Exploring the molecular mechanism of Xuebifang in the treatment of diabetic peripheral neuropathy based on bioinformatics and network pharmacology.

Background: Xuebifang (XBF), a potent Chinese herbal formula, has been employed in managing diabetic peripheral neuropathy (DPN). Nevertheless, the precise mechanism of its action remains enigmatic. Purpose: The primary objective of this investigation is to employ a bioinformatics-driven approach combined with network pharmacology to comprehensively explore the therapeutic mechanism of XBF in the context of DPN. Study design and Methods: The active chemicals and their respective targets of XBF were sourced from the TCMSP and BATMAN databases. Differentially expressed genes (DEGs) related to DPN were obtained from the GEO database. The targets associated with DPN were compiled from the OMIM, GeneCards, and DrugBank databases. The analysis of GO, KEGG pathway enrichment, as well as immuno-infiltration analysis, was conducted using the R language. The investigation focused on the distribution of therapeutic targets of XBF within human organs or cells. Subsequently, molecular docking was employed to evaluate the interactions between potential targets and active compounds of XBF concerning the treatment of DPN. Results: The study successfully identified a total of 122 active compounds and 272 targets associated with XBF. 5 core targets of XBF for DPN were discovered by building PPI network. According to GO and KEGG pathway enrichment analysis, the mechanisms of XBF for DPN could be related to inflammation, immune regulation, and pivotal signalling pathways such as the TNF, TLR, CLR, and NOD-like receptor signalling pathways. These findings were further supported by immune infiltration analysis and localization of immune organs and cells. Moreover, the molecular docking simulations demonstrated a strong binding affinity between the active chemicals and the carefully selected targets. Conclusion: In summary, this study proposes a novel treatment model for XBF in DPN, and it also offers a new perspective for exploring the principles of traditional Chinese medicine (TCM) in the clinical management of DPN.

Effectiveness and safety of traditional Chinese medicine decoction for diabetic gastroparesis: A network meta-analysis.

BACKGROUND: Diabetic gastroparesis (DGP) is a prevalent complication of diabetes that impairs people's quality of life and places a significant financial burden on them. The gastrointestinal symptoms of DGP patients can be improved by several Traditional Chinese Medicine (TCM) decoctions that have been shown to be effective in treating the disease. There are still many unanswered questions regarding the identification of appropriate therapeutic agents for the treatment of DGP in clinical practice. AIM: To analyze the efficacy of several TCM decoctions in the treatment of DGP using Bayesian network meta-analysis for reference. METHODS: PubMed, EMBASE, Cochrane Library, Web of Science, China National Kno-wledge Infrastructure, The China Biology Medicine DVD, Wanfang, and CQVIP were searched from inception to September 17, 2022, to collect randomized controlled trials (RCTs) about TCM decoctions for DGP. Clinical effects and symptom scores were the primary outcomes. Additionally, we assessed motilin (MOT), somatostatin (SS), gastrin (GAS), gastric emptying rate, gastric emptying time, and adverse drug events as secondary outcomes. RESULTS: A total of 67 eligible RCTs involving 4790 DGP patients and 7 TCM decoctions were included. The results of network meta-analysis (NMA) and surface under the cumulative ranking curve showed that with western medicine (WM) as a common control, the Banxia Xiexin Decoction (BXXD) + WM was most effective in clinical effects and enhancing early satiety scores; the Simo decoction (SMD) + WM was most effective in improving nausea and vomiting scores and anorexia scores, bloating scores; the Chaishao Liujunzi Decoction (CSLJD) was most effective in MOT, the Zhishi Xiaopi Decoction (ZSXPD) was most effective in SS and upgrading emptying rate; the Jianpi Xiaozhi Decoction was most effective in GAS; the CSLJD + WM was most effective in improving gastric emptying time. CONCLUSION: These NMA results suggest that the BXXD + WM and SMD + WM may be one of the potential optimal treatments. Due to various limitations, further large-sample, double-blind, multi-center randomized RCTs are needed.

Exploration of the mechanisms underlying the beneficial effect of Luo Tong formula on retinal function in diabetic rats via the "gut microbiota-inflammation-retina" axis.

BACKGROUND: Diabetic retinopathy (DR) is a common microvascular complication of diabetes. Luo Tong formula (LTF), a classical traditional Chinese medicine (TCM) prescription, consists of four plants that have been widely and effectively used to treat DR. Previous work in our laboratory has confirmed that LTF can effectively ameliorate DR. However, the potential mechanism underlying the therapeutic effect of LTF on DR has not been fully elucidated. To explore the potential mechanism of action through which LTF prevents and alleviates DR from an inflammation and gut microbiota perspective. MATERIALS AND METHODS: Metabolite profiling of LTF was performed using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). Type 1 diabetes was induced in male Sprague Dawley (SD) rats via tail vein injection of 45 mg/kg streptozotocin. Next, 100 SD rats were randomly divided into four groups, normal control; diabetic control; diabetic + insulin + calcium dobesilate; and diabetic + insulin + LTF. After 12 weeks of treatment, glucose metabolism, fundus oculi, blood-retinal barrier permeability, retinal thickness, microvascular damage, as well as cell junction expression in retinas were measured and the changes observed in different groups were compared. Finally, the alteration in gut microbiota and inflammatory cytokine expression in serum and tissues were monitored, and their correlation was analyzed. RESULTS: A total of 1024 valid peaks were obtained for LTF using GC-MS. The HbA1c and fasting blood glucose (FBG) levels in the LTF group were slightly decreased. LTF exerted protective effects on fundus oculi and the retina structure to different degrees. LTF attenuated systemic and local retinal inflammation by significantly decreasing the levels of seven pro-inflammatory cytokines, including ICAM-1, IL-6, IL-8, MCP-1, VCAM-1, VEGF, and IL-1ß. LTF restored the intestinal microbiota of diabetic rats to levels that were similar to those of normal rats. Further analysis revealed that Enterobacteriales, Prevotellaceae, Enterobacteriaceae, Bacteroides, and Klebsiella were significantly and positively correlated with the inflammatory factors in DR after LTF treatment. CONCLUSIONS: Our results revealed the mechanisms underlying the preventive effects of LTF on DR development and progression. LTF inhibited pathological changes in retinal histopathology, cell composition, and cell junction proteins while effectively ameliorating systemic and local retinal inflammation via regulating pivotal gut microbiota.

Effectiveness and safety analysis of SanHanHuaShi granules for the treatment of coronavirus disease 2019: Study protocol and statistical analysis plan for a randomized, parallel-controlled, open-label clinical trial.

Background: Coronavirus disease 2019 (COVID-19) was declared a global pandemic in March 2020 by the World Health Organization (WHO). As of July 2, 2022, COVID-19 has caused more than 545 million infections and 6.3 million deaths worldwide, posing a significant threat to human health. Currently, there is still a lack of effective prevention and control strategies for the variation and transmission of SARS-CoV-2. Traditional Chinese medicine (TCM), which has a unique theoretical system, has treated various conditions for thousands of years. Importantly, recent studies have revealed that TCM contributed significantly to COVID-19. SanHanHuaShi (SHHS) granules, a Chinese herbal medicine, which has been included in Protocol for the Diagnosis and Treatment of Novel Coronavirus Disease 2019 (6th to 9th editions) issued by the National Health Commission of China and used to prevent and treat COVID-19 disease. A previous retrospective cohort study showed that SHHS could significantly reduce the severity of mild and moderate COVID-19. However, there is an absence of high-quality randomized controlled clinical studies to confirm the clinical effectiveness of SHHS. Therefore, a clinical study protocol and a statistical analysis plan were designed to investigate the efficacy and safety of SHHS for the prevention and treatment of COVID-19. This study will increase the integrity and data transparency of the clinical research process, which is of great significance for improving the practical application of SHHS granules in the future. Methods and analysis: The study was designed as a 7-day, randomized, parallel controlled, open-label, noninferiority clinical trial of positive drugs. A total of 240 patients with mild and moderate COVID-19 will be enrolled and randomly assigned to receive SanHanHuaShi granules or LianHuaQingWen granules treatment in a 1:1 ratio. Disease classification, vital signs, SARS-CoV-2 nucleic acid testing, symptoms, medications, adverse events, and safety evaluations will be recorded at each visit. The primary outcome will be the clinical symptom recovery rate. Secondary outcomes will include the recovery time of clinical symptoms, negative conversion time of SARS-CoV-2 nucleic acid test negative conversion rate, hospitalization time, antipyretic time, rate of conversion to severe patients, and time and rate of single symptom recovery. Adverse incidents and safety assessments will be documented. All data will be analyzed using a predetermined statistical analysis plan, including our method for imputation of missing data, primary and secondary outcome analyses, and safety outcomes. Discussion: The results of this study will provide robust evidence to confirm the effectiveness and safety of SHHS in the treatment of COVID-19. Clinical Trial Registration: http://www.chictr.org.cn. Trial number: ChiCTR2200058080. Registered on 29 March 2022.

Gut microbiota and diabetic kidney diseases: Pathogenesis and therapeutic perspectives.

Diabetic kidney disease (DKD) is one of the major chronic complications of diabetes mellitus (DM), as well as a main cause of end-stage renal disease. Over the last few years, substantial research studies have revealed a contributory role of gut microbiota in the process of DM and DKD. Metabolites of gut microbiota like lipopolysaccharide, short-chain fatty acids, and trimethylamine N-oxide are key mediators of microbial-host crosstalk. However, the underlying mechanisms of how gut microbiota influences the onset and progression of DKD are relatively unknown. Besides, strategies to remodel the composition of gut microbiota or to reduce the metabolites of microbiota have been found recently, representing a new potential remedial target for DKD. In this mini-review, we will address the possible contribution of the gut microbiota in the pathogenesis of DKD and its role as a therapeutic target.

Non-Coding RNA as Biomarkers for Type 2 Diabetes Development and Clinical Management.

Diabetes, a metabolic disease characterized by high blood glucose and other complications, has undefined causes and multiple risk factors, including inappropriate diet, unhealthy lifestyles, and genetic predisposition. The two most distinguished types of diabetes are type 1 and type 2 diabetes, resulting from the autoimmune impairment of insulin-generating pancreatic ß cells and insulin insensitivity, respectively. Non-coding RNAs (ncRNAs), a cohort of RNAs with little transcriptional value, have been found to exert substantial importance in epigenetic and posttranscriptional modulation of gene expression such as messenger RNA (mRNA) silencing. This review mainly focuses on the pathology of type 2 diabetes (T2D) and ncRNAs as potential biomarkers in T2D development and clinical management. We consolidate the pathogenesis, diagnosis, and current treatments of T2D, and present the existing evidence on changes in multiple types of ncRNAs in response to various pathological changes and dysfunctions in different stages of T2D.

Diagnostic and Prognostic Value of Circulating CircRNAs in Cancer.

Cancer has been regarded as one of the leading causes of mortality worldwide. Diagnostic and prognostic biomarkers with high sensitivity and specificity for cancer play a crucial role in preventing or treating cancer. Circular RNAs (circRNAs), which hold great potential for the management of cancer patients due to their abundance, stable property, and high specificity in serum, plasma, and other body fluids, can be used as non-invasive and blood-based biomarkers in cancer diagnosis and prognosis. There are four types of circRNAs including exonic circRNAs (ecircRNA), intronic circRNAs, exon-intron circRNAs (EIciRNA), and intergenic circRNAs. CircRNAs can act as miRNA sponges, affect protein translation, interplay with RNA binding proteins, regulate protein recruitment, and modulate protein scaffolding and assembly. Therefore, the multifunctionalities of circRNAs make them ideal for detecting and predicting cancer. Indeed, circRNAs manifest high sensitivity and specificity in more than ten types of cancer. This review aims to consolidate the types and functions of circRNAs, as well as discuss the diagnostic and prognostic value of circulating circRNAs in cancer.

Understanding COVID-19 in Wuhan From the Perspective of Cold-Dampness: Clinical Evidences and Mechanisms.

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.

Positive RT-PCR Test Results in 420 Patients Recovered From COVID-19 in Wuhan: An Observational Study.

OBJECTIVE: During 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. METHODS: We 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. RESULTS: In 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. CONCLUSIONS: The 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 REGISTRATION: Chictr.org.cn, identifier ChiCTR2000030747.

Efficacy of Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules in treatment of COVID-19: A randomized controlled trial.

BACKGROUND: With the global epidemic of coronavirus disease (COVID-19), China has made progress in the prevention and control of the epidemic, and traditional Chinese medicine (TCM) has played a key role in dealing with the disease's effects on the respiratory system. This randomized controlled clinical trial evaluated the clinical efficacy and prognosis of Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules in patients with COVID-19. METHODS: A total of 283 patients participated in this clinical trial, and participants were randomly assigned to receive either 1) Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules or 2) Linahua granules, both combined with western medicine, or 3) western medicine alone for 14 days. At the end of the trial, the improvement and resolution rates of clinical symptoms and the rate of patients who progressed to severe disease status were evaluated. RESULTS: After 14 days of treatment, there was no significant difference in the improvement rate of clinical symptoms among the three groups (P > 0.05). Huoxiang Zhengqi dropping pills combined with Lianhua Qingwen granules has advantages in the treatment of nausea, vomiting and limb soreness. During treatment, all participants were treated with western medicine, and there was a significant difference in the use of macrolides among the three groups (P < 0.05). Specifically, the utilization rate of antibiotics in the western medicine group was significantly greater than that of the other two groups. Among the 182 diagnosed patients who completed this clinical trial, 13 patients progressed to severe disease, including one case in the Huoxiang + Lianhua group (1.6 %), five cases in the Lianhua group (8.6 %), and seven cases in the western medicine group (11.1 %). There was no statistical differences in this rate among the three groups (P > 0.05). However, the proportion of patients who progressed to severe disease in the Huoxiang + Lianhua group was the lowest, suggesting that the combination of TCM with western medicine has a potential advantage in improving the prognosis of patients with COVID-19. CONCLUSION: The use of Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules combined with western medicine may have clinical advantages for COVID-19 patients in improving clinical symptoms, reducing utilization rate of anti-infective drugs, and improving patient prognosis, which could pave the way for the use of complementary medicine in treating this infection.

The role played by traditional Chinese medicine in preventing and treating COVID-19 in China.

Traditional Chinese medicine (TCM), an ancient system of alternative medicine, played an active role in the prevention and control of COVID-19 in China. It improved the clinical symptoms of patients, reduced the mortality rate, improved the recovery rate, and effectively relieved the operating pressure on the national medical system during critical conditions. In light of the current global pandemic, TCM-related measures might open up a new channel in the control of COVID-19 in other countries and regions. Here, we summarize the TCM-related measures that were widely used in China, including TCM guidelines, the Wuchang pattern, mobile cabin hospitals, integrated treatment of TCM and modern medicine for critical patients, and non-medicine therapy for convalescent patients, and describe how TCM effectively treated patients afflicted with the COVID-19. Effective TCM therapies could, therefore, be recommended and practiced based on the existing medical evidence from increased scientific studies.

Interpretation of the Traditional Chinese Medicine portion of the diagnosis and treatment protocol for corona virus disease 2019 (Trial Version 7).

The TCM protocol in the Diagnosis and Treatment Protocol for corona virus disease 2019 (COVID-19) (Trial Version 7) has been updated from previous versions. The protocol was formulated under the direct leadership of the National Administration of Traditional Chinese Medicine, based on the experience of a panel of experts, supported by evidence from fever clinics and from the outcomes of emergency (EM) observation rooms and inpatients throughout China (especially in Wuhan, Hubei Province) in combination with the latest scientific research results and data. The present interpretation of the TCM protocol is based on an overall understanding of the revised content, and aims to guide and standardize its clinical application to provide a reference for clinicians.