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Abstract Diabetic vascular complications attract increased attention due to their high morbidity, mortality and disability rate. Comprehensive and in-depth exploration of the etiology and pathogenesis of diabetic vascular complications is important for diagnosis and treatment. Endothelial extracellular vesicles (EVs) serve as potential intercellular communicators, transmitting biological information from the donor cell to the recipient cell, exerting both harmful and beneficial effects on vascular function. Endothelial EVs are new diagnostic and therapeutic targets and biomarkers in diabetic vascular complications. This review summarizes the biogenesis and release of endothelial EVs, as well as isolation and characterization methods, and discusses the role of endothelial EVs in the maintenance of vascular homeostasis along with their contributions to vascular dysfunction. Finally, the article illustrates the impact of endothelial EVs on the pathogenesis of diabetic vascular complications and evaluates their potential as therapeutic tools and diagnostic markers in diabetic vascular complications.

This review examines the complexities of Type 2 Diabetes Mellitus (T2DM), focusing on the critical role of integrating omics technologies with traditional experimental methods. It underscores the advancements in understanding the genetic diversity of T2DM and emphasizes the evolution towards personalized treatment modalities. The paper analyzes a variety of omics approaches, including genomics, methylation, transcriptomics, proteomics, metabolomics, and intestinal microbiomics, delineating their substantial contributions to deciphering the multifaceted mechanisms underlying T2DM. Furthermore, the review highlights the indispensable role of non-omics experimental techniques in comprehending and managing T2DM, advocating for their integration in the development of tailored medicine and precision treatment strategies. By identifying existing research gaps and suggesting future research trajectories, the review underscores the necessity for a comprehensive, multidisciplinary approach. This approach synergistically combines clinical insights with cutting-edge biotechnologies, aiming to refine the management and therapeutic interventions of T2DM, and ultimately enhancing patient outcomes. This synthesis of knowledge and methodologies paves the way for innovative advancements in T2DM research, fostering a deeper understanding and more effective treatment of this complex condition.

Abstract Type 2 diabetes mellitus (T2DM) poses a significant global health burden. This is particularly due to its macrovascular complications, such as coronary artery disease, peripheral vascular disease, and cerebrovascular disease, which have emerged as leading contributors to morbidity and mortality. This review comprehensively explores the pathophysiological mechanisms underlying these complications, protective strategies, and both existing and emerging secondary preventive measures. Furthermore, we delve into the applications of experimental models and methodologies in foundational research while also highlighting current research limitations and future directions. Specifically, we focus on the literature published post-2020 concerning the secondary prevention of macrovascular complications in patients with T2DM by conducting a targeted review of studies supported by robust evidence to offer a holistic perspective.

ObjectiveGastrointestinal dysfunction are often associated with type 2 diabetes mellitus (T2DM), a complicated metabolic illness. Contributing factors have been proposed, including genetic predisposition, gene environmental, and lifestyle interactions, but the pathophysiology remains unknown.MethodsWe aim to explore the possible causes behind gastrointestinal dysfunction caused by type 2 diabetes in this study. A comprehensive analysis of the gastric sinus metabolome, transcriptome, and proteome in db/db mice with gastrointestinal dysfunction was conducted.ResultsThe model group of mice had considerably lower small intestine propulsion and gastric emptying rates, higher blood glucose levels, and were significantly obese compared to the control group. We identified 297 genes, 350 proteins, and 1,001 metabolites exhibiting significant differences between db/db and control mice (p < 0.05). Moreover, multi-omics analysis revealed that the genes, proteins, and metabolites in the T2DM-induced gastroenteropathy mice group were involved in arachidonic acid metabolism, glycerophospholipid metabolism and vitamin digestion and absorption. Specifically, Cbr3, Etnppl, and Apob were the major mRNAs associated with T2DM-induced gastrointestinal dysfunction, while Cyp2b10, Cyp2b19, Pgs1, Gpat3, Apoa4, and Tcn2 were the major proteins associated with T2DM-induced gastrointestinal injury, and 16(R)-HET, 5-HETE, LysoPC (22:0), and Pantothenic acid were the major metabolites associated with T2DM-induced gastrointestinal disorders.ConclusionThe mechanism of action of diabetic gastroenteropathy may be related to vitamin digestion and absorption, glycerophospholipid metabolism, and arachidonic acid metabolism.

BackgroundDiabetic foot complications impose a significant strain on healthcare systems worldwide, acting as a principal cause of morbidity and mortality in individuals with diabetes mellitus. While traditional methods in diagnosing and treating these conditions have faced limitations, the emergence of Machine Learning (ML) technologies heralds a new era, offering the promise of revolutionizing diabetic foot care through enhanced precision and tailored treatment strategies.ObjectiveThis review aims to explore the transformative impact of ML on managing diabetic foot complications, highlighting its potential to advance diagnostic accuracy and therapeutic approaches by leveraging developments in medical imaging, biomarker detection, and clinical biomechanics.MethodsA meticulous literature search was executed across PubMed, Scopus, and Google Scholar databases to identify pertinent articles published up to March 2024. The search strategy was carefully crafted, employing a combination of keywords such as “Machine Learning,” “Diabetic Foot,” “Diabetic Foot Ulcers,” “Diabetic Foot Care,” “Artificial Intelligence,” and “Predictive Modeling.” This review offers an in-depth analysis of the foundational principles and algorithms that constitute ML, placing a special emphasis on their relevance to the medical sciences, particularly within the specialized domain of diabetic foot pathology. Through the incorporation of illustrative case studies and schematic diagrams, the review endeavors to elucidate the intricate computational methodologies involved.ResultsML has proven to be invaluable in deriving critical insights from complex datasets, enhancing both the diagnostic precision and therapeutic planning for diabetic foot management. This review highlights the efficacy of ML in clinical decision-making, underscored by comparative analyses of ML algorithms in prognostic assessments and diagnostic applications within diabetic foot care.ConclusionThe review culminates in a prospective assessment of the trajectory of ML applications in the realm of diabetic foot care. We believe that despite challenges such as computational limitations and ethical considerations, ML remains at the forefront of revolutionizing treatment paradigms for the management of diabetic foot complications that are globally applicable and precision-oriented. This technological evolution heralds unprecedented possibilities for treatment and opportunities for enhancing patient care.

Single-cell sequencing is a novel and rapidly advancing high-throughput technique that can be used to investigating genomics, transcriptomics, and epigenetics at a single-cell level. Currently, single-cell sequencing can not only be used to draw the pancreatic islet cells map and uncover the characteristics of cellular heterogeneity in type 2 diabetes, but can also be used to label and purify functional beta cells in pancreatic stem cells, improving stem cells and islet organoids therapies. In addition, this technology helps to analyze islet cell dedifferentiation and can be applied to the treatment of type 2 diabetes. In this review, we summarize the development and process of single-cell sequencing, describe the potential applications of single-cell sequencing in the field of type 2 diabetes, and discuss the prospects and limitations of single-cell sequencing to provide a new direction for exploring the pathogenesis of type 2 diabetes and finding therapeutic targets.

Abstract The maintenance of iron homeostasis is essential for proper endocrine function. A growing body of evidence suggests that iron imbalance is a key factor in the development of several endocrine diseases. Nowadays, ferroptosis, an iron-dependent form of regulated cell death, has become increasingly recognized as an important process to mediate the pathogenesis and progression of type 2 diabetes mellitus (T2DM). It has been shown that ferroptosis in pancreas β cells leads to decreased insulin secretion; and ferroptosis in the liver, fat, and muscle induces insulin resistance. Understanding the mechanisms concerning the regulation of iron metabolism and ferroptosis in T2DM may lead to improved disease management. In this review, we summarized the connection between the metabolic pathways and molecular mechanisms of iron metabolism and ferroptosis in T2DM. Additionally, we discuss the potential targets and pathways concerning ferroptosis in treating T2DM and analysis the current limitations and future directions concerning these novel T2DM treatment targets.

Pollen cells require large amounts of sugars from the anther to support their development, which is critical for plant sexual reproduction and crop yield. Sugars Will Eventually be Exported Transporters (SWEETs) have been shown to play an important role in the apoplasmic unloading of sugars from anther tissues into symplasmically isolated developing pollen cells and thereby affect the sugar supply for pollen development. However, among the 17 CsSWEET genes identified in the cucumber (Cucumis sativus L.) genome, the CsSWEET gene involved in this process has not been identified. Here, a member of the SWEET gene family, CsSWEET5a, was identified and characterized. The quantitative real-time PCR and β-glucuronidase expression analysis revealed that CsSWEET5a is highly expressed in the anthers and pollen cells of male cucumber flowers from the microsporocyte stage (stage 9) to the mature pollen stage (stage 12). Its subcellular localization indicated that the CsSWEET5a protein is localized to the plasma membrane. The heterologous expression assays in yeast demonstrated that CsSWEET5a encodes a hexose transporter that can complement both glucose and fructose transport deficiencies. CsSWEET5a can significantly rescue the pollen viability and fertility of atsweet8 mutant Arabidopsis plants. The possible role of CsSWEET5a in supplying hexose to developing pollen cells via the apoplast is also discussed.

Glycolipid metabolism disorder are major threats to human health and life. Genetic, environmental, psychological, cellular, and molecular factors contribute to their pathogenesis. Several studies demonstrated that neuroendocrine axis dysfunction, insulin resistance, oxidative stress, chronic inflammatory response, and gut microbiota dysbiosis are core pathological links associated with it. However, the underlying molecular mechanisms and therapeutic targets of glycolipid metabolism disorder remain to be elucidated. Progress in high-throughput technologies has helped clarify the pathophysiology of glycolipid metabolism disorder. In the present review, we explored the ways and means by which genomics, transcriptomics, proteomics, metabolomics, and gut microbiomics could help identify novel candidate biomarkers for the clinical management of glycolipid metabolism disorder. We also discuss the limitations and recommended future research directions of multi-omics studies on these diseases.

Introduction Metformin (MET) can regulate glucose and lipid levels, and the gut microbiota may be involved in the control of metabolism. We hypothesized that MET alleviates glucolipid metabolism disorder by modulating gut microbiota and microbial metabolites.Research design and methods A total of 24 male C57BL/6 J mice were equally divided into three groups (normal control, model control (MC), and MET-treated groups). Model mice were established by feeding a high-fat diet for 6 weeks. The MET-treated group was administered MET solution (2.5 g/100 mL, 250 mg/kg). Fecal samples were collected to characterize the microbiota system using metagenomic shotgun sequencing and gas chromatography–time of flight–mass spectrometry analysis. Phenotypic and biochemical indices were obtained for further correlation analysis.Results Compared with the MC group, MET reduced the levels of weight, glucose, areas under the glucose curve in the glucose tolerance test, triglyceride (TG), and total cholesterol (TC). A decreasing abundance of bacteria, including Parabacteroides distasonis, and an increasing abundance of bacteria, including Bacteroides vulgatus, were observed in the MET-treated group. The 2-deoxytetronic acid declined after MET intervention and was positively correlated with species over-represented in the MC group and negatively correlated with species enriched in the MET-treated group. Additionally, species enriched in the MET-treated group negatively correlated with glucose, areas under the glucose curve in the glucose tolerance test, and TGs. Further, the correlation between the differential metabolites, which decreased after MET intervention, and the phenotypic indices was positive.Conclusions MET-induced restoration of intestinal homeostasis correlates with the amelioration of host glucolipid metabolism.

Berberine is a natural active ingredient extracted from the rhizome of Rhizoma Coptidis, which interacts with multiple intracellular targets and exhibits a wide range of pharmacological activities. Previous studies have preliminarily confirmed that the regulation of mitochondrial activity is related to various pharmacological actions of berberine, such as regulating blood sugar and lipid and inhibiting tumor progression. However, the mechanism of berberine’s regulation of mitochondrial activity remains to be further studied. This paper summarizes the molecular mechanism of the mitochondrial quality control system and briefly reviews the targets of berberine in regulating mitochondrial activity. It is proposed that berberine mainly regulates glycolipid metabolism by regulating mitochondrial respiratory chain function, promotes tumor cell apoptosis by regulating mitochondrial apoptosis pathway, and protects cardiac function by promoting mitophagy to alleviate mitochondrial dysfunction. It reveals the mechanism of berberine’s pharmacological effects from the perspective of mitochondria and provides a scientific basis for the application of berberine in the clinical treatment of diseases.

Cucurbita pepo L. is an essential economic vegetable crop worldwide, and its production is severely affected by powdery mildew (PM). However, our understanding of the molecular mechanism of PM resistance in C. pepo is very limited. Long non-coding RNAs (lncRNAs) play an important role in regulating plant responses to biotic stress. Here, we systematically identified 2,363 reliably expressed lncRNAs from the leaves of PM-susceptible (PS) and PM-resistant (PR) C. pepo. The C. pepo lncRNAs are shorter in length and expressed at a lower level than the protein-coding transcripts. Among the 2,363 lncRNAs, a total of 113 and 146 PM-responsive lncRNAs were identified in PS and PR, respectively. Six PM-responsive lncRNAs were predicted as potential precursors of microRNAs (miRNAs). In addition, 58 PM-responsive lncRNAs were predicted as targets of miRNAs and one PM-responsive lncRNA was predicted as an endogenous target mimic (eTM). Furthermore, a total of 5,200 potential cis target genes and 5,625 potential trans target genes were predicted for PM-responsive lncRNAs. Functional enrichment analysis showed that these potential target genes are involved in different biological processes, such as the plant-pathogen interaction pathway, MAPK signaling pathway, and plant hormone signal transduction pathway. Taken together, this study provides a comprehensive view of C. pepo lncRNAs and explores the putative functions of PM-responsive lncRNAs, thus laying the foundation for further study of the regulatory mechanisms of lncRNAs responding to PM.

Introduction: Glucose and lipid metabolism disturbances has become the third major disease after cancer and cardio-cerebrovascular diseases. Emerging evidence shows that berberine can effectively intervene glucose and lipid metabolism disturbances, but the underlying mechanisms of this remain unclear. To investigate this issue, we performed metagenomic and metabolomic analysis in a group of normal mice (the NC group), mice with disturbances in glucose and lipid metabolism (the MC group) and mice with disturbances in glucose and lipid metabolism after berberine intervention (the BER group).Result: Firstly, analysis of the clinical indicators revealed that berberine significantly improved the blood glucose and blood lipid of the host. The fasting blood glucose level decreased by approximately 30% in the BER group after 8 weeks and the oral glucose tolerance test showed that the blood glucose level of the BER group was lower than that of the MC group at any time. Besides, berberine significantly reduced body weight, total plasma cholesterol and triglyceride. Secondly, compared to the NC group, we found dramatically decreased microbial richness and diversity in the MC group and BER group. Thirdly, LDA effect size suggested that berberine significantly altered the overall gut microbiota structure and enriched many bacteria, including Akkermansia (p < 0.01), Eubacterium (p < 0.01) and Ruminococcus (p < 0.01). Fourthly, the metabolomic analysis suggested that there were significant differences in the metabolomics signature of each group. For example, isoleucine (p < 0.01), phenylalanine (p < 0.05), and arbutin (p < 0.05) significantly increased in the MC group, and berberine intervention significantly reduced them. The arbutin content in the BER group was even lower than that in the NC group. Fifthly, by combined analysis of metagenomics and metabolomics, we observed that there were significantly negative correlations between the reduced faecal metabolites (e.g., arbutin) in the BER group and the enriched gut microbiota (e.g., Eubacterium and Ruminococcus) (p < 0.05). Finally, the correlation analysis between gut microbiota and clinical indices indicated that the bacteria (e.g., Eubacterium) enriched in the BER group were negatively associated with the above-mentioned clinical indices (p < 0.05).Conclusion: Overall, our results describe that the changes of gut microbiota and metabolites are associated with berberine improving glucose and lipid metabolism disturbances.

The serine/threonine kinase Akt, also known as protein kinase B (PKB), is one of the key factors regulating glucose and lipid energy metabolism, and is the core focus of current research on diabetes and metabolic diseases. Akt is mostly expressed in key metabolism-related organs and it is activated in response to various stimuli, including cell stress, cell movement, and various hormones and drugs that affect cell metabolism. Genetic and pharmacological studies have shown that Akt is necessary to maintain the steady state of glucose and lipid metabolism and a variety of cellular responses. Existing evidence shows that metabolic syndrome is related to insulin resistance and lipid metabolism disorders. Based on a large number of studies on Akt-related pathways and reactions, we believe that Akt can be used as a potential drug target to effectively treat metabolic syndrome.

Background: Type 2 diabetes mellitus (T2DM) complicated with dyslipidaemia is associated with a high risk of cardiovascular diseases. The Jiangtang Tiaozhi (JTTZ) recipe is a Chinese herbal formula that has been used to regulate the blood glucose and lipid levels for many years. Interestingly, a previous study has demonstrated its efficacy; however, the associated mechanism remains unclear. We hypothesised that the therapeutic effect of the JTTZ on patients with T2DM may be mediated by the modulation of metabolites secreted by the gut microbiota. This study aims to examine this mechanism.Methods and analysis: This study is a randomised, positive drug parallel-controlled, open-label clinical trial in patients with T2DM and dyslipidaemia. A total of 96 patients will be recruited and randomly assigned to treatment with JTTZ or metformin for 12 weeks. The primary outcome will be the rates of effectively regulated blood glucose and lipid levels (measured with the levels of glycated haemoglobin, fasting plasma glucose, 2-h plasma glucose, triglyceride, and low-density lipoprotein cholesterol). The secondary outcomes will be the changes in body weight, body mass index, and waist circumference and Traditional Chinese Medicine symptom scores. In addition, 16S rRNA gene sequencing will be performed on the gut microbiota obtained from faeces, and metabolomics analysis will be performed based on blood and gut microbiota samples. Intention-to-treat, per-protocol analysis and safety analysis will be performed.Clinical trial registration number: https://clinicaltrials.gov/ct2/show/NCT04623567

The final outcome of diabetes is chronic complications, of which vascular complications are the most serious, which is the main cause of death for diabetic patients and the direct cause of the increase in the cost of diabetes. Type 1 and type 2 diabetes are the main types of diabetes, and their pathogenesis is completely different. Type 1 diabetes is caused by genetics and immunity to destroy a large number of β cells, and insulin secretion is absolutely insufficient, which is more prone to microvascular complications. Type 2 diabetes is dominated by insulin resistance, leading to atherosclerosis, which is more likely to progress to macrovascular complications. This article explores the pathogenesis of two types of diabetes, analyzes the pathogenesis of different vascular complications, and tries to explain the different trends in the progression of different types of diabetes to vascular complications, in order to better prevent diabetes and its vascular complications.

Gegen Qinlian Decoction (GQD) is a Chinese herbal medicine that has been reported to significantly decrease blood glucose levels, which is suggested to be related to interactions with the gut microbiota. However, the protective effect of GQD on intestinal barrier function with regard to its influence on the gut microbiota has not been explored to date. In this study, we investigated the role of the gut microbiota in mediating the hypoglycemic mechanism of GQD in type 2 diabetes mellitus (T2DM) rats induced by a single intraperitoneal injection of streptozotocin after 4 weeks of high-fat diet feeding. The T2DM rats were randomly allocated to receive GQD, metformin (Met), or saline for 12 consecutive weeks, and changes in metabolic parameters, intestinal barrier function, and inflammation were investigated. Gut microbiota was analyzed using 16S rRNA gene sequencing from fecal samples, and statistical analyses were performed to correlate microbiota composition with phenotypes of the T2DM rats. GQD administration decreased the levels of blood glucose and inflammatory cytokines, and increased the levels of tight junction proteins. Besides, GQD had a protective effect on islet function, restoring intestinal permeability, and inhibiting inflammation, as evidenced by increases in the levels of serum C-peptide, occludin, and claudin-1 in the colon, and also improved the expression of serum inflammatory factors. In addition, GQD regulated the structure of the gut microbiota by increasing the proportions of short-chain fatty acids-producing and anti-inflammatory bacteria, and decreasing the proportions of conditioned pathogenic bacteria associated with the diabetic phenotype. Overall, these findings suggest that GQD could ameliorate hyperglycemia and protect islet function by regulating the structure of the gut microbiota, thereby restoring intestinal permeability and inhibiting inflammation in T2DM rats. Our study thus suggests that the hypoglycemic mechanism of GQD is mediated by its modulation of the gut microbiota.

Objective: To conduct a randomized controlled clinical trial to evaluate the clinical efficacy and prognostic value of Jinhua Qinggan granules in patients with confirmed and suspected coronavirus disease 2019 (COVID-19).Methods: A total of 123 suspected and confirmed COVID-19 patients participated in this clinical trial and were randomly divided into Jinhua and Western medicine groups. For 14 days, the Jinhua group was treated with Jinhua Qinggan granules and antiviral drugs, and the Western medicine group was treated with antiviral drugs alone. We collected information on clinical symptoms, disease aggravation rates, and negative conversion rates of nucleic acids in patients, and observed the effects of anti-infective drugs.Results: There was no significant difference in symptom improvement rates between the two groups, both confirmed and suspected patients (P > 0.05). Both treatments relieved symptoms such as fever, fatigue, and diarrhea. However, the Jinhua treatment was superior in relieving fever and poor appetite. Anti-infective drug use rates were significantly lower in the Jinhua group than in the control group.Conclusion: Jinhua Qinggan granules combined with Western medicine could relieve the clinical symptoms of fever and poor appetite in COVID-19 patients, reduce the use of antibiotics to a certain extent.Clinical Trial Registration: The registration number at China Clinical Trial Registry is ChiCTR2000029601.

The pancreatic duodenum homeobox-1 (PDX-1) is a transcription factor encoded by a Hox-like homeodomain gene that plays a crucial role in pancreatic development, β-cell differentiation, and the maintenance of mature β-cell functions. Research on the relationship between PDX-1 and diabetes has gained much attention because of the increasing prevalence of diabetes melitus (DM). Recent studies have shown that the overexpression of PDX-1 regulates pancreatic development and promotes β-cell differentiation and insulin secretion. It also plays a vital role in cell remodeling, gene editing, and drug development. Conversely, the absence of PDX-1 increases susceptibility to DM. Therefore, in this review, we summarized the role of PDX-1 in pancreatic development and the pathogenesis of DM. A better understanding of PDX-1 will deepen our knowledge of the pathophysiology of DM and provide a scientific basis for exploring PDX-1 as a potential target for treating diabetes.

Traditional Chinese medicine (TCM) has played a significant role in the treatment of coronavirus disease 2019 (COVID-19) in Wuhan City. During the epidemic, Academician Tong Xiaolin suggested a close association of COVID-19 with cold-dampness, an etiological factor in TCM, by summarizing the characteristics of the COVID-19 patients in Wuhan. and the theory of Cold-dampness Plague was proposed. Based on the Cold-dampness Plague theory, a series of TCM drugs, such as Huoxiang Zhengqi Dropping Pills, Lianhua Qingwen Granules Hanshiyi Formula, and Tongzhi Granule were developed for the different stages, namely mild, moderate, severe, recovery, of the COVID-19. In addition, clinical evidences were obtained through randomized clinical trials or retrospective cohort studies. The Anti-SARS-CoV-2 mechanism of the TCM prescriptions were then summarized from the four aspects: targeting the ACE2 and 3CLPro, targeting cytokines, targeting acute immune responses to SARS-CoV-2, and targeting pulmonary fibrosis. Despite the clinical efficacy and therapeutic pharmacology speculation, more studies such as large-scale randomized clinical trials, cell and animal experiments are needed to further verify the theory of the Cold-dampness Plague in COVID-19 patients.

Grafting cultivation is implemented worldwide mainly to resist abiotic and biotic stresses and is an effective method to improve watermelon production. However, grafting may affect fruit development and quality. In our experiment, pumpkin-grafted (PG) watermelon fruits developed slower and the ripening period was extended compared to self-grafted (SG) fruits. We found that the concentrations of abscisic acid (ABA) among endogenous phytohormones were dramatically reduced by pumpkin grafting. In order to understand these changes at the gene expression level, we performed a comprehensive analysis of the fruit flesh transcriptomes between PG and SG during fruit development and ripening. A total of 1,675 and 4,102 differentially expressed genes (DEGs) were identified between PG and SG. Further functional enrichment analysis revealed that these DEGs were associated with carbohydrate biosynthesis, phytohormone signaling transmission, and cell wall metabolism categories. ABA centric phytohormone signaling and fruit quality-related genes including ABA receptor, PP2C proteins, AP2-EREBP transcription factors, sucrose transporter, and carotenoid isomerase were co-expressed with fruit ripening. These results provide the valuable resource for understanding the mechanism of pumpkin grafting effect on watermelon fruit ripening and quality development.

ObjectiveDuring the follow-up of patients recovered from coronavirus disease 2019 (COVID-19) in the quarantine and observation period, some of the cured patients showed positive results again. The recurrent positive RT-PCR test results drew widespread concern. We observed a certain number of cured COVID-19 patients with positive RT-PCR test results and try to analyze the factors that caused the phenomenon.MethodsWe conducted an observational study in COVID-19 patients discharged from 6 rehabilitation stations in Wuhan, China. All observed subjects met the criteria for hospital discharge and were in quarantine. Data regarding age, sex, body mass index (BMI), course of disease, comorbidity, smoking status and alcohol consumption, symptoms in and out of quarantine, and intervention were collected from the subjects’ medical records and descriptively analyzed. The main outcome of this study was the RT-PCR test result of the observed subjects at the end of quarantine (negative or positive). Logistic regression analysis was used to identify the influencing factors related to recurrent positive RT-PCR test results.ResultsIn this observational study, 420 observed subjects recovered from COVID-19 were included. The median age was 56 years, 63.6% of the subjects were above 50 years old, and 50.7% (213/420) were female. The most common comorbidities were hypertension [26.4% (111/420)], hyperlipidemia [10.7% (45/420)], and diabetes [10.5% (44/420)]. 54.8% (230/420) manifested one or more symptoms at the beginning of the observation period, the most common symptoms were cough [27.6% (116/420)], shortness of breath 23.8% (100/420)], and fatigue [16.2% (68/420)], with fever rare [2.6% (11/420)]. A total of 325 subjects were exposed to comprehensive intervention; 95 subjects were absence of intervention. The recurrence rate of positive RT-PCR test results with comprehensive intervention was 2.8% (9/325), and that with no intervention was 15.8% (15/95). The results of logistic regression analysis showed that after adjusted for factors such as age, sex, and comorbidity and found out that comprehensive intervention was correlated with the recurrent positive RT-PCR test results. There was appreciably less recurrence in the comprehensive intervention group.ConclusionsThe factors related to positive RT-PCR test results in observed subjects recovered from COVID-19 were age, comorbidity, and comprehensive intervention, among which comprehensive intervention might be a protective factor.Clinical Trial RegistrationChictr.org.cn, identifier ChiCTR2000030747.

Herbal medicines (HMs) are a major subset of complementary and alternative medicine. They have been employed for the efficient clinical management of type 2 diabetes mellitus (T2DM) for centuries. However, the related underlying mechanisms still remain to be elucidated. It has been found out that microbiota is implicated in the pathogenesis and treatment of T2DM. An interplay between gut microbiota and host occurs mainly at the gastrointestinal mucosal barrier. The host movements influence the composition and abundance of gut microbiota, whereas gut microbiota in turn modulate the metabolic and immunological activities of the host. Intestinal dysbiosis, endotoxin-induced metabolic inflammation, immune response disorder, bacterial components and metabolites, and decreased production of short-chain fatty acids are considered significant pathogenic mechanisms underlying T2DM. The interaction between gut microbiota and HMs during T2DM treatment has been investigated in human, animal, and in vitro studies. HMs regulate the composition of beneficial and harmful bacteria and decrease the inflammation caused by gut microbiota. Furthermore, the metabolism of gut microbiota modulates HM biotransformation. In this review, we have summarized such research findings, with the aim to improve our understanding of the pathogenesis and potential therapeutic mechanisms of HMs in T2DM and to provide new insights into specific targeted HM-based therapies and drug discovery.

Metabolic syndrome (MetS) is a multifarious metabolic disorder that could severely damage multiple organs. The emergence of MetS has markedly increased medical burden for patients. The treatment of MetS involves multitarget regulation, which is the advantage of traditional Chinese medicine (TCM). Many high-quality studies related to TCM for MetS have been conducted in recent years; however, no overall efficacy analysis has been reported. To evaluate the efficacy and safety of TCM against MetS, we reviewed randomized controlled trials of MetS published in the past decade and then selected and analyzed 16 high-quality articles from over 800 papers. The results showed that TCM might be beneficial in improving body weight as well as in regulating glucose and lipid metabolisms; thus, TCM might be an ideal alternative therapy for MetS management. Treatment safety was also estimated in our analysis. A more elaborately designed and long-term observation of TCM for MetS should be performed in the future.

Background. Diabetes mellitus (DM) belongs to the progressive and irreversible disease. With the development of the disease, the function of beta cells declines significantly. Current treatments cannot reverse the course of the disease. The role of traditional Chinese medicine (TCM) in the DM treatment has been recognized widely, while there are few long-term observation reports. In this study, we introduced a case of DM treated by classical prescription alone for 10 years, which would provide the reference for clinical practice. Case Presentation. A 64-year-old male complained of a 2-month history of dry mouth, frequent urination, and blurred vision and found increased blood glucose for 3 days. The patient’s glycated hemoglobin was 14.2%, fasting plasma glucose fluctuated at 12-15 mmol/L, and urinary albumin excretion rate (UAER) was 32.9 μg/min. The male was treated with 10 years of continuous classical prescription alone. After 3 months of TCM treatment, the patient’s blood glucose level decreased significantly and blurred vision symptoms improved. With continued TCM treatment, his UAER normalized. Subsequently, he continued outpatient consultation, and his TCM prescription was adjusted according to clinical symptoms. After 10 years of continuous TCM treatment, his blood glucose remained stable, urinary microalbumin quantitation showed no abnormalities, and blurred vision disappeared. Conclusions. This case provides specific treatment plans and effective references for long-term control of blood glucose, prevention and treatment of diabetes complications, delay of disease progression, and protection of impaired islet function in the treatment of diabetes with TCM. TCM may become a meaningful alternative DM treatment in the future.

ABSTRACT Accumulating evidence implicates gut microbiota as promising targets for the treatment of type 2 diabetes mellitus (T2DM). With a randomized clinical trial, we tested the hypothesis that alteration of gut microbiota may be involved in the alleviation of T2DM with hyperlipidemia by metformin and a specifically designed herbal formula (AMC). Four hundred fifty patients with T2DM and hyperlipidemia were randomly assigned to either the metformin- or AMC-treated group. After 12 weeks of treatment, 100 patients were randomly selected from each group and assessed for clinical improvement. The effects of the two drugs on the intestinal microbiota were evaluated by analyzing the V3 and V4 regions of the 16S rRNA gene by Illumina sequencing and multivariate statistical methods. Both metformin and AMC significantly alleviated hyperglycemia and hyperlipidemia and shifted gut microbiota structure in diabetic patients. They significantly increased a coabundant group represented by Blautia spp., which significantly correlated with the improvements in glucose and lipid homeostasis. However, AMC showed better efficacies in improving homeostasis model assessment of insulin resistance (HOMA-IR) and plasma triglyceride and also exerted a larger effect on gut microbiota. Furthermore, only AMC increased the coabundant group represented by Faecalibacterium spp., which was previously reported to be associated with the alleviation of T2DM in a randomized clinical trial. Metformin and the Chinese herbal formula may ameliorate type 2 diabetes with hyperlipidemia via enriching beneficial bacteria, such as Blautia and Faecalibacterium spp. IMPORTANCE Metabolic diseases such as T2DM and obesity have become a worldwide public health threat. Accumulating evidence indicates that gut microbiota can causatively arouse metabolic diseases, and thus the gut microbiota serves as a promising target for disease control. In this study, we evaluated the role of gut microbiota during improvements in hyperglycemia and hyperlipidemia by two drugs: metformin and a specifically designed Chinese herbal formula (AMC) for diabetic patients with hyperlipidemia. Both drugs significantly ameliorated blood glucose and lipid levels and shifted the gut microbiota. Blautia spp. were identified as being associated with improvements in glucose and lipid homeostasis for both drugs. AMC exerted larger effects on the gut microbiota together with better efficacies in improving HOMA-IR and plasma triglyceride levels, which were associated with the enrichment of Faecalibacterium spp. In brief, these data suggest that gut microbiota might be involved in the alleviation of diabetes with hyperlipidemia by metformin and the AMC herbal formula.

Background and Aim. Studies have shown an increasing number of type 2 diabetes (T2D) patients with concomitant obesity and hyperlipidemia syndromes, resulting from relevant metabolic disorders. However, there are few medications and therapies, which can thoroughly address these issues. Therefore, the current study evaluated the efficacy and safety of using JTTZ, a Chinese herbal formula, to treat T2D with obesity and hyperlipidemia. Methods. A total of 450 participants with T2D (HbA1c ≥ 7.0%; waist circumference ≥ 90 cm and 80 cm in males and females, resp.; and triglycerides (TG) ≥ 1.7 mmol/L) were randomly assigned, in equal proportions, to two groups in this multicenter randomized, positive-controlled, open-label trial. One group received JTTZ formula, and the other received metformin (MET) for 12 consecutive weeks. The primary efficacy outcomes were changes in HbA1c, TG, weight, and waist circumference. Adverse reactions and hypoglycemia were monitored. Results. HbA1c decreased by 0.75 ± 1.32% and 0.71 ± 1.2% in the JTTZ and MET groups, respectively, after 12 weeks of treatment. TG levels in the JTTZ and MET groups were reduced by 0.64 ± 2.37 mmol/L and 0.37 ± 2.18 mmol/L, respectively. Weight was decreased by 2.47 ± 2.71 kg in the JTTZ group and by 2.03 ± 2.36 kg in the MET group. JTTZ also appeared to alleviate insulin resistance and increase HOMA-β. In addition, symptoms were significantly relieved in participants in the JTTZ group compared to those in the MET group. One case of hypoglycemia was reported in the MET group. No severe adverse events were reported in either group. Conclusions. The JTTZ formula led to safe and significant improvements in the blood glucose, blood lipids, and weight levels; relieved symptoms; and enhanced β cell function for T2D patients with obesity and hyperlipidemia. The JTTZ formula has shown that it could potentially be developed as an alternative medicine for patients with T2D, particularly those who cannot tolerate metformin or other hypoglycemic drugs. This trial was registered with Clinicaltrials.gov NCT01471275.

BackgroundMetformin plays an important role in diabetes treatment. Studies have shown that the combined use of oral hypoglycemic medications is more effective than metformin monotherapy. In this double-blind, randomized, placebo-controlled, multicenter trial, we evaluated whether Jinlida, a Chinese herbal medicine, enhances the glycemic control of metformin in type 2 diabetes patients whose HbA1c was ineffectively controlled with metformin alone.MethodsA total of 186 diabetes patients were enrolled in this double-Blind, randomized, placebo-controlled, multicenter trial. Subjects were randomly allocated to receive either Jinlida (9 g) or the placebo TID for 12 consecutive weeks. All subjects in both groups also continuously received their metformin without any dose change. During this 12-week period, the HbA1c, FPG, 2 h PG, body weight, BMI were assessed. HOMA insulin resistance (HOMA-IR) and β-cell function (HOMA-β) were also evaluated.ResultsAt week 12, compared to the HbA1c level from week 0, the level of the Jinlida group was reduced by 0.92 ± 1.09% and that of the placebo group was reduced by 0.53 ± 0.94%. The 95% CI was 0.69-1.14 for the Jinlida group vs. 0.34-0.72 for the placebo group. There was a very significant HbA1c reduction between the two groups after 12 weeks (p < 0.01). Both FG and 2 h PG levels of the Jinlida group and placebo group were reduced from week 0. There were a very significant FG and 2 h PG level reductions between the two groups after 12 weeks (both p < 0.01). The Jinlida group also showed improved β-cell function with a HOMA-β increase (p < 0.05). No statistical significance was observed in the body weight and BMI changes. No serious adverse events were reported.ConclusionJinlida significantly enhanced the hypoglycemic action of metformin when the drug was used alone. This Chinese herbal medicine may have a clinical value as an add-on medication to metformin monotherapy.Trial registrationChinese Clinical Trial Register ChiCTR-TRC-13003159.

In woody crop plants, the oligosaccharide components of the cell wall are essential for important traits such as bioenergy content, growth, and structural wood properties. UDP-glucuronate decarboxylase (UXS) is a key enzyme in the synthesis of UDP-xylose for the formation of xylans during cell wall biosynthesis. Here, we isolated a multigene family of seven members (PtUXS1-7) encoding UXS from Populus tomentosa, the first investigation of UXSs in a tree species. Analysis of gene structure and phylogeny showed that the PtUXS family could be divided into three groups (PtUXS1/4, PtUXS2/5, and PtUXS3/6/7), consistent with the tissue-specific expression patterns of each PtUXS. We further evaluated the functional consequences of nucleotide polymorphisms in PtUXS1. In total, 243 single-nucleotide polymorphisms (SNPs) were identified, with a high frequency of SNPs (1/18 bp) and nucleotide diversity (πT = 0.01033, θw = 0.01280). Linkage disequilibrium (LD) analysis showed that LD did not extend over the entire gene (r (2)

Populus tomentosa is an economically important tree crop that produces wood for lumber, pulp, paper, and biofuels. Wood quality traits are likely to be strongly affected by the plant hormone gibberellic acid (GA), which regulates growth. GA20Ox encodes one of the major regulatory enzymes of GA biosynthesis and may therefore play a large role in growth and wood quality. Here, linkage disequilibrium (LD) studies were used to identify significant associations between single nucleotide polymorphisms (SNPs) within PtGA20Ox and growth and wood-quality traits of P. tomentosa. We isolated a full-length GA20Ox cDNA from Populus tomentosa by reverse transcription (RT)-PCR; this 1401 bp cDNA clone had an open reading frame of 1158 bp and encoded a protein of 385 amino acids. PtGA20Ox transcripts were maximally expressed in the mature xylem of vascular tissues, suggesting that PtGA20Ox is highly expressed and specifically associated with secondary xylem formation. Resequencing the PtGA20Ox locus of 36 individuals identified 55 SNPs, and the frequency of SNPs was 1/31 bp. The 29 most common SNPs (frequency>0.1) were genotyped in an association population (426 individuals) that was also phenotyped for key growth and wood quality traits. LD did not extend over the entire gene (r(2)