Characteristics of metabolic inflammatory syndrome among inpatients with type 2 diabetes: A cross-sectional study in China.

BACKGROUND: As meta-inflammation is a common feature for obesity, type 2 diabetes (T2D), nonalcoholic fatty liver disease and atherosclerosis, we have proposed a new concept, metabolic inflammatory syndrome (MIS), to cluster such diseases. We aimed to characterize MIS and explore its association with coronary heart disease (CHD) among T2D inpatients in China. METHODS: A total number of 8344 T2D participants were enrolled. Each component of MIS and metabolic syndrome (MS) was analyzed. Their association with the risk of CHD was assessed using a binary logistic analysis. RESULTS: Among the T2D inpatients, the detection rate of MIS was much higher than that of MS (93.6 % vs. 53.2 %). Among all the components of MIS and MS, carotid atherosclerosis (71.9 %) was most commonly detected, which increased with aging in subgroups. Surprisingly, the most common combination of MIS was with all 4 components in T2D patients, with a constituent ratio of 30.9 %. According to the odds ratios (ORs), MIS was a better predictor of CHD than MS, especially after adjustment for age, sex, smoking, and alcohol consumption (adjusted OR for MIS: 3.083; for MS: 1.515). The presence of more components of MIS was associated with a higher detection rate of CHD (P < 0.001). Among all the components of MIS and MS, carotid atherosclerosis best predicted the risk of CHD (adjusted OR: 1.787). CONCLUSIONS: MIS is an independent risk factor for CHD, with a bigger OR value than MS. Carotid atherosclerosis, with the highest detection rate, was the best individual predictor of CHD and thus a critical component of MIS. The concept of MIS represents the understanding of metabolic diseases from the perspective of holistic integrative medicine.

Therapeutic Effects of Huazhuojiedu Decoction on Precancerous Lesions of Gastric Cancer by Regulating Mitophagy.

This research aims to explore the therapeutic effect and potential mechanisms of Huazhuojiedu decoction (HZJD) for alleviating precancerous lesions of gastric cancer (PLGC) both in vivo and in vitro. HZJD is a traditional Chinese herbal formula consisting of 11 herbs. Sprague-Dawley (SD) rats were randomly divided into four subgroups: control group, model group, positive drug group, and HZJD group. Hematoxylin-eosin (H&E) staining, high iron diamine-alcian blue (HID-AB) staining, alcian blue-periodic acid Schiff (AB-PAS) staining, immunohistochemistry, immunofluorescence, RT-qPCR, and Western blot assays were performed after 10 weeks of HZJD treatment. In vitro, the cell counting kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to detect cell proliferation. RT-qPCR and Western blot assays were performed to evaluate mitophagy levels. The results indicated that HZJD could retard the pathological progression in PLGC rats and reduce PLGC cell proliferation. Treatment with HZJD significantly increased the mRNA and protein expression levels of Sirt3, Foxo3a, Parkin, and LC3 II/I, while decreasing the mRNA and protein expression levels of p62 and Tomm20. HZJD was found to have the ability to reverse the decline in mitophagy activity both in vivo and in vitro. In conclusion, the study assessed the impact of HZJD and provided evidence regarding its potential molecular mechanism.

Renoprotective Effect of Isoorientin in Diabetic Nephropathy via Activating Autophagy and Inhibiting the PI3K-AKT-TSC2-mTOR Pathway.

Diabetic nephropathy (DN) is one of the most serious complications of diabetes and the most common cause of death. The autophagy of podocytes plays an important role in the pathogenesis of DN. Here, through screening the constituent compounds of practical and useful Chinese herbal formulas, we identified that isoorientin (ISO) strongly promoted the autophagy of podocytes and could effectively protect podocytes from high glucose (HG)-induced injury. ISO significantly improved autophagic clearance of damaged mitochondria under HG conditions. Through a proteomics-based approach, we identified that ISO could reverse the excessive phosphorylation of TSC2 S939 under HG conditions and stimulate autophagy through inhibition of the PI3K-AKT-TSC2-mTOR pathway. Furthermore, ISO was predicted to bind to the SH2 domain of PI3Kp85[Formula: see text], which is crucial for the recruitment and activation of PI3K. The protective effect of ISO and its effects on autophagy and particularly on mitophagy were further proved using a DN mice model. To summarize, our study identified the protective effects of ISO against DN and demonstrated that ISO was a strong activator of autophagy, which could provide a basis for drug development.

Circadian rhythm of plasminogen activator inhibitor-1 and cardiovascular complications in type 2 diabetes.

Cardiovascular complications are a common death cause in type 2 diabetes patients, as they are often combined. Plasminogen-activator Inhibitor 1 (PAI-1) participates in the development and progression of cardiovascular complications in diabetes. Insulin resistance increases PAI-1 production, and high PAI-1 levels lead to an environment conducive to thrombosis and earlier and more severe vascular disease. Current evidence also suggests that PAI-1 has a rhythmic profile of circadian fluctuations and acrophase in the morning within a single day, which might explain the high morning incidence of cardiovascular events. Thus, PAI-1 is a possible drug target. Although several PAI-1 inhibitors have been developed, none have yet been allowed for clinical use. Research on rhythm has also led to the concept of "chronotherapy", a rhythm-based drug regimen expected to improve the treatment of cardiovascular complications in diabetic patients. Herein, we searched several databases and reviewed relevant articles to describe the circadian rhythm characteristics and endogenous molecular mechanisms of PAI-1, its relationship with insulin resistance, the causes of cardiovascular complications caused by PAI-1, and the current development of PAI-1 inhibitors. We also summarized the possibility of using the circadian rhythm of PAI-1 to treat cardiovascular complications in diabetic patients.

Comparison of Bisphosphonates Versus Teriparatide in Therapy of the Glucocorticoid-Induced Osteoporosis (GIOP): A Meta-Analysis of Randomized Controlled Trials.

Osteoporosis (OP) is characterized as decreased bone mineral density (BMD) and increased risk of bone fracture. Secondary OP resulting from excess endogenous or exogenous glucocorticoid is defined as glucocorticoid-induced osteoporosis (GIOP). Current therapeutic strategies for GIOP are similar to menopausal osteoporosis, including calcium and vitamin D supplementation, bisphosphonates, and parathyroid hormone (PTH) analogues (teriparatide). Previously, several published meta-analyses compared anti-osteoporotic agents for the menopausal or aging-dependent OP. However, the physiopathologic bone metabolism of GIOP is different. In this study, we investigated the efficacy of BMD enhancement, bone fracture rate and safety of bisphosphonates versus teriparatide in the therapy of GIOP. We searched databases including PubMed, Embase, and the Cochrane Library until Jan 2023, and selected ten random clinical trials (RCT)s that compared the efficacy and/or safety of bisphosphonate versus teriparatide for GIOP patients. Teriparatide therapy increased lumber spinal BMD by 3.96% (95% CI 3.01-4.9%, p<0.00001), 1.23% (95% CI 0.36-2.1%, p=0.006) at total hip, and 1.45% (95% CI 0.31-2.58%, p=0.01) at femoral neck, respectively, compared to bisphosphonates at 18-month therapy for GIOP. Teriparatide also reduced bone fracture especially in vertebral bone (p=0.0001, RR 6.27, 95% CI 2.44-16.07), and increased bone formation and resorption marker levels. There was no difference in the incidence of adverse effects in bisphosphonate and teriparatide groups. Teriparatide showed better performance over bisphosphonate in BMD enhancement, bone fracture reduction, and bone remodeling improvement, without increasing the incidence of adverse effects.

Mechanisms of Chinese Medicine in Gastroesophageal Reflux Disease Treatment: Data Mining and Systematic Pharmacology Study.

OBJECTIVE: To identify specific Chinese medicines (CMs) that may benefit patients with gastroesophageal reflux disease (GERD), and explore the action mechanism. METHODS: Domestic and foreign literature on the treatment of GERD with CMs was searched and selected from China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and PubMed from October 1, 2011 to October 1, 2021. Data from all eligible articles were extracted to establish the database of CMs for GERD. Apriori algorithm of data mining techniques was used to analyze the rules of herbs selection and core Chinese medicine formulas were identified. A system pharmacology approach was used to explore the action mechanism of these medicines. RESULTS: A total of 278 prescriptions for GERD were analyzed, including 192 CMs. Results of Apriori algorithm indicated that Evodiae Fructus and Coptidis Rhizoma were the highest confidence combination. A total of 32 active ingredients and 66 targets were screened for the treatment of GERD. Enrichment analysis showed that the mechanisms of action mainly involved pathways in cancer, fluid shear stress and atherosclerosis, advanced glycation end product (AGE), the receptor for AGE signaling pathway in diabetic complications, bladder cancer, and rheumatoid arthritis. CONCLUSION: Evodiae Fructus and Coptidis Rhizoma are the core drugs in the treatment of GERD and the potential mechanism of action of these medicines includes potential target and pathways.

16S rRNA sequencing-based evaluation of the protective effects of Hua-Zhuo-Jie-Du on rats with chronic atrophic gastritis.

BACKGROUND: Disturbance of the intestinal flora is a pathogenic factor for chronic atrophic gastritis (CAG). Hua-Zhuo-Jie-Du (HZJD) has been shown to be an effective Chinese herbal preparation for treating CAG. However, the effects of HZJD on the intestinal flora of CAG is unclear. In this study, we probed the regulating effects of HZJD on intestinal microbes in CAG rats using 16S rRNA gene sequencing. METHODS: High-performance liquid chromatography (HPLC) analysis was used to perform quality control of HZJD preparations. We then administered 1-methyl-3-nitro-1-nitrosoguanidine (200 µg/ml) to Sprague-Dawley rats to establish a CAG model. HZJD and vitacoenzyme were administered orally to these rats over a 10 week period. Hematoxylin and eosin (H&E) staining was performed to observe the histopathology of CAG rats. A rarefaction curve, species accumulation curve, Chao1 index, and ACE index were calculated to assess the alpha diversity. Principal component analysis (PCA), non-metric multi-dimensional scaling (NMDS), and unweighted pair group method with arithmetic mean (UPGMA) were conducted to examine the beta diversity. The LEfSe method was used to identify differential bacteria. Differential function analysis used PCA based on KEGG function prediction. RESULTS: HPLC showed that our HZJD preparation method was feasible. H&E staining showed that HZJD significantly improved the pathological state of the gastric mucosa in CAG rats. The rarefaction curve and species accumulation curve showed that the sequencing data were reasonable. The Chao1 and ACE indices were significantly increased in CAG rats compared to the N group. Following HZJD and vitacoenzyme treatment, the Chao1 and ACE indices were decreased. PCA, NMDS, and UPGMA results showed that the M group was separated from the N, HZJD, and V groups, and LEfSe results showed that the relative abundance of Akkermansia, Oscillospira, Prevotella, and CF231 were significantly higher in the N group. Proteobacteria and Escherichia were significantly enriched in the M group, Allobaculum, Bacteroides, Jeotgalicoccus, Corynebacterium, and Sporosarcina were significantly enriched in the V group, and Firmicutes, Lactobacillus, and Turicibacter were significantly enriched in the HZJD group. CONCLUSION: HZJD exhibited a therapeutic effect on the intestinal flora of CAG rats.

The therapeutic effect of Huazhuojiedu decoction on precancerous lesions in a gastric cancer model via the regulation of lnc 517368.

ETHNOPHARMACOLOGICAL RELEVANCE: Huazhuojiedu decoction, a Chinese herbal preparation, has been proven to be clinically effective in treating precancerous lesions in gastric cancer (PLGC). This formula is optimized from a classic formula called "Ganluxiaodu Dan." Although some experiments have shown that Huazhuojiedu decoction is effective against PLGC, the mechanism remains unclear. AIM OF THE STUDY: To investigate the treatment of PLGC with Huazhuojiedu decoction from the perspective of lncRNA in vitro and in vivo. MATERIALS AND METHODS: A PLGC rat model was prepared and randomly divided into a Huazhuojiedu decoction group (HG), a vitacoenzyme group (VG), a model group (MG), and a normal group (CG). Each group was given a corresponding concentration of medicine and distilled water for 10 weeks. The pathological changes in the gastric mucosa were observed by hematoxylin-eosin staining (HE). High-throughput sequencing was performed to detect the differentially expressed lncRNAs in the HG, MG, and CG. Quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR) was used to verify differentially expressed lncRNAs, and rat-human homology information was obtained from the University of California, Santa Cruz (UCSC) Genome Database. Human gastric mucosal epithelial cells (GES-1) were used to prepare precancerous lesions of gastric cancer cells (MC). A Huazhuojiedu decoction drug-containing serum was prepared to treat the MC cells. The effects of the Huazhuojiedu decoction and the lncRNA ENST00000517368 (lnc 517368) knockdown or overexpression on PLGC cell proliferation and apoptosis were evaluated in vitro using CCK-8, flow cytometry, and RT-qPCR. RESULTS: The HE results showed that gastric mucosal pathology was significantly improved in the HG. High-throughput sequencing results showed that compared with the CG, 91 lncRNAs upregulated in the MG were restored and downregulated in the HG (P < 0.05), and 115 lncRNAs downregulated in the MG were restored and upregulated in the HG (P < 0.05). The results of RT-qPCR were consistent with the sequencing results. The differentially expressed genomic rat lncRNA ENSRNOT00000079699 is homologous to human lnc 517368. In cell experiments, high expression of lnc 517368 promoted proliferation and reduced apoptosis in PLGC cells, while the Huazhuojiedu decoction reduced the expression of lnc 517368 and improved cell morphology. CONCLUSIONS: Huazhuojiedu decoction inhibited cell proliferation and promoted apoptosis in PLGC cells, and its effect may be partially dependent on the downregulation of lnc 517368.

Efficacy of Shaobei injection in the treatment of grade II-III hemorrhoids and the effect on fibulin protein expression: A study protocol of a randomized controlled trial.

BACKGROUND: Hemorrhoids are a common and seriously disruptive condition that seriously affects people's lives in terms of treatment. Injection therapy is an effective minimally invasive scheme for the treatment of grade II-III hemorrhoids, but its clinical application is limited by the adverse reactions caused by injection drugs. Some clinical studies have confirmed the efficacy and safety of Shaobei injection as a traditional Chinese medicine extract. However, there is no standard randomized controlled study to verify its efficacy and explore its potential mechanism. METHODS: This is a prospective, randomized, single blind, parallel controlled trial to study the efficacy of Shaobei injection in the treatment of grade II-III hemorrhoids and its effect on the expression of fibulin-3 and fibulin-5 in fibulin protein family. The patients will be randomly divided into a treatment group and control group. The treatment group will be treated with Shaobei injection, and the control group will be treated with rubber band ligation. The observation indexes include: visual analysis scale, postoperative hospital stay, total use of painkillers, fibulin-3 and fibulin-5, hemorrhoids recurrence, and adverse events. Finally, the data will be statistically analyzed by SPASS 18.0 software. DISCUSSION: This study will compare the efficacy of Shaobei injection with the rubber band ligation method in the treatment of grade II-III haemorrhoids and investigate its effect on the expression of fibulin-3 and fibulin-5 in the fibulin protein family. The results of this study will provide a basis for the clinical use of Paeoniflora injection as an alternative to traditional sclerosing agent in the treatment of grade II-III haemorrhoids.Trial registration: OSF Registration number:DOI 10.17605/OSF.IO/MKVDB.

Determination of the protective effects of Hua-Zhuo-Jie-Du in chronic atrophic gastritis by regulating intestinal microbiota and metabolites: combination of liquid chromatograph mass spectrometer metabolic profiling and 16S rRNA gene sequencing.

BACKGROUND: Hua-Zhuo-Jie-Du (HZJD), a Chinese herbal prescription consisting of 11 herbs, is commonly used in China to treat chronic atrophic gastritis (CAG). We aimed to determine the effect of HZJD on the microbiome-associated metabolic changes in CAG rats. METHODS: The CAG rat models were induced by 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) combined with irregular fasting and 2% sodium salicylate, which was intragastrically administrated in fasted animals for 24 weeks. The CAG rats in the Chinese medicine (CM) group were administered a daily dose of 14.81 g/kg/day HZJD, and the vitacoenzyme (V) group were administered a daily dose of 0.08 g/kg/day vitacoenzyme. All animals were treated for 10 consecutive weeks, consecutively. Hematoxylin and eosin (H&E) staining was used to assess the histopathological changes in the gastric tissues. An integrated approach based on liquid chromatograph mass spectrometer (LC-MS) metabolic profiling combined with 16S rRNA gene sequencing was carried out to assess the effects of HZJD on CAG rats. Spearman analysis was used to calculate the correlation coefficient between the different intestinal microbiota and the metabolites. RESULTS: The H&E results indicated that HZJD could improve the pathological condition of CAG rats. The LC-MS results indicated that HZJD could significantly improve 21 gastric mucosal tissue perturbed metabolites in CAG rats; the affected metabolites were found to be involved in multiple metabolic pathways, such as the central carbon metabolism in cancer. The results of 16S rRNA gene sequencing indicated that HZJD could regulate the diversity, microbial composition, and abundance of the intestinal microbiota of CAG rats. Following HZJD treatment, the relative abundance of Turicibacter was increased, and the relative abundance of Desulfococcus and Escherichia were decreased in the CM group when compared with the M group. Spearman analysis revealed that perturbed intestinal microbes had a strong correlation with differential metabolites, Escherichia exhibited a negative correlation with l-Leucine, Turicibacter was negatively correlated with urea, and Desulfococcus exhibited a positive correlation with trimethylamine, and a negative correlation with choline. CONCLUSIONS: HZJD could protect CAG by regulating intestinal microbiota and its metabolites.

A comparative study of acarbose, vildagliptin and saxagliptin intended for better efficacy and safety on type 2 diabetes mellitus treatment.

As a complicated metabolic disorder, type 2 diabetes mellitus (T2DM) is becoming a major health concern worldwide. Drugs including acarbose, saxagliptin and vildagliptin are applied, but their efficacy is still required to be compared. Therefore, the study aimed to evaluate the efficacy and safety of acarbose, saxagliptin and vildagliptin in the treatment of T2DM. Ninety patients diagnosed with T2DM were treated with acarbose, saxagliptin and vildagliptin, respectively (30 patients for each drug). All patients were examined at 0, 4 and 12 weeks after treatment with vital signs recorded. Fasting blood glucose and blood biochemical indices were analyzed. In addition, fecal samples were taken for microbial macrogenome sequencing and safety evaluation within 12 weeks after treatment. Blood glucose level decreased at 4 and 12 weeks after treatment, and the total cholesterol (TC) and high-density lipoprotein (HDL) levels at 12 weeks were different. Genus abundance of intestinal flora was altered at different time points. Acarbose increased Butyricimonas level first and then decreased it during drug treatment. Saxagliptin increased Megamonas and decreased Turicibacter genus level gradually. Pseudomonas, Klebsiella, Blautia, Faecalibacterium and Roseburia levels fluctuated after Vildagliptin treatment, which increased fasting C-peptide level greater than the other two drugs. Saxagliptin showed higher adverse reactions than acarbose and vildagliptin. Collectively, acarbose, vildagliptin, and saxagliptin can effectively reduce the HbA1c level and affect the intestinal flora distribution in T2DM patients, and the adverse reactions of acarbose and vildagliptin are less than saxagliptin, providing alternative strategies for the treatment of T2DM.

Integrating Network Pharmacology and Experimental Validation to Investigate the Mechanisms of Huazhuojiedu Decoction to Treat Chronic Atrophic Gastritis.

BACKGROUND: Chronic atrophic gastritis (CAG) is an important stage in the normal gastric mucosa's transformation into gastric cancer. Huazhuojiedu decoction (HZJD), a Chinese herbal preparation, has proven clinically effective to treat CAG. However, few studies have explored the mechanism of HZJD in CAG treatment. PURPOSE: This study aimed to shed light on the mechanisms underlying HZJD decoction CAG treatment using a network pharmacology approach and experimental validation. METHODS: The active components of HZJD decoction were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. Their targets were predicted through the SwissTargetPrediction database. Disease targets were screened using the GeneCards database. The disease and drug prediction targets were intersected to select the common potential therapeutic targets, which then were input into the Search Tool for the Retrieval of Interacting Genes to build a protein-protein interaction network. The "herb-compound-target-disease" and the "herb-target-pathway" network diagrams were constructed in Cytoscape 3.3.0. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of effective targets were performed using the Database for Annotation, Visualization, and Integrated Discovery. Finally, the core targets were preliminarily verified by CAG rat model. The gastric mucosa's histopathological changes were observed via hematoxylin-eosin staining. The expressions of MAPK1, AKT1, TNF, VEGFA, and EGFR were detected by western blot and quantitative real-time reverse transcription-polymerase chain reaction. RESULTS: A total of 155 nodes, including 20 putative targets of HZJD decoction, were selected as core hubs based on topological importance and were closely associated with the regulation of cell proliferation, apoptotic process, and cancer-related pathways (AKT1, TNF, VEGFA, and EGFR) in CAG. Further animal experiments showed that the expression of AKT1 in CAG rats was significantly increased, which was suppressed by HZJD decoction. TNF and VEGFA expression increased in the model group, but did not change in the HZJD group. MAPK1 and EGFR expression showed no significant differences among control, model, and HZJD groups. CONCLUSION: Taken together, the results suggest that the components of HZJD decoction can alleviate and prevent the severity of gastric precancerous lesions via AKT1 inhibition in CAG.

Identification of compound mutations of SLC12A3 gene in a Chinese pedigree with Gitelman syndrome exhibiting Bartter syndrome-liked phenotypes.

BACKGROUND: Gitelman syndrome is a rare salt-losing renal tubular disorder associated with mutation of SLC12A3 gene, which encodes the Na-Cl co-transporter (NCCT). Gitelman syndrome is characterized by hypokalemia, metabolic alkalosis, hypomagnesemia, hypocalciuria, and renin-angiotensin-aldosterone system (RAAS) activation. Different SLC12A3 variants may lead to phenotypic variability and severity. METHODS: In this study, we reported the clinical features and genetic analysis of a Chinese pedigree diagnosed with Gitelman syndrome. RESULTS: The proband exhibited hypokalaemia, hypomagnesemia, metabolic alkalosis, but hypercalciuria and kidney stone formation. The increased urinary calcium excretion made it confused to Bartter syndrome. The persistent renal potassium wasting resulted in renal tubular lesions, and might affect urinary calcium reabsorption and excretion. Genetic analysis revealed mutations of SLC12A3 gene with c.433C > T (p.Arg145Cys), c.1077C > G (p.Asn359Lys), and c.1666C > T (p.Pro556Ser). Potential alterations of structure and function of NCCT protein due to those genetic variations of SLC12A3 are predicted. Interestingly, one sibling of the proband carried the same mutant sites and exhibited similar clinical features with milder phenotypes of hypokalemia and hypomagnesemia, but hypocalciuria rather than hypercalciuria. Family members with at least one wild type copy of SLC12A3 had normal biochemistry. With administration of spironolactone, potassium chloride and magnesium supplement, the serum potassium and magnesium were maintained within normal ranges. CONCLUSIONS: In this study, we identified compound mutations of SLC12A3 associated with varieties of clinical features. Further efforts are needed to investigate the diversity in clinical manifestations of Gitelman syndrome and its correlation with specific SLC12A3 mutations.

A comparison of the efficacy and safety of complementary and alternative therapies for gastroesophageal reflux disease: A protocol for network meta-analysis.

BACKGROUND: Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal diseases in the world and is showing increasing prevalence in some countries. The disease has a chronic course that leads to a significant decline in the quality of life of patients and is associated with a high economic burden worldwide. And complementary and alternative medicine is used to treat the disease. Over the past few decades, a number of randomized controlled trials and systematic evaluations have been conducted to evaluate the effectiveness and safety of different types of complementary and alternative medicine methods, so there is an urgent need to summarize and further evaluate these studies. METHODS: We will search the following sources without restrictions for date, language, or publication status: PubMed, Cochrane Central Register of Controlled Trials (CENTRAL) Cochrane Library, and EMBASE, China National Knowledge Infrastructure, Chinese Bio-medicine Database, VIP Chinese Periodical Database, Wan Fang Database. We will apply a combination of Medical Subject Heading and free-text terms incorporating database-specific controlled vocabularies and text words to implement search strategies. We will also search the ongoing trials registered in the World Health Organization's International Clinical Trials Registry Platform. Besides, the previous relevant reviews conducted on complementary and alternative therapies for GERD and reference lists of included studies will also be searched. RESULTS: This study will provide a reliable basis for the treatment of GERD with complementary and alternative therapies. CONCLUSIONS: The findings will be an available reference to evaluate the efficacy and safety of complementary and alternative therapies on GERD and may provide decision-making reference on which method to choose for clinicians. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42020169332.

Selenium-doped two-photon fluorescent carbon nanodots for in-situ free radical scavenging in mitochondria.

Mitochondrial oxidative stress is associated with the occurrence and development of a wide range of human diseases. The development of methodologies to alleviate oxidative stress-mediated injury may have therapeutic potential. Herein, we report the design and preparation of triphenylphosphonium-functionalized selenium-doped carbon nanodots (TPP-Se-CDs) that can efficiently scavenging hydroxyl radicals (OH) and superoxide anions (O2-) in mitochondria region. Se-CDs with two-photon blue fluorescence were initially prepared by facile hydrothermal treatment of selenomethionine, followed by the covalent conjugation with TPP. The as-obtained TPP-Se-CDs showed high colloidal stability, strong scavenging abilities towards OH and O2-. Moreover, TPP-Se-CDs exhibited low cytotoxicity and mitochondria targeting ability. Taking advantages of these prominent features, TPP-Se-CDs have been successfully applied to combat H2O2 and phorbol 12-myristate 13-acetate (PMA) induced oxidative stress in mitochondria.

A novel biscoumarin compound ameliorates cerebral ischemia reperfusion-induced mitochondrial oxidative injury via Nrf2/Keap1/ARE signaling.

Some phytochemical-derived synthetic compounds have been shown to improve neurological disorders, especially in ischemic stroke. In this study, we identified a novel biscoumarin compound, known as COM 3, which had substantial antioxidant effects in neurons. Next, we found that COM 3 occupies a critical binding site between the Nrf2 and Keap1 dipolymer, impairing the inhibitory effects of Keap1 on Nrf2, both of which play central roles in increasing endogenous antioxidant activity. We verified that COM 3 could increase the survival of neurons experiencing oxygen and glucose deprivation (OGD) from 51.1% to 77.2% when exposure to 2.5 and 10 µg/mL of COM 3, respectively. In addition, the same concentrations of COM 3 could reduce brain infarct volumes by 33.8%to13.7%, respectively, while also reducing the neurobehavioral score from 3.3 to 1.4 on average in mice with a middle cerebral artery occlusion (MCAO). COM 3 reduced neuronal death from 36.5% to 13.9% and apoptosis from 35.1% to 18.2%. In addition, COM 3 could improve the neuronal mitochondrial energy metabolism after experiencing oxidative stress caused by OGD or MCAO. The present study suggests that COM 3 protects against OGD in neurons and MCAO in mice by interfering with the structure of Keap1 to activate the nuclear transcription of Nrf2, which balances endogenous redox activity and restores mitochondrial function. Hence, COM 3 might be a potential therapeutic agent for ischemic stroke in the clinic.

Progress in Treatment of Gout Using Chinese and Western Medicine.

Gout is a crystal-related arthropathy resulting from the deposition of monosodium urate. Identifying appropriate treatments and novel drugs to decrease serum uric acid (SUA) levels and gout risk has been a major focus. By performing extensive literature review on the pathogenesis and Chinese and Western medicine treatment of gout, this paper aimed to identify novel targets for effective control of acute gout attacks and long-term reduction of SUA. In addition, we aimed to provide new directions for the improvement of therapeutic measures and the development of drugs. Although Western medicine can significantly contribute to the treatment of gout, Chinese herbal medicine has unique advantages, including reduced adverse reactions and higher patient compliance. It may also fill in the shortcomings of Western medicine in the intermittent period treatment of gout. In addition to constantly exploring pathogenesis and drug targets, research on Chinese herbal medicine is equally important. The combination of Chinese and Western medicine has proven to become an important direction for gout treatment.

Non-targeted metabolomics reveals diagnostic biomarker in the tongue coating of patients with chronic gastritis.

Analysis of the properties of the tongue has been used in traditional Chinese medicine for disease diagnosis. Notably, tongue analysis, which is non-invasive and convenient compared with gastroscopy and pathological examination, can be used to assess chronic gastritis (CG). In order to find potential diagnostic biomarkers and study the metabolic mechanisms of the endogenous small molecules in the tongue coating related to CG, a non-targeted metabolomic analysis method was developed using ultra high performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UHPLC-Q/TOF-MS). It was performed using two different columns in positive and negative ion scanning modes separately. The stability of the samples was evaluated and the age and gender factors of the subjects were excluded to ensure the reliability of the data in this study. Finally, under the four analysis models, 130, 229, 113 and 92 differential compounds were found using multivariate statistical methods respectively. 37 potential biomarkers were putatively identified after removing the duplicate compounds and five potential diagnostic biomarkers were putatively identified by receiver operating characteristic (ROC) curve analysis, including inosine, oleamide, adenosine, N-acetylglucosamine (GlcNAc) and xanthine. The main metabolic pathways associated with CG were purine metabolism, amino acid metabolism, sphingolipid metabolism and energy metabolism, which suggested that oxygen free radicals and energy metabolism were altered in patients with CG. These results provided a potential new basis for the quantitative diagnosis and pathogenesis of CG.

Modified Chuanhu anti-gout mixture, a traditional Chinese medicine, protects against potassium oxonate-induced hyperuricemia and renal dysfunction in mice.

OBJECTIVE: Acute gout is a painful, inflammatory arthritis that features a rapidly escalating inflammatory response resulting from the formation of monosodium urate crystals in the affected joint space. Previously, we found that Chuanhu anti-gout mixture (CAGM) had similar effects as colchicine against gout in the clinic. Subsequently, to improve its effectiveness and efficacy, we modified the original formulation of CAGM. The current study evaluated the effectiveness of the modified formulation in mice. METHODS: Potassium oxonate (PO) was used to establish a mouse model of hyperuricemia. Plasma levels of uric acid and creatine were determined using the respective test kits. Hepatic xanthine oxidase (XOD) expression was examined by enzyme-linked immunosorbent assay. To explore the underlying mechanism, renal urate transporter 1 (URAT1) mRNA levels were evaluated by quantitative real-time PCR. Allopurinol and benzbromarone were used as reference drugs. RESULTS: The original CAGM and its modified high-dose formulation significantly reduced serum uric acid and creatine levels in hyperuricemic mice. In addition, the CAGM-treated groups displayed lower mRNA levels of hepatic XOD and renal URAT1. CONCLUSIONS: CAGM and its modified formulation significantly ameliorated PO-induced hyperuricemia in mice, which might be partially attributable to reductions of hepatic XOD and renal URAT1 levels.

A Randomized Controlled Trial of Chuanhutongfeng Mixture for the Treatment of Chronic Gouty Arthritis by Regulating miRNAs.

BACKGROUND: We investigated whether Chuanhutongfeng mixture has actions on chronic gouty arthritis (CGA) by regulating miRNAs. METHODS: A total of 255 patients with CGA and 30 controls were enrolled. miRNA expression profiles and cluster analysis were preformed; RT-qPCR was used to detect miRNAs associated with CGA. Patients were allocated into Chuanhutongfeng mixture, allopurinol (positive control), and control (etoricoxib) groups. Expression of plasma miRNAs was measured before and after treatments; expression of chemokine 2 (CCL2) and interleukin 8 (CXCL8) was determined by ELISA. RESULTS: 48 miRNAs were differentially expressed and compared to controls. 36 miRNAs expression levels were > 1.5 times and 12 miRNAs < 1.5 times compared to the controls. miR-339-5p, miR-486-5p, and miR-361-5p levels in patients with CGA were lower than in controls (P < 0.05). This trial showed that the Chuanhutongfeng mixture and allopurinol groups had upregulated the expressions of miR-486-5, miR-339-5p, and miR-361-5p and decreased levels of CCL2 and CXCL8 proteins. After 8 weeks of treatment, Chuanhutongfeng mixture decreased serum uric acid levels more than allopurinol (P < 0.05) and reduced levels of CCL2 and CXCL8 protein significantly more than in the allopurinol and control groups. CONCLUSIONS: The therapeutic actions of Chuanhutongfeng mixture inhibit the expression of proteins CCL2 and CXCL8 in plasma and upregulated the expressions of three miRNAs (miR-486-5p, miR-339-5p, and miR-361-5p).