Gut virome alterations in patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is one of the primary causes of mortality and morbidity worldwide. The gut microbiome, particularly the bacteriome, has been demonstrated to contribute to the progression of COPD. However, the influence of gut virome on the pathogenesis of COPD is rarely studied. Recent advances in viral metagenomics have enabled the rapid discovery of its remarkable role in COPD. In this study, deep metagenomics sequencing of fecal virus-like particles and bacterial 16S rRNA sequencing was performed on 92 subjects from China to characterize alterations of the gut virome in COPD. Lower richness and diversity of the gut virome were observed in the COPD subjects compared with the healthy individuals. Sixty-four viral species, including Clostridium phage, Myoviridae sp., and Synechococcus phage, showed positive relationships with pulmonary ventilation functions and had markedly declined population in COPD subjects. Multiple viral functions, mainly involved in bacterial susceptibility and the interaction between bacteriophages and bacterial hosts, were significantly declined in COPD. In addition, COPD was characterized by weakened viral-bacterial interactions compared with those in the healthy cohort. The gut virome showed diagnostic performance with an area under the curve (AUC) of 88.7%, which indicates the potential diagnostic value of the gut virome for COPD. These results suggest that gut virome may play an important role in the development of COPD. The information can provide a reference for the future investigation of diagnosis, treatment, and in-depth mechanism research of COPD. IMPORTANCE: Previous studies showed that the bacteriome plays an important role in the progression of chronic obstructive pulmonary disease (COPD). However, little is known about the involvement of the gut virome in COPD. Our study explored the disease-specific virome signatures of patients with COPD. We found the diversity and compositions altered of the gut virome in COPD subjects compared with healthy individuals, especially those viral species positively correlated with pulmonary ventilation functions. Additionally, the declined bacterial susceptibility, the interaction between bacteriophages and bacterial hosts, and the weakened viral-bacterial interactions in COPD were observed. The findings also suggested the potential diagnostic value of the gut virome for COPD. The results highlight the significance of gut virome in COPD. The novel strategies for gut virome rectifications may help to restore the balance of gut microecology and represent promising therapeutics for COPD.

The protective effects of icariin against testicular dysfunction in type 1 diabetic mice Via AMPK-mediated Nrf2 activation and NF-κB p65 inhibition.

BACKGROUND: Owing to the early suffering age and the rising incidence of type 1 diabetes (T1D), the resulting male reproductive dysfunction and fertility decline have become a disturbing reality worldwide, with no effective strategy being available. Icariin (ICA), a flavonoid extracted from Herba Epimedium, has been proved its promising application in improving diabetes-related complications including diabetic nephropathy, endothelial dysfunction and erectile dysfunction. Ensuring the future reproductive health of children and adolescents with T1D is crucial to improve global fertility. However, its roles in the treatment of T1D-induced testicular dysfunction and the potential mechanisms remain elusive. PURPOSE: The purpose of this present study was to investigate whether ICA ameliorates T1D-induced testicular dysfunction as well as its potential mechanisms. METHODS: T1D murine model was established by intraperitoneal injection of STZ with or without treated with ICA for eleven weeks. Morphological, pathological and serological experiments were used to determine the efficacy of ICA on male reproductive function of T1D mice. Western blotting, Immunohistochemistry analysis, qRT-PCR and kit determination were performed to investigated the underlying mechanisms. RESULTS: We found that replenishment of ICA alleviated testicular damage, promoted testosterone production and spermatogenesis, ameliorated apoptosis and blood testis barrier impairment in streptozotocin-induced T1D mice. Functionally, ICA treatment triggered adenosine monophosphate protein kinase (AMPK) activation, which in turn inhibited the nuclear translocation of nuclear factor kappa B p65 (NF-κB p65) to reduce inflammatory responses in the testis and activated nuclear factor erythroid 2-related factor 2(Nrf2), thereby enhancing testicular antioxidant capacity. Further studies revealed that supplementation with the AMPK antagonist Compound C or depletion of Nrf2 weakened the beneficial effects of ICA on testicular dysfunction of T1D mice. CONCLUSION: Collectively, these results demonstrate the feasibility of ICA in the treatment of T1D-induced testicular dysfunction, and reveal the important role of AMPK-mediated Nrf2 activation and NF-κB p65 inhibition in ICA-associated testicular protection during T1D.

Effects of Traditional Chinese Medicine Five-Element Music Therapy Combined with Mirtazapine on Depression and Limb Function Recovery After Ischemic Stroke.

Objective: To observe the effects of traditional Chinese medicine (TCM) five-element music therapy combined with mirtazapine on depression and limb function recovery after ischemic stroke. Methods: A total of 110 patients treated in the Departments of Geriatrics, Cardiology, and Psychology of three hospitals in Qinhuangdao City, Hebei Province, China from October 2022 to August 2023 were selected. Based on the scores of 24-item Hamilton Depression Scale (HAMD-24), Barthel (BL) index, and National Institute of Health Stroke Scale (NIHSS) before enrollment, the patients were randomly divided into control group (n = 58) and experimental group (n = 52). The patients in control group were treated with limb rehabilitation, while those in experimental group underwent limb rehabilitation combined with five-element music therapy and mirtazapine. Results: After 12 weeks of treatment and observation, 11 patients in control group and 9 patients in experimental group withdrew from this trail. As for the proportions of score changes, experimental group had higher decline proportions of HAMD-24 score and NIHSS score as well as an increased proportion of BL index score than control group, which were 43.97%, 69.32%, and 44.12%, respectively. Conclusion: TCM five-element music therapy combined with mirtazapine significantly improves depression and limb function recovery after ischemic stroke.

A Preliminary Study on Warm Acupuncture and Moxibustion for Treating Chronic Obstructive Pulmonary Disease with Abdominal Distension.

Most patients with COPD have a combination of abdominal distension, which has been shown to adversely affect pulmonary symptoms, frequency of acute exacerbations, and quality of life in patients with COPD. Warm acupuncture and moxibustion have been shown to be effective in relieving symptoms in patients with COPD combined with abdominal distention. Warm acupuncture and moxibustion are highly effective, easy to perform, and inexpensive forms of traditional Chinese medicine treatments. The standardized practice of warm acupuncture and moxibustion is very important for the treatment of COPD combined with abdominal distension. The specific steps include selecting the appropriate acupoints for needling through syndrome differentiation treatment and selecting moxa sticks of appropriate length for moxibustion for about 30 min after the De-qi. The course of treatment lasts for one week. The following indicators are specifically assessed: the score of the COPD Assessment Test (CAT) and the abdominal distension visual analog scale (VAS). This article will clearly illustrate how to standardize the manipulation of warm acupuncture and moxibustion to relieve COPD combined with abdominal distention.

Pretreatment with Eupatilin Attenuates Inflammation and Coagulation in Sepsis by Suppressing JAK2/STAT3 Signaling Pathway.

Purpose: Sepsis is an aggressive and life-threatening organ dysfunction induced by infection. Excessive inflammation and coagulation contribute to the negative outcomes for sepsis, resulting in high morbidity and mortality. In this study, we explored whether Eupatilin could alleviate lung injury, reduce inflammation and coagulation during sepsis. Methods: We constructed an in vitro sepsis model by stimulating RAW264.7 cells with 1 µg/mL lipopolysaccharide (LPS) for 6 hours. The cells were divided into control group, LPS group, LPS+ Eupatilin (Eup) group, and Eup group to detect their cell activity and inflammatory cytokines and coagulation factor levels. Cells in LPS+Eup and Eup group were pretreated with Eupatilin (10µM) for 2 hours. In vivo, mice were divided into sham operation group, cecal ligation and puncture (CLP) group and Eup group. Mice in the CLP and Eup groups were pretreated with Eupatilin (10mg/kg) for 2 hours by gavage. Lung tissue and plasma were collected and inflammatory cytokines, coagulation factors and signaling were measured. Results: In vitro, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and tissue factor (TF) expression in LPS-stimulated RAW264.7 cells was downregulated by Eupatilin (10µM). Furthermore, Eupatilin inhibited phosphorylation of the JAK2/STAT3 signaling pathway and suppressed p-STAT3 nuclear translocation. In vivo, Eupatilin increased the survival rate of the mice. In septic mice, plasma concentrations of TNF-α, IL-1ß and IL-6, as well as TF, plasminogen activator inhibitor 1 (PAI-1), D-dimer, thrombin-antithrombin complex (TAT) and fibrinogen were improved by Eupatilin. Moreover, Eupatilin alleviated lung injury by improving the expression of inflammatory cytokines and TF, fibrin deposition and macrophage infiltration in lung tissue. Conclusion: Our results revealed that Eupatilin may modulate inflammation and coagulation indicators as well as improve lung injury in sepsis via the JAK2/STAT3 signaling pathway.

Fibroblast growth factor 2 (FGF2) ameliorates the coagulation abnormalities in sepsis.

BACKGROUND: Sepsis is defined as a life-threatening organ dysfunction caused by dysregulation of the host response to infection. There is still a lack of specific treatment for sepsis. Here, we report that Fibroblast growth factor-2 (FGF2) can reduce the mortality of sepsis by ameliorating the coagulation abnormalities. METHODS: FGF2 was intraperitoneally injected into septic mice induced by lipopolysaccharide (LPS) and then assessed for coagulation response, organ damage and survival. RAW264.7 cells with or without FGF2 pretreating were exposed to LPS, and then changes in coagulation related factors expression and signaling were tested. RESULTS: The findings showed that intraperitoneal injection of FGF2 inhibited coagulation activity, reduced lung and liver damage, and increased survival in septic mice. In RAW264.7 cells, LPS upregulated the expression of tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1); however, pretreatment with FGF2 prevented this upregulation, while FGF2 knockdown exacerbated TF upregulation. Moreover, FGF2 suppressing the AKT/mTOR/S6K1 signaling pathway in septic mice and RAW264.7 cells stimulated by LPS. CONCLUSIONS: This study revealed a therapeutic role of FGF2 in ameliorating the coagulation abnormalities during sepsis.

[Analysis of traditional Chinese medicine syndromes in patients with coronavirus disease 2019 in plateau areas].

OBJECTIVE: To analyze the distribution characteristics of traditional Chinese medicine (TCM) syndromes in patients with coronavirus disease 2019 (COVID-19) in plateau areas, and to provide theoretical basis for further clinical treatment of patients with COVID-19. METHODS: From August 9 to August 24, 2022, patients with COVID-19 admitted to the Third People's Hospital of Tibet Autonomous Region (designated hospital for COVID-19) were included, and their baseline characteristics (age, gender, source), clinical classification and distribution of TCM syndrome types were collected and analyzed. Data analysis was performed using SPSS 26.0 statistical software. RESULTS: A total of 161 COVID-19 patients were enrolled with ethnic distribution: 124 (77.02%) Tibetans, 35 (21.74%) Han, and 2 (1.24%) Hui, 68 males and 93 females. The male-to-female ratio was 0.73:1. Aged 1 to 94 years, the average age was (39.06±23.64) years old, of which 4 patients were under 1 year old (excluded because the information was missing). A total of 157 patients were enrolled, and 124 patients (78.9%) were under 60 years old, including 120 cases of common type, 4 cases of severe type, 0 cases of critical type, 7 cases over 80 years old, 1 case over 90 years old, and 32 cases under 18 years old. The clinical manifestations of the patient are mainly cough, expectoration, fever, aversion to cold, dry throat, headache, fatigue, running nose, dry mouth, bitter mouth, etc. Most of the tongue is pale, red, and white greasy moss or thin white coating. In TCM, the most common syndrome was cold-dampness blocking lung syndrome (99 cases, 63.06%), followed by cold-dampness stagnant lung syndrome (22 cases, 14.01%), damp-heat accumulating lung syndrome (22 cases, 14.01%), and humidity stagnant lung syndrome (11 cases, 7.01%). Syndromes of epidemic (2 cases, 1.27%), epidemic toxins blocking the lung pattern (1 cases, 0.64%), toxins with dryness intense heat in both qi and ying phases pattern (0 cases) accounted for less than 2%, and the distribution of various syndrome types in COVID-19 patients was uneven (χ 2 = 0.48, P < 0.05). CONCLUSIONS: The most common TCM syndromes of COVID-19 patients in Lhasa are cold-dampness blocking lung syndrome, followed by cold-dampness stagnant lung syndrome, damp-heat accumulating lung syndrome, and humidity stagnant lung syndrome.

Molecular Mechanism of Curcumin and Its Analogs as Multifunctional Compounds against Pancreatic Cancer.

Pancreatic cancer (PC) is one of the most common malignant tumors with a poor prognosis and high mortality. Surgical resection is the most effective treatment for PC; however, only a minority of patients have resectable tumors. Chemotherapy is the primary treatment for PC. Curcumin is a natural chemical substance obtained from plants with a wide range of pharmacological activities. Research evidence suggests that curcumin can influence PC development through multiple molecular mechanisms. The synthesis of novel curcumin analogs and preparation of curcumin nano-formulations are effective strategies to overcome the low bioavailability of curcumin in the treatment of PC. This review aims to summarize the mechanisms of action of curcumin in preclinical and clinical studies on PC and research progress in enhancing its bioavailability.

Demethylzeylasteral Exerts Antitumor Effects via Disruptive Autophagic Flux and Apoptotic Cell Death in Human Colorectal Cancer Cells and Increases Cell Chemosensitivity to 5-Fluorouracil.

BACKGROUND: Demethylzeylasteral (ZST93), a pharmacologically active triterpenoid monomer extracted from Tripterygium wilfordii Hook F (TWHF), has been reported to exert antineoplastic effects in several cancer cell types. However, the anti-tumour effects of ZST93 in human colorectal cancer (CRC) cells are unknown. OBJECTIVE: The aim of the present study was to evaluate the antitumor effects of ZST93 on cell cycle arrest, disruptive autophagic flux, apoptotic cell death and enhanced chemosensitivity to 5-FU in human CRC cells. METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, colony formation assay, flow cytometry, immunoblotting, immunofluorescence, 5-ethynyl-20-deoxyuridine (EdU) incorporation assay and autophagy analysis were used to evaluate the effects of ZST93 on cell viability, cell cycle progression, apoptosis and autophagy in two human CRC cell lines. Moreover, ZST93's combined anti-tumour effects with 5-fluorouracil (5-FU) were evaluated. RESULTS: ZST93 inhibited CRC cell proliferation and growth. It was responsible for blocked cell cycle transition by arresting CRC cells in the G0/G1 phase via down-regulation of CDK4, CDK6, Cyclin D1 and c-MYC. Moreover, ZST93 induced suppressive autophagic flux and caspase-3-dependent cell death, which was further strengthened by the blocking of the autophagy process using chloroquine (CQ). Moreover, ZST93 enhanced CRC cells' chemosensitivity to 5-FU via modulation of autophagy and apoptosis. CONCLUSION: ZST93 exerts anti-tumor effects via disruptive autophagic flux and apoptotic cell death in human CRC cells and increases cell chemosensitivity to 5-FU. These results provide insights into the utilisation of ZST93 as an adjuvant or direct autophagy inhibitor and suggest ZST93 as a novel therapeutic strategy for treating CRC.

Metal-organic framework as a mimetic enzyme with excellent adaptability for sensitive chemiluminescence detection of glutathione in cell lysate.

A novel [Co(L)(H2O)2] (1) was obtained by hydrothermal method and it exhibited a 1D chain with exposed carboxyl groups, the unique coordination mode made it have unusual physical and chemical stability. Meanwhile, 1 showed peroxidase-like and weak oxidase-like activity. 1 as a peroxidase mimic enzyme had an excellent affinity for the substrates luminol and H2O2. Compared with HRP, 1 had catalytic activity in a wide pH range and showed the best catalytic activity at pH 7.4. Meanwhile, the catalysis process of 1 was reversible and recyclable, and the catalytic activity remained stable after different pH and temperatures and long-time storage. Based on the inhibition of glutathione on luminol-H2O2-MOF 1 chemiluminescence signal, a chemiluminescence method for the determination of glutathione has been proposed with high sensitivity and selectivity and had been applied for detecting glutathione in cell lysate with satisfactory results.

A novel copper-based metal-organic framework as a peroxidase-mimicking enzyme and its glucose chemiluminescence sensing application.

A novel copper-based metal-organic framework (Cu-MOF) with a large specific surface area and high porosity was synthesized. The Cu-MOF was a good peroxidase-mimicking enzyme and showed a high affinity with hydrogen peroxide in a wide pH range. The catalytic mechanism of Cu-MOF has been studied further based on comparing the characteristic of the Cu-MOF with some isomorphic MOFs. The catalytic activity center of Cu-MOF was determined to be the cupric ion rather than the ligand, which effectively promoted the generation of free radicals and electron transfer in the reaction progress. The high affinity of Cu-MOF to hydrogen peroxide proved it as an ideal catalyst for the chemiluminescence (CL) reaction involving hydrogen peroxide. Therefore, the CL method with high sensitivity could be established for detecting various substrates. A double-enzyme CL glucose biosensing platform was constructed for the determination of serum glucose employing the peroxidase-mimicking properties of Cu-MOF as well as glucose oxidase (GOx).

Chinese herbal medicine on treating obese women with polycystic ovary syndrome: A systematic review and meta-analysis protocol.

INTRODUCTION: Known as an endocrine disorder, Polycystic ovary syndrome (PCOS) has posed an influence on 6% to 20% reproductive females worldwide. The commonly used pharmaceutical agents currently are Oral Contraceptives (OCs) and insulin-sensitizing agents. However, OCs is not appropriate for females pursuing pregnancy. Furthermore, some of insulin-sensitizing agents are found to be related to a high incidence of gastrointestinal adverse effects. In this regard, the effectiveness of Chinese herbal medicine in handling reproductive and metabolic defects simultaneously has been proved by extensive evidence. In this research, the effectiveness and safety of Chinese herbal medicine for obese females with PCOS were examined. METHODS AND ANALYSIS: In the systematic review, we searched databases of AMED, Science Online, EMbase, WorldSciNet, the Cochrane Library, PubMed, Nature, MEDLINE, China National Knowledge Infrastructure, the Wanfang Databse and China Biology Medicine Disc and the Chongqing VIP Chinese Science and Technology Periodical Database, to find out the papers published in Chinese or English by September 25, 2020 in this field. In addition, potential reference lists, relevant conference proceedings, qualified studies, related system reviews and other resources were also considered. Two researchers were responsible for independently selecting the research papers, collecting data, and evaluating research quality. Moreover, the data were synthesized with the combination of a fixed-effects or random-effects model with the heterogeneity test. According to the objective and self-reported assessment, the primary outcomes will be Nausea and vomiting were primary outcomes. RevMan 5 software was used to analyze the collected data, the evidence level of which was evaluated by GRADE. The selection between the fixed-effects and random-effects models was determined by the heterogeneity level. In addition to the 95% Confidence Interval (CI), odds ratio (OR), or risk ratio (RR) was applied to the 2 categories. Moreover, 95% CI and standardized mean difference (SMD) or the weighted mean difference (WMD) were taken as the continuous variables. When existing meaningful heterogeneity could not be explained by any assessment such as subgroup analysis, we would not conduct a meta-analysis. During the subgroup analysis, each subgroup in specific cases should be comprehensively considered. ETHICS AND DISSEMINATION: The evaluation of rights or personal information of patients was not involved in the systematic review. Hence, we need not gain approval from ethical institutions. This paper will be present at related conferences for communication and published in journals. REGISTRATION: Open Science Framework (OSF) Preregistration: osf.io/yp86h.

Study on metabonomics of Chinese herbal medicine in the treatment of type 2 diabetes mellitus complicated with community-acquired pneumonia.

INTRODUCTION: Community-acquired pneumonia (CAP) is the main acute complication of type 2 diabetes mellitus (T2DM) and the main cause of hospitalization for infectious diseases. Unfortunately, in the treatment of type 2 diabetes mellitus complicated with community-acquired pneumonia (T2DM-CAP), modern medicine is still faced with enormous challenges because of insulin resistance and drug-resistant bacteria. In recent decades, clinical and experimental evidence shows that Chinese herbal medicine (CHM) has a certain beneficial effect on diabetes and pneumonia. Therefore, this trial aims to assess the efficacy and safety of CHM plus western medicines for the treatment of T2DM-CAP. METHODS: We propose a double-blind, placebo-controlled, randomized superiority trial.A total of 92 participants with T2DM-CAP will be randomly allocated at a 1:1 ratio to either the experimental group, which will receive modified Ban-Xia-Xie-Xin-Decotion and basic treatment, or the control group, which will receive basic treatment only. The study duration will be 14 days. The primary outcome will be the total clinical effective rate. The secondary outcomes are traditional Chinese medicine symptom score scale, pneumonia severity index, usage time of antibiotic, time required for blood sugar to reach the required level, frequency of hypoglycemia, and chest CT. Liquid chromatograph-mass spectrometry method will be used to explore the blood metabolism profiles of the subjects, to explore the pathogenesis of T2DM-CAP and the mechanism of CHM on T2DM-CAP. Adverse events will also be evaluated. DISCUSSION: This trial will provide evidence of the effectiveness and safety of traditional CHM in treating patients with T2DM-CAP. TRIAL REGISTRATION NUMBER: ChiCTR2000035204.

Large dosage Huangqin (Scutellaria) and Huanglian (Rhizoma Coptidis) for T2DM: A protocol of systematic review and meta-analysis of randomized clinical trials.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a metabolic disease with widespread concern in the world. It has the characteristics of high incidence rate and high disability rate, which seriously affects economic and social development. large dose herb Rhizoma Coptidis (Huanglian) and Scutellaria (Huangqin) or compound prescription contain large dose Huanglian and Huanglian for treatment of T2DM has already been confirmed. However, due to the lack of evidence, there is no specific method or suggestion, so it is necessary to carry out systematic evaluation on Coptidis and Scutellaria and provide effective evidence for further research. METHODS AND ANALYSIS: The following databases will be searched from their inception to June 2020: Electronic database includes PubMed, Embase, Cochrane Library, Web of Science, Nature, Science online, Chinese Biomedical Database WanFang, VIP medicine information, and China National Knowledge Infrastructure. Primary outcomes: fasting blood-glucose (FBG), 2 Hours Postprandial Blood Glucose (2hPBG), Glycosylated hemoglobin A1c (HbA1c). additional outcomes: Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL), triglycerides (TG), total serum cholesterol (TC). Data will be extracted by 2 researchers independently, risk of bias of the meta-analysis will be evaluated based on the Cochrane Handbook for Systematic Reviews of Interventions. All data analysis will be conducted by data statistics software Review Manager V.5.3. and Stata V.12.0. RESULTS: The results of this study will systematically evaluate the effectiveness and safety of large dose Huanglian and Huangqin intervention for people with T2DM. CONCLUSION: The systematic review of this study will summarize the current published evidence of large dose Huanglian and Huangqin for the treatment of T2DM, which can further guide the promotion and application of it. ETHICS AND DISSEMINATION: This study is a systematic review, the outcomes are based on the published evidence, so examination and agreement by the ethics committee are not required in this study. We intend to publish the study results in a journal or conference presentations. OPEN SCIENCE FRAMEWORK (OSF) REGISTRATION NUMBER: July 21, 2020. osf.io/b6r3z. (https://osf.io/b6r3z).

Large dosage Huanglian (Rhizoma Coptidis) for T2DM: A protocol of systematic review and meta-analysis of randomized clinical trials.

INTRODUCTION: Type 2 diabetes mellitus(T2DM) is a widespread attention of the world's major health problems. The international diabetes federation (IDF) has released the "global overview of diabetes (ninth edition)". By 2019. It can lead to complications and even death. Among them, the use of Rhizoma Coptidis (Huanglian) at large dose has also been proved to be effective in clinical practice. However, due to the lack of evidence, there is no specific method or suggestion, so it is necessary to carry out systematic evaluation on coptis coptis and provide effective evidence for further research. METHODS AND ANALYSIS: We will search the following electronic databases from their inception to May 2020: Electronic database includes PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure. Primary outcomes:fasting blood glucose and glycosylated haemoglobin (A1c). SECONDARY OUTCOMES: plasma insulin,blood lipid profile,adverse events,and cost associated with the intervention and hospital visit. Data will be extracted by 2 researchers independently, risk of bias of the meta-analysis will be evaluated based on the Cochrane Handbook for Systematic Reviews of Interventions. All data analysis will be conducted by data statistics software Review Manager V.5.3. and Stata V.12.0. RESULTS: The results of this study will systematically evaluate the effectiveness and safety of large dose of Huanglian intervention for people with T2DM. CONCLUSION: The systematic review of this study will summarize the current published evidence of large dose of Huanglian for the treatment of T2DM, which can further guide the promotion and application of it. ETHICS AND DISSEMINATION: This study is a systematic review, the outcomes are based on the published evidence, so examination and agreement by the ethics committee are not required in this study. We intend to publish the study results in a journal or conference presentations.Open Science Framework(OSF)registration number: July 21, 2020. https://osf.io/w7bj6.

Association of matrix metalloproteinase-12 polymorphisms with chronic obstructive pulmonary disease risk: A protocol for systematic review and meta analysis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a multifactorial disease with gene-environment interaction leading to airflow limitation through the respiratory tract. Reports on the association of matrix metalloproteinase 12 (MMP-12) polymorphisms with COPD have been controversial. A new systematic evaluation which could examine whether MMP-12 mutations are associated with the susceptibility to COPD is needed. METHODS: We will search PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure and Google Scholar to obtain eligible case-control studies for meta-analysis. The time is limited from the construction of the library to July 2020. Two investigators systematically will extract relevant data within those included studies.The odds ratio and 95% confidence intervals will be used to assess the genetic association between the allelic, dominant and recessive models of MMP-12 gene polymorphisms and COPD risk. Stata 12.0 software and Revman 5.3 will be adopted for statistical analysis. This protocol reported under the Preferred Reporting ltems for Systematic Reviews and Meta-Analyses Protocols statement. RESULTS: This study will provide a better understanding of the association between MMP-12 polymorphisms and COPD risk. CONCLUSION: Publishing this protocol will minimise the possibility of bias due to post hoc changes to the analysis protocol.

Effects of Fusu mixture (Wen-Shen-Qian-Yang Method) on sepsis-induced acute respiratory distress syndrome.

INTRODUCTION: Sepsis is the most common etiology of acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Capillary leakage caused by lung endothelial injury is the central cause of ARDS. The results of research in modern medicine in reducing endothelial damage and restoring endothelial functions are limited. In the previous clinical observations, we found that the Fusu mixture not only improves the clinical symptoms but also reduces the leakage of pulmonary capillaries. Therefore, the purpose of this study is to determine the clinical efficacy of the Fusu mixture combined with Western medicine in the treatment of ARDS caused by sepsis and to explore the mechanism of traditional Chinese medicine. METHODS: This is a prospective, single-center, randomized, single-blind, and controlled clinical study involving 620 eligible patients. The patients will be randomly divided into 2 groups: the Western medicine treatment group and the combination of Chinese and Western medicine treatment group. After 14 days of intervention, the clinical efficacy and safety of the Fusu mixture on sepsis-induced ARDS patients will be observed. The primary outcome will be measured as 28-day mortality. The secondary outcome indices include inflammatory markers (CRP, PCT, IL-6, TNF - α), APACHE II score, SOFA score, days without a ventilator, blood gas analysis (Lac, PaO2 / FiO2), intensive care unit hospital stay time, intensive care unit mortality. Simultaneously, the analysis of the exploratory results will be carried out to analyze the possible mechanism of Fusu mixture in the treatment of sepsis-induced ARDS by the high-throughput sequencing and bioinformatics. DISCUSSION: The purpose of this study is to evaluate the clinical efficacy of Fusu mixture in the treatment of sepsis-induced ARDS and explore its possible mechanism of action. If successful, it will provide evidence-based adjuvant therapy for the clinical treatment of ARDS.

Xiaoqinglong Decoction Protects the Lungs of AECOPD Mice through the AMPK/mTOR Signaling Pathway.

METHOD: Male C57BL/6J mice were used to establish AECOPD model by cigarette smoke and bacterial exposure. Mice were randomly divided into normal control (NC), AECOPD, XQLD, Compound C (Com C), Com C + XQLD, and Clarithromycin (CLA) groups. After treatment, the pulmonary function was evaluated by whole-body plethysmograph. The lung histopathology was observed by HE staining. The serum levels of IL-6, TNF-α, and COX-2 were detected by ELISA assay. The apoptotic index was measured by TUNEL assay, and the protein expressions of Bax, Bcl-2, Caspase-3, GRP78, and CHOP in the lung tissues were measured by western blot assay. RESULTS: XQLD treatment can improve pulmonary function (PF), ameliorate lung injury, and suppress inflammation and apoptosis of lung tissues. In addition, XQLD also markedly attenuated endoplasmic reticulum stress (ERS) and activated AMPK/mTOR pathway in the lung tissues of mice with AECOPD. However, the AMPK inhibitor Compound C decreased the protective effect of XQLD in AECOPD mice. CONCLUSION: These findings suggested that XQLD has protective effect against inflammation and apoptosis in AECOPD mice by attenuating ER stress via AMPK/mTOR pathway.

Traditional Chinese medicine may reduce the dosage of systemic glucocorticoids in required patients with acute exacerbation of chronic obstructive pulmonary disease: Study protocol for a randomized placebo-controlled trial.

INTRODUCTION: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) involves a severe inflammatory response. Systemic glucocorticoids are very important for the treatment of the acute exacerbation period; however, their use causes serious adverse effects. There is still no evidence on whether traditional Chinese medicine (TCM) can be used to reduce the dosage of systemic glucocorticoids in the treatment of patients with AECOPD. METHODS: In this trial, we plan to enroll 204 eligible patients with AECOPD who will be randomly assigned to receive TCM or a placebo. The effect of TCM in the treatment of patients with AECOPD will be measured by the dosage of systemic glucocorticoids (at which COPD assessment test [CAT] scores improve by 50%). Safety will also be assessed. TRIAL REGISTRATION: ChiCTR2000029568.

A randomized controlled trial for prevention of acute exacerbation of stable chronic obstructive pulmonary disease with acupoint application of traditional Chinese medicine: Study protocol clinical trial (SPIRIT Compliant).

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a major public health problem that severely affects the quality of life of patients and may even endanger their lives. Although modern medicine has achieved significant results in relieving the clinical manifestations of COPD, it is difficult to prevent its progression and acute exacerbation entirely. As one of the classic aspects of acupuncture and moxibustion therapy, acupoint application of traditional Chinese medicine (TCM) can improve the clinical efficacy of western medicine in treating COPD. To date, however,there is no high-quality clinical trial to assess the effectiveness of TCM acupoint application directly in preventing acute exacerbation of stable COPD. METHODS: The study is a randomized, double-blind, placebo-controlled trial, in which 200 stable COPD patients will be randomly and equally divided into the experimental group or control group. Both groups will undergo standard Western medicine treatment; however, the patients in the experimental group will be also treated with TCM acupoint application, while the control group will be given placebo acupoint application. The duration of the treatment will be 1 month and a follow-up for 11 months. The primary outcome will be the number of acute exacerbation episodes of COPD, and the secondary outcomes will include the lung function, St George's Respiratory Questionnaire, COPD Assessment Test, and 6-Minute Walk Test. A safety assessment will also be performed during the trial. DISCUSSION: The aim of this study is to evaluate the efficacy and safety of TCM acupoint application in preventing acute exacerbation of stable COPD. Our study will provide sound evidence to support the evidence-based medicine of TCM acupoint application as an additional measure in the prevention of acute exacerbation of stable COPD. TRIAL REGISTRATION: ChiCTR1900026564, Registered 14 October, 2019.