Background This study estimates the prevalence of five chronic non-communicable disease (NCDs) (hypertension, diabetes, CHD, COPD and stroke) and its multimorbidity, and examines the relationship between SES and lifestyle factors and multimorbidity among older adults in rural southwest China. Methods A cross-sectional survey of 4833 consenting adults aged ≥60 years was conducted in 2017. Data on the demographics, smoking, drinking, height, weight, blood pressure and fasting blood glucose were collected. Results Among the participants, the overall prevalence of hypertension, diabetes, stroke, COPD and CHD was 50.6, 10.2, 6.4, 5.4 and 5.5%, respectively, and of multimorbidity was 16.1%. Females had a higher prevalence of hypertension, diabetes and multimorbidity of chronic NCDs, but a lower prevalence of COPD than males (P < 0.05). Older adults with good household assets and access to medical services were less likely to experience multimorbidity, whereas obese and centrally obese participants, current smokers, current drinkers and those with a family history of chronic NCDs had a greater probability of multimorbidity. Conclusions The findings suggest that effective strategies for prevention and control of chronic NCDs and its multimorbidity are urgently needed, especially for low-income, elderly, ethnic minority adults with poor access to medical services.

Epigenetic mechanisms have an important role in the pre- and peri-conceptional programming by maternal nutrition. Yet, whether or not RNA m6A methylation—an old epigenetic marker receiving increased attention recently—is involved remains an unknown question. In this study, mouse high-fat feeding prior to conception was shown to induce overweight and glucose intolerant dams, which then continued to be exposed to a high-fat diet during gestation and lactation. The dams on a standard diet throughout the whole experiment were used as a control. Results showed that maternal high-fat intake impaired postnatal growth in male offspring, indicated by decreased body weight and Lee’s index at 3, 8 and 15 weeks old, but the percentages of visceral fat and tibialis anterior relative to the whole body weights were significantly increased at eight weeks of age. The maternal high-fat exposure significantly increased mRNA N6-methyladenosine (m6A) levels in visceral fat at three weeks old, combined with downregulated Fat mass and obesity-associated gene (FTO) and upregulated Methyltransferase like 3 (METTL3) transcription, and these changes were reversed at eight weeks of age. In the tibialis anterior muscle, the maternal high-fat diet significantly enhanced m6A modifications at three weeks, and lowered m6A levels at 15 weeks of age. Accordingly, FTO transcription was significantly inhibited at three weeks and stimulated at 15 weeks of age, and METTL3 transcripts were significantly improved at three weeks. Interestingly, both FTO and METTL3 transcription was significantly elevated at eight weeks of age, and yet the m6A modifications remained unchanged. Our study showed that maternal high-fat intake could affect mRNA m6A modifications and its related genes in offspring in a tissue-specific and development-dependent way, and provided an interesting indication of the working of the m6A system during the transmission from maternal nutrition to subsequent generations.

These results suggest that ECS can reverse the harmful behavioral effects of CUMS in rats and that the behavioral alterations induced by ECS and/or CUMS may be associated with hippocampal neuroplasticity and SYP levels.

BackgroundCREBZF is a member of the mammalian ATF/CREB family of the basic region-leucine zipper (bZIP) transcription factors. Two isoforms of CREBZF have been identified from the alternative usage of initiation codons, SMILE (long isoform of CREBZF) and Zhangfei (short isoform of CREBZF). Until recently, the physiological function of CREBZF in mammalian reproductions has not been reported.MethodsMultiple techniques were performed to investigate the spatiotemporal expression and hormonal regulation of the CREBZF gene in the mouse uterus and its role in embryo implantation.ResultsZhangfei was not detected in the mouse uterus. SMILE immunostaining was mainly expressed in the uterine luminal and glandular epithelium, and the expression levels of both SMILE mRNA and protein gradually decreased from days 1–3 of pregnancy, peaked on day 4, and then declined again on day 6. On day 5 of pregnancy, SMILE protein expression was detected only in the luminal epithelium at implantation sites compared with the expression at inter-implantation sites. SMILE protein was not detected in decidual cells from days 6–8 of pregnancy or artificial decidualisation. Furthermore, SMILE protein was not detected in the mouse uterus on days 3–6 of pseudopregnancy, and SMILE expression was also induced in the delayed-implantation uterus, indicating that the presence of an active blastocyst was required for SMILE expression at the implantation site. Oestrogen significantly stimulated SMILE expression in the ovariectomised mouse uterus. In addition, in cycling mice, high levels of SMILE protein and mRNA expression were also observed in proestrus and oestrus uteri.ConclusionsTaken together, these results suggested that SMILE expression was closely related to mouse implantation and up-regulated by oestrogen.

The aim of this study was to investigate the spatiotemporal expression and regulation of GRP78 in the mouse uterus during the peri-implantation period. The GRP78 protein was mainly detected in the luminal and glandular epithelia on days 1-4 of pregnancy. On day 5 of pregnancy, the GRP78 protein was more highly observed around the implanted embryo at the implantation site. There was no detectable GRP78 protein signal on day 5 of pseudopregnancy. GRP78 mRNA and protein levels gradually increased on days 6-8 of pregnancy, and the expression pattern was also expanded, coinciding with the development of decidua. Similarly, GRP78 expression was also strongly expressed in decidualised cells following artificial decidualisation. Compared with the results obtained with the delayed uterus, a high level of GRP78 expression was detected in the implantation-activated uterus. In the uteri of ovariectomised mice, GRP78 expression increased and reached its highest level after injection of oestrogen, and progesterone seemed to have an antagonistic effect on oestrogen up-regulation of GRP78 expression. Our data indicate that GRP78 might play an important role during the process of mouse embryo implantation, and GRP78 expression was mainly regulated by active blastocysts and maternal oestrogen.

Mineralocorticoid receptor (MR) inactivation in mice results in early postnatal lethality. Therefore we generated mice in which MR expression can be silenced during adulthood by administration of doxycycline (Dox). Using a lentiviral approach, we obtained two lines of transgenic mice harboring a construct that allows for regulatable MR inactivation by RNAi and concomitant expression of eGFP. MR mRNA levels in heart and kidney of inducible MR knock-down mice were unaltered in the absence of Dox, confirming the tightness of the system. In contrast, two weeks after Dox administration MR expression was significantly diminished in a variety of tissues. In the kidney, this resulted in lower mRNA levels of selected target genes, which was accompanied by strongly increased serum aldosterone and plasma renin levels as well as by elevated sodium excretion. In the healthy heart, gene expression and the amount of collagen were unchanged despite MR levels being significantly reduced. After transverse aortic constriction, however, cardiac hypertrophy and progressive heart failure were attenuated by MR silencing, fibrosis was unaffected and mRNA levels of a subset of genes reduced. Taken together, we believe that this mouse model is a useful tool to investigate the role of the MR in pathophysiological processes.

Background: The efficacy and safety of tacrolimus (TAC) and cyclophosphamide (CTX) were prospectively examined in steroid-dependent or steroid-resistant primary focal segmental glomerulosclerosis (FSGS). Methods: Patients with biopsy-proven FSGS were enrolled and randomly divided into two groups: CTX and TAC. Patients treated with CTX (0.5–0.75 g/m²·month, i.v.) received prednisone at 0.8 mg/kg·day, while patients treated with TAC (0.1 mg/kg·day) received prednisone at 0.5 mg/kg·day. The plasma concentration of TAC was monitored and maintained at 5–10 ng/ml. After a 6-month treatment the patients were evaluated. Patients with complete remission (CR) and partial remission (PR) continued the treatment for 12 months with the dose tapered, whereas the patients with no response were excluded from the study and underwent an alternative treatment. Results: A total of 33 patients were recruited and 27 completed the 12-month follow-up. The TAC-treated patients (n = 15) showed a quick remission. The initial remission time averaged 1.23 ± 0.21 versus 2.21 ± 0.77 months in the CTX group (n = 18), but no significant difference was achieved (p > 0.05). At 6 months, the two groups showed a similar outcome. Ten patients from each group showed remission (7 CR and 3 PR). At 12 months, the CTX group had 9 CR and 3 PR while the TAC group had 6 CR and 5 PR. Remission rates in TAC tended to be higher than that in CTX, but there was no difference. CTX patients had a high prevalence of infections (50.0 vs. 13.3% in TAC, p < 0.05). In contrast, TAC-treated patients showed a high incidence of hyperglycemia (26.7 vs. 0.0% in CTX, p < 0.05). Conclusion: These results suggest that CTX and TAC had a similar efficacy in steroid-dependent and steroid-resistant FSGS as manifested by reduced proteinuria, improved serum albumin level and renal function.

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