Promising therapeutic mechanism for Chinese herbal medicine in ameliorating renal fibrosis in diabetic nephropathy.

Diabetic nephropathy (DN) is one of the most serious chronic microvascular abnormalities of diabetes mellitus and the major cause of uremia. Accumulating evidence has confirmed that fibrosis is a significant pathological feature that contributes to the development of chronic kidney disease in DN. However, the exact mechanism of renal fibrosis in DN is still unclear, which greatly hinders the treatment of DN. Chinese herbal medicine (CHM) has shown efficacy and safety in ameliorating inflammation and albuminuria in diabetic patients. In this review, we outline the underlying mechanisms of renal fibrosis in DN, including oxidative stress (OS) generation and OS-elicited ASK1-p38/JNK activation. Also, we briefly summarize the current status of CHM treating DN by improving renal fibrosis. The treatment of DN by inhibiting ASK1 activation to alleviate renal fibrosis in DN with CHM will promote the discovery of novel therapeutic targets for DN and provide a beneficial therapeutic method for DN.

Machine learning algorithms for improved prediction of in-hospital outcomes after moderate-to-severe traumatic brain injury: a Chinese retrospective cohort study.

AIM: Controversy remains high over the superiority of advanced machine learning (ML) algorithms to conventional logistic regression (LR) in the prediction of prognosis after traumatic brain injury (TBI). This study aimed to compare the performance of ML and LR models in predicting in-hospital prognosis after TBI. METHOD: In a single-center retrospective cohort of adult patients hospitalized for moderate-to-severe TBI (Glasgow coma score ≤12) in our hospital from 2011 to 2020, LR and three ML algorithms (XGboost, lightGBM, and FT-transformer) were run to build prediction models for in-hospital mortality and the Glasgow Outcome Scale (GOS) functional outcomes using either all 19 clinical and laboratory features or the 10 non-laboratory ones collected at admission to the neurological intensive care unit. The Shapley (SHAP) value was used for model interpretation. RESULT: In total, 482 patients had an in-hospital mortality rate of 11.0%. A total of 23.0% of the patients had good functional scores (GOS ≥ 4) at discharge. All ML models performed better than the LR model in predicting in-hospital prognosis after TBI, among which the lightGBM model showed the best performance: When predicting mortality, the lightGBM model yielded an area under the curve (AUC) of 0.953 using all 19 features (the LR model: 0.813) and an AUC of 0.935 using 10 non-laboratory features (the LR model: 0.803); when predicting GOS functional outcomes, it yielded an AUC of 0.913 using all 19 features (the LR model: 0.832) and an AUC of 0.889 using non-laboratory data (the LR model: 0.818). The SHAP method identified key contributors to explain the lightGBM models. Finally, the integration of the lightGBM models with different prediction purposes was found to provide refined prognostic information, particularly for patients who survived moderate-to-severe TBI. CONCLUSION: The study supported the superiority of ML to LR in predicting prognosis after moderate-to-severe TBI and highlighted its potential use for clinical application.

Exploring the mechanism of Taohong Siwu Decoction on the treatment of blood deficiency and blood stasis syndrome by gut microbiota combined with metabolomics.

BACKGROUND: Taohong Siwu Decoction (THSWD) is a prescription which included in the "List of Ancient Classic Prescriptions (First Batch)" issued by the National Administration of Traditional Chinese Medicine (TCM) and the National Medical Products Administration of the People's Republic of China. THSWD is effective and widely applied clinically for many diseases caused by blood deficiency and stasis syndrome in TCM, such as primary dysmenorrhea, menopausal syndrome, coronary heart disease, angina pectoris, and diabetes. METHODS: The TCM model of blood deficiency and blood stasis syndrome was prepared by ice water bath combined with cyclophosphamide, and the rats were randomly divided into control group, blood deficiency, and blood stasis model group, positive group, and THSWD treatment group. Pharmacodynamics measured the blood routine, blood coagulation, and other related indexes in rats. UHPLC-MS technology was used to analyze the changes in the fingerprints of metabolites in the plasma of rats with blood deficiency and blood stasis syndrome, and combined with mass spectrometry information and public database retrieval, to find potential biomarkers for screening metabolites. At the same time, 16S rDNA sequencing technology was used to identify intestinal flora, and statistical analysis was used to find differences in strain diversity between groups. RESULTS: THSWD administration can significantly improve the physical signs, blood routine, and hematopoietic factors caused by the blood deficiency and blood stasis syndrome model, and improve the symptoms of blood deficiency. The results of the general pharmacological studies showed THSWD groups improved changes in blood plasma viscosity and coagulation-related factors caused by modeling, and improved coagulation function significantly. The metabolomic analysis found that compared to the model group, THSWD exerted better effects on ß-alanine, taurine, L-tyrosine, L-arginine, Eugenol, sodium deoxycholate, and deethylatrazine. Twenty-three potential differential metabolites showed intervention effects, mainly involved in eight metabolic pathways, including amino acid metabolism, taurine and hypotaurine metabolism, vitamin metabolism, and nucleotide metabolism. Gut microbiota data showed that, compared to the control group, the relative abundance and value of Firmicutes and Bacteroidota of the blood deficiency and blood stasis model group was significantly reduced, while the relative abundance of Actinobacteria, Spirochaetota, Proteobacteria, Campilobacterota, and other pathogenic bacteria was significantly increased. Following THSWD intervention, the abundance of beneficial bacteria increased, and the abundance of pathogenic bacteria decreased. Correlation analysis between the gut microbiota and differential metabolites showed that the two are closely related. THSWD affected the host blood system through mutual adjustment of these two factors, and improved blood deficiency and blood stasis syndrome in rats. CONCLUSION: The blood deficiency and blood stasis syndrome model of TCM disease caused by ice bath combined with cyclophosphamide lead to changes in the pharmacology, metabolomics, and gut microbiota. The intervention of THSWD can improve the symptoms caused by blood deficiency and blood stasis. The mechanism is mainly through the regulation of platelet function and amino acid metabolism.

A comparative study on the traditional versus modern yellow rice wine processing methods using Taohong Siwu Decoction for pharmaceutical production.

ETHNOPHARMACOLOGICAL RELEVANCE: Taohong Siwu Decoction (THSWD) is based on the "First Recipe of Gynecology." It is widely used in various blood stasis and deficiency syndromes, mainly in gynecological blood stasis, irregular menstruation, and dysmenorrhea. THSWD has great demand in traditional Chinese medicine (TCM), gynecology, orthopedics, and internal medicine. According to classical records, three medicinal materials, namely Rehmanniae radix, Angelica sinensis, and Carthamus tinctorius, used in THSWD need to be "washed with yellow rice wine." In the study of TCM prescriptions, the processing methods of medicinal materials not only needed to follow traditional records but also should consider modern technical conditions. Many medicinal materials in the repertoire of classical prescriptions involve yellow rice wine processing. Determining the processing method for medicinal materials is a key and difficult problem in the research and development of classical prescriptions. AIM OF THE STUDY: With THSWD as the representative, this study analyzed differences between no processing method, the modern processing method of "stir-frying the materials with yellow rice wine," and the traditional processing method of "washing with yellow rice wine." We focused on three aspects: composition, efficacy, and endogenous metabolism. This study aimed to provide a reference for research on the processing methods of medicinal materials used in classical prescriptions. MATERIALS AND METHODS: UPLC-Q-Orbitrap HRMS was used to quickly identify and classify the main chemical compounds of THSWD. A model of primary dysmenorrhea (PD) was established using estradiol benzoate combined with oxytocin. The latent period and writhing time; the levels of serum PGF2α, PGE2, ET-1, and ß-EP; and the pathological sections of the uterus were observed to determine their pharmacodynamic differences. GC-TOF/MS was used to analyze the differences in serum metabolites in rats. RESULTS: A total of 54 active compounds were identified, and the results showed that catalpol and rehmapicroside disappeared following yellow rice wine processing. Compared with materials processed by the traditional method, the relative contents of 15 components, such as 5-hydroxymethylfurfural and digitalis C, increased in materials processed by the modern method. However, the relative contents of 16 components, such as hydroxysafflor yellow A, verbascoside, and ferulic acid, decreased in the modern processing method. The modern and classic processing methods acted on PD through different metabolic pathways. THSWD obtained by classical processing methods mainly treated PD through anti-inflammatory and estrogen metabolism pathways, whereas THSWD obtained by modern processing methods mainly treated PD through anti-inflammatory metabolic pathways. CONCLUSION: The study revealed the differences in different yellow rice wine processing methods in terms of chemical composition of the THSWD obtained, as well as the mechanisms of action for the treatment of PD. This study provides a reference for the clinical application of THSWD and development of classical prescription preparations.

Traditional Chinese Medicine for adjuvant treatment of breast cancer: Taohong Siwu Decoction.

The high incidence of breast cancer is the greastest threat to women' health all over the world. Among them, HER-2 positive breast cancer has the characteristics of high malignancy, easy recurrence and metastasis, and poor prognosis. Traditional Chinese medicine (TCM) has a rich theoretical basis and clinical application for breast cancer. TCM believes that blood stasis syndrome is one of the important pathogenesis of breast formation and development. Taohong Siwu Decoction (TSHWD) is based on the "First Prescription of Gynecology" Siwu Decoction. It is widely used in various blood stasis and blood deficiency syndromes, mainly in gynecological blood stasis. Clinical studies have found that THSWD can treat breast cancer by reducing blood vessel and lymphangiogenesis with auxiliary chemotherapy. In this study, we aim to explore the material basis and mechanism of THSWD in the treatment of HER-2 positive breast cancer through literature review and network pharmacology studies. Through a literature review of the traditional application, chemical composition of Chinese herbal medicine of THSWD, as well as its clinical reports and pharmacological research on breast cancer treatment. Meanwhile, we conducted "component-pathway-target" network through network pharmacology reveals the main material basis, possible targets and pathways of THSWD in inhibiting HER-2 positive breast cancer. Literature review and network pharmacology research results had predicted that, baicalein, kaempferol, caffeic acid, amygdalin, quercetin, ferulic acid, gallic acid, catalpol, hydroxysafflor yellow A, paeoniflorin in THSWD are the main effective chemical composition. THSWD regulates 386 protein targets and 166 pathways related to breast cancer. The molecular mechanism is mainly to improve the microenvironment of tumor cells, regulate the process of tumor cell EMT, and inhibit tumor cell proliferation and metastasis. This study revealed the mechanism of action of THSWD in the treatment of HER-2 positive breast cancer through literature review and network pharmacology studies, providing a scientific basis for clinical application.

Effect of Electroacupuncture on Bladder Dysfunction via Regulation of MLC and MLCK Phosphorylation in a Rat Model of Type 2 Diabetes Mellitus.

Previous studies observed have reported that electroacupuncture (EA) is effective in relieving diabetic bladder dysfunction (DBD); however, little is known about the mechanism. Therefore, we explored the effects and mechanisms of EA on DBD in streptozotocin-high-fat diet- (STZ-HFD-) induced diabetic rats. The Sprague-Dawley male rats were divided randomly into four groups: normal group, diabetes mellitus group (DM group), DM with EA treatment group (EA group), and DM with sham EA treatment group (sham EA group). After 8 weeks of EA treatment, the body weight, serum glucose, bladder weight, and cystometrogram were evaluated. The bladder wall thickness was examined by abdominal ultrasound imaging. After the transabdominal ultrasound measurements, hematoxylin-eosin (HE) staining was used to observe the bladder mucosa layer. The bladder detrusor smooth muscle cells (SMCs) and fibroblasts were observed under transmission electron microscopy (TEM). The phospho-myosin light chain (p-MLC), phospho-myosin light chain kinase (p-MLCK), and phospho-myosin phosphatase target subunit 1 (p-MYPT1) levels in the bladder were examined using Western blot. The bladder weight, serum glucose, bladder wall thickness, volume threshold for micturition, and postvoid residual (PVR) volume in the diabetic rats were significantly higher than those in the control animals. EA treatment significantly reduced the bladder weight, bladder wall thickness, volume threshold for micturition, and PVR volume in diabetic rats. EA caused a significant increase in the MLC dephosphorylation and MLCK phosphorylation levels in the group compared to the sham EA and model groups. EA reduced the infiltration of inflammatory cells in the bladder mucosa layer of diabetic rats. In addition, EA repaired the damaged bladder detrusor muscle of diabetic rats by reducing mitochondrial damage of the SMCs and fibroblasts. Therefore, EA could reduce the bladder hypertrophy to ameliorate DBD by reversing the impairment in the mucosa layer and detrusor SMCs, which might be mainly mediated by the regulation of p-MLC and p-MLCK levels.

Integrated serum pharmacochemistry and network pharmacological analysis used to explore possible anti-rheumatoid arthritis mechanisms of the Shentong-Zhuyu decoction.

ETHNOPHARMACOLOGICAL RELEVANCE: Shentong-Zhuyu decoction (STZYD) has been recognized by the Chinese National Administration of Traditional Chinese Medicine (TCM) as a classic TCM formula. Use of STZYD has shown a satisfactory clinical therapeutic outcome for rheumatoid arthritis (RA); despite this, its bioactive chemical composition and relevant mechanism(s) of this action have not been clearly elucidated. AIM OF THE STUDY: To explore the bioactive chemical composition of STZYD used for RA treatment and its possible mechanism(s) of action. MATERIALS AND METHODS: Serum pharmacochemistry mediated by the UPLC-Q-Exactive MS/MS method was employed to identify the absorbed phytochemical compounds in serum derived from STZYD, which were commonly considered as the potential bioactive compounds. And then, these components were used to construct a compound-target network for RA using a network pharmacology approach, to predict the possible biological targets of STZYD along with potential signaling pathways. Afterwards, we established a Complete Freund's adjuvant (CFA)-induced RA rat model, and observed the anti-RA effect of STZYD by a series of indexes, including foot swelling, ankle diameter, arthritis score, morphological and radiographic analysis, serum inflammatory factors, and histopathological analysis of synovial tissues. Particularly, the predicted pathway by the combination of serum pharmacochemistry and network pharmacology was further validated using RT-qPCR, Western blot, and immunohistochemical analyses in animal experiment. RESULTS: Totally, 38 compounds derived from STZYD have been identified by serum sample analysis. Based on it, 387 genes related to these identified compounds in STZYD and 3807 genes related to RA were collected by network pharmacology. Critically, KEGG analysis indicated that the PI3K/AKT signaling pathway was recommended as one of the main pathway related to anti-RA effect of STZYD. Experimentally, STZYD significantly alleviated CFA-induced arthritis without any visible side-effects. Compared to the RA model group without any treatment, the treatment of STZYD significantly reduced the expression of both mRNA and protein targets in the PI3K/AKT signaling pathway. Furthermore, this result was also corroborated by immunohistochemistry analysis. All these studies could effectively corroborate the predicted result as above, suggested that the feasibility of this integrated strategy. CONCLUSION: This study provided a useful strategy to identify bioactive compounds and the potential mechanisms for TCM formula by integrating serum pharmacochemistry and network pharmacology.

Berberine as a Potential Multi-Target Agent for Metabolic Diseases: A Review of Investigations for Berberine.

Berberine (BBR) is a botanic alkaloid extracted from Coptis chinensis (Huanglian), which has various properties, compassing anti-hyperglycemia, anti-obesity, anti-inflammation, and improves insulin resistance, etc. Several researches have confirmed that BBR has effective actions in treating glycolipid metabolic abnormalities. BBR is also beneficial in regulating intestinal flora. Metabolic diseases are strongly associated with metabolic disorders, which are growing in the population and dramatically impacting human health, which also have been considered as a leading cause of diseases and death globally. This review is to evaluate the metabolic properties of BBR, and its potential application to the treatment of metabolic diseases by its effective actions on metabolic disorders.

Clinical efficacy and safety of Chinese herbal medicine for the treatment of patients with early diabetic nephropathy: A protocol for systematic review and meta-analysis.

BACKGROUND: Diabetic nephropathy (DN) is among the common and serious complications of diabetes and is also a major cause of end-stage kidney disease. Early DN is also called diabetic microalbumin period, the main treatment is in the control of blood sugar on the basis of kidney protection and urine lowering protein. There are few effective methods of western medicine treatment, and most of them are accompanied by adverse reactions. But some studies have shown that traditional Chinese medicine has achieved the curative effect and has certain superiority. However, there are few systematic reviews on the treatment of traditional Chinese herbal medicine for early DN currently. Therefore, this study conducted a systematic review of clinical efficacy and safety of Chinese herbal medicine for the treatment of patients with early DN, aim to comprehensively analyze the role of traditional Chinese herbal medicine in the treatment of early DN. METHODS AND ANALYSIS: The protocol of this systematic review and meta-analysis was registered on the INPLASY website (https://inplasy.com/inplasy-2020-4-0139/) and INPLASY registration number is INPLASY202040139. A systematic literature search will be conducted in 3 English database and 4 Chinese databases with a language limitation of English and Chinese. Search for clinical research literature on Chinese herbal medicine treatment of DN published in domestic and foreign biomedical journals. The time is limited from January 2010 to February 2020. We will investigate heterogeneity across studies and publication bias. To assess the risk of bias and quality of the included studies, we will use the Cochrane Collaboration's ROB tool. According to the relevant standards in the Cochrane Intervention System Evaluation Manual, it will be divided into low risk, high risk, and unclear. We will also use the RevMan 5.3 software and Stata 13.0 software for meta-analysis of the effectiveness and symptom scores of DN proteinuria. ETHICS AND DISSEMINATION: The ethical considerations are not required because the systematic review is based on published studies. The systematic review and meta-analysis will be published in a peer-reviewed Journal.

Therapies for diabetic gastroparesis: A protocol for a systematic review and network meta-analysis.

BACKGROUND: Diabetic gastroparesis (DG) is a common autonomic neuropathy which impacts on nutritional state and quality of life in diabetic patients, and it also adversely affects glycemic control in diabetes. The prevalence of DG is growing with the number of patients with diabetes continues to increase. However, there is no definitive answer as to which of the current therapies is the best for the clinical treatment of the different manifestations of DG. The subject of this study is to answer the following question: what is the best intervention for diabetic patients with gastroparesis? METHODS: Comprehensive searches of the Cochrane Library, PubMed, Embase, Medline, Central and Web of Science, and 4 Chinese databases, including China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, Chinese Biomedical Literature Database, and WanFang will be completed using the following keywords DG and therapies and related entry terms. Studies will be included, according to the eligibility criteria (randomized controlled trials and controlled clinical trials, considering specific outcome measures for DG). The reference lists of included studies will be manual searched. Relevant data will be extracted from included studies using a specially designed data extraction sheet. Risk of bias of the included studies will be assessed, and the overall strength of the evidence will be summarized through GRADE. A random effects model will be used for all pairwise meta-analyses (with a 95% confidence interval). A Bayesian network meta-analysis will explore the relative benefits between the various therapies. The review will be reported using the Preferred Reporting Items for Systematic Reviews incorporating Network Meta-Analyses statement. Network meta-analysis will be performed using a Bayesian framework through the Winbugs software. RESULTS: This network meta-analysis will identify the best effective therapy for DG. CONCLUSION: This study will compare and evaluate current therapies for DG, and find the best treatment of DG.

Adjunctive rifampin therapy for diabetic foot osteomyelitis: A protocol for systematic review and meta-analysis.

INTRODUCTION: The prevalence of diabetes continues to rise around the world. Diabetic foot is a serious complication of diabetes, and diabetic patients with diabetic foot osteomyelitis (DFO) have a fourfold increased risk of amputation, usually indicating death. Therefore, it is particularly important to seek a more effective treatment for DFO. The treatment of DFO varies from person to person, and antimicrobial therapies vary widely. A large number of clinical studies have shown that rifampicin adjuvant therapy can reduce the rate of amputation and mortality in DFO patients. However, there is no systematic summary of clinical evidence, which limits the clinical application of rifampicin. Therefore, we attempted to provide high-quality evidence for the clinical efficacy and safety of rifampin in the adjuvant treatment of DFO through this meta-analysis. METHODS: English literature is mainly searched in Cochrane Library, PubMed, EMBASE and Web of Science, while Chinese literature is from CNKI, CBM, VIP and Wangfang databases. At the same time, we will search clinical registration tests and gray literature. Two methodologically trained researchers will read the title, abstract, and full text, and independently select qualified literature based on inclusion and exclusion criteria. Binary data is expressed as relative risk, continuous data is expressed as mean difference or standard mean difference. The final data are synthesized using a fixed effect model or a random effect model, depending on the presence of heterogeneity. In the end, the patient's amputation rate and mortality were the main research indicators. Survival rate, HbA1c, serum creatinine, changes in ulcer area, and SF-36 quality of life assessment were used as secondary indicators. We will perform a sensitivity analysis to assess the stability of the results. Then the publication bias was evaluated by funnel plot analysis and Egger test. Finally, we will use a "recommendation grading, evaluation, formulation and evaluation" system to assess the quality of the evidence. All data analysis will be meta-analyzed by the statistical software RevMan software version 5.3. RESULTS: This study will provide a high-quality comprehensive report on the effectiveness and safety of rifampicin in the treatment of DFO, and our findings will be published in peer-reviewed journals. CONCLUSION: This systematic review and meta-analysis will provide a comprehensive summary and careful evaluation of rifampicin as an adjuvant treatment of DFO with a view to providing multiple options for clinical treatment of the disease. REGISTRATION NUMBER:: is INPLASY202040084.

Total glucosides of paeony: A review of its phytochemistry, role in autoimmune diseases, and mechanisms of action.

ETHNOPHARMACOLOGICAL RELEVANCE: Paeoniae Radix Alba (PRA, called baishao in China), the root of Paeonia lactiflora Pall., has shown a rich medicinal value for more than 2000 years. PRA is used in local medicine and traditional medicine for autoimmune diseases associated with inflammation. At present, total glucosides of paeony (TGP), the main active ingredient of PRA, has been developed into a preparation for the treatment of autoimmune diseases, as TGP exhibits the effect of regulating immunity, anti-inflammatory, and analgesic effects. AIM OF THE REVIEW: TGP was developed and applied to inflammation-related autoimmune diseases in modern clinical practice. Based on its application in traditional prescriptions, this article reviews PRA's botany and phytochemistry (including its extraction process and quality control), and discusses the clinical application and pharmacological research of TGP as an anti-inflammatory drug from the perspective of ethnopharmacology. Additionally, we review modern pharmacological and molecular-target research on TGP and discuss the mechanisms of TGP in treating autoimmune diseases. Through a systematic literature review, we also highlight the clinical efficacy of TGP in the treatment of immune diseases, and provide a reference for the continued scientific development and quality control of TGP so that its wider application and clinical value can be fully realized. MATERIALS AND METHODS: Literature search was conducted through the Web of Science, Baidu Scholar, ScienceDirect, PubMed, CNKI, and WanFang DATA using the keywords "Total glucosides of paeony", "Paeonia lactiflora Pall. ", "Paeonia veitchii Lynch", "Paeoniae Radix Alba or white peony", "Paeoniae Radix Rubra or red peony", "Paeoniflorin", "Albiflorin", "Autoimmune diseases", and their combinations. In addition, information was collected from relevant textbooks, reviews, and documents. RESULTS: Approximately 15 compounds have been identified in TGP, of which paeoniflorin and albiflorin are the most common constituents. In recent years, studies have found that TGP and its main chemical components are effective in the treatment of autoimmune diseases, such as rheumatoid arthritis, psoriasis, oral lichen planus, and Sjogren's syndrome. TGP has a variety of pharmacological effects related to PRA traditional effects, including anti-organ-damage, anti-inflammatory, analgesic, antioxidant, cardiovascular, and nervous-system protection. Previously published reports on TGP treatment of autoimmune diseases have shown that TGP regulates intracellular pathways, such as the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathways. However, there is no standardized preparation method for TGP, and there is insufficient quality control of formulations. Many related pharmacological studies have not tested TGP components, and the validity of such pharmacological results requires further verification. CONCLUSIONS: Modern pharmacological research on TGP is based on the traditional usage of PRA, and its folk medicinal value in the treatment of autoimmune diseases has now been verified. In particular, TGP has been developed into a formulation used clinically for the treatment of autoimmune diseases. The combination of TGP capsules and chemicals to treat autoimmune diseases has the effect of increasing efficacy and reducing toxicity. Based on further research on its preparation, quality control, and mechanisms of action, TGP is expected to eventually play a greater role in the treatment of autoimmune diseases.

Vitamin D supplementation for nonalcoholic fatty liver disease in type 2 diabetes mellitus: A protocol for a systematic review and meta-analysis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is strongly associated with type 2 diabetes mellitus (T2DM), and low vitamin D levels are positively associated with NAFLD and T2DM. But there is absence of convincing evidence-based medicine to confirm the efficacy of vitamin D supplementation for T2DM with NAFLD. Thus, we aimed to conduct this meta-analysis to summarize the efficacy of vitamin D supplementation for T2DM combined with NAFLD, and help to further clarify its beneficial action on diabetic patients with NAFLD. METHODS: The study only selects clinical randomized controlled trials of vitamin D supplementation for T2DM combined with NAFLD. We will search each database from the built-in until July 2020. The English literature mainly searches Cochrane Library, Pubmed, EMBASE, and Web of Science. While the Chinese literature comes from CNKI, CBM, VIP, and Wangfang database. Meanwhile, we will retrieve clinical trial registries and grey literature. Two researchers worked independently on literature selection, data extraction, and quality assessment. The dichotomous data is represented by relative risk (RR), and the continuous is expressed by mean difference (MD) or standard mean difference (SMD), eventually the data is synthesized using a fixed effect model (FEM) or a random effect model (REM) depending on the heterogeneity. The imaging markers of liver, biomarkers of hepatic steatosis, serological indexes of hepatic fibrosis, serum NAFLD liver fat score were evaluated as the main outcomes. While several secondary outcomes were also evaluated in this study. The statistical analysis of this meta-analysis was conducted by RevMan software version 5.3. RESULTS: This meta-analysis will further determine the beneficial efficacy of vitamin D supplementation for T2DM combined with NAFLD. CONCLUSION: This study determines the positive efficacy of vitamin D supplementation for diabetic patients with NAFLD.

The effect of vitamin D supplementation on the progression of fibrosis in patients with chronic liver disease: A protocol for a systematic review and meta-analysis.

BACKGROUND: Hepatic fibrosis (HF) is the common pathological basis of chronic liver disease (CLD). Many data indicate that serum vitamin D (VD) levels in patients with liver fibrosis are significantly lower than those without liver fibrosis, and lower level of serum 1,25(OH)2D3 is also an independent risk factor for patients with liver fibrosis combined with other diseases. VD has the functions of anti-fibrosis, regulating cell proliferation and differentiation, anti-inflammatory, and immune regulation, Therefore, serum 1,25(OH)2D3 level may be negatively correlated with the progression of liver fibrosis. But there is absent convincing evidence-based medicine to confirm the efficacy of VD supplementation for CLD. Thus, we aimed to conduct this meta-analysis to summarize the efficacy of VD supplementation on the progression of fibrosis in patients with CLD. METHODS: The study only selects clinical randomized controlled trials of VD supplementation for CLD. We will search each database from the built-in until September 2020. The English literature mainly searches Cochrane Library, Pubmed, EMBASE, and Web of Science. While the Chinese literature comes from CNKI, CBM, VIP, and Wangfang database. Meanwhile, we will retrieve clinical trial registries and gray literature. Two researchers worked independently on literature selection, data extraction and quality assessment. The dichotomous data is represented by relative risk (RR), and the continuous is expressed by mean difference (MD) or standard mean difference (SMD), eventually the data is synthesized using a fixed effect model (FEM) or a random effect model (REM) depending on the heterogeneity. The serum VD level, hepatic function and serological indexes of hepatic fibrosis were evaluated as the main outcomes. While several secondary outcomes were also evaluated in this study. The statistical analysis of this Meta-analysis was conducted by RevMan software version 5.3. RESULTS: This meta-analysis will further determine the beneficial efficacy of VD supplementation on the progression of fibrosis in patients with CLD. CONCLUSION: This study determines the positive efficacy of VD supplementation for CLD. ETHICS AND DISSEMINATION: This review is based solely on a secondary study of published literatures and does not require ethics committee approval. Its conclusion will be disseminated in conference papers, magazines or peer-reviewed journals. REGISTRATION NUMBER: INPLASY202040054.

Effect of electroacupuncture on diabetic neurogenic bladder: A randomized controlled trial protocol.

BACKGROUND: The most common and bothersome lower urinary tract complication of diabetes mellitus is diabetic neurogenic bladder (DNB). Acupuncture has certain advantages in treating bladder dysfunction including urinary retention and incontinence. Therefore, we think that electroacupuncture (EA) may be beneficial to DNB patients. However, it is not clear whether EA combined with basic western medicine could optimize the therapeutic effect for DNB. METHOD/DESIGN: This is a sham-controlled, patient-blinded, pioneer randomized controlled trial (RCT). One hundred fifty eligible patients will be randomly divided into 3 groups: A. basic western medicine (BWC), B. EA with BWC, C. sham EA with BWC. EA treatment will be given twice a week for 12 weeks at bilateral BL23, BL32, BL33, and BL35. The BWC group will received Alpha-lipoic acid (ALA) and methylcobalamin (MC) treatment for 12 weeks, 2 treatment sessions per week. The primary outcome is scored by the 72-hour bladder diary (72h-BD). The secondary outcomes will be scored by the American Urological Association symptom index (AUA-SI), Post-void residual urine volume (PVR) and urodynamic tests. All the assessments will be conducted at baseline and the 12th weeks after the intervention starts. The follow-up assessments will be performed with 72h-BD and AUA-SI in the 4th, 12th, and 24th weeks after intervention ends. DISCUSSION: This trial protocol provides an example of the clinical application acupuncture treatment in the management of DNB. This RCT will provide us information on the effect of treating DNB patients with only acupuncture, western medicine therapy (ALA + MC) as well as the combination of both. The additive effect or synergistic effect of acupuncture and basic western medicine will then be analyzed. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000030421.

Lovastatin derivative dehydrolovastatin ameliorates ulcerative colitis in mice by suppressing NF-κB and inflammatory cytokine expression.

Ulcerative colitis (UC) is associated with intestinal immune imbalance and inflammatory response. Because dehydrolovastatin (DLVT), a derivative of lovastatin, has been recently shown to inhibit inflammation and relieve immune arthritis induced by chemical stimuli, we studied its effect and possible mechanism on UC induced by dextran sulfate sodium. The BALB/c mice were classified into six groups: normal control group, model group, DLVT high dose group, DLVT low dose group, salazosulfapyridine (SASP) group and lovastatin (LVT) group. The disease activity indices of UC and pathological changes were investigated. The myeloperoxidase (MPO) activity in colon tissue and inflammatory factors such as IL-6, IL-10, IL-17, and TNF-α in the serum were analyzed by ELISA, while the expression of NF-κB p65 protein in colon tissue was detected by immunohistochemistry and western blot. DLVT relieved the disease activity indices and pathological damage of the UC mice. Furthermore, DLVT significantly decreased MPO activity and improved the imbalance of inflammatory cytokines through inhibiting the expression of NF-κB p65. Meanwhile, the positive drug of SASP has a similar effect to DLVT, but the effect of DLVT in both decreasing IL-17, TNF-α, and increasing IL-10 was significantly stronger than that of SASP. These results suggest that DLVT may ameliorates the symptoms of UC.

The effect of wuling capsule on depression in Type 2 diabetic patients.

OBJECTIVE: Depression is a common complication in Type 2 diabetes mellitus (T2DM); however, it has long been underrecognized and undertreated. In the present study, we aimed to evaluate the clinical effects of Wuling capsule, a compound traditional Chinese herbal medicine, on T2DM complicated with depression. METHOD: 66 patients were enrolled and randomly divided into Wuling capsule treatment group and placebo group, and finally 64 cases finished the present study. The levels of FPG, 2hPG, HbAlc, TNF-α, IL-6, SOD, MDA, Cor, ACTH, HOMA-ß, HOMA-IR and ISI of patients were evaluated and compared. The HAMD scale for patients were recorded. RESULT: After 12-week treatment, the HAMD scale decreased in both groups, and was lower in Wuling capsule group. The level of FPG in Wuling capsule group was significantly lower than in placebo group; however, no obvious changes of 2hPG and HbA1c were found. The levels of IL-6 and TNF-α were significantly decreased in both groups, and more obviously in Wuling capsule group. The level of SOD was increased while the level of MDA was decreased significantly in both groups, and the changes were more obviously in Wuling capsule group. The levels of Cor and ACTH were significantly decreased in both groups; however, there was no statistically significance between the two groups. Besides, the comparisons of HOMA-ß, HOMA-IR and ISI between the two groups were not statistically significant. CONCLUSION: Our results suggested that Wuling capsule ameliorated the depression in patients with T2DM, and also improved the state of inflammation and oxidative stress state. These results also strongly indicated the ability of clinical transformation of Wuling capsule in patients with T2DM in the future.