an independent protective factor against different kinds of cholesteral metabolic disorders in both sexes, while the SMI was a risk factor. In the overweight subgroup, the protective effect on HDL and nonHDL metabolism remained in the male subgroup but disappeared in the female subgroup. However, the SMI was an independent risk factor for different kinds of cholesteral metabolic disorders in both sexes. CONCLUSIONS: SMR was an independent protective factor against cholesterol metabolic disorders in both males and females, especially in the normal weight group. SMI was an independent risk factor, especially in the overweight group.

Exosomal miR-23a and miR-192, Potential Diagnostic Biomarkers for Type 2 Diabetes.

BACKGROUND: Type 2 diabetes mellitus (T2D) is a common chronic disease, which lacks a specific diagnostic method. A substantial body of literature has demonstrated that the molecular constituents of extracellular vesicles (EVs) are promising as a novel biomarker for clinical diagnosis, especially exosomal miRNAs in biological fluids. METHODS: To find a diagnostic biomarker for T2D, we isolated exosomes from plasma and then quantitative PCR (qPCR) was used to detect the miRNA expression in plasma and exosomes from control subjects and T2D subjects. The ROC (receiver operating characteristic) curve and AUC (area under curve) were used to evaluate the diagnostic value of exosomal miRNAs. RESULTS: We found the exosomal levels of miR-23a and miR-192 were both significantly higher in T2D subjects. The AUC of miR-23a and miR-192 were 0.828 and 0.717, respectively. Further bioinformatics analysis was performed to speculate possible mechanisms. CONCLUSIONS: In conclusion, exosomal miR-23a and miR-192 have good potential as diagnostic biomarkers for type 2 diabetes.

Risk of reduced platelet counts in patients with nonalcoholic fatty liver disease (NAFLD): a prospective cohort study.

BACKGROUND: The production of peripheral platelet is mainly regulated by thrombopoietin, which is a glycoprotein hormone predominantly synthesized in the liver. Previously, many studies have reported that there was an inverse correlation between the degree of chronic viral hepatitis and the peripheral platelet count. However, the effect of nonalcoholic fatty liver disease (NAFLD) on the peripheral platelet counts remains unclear. METHODS: With 1303 participants from "The prevention of MS and multi-metabolic disorders in Jiangsu province of China (PMMJS)" cohort study, we investigated the associations between NAFLD and the risk of platelet counts reduction in Chinese adults. The paired-samples T test was used to explore the platelet counts changes between baseline and follow-up. Multivariate logistic regression was used to examine the association between presence of NAFLD and the risk of platelet reduction by calculating the odds ratios (ORs) and 95% confidence interval (CI). RESULTS: After five years of follow-up, platelet counts were markedly reduced from 220.6 ± 42.22 (109/L) at baseline to 208.41 ± 40.70 (109/L) at follow-up in NAFLD group (P < 0.0001). However, platelet counts were slightly lowered from 213.2 ± 43.26(109/L) at baseline to 211.8 ± 41.65 (109/L) at follow-up in non-NAFLD people (P = 0.2349). Meanwhile, there was a significant association between NAFLD and the risks of platelet count reduction, even after adjustment for confounding variables (OR: 1.68, 95% CI: 1.06-2.67). Additionally, among the participants with BMI ≤ 23 kg/m2 and SUA ≤ 344.3 µmol/L, the NAFLD participants have an increased risk of platelet count reduction compared to the persons in non-NAFLD group. CONCLUSIONS: Our present results suggested that NAFLD individuals have an increased risk of platelet counts reduction.

Application of 3D-PCASL combined with t-ASL and MRA in the diagnosis of patients with isolated vertigo induced by posterior circulation ischemia.

OBJECTIVES: Isolated vertigo induced by posterior circulation ischemia (PCIV) can further progress into posterior circulation infarction. This study aimed to explore the diagnostic values of three-dimensional pseudo-continuous arterial spin labeling (3D-PCASL) combined with territorial arterial spin labeling (t-ASL) and magnetic resonance angiography (MRA) in visualizing and evaluating PCIV, seeking improved diagnostic tools for clinical guidance. METHODS: 28 PCIVs (11 males, 17 females, aged from 55 to 83 years, mean age: 69.68 ± 9.01 years) and 28 healthy controls (HCs, 12 male, 16 female, aged from 56 to 87 years, mean age: 66.75 ± 9.86 years) underwent conventional magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), MRA, 3D-PCASL, and t-ASL. We compared the incidence of anatomic variants of the posterior circle of Willis in MRA, cerebral blood flow (CBF) and anterior collateral blood flow on postprocessing maps obtained from 3D-PCASL and t-ASL sequence between PCIVs and HCs. Chi-square test and paired t-test were analyzed statistically with SPSS 24.0 software. RESULTS: 7 PCIVs (7/28, 25%) and 6 HCs (6/28, 21%) showed fetal posterior cerebral artery (FPCA) on MRA, including 1 HC, and 6 PCIVs with FPCA appeared hypoperfusion. 18 PCIVs (64%) and 2 HCs (7%) showed hypoperfusion in the posterior circulation (PC), including 1 HC and 7 PCIVs displayed anterior circulation collateral flow. Chi-square analyses demonstrated a difference in PC hypoperfusion between PCIVs and HCs, whether in the whole or FPCA-positive group assessment (P < 0.05). Paired t-test showed that the CBF values were significant difference for the bilateral PC asymmetrical perfusion in the PCIVs (P < 0.01). When compared to the bilateral PC symmetrical non-hypoperfusion area in the PCIVs and HCs, the CBF values were not significant (P > 0.05). The CBF values of the PC in PCIVs were lower than in HCs (P < 0.05). The reduction rate in the hypoperfusion side of the bilateral PC asymmetrical perfusion of the PCIVs ranged from 4% to 37%, while the HCs reduction rate was 7.7%. The average PC symmetrical perfusion average reduction rate of the PCIVs was 52.25%, while the HCs reduction rate was 42.75%. CONCLUSION: 3D-PCASL is a non-invasive and susceptible method for detecting hypoperfusion in PC, serving as a potential biomarker of PCIV. The suspected hypoperfusion in PC may be attributed to the emergence of FPCA and the manifestation of anterior collateral flow when combining t-ASL and MRA sequences. These findings demonstrated that 3D-PCASL combined with t-ASL and MRA sequences are the potential method to identify PCIV, leading to early diagnosis of PCIV and reducing the risk of progressing into infarction.

Glutamine synthetase functions as a negative growth regulator in glioma.

Our recent study demonstrated that glutamine synthetase (GS) may not only serve as a glutamate-converting enzyme in glial cells, but may also function as a regulator of astrocyte migration after injury. In this report, we showed that GS expression increased in cultured rat C6 glioma cells that underwent long-term serially propagation. The stable overexpression of GS in C6 glioma cells resulted in growth arrest and motility suppression; however the stable knockdown of GS resulted in motility enhancement. In correlation with cell aggregation, N-cadherin levels increased at sites of cell-cell contact in C6 cells overexpressing GS, and decreased in C6 cells with stable GS knockdown; total N-cadherin expression levels remained unchanged in these cells. In addition, levels of p21, a potent cyclin-dependent kinase inhibitor, increased, while cyclin D1 levels decreased in C6 cells overexpressing GS. Our additional studies showed that N-cadherin-mediated cell-cell contacts were implicated in GS-induced cell growth arrest and impairment of cell migration, as evidenced by the inhibition of GS on cell growth and motility by the neutralizing anti-N-cadherin monoclonal antibody (GC-4 mAb). Collectively, these observations suggest a novel mechanism of growth regulation by GS that involves N-cadherin mediated cell-cell contact.

Association between total bilirubin and gender-specific incidence of fundus arteriosclerosis in a Chinese population: a retrospective cohort study.

To investigate the gender-specific relationship between total bilirubin (TBIL) and fundus arteriosclerosis in the general population, and to explore whether there is a dose-response relationship between them. In a retrospective cohort study, 27,477 participants were enrolled from 2006 to 2019. The TBIL was divided into four groups according to the quartile. The Cox proportional hazards model was used to estimate the HRs with 95% CIs of different TBIL level and fundus arteriosclerosis in men and women. The dose-response relationship between TBIL and fundus arteriosclerosis was estimated using restricted cubic splines method. In males, after adjusting for potential confounders, the Q2 to Q4 level of TBIL were significantly associated with the risk of fundus arteriosclerosis. The HRs with 95% CIs were 1.217 (1.095-1.354), 1.255 (1.128-1.396) and 1.396 (1.254-1.555), respectively. For females, TBIL level was not associated with the incidence of fundus arteriosclerosis. In addition, a linear relationship between TBIL and fundus arteriosclerosis in both genders (P < 0.0001 and P = 0.0047, respectively). In conclusion, the incidence of fundus arteriosclerosis is positively correlated with serum TBIL level in males, but not in females. In addition, there was a linear dose-response relationship between TBIL and incidence of fundus arteriosclerosis.

Sex-specific association of serum uric acid trajectories with risk of incident retinal arteriosclerosis in Chinese population: A population-based longitudinal study.

Background: The impact of serum uric acid (SUA) trajectories on the development of retinal arteriosclerosis is uncertain. The purpose of this study was to identify adult SUA trajectories by sex and determine their association with risk of retinal arteriosclerosis. Methods: In this longitudinal study, 4,324 participants who were aged between 18 and 60 years without retinal arteriosclerosis at or before baseline (from January 1, 2010, through December 31, 2010) were included. Group-based trajectory modeling was used to identify SUA trajectories during the exposure period (from January 1, 2006, through December 31, 2010). Cox proportional-hazards models were applied to evaluate the associations between SUA trajectories and the risk of incident retinal arteriosclerosis during the outcome period (from January 1, 2011, through December 31, 2019). Results: 4 distinct SUA trajectories were identified in both women and men: low, moderate, moderate-high, and high. During a median follow-up of 9.54 years (IQR 9.53-9.56), 97 women and 295 men had developed retinal arteriosclerosis. In the fully adjusted model, a significant association between the moderate-high SUA trajectory group and incidence of retinal arteriosclerosis was observed only in men (HR: 1.76, 95% CI: 1.17-2.65) compared with the low trajectory group, but not in women (HR: 0.77, 95% CI: 0.39-1.52). Also, the high SUA trajectory group had the highest risk with an adjusted HR of 1.81 (95% CI, 1.04-3.17) in men. However, they did not exhibit a substantially increased risk in women. Conclusion: Higher SUA trajectory groups were significantly associated with an increased risk of incident retinal arteriosclerosis in men but not in women.

Sex-specific association between carotid atherosclerosis and fundus arteriosclerosis in a Chinese population: a retrospective cross-sectional study.

OBJECTIVES: Vascular stiffening is highly predictive of major adverse cardiovascular events. It is not clear whether microangiopathy, such as fundus arteriosclerosis, is related to carotid atherosclerosis. Hence, this study was designed to investigate the relationship between carotid atherosclerosis and fundus arteriosclerosis among individuals of different sexes in the Chinese health-examination population. METHODS: This retrospective cross-sectional study involved 20,836 participants, including 13050 males and 7786 females. All participants underwent a detailed health examination, including medical history assessment, physical examination, assessment of lifestyle factors, fundus photography, Doppler ultrasound examination of the neck, and laboratory examinations. Two trained ophthalmologists analysed fundus arteriosclerosis based on fundus photographs, while carotid atherosclerosis was diagnosed using colour Doppler sonography of the neck. Binary logistic regression was used to analyse the relationship between carotid atherosclerosis and fundus arteriosclerosis. RESULTS: In participants with fundus arteriosclerosis, the incidence of carotid atherosclerosis was higher than that of participants without fundus arteriosclerosis (52.94% vs. 47.06%). After adjustments for potential confounding factors, fundus arteriosclerosis was significantly associated with the risk of carotid atherosclerosis. The OR with 95% CI for fundus arteriosclerosis was 1.17 (1.02, 1.34) with p = 0.0262, and individuals who did not have fundus arteriosclerosis were used as a reference in the total population. Fundus arteriosclerosis was associated with the incidence of carotid atherosclerosis in males (p = 0.0005) but not in females (p = 0.0746). CONCLUSIONS: Fundus arteriosclerosis was closely associated with carotid atherosclerosis in the Chinese population. This association was found in males but not in females.

[Prevalence of diabetes mellitus and impaired fasting glucose of health check-up in a sanatorium of Shanghai in 2003 and 2010].

OBJECTIVE: To examine the prevalence changes of diabetes mellitus (DM) and impaired fasting glucose (IFG) from 2003 to 2010 in the health check-up subjects in Shanghai. METHODS: Health check-up subjects were divided into ten groups by sex and each 5 years old, and the prevalence of crude DM, crude IFG were calculated first. According to Chinese sex and age structure of China Population Statistics Yearbook 2006, sex and age standardized DM and standardized IFG were computed. RESULTS: In the same year, the prevalences of crude DM and IFG increased with increasing age for both male and female, reached the summit at 60 - 69 age group, when at ≥ 70 age group, they had a down trend and were still at higher level. The prevalences of crude DM were 3.99% (986/24 699) in male and 1.61% (176/10 948) in female in 2003, and were 7.85% (3366/42 899) and 2.55% (531/20 820) in 2010. The prevalences of crude IFG were 9.97% (2462/24 699) in male and 5.88% (644/10 948) in female in 2003, and were 30.96% (13 283/42 899) and 17.16% (3573/20 820) in 2010. The prevalences of age standardized DM in 2003 and 2010 were 3.89% and 6.90% for male (χ(2) = 371.89, P < 0.01), 2.12% and 3.23% for female (χ(2) = 29.32, P < 0.01), respectively. The prevalences of age standardized IFG in 2003 and 2010 were 9.51% and 28.55% (χ(2) = 3865.56, P < 0.01) for male, 6.97% and 17.88% (χ(2) = 790.81, P < 0.01) for female. The prevalences of age and sex standardized DM were 3.00% and 5.05% (χ(2) = 385.39, P < 0.01), and prevalences of age and sex standardized IFG were 8.23% and 23.17% (χ(2) = 4480.21, P < 0.01). CONCLUSION: From 2003 to 2010, prevalences of DM and IFG had increased greatly. It concluded that first-level prevention of DM for health check-up subjects should start from youth, and should lay emphasis on population of IFG, especially for male.

Gender-Specific Association between Serum Uric Acid and Incident Fundus Arteriosclerosis in Chinese Population: A Retrospective Cross-Sectional Study.

Elevated levels of serum uric acid (SUA) were considered to be risk factors for cardiovascular disease, it has been found to be associated with increased arteriosclerosis. The aim of this study was to explore the gender specific relationship between SUA and fundus arteriosclerosis in a healthy population. In a retrospective cross-sectional study, 23474 individuals without diabetes and hypertension were included in the present study. SUA levels were cut to four groups as Q1 to Q4, according to the quartiles. The odds ratio and 95% confidence interval of different SUA levels were estimated by a binomial logistic regression model. A restrictive cubic spline method was used to estimate the dose-response relationship between SUA and fundus arteriosclerosis. Subgroup analysis was performed to find the gender-specific association between SUA and incident fundus arteriosclerosis. In males, after adjusting for confounding factors, the highest SUA level was significantly associated with the risk of incident fundus arteriosclerosis. The OR with 95%CI for Q4 was 1.44(1.18, 1.76), Q1 as a reference. Specially, for females, SUA level was not associated with the incidence of fundus arteriosclerosis. In conclusion, elevated levels of SUA were associated with the incidence of fundus arteriosclerosis in males, but not in females.

Factors influencing uptake of pre-exposure prophylaxis: some qualitative insights from an intervention study of men who have sex with men in China.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is a biomedical approach for preventing the acquisition of HIV in populations at substantial risk for HIV. However, its uptake among men who have sex with men (MSM) is low in China. The study aimed to identify factors that might influence MSM's uptake and use of PrEP. METHODS: In-depth interviews were conducted with 32 self-identified MSM from a PrEP intervention study evaluating daily oral tenofovir disoproxil fumarate (TDF) to prevent HIV infection. Of these men, 11 were presently using the 'TDF' group; 8 from the 'change-over' group (i.e. initially used PrEP but subsequently quitted); and 13 from the non-user group. Data were analysed using thematic approach. RESULTS: Perception of low HIV risk, mistrust of the national PrEP program, and concerns of side effects were the main reasons for not wanting to use PrEP. Also, lack of main sexual partner's support, difficulties in adhering to the daily TDF regimen, and the inconvenient schedules in securing the medicine were the major reasons for not wanting to use or quitting the use of PrEP. On the other hand, perceived high HIV risk, beliefs in efficacy of PrEP, and worries of transmitting HIV to families were the major motives for PrEP uptake. CONCLUSIONS: Findings suggest that PrEP implementation strategies should first address issues including but not limited to accurate self-assessment of HIV risk, mistrust and limited knowledge about medical trials and PrEP, and ease of accessing PrEP.

Associations between fatty liver index and asymptomatic intracranial vertebrobasilar stenosis in Chinese population.

Metabolic diseases such as type 2 diabetes mellitus (T2DM) and metabolic syndromes (MetS) have been recognized as the important risk factors for asymptomatic intracranial vertebrobasilar stenosis (IVBS). Although fatty liver index (FLI) is significantly related with these diseases, the association between FLI and IVBS remains unclear. In the present study, 2368 participants (30-75 years) were recruited from a Chinese prospective cohort study of PMMJS. Amongst them, 2281 individuals who did not have IVBS at baseline were enrolled in the 6-year following-up study. In cross-sectional analysis based on the baseline characteristics, the results showed that FLI was positively related with IVBS prevalence. Compared to the participants with FLI < 30, the adjusted OR (95% CI) of IVBS was 2.07 (1.18, 3.62) and 2.85 (1.39, 5.18) in the groups of 30 ≤ FLI < 60 and FLI ≥ 60, respectively. In longitudinal analysis, the results showed that the participants with FLI ≥ 60 had an increased risk of asymptomatic IVBS compared to those with FLI < 30 [adjusted HR (95%CI): 1.65 (1.05, 2.60)]. Moreover, exclusion of persons with hypertension, T2DM and MetS did not alter the associations between FLI and asymptomatic IVBS. Therefore, our results suggest that elevated FLI is an independent risk factor for asymptomatic IVBS in Chinese adults.

Associations between Serum Uric Acid and the Remission of Non-Alcoholic Fatty Liver Disease in Chinese Males.

Epidemiological studies suggest that higher serum uric acid (sUA) level is significantly associated with nonalcoholic fatty liver disease (NAFLD) development. However, little information is available on the relationships between sUA and NAFLD remission. In the present study, 841 NAFLD males (30-75 years) were recruited from a Chinese prospective cohort study (PMMJS) and followed up for five years. The baseline sUA levels of participants were categorized into four quartiles: 191 µmol/L≤ sUA ≤ 347 µmol/L, 347 µmol/L < sUA ≤ 392 µmol/L, 392 µmol/L < sUA ≤ 441 µmol/L and 441 µmol/L

MDC and BLC are independently associated with the significant risk of early stage lung adenocarcinoma.

BACKGROUND: This prospective study was designed to investigate the association between ten circulating inflammatory biomarkers and the risk for early stage lung adenocarcinoma. METHODS: All inflammatory biomarkers were measured in 228 patients with early stage (IA to IIB) lung adenocarcinoma and 228 age-, sex- and smoking-matched healthy controls by using the Luminex bead-based assay. RESULTS: Only two biomarkers were significantly associated with the risk of early stage lung adenocarcinoma after the Bonferroni correction: the multivariate odd ratio (OR) (95% confidence interval or CI) was 0.29 (0.16-0.53) for MDC and 4.17 (2.23-7.79) for BLC for the comparison of patients in the 4th quartile with the 1st quartile (both P<0.0001). When analysis was restricted to never smokers (196 patients/196 controls), MDC and BLC were still significantly associated with the risk of early stage lung adenocarcinoma (OR, 95% CI, P: 0.37, 0.21-0.66, P<0.0001 for MDC and 2.78, 1.48-5.22, P =0.001 for BLC). Furthermore, elevated BLC was associated with a 2.90-fold (95% CI: 1.03-8.17, P=0.037) increased risk of subcentimeter lung adenocarcinoma, and there was an increasing trend for BLC with the progression of subcentimeter lung adenocarcinoma. CONCLUSION: Our findings demonstrated that MDC and BLC were independently associated with the significant risk of early stage lung adenocarcinoma, even in non-smokers and in stage IA patients. BLC was further identified to play a carcinogenic role in the progression of lung adenocarcinoma.

Temporospatial expression and cellular localization of glutamine synthetase following traumatic spinal cord injury in adult rats.

Glutamine synthetase (GS) is an enzyme involved in an endogenous mechanism of protection against glutamate neurotoxicity and is important in the regulation of astrocyte migration. To date, limited information is available concerning the expression of GS in normal spinal cords and following injury. In the present study, GS expression was identified in astrocytes, oligodendrocytes and microglia in normal rat spinal cords. Following traumatic spinal cord injury (SCI), the glutamate concentration increased rapidly at 1 h and returned to baseline rapidly. However, the GS activity and protein levels were found to decrease at 4 h and then increase gradually from day 3 following SCI. The quantification of astrocytes, oligodendrocytes and activated microglia/macrophages, as well as immunohistochemistry staining of day 7 post­injured spinal cords, indicated that the astrocytes and microglia/macrophages contributed to the increase in GS. Collectively, the results provided evidence for the temporospatial expression and location of GS following SCI and suggested that the changes in GS levels may contribute to glutamate neurotoxicity and glial cell response following SCI.

Hepatitis B virus status and risk of pancreatic ductal adenocarcinoma: a case-control study from China.

OBJECTIVES: This study was to assess the role of hepatitis B virus (HBV) infection in pancreatic ductal adenocarcinoma (PDAC) risk using a hospital-based case-control design. METHODS: Patients with pathologically confirmed PDAC (943) and 1128 matched controls were recruited from 2 hospitals. We evaluated the associations between risk of PDAC and age, sex, history of diabetes mellitus (DM), etc. In addition, we examined the interactive effects of HBV status and known risk factors for pancreatic cancer. RESULTS: Chronic hepatitis B and inactive hepatitis B surface antigen (HBsAg) carrier state (HBsAg positive) had a significantly increased risk of pancreatic cancer, with an adjusted odds ratio of 1.60 (95% confidence interval [CI], 1.15-2.24). Furthermore, significant interactions were detected between a history of DM and chronic hepatitis B and inactive HBsAg positive, but not with antibodies to hepatitis B core antigen (anti-HBc) positive/antibodies to HBsAg (anti-HBs) negative, with an adjusted odds ratio of 5.42 (95% CI, 2.76-10.64), compared with those who were HBsAg negative/anti-HBc negative without a history of DM. CONCLUSIONS: These results suggest that HBsAg-positive or anti-HBc-positive/anti-HBs-negative patients have an increased risk for PDAC independent of other risk factors. Significant interactions were found between a history of DM and chronic HBV infection for PDAC risk.