Incidence and predictive value of social frailty among community-dwelling older adults in Southwest China: A prospective cohort study.

Background: Few studies have focused on the incidence and correlation of social frailty (SF) with adverse health events in Southwest China. This study aims to explore the predictive value of SF for adverse health events. Methods: A 6-year prospective cohort study was employed, a total of 460 community-dwelling older adults aged 65 years and above were analyzed to provide a baseline in 2014. Participants completed two longitudinal follow-ups at 3 (2017, 426 participants involved) and 6 (2020, 359 participants involved) years later. A modified social frailty screening index was used in this study, and adverse health events such as physical frailty (PF) deterioration, disability, hospitalization, falls, and mortality were evaluated. Results: Among these participants in 2014, the median age was 71 years, 41.1% were male, and 71.1% were married or cohabiting, up to 112 (24.3%) of them were classified as SF. It was observed that aging (OR = 1.04, 95% CI = 1.00-1.07, P = 0.047) and having family members die in the past year (OR = 2.60, 95% CI = 0.93-7.25, P = 0.068) were risk factors of SF, whereas having a mate (OR = 0.40, 95% CI = 0.25-0.66, P = 0.000) and having family members to help with care (OR = 0.53, 95% CI = 0.26-1.11, P = 0.092) were protective factors of SF. The cross-sectional study demonstrated that SF was only significantly associated with disability (OR = 12.89, 95% CI = 2.67-62.13, P = 0.001) at wave 1. Baseline SF significantly explained the incidence of mortality at the 3-year (medium-term, OR = 4.89, 95% CI = 2.23-10.71, P = 0.000) and 6-year follow-ups (long-term, OR = 2.22, 95% CI = 1.15-4.28, P = 0.017). Conclusion: SF prevalence was higher in the Chinese older population. Older adults with SF had a significantly increased incidence of mortality at the longitudinal follow-up. Consecutive comprehensive health management of SF (e.g., avoiding living alone and increasing social engagement) is urgently needed for the purposes of early prevention and multidimensional intervention in adverse health events, including disability and mortality.

Factors that Affect Pancreatic Islet Cell Autophagy in Adult Rats: Evaluation of a Calorie-Restricted Diet and a High-Fat Diet.

Aging may be a risk factor for type 2 diabetes in the elderly. Dietary intervention can affect glucose tolerance in adults, which may be due to body composition and islet cell autophagy. The aim of this study was to determine the effects of various dietary interventions on islet cell autophagy. Pancreatic tissue and blood samples were collected from Sprague Dawley rats (14-16 months old, n = 15 for each group) that received a normal diet (ND), a high-fat diet (HFD), or a calorie-restricted diet (CRD). The body weight (BW), visceral fat, serum lipid levels, fasting serum glucose, insulin levels, and ß/α cell area were determined in 14-16-(0-w), 16-18-(8-w), and 18-20(16-w)-month-old rats. Pancreatic islet autophagy (LC3B and LAMP2), AP (Acid Phosphatase) and apoptosis (apoptosis index, AI (TUNEL assay) and cleaved caspase-3) were detected using immunohistochemistry, ELISA and western blot. At 16 weeks, the expressions of LC3B, LAMP2 and AP markedly increased in both the HFD (P<0.01) and CRD (P<0.05) groups; however, an increase in the AI (P<0.05), cleaved caspase-3 and Beclin1 expression and a decrease in the expressions of BCL2 and BCLXL (P<0.05) were observed in only the HFD group. FFA, triglyceride levels, HOMA-IR, insulin levels and glucagon levels were significantly increased in the HFD group but decreased in the CRD group at 16 weeks (P<0.05). The degree of islet cell autophagy was potentially regulated by the levels of FFA and islet cell insulin and glucagon, which may have been due to the effects of Beclin1/BCL2.

Bioinformatics analysis of abnormal DNA methylation in muscle samples from monozygotic twins discordant for type 2 diabetes.

The present study aimed to examine the changes in DNA methylation of gene promoters associated with type 2 diabetes (T2D). The DNA methylation profile dataset GSE38291 was downloaded from the Gene Expression Omnibus database. A paired t-test was used to analyze differences in the DNA methylation of gene promoters between T2D and normal muscle samples. Gene Ontology (GO) enrichment analysis was performed using online tool, The Database for Annotation, Visualization and Integrated Discovery. Whole-Genome rVISTA was used to analyze the enriched transcription factor (TF) binding sites upstream of the transcription start site in the differentially methylated genes. A total of 38 genes, including Sirtuin 1, N-acetyltransferase 6, phospholipase A2 group XIIB and nuclear factor of activated T cells calcineurin-dependent 1, were identified to be differentially methylated between these two groups. One GO term, DNA geometric change (GO:0032392), was significantly enriched (P<0.05) by the hyper-methylated genes. In addition, the binding sites of one gene, zinc finger E-box binding homeobox 1, and three TFs, methyl CpG binding protein 2, TFEB and TFAP4, were significantly enriched in the hyper- and hypo-methylated genes, respectively. The resulting T2D­associated genes and potential TFs provided a novel insight into the molecular mechanisms underlying the pathology of T2D. These genes may become promising target genes for the development of treatments for T2D.

Association of hsa-miR­145 overexpression in human testicular cells with male infertility.

MicroRNAs (miRs) have crucial functions in spermatogenesis and implications for male infertility. In the present study, Homo sapiens (hsa)­miR­145 was designed and cloned into the eukaryotic expression plasmid pGenesil­1. The recombinant plasmids were transfected into Hs 1.tes normal testicular cells and NTERA­2 testicular cancer cells. Quantitative polymerase chain reaction of hsa­miR­145 indicated that pGenesil­1­miR­145 effectively upregulated the expression of hsa­miR­145 in vitro. hsa­miR­145 overexpression inhibited the mRNA and protein expression of sex-determining region Y Box 9 in Hs 1.tes cells. The proliferation rates of NTERA­2 cells transfected with pGenesil­1­miR­145 were significantly decreased. High expression levels of miR­145 promoted cell apoptosis in NTERA­2 cells. The results revealed that altered hsa­miR­145 expression in testicular cells affects the regulation of target genes associated with male infertility.

[Association study between Y-chromosome haplo group and susceptibility to spermatogenisis impairment in Han People from Southwest China].

Idiopathic azoospermia and oligospermia are one of the most important reasons for male infertility. Abnormal karyotype and azoospermia factor (AZF) microdeletion are two widely acknowledged reasons, but the most causes remain unclear. Y chromosome, as the male-specific chromosome, is closely related to the development of male reproductive system. To understand better the etiology of idiopathic azoospermia and oligospermia, we investigated the possible association between Y-haplogroup distributions and susceptibility to idiopathic azoospermia and severe oligospermia. Peripheral blood was collected from 193 men with normal reproductive history, 193 men with idiopathic azoospermia, and 72 men with idiopathic severe oligospermia. All the subjects underwent karyotyping and AZF deletion analysis to screen out those with AZF deletion and abnormal karyotype. The comparison of Y-haplogroup distribution between experimental group and control group was performed with SPSS V.18.0 software. Significant difference of Y-haplogroup distribution was observed in D1*, F*, K*, N1* and O3*(P=0.032, 0.022, 0.009, 0.009, 0.017, <0.05). The results suggest that Y chromosome haplogroup plays a important role in spermatogenic impairment.

[Screening and clinical phenotype analysis of microdeletions of azoospermia factor region on Y chromosome in 1011 infertile men].

OBJECTIVE: To investigate the prevalence and subtypes of microdeletions in azoospermia factor (AZF) region in infertile men from Sichuan in order to correlate genotypes with phenotypes. METHODS: Multiplex-PCR was used to detect sequence tagged sites (STS) of AZF microdeletions in 1011 infertile men including 713 cases of non-obstructive azoospermia and 298 cases of severe oligospermia. RESULTS: The overall prevalence of microdeletions was 10.48% (106/1011), and the deletion rates were 11.08% (79/713) in non-obstructive azoospermia and 9.06% (27/298) in severe oligospermia. Complete AZFa or AZFb deletions were associated with azoospermia, whereas AZFc deletion (60.38%) was the most frequent deletion. The deletions were associated with variable spermatogenic phenotypes, and 37.50% of the patients with a deletion had sperms in the ejaculate. A mild decline in sperm concentration was found in two cases with partial AZFb deletion and one case with partial AZFb-c deletion. CONCLUSION: Deletions of the AZFc region were most commonly found in our patients. All cases with complete AZFa or AZFb deletions and a proportion of cases with AZFc deletion were associated with azoospermia. Our study has provided more insight into the genotype-phenotype correlation, and confirmed that Yq microdeletion screening has a significant value for the diagnosis for male infertility.

Genetic screening for chromosomal abnormalities and Y chromosome microdeletions in Chinese infertile men.

PURPOSES: To investigate the frequency and type of both chromosomal abnormalities and Y chromosome microdeletions and analyze their association with defective spermatogenesis in Chinese infertile men. METHODS: This is a single center study. Karyotyping using G-banding and screening for Y chromosome microdeletion by multiplex polymerase chain reaction(PCR)were performed in 200 controls and 1,333 infertile men, including 945 patients with non-obstructive azoospermia and 388 patients with severe oligozoospermia. RESULTS: Out of 1,333 infertile patients, 154(11.55%) presented chromosomal abnormalities. Of these, 139 of 945 (14.71%) were from the azoospermic and 15 of 388 (3.87%) from the severe oligozoospermic patient groups. The incidence of sex chromosomal abnormalities in men with azoospermia was 11.53% compared with 1.03% in men with severe oligozoospermia (P < 0.01). Also 144 of 1,333(10.80%) patients presented Y chromosome microdeletions. The incidence of azoospermia factor(AZF) microdeletion was 11.75% and 8.51% in patients with azoospermia and severe oligozoospermia respectively. Deletion of AZFc was the most common and deletions in AZFa or AZFab or AZFabc were found in azoospermic men. In addition, 34 patients had chromosomal abnormalities among the 144 patients with Y chromosome microdeletions. No chromosomal abnormality and microdeletion in AZF region were detected in controls. CONCLUSIONS: There was a high incidence (19.80%) of chromosomal abnormalities and Y chromosomal microdeletions in Chinese infertile males with azoospermia or severe oligozoospermia. These findings strongly suggest that genetic screening should be advised to infertile men before starting assisted reproductive treatments.