TOMM40 Correlates with Cholesterol and is Predictive of a Favorable Prognosis in Endometrial Carcinoma.

BACKGROUND: A link between cholesterol and endometrial cancer has been established, but current studies have been limited in their findings. We aimed to elucidate the causal relationship between cholesterol and endometrial cancer and to find prognostic genes for endometrial cancer. METHODS: We first explored the causal relationship between total cholesterol and endometrial cancer using two-sample Mendelian randomization and then obtained differential genes to screen for prognosis-related genes in endometrial cancer. Then, we utilized pan-cancer analysis based on RNA sequencing data to evaluate the expression pattern and immunological role of the Translocase of Outer Mitochondrial Membrane 40 (TOMM40). Through multiple transcriptome datasets and multi-omics in-depth analysis, we comprehensively explore the relationship of TOMM40 expression with clinicopathologic characteristics, clinical outcomes and mutations in endometrial cancer. Lastly, we systematically associated the TOMM40 with different cancers from immunological properties from numerous perspectives, such as immune cell infiltration, immune checkpoint inhibitors, immunotherapy, gene mutation load and microsatellite instability. RESULTS: We found a negative association between cholesterol and endometrial cancer. A total of 78 genes were enriched by relevant single nucleotide polymorphisms (SNPs), of which 12 upregulated genes and 5 downregulated genes in endometrial cancer. TOMM40 was found to be a prognostic gene associated with endometrial cancer by prognostic analysis. TOMM40 was found to be positively correlated with the infiltration of most immune cells and immunization checkpoints in a subsequent study. Meanwhile, TOMM40 also was an oncogene in many cancer types. High TOMM40 was associated with lower genome stability. CONCLUSION: The findings of our study indicate that the maintenance of normal total cholesterol metabolism is associated with a decreased risk of developing endometrial cancer. Moreover, TOMM40 may have potential as a prognostic indicator for endometrial cancer.

Effectiveness and safety of acupuncture in post-stroke depression (PSD): Protocol for a Bayesian analysis.

BACKGROUND: Post-stroke depression (PSD) is the most common emotional problem after stroke. It can lower the quality of life and increase the recurrence and mortality. Pharmacological agents have been shown to treat PSD. However, the benefits of pharmacotherapy are debatable and the side-effects are significant. More and more clinical trials suggest that acupuncture plays an important role in patients with PSD. The primary purposes of the study are to conduct a Bayesian analysis of randomized trials to determine the effect of acupuncture and investigate the effect of several acupuncture therapies on PSD. METHODS: We will retrieve articles from 5 English databases [PubMed, Web of Science, EMBASE, the Cochrane Central Register of Controlled Trials, and WHO International Clinical Trials Registry (TCTRP)] and 4 Chinese databases [Chinese National Knowledge Infrastructure (CNKI), Chinese VIP Information, Wanfang Database, and Chinese Biomedical Literature Database (CBM)]. The publication period will be from inception to January 2019. All randomized controlled trials that evaluate the safety and efficacy of acupuncture on PSD will be included. The primary outcomes will be the change in the degree of depression as measured by the Hamilton Depression Scale and Beck Depression Inventory. Two reviewers will separately extract the data and assess the risk of bias by using the Cochrane Collaboration's risk of bias tool. Bayesian analysis will be conducted to pool the effects of several acupunctures. The ranking probabilities for several acupunctures (simple acupuncture, fire needle, warm acupuncture, auriculo-acupuncture, or electroacupuncture) will be estimated by the surface under the cumulative ranking curve. RESULT: This study will provide reliable evidence for acupuncture on PSD. CONCLUSION: The results of this review will introduce a safe and effective treatment and provide reliable evidence to evaluate the effectiveness of several acupuncture therapies on PSD. TRIAL REGISTRATION NUMBER: CRD42019132725.

Enhancement of anticancer activity of docetaxel by combination with Fuzheng Yiliu decoction in a mouse model of castration-resistant prostate cancer.

Docetaxel (Doc) is the gold standard of care for castration-resistant prostate cancer (CRPC) patients, although the therapeutic effects are modest. Fuzheng Yiliu decoction (FZYL) comprises multiple herbs, and has been used for >10 years to treat various cancers, including hepatocellular tumors, malignant gastrointestinal tumors, and prostate cancer. In the study reported, we evaluated the anticancer effects of FZYL and of a combination of Doc and FZYL in CRPC tumor-bearing mice, and explored the underlying mechanisms. PC-3 tumor-bearing mice were treated with FZYL, Doc, Doc + FZYL or vehicle solution. Tumor volume was monitored, and tumor weight, proliferation and apoptosis of tumor tissues were measured. Deep sequencing was used to profile the miRNA expression patterns in tumor tissues. Our results suggested that FZYL alone could depress tumor growth, and the combination of Doc and FZYL treatment exhibited enhanced anticancer effects. Doc + FZYL regulated the expression of 10 miRNAs: miR-34b-5p, miR-674-3p, miR-140-3p, miR-342-3p, miR-214-3p, miR-149-5p, miR-378c, miR-29b-3p, miR-218-5p, and miR-378a-3p, involving in the PI3K-Akt pathway in the treatment of CRPC.

Yixinshu capsule combined with conventional treatment for chronic heart failure: Protocol for a systematic review and trial sequential analysis.

BACKGROUND: Yixinshu Capsule is widely utilized in Asia for the treatment of chronic heart failure (CHF) as a conventional drug, but a comprehensive conclusion is lacking. Here, we will provide a protocol to perform a meta-analysis and trial sequential analysis to evaluate the efficacy of Yixinshu Capsule combined with conventional treatment for chronic heart failure. METHODS: We will conduct a thorough search in six databases, PubMed, EMBASE, Cochrane Library Database, Chinese National Knowledge Infrastructure (CNKI), Chinese Science Journal Database (VIP), and Chinese Biomedical and Medical Database (CBM). Inclusion criteria will be randomized control trials (RCTs) with one group receiving Yixinshu Capsule based on conventional treatment and another group receiving conventional treatment alone. Modified Jadad scale and Cochrane's risk of bias assessment will be used to assess methodological quality. Only studies with modified Jadad scale score ≥3 will be included in meta-analysis for efficacy, which will be defined as moderate methodological quality. The total effective rate will be considered as the primary outcome and the secondary outcome will include mortality, rehospitalized rate, left ventricular ejection fraction (LVEF), 6-minute walking distance, E/A, left ventricular end-diastolic diameter (LVEDD), BNP, and NT-proBNP. We will conduct trial sequential analysis to evaluate the reliability of the primary outcome. RESULTS: This study will provide a rational synthesis of current evidences for Yixinshu Capsule on chronic heart failure. CONCLUSION: The conclusion of this study will provide evidence for judging the efficacy of Yixinshu Capsule on chronic heart failure. REGISTRATION: PROS-PERO CRD42019119612.

Effectiveness and safety of fire-needle moxibustion on insomnia: Protocol for a systematic review and meta-analysis.

BACKGROUND: Fire-needle moxibustion (FNM) is an ancient method of external therapy that combines acupuncture with moxibustion, and has the property of high temperature resistance. Insomnia is a major public health problem and strongly associated with a high prevalence, impact on daily life, comorbidity with other disorders, and societal costs. The clinical practice demonstrates that FNM has a therapeutic effect on insomnia. Here we will provide a protocol to evaluate the effectiveness and safety of FNM for insomnia. METHODS: We will search the randomized controlled trial literatures of FNM for insomnia in 7 electronic databases, including 3 English databases (PubMed, EMBASE, the Cochrane Central Register of Controlled Trials [Cochrane Library]) and 4 Chinese databases (Chinese National Knowledge Infrastructure, Chinese VIP Information, Wanfang Database, and Chinese Biomedical Literature Database). Pittsburgh Sleep Quality Index will be considered as the primary outcome, and the secondary outcome will include biochemical, indicators total scores on the insomnia severity index, quality of life, adverse events caused by FNM, and changes of TCM syndromes scores. Review Manager 5.2 software will be use for assessment of risk of bias, data synthesis. Begg and Egger tests will be use for assessing symmetries of funnel plot by software Stata 12.0. Methodological quality will be assessed with the risk of bias according to Cochrane Handbook. RESULT: This study will provide a rational synthesis of current evidences for Fire-needle moxibustion on insomnia. CONCLUSION: The conclusion of this study will provide evidence to judge the effectiveness and safety of Fire-needle moxibustion on insomnia. REGISTRATION: PROS-PERO CRD42019120875.

Effectiveness and safety of warm needle acupuncture on insomnia: Protocol for a systematic review and meta-analysis.

BACKGROUND: Warm needle acupuncture (WNA) combines acupuncture and moxibustion, which is an integral part of the acupuncture therapy. Insomnia is a common sleep disorder, which affects sub-healthy people and patients with chronic disease. The clinical practice indicates that WNA has a therapeutic effect on insomnia. Here we will provide a protocol to explore the effectiveness and safety of WNA for insomnia. METHODS: We will search the randomized controlled trails (RCT) literatures of WNA for insomnia in 9 electronic databases, including 5 English databases [PubMed, Web of Science, EMBASE, the Cochrane Central Register of Controlled Trials (Cochrane Library), and WHO International Clinical Trials Registry Platform (TCTRP)] and 4 Chinese databases [Chinese National Knowledge Infrastructure (CNKI), Chinese VIP Information, Wanfang Database, and Chinese Biomedical Literature Database (CBM)]. Sleep quality value of the patient will be considered as the primary outcome and the secondary outcome will include biochemical, indicators total scores on the insomnia severity index, quality of life, adverse events caused by WNA, and changes of symptom in Traditional Chinese Medicine. The selection of the studies will be performed by EndnoteX7 software. All analyses will be conducted by using RevMan software V5.3. RESULT: This study will provide a rational synthesis of current evidences for warm needle acupuncture on insomnia. CONCLUSION: The conclusion of this study will provide evidence to judge the effectiveness and safety of WNA on insomnia. REGISTRATION: PROS-PERO CRD42018112645.