Aims The main objective of this study was to analyze the changes of intestinal microflora and how bile acid metabolic pathways affect lipid metabolism in T2DM through the gut-liver axis. Methods Firstly, 16S rRNA sequencing, metabolomics and transcriptomic sequencing were performed on plasma and feces of clinical subjects to determine the changes of intestinal flora and its metabolites. Finally, T2DM mice model was verified in vivo. Results T2DM patients have significant intestinal flora metabolism disorders. The differential fecal metabolites were mainly enriched in primary bile acid biosynthesis and cholesterol metabolism pathways in T2DM patients. After verification, the changes in gut microbiota and metabolites in T2DM patients (including up-regulated bacteria associated with BA metabolism, such as lactobacillus and bifidobacterial, and down-regulated bacteria capable of producing SCFAs such as Faecalibacterium, Bacteroides, Romboutsia and Roseburia); and the changes in the flora and metabolites that result in impairment of intestinal barrier function and changes of protein expression in the blood, intestine and liver of T2DM patients (including FGFR4↑, TRPM5↑ and CYP27A1↓, which are related to BA and lipid metabolism homeostasis, and TLR6↑, MYD88↑ and NF-κB↑, which are related to inflammatory response). These aspects together contribute to the development of further disorders of glucolipid metabolism and systemic inflammation in T2DM patients. Conclusions Changes in intestinal flora and its metabolites may affect lipid metabolism and systemic inflammatory response in T2DM patients through the gut-liver axis mediated by bile acids.

Moringa oleifera leaf (MLP) contains abundant complex nutrients with anti-osteoporosis potential. However, its efficacy and mechanisms against osteoporosis remain unknown. The purpose of this research is to investigate MLP's anti-osteoporotic effects and mechanisms. Animal experiments were used in this work to validate MLP's anti-osteoporotic efficacy. We investigated the mode of action of MLP, analyzed its impact on the gut microbiota, and predicted and validated its anti-osteoporosis-related molecular targets and pathways through network pharmacology, molecular docking, and western blotting. In an ovariectomized osteoporosis rat model, MLP significantly increased bone mineral density and improved bone metabolism-related indicators, bone microstructure, and lipid profile. Moreover, it improved gut microbiota composition and increased the expression of Occludin and Claudin-1 protein in the duodenum. Network pharmacology identified a total of 97 active ingredients and 478 core anti-osteoporosis targets. Of these, MAPK1 (also known as ERK2), MAPK3 (also known as ERK1), and MAPK8 (also known as JNK) were successfully docked with the active constituents of MLP. Interestingly, MLP increased ERK and VAV3 protein expression and decreased p-ERK and JNK protein expression in the femur. These findings confirm MLP's anti-osteoporotic efficacy, which could be mediated via regulation of gut microbiota and MAPK signaling.

AbstractThis study investigated the effects of supplementation Moringa oleifera leaf (MOL) on relieving oxidative stress, anti‐inflammation, changed the relative abundance of multiple intestinal flora and blood biochemical indices during letrozole‐induced polycystic ovary syndrome (PCOS). Previous studies have shown that MOL has anti‐inflammatory, anti‐oxidation, insulin‐sensitizing effects. However, whether MOL has beneficial effects on PCOS remains to be elucidated. In the current study, 10‐week‐old female Sprague–Dawley rats received letrozole to induce PCOS‐like rats, and subsequently were treated with a MOL diet. Then, the body weight and estrus cycles were measured regularly in this period. Finally, the ovarian morphology, blood biochemical indices, anti‐oxidative, intestinal flora, and anti‐inflammation were observed at the end of the experiment. We found that MOL supplementation markedly decreased the body weight, significantly upregulated the expression of Sirt1, FoxO1, PGC‐1α, IGF1, and substantially modulated the sex hormone level and improved insulin resistance, which may be associated with the relieves oxidative stress. Moreover, the supplementation of MOL changed the relative abundance of multiple intestinal flora, the relative abundance of Fusobacterium, Prevotella were decreased, and Blautia and Parabacteroides were increased. These results indicate that MOL is potentially a supplementary medication for the management of PCOS.

Background The principal objective of this study was to gain a better understanding of the mechanisms of type 2 diabetes mellitus (T2DM) patients with fatigue (D-T2DM) through exome and transcriptome sequencing. Methods After whole-exome sequencing on peripheral blood of 6 D-T2DM patients, the consensus mutations were screen out and analyzed by a series of bioinformatics analyses. Then, we combined whole-exome sequencing and transcriptome sequencing results to find the important genes that changed at both the DNA and RNA levels. Results The results showed that a total of 265,393 mutation sites were found in D-T2DM patients compared with normal individuals, 235 of which were consensus mutations shared with D-T2DM patients. These genes significantly enriched in HIF-1 signaling pathway and sphingolipid signaling pathway. At the RNA level, a total of 375 genes were identified to be differentially expressed. After the DNA-RNA joint analysis, eight genes were screened that changed at both DNA and RNA levels. Among these genes, FUS and LMNA were related to carbohydrate metabolism, energy metabolism, and mitochondrial function. Subsequently, we predicted the herbs, including Qin Pi and Hei Zhi Ma, that might play a therapeutic role in D-T2DM through the SymMap database. Conclusion These findings have significant implications for understanding the mechanisms of D-T2DM and provide potential targets for D-T2DM diagnosis and treatment.

围绕王琦教授提出的中医体质学说,由治未病—体质—辨体施灸,层层深入,浅谈"辨体施灸"的可行性.从保健灸的发展史中,提取出古今使用艾灸治未病的经验,同时将治未病与体质的关系转化为研究的3个关键问题,即中医体质的分类、体质与疾病的关系和纠正体质,分析如何把中医体质学与临床诊疗预防相结合.文章通过回顾近年来艾灸结合中医体质学防治疾病的研究进展,可初步总结出"辨体施灸"的基本取穴方,为扩大艾灸在临床的适用范围提供理论依据.

Abstract Objective To explore the effects of the quinoa diet on glycolipid metabolism and endoplasmic reticulum (ER) stress in an obese mouse model. Methods Six-week-old C57BL/6J female mice have received a high-fat diet (HFD) to induce obesity and subsequently were treated with a quinoa diet for 12 weeks. During this period, fasting blood glucose, body fat and insulin resistance were measured regularly. At the end of the experiment, mouse serum and liver tissue were collected. The differences in glucose and lipid metabolism were analyzed, and liver tissue pathological morphology, liver endoplasmic reticulum stress-related mRNA and protein levels, and serum oxidative stress levels were measured. Results Quinoa diet could significantly reduce the level of blood glucose, triglyceride, cholesterol, low-density lipoprotein, improve glucose tolerance, as well as improve histological changes of liver tissues in obese mice (P < 0.05 or < 0.01). Besides, quinoa could improve oxidative stress indicators such as GSH, and MDA (P < 0.05 or < 0.01). Furthermore, quinoa can down-regulate mRNA expression of ER stress markers eIF2α, GRP78, and CHOP in the liver of obese mice (P < 0.05 or < 0.01). Conclusions Quinoa supplementation can improve glycolipid metabolism, regulate ER stress, and alleviate obesity in HFD-induced mice.

ETHNOPHARMACOLOGICAL RELEVANCE:Salvianolic acid B (SalB) is a polyphenolic compound in Salvia miltiorrhiza Bunge ("Danshen"), which has been largely used in Traditional Chinese Medicine for the treatment of metabolic syndrome, obesity, diabetes, among others. AIM OF STUDY:This study was to investigate the effects of Salvianolic acid B (SalB) on mRNA, lncRNA and circRNA's expression profile in brown adipose tissue (BAT) of obese mice. MATERIALS AND METHODS:High-fat-diet induced obese C57BL/6J mice were treated with SalB (100 mg/kg/day) for 8 weeks. Then, BAT was harvested for RNA-Seq analysis. Differentially expressed mRNAs, lncRNAs and circRNAs were analyzed using the Illumina Hiseq 4000. Following this procedure, bioinformatic tools including Gene ontology (GO), KEGG pathway and lncRNA-mRNA co-network analysis were utilized. Finally, RT-qPCR was performed to validate the differentially expressed RNAs. RESULTS:Compared with control group, 2532 mRNAs, 774 lncRNAs and 25 circRNAs were differentially expressed in SalB group. Additionally, 40 upregulated and 109 downregulated gene-related pathways were identified in the SalB group. Among them, metabolic pathways showed the highest enrichment coefficient in upregulated genes. Moreover, 54 up-regulated and 626 down-regulated coding mRNAs associated with lncRNA-Hsd11b1 and lncRNA-Vmp1. CONCLUSIONS:SalB may play an anti-obesity role by adjusting the expression of mRNAs correlated with inflammatory response and energy metabolism through regulating the expression of lncRNA-Hsd11b1. The findings of this research provide new directions to study the mechanisms of SalB, and would open therapeutic avenues for the treatment of obesity.

目前我国蒙医药博士研究生教育正处于起步阶段,尚未形成成熟的培养体系.梳理我国蒙医药博士研究生培养现状,深入分析我国蒙医药博士研究生培养存在着招收专业少,专业学位培养尚属空白;课程设置有待加强,教学方法亟需完善;师资力量薄弱等问题,并提出改进措施,为蒙医药事业发展过程中所需的高层次、拔尖创新人才的培养献言建策.

Background: Subthreshold depression (StD) is a prevalent condition that may increase the risk of incident major depressive disorder (MDD). However, the relationship between StD and MDD remains unclear. Methods: A total of 153 adult subjects, including 53 drug-naive MDD, 50 StD and 50 healthy control (HC) subjects, underwent a T1-weighted magnetic resonance imaging scan, and the gray matter volume (GMV) alterations among the three groups were quantitatively analyzed using voxel-based morphometry (VBM). Then, to capture the whole-brain connectivity characteristics, we constructed morphological brain networks (MBN) based on the similarity among brain regions of individual VBM images and compared the network connection strengths among the three groups. Results: The StD and MDD subjects had similar patterns of GMV reductions in the orbitofrontal cortex and left temporal gyrus, although the magnitude of the reductions was smaller in StD subjects. Moreover, a total of 21 morphological connections were significantly different among the three groups. For the majority of the different connections (15/21), the connection strength of the StD group took an intermediate position between that of the MDD and HC groups. Limitations: There is still a lack of a consistent definition of StD, and the age range of the subjects in this study was wide. Meanwhile the mechanisms and biological significance of the MBN remains to be clarified. Conclusions: These results may support the hypothesis that depression is better expressed as a spectrum and that StD exists on a spectrum with MDD.

Purpose: The purpose of this study is to explore the differences in transcriptome expression profiles between healthy subjects and type 2 diabetes mellitus patients with thirst and fatigue (D-T2DM) and, in addition, to investigate the possible role of noncoding ribonucleic acids (RNAs) in the pathogenesis of D-T2DM. Methods: We constructed the expression profiles of RNAs by RNA sequencing in the peripheral blood of D-T2DM patients and healthy subjects and analyzed differentially expressed RNAs. Results: Compared with healthy subjects, a total of 469 mRNAs, 776 long non-coding RNAs (lncRNAs), and 21 circular RNAs (circRNAs) were differentially expressed in D-T2DM patients. Furthermore, several genes associated with insulin resistance, inflammation, and mitochondrial dysfunction were identified within the differentially expressed mRNAs. Differentially expressed lncRNAs were primarily involved in biological processes associated with immune responses. In addition, differentially expressed circRNAs may target miRNAs associated with glucose metabolism and mitochondrial function. Conclusions: Our results may bring a new perspective on differential RNA expression involved in the pathogenesis of D-T2DM and promote the development of novel treatments for this disease.

Background : Polycystic ovary syndrome (PCOS) is a common female endocrinopathy, which severely affect the menstruation and fertility of patients. Naringenin, a natural flavanone, has emerged as a potential therapeutic agent for the management a variety of diseases. However, the underlying mechanism of naringenin in anti‑PCOS is unclear. This study was focused on investigating the effects of naringenin on body weight, ovarian tissue, serum hormone level, glucose metabolism level and gut microbiome in letrozole-induced PCOS model rats. Methods: First, we administered letrozole gavage to 10-week-old SD female rats for 4 weeks to induce PCOS rats model, the estrus cycle was observed through the vaginal smear of rats to determine the establishment successful of a PCOS rat model. Then, the successfully modeled PCOS rats were treated with naringenin for 2 months. Finally, observed the changes of rat body weight, ovarian tissue, serum hormone level, glucose metabolism level and gut microbiome after naringenin treatment. Results: The naringenin treatment ameliorate the hormone levels, such testosterone (T), estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), improve insulin resistance and the ovarian tissue pathological changes, reduced body weight in the PCOS model rat. Meanwhile, through the detection of rDNA in the faeces of the PCOS model rat, we found some beneficial microbes such [Ruminococcus], Faecalibacterium, Butyricimonas, Lachnospira, Parabacteroides, Butyricicoccus and Roseburia were enrichment in naringenin group when compared with the PCOS rats. Conclusions: In summary, our results indicated that naringenin could play an anti-PCOS role, and its mechanism may be closely related to regulating the beneficial microbes of gut microbiome. Our research could provide a new perspective for the treatment of PCOS and its related disease.

OBJECTIVE: To assess the toxicity of moxa smoke in rats.METHODS: Forty-eight female Wister rats were randomly divided into 4 groups(n = 12/group) to simulate moxa smoke exposure in Chinese medicine clinics(CMCs): the control group, and three moxa-smoke exposed groups of PM10 mass concentrations 3-5, 7-9 and 27-30 mg/m 3 , respectively.These concentrations were 1 ×, 2-3 ×, and 7-9 ×fold the concentrations found in CMCs. Exposures continued for 12 weeks(200 min/d, 5 d/week).RESULTS: No deaths were noted. After the exposure, the body weights, ratios of organ weight to body weight, urinary parameters, hematological parameters, clinical chemistry parameters and microscopic examinations revealed no obvious toxicity.CONCLUSION: Moxa smoke did not induce toxic effects in female rats in the study. These findings provide new evidence to the toxicity of moxa smoke.

To develop a more effective and safer drug for the treatment of type 2 diabetes mellitus (T2DM)-induced liver damage, we investigated the protective effects of punicalagin, a major component in pomegranate peel, on the liver of mice with T2DM. After five weeks of punicalagin treatment, blood and liver samples were obtained for the subsequent analyses. Western blotting, reverse transcription polymerase chain reaction, and immunohistochemical staining were performed to determine the expression of endoplasmic reticulum (ER) stress markers in the liver tissue. The results showed that punicalagin alleviated glucose and insulin resistance, increased insulin sensitivity, and reduced serum free fatty acids levels and hepatic steatosis in the mice with T2DM. Furthermore, punicalagin down-regulated the elevated mRNA expression of the ER stress markers eIF2α, GRP78, ATF4, and CHOP in the liver of mice with T2DM. Our results suggest that punicalagin is a potential natural agent for the prevention of T2DM-induced liver damage.

Background/Aims: The adverse effects of obesity on male fertility have been widely reported. In recent years, the relationship between the differential expression of proteins and long non-coding RNAs with male reproductive disease has been reported. However, the exact mechanism in underlying obesity-induced decreased male fertility remains unclear. Methods: We used isobaric tags for relative and absolute quantification to identify differential protein expression patterns in the testis of rats fed a high-fat diet and normal diet. A microarray-based gene expression analysis protocol was used to compare the differences in long non-coding RNAs in high-fat diet-fed and normal diet-fed rats. Five obviously upregulated or downregulated proteins were examined using western blot to verify the accuracy of their expression. Then, we carried out functional enrichment analysis of the differentially expressed proteins using gene ontology and pathway analysis. Finally, the metabolic Gene Ontology terms and pathways involved in the differential metabolites were analyzed using the MetaboAnalyst 2.0 software to explore the co-expression relationship between long non-coding RNAs and proteins. Results: We found 107 proteins and 263 long non-coding RNAs differentially expressed between rats fed a high-fat diet and normal diet. The Gene Ontology term enrichment analysis showed that the protein function most highly enriched was related to negative regulation of reproductive processes. We also found five Gene Ontology terms and two metabolic pathways upregulated or downregulated for both proteins and long non-coding RNAs. Conclusion: The study revealed different expression levels for both proteins and long non-coding RNAs and showed that the function and metabolic pathways of differently expressed proteins were related to reproductive processes. The Gene Ontology terms and metabolic pathways upregulated or downregulated in both proteins and long non-coding RNAs may provide new candidates to explore the mechanisms of obesity-induced male infertility for both protein and epigenetic pathways.

目的:探讨神经网络方法在抑郁症早期筛查中应用的可行性.方法:应用神经网络方法构建抑郁症早期筛查模型,收集高校学生和企业员工两个人群的抑郁症早期筛查数据形成神经网络训练和测试样本,筛选与抑郁症发病密切相关的背景因素,将其作为神经网络的输入变量,将抑郁自评量表评分作为输出变量,分析其临床应用的可行性.结果:神经网络模型对两个人群的量表评分的预测符合率分别为76.03％和73.93％.结论:将神经网络方法应用于抑郁症早期筛查具有较大潜力,值得深入研究.

Through checking the ancient books and the articles at the modern times and combining the disciplinary characteristics of techniques of acupuncture and moxibustion, the training of manipulation skills was discussed. It is proposed that during the teaching of the techniques of acupuncture and moxibustion, the most basic ability of needling technique should be trained in the first place. This ability includes the ability of spiritual cultivation, the ability of tactile perception and the specific training for the needling techniques. The ability of spiritual cultivation refers to the consciousness concentration to the patient when providing acupuncture, which may promotes deqi and conducts qi to the affected area. The ability of tactile perception refers to the different feelings of different tissues under the hands before and after acupuncture, the perception to the different needling sensations corresponding to the chief complains of patients as well as the different body responses after acupuncture. In order to ensure the better learning results, the specific manipulations of needling techniques should be provided accordingly on the base of these basic training skills of acupuncture.

Objective To investigate the mental states of the community-dwelling elderly in Beijing ,and to explore their relationship with depression using multivariate analysis ,in order to provide evidence for strategies to prevent depression in the elderly. Methods A total of 400 community elderly residents in Chaoyang District of Beijing were recruited in this cross-sectional study. The mental states of older adults were assessed by using the Zung Self-Rating Depression Scale(SDS) ,the Medical Outcomes Study(Mos)36-item Short Form Health Survey (SF-36) ,and the Social Support Rating Scale(SSRS).The correlations of the mental state with demographic data ,quality of life and social support were examined via multivariate analysis. Results Of 400 questionnaires ,364 were valid.Depression occurred in 64 older adults ,and the detection rate was 17.6% (64/364).Multivariate linear regression analysis showed that depression was closely correlated with age ( P = 0.049 ) , physiological function(P=0.009) ,vitality(P=0.028) ,mental health(P＜0.001) ,self-reported health transition(P=0.003) ,objective support(P=0.001)and subjective support(P=0.001)in community-dwelling elderly residents in Beijing.Bivariate Logistic regression analysis showed that five factors , including vitality (OR = 0.595 ,P= 0.036 ) ,mental health (OR = 0.548 ,P = 0.021 ) ,self-reported health transition(OR=1.597 ,P= 0.048) ,objective support (OR= 0.524 ,P= 0.018)and subjective support(OR=1.787 ,P=0.027) ,were influencing factors for depression in the elderly.Self-reported health transition and subjective support had the greatest impact on depression in the elderly . Conclusions Critical approaches to preventing depression in the elderly include a focus on the mental health and social needs as well as measures to enhance self-confidence in the health of these individuals.

Purpose: To investigate the effect of JTXK granule on the expression pattern of miRNA in pancreatic tissue of KKAy diabetic mice, and to explore the molecular mechanism and pathways of JTXK granule in anti-diabetic effect. Methods: We used high fat diet (HFD) to induce the KKAy diabetic mice and screened the differentially expressed miRNAs (DEMs) between JTXK-treated group (n = 6) and the diabetic group (n = 6) using MicroRNA (miRNA) Microarray. C57BL/6J mice were given a normal diet as the control group (n = 6). Subsequently, miRNA target gene prediction, GO and Pathway analysis were used to explore the function of DEMs. Finally, the mechanism of anti-diabetic effects of JTXK granule was tested by in vitro INS-1 pancreatic β-cell experiment. Results: The blood glucose and body weight of JTXK-treated group was significantly lower compared with the model group. Moreover, a total of 45 miRNAs with significant differences were detected in the model group and the JTXK-treated group (P ≤ 0.05, Fold Change > 2). Further, miRNA-mRNA analysis showed that the differential expression of mmu-miR-192-5p, mmu-miR-291a-3p, mmu-miR-320-3p, mmu-miR-139-5p and mmu-miR-378a-3p are closely related to pancreatic histological changes. In addition, pathway analysis showed that the DEMs were closely related to PI3K-Akt Signaling Pathway. Furthermore, the levels of serine/threonine-protein kinase (Akt), phosphorylated Akt (p-Akt) and phosphorylated forkhead transcription factor O1 (p-Foxo1) in INS-1-FOXO1 overexpressing model cells were lower than those in normal group, while JTXK granules could increase the expression of Akt, p-Akt and p-Foxo1. Conclusions: The results showed that JTXK granule could play an anti-diabetic role by regulating the mRNA and miRNAs associated with PI3K-Akt pathway in diabetic mice pancreatic tissue.

Electroacupuncture (EA) has been shown to alleviate the symptoms associated with major depressive disorder; however, the underlying mechanisms remain unclear. While the mainstay treatment for depression are pharmacological agents that modulate serotonergic and/or noradrenergic activity of the brain, recent data suggest that, neurotrophins may play a larger role in the pathogenesis of depression and may offer better therapeutic potential in alleviating symptoms associated with depression. One downstream target of neurotrophins is the extracellular signal-regulated kinase (ERK)/Mitogen-activated protein kinase (MAPK) cascade, a major mediator of cellular stress often associated with clinical depression. In this study, we assessed whether the efficacy of EA is due to regulation of these novel pathways using an animal model of depression induced by chronic unpredictable mild stress (CUMS). We found that EA stimulation at specific locations, Baihui (GV20), and Yintang (GV29) ameliorated the behavioral responses of CUMS, which included reduced locomotion, decreased sucrose intake and weight loss. Furthermore, EA increased the activation of ERK and ribosomal s6 kinase (RSK) levels under stress. Both the behavioral and biochemical responses to EA were attenuated with administration of ERK inhibitor, suggesting that EA improves depression-like symptoms in stressed rats, in part, by activation of ERK signaling.