Network meta-analysis on the effects of finerenone versus SGLT2 inhibitors and GLP-1 receptor agonists on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus and chronic kidney disease.

OBJECTIVE: To evaluate the cardiovascular and renal benefits of finerenone, sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagonlike peptide-1 receptor agonists (GLP-1 RA) in patients with Type 2 Diabetes Mellitus (T2DM) and chronic kidney disease (CKD) with network meta-analysis. METHODS: Systematic literature searches were conducted of PubMed, Cochrane Library, Web of Science, Medline and Embase covering January 1, 2000 to December 30, 2021. Randomized control trials (RCTs) comparing finerenone, SGLT-2i and GLP-1 RA in diabetics with CKD were selected. We performed a network meta-analysis to compare the two drugs and finerenone indirectly. Results were reported as risk ratio (RR) with corresponding 95% confidence interval (CI). RESULTS: 18 RCTs involving 51,496 patients were included. Finerenone reduced the risk of major adverse cardiovascular events (MACE), renal outcome and hospitalization for heart failure (HHF) (RR [95% CI]; 0.88 [0.80-0.97], 0.86 [0.79-0.93], 0.79 [0.67,0.92], respectively). SGLT-2i were associated with reduced risks of MACE (RR [95% CI]; 0.84 [0.78-0.90]), renal outcome (RR [95% CI]; 0.67 [0.60-0.74], HHF (RR [95% CI]; 0.60 [0.53-0.68]), all-cause death (ACD) (RR [95% CI]; 0.89 [0.81-0.91]) and cardiovascular death (CVD) (RR [95% CI]; 0.86 [0.77-0.96]) compared to placebo. GLP-1 RA were associated with a lower risk of MACE (RR [95% CI]; 0.86 [0.78-0.94]). SGLT2i had significant effect in comparison to finerenone (finerenone vs SGLT2i: RR [95% CI]; 1.29 [1.13-1.47], 1.31 [1.07-1.61], respectively) and GLP-1 RA (GLP-1 RA vs SGLT2i: RR [95% CI]; 1.36 [1.16-1.59], 1.49 [1.18-1.89], respectively) in renal outcome and HHF. CONCLUSIONS: In patients with T2DM and CKD, SGLT2i, GLP-1 RA and finerenone were comparable in MACE, ACD and CVD. SGLT2i significantly decreased the risk of renal events and HHF compared with finerenone and GLP-1 RA. Among GLP-1 RA, GLP-1 analogues showed significant effect in reducing cardiovascular events compared with exendin-4 analogues.

[Expert consensus statement on treatment of type 2 diabetes with Xiaoke Pills in clinical practice].

Xiaoke Pills are Chinese and Western medicine compound preparations with effects of nourishing kidney and Yin,and supplementing Qi and promoting fluid. It is widely used in clinical treatment of type 2 diabetes( Qi and Yin deficiency syndrome),and continuously included in 2010,2013 and 2017 editions of Chinese prevention guide for type 2 diabetes. For the purpose of accurate positioning and rational use in clinic,it is necessary to further define the curative effect,indications,medication precautions and contraindications of Xiaoke Pills,in order to improve medication safety. This consensus was reached by reference of international clinical guidelines and expert consensus approach based on clinical evidence-based evidence,expert experience and standard specification. The evidence-based evaluation was oriented to clinical problems summarized by no less than 200 front-line clinical physicians in two rounds.GRADE system was adopted for quality classification and evaluation of the evidences,and then the nominal group method was used to form consensus recommendations or suggestions. This consensus defined the curative effect advantages,target users,dosage,administration method,contraindications and precautions of Xiaoke Pills,and provided valuable reference for the clinical use of the drug. Thisconsensus still needs to be updated and revised based on new clinical problems and evidence-based evidence in practical application in the future.

Differential ischemic stroke risk linked to novel subtypes of type 2 diabetes: insights from a Mendelian randomization analysis.

PURPOSE: This study employs a two-sample Mendelian randomization (MR) approach to investigate the variation in ischemic stroke risk across novel subtypes of adult-onset type 2 diabetes. METHODS: Leveraging pooled genome-wide association study (GWAS) data from the Swedish ANDIS cohort, we explored the association of four newly identified type 2 diabetes subtypes-severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD), and mild age-related diabetes (MARD)-with ischemic stroke risk. The outcome data for ischemic stroke and its three subtypes (large artery, cardioembolic, and small vessel stroke) were sourced from the MEGASTROKE Consortium. Our analysis applied multiple MR methods, focusing on the inverse-variance weighted (IVW) technique, complemented by thorough sensitivity analyses to examine heterogeneity and potential horizontal pleiotropy. RESULTS: Our findings reveal a significant causal relationship between the SIDD subtype and small vessel stroke (OR = 1.06, 95% CI: 1.01-1.11, p = 0.025), while no causal associations were observed for SIRD with any stroke subtype. MOD was causally linked to small vessel stroke (OR = 1.07, 95% CI: 1.02-1.12, p = 0.004) and large artery stroke (OR = 1.07, 95% CI: 1.01-1.13, p = 0.015). Similarly, MARD showed a causal relationship with small vessel stroke (OR = 1.09, 95% CI: 1.03-1.16, p = 0.006) and overall ischemic stroke risk (OR = 1.04, 95% CI: 1.01-1.08, p = 0.010). CONCLUSIONS: Our study highlights distinct causal links between specific type 2 diabetes subtypes and ischemic stroke risks, emphasizing the importance of subtype-specific prevention and treatment strategies.

A Prospective, Multicentered, Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Keluoxin Capsules in the Treatment of Microalbuminuria in Patients with Type 2 Early Diabetic Kidney Disease.

Background: To evaluate the efficacy and safety of Keluoxin (KLX) capsules and provide validated evidence for the application of KLX in the treatment of diabetic kidney disease (DKD). Methods: A multicenter, randomized, double-blind, placebo-controlled trial design was used to screen 129 patients with DKD (urinary albumin-to-creatinine ratio [UACR]: male, 2.5-30 mg/mmol; female, 3.5-30 mg/mmol) and with Qi and Yin deficiency and blood stasis symptoms. Written informed consent was obtained from all patients. The patients were randomly divided into KLX and control groups. The KLX group was orally administered KLX (6 g/day) and irbesartan tablets (150 mg/day), whereas the control group was administered KLX placebo (6 g/day) and irbesartan tablets (150 mg/day). Patients were observed for 24 weeks to evaluate the natural logarithm of the UACR (log-UACR), the odds ratio (OR) for a sustained increase in the UACR of at least 30% and 40%, estimated glomerular filtration rate (eGFR), changes in symptoms and quality-of-life scores, and adverse events. Results: The changes of the natural log-UACR during the 24 weeks compared with baseline in the KLX group were better than those in the control group (LS mean ± standard error, -0.26 ± 0.10 vs. 0.01 ± 0.09, p = 0.0292). The incidence of a sustained increase in the UACR of at least 30% and 40% was found to be significantly lower in the KLX group (OR, 0.26; 95% confidence interval [CI], 0.09-0.75; OR, 0.29; 95% CI, 0.10-0.82). Changes in symptoms and quality-of-life scores in the KLX group were better than those in the control group. There was no statistically significant difference in eGFR or the incidence of adverse events between the groups. Conclusions: Overall, these results suggest that KLX capsules combined with irbesartan can reduce microalbuminuria, relieve the symptoms, and improve the quality of life for patients with type 2 early DKD compared with the use of irbesartan alone. Trial registration: Chinese Clinical Trial Registry, registration number: ChiCTR2100052764.

Greenhouse gas emissions from the growing season are regulated by precipitation events in conservation tillage farmland ecosystems of Northeast China.

Reducing greenhouse gas (GHG) emissions from agricultural ecosystems is vital to mitigate global warming. Conservation tillage is widely used in farmland management to improve soil quality; however, its effects on soil GHG emissions remain poorly understood, particularly in high-yield areas. Therefore, our study aimed to evaluate the effects of no-tillage (NT) combined with four straw-mulching levels (0 %, 33 %, 67 %, and 100 %) on GHG emission risk and the main influencing factors. We conducted in-situ observations of GHG emissions from soils under different management practices during the maize-growing season in Northeastern China. The results showed that NT0 (705.94 g m-2) reduced CO2 emissions by 18 % compared to ridge tillage (RT, 837.04 g m-2). Different straw mulching levels stimulated N2O emissions after rainfall, particularly under NT combined with 100 % straw mulching (2.89 kg ha-1), which was 45 % higher than that in any other treatments. The CH4 emissions flux among different treatments was nearly zero. Overall, straw mulching levels had no significant effect on the GHG emissions. During the growing season, soil NH4+-N (< 20 mg kg-1) remained low and decreased with the extension of growth stage, whereas soil NO3--N initially increased and then decreased. More importantly, the results of structural equation modeling indicate that: a) organic material input and soil moisture are key factors affecting CO2 emissions, b) nitrogen fertilizer and soil moisture promote N2O emissions, and c) climatic factors exert an inexorable influence on the GHG emissions process. Our conclusions emphasize the necessity of incorporating precipitation-response measures into farmland management to reduce the risk of GHG emissions.

Qufeng tongluo decoction decreased proteinuria in diabetic mice by protecting podocytes via promoting autophagy.

Background: Diabetic kidney disease (DKD) is one of diabetic complications, which has become the leading cause of end-stage kidney disease. In addition to angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker(ACEI/ARB) and sodium-glucose cotransporter-2 inhibitor (SGLT2i), traditional Chinese medicine (TCM) is an effective alternative treatment for DKD. In this study, the effect of Qufeng Tongluo (QFTL) decoction in decreasing proteinuria has been observed and its mechanism has been explored based on autophagy regulation in podocyte. Methods: In vivo study, db/db mice were used as diabetes model and db/m mice as blank control. Db/db mice were treated with QFTL decoction, rapamycin, QFTL + 3-Methyladenine (3-MA), trehalose, chloroquine (CQ) and QFTL + CQ. Mice urinary albumin/creatinine (UACR), nephrin and autophagy related proteins (LC3 and p62) in kidney tissue were detected after intervention of 9 weeks. Transcriptomics was operated with the kidney tissue from model group and QFTL group. In vitro study, mouse podocyte clone-5 (MPC-5) cells were stimulated with hyperglycemic media (30 mmol/L glucose) or cultured with normal media. High-glucose-stimulated MPC-5 cells were treated with QFTL freeze-drying powder, rapamycin, CQ, trehalose, QFTL+3-MA and QFTL + CQ. Cytoskeletal actin, nephrin, ATG-5, ATG-7, Beclin-1, cathepsin L and cathepsin B were assessed. mRFP-GFP-LC3 was established by stubRFP-sensGFP-LC3 lentivirus transfection. Results: QFTL decoction decreased the UACR and increased the nephrin level in kidney tissue and high-glucose-stimulated podocytes. Autophagy inhibitors, including 3-MA and chloroquine blocked the effects of QFTL decoction. Further study showed that QFTL decoction increased the LC3 expression and relieved p62 accumulation in podocytes of db/db mice. In high-glucose-stimulated MPC-5 cells, QFTL decoction rescued the inhibited LC3 and promoted the expression of ATG-5, ATG-7, and Beclin-1, while had no effect on the activity of cathepsin L and cathepsin B. Results of transcriptomics also showed that 51 autophagy related genes were regulated by QFTL decoction, including the genes of ATG10, SCOC, ATG4C, AMPK catalytic subunit, PI3K catalytic subunit, ATG3 and DRAM2. Conclusion: QFTL decoction decreased proteinuria and protected podocytes in db/db mice by regulating autophagy.

The burden of mental disorders in Asian countries, 1990-2019: an analysis for the global burden of disease study 2019.

Mental disorders are the leading contributors to the globally nonfatal burden of disease. This study was aimed to estimate the burden of mental disorders in Asian countries. Based on GBD 2019, the prevalence and disability-adjusted life of years (DALYs) rates with 95% uncertainty intervals (UI) were estimated in Asian countries. Predictions for the future burden of 8 selected countries, ranks of the burden of mental disorders and correlations with Sociodemographic Index (SDI) were also estimated. During the past 3 decades, while the number of DALYs of mental disorders increased from 43.9 million (95% UI: 32.5-57.2) to 69.0 million (95% UI: 51.0-89.7), the age-standardized rates of DALYs of mental disorders remained largely consistent from 1452.2 (95% UI: 1080.16-1888.53) per 100,000 population in 1990 to 1434.82 (95% UI: 1065.02-1867.27) per 100,000 population in 2019, ranked as the eighth most significant disease burden in Asia in 2019. Depressive disorders (37.2%) were the leading contributors to the age-standardized DALY rates of mental disorders in Asia, followed by anxiety disorders (21.5%). The age-standardized DALY rates in females were higher than their male counterparts, both peaked at 30-34 years. The age-standardized DALY rates were predicted to remain stable, with the number of DALYs presented an upward trend in the future. There was no significant correlation between the burden of mental disorders and SDI. All mental disorders ranked higher in 2019, compared in 1990. To reduce this burden, urgent measures for prevention, treatment, and rehabilitation for mental disorders need to be taken by Asian governments.

[An approach for the measurement of the surface area of scalp flap over the cranial defect after decompressive craniectomy].

OBJECTIVE: To introduce a simple, fast and universal measuring method used in measurement of the surface area of scalp flap over the cranial defect after decompressive craniectomy. METHODS: The first step: CT images of the patient with craniocerebral trauma after decompressive craniectomy were obtained and imported into Mimics. The second step: based on the defined threshold, the 3D geometric models of brain and skull were reconstructed after the original Dicom format pictures three-dimensional processed by Mimics. The third step: based on the two builded 3D models, utilizing the segmentation and measurement tools of Mimics to conduct cutting, splitting and measuring operations for the 3D model of brain. The forth step: estimating the surface area of scalp flap over the removed bone flap by using mathematical computation methods. RESULTS: The application of the introduced method estimated the surface area of scalp flap over the cranial defect of different people with different position of craniocerebral trauma. CONCLUSIONS: This paper introduces a simple, fast and universal new measuring method. We can conveniently estimate the surface area of scalp flap by using the introduced method.

Paris saponin â induce toxicity in zebrafish by up-regulation of p53 pathway and down-regulation of wnt pathway.

Paris saponin I, II, and VII are three important components in Paris polyphylla, which have been widely studied as tumor cytotoxic drugs, but their safety in vivo has not been reported. Therefore, this study evaluated the safety of these three drugs based on the zebrafish model. Firstly, the lethality curves and lethal concentration of 50% (LC50) values of the three saponins were determined and the results showed the values of LC50 of Paris saponin I, II, and VII were 122.2, 210.7, 566.2 ng/mL, respectively. And then our data revealed that Paris saponin I, II and VII had definite hepatotoxicity, as shown by their significant reduction in the liver area and fluorescence intensity of zebrafish. Besides, Paris saponin Ⅰ affected the heart rate of zebrafish obviously, suggesting its cardiovascular toxicity. Afterwards, we found Paris saponin Ⅰ and Ⅶ reduced the area and fluorescence intensity of kidney in zebrafish, and had mild nephrotoxicity. And when treated with Paris saponin I, the pathological section of liver tissue in zebrafish showed vacuoles, severe necrosis of hepatocytes, and then the apoptosis of hepatocytes could be observed by TUNEL staining. Eventually, we found that the genes expression of p53, Bax and ß-catenin changed significantly in the administration group of Paris saponin I. In general, our study proved Paris saponin Ⅰ was the most toxic of the three saponins, and the most definite toxic target sites were liver and cardiovascular. And it was further inferred that the totoxicity of Paris saponin Ⅰ may be related to the regulation of p53 pathway and Wnt pathway. These results above showed the toxicity of the three saponins in zebrafish, suggesting their safety should be paid more attention in the future.

CCDC103 as a Prognostic Biomarker Correlated with Tumor Progression and Immune Infiltration in Glioma.

Background: The Coiled-coil domain-containing proteins (CCDCs) are expressed in many cancers, but the role of Coiled-coil domain-containing protein 103 (CCDC103) in cancers remains unclear. Further investigations are necessary to ascertain its diagnostic significance and understand its biological function in cancers. This study aims to elucidate the biological functionalities of CCDC103 in glioma and evaluate the correlation between CCDC103 expression with glioma progression. Methods: Clinical data on glioma patients were acquired from The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), and the Gene Expression Omnibus (GEO). The evaluation encompassed the examination of correlations between CCDC103 expression, pathological characteristics, and clinical outcomes. Furthermore, the analysis included the assessment of the correlations between CCDC103 expression and immune cell infiltration as well as glioma progression. Results: Gliomas have higher levels of CCDC103 expression than the para-carcinoma tissues. Poorer prognosis, unfavorable histological characteristics, the absence of IDH gene mutations, and the absence of chromosome 1p and 19q deletions were all associated with higher expression of CCDC103 in gliomas. In addition to patient age, tumor grade, the absence of IDH mutations, and the absence of chromosome 1p and 19q deletions, univariate and multivariate Cox analyses showed that CCDC103 expression was independently prognostic of overall survival, disease-free survival, and progression-free survival in patients with glioma. Furthermore, tumor infiltration of B cells, neutrophils, macrophages, and dendritic cells were all linked with elevated expression of CCDC103. High CCDC103 expression was linked to immune response-related signaling pathways and cell proliferation, according to gene set enrichment analysis (GSEA). Notably, the knockdown of CCDC103 in glioma cell lines resulted in a significant reduction in cell proliferation and migration. Conclusion: The correlation between CCDC103 expression and both glioma progression and immune cell infiltration implies that CCDC103 expression holds promise as a valuable prognostic biomarker for glioma.

Network meta-analysis on the efficacy and safety of finerenone versus SGLT2 inhibitors on reducing new-onset of atrial fibrillation in patients with type 2 diabetes mellitus and chronic kidney disease.

OBJECTIVE: To evaluate the efficacy and safety of finerenone and sodium-glucose cotransporter-2 inhibitors (SGLT2i) on reducing new-onset of atrial fibrillation (AF) in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). METHOD: We searched the PubMed, Cochrane Library, Web of Science, Medline and Embase covering January 1, 2000 to April 30, 2022. Randomized control trials comparing finerenone or SGLT2i with placebo in patients with T2DM and CKD were selected. Results were reported as risk ratio (RR) with corresponding 95% confidence interval (CI). RESULTS: A total of 10 studies (35,841 patients) were included. Finerenone (RR 0.79, 95% CI 0.62-0.99) was associated with a decreased risk of AF compared with placebo, while SGLT2i were not. SGLT2i were associated with a decreased risk of hospitalization for heart failure (RR 0.78, 95% CI 0.63-0.98) compared with finerenone. They were comparable in AF(RR 0.84, 95% CI 0.48,1.46), major adverse cardiovascular events(MACE) (RR 0.93, 95% CI 0.81,1.06) and nonfatal stroke(RR 0.78, 95% CI 0.58,1.05). They both showed no significant risk of adverse events compared with placebo. CONCLUSION: There was no significant difference in the reduction of new-onset of atrial fibrillation between Finerenone and SGLT2i based on the indirect comparisons of currently available clinical studies. The large-sampled head-to-head trials was needed for the more precise conclusion.

F-Box Protein 11 Suppresses Cell Proliferation and Aerobic Glycolysis in Glioblastomas by Mediating the Ubiquitin Degradation of Cdc25A.

Glioblastoma is a malignant CNS tumor with an extremely poor prognosis. F-box protein 11 (FBXO11) has E3 ubiquitin ligase activity and participates in the pathogenesis of multiple tumors but the role and mechanism of FBXO11 activity in glioblastoma remain unknown. In this study, FBXO11 was first observed to be downregulated in glioblastoma tissues and cell lines. 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) and colony formation assays and enzyme linked immunosorbent assay (ELISA) demonstrated that overexpression of FBXO11 suppressed proliferation and aerobic glycolysis and induced cell cycle arrest in U251-MG and A172 cells. FBXO1 decreased cell division cycle 25 A (Cdc25A) expression through ubiquitin degradation in a coprecipitation assay. A Western blot assay validated FBXO11 suppression of PKM2 dephosphorylation and c-Myc-mediated aerobic glycolysis via reduction of Cdc25A. In addition, a rescue experiment revealed that FBXO11 suppressed proliferation and aerobic glycolysis, both of which were reversed by overexpression of Cdc25A. FBXO11 overexpression also inhibited tumorigenesis via suppressing Cdc25A expression in vivo. These findings indicate that FBXO11 suppresses cell proliferation and aerobic glycolysis in glioblastomas by mediating the ubiquitin degradation of Cdc25A thereby providing insight into mechanisms of glioblastoma tumorigenesis and identifying a new potential therapeutic strategy.

Comparative efficacy of 6 traditional Chinese patent medicines combined with lifestyle modification in patients with prediabetes: A network meta-analysis.

OBJECTIVE: To evaluate the efficacy of 6 Traditional Chinese patent medicines combined with lifestyle modification in the treatment of prediabetes with network meta-analysis. METHOD: The randomized controlled trials (RCTs) of Shen qi jiang tang capsule/granule (Shenqi), Tian mai xiao ke tablet (Tianmai), Tian qi capsule (Tianqi), Jin qi jiang tang tablet (Jinqi), Jin li da granule (Jinlida), Tang mai kang granule (Tangmaikang) in the treatment of prediabetes in PubMed, Web of Science, The Cochrane Library, EMbase, China Knowledge Network (CNKI), WanFang and Weipu databases were searched. Three reviewers independently conducted the screening, extracted the data and assessed methodological quality. Data analysis was performed using Rev Man 5.3 and STATA 15.0 software. RESULTS: A total of 50 RCTs, including 4594 patients, were included. The addition of Shenqi (OR 0.19 [95 %CI: 0.07, 0.52]) and Jinqi (OR 0.32 [95 %CI: 0.15, 0.71]) to existing lifestyle modification resulted in significant lower incidence rate of DM compared with none/placebo added to lifestyle modification. The addition of Jinlida (SMD -0.41% [95 %CI:-0.81, -0.01]) and Tangmaikang (SMD -0.83%[95 %CI: -1.46,-0.20]) resulted in significant additional HbA1c reductions compared with none/placebo added to lifestyle modification. The addition of all CTPMs except Tianqi resulted in significant additional FBG reductions and the addition of Shenqi (SMD -1.96[95 %CI: -3.64, -0.28]) resulted in significant additional PBG reductions. CONCLUSION: For patients with prediabetes, Shenqi + LM was among the most effective in reducing the incidence of diabetes for patients with prediabetes, while Jinlida + LM was among the least effective. Jinqi + LM and Tianqi + LM might be among the most effective, while western oral drugs + LM, Tianmai + LM, Tangmaikang + LM and Placebo + LM might be among the least effective. In addition, Tangmaikang + LM and Jinlida + LM might be among the most effective in reducing HbA1c, while Tianmai + LM, Tangmaikang + LM, Shenqi + LM, Jinlida + LM and Jinqi + LM might be among the most effective in reducing FPG for patients with prediabetes. Yet direct comparison and further investigation to explore mechanisms are warranted.

DUSP10 upregulation is a poor prognosticator and promotes cell proliferation and migration in glioma.

Dual-specificity phosphatase 10 (DUSP10) correlates with inflammation, cytokine secretion, cell proliferation, survival, and apoptosis. However, its role in glioma is unclear. Herein, we sought to examine the expression and the underlying carcinogenic mechanisms of DUSP10 action in glioma. DUSP10 expression in glioma was significantly higher than that in normal brain tissues. High DUSP10 expression indicated adverse clinical outcomes in glioma patients. Increased DUSP10 expression correlated significantly with clinical features in glioma. Univariate Cox analysis showed that high DUSP10 expression was a potential independent marker of poor prognosis in glioma. Furthermore, DUSP10 expression in glioma correlated negatively with its DNA methylation levels. DNA methylation level of DUSP10 also correlated negatively with poor prognosis in glioma. More importantly, DUSP10 expression correlated positively with the infiltration of B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells in glioma. Gene set enrichment analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis confirmed that DUSP10 participated in signaling pathways involved in focal adhesion, TNF cascade, Th17 cell differentiation, and NF-kappa B cascade. Finally, we uncovered that DUSP10 was dramatically upregulated in glioblastoma (GBM) cells and that the knockdown of DUSP10 inhibited glioma cell proliferation and migration. Our findings suggested that DUSP10 may serve as a potential prognostic biomarker in glioma.

Treatment options of traditional Chinese patent medicines for dyslipidemia in patients with prediabetes: A systematic review and network meta-analysis.

Objective: To compare the clinical efficacy and safety of SIX Traditional Chinese Patent Medicines (TCPM) recommended by guidelines in improving lipids for patients with prediabetes by network meta-analysis. Methods: Randomized controlled trials of 6 TCPM in the treatment of prediabetes were searched systematically in various databases. After extracting effective data, the risk of bias was assessed using Review Manager 5.3 and Cochrane Collaboration Systems Evaluator's Manual. Network meta-analysis was performed using STATA 15.0 based on the frequency statistical model. The effect size and credibility of the evidence for the intervention were summarized based on a minimal contextualized framework. Results: A total of 27 studies involving 2,227 patients were included. Compared with lifestyle modification (LM), Shenqi + LM [SMD -0.49 (95% CI: -0.85, -0.12)] and Jinqi + LM [SMD -0.44 (95% CI: -0.81, -0.06)] showed statistically significant effect in lowering TG, Shenqi + LM [SMD -0.51 (95%CI: -0.86, -0.17)] and Jinqi + LM [SMD -0.44 (95%CI: -0.80, -0.08)] in lowering TC, Jinlida + LM [SMD -0.31 (95%CI: -0.59, -0.04)] in lowering LDL-C, Shenqi + LM [SMD 0.29 (95%CI: 0.06, 0.51)] and Jinqi + LM [SMD 0.16 (95%CI: 0.01, 0.31)] in increasing HDL-C. Conclusion: For patients with prediabetes, Traditional Chinese patent medicine Jinqi and Shenqi combined with lifestyle modification were associated with a significant reduction in TG and TC, while Shenqi + LM was among the most effective. Jinlida + LM was among the least effective. Systematic Review Registration: https://clinicaltrials.gov/, identifier PROSPERO(CRD42021279332).

Shenlian (SL) Decoction, a Traditional Chinese Medicine Compound, May Ameliorate Blood Glucose via Mediating the Gut Microbiota in db/db Mice.

Shenlian (SL) decoction is a herbal formula composed of Coptis and ginseng, of which berberine and ginsenoside are the main constituents. Even though SL decoction is widely used in treating diabetes in China, the mechanism of its antidiabetes function still needs further study. Gut microbiota disorder is one of the important factors that cause diabetes. To explore the effect of SL decoction on intestinal microbiota, gut microbiota of mice was analyzed by sequencing the gut bacterial 16S rRNA V3+V4 region and metagenomics. In this study, results demonstrated that SL decoction had a better hypoglycemic effect and ß cell protection effect than either ginseng or Coptis chinensis. Alpha diversity analysis showed that all interventions with ginseng, Coptis, and SL decoction could reverse the increased diversity and richness of gut microbiota in db/db mice. PCoA analysis showed oral SL decoction significantly alters gut microbiota composition in db/db mice. 395 OTUs showed significant differences after SL treatment, of which 37 OTUs enriched by SL decoction showed a significant negative correlation with FBG, and 204 OTUs decreased by SL decoction showed a significant positive correlation with FBG. Results of KEGG analysis and metagenomic sequencing showed that SL decoction could reduce the Prevotellaceae, Rikenellaceae, and Helicobacteraceae, which were related to lipopolysaccharide biosynthesis, riboflavin metabolism, and peroxisome, respectively. It could also upregulate the abundance of Bacteroidaceae, which contributed to the metabolism of starch and sucrose as well as pentose-glucuronate interconversions. In the species level, SL decoction significantly upregulates the relative abundance of Bacteroides_acidifaciens which showed a significant negative correlation with FBG and was reported to be a potential agent for modulating metabolic disorders such as diabetes and obesity. In conclusion, SL decoction was effective in hypoglycemia and its mechanism may be related to regulating gut microbiota via upregulating Bacteroides_acidifaciens.

Effect of RG (Coptis root and ginseng) formula in patients with type 2 diabetes mellitus: a study protocol for a randomized controlled and double-blinding trial.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a common metabolic disease with significant health, social, and economic consequences. Traditional Chinese medicine (TCM) could effectively regulate blood sugar and influence gut microbiota in T2DM patients. Preliminary studies showed that the Coptis root and ginseng (RG) formula could relieve insulin resistance and prevent the progression of diabetes in mice. OBJECTIVES: The purpose of this study is to explore the efficacy and safety of RG formula in the treatment of adult patients with T2DM, as well as observing its effects on gut microbiota. METHODS AND ANALYSIS: This trial is a randomized, double-blind, placebo-controlled study. A total of 60 participants will be randomized in a 1:1 ratio into an experiment group (RG formula) and a control group (placebo). Patients in both groups will be given diabetes education and basic blood glucose control. Glucose-lowering drugs with significant influence on gut microbiota will be avoided. This trial will last 25 weeks including 1-week run-in, 12-week intervention, and 12-week follow-up visit. The primary outcome is the change in the HbA1c. The secondary outcomes comprise the change in the fasting blood glucose (FBG), postprandial blood glucose (PBG), fasting insulin (FIL), fasting C-peptide(C-P), insulin resistance index (IRI), inflammatory factors, and species abundance of gut microbiota between the two groups. Safety of medication will also be evaluated. The correlation analysis will be explored between the glycemic indicators, inflammatory factors, and abundance of gut microbiota. DISCUSSION: This study will provide the clinical evidence for the efficacy of RG formula in regulating blood sugar and influencing gut microbiota, which will be beneficial to form the integrated therapeutic regimen in T2DM with TCM. TRIAL REGISTRATION: "Clinical Study on the Intervention of Coptis Root and Ginseng," Chinese Clinical Trials Registry ChiCTR 2100042126 . Registered on 14 January 2021.

Qingre Yiqi Method along with Oral Hypoglycemic Drugs in Treating Adults with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the efficacy of the Qingre Yiqi method in the treatment of type 2 diabetes mellitus (T2DM) with meta-analysis. METHOD: The randomized controlled trials (RCTs) of the Qingre Yiqi method in the treatment of T2DM in the PubMed, Medline, EMBase, Cochrane Library, Web of Science, Weipu Journal, China Knowledge Network (CNKI), and Wanfang database were conducted. Three reviewers independently conducted the screening, extracted the data, and assessed methodological quality. Data analysis was performed using Rev Man 5.3 software for statistical analysis. RESULTS: A total of 15 RCTs, including 1440 patients, were included. The results showed that compared with oral hypoglycemic drugs alone, the add-on treatment of the Qingre Yiqi method could significantly improve Chinese medicine syndrome (OR (95%CI) = 3.66 [2.47,5.42], P < 0.00001) and lower the level of HbA1c (MD (95%CI) = -0.68 [0.91, -0.45], P < 0.00001), triglyceride (TG) (MD (95%CI) = -0.38 [-0.58,-0.17], P=0.0004), low-density lipoprotein cholesterol (LDL-C) (MD (95%CI) = -0.25 [-0.37, -0.13], P < 0.0001), and total cholesterol(TC) (MD(95%CI) = -0.40[-0.67, -0.13], P=0.003). In terms of fasting blood glucose (FBG) and postprandial blood sugar (PBG), subgroup analysis showed that the baseline of FBG and the number of combined oral hypoglycemic drugs of PBG were the major sources of heterogeneity. CONCLUSION: Compared with the standard treatment, the Qingre Yiqi method along with oral hypoglycemic drugs showed the more beneficial effects for T2DM on improving TCM syndromes and reducing the blood glucose and partial lipid parameter.

Tripterygium and its extracts for diabetic nephropathy: Efficacy and pharmacological mechanisms.

Diabetic nephropathy (DN) is a common but intractable diabetic microvascular complication. Tripterygium, a Chinses herb, has been proven to be effective for DN treatment. In this review, the efficacy and pharmacological mechanism of tripterygium and its extracts on DN is elucidated. Tripterygium and its extracts could effectively reduce urine protein and protect renal function. Its pharmacological mechanism involves anti-inflammation, anti-oxidation, anti-glomerulosclerosis and anti-fibrosis, which is achieved by balancing the Th1/Th2 cells, regulating macrophage infiltration, and regulating the following pathways: p38 MAPK, NF-κB, TGF-ß, Wnt/ß-catenin, Akt and Notch1. Although tripterygium and its extracts may result in some adverse effects, including liver-function damage, gastrointestinal reaction, menstrual disorders, and reproductive problems, they are considered good alternative medicines for DN if used with caution and in the proper manner.

A density-based competitive data stream clustering network with self-adaptive distance metric.

Data stream clustering is a branch of clustering where patterns are processed as an ordered sequence. In this paper, we propose an unsupervised learning neural network named Density Based Self Organizing Incremental Neural Network(DenSOINN) for data stream clustering tasks. DenSOINN is a self organizing competitive network that grows incrementally to learn suitable nodes to fit the distribution of learning data, combining online unsupervised learning and topology learning by means of competitive Hebbian learning rule. By adopting a density-based clustering mechanism, DenSOINN discovers arbitrarily shaped clusters and diminishes the negative effect of noise. In addition, we adopt a self-adaptive distance framework to obtain good performance for learning unnormalized input data. Experiments show that the DenSOINN can achieve high standard performance comparing to state-of-the-art methods.