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.

[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.

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.

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.

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.

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.

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.

A randomized controlled trial study protocol for Xiao-Qing-Long decoction in the treatment of refractory asthma: Study protocol clinical trial (spirit compliant).

INTRODUCTION: People with refractory asthma (RA) often seek help from Chinese medicine due to dissatisfaction with conventional treatments. External cold and internal fluid syndrome is the most common type of asthma and the Chinese herbal medicine formula Xiao-Qing-Long (XQL) decoction is commonly prescribed for patients with asthma with this syndrome. However, there is no direct evidence to support the efficacy and safety of XQL decoction for RA treatment and its potential mechanism is still unclear. METHODS: We propose a double-blind, placebo-controlled, randomized superiority trial. After a 2-week run-in period, 112 eligible participants will be recruited and randomly allocated to an experimental group or control group in a 1:1 ratio. Patients in the experimental group will take XQL decoction, while patients in the control group will receive a matched placebo. Symbicort Turbuhaler and Montelukast sodium tablets will be provided as the basic treatment for the 2 groups. All participants will receive 4 weeks of treatment and 12 weeks of follow-up. The primary outcome is the mean change in the asthma control test score from the baseline to 4 weeks posttreatment. The secondary outcomes include quality of life, lung function, curative effect of traditional Chinese medicine, and rescue medication used. This trial will also include analyses of the associations between intestinal microbiota and RA treatment. Any side effects of the treatment will be recorded. DISCUSSION: The results of this trial will provide consolidated evidence of the effect of XQL decoction for RA and the potential mechanism by which XQL decoction acts, which will inform treatment options for patients with RA.