Statin use and the risk of CVD events, stroke, and all-cause mortality in patients with diabetes: A systematic review and meta-analysis.

AIMS: Considering the lack of evidence on statin use and the risk of cardiovascular disease (CVD) in patients with diabetes in primary and secondary prevention, this study aimed to evaluate the effect of statin use in individuals with diabetes for primary and secondary prevention. DATA SYNTHESIS: The MEDLINE, Web of Science, Embase, ClinicalTrials.gov, and Cochrane Central Register for Controlled Trials databases were searched. We included studies that assessed the effect of statin use in individuals with diabetes for at least 1 year. The outcomes included CVD, all-cause mortality, and stroke. A total of 24 studies including 2,152,137 patients with diabetes were included in the meta-analysis. Compared with statin non-users, patients who received statins showed a lower risk of CVD events (primary prevention: risk ratio [RR] = 0.80, 95% confidence interval [CI] 0.69-0.94, P = 0.006; secondary prevention: RR = 0.75, 95% CI 0.65-0.87, P < 0.0001). No association was observed between statin and non-statin users and the risk of all-cause mortality. The pooled results also revealed that statin use reduced the risk of ischemic stroke in patients with diabetes (primary prevention: RR = 0.83, 95% CI 0.70-0.97, P = 0.020; secondary prevention: RR = 0.74, 95% CI 0.63-0.85, P < 0.0001). CONCLUSIONS: Statin use significantly reduced the risk of CVD events and stroke, but not all-cause mortality, in individuals with diabetes undergoing both primary and secondary prevention. More data are required to verify the effects of statins in patients with diabetes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021281132.

TRUSS Exacerbates NAFLD Development by Promoting IκBα Degradation in Mice.

There is no effective treatment method for nonalcoholic fatty liver disease (NAFLD), the most common liver disease. The exact mechanism underlying the pathogenesis of NAFLD remains to be elucidated. Here, we report that tumor necrosis factor receptor-associated ubiquitous scaffolding and signaling protein (TRUSS) acts as a positive regulator of NAFLD and in a variety of metabolic disorders. TRUSS expression was increased in the human liver specimens with NAFLD or nonalcoholic steatohepatitis, and in the livers of high-fat diet (HFD)-induced and genetically obese mice. Conditional knockout of TRUSS in hepatocytes significantly ameliorated hepatic steatosis, insulin resistance, glucose intolerance, and inflammatory responses in mice after HFD challenge or in spontaneous obese mice with normal chow feeding. All of these HFD-induced pathological phenotypes were exacerbated in mice overexpressing TRUSS in hepatocytes. We show that TRUSS physically interacts with the inhibitor of nuclear factor κB α (IκBα) and promotes the ubiquitination and degradation of IκBα, which leads to aberrant activation of nuclear factor κB (NF-κB). Overexpressing IκBαS32A/S36A , a phosphorylation-resistant mutant of IκBα, in the hepatocyte-specific TRUSS overexpressing mice almost abolished HFD-induced NAFLD and metabolic disorders. Conclusion: Hepatocyte TRUSS promotes pathological stimuli-induced NAFLD and metabolic disorders, through activation of NF-κB by promoting ubiquitination and degradation of IκBα. Our findings may provide a strategy for the prevention and treatment of NAFLD by targeting TRUSS.

Highly efficient generation of 0.2 mJ terahertz pulses in lithium niobate at room temperature with sub-50 fs chirped Ti:sapphire laser pulses.

We demonstrate generation of 0.2 mJ terahertz (THz) pulses in lithium niobate driven by Ti:sapphire laser pulses at room temperature. Employing tilted pulse front technique, the 800 nm-to-THz energy conversion efficiency has been optimized to 0.3% through chirping the sub-50 fs pump laser pulses to overcome multi-photon absorption and to extend effective interaction length for phase matching. Our approach paves the way for mJ-level THz generation via optical rectification using existing Ti:sapphire laser systems which can deliver Joule-level pulse energy with sub-50 fs pulse duration.

[Serum homocysteine and metabolic syndrome in middle-aged and elderly men].

OBJECTIVE: To investigate the relationship among serum reproductive hormone levels, serum homocysteine (Hcy) levels, metabolic syndrome (MS), and the components of MS in middle-aged and elderly males. METHODS: Using the cluster and stratified sampling methods and a unified structured questionnaire, we conducted a survey among 948 men aged 40 - 80 years in the rural community, measured their basic physical parameters, and obtained their reproductive hormone levels, serum Hcy concentrations, and metabolism-related indicators. We collected 868 valid questionnaires along with their serum samples, divided the subjects into an MS and a non-MS control group in a 1:1 ratio, and measured their serum Hcy concentrations. RESULTS: Among the subjects included, 132 were diagnosed with MS. Nonparametric tests showed statistically significant differences between the MS and non-MS groups in the waist circumference (WC), waist-hip ratio (WHR), body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP) (P < 0.05), but not in age (P > 0.05). Significant differences were also observed between the two groups in the levels of serum tT, SHBG, LH, and FTI (P < 0.05) , but not in the concentrations of serum Hcy (P > 0.05). The concentration of serum Hcy exhibited no correlation with BMI, SBP, DBP, FBG, TG, and HDL-C (P > 0.05) and had no influence on MS. CONCLUSION: The concentration of serum Hcy is not significantly correlated with MS, nor with its components. The levels of male serum reproductive hormones are associated both with MS and with its components.

Severe emphysematous pyelonephritis mimicking intestinal obstruction.

Emphysematous pyelonephritis is a severe necrotizing infection characterized by the presence of gas and/or fluid in the renal parenchyma, collecting system, or perirenal tissues. Emphysematous pyelonephritis with approximately 15 cm air-fluid level, diffused ureteral involvement, and the accumulation of gas in liver and peritoneal cavity is very rare. Here, we reported a severe emphysematous pyelonephritis with multiple huge air-fluid level mimicking intestinal obstruction and with the accumulation of gas in liver and ureter in computed tomography imaging. The patient was successfully managed by percutaneous nephrostomy combined with medical treatment.

Characterization and expression analysis of peroxiredoxin family genes from the silkworm Bombyx mori in response to phoxim and chlorpyrifos.

The organophosphorus pesticide poisoning of the silkworm Bombyx mori is one of the major events causing serious damage to sericulture. Some antioxidant enzymes play roles in regulating generation of reactive oxygen species (ROS) by pesticides including phoxim and chlorpyrifos, but relatively little is known about their effects on the silkworm peroxiredoxin family genes. Here, five peroxiredoxin (Prx) genes have been identified in silkworm genome, and Prx genes of silkworm and mammalian homologs have apparent ortholog relationship. Based on the genomic DNA sequence, putative 5'-flanking region of five BmPrxs were obtained and the transcription factor binding sites were predicted. Their expression profiles exposed to different concentrations of phoxim and chlorpyrifos for 24 h, 48 h and 72 h in midgut of silkworm were investigated using quantitative RT-PCR (qRT-PCR). The results showed that five BmPrxs and dual oxidase (BmDUOX) gene were all expressed in midgut of silkworm. After feeding with 0.375 mg/L and 0.75 mg/L phoxim, the transcription levels of BmPrx3 and BmPrx5 that can be located in mitochondria reached their peak levels at an early time point (24h). However, the transcription levels of BmPrx4 and BmPrx6 that can be addressed to secrete from the cell and cytosol, respectively, reached their peak levels at a later time point (72 h). Similar to expose to phoxim, the transcription levels of BmPrx3 and BmPrx5 that can be located in mitochondria reached their peak levels at an early time point (24 h) under chlorpyrifos stress. However, the transcription levels of BmPrx4 and BmPrx6 that can be addressed to secrete from the cell and cytosol, respectively, reached their peak levels at a later time point (72 h) under chlorpyrifos stress. These results revealed that BmPrxs that can be located in mitochondria were able to protect cells even more efficiently than cytosolic from an oxidative stress caused by OP. In addition, BmDUOX was also induced by phomix and chlorpyrifos. Overall, our results indicate that a complex expression regulation of Prxs that play important roles in maintaining redox equilibrium state of silkworm to reduce oxidative damage caused by pesticide.

Febuxostat provides renoprotection in patients with hyperuricemia or gout: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: It is unknown whether febuxostat can delay the progression of kidney dysfunction and reduce kidney endpoint events. The aim was to evaluate the renoprotective effect of febuxostat in patients with hyperuricemia or gout by performing a meta-analysis of randomized controlled trials (RCTs). METHODS: MEDLINE, Web of science, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register for Randomized Controlled Trials were searched. The main outcomes included kidney events (serum creatinine doubling or progression to end-stage kidney disease or dialysis). The secondary outcomes were the rate of change in the estimated glomerular filtration rate (eGFR) and changes in the urine protein or urine albumin to creatinine ratio from baseline to the end of follow-up. We used random-effects models to calculate the pooled risk estimates and 95% CIs. RESULTS: A total of 16 RCTs were included in the meta-analysis. In comparison with the control group, the patients who received febuxostat showed a reduced risk of kidney events (RR = 0.56, 95% CI 0.37-0.84, p = 0.006) and a slower decline in eGFR (WMD = 0.90 mL/min/1.73 m2, 95% CI 0.31-1.48, p = 0.003). The pooled results also revealed that febuxostat use reduced the urine albumin to creatinine ratio (SMD = -0.21, 95% CI -0.41 to -0.01, p = 0.042). CONCLUSION: Febuxostat use is associated with a reduced risk of kidney events and a slow decline in eGFR. In addition, the urine albumin to creatinine ratio decreased in febuxostat users. Accordingly, it is an effective drug for delaying the progression of kidney function deterioration in patients with gout.Systematic review registration: PROSPERO CRD42021272591.

Association of remnant cholesterol with risk of cardiovascular disease events, stroke, and mortality: A systemic review and meta-analysis.

BACKGROUND AND AIMS: Lipid disorders are associated with the risk of cardiovascular diseases (CVDs). Remnant cholesterol (RC), a non-traditional previously neglected risk factor for CVD, has received much attention in recent years. The aim of this study is to evaluate the association of RC with the risks of CVD, stroke, and mortality. METHODS: MEDLINE, Web of Science, EMBASE, ClinicalTrials.gov, and Cochrane Central Register for Controlled Trials were searched. We included randomized controlled trials (RCTs), non-RCTs, and observational cohort studies assessing the association of RC with the risks of cardiovascular (CV) events, coronary heart disease (CHD), stroke, and mortality. RESULTS: Overall, 31 studies were included in this meta-analysis. Compared with low RC, elevated RC was associated with an increased risk of CVD, CHD, stroke, CVD mortality, and all-cause mortality (RR = 1.53, 95% CI 1.41-1.66; RR = 1.41, 95% CI 1.19-1.67; RR = 1.43, 95% CI 1.24-1.66; RR = 1.83, 95% CI 1.53-2.19; and RR = 1.39, 95% CI 1.27-1.50; respectively). A subgroup analysis demonstrated that each 1.0 mmol/L increase in RC was associated with an increased risk of CVD events and CHD. The association of RC with an increased CVD risk was not dependent on the presence or absence of diabetes, a fasted or non-fasted state, total cholesterol, or triglyceride or ApoB stratification. CONCLUSIONS: Elevated RC is associated with an increased risk of CVD, stroke, and mortality. In addition to the traditional cardiovascular risk factors, such as total cholesterol and LDL-C, clinicians should also pay attention to RC in clinics.

Association of the Coexistence of Somnipathy and Diabetes With the Risks of Cardiovascular Disease Events, Stroke, and All-Cause Mortality: A Systematic Review and Meta-analysis.

Background Somnipathy and diabetes are independently associated with an increased risk of cardiovascular disease (CVD). However, whether a combination of both conditions is associated with a higher risk of CVD events remains uncertain. Therefore, the aim of this meta-analysis was to clarify this association. Methods and Results We searched MEDLINE, Web of Science, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register for Controlled Trials. We included randomized controlled trials, nonrandomized trials, and prospective observational cohort studies that assessed the combined effect of diabetes and comorbid somnipathy on CVD risk and mortality for at least 1 year. Outcomes included CVD, coronary heart disease, stroke, and all-cause mortality. Twelve studies involving 582 267 participants were included in the meta-analysis. Patients with somnipathy and comorbid diabetes exhibited increased risks of CVD, coronary heart disease, stroke, and all-cause mortality (risk ratio [RR], 1.27 [95% CI, 1.12-1.45], P<0.0001; RR, 1.40 [95% CI, 1.21-1.62], P<0.0001; RR, 1.28 [95% CI, 1.08-1.52], P=0.004, and RR, 1.56 [95% CI, 1.26-1.94], P<0.0001, respectively). Conclusions The coexistence of somnipathy and diabetes is associated with higher risks of CVD, coronary heart disease, stroke, and mortality than somnipathy or diabetes alone. Resolving sleep problems in patients with diabetes may reduce the risks of CVD, stroke, and mortality. Registration Information https://www.crd.york.ac.uk/prospero/. Identifier: PROSPERO CRD42021274566.

Identification of differentially expressed genes in diabetic kidney disease by RNA-Seq analysis of venous blood platelets.

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. However, because of shared complications between DKD and chronic kidney disease (CKD), the description and characterization of DKD remain ambiguous in the clinic, hindering the diagnosis and treatment of early-stage DKD patients. Although estimated glomerular filtration rate and albuminuria are well-established biomarkers of DKD, early-stage DKD is rarely accompanied by a high estimated glomerular filtration rate, and thus there is a need for new sensitive biomarkers. Transcriptome profiling of kidney tissue has been reported previously, although RNA sequencing (RNA-Seq) analysis of the venous blood platelets in DKD patients has not yet been described. In the present study, we performed RNA-Seq analysis of venous blood platelets from three patients with CKD, five patients with DKD and 10 healthy controls, and compared the results with a CKD-related microarray dataset. In total, 2097 genes with differential transcript levels were identified in platelets of DKD patients and healthy controls, and 462 genes with differential transcript levels were identified in platelets of DKD patients and CKD patients. Through Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, we selected 11 pathways, from which nine potential biomarkers (IL-1B, CD-38, CSF1R, PPARG, NR1H3, DDO, HDC, DPYS and CAD) were identified. Furthermore, by comparing the RNA-Seq results with the GSE30566 dataset, we found that the biomarker KCND3 was the only up-regulated gene in DKD patients. These biomarkers may have potential application for the therapy and diagnosis of DKD, as well aid in determining the mechanisms underlying DKD.

Febuxostat Use and Risks of Cardiovascular Disease Events, Cardiac Death, and All-cause Mortality: Metaanalysis of Randomized Controlled Trials.

OBJECTIVE: To assess whether febuxostat use increases the risk of developing cardiovascular (CV) events, cardiac death, and all-cause mortalities. METHODS: The relevant literature was searched in several databases including MEDLINE (PubMed, January 1, 1966-February 29, 2020), Web of Science, EMBASE (January 1, 1974-February 29, 2020), ClinicalTrials. gov, and Cochrane Central Register of Controlled Trials. Manual searches for references cited in the original studies and relevant review articles were also performed. All studies included in this metaanalysis were published in English. RESULTS: In the end, 20 studies that met our inclusion criteria were included in our metaanalysis. Use of febuxostat was found not to be associated with an increased risk of all-cause mortality (RR 0.87, 95% CI 0.57-1.32, P = 0.51). Also, there was no association between febuxostat use and mortalities arising from CV diseases (CVD; RR 0.84, 95% CI 0.49-1.45, P = 0.53). The RR also revealed that febuxostat use was not associated with CVD events (RR 0.98, 95% CI 0.83-1.16, P = 0.83). Further, the likelihood of occurrence of CVD events was found not to be dependent on febuxostat dose (RR 1.04, 95% CI 0.84-1.30, P = 0.72). CONCLUSION: Febuxostat use is not associated with increased risks of all-cause mortality, death from CVD, or CVD events. Accordingly, it is a safe drug for the treatment of gout.

Cholesterol Stimulates the Transient Receptor Potential Melastatin 4 Channel in mpkCCDc14 Cells.

We have shown that cholesterol regulates the activity of ion channels in mouse cortical collecting duct (CCD) mpkCCDc14 cells and that the transient receptor potential melastatin 4 (TRPM4) channel is expressed in these cells. However, whether TRPM4 channel is regulated by cholesterol remains unclear. Here, we performed inside-out patch-clamp experiments and found that inhibition of cholesterol biosynthesis by lovastatin significantly decreased, whereas enrichment of cholesterol with exogenous cholesterol significantly increased, TRPM4 channel open probability (Po) by regulating its sensitivity to Ca2+ in mpkCCDc14 cells. In addition, inside-out patch-clamp data show that acute depletion of cholesterol in the membrane inner leaflet by methyl-ß-cyclodextrin (MßCD) significantly reduced TRPM4 Po, which was reversed by exogenous cholesterol. Moreover, immunofluorescence microscopy, Western blot, cell-surface biotinylation, and patch clamp analysis show that neither inhibition of intracellular cholesterol biosynthesis with lovastatin nor application of exogenous cholesterol had effect on TRPM4 channel protein abundance in the plasma membrane of mpkCCDc14 cells. Sucrose density gradient centrifugation studies demonstrate that TRPM4 was mainly located in cholesterol-rich lipid rafts. Lipid-protein overlay experiments show that TRPM4 directly interacted with several anionic phospholipids, including PI(4,5)P2. Depletion of PI(4,5)P2 with either wortmannin or PGE2 abrogated the stimulatory effects of exogenous cholesterol on TRPM4 activity, whereas exogenous PI(4,5)P2 (diC8-PI(4,5)P2, a water-soluble analog) increased the effects. These results suggest that cholesterol stimulates TRPM4 via a PI(4,5)P2-dependent mechanism.

Endothelial epithelial sodium channel involves in high-fat diet-induced atherosclerosis in low-density lipoprotein receptor-deficient mice.

We previously showed that increased epithelial sodium channel (ENaC) activity in endothelial cells induced by oxidized low-density lipoprotein (ox-LDL) contributes to vasculature dysfunction. Here, we investigated whether ENaC participates in the pathological process of atherosclerosis using LDL receptor-deficient (LDLr-/-) mice. Male C57BL/6 and LDLr-/- mice were fed a normal diet (ND) or high fat diet (HFD) for 10 weeks. Our data show that treatment of LDLr-/- mice with a specific ENaC blocker, benzamil, significantly decreased atherosclerotic lesion formation and expression of matrix metalloproteinase 2 (MMP2) and metalloproteinase 9 (MMP9) in aortic arteries. Furthermore, benzamil ameliorated HFD-induced impairment of aortic endothelium-dependent dilation by reducing expression of proinflammatory cytokines, including TNF-α, IL-1ß, and IL-6 and production of adhesion molecules including VCAM-1 and ICAM-1 in both C57BL/6 and LDLr-/- mice fed with HFD. In addition, HFD significantly increased ENaC activity and the levels of serum lipids, including ox-LDL. Our in vitro data further demonstrated that exogenous ox-LDL significantly increased the production of TNF-α, IL-1ß, IL-6, VCAM-1 and ICAM-1. This ox-LDL-induced increase in inflammatory cytokines and adhesion molecules was reversed by γ-ENaC silencing or by treatment with the cyclooxygenase-2 (COX-2) antagonist celecoxib. Benzamil inhibited HFD-induced increase in COX-2 expression in aortic tissue in both C57BL/6 and LDLr-/- mice, and γ-ENaC gene silencing attenuated ox-LDL-induced COX-2 expression in HUVECs. These data together suggest that HFD-induced activation of ENaC stimulates inflammatory signaling, thereby contributes to HFD-induced endothelial dysfunction and atherosclerotic lesion formation. Thus, targeting endothelial ENaC may be a promising strategy to halt atherogenesis.

EGCG Attenuates Renal Damage via Reversing Klotho Hypermethylation in Diabetic db/db Mice and HK-2 Cells.

To explore whether epigallocatechin-3-gallate (EGCG) improves renal damage in diabetic db/db mice and high-glucose- (HG-) induced injury in HK-2 cells by regulating the level of Klotho gene promoter methylation. Western blotting was used to detect the protein expression levels of DNA methyltransferase 1 (DNMT1), DNMT3a, DNMT3b, transforming growth factor-ß1 (TGF-ß1), α-smooth muscle actin (α-SMA), and Klotho. The methylation level of the Klotho gene promoter was detected by pyrosequencing. Chromatin immunoprecipitation was used to detect the binding of the Klotho gene promoter to DNMT1 and DNMT3a. The expression of oxidative stress markers (reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), and 8-hydroxy-2'-deoxyguanosine (8-OHdG)) and inflammatory cytokines (interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α)) in kidney homogenates was also measured using ELISA. Klotho and DNMT3b protein expression was upregulated, while DNMT1, DNMT3a, TGF-ß1, and α-SMA protein expression was downregulated after EGCG treatment. EGCG treatment also reduced the methylation level of the Klotho gene promoter as well as the binding of DNMT3a to the Klotho gene promoter. In addition, EGCG treatment significantly decreased the levels of ROS, MDA, 8-OHdG, IL-1ß, IL-6, and TNF-α and increased the levels of CAT and SOD. Under HG conditions, EGCG regulated Klotho gene promoter methylation via DNMT3a and decreased the methylation level of the Klotho gene promoter, thereby upregulating the expression of the Klotho protein to exert its protective effect.

The Epidemiological Characteristics of Late-Onset Hypogonadism in Chinese Middle-Aged and Elderly Men: Two Cross-Sectional Studies in the Same Community.

The purpose of this study was to investigate the prevalence and epidemiological characteristics of late-onset hypogonadism (LOH) in middle-aged and elderly Chinese men. Two cross-sectional studies were conducted at 5-year intervals in community-dwelling men living in the same area. A total of 1472 (Study 1, S1) and 944 (Study 2, S2) men aged 40-69 years old were recruited as subjects. Subjects were evaluated through combining serum reproductive hormone levels with the Androgen Deficiency in Aging Males (ADAM) questionnaire and the Aging Males' Symptoms (AMS) scale. A significant difference was found in mean testosterone deficiency (TD) prevalence between S1 and S2, using either serum total testosterone (TT; 14.02% vs. 6.36%) or serum calculated free testosterone (cFT; 43.69% vs. 16.53%) cutoff values. According to the S1 or S2 data, the mean prevalence of LOH was 37.85%/15.47% in the positive ADAM test and 15.42%/9.43% in the positive AMS test (p < .01). According to classifications of TD based on gonadal status, the prevalence of secondary TD (27.34%) was higher than the primary (16.36%) and compensated (15.42%) TD in S1 (p < .01). However, there were significant differences among the prevalence of primary (6.89%), secondary (9.64%), and compensated (27.65%) TD in S2 (p < .05). Different types of testosterone levels, TD cutoff values, and questionnaires influenced the prevalence of TD and LOH. The serum FT cutoff value was an optimal threshold for evaluating and diagnosing TD and LOH, whose prevalence increased gradually with male aging.

Age-related changes in serum reproductive hormone levels and prevalence of androgen deficiency in Chinese community-dwelling middle-aged and aging men: Two cross-sectional studies in the same population.

To investigate the age-related nomograms and change trends of reproductive hormones, and prevalence of androgen deficiency (AD) in middle-aged and aging men from 2 studies.Two cross-sectional studies were conducted at 5-year intervals in Chinese community-dwelling men living in the same area. A total of 434 (Study 1, S1) and 944 (Study 2, S2) men aged 40 to 69 years were recruited as subjects and 59 (S1) and 98 (S2) men aged 20 to 39 years as controls to measure serum reproductive hormone levels.Serum total testosterone (TT) levels did not change significantly in S1, whereas TT levels increased in S2 with aging. Serum calculated free testosterone (cFT) levels gradually decreased with aging; however, only men aged 40 to 69 years showed this trend in S2. Serum luteinizing hormone (LH) and sex hormone binding globulin (SHBG) levels gradually increased, and serum testosterone secretion index (TSI) and free testosterone index (FTI) levels gradually decreased with male aging. The mean annual decrease values of serum cFT were 2.705 pmol/l in S1 and 1.060 pmol/l in S2. The cut-off values for AD in S1 and S2 were 9.13 nmol/l and 9.35 nmol/l for TT, and 169.00 pmol/l and 213.90 pmol/l for cFT. Using TT or cFT cut-off values, mean AD prevalence was 14.52% or 44.70% in S1, and 6.36% or 16.53% in S2. Based on cFT cut-off values, prevalence of AD increased gradually with male aging in a range of 25.30% to 61.63% in S1 and 1.20% to 23.03% in S2.The change patterns of serum LH, SHBG, TSI and FTI levels in middle-aged and aging males were consistent; however, there were differences in serum TT and cFT change patterns in S1 and S2 with male aging. cFT cut-off values were the optimal metric to evaluate AD, which can be present a ladder-like change in prevalence of different age groups.

[Changes of serum reproductive hormones with aging among healthy males in a community population of Hebei Province].

OBJECTIVE: To investigate the changes of serum reproductive hormones with male aging and to compare the differences in the hormone levels among different age groups or between township and rural males of the same age group. METHODS: Using cluster and stratified sampling, we recruited 434 healthy old and middle-aged (40-69 years) males, 198 from the township and 236 from the rural communities. We determined the concentrations of serum total testosterone (tT), luteinizing hormone (LH) and sex hormone binding globulin (SHBG), free testosterone (fT), bio-available testosterone (Bio-T), and obtained the testosterone secretion index (TSI) and free testosterone index (fTI). Meanwhile, we included fifty-nine 20-39 years old males from the same communities in a control group. RESULTS: With the increase of age, the serum tT levels did not change significantly, while the levels of serum LH and SHBG increased, and those of fT, Bio-T, TSI and fTI decreased gradually. Statistically significant differences were found among the four different age groups in all the parameters of reproductive hormones (P < 0.01), except in the serum tT level (P > 0.05). The serum tT level was not significantly correlated with aging and LH (P > 0.05). Serum LH and SHBG had a marked positive correlation with aging, and SHBG with LH (P < 0.01), while fT, Bio-T, TSI and fTI were negatively correlated with aging and the LH level (P < 0.01). Serum LH, TSI and fTI showed statistical differences (P < 0.05), while fT and Bio-T exhibited extremely significant differences (P < 0.01) between the township and rural males in the 40 -49 yr group, and in the same age group, the increase rates of serum LH and SHBG and reduction rates of fT, Bio-T, TSI and fTI were higher in the rural men than in the township residents. However, the results were just the opposite in the 50 - 59 and 60 - 69 yr groups. CONCLUSION: The levels of serum LH, SHBG, fT, Bio-T, TSI and fTI changed with aging in a gradientmanner in the old and middle-aged males, but no significant changes were observed in the level of serum tT. There were statistical differences in many parameters of serum reproductive hormones among different age groups or between township and rural males.

Lovastatin attenuates hypertension induced by renal tubule-specific knockout of ATP-binding cassette transporter A1, by inhibiting epithelial sodium channels.

BACKGROUND AND PURPOSE: We have shown that cholesterol is synthesized in the principal cells of renal cortical collecting ducts (CCD) and stimulates the epithelial sodium channels (ENaC). Here we have determined whether lovastatin, a cholesterol synthesis inhibitor, can antagonize the hypertension induced by activated ENaC, following deletion of the cholesterol transporter (ATP-binding cassette transporter A1; ABCA1). EXPERIMENTAL APPROACH: We selectively deleted ABCA1 in the principal cells of mouse CCD and used the cell-attached patch-clamp technique to record ENaC activity. Western blot and immunofluorescence staining were used to evaluate protein expression levels. Systolic BP was measured with the tail-cuff method. KEY RESULTS: Specific deletion of ABCA1 elevated BP and ENaC single-channel activity in the principal cells of CCD in mice. These effects were antagonized by lovastatin. ABCA1 deletion elevated intracellular cholesterol levels, which was accompanied by elevated ROS, increased expression of serum/glucocorticoid regulated kinase 1 (Sgk1), phosphorylated neural precursor cell-expressed developmentally down-regulated protein 4-2 (Nedd4-2) and furin, along with shorten the primary cilium, and reduced ATP levels in urine. CONCLUSIONS AND IMPLICATIONS: These data suggest that specific deletion of ABCA1 in principal cells increases BP by stimulating ENaC channels via a cholesterol-dependent pathway which induces several secondary responses associated with oxidative stress, activated Sgk1/Nedd4-2, increased furin expression, and reduced cilium-mediated release of ATP. As ABCA1 can be blocked by cyclosporine A, these results suggest further investigation of the possible use of statins to treat CsA-induced hypertension.