Association between body mass index and body fat measured by dual-energy X-ray absorptiometry (DXA) in China: a systematic review and meta-analysis

Objective:We examined the association between body mass index(BMI)and body fat percentage(BF%)measured by dual-energy X-ray absorptiometry(DXA)among adults and children in China.Methods:We searched four databases-PubMed,China National Knowledge Infrastructure,Wanfang,and Vip for studies published in the past 22 years.Meta-analysis was conducted using random-or fixed-effect models.Results:In total of 21 studies met inclusion criteria and were included in review,and 17 ot them in meta-analysis.They were conducted across China.Their sample size ranged from 62 to 5726,and participants'age ranged from 6-80 years.Meta-analysis revealed strong associations between BMI and BF% measured by DXA in adults(pooled r=0.71,95% CI:0.66 to 0.74)and children(pooled r=0.60,95% CI:0.52 to 0.68).The association was stronger in Northern China than in East China in children(β=-0.40,95%CI:-0.65 to-0.14)and in Central China in adults(β=-0.25;95% CI:-0.51 to-0.01).Urban children's BMI was strongly associated with BF%than rural(β=0.19;95%CI:0.04 to 0.35),whereas it was stronger in adults living in rural than in urban(β=-0.35;95% CI:-0.66 to-0.05).Conclusions:BMI was strongly associated with BF%measured by DXA,and the association in children and adults in China varied by residence and region.

Metabolic basis of solute carrier transporters in treatment of type 2 diabetes mellitus

Solute carriers(SLCs) constitute the largest superfamily of membrane transporter proteins.These transporters, present in various SLC families, play a vital role in energy metabolism by facilitating the transport of diverse substances, including glucose, fatty acids, amino acids, nucleotides, and ions.They actively participate in the regulation of glucose metabolism at various steps, such as glucose uptake(e.g., SLC2A4/GLUT4), glucose reabsorption(e.g., SLC5A2/SGLT2), thermogenesis(e.g., SLC25A7/UCP-1), and ATP production(e.g., SLC25A4/ANT1 and SLC25A5/ANT2). The activities of these transporters contribute to the pathogenesis of type 2 diabetes mellitus(T2DM). Notably, SLC5A2 has emerged as a valid drug target for T2DM due to its role in renal glucose reabsorption, leading to groundbreaking advancements in diabetes drug discovery. Alongside SLC5A2, multiple families of SLC transporters involved in the regulation of glucose homeostasis hold potential applications for T2DM therapy. SLCs also impact drug metabolism of diabetic medicines through gene polymorphisms, such as rosiglitazone(SLCO1B1/OATP1B1) and metformin(SLC22A1-3/OCT1-3 and SLC47A1, 2/MATE1, 2). By consolidating insights into the biological activities and clinical relevance of SLC transporters in T2DM, this review offers a comprehensive update on their roles in controlling glucose metabolism as potential drug targets.

Nonalcoholic fatty liver disease and vascular disease:State-of-the-art

Nonalcoholic fatty liver disease(NAFLD), the most common of chronic liver disease in Western Country, is closely related to insulin resistance and oxidative stress and includes a wide spectrum of liver diseases ranging from steatosis alone, usually a benign and non-progressive condition, to nonalcoholic steatohepatitis(NASH), which may progress to liver fibrosis and cirrhosis. NAFLD is considered the hepatic manifestation of the metabolic syndrome with which shares several characteristics, however recent data suggest that NAFLD is linked to increased cardiovascular risk independently of the broad spectrum of risk factors of metabolic syndrome. Accumulating evidence suggests that the clinical burden of NAFLD is not restricted to liver-related morbidity and mortality, with the majority of deaths in NAFLD patients related to cardiovascular disease and cancer and not to the progression of liver disease. Retrospective and prospective studies provide evidence of a strong association between NAFLD and subclinical manifestation of atherosclerosis(increased intima-media thickness, endothelial dysfunction, arterial stiffness, impaired left ventricular function and coronary calcification). A general agreement emerging from these studies indicates that patients with NASH are at higher risk of cardiovascular diseases than those with simple steatosis, emphasizing the role of chronic inflammation in the pathogenesis of atherosclerosis of these patients. It is very likely that the different mechanisms involved in the pathogenesis of atherosclerosis in patients with NAFLD have a different relevance in the patients according to individual genetic background. In conclusion, in the presence of NAFLD patients should undergo a complete cardiovascular evaluation to prevent future atherosclerotic complications. Specific lifestyle modification and aggressive pharmaceutical modification will not only reduce the progression of liver disease, but also reduce morbidity for cardiovascular disease improving overall prognosis and survival.

Research Progress on Prevention and Treatment of Glucolipid Metabolic Disease with Integrated Traditional Chinese and Western Medicine

Hyperlipidemia, type 2 diabetes mellitus, nonalcoholic fatty liver and many other metabolic disorder are frequently co-existing in patients. In addition, these diseases are closely related in pathophysiological settings. However, increasing of the disease incidence, lacking of comprehensive prevention and control measurements against the key pathology point concomitant occurrence with the pattem of the single disease, single target therapy, that is leading therapeutic strategy for these metabolic disorders in the setting of Western medicine （WM）. On the basis of the combination of the advantages of integrated Chinese medicine （CM） and WM, with unified understanding of such diseases, the new concept of glucolipid metabolic disease （GLMD） is introduced. In this new concept, disorders in glucose and lipid metabolism are recognized as the key trigger and major driving force for the progress of GLMD. The key points of pathology included dysfunction of neuronal-endocrine-immune system,insulin resistance, oxidative stress, inflammation and intestinal flora imbalance. In the core pathogenic perspective of CM, it can be explained as ＂Gan （Liver） Shi Shu Xie＂ （dysfunction of Gan in metabolism and emotion regulation） that will lead to the occurence/production of endogenous dampness and phlegm, blood stasis and turbid. This leads to the new concept of ＂Liver-based regulatory system for metabolic homeostasis＂ to be introduced further. The comprehensive prevention and control strategy ＂Tiao Gan Qi Shu Hua Zhuo＂ （modulating Gan, trigging key metabolic system to resolve pathogenic factors such as phlegm retention and dampness）. Its representative formula Fufang Zhenzhu Tiaozhi Capsule （复方贞术调脂胶囊） is innovated under such rationales. Comment for some commonly-used CM GLMD therapeutic drugs was presented. High-level evidence-based and epidemiological and mechanism studies should be carded out to further interpret and explain of the scientific connotation of GLMD.

A randomized trial of iron depletion in patients with nonalcoholic fatty liver disease and hyperferritinemia

AIM: To compare iron depletion to lifestyle changes alone in patients with severe nonalcoholic fatty liver disease (NAFLD) and hyperferritinemia, a frequent feature associated with more severe liver damage, despite at least 6 mo of lifestyle changes.

Alzheimer’s disease and type 2 diabetes mellitus:Pathophysiologic and pharmacotherapeutics links

At present,Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2DM)are two highly prevalent disorders worldwide,especially among elderly individuals.T2DM appears to be associated with cognitive dysfunction,with a higher risk of developing neurocognitive disorders,including AD.These diseases have been observed to share various pathophysiological mechanisms,including alterations in insulin signaling,defects in glucose transporters(GLUTs),and mitochondrial dysfunctions in the brain.Therefore,the aim of this review is to summarize the current knowledge regarding the molecular mechanisms implicated in the association of these pathologies as well as recent therapeutic alternatives.In this context,the hyperphosphorylation of tau and the formation of neurofibrillary tangles have been associated with the dysfunction of the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways in the nervous tissues as well as the decrease in the expression of GLUT-1 and GLUT-3 in the different areas of the brain,increase in reactive oxygen species,and production of mitochondrial alterations that occur in T2DM.These findings have contributed to the implementation of overlapping pharmacological interventions based on the use of insulin and antidiabetic drugs,or,more recently,azeliragon,amylin,among others,which have shown possible beneficial effects in diabetic patients diagnosed with AD.

Clinical Characteristics and Outcomes of Type 2 Diabetes Patients Infected with COVID-19: A Retrospective Study

据报道,糖尿病及其相关的代谢性疾病是新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)患者的主要合并症。这项临床研究旨在调查有或没有合并糖尿病的COVID-19患者的临床特征、影像学和实验室检查、并发症、治疗方法以及临床结局。这项回顾性研究纳入2020年1月12日至3月25日208例经实验室确认的COVID-19的住院患者(≥45岁)。分析病历信息包括临床特征、影像学和实验室检查、并发症、治疗和临床结果。其中,96名(46.2%)患者患有2型糖尿病。在COVID-19合并2型糖尿病患者中,高血压(58.3%vs.31.2%)、冠心病(17.1%vs.8.0%)和慢性肾脏病(6.2%vs.0%)的共存率明显高于没有2型糖尿病的COVID-19患者。COVID-19合并2型糖尿病患者的CT胸部扫描异常频率和程度显著增加,包括毛玻璃样混浊(85.6%vs.64.9%,P<0.001)和双侧斑片状阴影(76.7%vs.37.8%,P<0.001)。此外,患有糖尿病的COVID-19患者的血糖水平[7.23 mmol·L^-1(IQR:5.80~9.29)vs.5.46 mmol·L^-1(IQR:5.00-6.46)]、血液中低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)[2.21 mmol·L^-1(IQR:1.67~2.76)vs.1.75 mmol·L^-1(IQR:1.27~2.01)]和收缩压[130 mmHg(IQR:120~142)vs.122 mmHg(IQR:110~137),P<0.001]显著高于没有糖尿病的患者(P<0.001)。2型糖尿病和其他代谢性疾病共存于COVID-19患者中,这可能会增加发病率并加重COVID-19的病情。血糖和脂质代谢的最佳管理是确保更好的临床结果的关键。对于患有糖尿病及其他基础和慢性代谢性疾病的COVID-19患者,应提高临床警惕性。

Severe acute respiratory syndrome coronavirus 2 infection: Role of interleukin-6 and the inflammatory cascade

Since December 2019,a novel coronavirus that represents a serious threat to human lives has emerged.There is still no definite treatment for severe cases of the disease caused by this virus,named coronavirus disease 2019(COVID-19).One of the most considered treatment strategies targets the exaggerated immune regulator,and interleukin(IL)-6 is a crucial pro-inflammatory mediator.Severe acute respiratory syndrome coronavirus 2(SARSCoV-2)cases show an elevated level of IL-6 related to disease severity.IL-6 activity can be inhibited by the following:IL-6 itself,IL-6 signaling pathways such as Janus kinase and signal transducer and activator of transcription(JAK-STAT),gp130,IL-6R,and downstream activated ILs,such as IL-17 and IL-6 cytokine.Currently,according to these studies and their results,IL-6 blockade with anti-IL-6 or its receptor antibodies such as tocilizumab in COVID-19 is beneficial in severe cases and may reduce the mortality rate.JAK-STAT inhibitors block the cytokine storm by inhibiting several crucial pro-inflammatory mediators such as TNF-αand IL-6 and have shown various results in clinical trials.IL-6 induces IL-17 secretion,and IL-17 is involved in the pathogenesis of inflammatory processes.Clinical trials of anti-IL-17 drugs are currently recruiting,and anti-gp130 antibody is preclinical.However,this agent has shown positive effects in inflammatory bowel disease clinical trials and could be tested for SARS-CoV-2.This study aimed to review the role of IL-6 in the cytokine storm and studies regarding IL-6 and blockade of its inflammatory pathways in COVID-19 to determine if any of these agents are beneficial for COVID-19 patients.

The Effect of Soy Nuts on Glycemic Control, Lipid Profile and Insulin-Resistance in Type 2 Diabetic Patients

Type 2 diabetes has a high prevalence and a growing trend. The use of a proper diet treatment is one of the therapeutic approaches of patients. The use of the soy has shown the effective results in glycemic control of patients with type 2 diabetes;however, data are paradoxical. The present study aimed to examine the effectiveness of soy nuts on glycemic control, blood pressure and lipid profile and insulin-resistance of the diabetic patients. Methods: In this case-control study 69 type 2 diabetic patients were randomly divided into two groups: intervention (n = 35) and control (n = 34). The patients in the intervention group substituted 60 grams of soy nuts as a part of the daily protein requirement for eight weeks. In contrast, the patients in the control group received usual diet of diabetes (no soy). The drugs received by patients had not been changed during the intervention period. Before and at the end of the intervention, Hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), serum insulin levels, insulin-resistance, systolic and diastolic blood pressure, low density lipoprotein-cholesterol (LDL-c), high density lipoprotein-cholesterol (HDL-c) and total cholesterol, and triglycerides (TG) were measured in the patients. Insulin-resistance was calculated by Homeostatic model assessment-IR formula (HOMA-IR). Results: Soy consumption significantly lowered FPG (P = 0.03), HbA1c (P P = 0.01), insulin-resistance (P = 0.01), total cholesterol (P P = 0.01), but did not have any significant effect on systolic blood pressure (P = 0.4), diastolic blood pressure (P = 0.2), HDL-c (P = 0.4) and TG (P = 0.2). Conclusion: Consumption of soy nuts in type 2 diabetic patients can cause an improvement in the glycemic control and insulin-resistance, and the lipid profile does not have any significant effect on blood pressure.

Mechanism of action of the bile acid receptor TGR5 in obesity

G protein-coupled receptors(GPCRs)are a large family of membrane protein receptors,and Takeda G protein-coupled receptor 5(TGR5)is a member of this family.As a membrane receptor,TGR5 is widely distributed in different parts of the human body and plays a vital role in regulating metabolism,including the processes of energy consumption,weight loss and blood glucose homeostasis.Recent studies have shown that TGR5 plays an important role in glucose and lipid metabolism disorders such as fatty liver,obesity and diabetes.With the global obesity situation becoming more and more serious,a comprehensive explanation of the mechanism of TGR5 and filling the gaps in knowledge concerning clinical ligand drugs are urgently needed.In this review,we mainly explain the anti-obesity mechanism of TGR5 to promote the further study of this target,and show the electron microscope structure of TGR5 and review recent studies on TGR5 ligands to illustrate the specific binding between TGR5 receptor binding sites and ligands,which can effectively provide new ideas for ligand research and promote drug research.

Bioactive components,pharmacological properties and underlying mechanism of Ganoderma lucidum spore oil:A review

Ganoderma lucidum is a Chinese medicinal fungus with a long history of use in healthcare and disease treatment.G.lucidum spores(GLS)are tiny germ cells released from the mushroom cap during the mature stage of growth.They contain all the genetic active substances of G.lucidum.G.lucidum spore oil(GLSO)is a lipid component extracted from broken-walled Ganoderma spores using supercritical CO_(2)extraction technology.GLSO contains fatty acids,Ganoderma triterpenes,sterols and other bioactive compounds.Previous studies have demonstrated that GLSO has a wide range of pharmacological properties,including anti-tumor,anti-aging,neuroprotection,immunomodulation,hepatoprotection and modulation of metabolic diseases.This review summarizes the research progress of GLSO over the past two decades in terms of its bioactive components,extraction and processing techniques,pharmacological effects and safety evaluation.This provides a solid foundation for further research and application of GLSO.

Commentary:Gut microbiota reduce the risk of hyperuricemia and gout in the human body

Gout,a prevalent and painful metabolic disease often associated with obesity and aging,is caused by the deposition of urate crystals in joints,bones,or soft tissues1.Urate is an intermediate metabolite within the purine degradation pathway,predominantly derived from uric acid under physiological pH levels.Hyperuricemia occurs due to excessive uric acid production or insufficient excretion2,which is associated with various chronic diseases,including type 2 diabetes.

Commentary:Mammokine directs beige adipocytes to reserve energy for milk production in breast

Beige/brown adipocytes play a crucial role in regulating the body’s overall energy balance.The thermogenic function is under the influence of various tissues,including the brain,muscles,and liver.However,the breast tissue is not in the list.

Commentary:The central lymphatic drainage in pharmacological,surgical and physical therapies of Alzheimer’s disease

Alzheimer’s disease(AD)is a prevalent neurodegenerative disease in the aged population1.Etiology of AD remains largely unknown and no effective drugs are available in clinical settings to reverse or delay the disease progress2.In recent years,the brain’s lymphatic systems,including glymphatic3 that exists in the brain interstitial space and meningeal lymphatic vessels4 that presents within the dural sinuses,have been found to play an important role in the AD pathogenesis.

Network Pharmacology in Research of Chinese Medicine Formula: Methodology, Application and Prospective

Chinese medicine(CM) is usually prescribed as CM formula to treat disease. The lack of effective research approach makes it difficult to elucidate the molecular mechanisms of CM formula owing to its complicated chemical compounds. Network pharmacology is increasingly applied in CM formula research in recent years, which is identified suitable for the study of CM formula. In this review, we summarized the methodology of network pharmacology, including network construction, network analysis and network verification. The aim of constructing a network is to achieve the interaction between the bioactive compounds and targets and the interaction between various targets, and then find out and validate the key nodes via network analysis and network verification. Besides, we reviewed the application in CM formula research, mainly including targets discovery, bioactive compounds screening, toxicity evaluation, mechanism research and quality control research. Finally, we proposed prospective in the future and limitations of network pharmacology, expecting to provide new strategy and thinking on study for CM formula.

Biallelic mutations in WDR12 are associated with male infertility with tapered-head sperm

Teratozoospermia is a rare disease associated with male infertility.Several recurrent genetic mutations have been reported to be associated with abnormal sperm morphology,but the genetic basis of tapered-head sperm is not well understood.In this study,whole-exome sequencing(WES)identified a homozygous WD repeat domain 12(WDR12;p.Ser162Ala/c.484T>G)variant in an infertile patient with tapered-head spermatozoa from a consanguineous Chinese family.Bioinformatic analysis predicted this mutation to be a pathogenic variant.To verify the effect of this variant,we analyzed WDR12 protein expression in spermatozoa of the patient and a control individual,as well as in the 293T cell line,by Western blot analysis,and found that WDR12 expression was significantly downregulated.To understand the role of normal WDR12,we evaluated its mRNA and protein expression in mice at different ages.We observed that WDR12 expression was increased in pachytene spermatocytes,with intense staining visible in round spermatid nuclei.Based on these results,the data suggest that the rare biallelic pathogenic missense variant(p.Ser162Ala/c.484T>G)in the WDR12 gene is associated with tapered-head spermatozoa.In addition,after intracytoplasmic sperm injection(ICSI),a successful pregnancy was achieved.This finding indicates that infertility associated with this WDR12 homozygous mutation can be overcome by ICSI.The present results may provide novel insights into understanding the molecular mechanisms of male infertility.

Commentary: Inhibitors of mitochondrial respiratory chain in the treatment of type 2 diabetes

Prevalence of type 2 diabetes has been increased worldwide following the high incidence of obesity and growing population of aging, which are two conditions for absolute energy excess with accumulation of TAG in the body and relative energy excess due to reduced energy expense, respectively. It appears that type 2 diabetes is a compensatory mechanism of body to energy excess through urine discharge of glucose.

Evaluation of Renal Impairment in Patients with Diabetic Kidney Disease by Integrated Chinese and Western Medicine

Objective:To investigate the factors related to renal impairment in patients with diabetic kidney disease(DKD)from the perspective of integrated Chinese and Western medicine.Methods:Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included.According to Kidney Disease Improving Global Outcomes(KDIGO)staging guidelines,patients were divided into a chronic kidney disease(CKD)1-3 group and a CKD 4-5 group.Clinical data were collected,and logistic regression was used to analyze the factors related to different CKD stages in DKD patients.Results:Demographically,male was a factor related to increased CKD staging in patients with DKD(OR=3.100,P=0.002).In clinical characteristics,course of diabetes>60 months(OR=3.562,P=0.010),anemia(OR=4.176,P<0.001),hyperuricemia(OR=3.352,P<0.001),massive albuminuria(OR=4.058,P=0.002),atherosclerosis(OR=2.153,P=0.007)and blood deficiency syndrome(OR=1.945,P=0.020)were factors related to increased CKD staging in patients with DKD.Conclusion:Male,course of diabetes>60 months,anemia,hyperuricemia,massive proteinuria,atherosclerosis,and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD.(Registration No.NCT03865914).

CCAAT/Enhancer-Binding Proteins in Fibrosis:Complex Roles Beyond Conventional Understanding

CCAAT/enhancer-binding proteins(C/EBPs)are a family of at least six identified transcription factors that contain a highly conserved basic leucine zipper domain and interact selectively with duplex DNA to regulate target gene expression.C/EBPs play important roles in various physiological processes,and their abnormal function can lead to various diseases.Recently,accumulating evidence has demonstrated that aberrant C/EBP expression or activity is closely associated with the onset and progression of fibrosis in several organs and tissues.During fibrosis,various C/EBPs can exert distinct functions in the same organ,while the same C/EBP can exert distinct functions in different organs.Modulating C/EBP expression or activity could regulate various molecular processes to alleviate fibrosis in multiple organs;therefore,novel C/EBPs-based therapeutic methods for treating fibrosis have attracted considerable attention.In this review,we will explore the features of C/EBPs and their critical functions in fibrosis in order to highlight new avenues for the development of novel therapies targeting C/EBPs.

Sodium butyrate activates HMGCS2 to promote ketone body production through SIRT5-mediated desuccinylation

Ketone bodies have beneficial metabolic activities,and the induction of plasma ketone bodies is a health promotion strategy.Dietary supplementation of sodium butyrate(SB)is an effective approach in the induction of plasma ketone bodies.However,the cellular and molecular mechanisms are unknown.In this study,SB was found to enhance the catalytic activity of 3-hydroxy-3-methylglutaryl-CoA synthase 2(HMGCS2),a rate-limiting enzyme in ketogenesis,to promote ketone body production in hepatocytes.SB administrated by gavage or intraperitoneal injection significantly induced bloodβ-hydroxybutyrate(BHB)in mice.BHB production was induced in the primary hepatocytes by SB.Protein succinylation was altered by SB in the liver tissues with down-regulation in 58 proteins and up-regulation in 26 proteins in the proteomics analysis.However,the alteration was mostly observed in mitochondrial proteins with 41%down-and 65%up-regulation,respectively.Succinylation status of HMGCS2 protein was altered by a reduction at two sites(K221 and K358)without a change in the protein level.The SB effect was significantly reduced by a SIRT5 inhibitor and in Sirt5-KO mice.The data suggests that SB activated HMGCS2 through SIRT5-mediated desuccinylation for ketone body production by the liver.The effect was not associated with an elevation in NAD+/NADH ratio according to our metabolomics analysis.The data provide a novel molecular mechanism for SB activity in the induction of ketone body production.