Correlation of obesity, dietary patterns, and blood pressure with uric acid: data from the NHANES 2017-2018.

BACKGROUND: Prevalence rates of hyperuricemia and gout are increasing. Clinical investigations of hyperuricemia-related risk factors aid in the early detection, prevention, and management of hyperuricemia and gout. Ongoing research is examining the association of obesity, dietary patterns, and blood pressure (BP) with serum uric acid (sUA). METHODS: A cross-sectional study was conducted based on the National Health and Nutrition Examination Survey. The exposures included body mass index (BMI), dietary patterns, and BP. The outcome variable was sUA level. The weighted multivariate linear regression models and smooth curve fittings were used to assess the association of BMI, dietary patterns, and BP with sUA. RESULTS: There was a significantly positive correlation between BMI and sUA (ß = 0.059, 95% CI: 0.054 to 0.064, P < 0.00001). Overweight and obese individuals had higher sUA levels than those with the normal BMI (ß = 0.451, 95% CI: 0.357 to 0.546, P < 0.00001; ß = 0.853, 95% CI: 0.760 to 0.946, P < 0.00001; respectively). Dietary energy intake was positively correlated with sUA (ß = 0.000, 95% CI: 0.000 to 0.000, P = 0.01057). Dietary intake of carbohydrate and fiber were negatively correlated with sUA (ß = - 0.001, 95% CI: - 0.002 to - 0.000, P < 0.00001; ß = - 0.008, 95% CI: - 0.011 to - 0.004, P = 0.00001; respectively). Moreover, systolic BP was positively correlated with sUA (ß = 0.006, 95% CI: 0.003 to 0.009, P = 0.00002). However, no statistical differences were found about the associations of dietary intake of total sugars, protein, total fat, cholesterol, and diastolic BP with sUA. CONCLUSIONS: The current cross-sectional investigation of a nationally representative sample of US participants showed that BMI, dietary energy intake, and systolic BP were positively correlated with sUA levels; dietary carbohydrate and fiber intake were negatively correlated with sUA levels. The findings might be helpful for the management and treatment of hyperuricemia and gout.

Urine proteomics identifies biomarkers for diabetic kidney disease at different stages.

BACKGROUND: Type 2 diabetic kidney disease is the most common cause of chronic kidney diseases (CKD) and end-stage renal diseases (ESRD). Although kidney biopsy is considered as the 'gold standard' for diabetic kidney disease (DKD) diagnosis, it is an invasive procedure, and the diagnosis can be influenced by sampling bias and personal judgement. It is desirable to establish a non-invasive procedure that can complement kidney biopsy in diagnosis and tracking the DKD progress. METHODS: In this cross-sectional study, we collected 252 urine samples, including 134 uncomplicated diabetes, 65 DKD, 40 CKD without diabetes and 13 follow-up diabetic samples, and analyzed the urine proteomes with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). We built logistic regression models to distinguish uncomplicated diabetes, DKD and other CKDs. RESULTS: We quantified 559 ± 202 gene products (GPs) (Mean ± SD) on a single sample and 2946 GPs in total. Based on logistic regression models, DKD patients could be differentiated from the uncomplicated diabetic patients with 2 urinary proteins (AUC = 0.928), and the stage 3 (DKD3) and stage 4 (DKD4) DKD patients with 3 urinary proteins (AUC = 0.949). These results were validated in an independent dataset. Finally, a 4-protein classifier identified putative pre-DKD3 patients, who showed DKD3 proteomic features but were not diagnosed by clinical standards. Follow-up studies on 11 patients indicated that 2 putative pre-DKD patients have progressed to DKD3. CONCLUSIONS: Our study demonstrated the potential for urinary proteomics as a noninvasive method for DKD diagnosis and identifying high-risk patients for progression monitoring.

Identification of metabolism genes related to hepatocarcinogenesis and progression in type 2 diabetes mellitus via co-expression networks analysis.

BACKGROUND: Type 2 Diabetes Mellitus (T2DM) is an independent risk factor of hepatocellular carcinoma (HCC). However, the related genes and modules to hepatocarcinogenesis and progression in T2DM remain unclear. METHODS: The microarray data from Gene Expression Omnibus (GEO) were analyzed to screen differentially expressed genes (DEGs) of T2DM and HCC dataset. Then, weighted gene co-expression network analysis (WGCNA) was performed on these DEGs to detect the modules and genes, respectively. Common genes in modules with clinical interests of T2DM and HCC were obtained and annotated via GOSemSim package and Metascape. Genes related to late-stage HCC and high glycated haemoglobin (HbA1c) were also identified. These genes were validated by UALCAN analysis and univariate cox regression based on The Cancer Genome Atlas (TCGA). Finally, another two independent datasets were applied to confirm the results of our study. RESULTS: A total of 1288 and 1559 DEGs of T2DM and HCC were screened, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment revealed several shared pathways in two diseases, such as pathways in cancer and metabolism. A total of 37 common genes correlated with T2DM and HCC were then identified with WGCNA. Furthermore, 12 genes from modules associated with late-stage HCC and high HbA1c were regarded as hub genes. Among these genes, 8 genes associated with tumor invasion and metastasis were validated by UALCAN analysis. Moreover, downregulations of ACAT1, SLC2A2, PCK1 and ABAT were significantly associated with poorer prognosis in HCC patients with elevated HbA1c. Additionally, the expressions of PCK1 and ABAT were raised in HepG2 cells pre-treated with metformin and phenformin. CONCLUSIONS: The present study confirmed several metabolic genes related to hyperglycemia and malignant tumor, which may provide not only new insights into the pathogenesis of hepatocarcinogenesis and progression in T2DM, but also novel therapeutic targets for T2DM patients with HCC in the future.

The improvement of modified Si-Miao granule on hepatic insulin resistance and glycogen synthesis in type 2 diabetes mellitus involves the inhibition of TNF-α/JNK1/IRS-2 pathway: network pharmacology, molecular docking, and experimental validation.

BACKGROUND: Modified Si-Miao granule (mSMG), a traditional Chinese medicine, is beneficial for T2DM and insulin resistance (IR), but the underlying mechanism remains unknown. METHODS: Using network pharmacology, we screened the compounds of mSMG and identified its targets and pathway on hepatic IR in T2DM. Using molecular docking, we identified the affinity between the compounds and hub target TNF-α. Then these were verified in KK-Ay mice and HepG2 cells. RESULTS: 50 compounds and 170 targets of mSMG against IR in T2DM were screened, and 9 hub targets such as TNF and MAPK8 were identified. 170 targets were mainly enriched in insulin resistance and TNF pathway, so we speculated that mSMG might act on TNF-α, JNK1 and then regulate insulin signaling to mitigate IR. Experimental validation proved that mSMG ameliorated hyperglycemia, IR, and TNF-α, enhanced glucose consumption and glycogen synthesis, relieved the phosphorylation of JNK1 and IRS-2 (Ser388), and elevated the phosphorylation of Akt (Ser473) and GSK-3ß (Ser9) and GLUT2 expression in KK-Ay mice. Molecular docking further showed berberine from mSMG had excellent binding capacity with TNF-α. Then, in vitro validation experiments, we found that 20% mSMG-MS or 50 µM berberine had little effect in IR-HepG2 cell viability, but significantly increased glucose consumption and glycogen synthesis and regulated TNF-α/JNK1/IRS-2 pathway. CONCLUSION: Network pharmacology and molecular docking help us predict potential mechanism of mSMG and further guide experimental validation. mSMG and its representative compound berberine improve hepatic IR and glycogen synthesis, and its mechanism may be related to the inhibition of TNF-α/JNK1/IRS-2 pathway.

Integrated metabolomics and transcriptomics analysis reveals the mechanism of Tangbi capsule for diabetic lower extremities arterial disease.

Objective: Tangbi capsule (TBC) is a traditional Chinese medicine prescription, which has the potential to improve the vascular insufficiency of lower extremities and limb numbness in diabetes. However, the potential mechanism remains unknown. This study aims to investigate the pharmacological effects and mechanism of TBC on rats with diabetic lower extremities arterial disease (LEAD). Methods: The mechanism of TBC on diabetic LEAD was investigated through metabolomics and transcriptomics analysis, and the main components of TBC were determined by mass spectrometry. The efficacy and mechanism of TBC on diabetic LEAD rats were investigated through in vitro experiments, histopathology, blood flow monitoring, western blot, and real-time polymerase chain reaction. Results: Mass spectrometry analysis identified 31 active chemical components in TBC including (2R)-2,3-Dihydroxypropanoic acid, catechin, citric acid, miquelianin, carminic acid, salicylic acid, formononetin, etc. In vitro analysis showed that TBC could reduce endothelial cell apoptosis and promote angiogenesis. Histopathological analysis showed that TBC led to an obvious improvement in diabetic LEAD as it improved fibrous tissue proliferation and reduced arterial wall thickening. In addition, TBC could significantly increase the expression levels of HIF-1α, eNOS, and VEGFA proteins and genes while reducing that of calpain-1 and TGF-ß, suggesting that TBC can repair vascular injury. Compared with the model group, there were 47 differentially expressed genes in the whole blood of TBC groups, with 25 genes upregulated and 22 downregulated. Eighty-seven altered metabolites were identified from the serum samples. Combining the changes in differentially expressed genes and metabolites, we found that TBC could regulate arginine biosynthesis, phenylalanine metabolism, pyrimidine metabolism, arachidonic acid metabolism, pyrimidine metabolism, arachidonic acid metabolism, nucleotide metabolism, vitamin B6 metabolism and other metabolic pathways related to angiogenesis, immune-inflammatory response, and cell growth to improve diabetic LEAD. Conclusion: TBC improved vascular endothelial injury, apoptosis, lipid accumulation, liver and kidney function, and restored blood flow in the lower extremities of diabetic LEAD rats. The mechanism of TBC in the treatment of diabetic LEAD may be related to the modulation of inflammatory immunity, lipid metabolism, and amino acid metabolism. This study presented preliminary evidence to guide the use of TBC as a therapy option for diabetic LEAD.

Intense simplified strategy for newly diagnosed type 2 diabetes in patients with severe hyperglycaemia: multicentre, open label, randomised trial.

OBJECTIVE: To evaluate whether the intense simplified strategy, which comprises short term intensive insulin therapy (SIIT) followed by subsequent oral antihyperglycaemic regimens, could improve long term glycaemic outcomes in patients with newly diagnosed type 2 diabetes mellitus and severe hyperglycaemia. DESIGN: Multicentre, open label, randomised trial. SETTING: 15 hospitals in China between December 2017 and December 2020. PARTICIPANTS: 412 patients with newly diagnosed type 2 diabetes and significant hyperglycaemia (HbA1c ≥8.5%). INTERVENTIONS: All randomised participants initially received SIIT for 2-3 weeks, followed by linagliptin 5 mg/day, metformin 1000 mg/day, combination linagliptin plus metformin, or lifestyle modification alone (control) for 48 weeks. MAIN OUTCOME MEASURES: The primary outcome was the percentage of participants achieving HbA1c <7.0% at week 48 after SIIT. Secondary outcomes included glycaemic control, ß cell function, and variations in insulin sensitivity. RESULTS: 412 participants were randomised. At baseline, the mean age was 46.8 (standard deviation 11.2) years, mean body mass index was 25.8 (2.9), and mean HbA1c was 11.0% (1.9%). At week 48, 80% (78/97), 72% (63/88), and 73% (69/95) of patients in the linagliptin plus metformin, linagliptin, and metformin groups, respectively, achieved HbA1c <7.0%, compared with 60% (56/93) in the control group (P=0.02 overall; P=0.003 for linagliptin plus metformin versus control; P=0.12 for linagliptin versus control; P=0.09 for metformin versus control). Additionally, 70% (68/97), 68% (60/88), and 68% (65/95) of patients in the linagliptin plus metformin, linagliptin, and metformin group, respectively, achieved HbA1c <6.5% compared with 48% (45/93) in the control group (P=0.005 overall; P=0.005 for linagliptin plus metformin versus control; P=0.01 for linagliptin versus control; P=0.008 for metformin versus control; all were significant after adjustment for multiple comparisons). Thus, compared with the control group, participants in the linagliptin plus metformin group were more likely to achieve HbA1c <7.0% at week 48 (odds ratio 2.78, 95% confidence interval 1.37 to 5.65; P=0.005). Moreover, the linagliptin plus metformin group showed the most significant improvement in fasting plasma glucose and ß cell function indices. All treatments were well tolerated. CONCLUSIONS: The intense simplified strategy using subsequent oral therapies post-SIIT, especially the linagliptin plus metformin combination, sustainably improved glycaemic control and ß cell function in patients with newly diagnosed type 2 diabetes mellitus and severe hyperglycaemia. This approach offers a promising direction for decision making in the clinical management of type 2 diabetes mellitus. TRIAL REGISTRATION: ClinicalTrials.gov NCT03194945.

Effect and Safety of Herbal Medicine Foot Baths in Patients with Diabetic Peripheral Neuropathy: A Multicenter Double-Blind Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect and safety of foot baths with Tangbi Waixi Decoction (TW) in treating patients with diabetic peripheral neuropathy (DPN). METHODS: It is a multicenter double-blinded randomized controlled trial. Participants with DPN were recruited between November 18, 2016 and May 30, 2018 from 8 hospitals in China. All patients received basic treatments for glycemic management. Patients received foot baths with TW herbal granules either 66.9 g (intervention group) or 6.69 g (control group) for 30 min once a day for 2 weeks and followed by a 2-week rest, as a therapeutic course. If the Toronto Clinical Scoring System total score (TCSS-TS) ⩾6 points, the patients received a total of 3 therapeutic courses (for 12 weeks) and were followed up for 12 weeks. The primary outcome was change in TCSS-TS score at 12 and 24 weeks. Secondary outcomes included changes in bilateral motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of the median and common peroneal nerve. Safety was also assessed. RESULTS: Totally 632 patients were enrolled, and 317 and 315 were randomized to the intervention and control groups, respectively. After the 12-week intervention, patients in both groups showed significant declines in TCSSTS scores, and significant increases in MNCV and SNCV of the median and common peroneal nerves compared with pre-treatment (P<0.05). The reduction of TCSS-TS score at 12 weeks and the increase of SNCV of median nerve at 24 weeks in the control group were greater than those in the intervention group (P<0.05). The number of adverse events did not differ significantly between groups (P>0.05), and no serious adverse event was related with treatment. CONCLUSION: Treatment of TW foot baths was safe and significantly benefitted patients with DPN. A low dose of TW appeared to be more effective than a high dose. (Registry No. ChiCTR-IOR-16009331).

Short-Term Effect of Continuous Subcutaneous Insulin Infusion and Multiple Daily Injection in Perioperative Patients with Type 2 Diabetes Mellitus.

Background: Hyperglycemia is common and difficult to control in perioperative patients with type 2 diabetes mellitus (T2DM), which impacts their prognosis after operation. Our study investigated the short-term effect of continuous subcutaneous insulin infusion (CSII) and multiple daily injection (MDI) in perioperative T2DM patients using the data envelopment analysis (DEA). Methods: T2DM patients (n = 639) who underwent surgeries in Guangdong Provincial Hospital of Traditional Chinese Medicine (2009.01-2017.12) were included. Insulin was provided to each patient during the study and separated into a CSII group (n = 369) and an MDI group (n = 270). DEA was performed to compare the therapeutic indexes and investigate the short-term effect of the CSII group and MDI group. Results: Scale efficiencies of the CSII group with CCR model and BCC model were better than that of the MDI group. Regarding slack variables, with higher surgical levels, the CSII group was closer to the ideal state than the MDI group, which indicated in improving the average fasting blood glucose (AFBG), antibiotic use days (AUD), preoperative blood glucose control time (PBGCT), first postoperative day fasting blood glucose (FPDFBG), and postoperative hospitalization days (PHD). Conclusion: CSII could effectively control blood glucose levels and shorten perioperative hospitalizing time for T2DM patients, indicating that CSII was beneficial in perioperative period and should be promoted clinically.

Efficacy of flavonoids-containing supplements on insulin resistance and associated metabolic risk factors in overweight and obese subjects: a systematic review and meta-analysis of 25 randomized controlled trials.

Background: Obesity is becoming a global epidemic. Flavonoids, with anti-inflammatory and antioxidative functions, are proposed to treat insulin resistance (IR) in obese subjects. We aimed to evaluate the effectiveness and safety of flavonoids-containing supplements on IR and associated metabolic risk factors in overweight and obese participants. Methods: Randomized controlled trials (RCTs) involving flavonoids-containing supplements used to treat overweight and obese subjects with results of IR, other associated metabolic risk factors, and adverse effects published were retrieved from 5 electronic databases from the year of inception to January 2, 2022. Results: Twenty-five RCTs (n = 1950) were included. Pooled results demonstrated that HOMA-IR in the group receiving flavonoids-containing supplements significantly decreased versus the control group (WMD = -0.132, 95% CI: -0.236 to -0.027, p = 0.013). Subgroup analyses showed that HOMA-IR in the subgroup receiving flavonoid-containing mixtures significantly decreased (WMD = -0.25, 95% CI: -0.43 to -0.06, p = 0.008), whereas such result was not found in the singly-used flavonoids subgroup (WMD = -0.08, 95% CI: -0.20 to 0.05, p = 0.240). In addition, QUICKI in the experimental group had an increasing trend compared to that in the control group (WMD = 0.01, 95% CI: -0.00 to 0.02, p = 0.065). For secondary outcomes, FBG, FBI, TC, TG, SBP, weight, BMI, and WHR in the group receiving flavonoids-containing supplements dropped significantly compared to those in the controls (WMD = -0.05, 95% CI: -0.08 to -0.02, p = 0.002; WMD = -0.58, 95% CI: -1.04 to -0.12, p = 0.014; WMD = -0.04, 95% CI: -0.06 to -0.03, p < 0.001; WMD = -0.04, 95% CI: -0.05 to -0.03, p < 0.001; WMD = -2.01, 95% CI: -3.17 to -0.86, p = 0.001; WMD = -0.29, 95% CI: -0.49 to -0.09, p = 0.004; WMD = -0.10 95% CI: -0.17 to -0.04, p = 0.003; WMD = -0.10, 95% CI: -0.01 to -0.00, p = 0.015; respectively). Adverse reactions did not differ between the group receiving flavonoids-containing supplements and the control group (RR = 0.97, 95% CI: 0.62 to 1.52, p = 0.905). Conclusion: This study showed that flavonoids-containing supplements may be efficacious and safe in improving IR and associated metabolic risk factors in overweight and obese participants. Nevertheless, doubt over the findings remains because limited RCTs per type of flavonoids-containing supplement were investigated, and many of the RCTs had a small sample size. Therefore, the findings must be validated in future research. Systematic Review Registration: https://inplasy.com/inplasy-2022-2-0011/, identifier INPLASY202220011.

Flavonoid-containing supplements for preventing acute respiratory tract infections: A systematic review and meta-analysis of 20 randomized controlled trials.

BACKGROUND: This systematic review and meta-analysis was conducted to investigate the efficacy and safety of flavonoid-containing supplements in preventing acute respiratory tract infection (ARTI). METHODS: Randomized controlled trials (RCTs) investigating the effects of flavonoid-containing supplements on ARTI prevention in the aspects of ARTI incidence, mean ARTI sick days, symptoms, bio-immune markers, and adverse effects were searched in 5 databases. Data were searched from inception to November 26, 2021. Stata 16.0 was used to perform the meta-analysis. RESULTS: Twenty RCTs (n = 4521) were included in this systematic review and meta-analysis. Pooled results showed that in the flavonoid-containing supplement group, the ARTI incidence and mean ARTI sick days were significantly decreased compared to those in the control group (RR = 0.81, 95% CI: 0.74-0.89, p < 0.001; WMD = -0.56, 95% CI: -1.04 to -0.08, p = 0.021; respectively). In 8 RCTs, flavonoids were singly used for interventions, ARTI incidence in the experimental group significantly decreased compared to that in the control group (RR = 0.85, 95% CI: 0.72-1.00, p = 0.047). In ten RCTs, flavonoid-containing mixtures were applied for interventions, and ARTI incidence in the experimental group significantly decreased compared to that in the control group (RR = 0.79, 95% CI: 0.71-0.89, p < 0.001). Furthermore, the ARTI incidence and mean ARTI sick days were significantly decreased in the experimental group compared to those in the control group in the flavan-3-ols subgroup (RR = 0.79, 95% CI: 0.67-0.92, p = 0.002; WMD = -2.75, 95% CI: -4.30 to -1.21, p < 0.001; respectively) and the multiple subclasses subgroup (RR = 0.75, 95% CI: 0.63-0.88, p = 0.001; WMD = -0.56, 95% CI: -1.11 to -0.01, p = 0.046; respectively). However, the bio-immune markers including interleukin-6, hypersensitive-c-reactive-protein, tumor necrosis factor-α, and interferon-γ did not differ between the flavonoid group and the control group. Moreover, in the flavonoid-containing supplement group, the incidence of adverse reactions did not increase compared to that in the control group (RR = 1.16, 95% CI: 0.78-1.73, p = 0.469). CONCLUSIONS: This systematic review and meta-analysis showed that flavonoid-containing supplements were efficacious and safe in preventing ARTIs. The most important limitations result from the small number of trials, poor quality of some included RCTs, differences in the composition and types of interventions, principal subclasses of flavonoids, methods of administration, and methodology. Moreover, only a few RCTs conducted independent verification of the flavonoid supplements used in the trial in terms of purity and potency, which may lead to a potential source of bias. Thus, larger and better-designed studies are needed to further verify this conclusion.

Flavonoids for Treating Viral Acute Respiratory Tract Infections: A Systematic Review and Meta-Analysis of 30 Randomized Controlled Trials.

BACKGROUND: This meta-analysis aimed to investigate the efficacy and safety of flavonoids in treating viral acute respiratory tract infections (ARTIs). METHODS: Randomized controlled trials (RCTs) were entered into meta-analyses performed separately for each indication. Efficacy analyses were based on changes in disease-specific symptom scores. Safety was analyzed based on the pooled data from all eligible trials, by comparing the incidence of adverse events between flavonoids and the control. RESULTS: In this study, thirty RCTs (n = 5,166) were included. In common cold, results showed that the flavonoids group decreased total cold intensity score (CIS), the sum of sum of symptom intensity differences (SSID) of CIS, and duration of inability to work vs. the control group. In influenza, the flavonoids group improved the visual analog scores for symptoms. In COVID-19, the flavonoids group decreased the time taken for alleviation of symptoms, time taken for SARS-CoV-2 RT-PCR clearance, the RT-PCR positive subjects at day 7, time to achievement of the normal status of symptoms, patients needed oxygen, patients hospitalized and requiring mechanical ventilation, patients in ICU, days of hospitalization, and mortality vs. the control group. In acute non-streptococcal tonsillopharyngitis, the flavonoids group decreased the tonsillitis severity score (TSS) on day 7. In acute rhinosinusitis, the flavonoids group decreased the sinusitis severity score (SSS) on day 7, days off work, and duration of illness. In acute bronchitis, the flavonoids group decreased the bronchitis severity score (BSS) on day 7, days off work, and duration of illness. In bronchial pneumonia, the flavonoids group decreased the time to symptoms disappearance, the level of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α). In upper respiratory tract infections, the flavonoids group decreased total CIS on day 7 and increased the improvement rate of symptoms. Furthermore, the results of the incidence of adverse reactions did not differ between the flavonoids and the control group. CONCLUSION: Results from this systematic review and meta-analysis suggested that flavonoids were efficacious and safe in treating viral ARTIs including the common cold, influenza, COVID-19, acute non-streptococcal tonsillopharyngitis, acute rhinosinusitis, acute bronchitis, bronchial pneumonia, and upper respiratory tract infections. However, uncertainty remains because there were few RCTs per type of ARTI and many of the RCTs were small and of low quality with a substantial risk of bias. Given the limitations, we suggest that the conclusions need to be confirmed on a larger scale with more detailed instructions in future studies.Systematic Review Registration: inplasy.com/inplasy-2021-8-0107/, identifier: INPLASY20218010.

Flavonoids for viral acute respiratory tract infections: protocol for a systematic review and meta-analysis of randomised controlled trials.

INTRODUCTION: Herbal and 'natural' products are a growing industry in today's society because they reportedly help with numerous diseases and ailments. To date, there are some randomised controlled trials (RCTs) conducted on patients concerning the efficacy of flavonoids against viral acute respiratory tract infection (ARTI) showing inconsistent results. On this basis, we will summarise the available evidence to investigate the efficacy of flavonoids on viral ARTI by conducting a systematic review and meta-analysis. METHODS AND ANALYSIS: This protocol has been registered. The systematic review and meta-analysis will be conducted by Cochrane guidelines and reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. RCTs comparing the flavonoids group with the control group for treating virus-induced ARTI will be included. RCTs published with relative outcomes will be searched through 12 databases. Data were searched from inception to 25 March 2022. Relevant literature search, data extraction and quality assessment will be performed by pairs of reviewers independently, and the third researcher will be involved in a discussion for disagreements. Stata V.16.0 software will be used for statistical analysis. Dichotomous data will use the ORs with 95% CIs. Continuous data will use the weighted mean difference with 95% CIs. Heterogeneity will be tested by χ2-based Cochran Q statistic and I2 statistic. Sensitivity analyses and subgroup analyses will be used to observe the heterogeneity between included studies. The funnel plot, Egger's test and Begg's test will be used to judge the publication bias. A p<0.05 will be considered to indicate a statistically significant result. TRAIL REGISTRATION NUMBER: INPLASY202180107.

Benefits of herbal formulae containing Poria cocos (Fuling) for type 2 diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND: Poria cocos (Schw.) Wolf or Fuling is one of the top 10 most frequently prescribed herbs in China for the treatment of type 2 diabetes mellitus (T2DM). OBJECTIVE: The purpose of this systematic review is to determine the additional benefit of Fuling formulae use in addition to hypoglycaemic agents for T2DM in randomised clinical trials. METHODS: English (5) and Chinese (4) medical databases were searched from their inception to August 2021. RCTs that included Fuling in herbal formulae for T2DM were included. Risk of bias were assessed using the Cochrane Collaboration's procedures. Stata software (13.0) was used for data analysis. RESULTS: Seventy-three RCTs (6,489 participants) with herbal formulae containing Fuling were included. Most studies were at risk of bias and strength of the evidence were low to moderate. Meta-analysis findings showed that the addition of formulae containing Fuling to hypoglycaemic agent-treatments could benefit people with T2DM by reducing fasting blood glucose (MD -0.82 [-0.93, -0.71]; I2 = 79.6%, P = 0.00), 2-hour postprandial blood glucose (MD-1.15 [-1.31, -0.98], I2 = 80%, P = 0.00) and haemoglobin A1c (MD-0.64 [-0.75, -0.53], I2 = 84.7%, P = 0.00). Adverse events were also significantly lower in the integrative group than in the hypoglycaemic alone group (RR 0.99 [0.93, 1.06], P = 0.87). CONCLUSION: Evidence from this study supports the use of Fuling formulae combined with hypoglycaemic agents for T2DM. The combined therapies appear to be well tolerated. TRAIL REGISTRATION: This review is registered with the PROSPERO international prospective register of systematic reviews (CRD42020214635).

Xiaoketongbi Formula vs pregabalin for painful diabetic neuropathy: A single-center, randomized, single-blind, double-dummy, and parallel controlled clinical trial.

BACKGROUND: We assessed the efficacy and safety of the Xiaoketongbi Formula (XF) vs. pregabalin in patients with painful diabetic neuropathy (PDN). METHODS: Patients with PDN (n = 68) were included in a single-center, randomized, single-blind, double-dummy, parallel controlled clinical trial. The primary outcome was the change in the Brief Pain Inventory for Diabetic Peripheral Neuropathy (BPI-DPN). Secondary outcomes evaluated included the reduction of BPI-DPN >50%, changes in the numeric rating scale-11 (NRS-11) score for pain, Daily Sleep Interference Diary (DSID), Patient Global Impression of Change (PGIC), nerve conduction velocity (NCV), and adverse events. RESULTS: After 10 weeks of treatment, the BPI-DPN score reduced from 42.44 ± 17.56 to 26.47 ± 22.22 and from 52.03 ± 14.30 to 37.85 ± 17.23 in the XF and pregabalin group (Ps < 0.001), respectively. The difference in the absolute change in BPI-DPN score between both groups was -1.79 (95% CI: -9.09, 5.50; p = 0.625). In the XF and pregabalin groups, 44.1% (15/34) and 20.6% (7/34) of patients reported a BPI-DPN reduction >50% (p = 0.038), respectively. There were no significant differences between groups in NRS-11 and DSID (Ps > 0.05). A significantly greater number of patients in the XF group felt "significantly improved" or "improved" than in the pregabalin group (35.3% (12/34) vs. 11.8% (4/34), p = 0.045). The absolute change in motor nerve conduction velocity of the right median nerve was significantly different between both groups (XF group 0.7 ± 2.3 vs. pregabalin group -2.2 ± 4.1, p = 0.004). No serious adverse events were reported in either group. CONCLUSIONS: XF is equivalent to pregabalin in reducing pain symptoms and improves the quality of life in patients with PDN. In addition, XF has the potential to improve nerve function by increasing NCV.

Angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers on insulin sensitivity in hypertensive patients: A meta-analysis of randomized controlled trials.

INTRODUCTION: This meta-analysis aimed to summarize the available evidence to compare angiotensin-converting enzyme (ACE) inhibitors with angiotensin II receptor blockers (ARBs) on improving insulin sensitivity in hypertensive patients. METHODS: Randomized controlled trials (RCTs) comparing ACE inhibitors versus ARBs published with outcomes on homeostasis model assessment of IR (HOMA-IR), glucose infusion rate (GIR), the quantitative insulin sensitivity check index (QUICKI), insulin sensitivity index (ISI) composite, fasting plasma glucose (FPG), fasting plasma insulin (FPI), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were searched through 5 databases. Data were searched from their inception to July 5, 2020. Stata 14.0 was used to perform the meta-analysis. RESULTS: Eleven RCTs (n = 1015) were included in this meta-analysis. Pooled analysis of studies showed no significant difference in HOMA-IR between ARBs and ACE inhibitors (WMD = -0.09, 95% CI: -0.69 to 0.50, P = 0.755); however, subgroup analysis of therapeutic duration showed a significant difference in HOMA-IR between ARBs and ACE inhibitors among the long-term intervention subgroup (>12 weeks) (WMD = 0.41, 95% CI: 0.06 to 0.76, P = 0.022) and hypertensive patients with diabetes mellitus subgroup (WMD = 0.55, 95% CI: 0.49 to 0.61, P < 0.001); results showed no significant difference between ARBs and ACE inhibitors on QUICKI score (WMD = -0.00, 95% CI: -0.03 to 0.03, P = 0.953) in hypertensive patients; however, the efficacy of ACE inhibitors on improving GIR and ISI composite was significantly better than that of ARBs (WMD = -1.09, 95% CI: -1.34 to -0.85, P < 0.001; WMD = -0.80, 95% CI: -1.24 to -0.36, P < 0.001, respectively). Furthermore, no significant differences were noted on FPG (WMD = 0.72, 95% CI: -1.39 to 2.83, P = 0.505), FPI (WMD = -0.48, 95% CI: -1.60 to 0.64, P = 0.398), SBP (WMD = -0.65, 95% CI: -1.76 to 0.46, P = 0.254), and DBP (WMD = -0.30, 95% CI: -1.70 to 1.10, P = 0.675) between ARBs and ACE inhibitors. CONCLUSION: Results from this meta-analysis showed that ACE inhibitors resulted in more effective improvement of HOMA-IR compared with ARBs among the long-term intervention and hypertensive patients with DM subgroup; furthermore, the efficacy of ACE inhibitors on improving GIR and ISI composite was significantly better than that of ARBs in hypertensive patients. However, ARBs had no significant difference in QUICKI score, FPG, FPI, SBP, and DBP compared with ACE inhibitors. Larger and better-designed studies are needed to further verify this conclusion.

Effects of acupoint therapy on nonalcoholic fatty liver disease: A systematic review and meta-analysis.

BACKGROUND: and purpose: Acupoint therapy is suggested as a potential intervention for treating nonalcoholic fatty liver disease (NAFLD). This review assessed current evidence for the effect of acupoint therapy on NAFLD. METHODS: Eight electronic databases were searched to identify randomized controlled trials (RCTs) of patients with NAFLD treated by acupoint therapy from their inception to August 2020. A meta-analysis of outcomes was conducted by RevMan 5.3. RESULTS: Sixteen RCTs with 1320 patients were included. Acupoint therapy was significantly associated with improvements in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Additionally, acupoint therapy significantly reduced triglyceride (TG), total cholesterol (TC) and low-density lipoprotein (LDL) levels. High-density lipoprotein (HDL) levels were also increased in NAFLD patients. CONCLUSION: Compared with other treatments, acupoint therapy may improve liver function and lipid metabolism, making it an available treatment for NAFLD. However, these findings need to be confirmed in large-scale, rigorously designed RCTs.

Single-cell analysis of the human pancreas in type 2 diabetes using multi-spectral imaging mass cytometry.

Type 2 diabetes mellitus (T2D) is a chronic age-related disorder characterized by hyperglycemia due to the failure of pancreatic beta cells to compensate for increased insulin demand. Despite decades of research, the pathogenic mechanisms underlying T2D remain poorly defined. Here, we use imaging mass cytometry (IMC) with a panel of 34 antibodies to simultaneously quantify markers of pancreatic exocrine, islet, and immune cells and stromal components. We analyze over 2 million cells from 16 pancreata obtained from donors with T2D and 13 pancreata from age-similar non-diabetic controls. In the T2D pancreata, we observe significant alterations in islet architecture, endocrine cell composition, and immune cell constituents. Thus, both HLA-DR-positive CD8 T cells and macrophages are enriched intra-islet in the T2D pancreas. These efforts demonstrate the utility of IMC for investigating complex events at the cellular level in order to provide insights into the pathophysiology of T2D.

Efficacy of Integrated Traditional Chinese and Western Medicine for Treating COVID-19: A Systematic Review and Meta-Analysis of RCTs.

Background: Integrated Chinese and Western medicine (integrated medicine) is routinely used in the treatment of coronavirus disease 2019 (COVID-19) in China. In this study, we undertook a systematic review and meta-analysis of published randomized controlled trials (RCTs) to evaluate the efficacy of integrated medicine therapy for patients with COVID-19. Methods: In this meta-analysis, we searched PubMed, Embase, Web of Science, SinoMed, China National Knowledge Infrastructure (CNKI), Chongqing VIP (CQVIP), and Wanfang databases from inception to April 12, 2021, to identify RCTs of integrated medicine in the treatment of COVID-19. The quality of RCTs was assessed by the Cochrane risk of bias tool. RevMan v5.3 and Stata software packages were used for statistical analysis. Results: Nineteen RCTs involving 1,853 patients met our inclusion criteria. Compared with patients treated by conventional Western medicine (CWM), patients treated by integrated medicine have a higher overall effective rate [RR = 1.17, 95% CI: (1.10, 1.26), p < 0.00001], fever disappearance rate [RR = 1.25, 95% CI: (1.04, 1.50), p = 0.02], fatigue disappearance rate [RR = 1.28, 95% CI: (1.00, 1.63), p = 0.05], and chest CT improvement rate [RR = 1.24, 95% CI: (1.14, 1.34), p < 00001]. Beneficial effects of the integrated medicine therapy were also seen in C-reactive protein (CRP) level [WMD = -4.14, 95% CI: (-6.38, -1.91), p = 0.0003] and white blood cell (WBC) count [WMD = 0.35, 95% CI: (0.11, 0.58), p = 0.004]. Subgroup analyses showed that, when the treatment time is <2 weeks, the effect of integrated medicine treatment is more obvious in improving the overall effective rate, clinical symptoms (fever, fatigue, and cough), the CRP level, and WBC count compared with that of the CWM treatment. For patients with severe and non-severe COVID-19, integrated medicine is more effective in improving fever and cough symptoms and WBC count than using CWM alone. Conclusion: The results of the current meta-analysis suggested that the integrated medicine can improve the clinical symptoms, chest CT and infection indicators of COVID-19 patients. Even if the treatment time is <2 weeks, the effect of integrated medicine in improving symptoms is more obvious compared with the treatment of CWM. However, the results should be interpreted cautiously due to the heterogeneity among the studies.

Molecular Mechanism of the Effect of Huanglian Jiedu Decoction on Type 2 Diabetes Mellitus Based on Network Pharmacology and Molecular Docking.

BACKGROUND: Huanglian Jiedu Decoction (HLJDD) is a Traditional Chinese Medicine (TCM) formula comprising four herbal medicines. This decoction has long been used in China for clinically treating T2DM. However, the molecular mechanism of HLJDD treat for T2DM is still not fully known. Hence, this study was designed to reveal the synergistic mechanism of HLJDD formula in the treatment of T2DM by using network pharmacology method and molecular docking. METHODS: Retrieving and screening of active components of different herbs in HLJDD and corresponding T2DM-related target genes across multiple databases. Subsequently, STRING and Cytoscape were applied to analysis and construct PPI network. In addition, cluster and topological analysis were employed for the analysis of PPI networks. Then, the GO and KEGG enrichment analysis were performed by using ClueGO tool. Finally, the differentially expressed analysis was used to verify whether the expression of key target genes in T2DM and non-T2DM samples was statistically significant, and the binding capacity between active components and key targets was validated by molecular docking using AutoDock. RESULTS: There are 65 active components involved in 197 T2DM-related targets that are identified in HLJDD formula. What is more, 39 key targets (AKT1, IL-6, FOS, VEGFA, CASP3, etc.) and 3 clusters were obtained after topological and cluster analysis. Further, GO and KEGG analysis showed that HLJDD may play an important role in treating T2DM and its complications by synergistically regulating many biological processes and pathways which participated in signaling transduction, inflammatory response, apoptotic process, and vascular processes. Differentially expressed analysis showed that AKT1, IL-6, and FOS were upregulated in T2DM samples and a significant between sample differential expression. These results were validated by molecular docking, which identified 5 high-affinity active components in HLJDD, including quercetin, wogonin, baicalein, kaempferol, and oroxylin A. CONCLUSION: Our research firstly revealed the basic pharmacological effects and relevant mechanisms of the HLJDD in the treatment of T2DM and its complications. The prediction results might facilitate the development of HLJDD or its active compounds as alternative therapy for T2DM. However, more pharmacological experiments should be performed for verification.

Additional Benefit of Chinese Medicine Formulae Including Dioscoreae rhizome (Shanyao) for Diabetes Mellitus: Current State of Evidence.

Background: Chinese medicine has been used to treat diabetes symptoms for thousands of years. Dioscoreae rhizome or Shanyao is a Chinese medicinal herb that is routinely used in the treatment of diabetes mellitus (DM). Objective: The purpose of this study is to evaluate the evidence of the added benefits and safety of herbal formulae containing Shanyao in clinical studies and the possible mechanisms of Shanyao in the prevention and treatment of DM in experimental studies. Methods: We searched nine databases for randomized controlled trials (RCTs) that included Shanyao in the formulae in the treatment of type 2 DM. Furthermore, experimental studies on the prevention and treatment of DM by Shanyao in English- and Chinese-language databases were identified. Results: Fifty-three moderate quality RCTs with herbal formulae containing Shanyao were identified. Results from meta-analysis indicated that Shanyao alone or formulae containing Shanyao in addition to conventional treatments could benefit people with type 2 DM in lowering blood glucose, blood lipids and reducing insulin resistance. Moreover, adverse events were significantly lower in the CHM plus conventional group than those in the conventional group. Shanyao may exert the benefit through various mechanisms including inhibition of α-glucosidase and DPP-IV activity, increase of endogenous GLP-1 and immune regulating activities. Conclusion: Evidence from this review suggested that there appeared to be added clinical benefits associated with the use of Shanyao for DM, whether as a food supplement or as a CHM combined with hypoglycemic agents with a good safety profile.