Scorpiones, Scolopendra and Gekko Inhibit Lung Cancer Growth and Metastasis by Ameliorating Hypoxic Tumor Microenvironment via PI3K/AKT/mTOR/HIF-1α Signaling Pathway.

OBJECTIVE: To investigate whether Buthus martensii karsch (Scorpiones), Scolopendra subspinipes mutilans L. Koch (Scolopendra) and Gekko gecko Linnaeus (Gekko) could ameliorate the hypoxic tumor microenvironment and inhibit lung cancer growth and metastasis by regulating phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin/hypoxia-inducible factor-1α (PI3K/AKT/mTOR/HIF-1α) signaling pathway. METHODS: Male C57BL/6J mice were inoculated with luciferase labeled LL/2-luc-M38 cell suspension to develop lung cancer models, with rapamycin and cyclophosphamide as positive controls. Carboxy methyl cellulose solutions of Scorpiones, Scolopendra and Gekko were administered intragastrically as 0.33, 0.33, and 0.83 g/kg, respectively once daily for 21 days. Fluorescent expression were detected every 7 days after inoculation, and tumor growth curves were plotted. Immunohistochemistry was performed to determine CD31 and HIF-1α expressions in tumor tissue and microvessel density (MVD) was analyzed. Western blot was performed to detect the expression of PI3K/AKT/mTOR/HIF-1α signaling pathway-related proteins. Enzyme-linked immunosorbent assay was performed to detect serum basic fibroblast growth factor (bFGF), transforming growth factor-ß1 (TGF-ß1) and vascular endothelial growth factor (VEGF) in mice. RESULTS: Scorpiones, Scolopendra and Gekko prolonged the survival time and inhibited lung cancer metastasis and expression of HIF-1α (all P<0.01). Moreover, Scorpiones, Scolopendra and Gekko inhibited the phosphorylation of AKT and ribosomal protein S6 kinase (p70S6K) (P<0.05 or P<0.01). In addition, they also decreased the expression of CD31, MVD, bFGF, TGF-ß1 and VEGF compared with the model group (P<0.05 or P<0.01). CONCLUSION: Scorpiones, Scolopendra and Gekko all showed beneficial effects on lung cancer by ameliorating the hypoxic tumor microenvironment via PI3K/AKT/mTOR/HIF-1α signaling pathway.

Identification and analysis of differential miRNA-mRNA interactions in coronary heart disease: an experimental screening approach.

Objective: This aim of this study is to screen the differential molecules of kidney deficiency and blood stasis (KDBS) syndrome in coronary heart disease by high-throughput sequencing. In addition, the study aims to verify the alterations in the expression levels of miR-4685-3p and its regulated downstream, namely, C1QC, C4, and C5, using quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA), and to determine whether the complement and coagulation cascade pathway is the specific pathogenic pathway. Methods: Patients diagnosed with unstable angina pectoris with KDBS syndrome, patients with non-kidney deficiency blood stasis (NKDBS) syndrome, and a Normal group were recruited. The clinical symptoms of each group were further analyzed. Illumina's NextSeq 2000 sequencing platform and FastQC software were used for RNA sequencing and quality control. DESeq software was used for differential gene expression (DGE) analysis. qPCR and ELISA verification were performed on DGE analysis. Results: The DGE profiles of 77 miRNA and 331 mRNA were selected. The GO enrichment analysis comprised 43 biological processes, 49 cell components, and 42 molecular functions. The KEGG enrichment results included 40 KEGG pathways. The PCR results showed that, compared with the Normal group, the miR-4685-3p levels decreased in the CHD_KDBS group (P = 0.001), and were found to be lower than those observed in the CHD_NKDBS group. The downstream mRNA C1 regulated by miR-4685-3p showed an increasing trend in the CHD_KDBS group, which was higher than that in the Normal group (P = 0.0019). The mRNA C4 and C5 in the CHD_KDBS group showed an upward trend, but the difference was not statistically significant. ELISA was utilized for the detection of proteins associated with the complement and coagulation cascade pathway. It was found that the expression level of C1 was significantly upregulated in the CHD_KDBS group compared with the Normal group (P < 0.0001), which was seen to be higher than that in the CHD_NKDBS group (P < 0.0001). The expression levels of C4 and C5 in the CHD_KDBS group were significantly lower than the Normal group, and were lower than that in the CHD_NKDBS group (P < 0.0001). Conclusion: The occurrence of CHD_KDBS might be related to the activation of the complement and coagulation cascade pathway, which is demonstrated by the observed decrease in miR-4685-3p and the subsequent upregulation of its downstream C1QC. In addition, the expression levels of complement C4 and C5 were found to be decreased, which provided a research basis for the prevention and treatment of this disease.

Publication trends and hotspots of colorectal adenoma during 2002-2022: a bibliometric and visualized analysis.

Background: Prevention and treatment of colorectal adenoma (CRA) are great significant to reduce morbidity and mortality of colorectal cancer. Although there have been numerous studies on CRA recently, few publications utilized the bibliometrics to evaluate this field. The objective of current study was to provide a comprehensive analysis of the current state and frontier progress of CRA over the past 20 years. Methods: The Web of Science Core Collection was utilized to extracted all studies of CRA during 2002-2022. Bibliometric tools including CiteSpace, VOSviewer, and the Online Analysis Platform of Literature Metrology were used for statistical analysis. CiteSpace and the Online Analysis Platform were used to evaluate the contributions of various countries/regions, institutions, authors, and journals in this field. Research hotspots and trends were identified through keywords and references analysis by VOSviewer and CiteSpace. Results: 2,268 publications from 2002 to 2022 in total were identified. The number of global publications in this field has increased annually. The USA was the most productive country, contributing nearly 30% of global publications. But in recent years, China's publications grew rapidly and had the highest citation strength. The most productive institutions was the National Cancer Institute. Baron JA from the USA was the most productive and the one of most co-cited authors. Cancer Epidemiology Biomarkers & Prevention had the highest number of publications and Gastroenterology was the most co-cited journals. Analysis of keywords clusters showed that "mechanism/pathophysiology", "risk factors and prevention", "colonoscopy screening and treatment", "metabolism", and "microbiota" were the major frontier topics and the main research directions. Conclusions: CRA publications have shown a gradual upward trend in recent years, most of which have been published by developed countries. Developing countries should further focus on CRA research and transnational cooperation with developed countries in the future, in order to better improve the situation of the increasing morbidity and mortality of CRC. Baron JA was the most outstanding researcher in this field. More attention should be devoted to "pathogenesis of CRA", "less invasive diagnostic methods", "chemoprevention", and "screening and risk prediction of CRA including gut microbiome and metabolism", which will be frontiers in the future.

Functional compounds of ginseng and ginseng-containing medicine for treating cardiovascular diseases.

Ginseng (Panax ginseng C.A.Mey.) is the dry root and rhizome of the Araliaceae ginseng plant. It has always been used as a tonic in China for strengthening the body. Cardiovascular disease is still the main cause of death in the world. Some studies have shown that the functional components of ginseng can regulate the pathological process of various cardiovascular diseases through different mechanisms, and its formulation also plays an irreplaceable role in the clinical treatment of cardiovascular diseases. Therefore, this paper elaborates the current pharmacological effects of ginseng functional components in treating cardiovascular diseases, summarizes the adverse reactions of ginseng, and sorts out the Chinese patent medicines containing ginseng formula which can treat cardiovascular diseases.

Traditional Chinese Medicine in Cancer Care: An Overview of 5834 Randomized Controlled Trials Published in Chinese.

BACKGROUND: Traditional Chinese medicine (TCM) is widely integrated into cancer care in China. An overview in 2011 identified 2384 randomized and non-randomized controlled trials (RCTs, non-RCTs) on TCM for cancer published in the Chinese literature. This article summarizes updated evidence of RCTs on TCM for cancer care. METHODS: We searched 4 main Chinese databases: China National Knowledge Infrastructure, Chinese Scientific Journal Database, SinoMed, and Wanfang. RCTs on TCM used in cancer care were analyzed in this bibliometric study. RESULTS: Of 5834 RCTs (477 157 cancer patients), only 62 RCTs were indexed in MEDLINE. The top 3 cancers treated were lung, stomach, and breast cancer. About 4752 RCTs (81.45%) tested TCM combined with conventional treatment, and 1082 RCTs (18.55%) used TCM alone for treating symptoms and side-effects. Herbal medicine was the most frequently used TCM modality (5087 RCTs; 87.20%). The most frequently reported outcome was symptom improvement (3712 RCTs; 63.63%) followed by quality of life (2725 RCTs; 46.71%), and biomarkers (2384 RCTs; 40.86%). The majority of RCTs (4051; 69.44%) concluded there were beneficial effects using either TCM alone or TCM plus conventional treatment compared with conventional treatment. CONCLUSION: Substantial randomized trials demonstrated different types/stages of cancer were treated by various TCM modalities, alone or in combination with conventional medicine. Further evaluation on the effects and safety of TCM modalities focusing on outcomes such as quality of life is required.

The Effectiveness and Safety of Bushen Huoxue Decoction on Treating Coronary Heart Disease: A Meta-Analysis.

OBJECTIVE: The aim of this meta-analysis was to systematically evaluate the effectiveness and safety of the traditional Chinese medicine (TCM) formula Bushen Huoxue Decoction (BSHXD) in treating coronary heart disease (CHD). METHODS: Randomized controlled trials (RCTS) of BSHXD in treating CHD were searched until March 2020, through six electronic databases: PubMed, Cochrane Library, CNKI, WanFang, SinoMed, and VIP. This study used the Cochrane Risk Test bias tool in the Cochrane Handbook to assess the quality of the methodology. Review Manager (RevMan) 5.3 was used to analyze the results. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria were applied in the classification of evidence quality. RESULTS: Ten RCTs involving 901 patients were finally included in this meta-analysis. It revealed that the effectiveness of BSHXD in treating CHD was significantly better than that of the conventional western medicine (CWM) treatment (P < 0.00001). The effective rate of BSHXD treatment group on ECG was also significantly higher than that of CWM group (P < 0.00001). The low-density lipoprotein cholesterol was decreased in the treatment groups compared with those in the control groups (P < 0.00001). There was also a reduction in frequency and duration of angina pectoris (P < 0.00001). There were no significant differences in TC level (P=0.08), TG level (P=0.86), and HDL level (P=0.76) between the treatment and control groups. Five studies had informed adverse events, including nausea and diarrhea. CONCLUSION: Our findings laid the foundation to the use of TCM Formula BSHXD in combination with conventional western medicine for treating CHD. However, due to the limitation of the quality of the included researches, in addition to potential reporting bias, the above conclusions still need verification by higher-quality and better-designed studies.

Effects of Qigong, Tai Chi, acupuncture, and Tuina on cancer-related fatigue for breast cancer patients: A protocol of systematic review and meta-analysis.

BACKGROUNDS: Cancer-related fatigue (CRF) is one of the most common and disabling outcomes in patients with breast cancer (BC). Traditional Chinese medicine (TCM) nonpharmacological interventions are becoming increasingly popular for cancer treatment and rehabilitation interventions. However, their efficacy and safety remain unclear and there is no systematic review or meta-analysis focusing fully on this issue. We aim to evaluate the effects of representative TCM nonpharmacological interventions, including Qigong, Tai Chi, acupuncture, and Tuina, on CRF in BC patients. METHODS: Published randomized controlled trials (RCTs) that assessed the efficacy of these interventions on CRF for BC patients will be included. We will search from the following electronic databases: PubMed, Cochrane Library, EMBASE, MEDLINE, Web of Science, Scopus, PsycINFO, PSYINDEX, CINAHL, China National Knowledge Infrastructure (CNKI), WanFang Database, and Chinese Biomedical Literature Database (CBM). The primary outcomes are the improvement of CRF, which will be evaluated by the Piper Fatigue Scale (PFS), the Functional Assessment of Cancer Therapy (FACT)-Fatigue Scale, Schwartz Cancer Fatigue Scale (SCFS), the Multidimensional Fatigue Inventory (MFI). The secondary outcomes are quality of life and safety. The meta-analysis will be performed using RevMan ver 5.3(Cochrane) statistical software. RESULTS: We will provide more practical results investigating the efficacy of Qigong, Tai Chi, acupuncture, Tuina for BC patients with CRF from several respects including the improvement of fatigue, quality of life, and safety. CONCLUSIONS: This review will generate more stronger evidence in BC patients for TCM nonpharmacological interventions, including Qigong, Tai Chi, acupuncture, Tuina, in the treatment of CRF and help to inform clinicians and policymakers. ETHICS DISSEMINATION: Ethical approval is not necessary because all of the study base in our review will be based on published research. We will submit our results to a peer-reviewed journal. STUDY REGISTRATION NUMBER: The study is priorly registered through International Platform of Registered Systematic Review and Meta-analysis Protocol on October 2, 2020 (INPLASY 2020100003).

Shengmai injection combined with conventional therapy in treating Adriamycin-related cardiotoxicity: A protocol for systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Tumor is a common and frequently-occurring disease that seriously threatens human health, and is one of the main causes of death. Adriamycin (ADM) is the most commonly used and effective anti-tumor chemotherapeutics in clinical practice, but they can cause severe cardiotoxicity, which obviously limits their clinical application. Shengmai injection is a modern injection form of traditional Chinese medicine widely used for heart failure, myocardial infarction, cardiogenic shock, and cardiotoxicity patients in China. Therefore, we design this systematic review and meta-analysis to assess the effectiveness and safety of Shengmai injection for treating ADM-related cardiotoxicity. METHODS: We will methodically search PubMed, EMBASE, Cochrane Library, Science Network, China National Knowledge Infrastructure, Wanfang Database, Chinese Journal Database, and China Biomedical Literature Database, in order to include randomized controlled trials which used Shengmai injection in treating ADM-related cardiotoxicity up to September 2020. The search strategies will use the following phrase: "Shengmai injection," "Adriamycin," "doxorubicin," "cardiotoxicity," "cardiomyopathy," "randomized controlled trial." The outcomes included cardiotoxicity rate, echocardiography, electrocardiogram, myocardial enzymes. Two researchers will independently select the study, extract the data and assess the quality by using Stata 14.0 and RevMan 5.3 software. The plan follows the preferred reporting items declared by the systematic review and meta-analysis plan, and the complete systematic review will follow the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement. CONCLUSION: The effectiveness and safety of Shengmai injection will be assessed in treating ADM-related cardiotoxicity which can give some evidence for clinical decision making. TRIAL REGISTRATION NUMBER: INPLASY202090040.

Voxel-based micro-finite element analysis of dental implants in a human cadaveric mandible: Tissue modulus assignment and sensitivity analyses.

The success of dental implant treatment is related to the complex 3-dimensional (3D) biomechanics of the implant-bone interaction. In this work, 3D numerical models are built based on micro X-ray computed tomography (micro-CT) images of a cadaveric mandible specimen with implants placed in it. The simulation results show that the computed strain values in bone are sensitive to the uncertainties in trabecular tissue modulus and fairly insensitive to the modulus of implants and teeth and the detailed geometry of the fixed boundary condition. A bone-volume-fraction (BV/TV) based method is proposed to assign the tissue moduli of bone elements based on their BV/TV to increase the connectivity of the mesh and to improve the accuracy of the models. These models are potentially powerful for calculating the 3D full-field bone strain under implant loading, enabling in silico testing of different implant designs, but demand validation of the models. The computed results reveal high strain concentration at bone-implant contact areas and, more importantly, in the buccal (lip-side) bone that is not making contact with the implant. The computed strain concentration patterns are found to be in good agreement with the observations from our prior experiments using 3D full-field mechanical testing coupled with micro-CT and digital volume correlation. The buccal bone is thinner and less stiff than other areas of bone and is also the commonly observed area of bone resorption after dental implant treatment.