Association between Vitamin B6 and Risk of Gastric Cancer: A Systematic Review and Meta-Analysis of Epidemiological Studies.

Inconsistent findings have emerged from epidemiological research investigating the association between vitamin B6 and the risk of gastric cancer. To obtain a more precise assessment, we conducted a comprehensive search of published data and performed a meta-analysis. PubMed, Web of Science, EMBASE and Cochrane Library databases were systematically searched. A total of 12 studies (5 prospective cohort and 7 case-control studies) involving 5,692 cases and 814,157 participants were included in the meta-analysis. The results showed that high intake of vitamin B6 may reduce the odds of gastric cancer (OR = 0.83, 95% CI: 0.73-0.95, p = 0.006). However, this association was only observed in the case-control studies (OR = 0.68, 95% CI: 0.51-0.89, p = 0.006) but not in the cohort studies (RR = 1.01, 95% CI: 0.94-1.08, p = 0.819). Additionally, the negative association between vitamin B6 intake and gastric cancer risk was found in the United States of America (OR = 0.71, 95% CI: 0.62-0.82, p = 10-4), but not in Europe (OR = 0.88, 95% CI: 0.74-1.05, p = 0.169) or the other regions (OR = 0.86, 95% CI: 0.66-1.13, p = 0.280). In conclusion, there is not sufficient evidence to assume that vitamin B6 intake is associated with gastric cancer risk, which needs further confirmation.

A survey on identification and quantification of alternative polyadenylation sites from RNA-seq data.

Alternative polyadenylation (APA) has been implicated to play an important role in post-transcriptional regulation by regulating mRNA abundance, stability, localization and translation, which contributes considerably to transcriptome diversity and gene expression regulation. RNA-seq has become a routine approach for transcriptome profiling, generating unprecedented data that could be used to identify and quantify APA site usage. A number of computational approaches for identifying APA sites and/or dynamic APA events from RNA-seq data have emerged in the literature, which provide valuable yet preliminary results that should be refined to yield credible guidelines for the scientific community. In this review, we provided a comprehensive overview of the status of currently available computational approaches. We also conducted objective benchmarking analysis using RNA-seq data sets from different species (human, mouse and Arabidopsis) and simulated data sets to present a systematic evaluation of 11 representative methods. Our benchmarking study showed that the overall performance of all tools investigated is moderate, reflecting that there is still lot of scope to improve the prediction of APA site or dynamic APA events from RNA-seq data. Particularly, prediction results from individual tools differ considerably, and only a limited number of predicted APA sites or genes are common among different tools. Accordingly, we attempted to give some advice on how to assess the reliability of the obtained results. We also proposed practical recommendations on the appropriate method applicable to diverse scenarios and discussed implications and future directions relevant to profiling APA from RNA-seq data.

movAPA: modeling and visualization of dynamics of alternative polyadenylation across biological samples.

MOTIVATION: Alternative polyadenylation (APA) has been widely recognized as a widespread mechanism modulated dynamically. Studies based on 3' end sequencing and/or RNA-seq have profiled poly(A) sites in various species with diverse pipelines, yet no unified and easy-to-use toolkit is available for comprehensive APA analyses. RESULTS: We developed an R package called movAPA for modeling and visualization of dynamics of alternative polyadenylation across biological samples. movAPA incorporates rich functions for preprocessing, annotation and statistical analyses of poly(A) sites, identification of poly(A) signals, profiling of APA dynamics and visualization. Particularly, seven metrics are provided for measuring the tissue-specificity or usages of APA sites across samples. Three methods are used for identifying 3' UTR shortening/lengthening events between conditions. APA site switching involving non-3' UTR polyadenylation can also be explored. Using poly(A) site data from rice and mouse sperm cells, we demonstrated the high scalability and flexibility of movAPA in profiling APA dynamics across tissues and single cells. AVAILABILITY AND IMPLEMENTATION: https://github.com/BMILAB/movAPA. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Association between Vitamin B12 and Risk of Gastric Cancer: A Systematic Review and Meta-Analysis of Epidemiological Studies.

Epidemiological studies focusing on the association between vitamin B12 and gastric cancer risk reported inconsistent findings. We conducted a systematic review and meta-analysis to assess the relationship. PubMed (Medline), Web of science and EMBASE databases were systematically searched. A total of nine studies involving 3,494 cases of with gastric cancer and 611,638 participants were included. The result showed that there is no significant association between vitamin B12 intake and the risk of gastric cancer (OR = 0.88, 95% CI: 0.69-1.12, P = 0.303). Nevertheless, high intake of vitamin B12 might decrease the risk of gastric cancer in Helicobacter pylori (Hp)-negative people (OR = 0.83, 95% CI: 0.62-0.99, P = 0.044), but increase the cancer risk in Hp-positive populations (OR = 1.66, 95% CI: 1.27-2.16, P = 10-4). Additionally, further analysis indicated that excessive vitamin B12 might increase the risk of non-cardia gastric cancer (OR = 1.15, 95% CI: 1.01-1.33, P = 0.006). A negative association between vitamin B12 intake and gastric cancer risk was found in nonsmokers (OR = 0.83, 95% CI: 0.71-0.96, P = 0.012) but not in smokers (OR = 1.08, 95% CI: 0.71-1.47, P = 0.619). In conclusion, although we found no convincing evidence that vitamin B12 intake is associated with the risk of gastric cancer, it is important to maintain the relative stability of vitamin B12 for people with Hp infection.

Folate Intake and Risk of Urothelial Carcinoma: A Systematic Review and Meta-Analysis of Epidemiological Studies.

We aimed to investigate the association between folate intake and the risk of urothelial carcinoma (UC). A systematic literature search using Pubmed and EMBASE databases was performed to find prospective cohort studies, population-based case-control study or hospital-based case-control study investigating the association of folate intake and the risk of UC. A total of 19 studies involving 11,175 cases and 656,161 individuals were included. High intake of folate was associated with a decreased risk of UC, with a pooled OR of 0.78 (95% CI: 0.66-0.93, P = 0.006) for the highest category of intake vs. the lowest. The data suggested that folate may contribute to the prevention of urothelial cancer. However, the association was observed only in case-control studies (OR = 0.56, 95% CI: 0.39-0.79, P = 0.001), but not in cohort studies (RR = 0.97, 95% CI: 0.87-1.09, P = 0.638). Dose-response meta-analysis showed that an increment of folate intake (100 µg/day) corresponded to an 8% deceased risk of invasive UC (RR = 0.92, 95% CI: 0.87-0.98, P = 0.004). High folate intake might be inversely associated with risk of UC particularly invasive UC, which needs to be confirmed.

scAPAmod: Profiling Alternative Polyadenylation Modalities in Single Cells from Single-Cell RNA-Seq Data.

Alternative polyadenylation (APA) is a key layer of gene expression regulation, and APA choice is finely modulated in cells. Advances in single-cell RNA-seq (scRNA-seq) have provided unprecedented opportunities to study APA in cell populations. However, existing studies that investigated APA in single cells were either confined to a few cells or focused on profiling APA dynamics between cell types or identifying APA sites. The diversity and pattern of APA usages on a genomic scale in single cells remains unappreciated. Here, we proposed an analysis framework based on a Gaussian mixture model, scAPAmod, to identify patterns of APA usage from homogeneous or heterogeneous cell populations at the single-cell level. We systematically evaluated the performance of scAPAmod using simulated data and scRNA-seq data. The results show that scAPAmod can accurately identify different patterns of APA usages at the single-cell level. We analyzed the dynamic changes in the pattern of APA usage using scAPAmod in different cell differentiation and developmental stages during mouse spermatogenesis and found that even the same gene has different patterns of APA usages in different differentiation stages. The preference of patterns of usages of APA sites in different genomic regions was also analyzed. We found that patterns of APA usages of the same gene in 3' UTRs (3' untranslated region) and non-3' UTRs are different. Moreover, we analyzed cell-type-specific APA usage patterns and changes in patterns of APA usages across cell types. Different from the conventional analysis of single-cell heterogeneity based on gene expression profiling, this study profiled the heterogeneous pattern of APA isoforms, which contributes to revealing the heterogeneity of single-cell gene expression with higher resolution.

PlantAPAdb: A Comprehensive Database for Alternative Polyadenylation Sites in Plants.

Alternative cleavage and polyadenylation (APA) is increasingly recognized as an important regulatory mechanism in eukaryotic gene expression and is dynamically modulated in a developmental, tissue-specific, or environmentally responsive manner. Given the functional importance of APA and the rapid accumulation of APA sites in plants, a comprehensive and easily accessible APA site database is necessary for improved understanding of APA-mediated gene expression regulation. We present a database called PlantAPAdb that catalogs the most comprehensive APA site data derived from sequences from diverse 3' sequencing protocols and biological samples in plants. Currently, PlantAPAdb contains APA sites in six species, Oryza sativa (japonica and indica), Arabidopsis (Arabidopsis thaliana), Medicago truncatula, Trifolium pratense, Phyllostachys edulis, and Chlamydomonas reinhardtii APA sites in PlantAPAdb are available for bulk download and can be queried in a Google-like manner. PlantAPAdb provides rich information of the whole-genome APA sites, including genomic locations, heterogeneous cleavage sites, expression levels, and sample information. It also provides comprehensive poly(A) signals for APA sites in different genomic regions according to distinct profiles of cis-elements in plants. In addition, PlantAPAdb contains events of 3' untranslated region shortening/lengthening resulting from APA, which helps to understand the mechanisms underlying systematic changes in 3' untranslated region lengths. Additional information about conservation of APA sites in plants is also available, providing insights into the evolutionary polyadenylation configuration across species. As a user-friendly database, PlantAPAdb is a large and extendable resource for elucidating APA mechanisms, APA conservation, and gene expression regulation.

Folate Intake and Risk of Pancreatic Cancer: A Systematic Review and Updated Meta-Analysis of Epidemiological Studies.

INTRODUCTION: Pancreatic cancer is one of the most fatal malignancies and primary prevention strategies are limited. Epidemiological studies focusing on the association between folate intake and pancreatic cancer risk have reported inconsistent findings. METHODS: A systematic search of the literature was conducted using the PubMed and EMBASE databases. A systematic review and meta-analysis of eligible studies was performed to assess the association between folate intake and risk of pancreatic cancer. RESULTS: A total of 16 studies involving 5654 cases and 1,009,374 individuals were included. The result showed a significant association of folate intake with a decreased risk of pancreatic cancer, with a pooled OR of 0.82 (95% CI: 0.69-0.97, P = 0.019) for the highest category of intake vs. the lowest. The data suggested that high intake of folate may contribute to the prevention of pancreatic cancer. However, the association was observed only in case-control studies (OR = 0.78, 95% CI: 0.65-0.93, P = 0.006), but not in cohort studies (RR = 0.85, 95% CI: 0.66-1.09, P = 0.244). Dose-response meta-analysis showed that an increment of folate intake (100 µg/day) was marginally associated with the risk of pancreatic cancer, with a pooled OR of 0.97 (95% CI: 0.93-1.00, P = 0.053). CONCLUSION: High folate intake might be inversely associated with pancreatic cancer risk, which needs to be confirmed.

Theaflavin alleviates oxidative injury and atherosclerosis progress via activating microRNA-24-mediated Nrf2/HO-1 signal.

Theaflavin (TF) in black tea has been shown to have significant antioxidant and anti-inflammatory capacity; however, the effects and the underlying mechanism of TF on atherosclerosis (AS) remain unclear. Herein, we investigated the effects and the potential mechanism of TF on AS progression in vivo and in vitro. ApoE-/- mice were administrated with high fat diet (HFD) or HFD + TF (5 or 10 mg, i.g.) for 12 weeks. The results indicated that TF administration effectively decreases the serum lipid levels and the production of MDA in HFD-fed mice. Meanwhile, TF promotes the activities of antioxidant enzymes (SOD, CAT, and GSH-Px) and inhibits the formation of atherosclerotic plaque and the process of histological alterations in the aorta. In vitro, TF pretreatment could protect against cholesterol-induced oxidative injuries in HUVEC cells, decreasing the level of ROS and MDA, maintaining the activities of antioxidant enzymes. Further study revealed that TF upregulates Nrf2/HO-1 signaling pathway in vascular endothelial cells. Moreover, TF increases the level of microRNA-24 (miR-24), and miR-24 inhibition markedly compromises TF-induced Nrf2 activation and protective effects. In conclusion, the present study indicated that theaflavins may achieve the anti-atherosclerotic effect via activating miR-24-mediated Nrf2/HO-1 signaling pathway.

Cluster analysis of replicated alternative polyadenylation data using canonical correlation analysis.

BACKGROUND: Alternative polyadenylation (APA) has emerged as a pervasive mechanism that contributes to the transcriptome complexity and dynamics of gene regulation. The current tsunami of whole genome poly(A) site data from various conditions generated by 3' end sequencing provides a valuable data source for the study of APA-related gene expression. Cluster analysis is a powerful technique for investigating the association structure among genes, however, conventional gene clustering methods are not suitable for APA-related data as they fail to consider the information of poly(A) sites (e.g., location, abundance, number, etc.) within each gene or measure the association among poly(A) sites between two genes. RESULTS: Here we proposed a computational framework, named PASCCA, for clustering genes from replicated or unreplicated poly(A) site data using canonical correlation analysis (CCA). PASCCA incorporates multiple layers of gene expression data from both the poly(A) site level and gene level and takes into account the number of replicates and the variability within each experimental group. Moreover, PASCCA characterizes poly(A) sites in various ways including the abundance and relative usage, which can exploit the advantages of 3' end deep sequencing in quantifying APA sites. Using both real and synthetic poly(A) site data sets, the cluster analysis demonstrates that PASCCA outperforms other widely-used distance measures under five performance metrics including connectivity, the Dunn index, average distance, average distance between means, and the biological homogeneity index. We also used PASCCA to infer APA-specific gene modules from recently published poly(A) site data of rice and discovered some distinct functional gene modules. We have made PASCCA an easy-to-use R package for APA-related gene expression analyses, including the characterization of poly(A) sites, quantification of association between genes, and clustering of genes. CONCLUSIONS: By providing a better treatment of the noise inherent in repeated measurements and taking into account multiple layers of poly(A) site data, PASCCA could be a general tool for clustering and analyzing APA-specific gene expression data. PASCCA could be used to elucidate the dynamic interplay of genes and their APA sites among various biological conditions from emerging 3' end sequencing data to address the complex biological phenomenon.

Genetic polymorphisms in VDR, ESR1 and ESR2 genes may contribute to susceptibility to Parkinson's disease: a meta-analysis.

We conducted this meta-analysis of relevant case-control studies to investigate the relationships between genetic polymorphisms in VDR, ESR1 and ESR2 genes to the susceptibility of Parkinson's disease (PD). A search on electronic databases without any language restrictions was conducted: MEDLINE (1966-2013), the Cochrane Library Database (Issue 12, 2013), EMBASE (1980-2013), CINAHL (1982-2013), Web of Science (1945-2013) and the Chinese Biomedical Database (1982-2013). Meta-analysis was performed using the STATA statistical software. Crude odds ratio (OR) with their 95% confidence interval (95% CI) was calculated. Fourteen case-control studies with a total of 3,689 PD patients and 4,627 healthy subjects were included in our meta-analysis. The results of our meta-analysis demonstrated that the VDR genetic polymorphisms might be closely related to increased risks of PD (allele model: OR = 1.18, 95% CI 1.09-1.29, P < 0.001; dominant model: OR = 1.37, 95% CI 1.16-1.63, P < 0.001; respectively), especially for the polymorphisms rs7976091 and rs10735810. Our findings also illustrated that ESR1 genetic polymorphisms might increase the risk of PD (allele model: OR = 1.56, 95% CI 1.17-2.07, P = 0.002; recessive model: OR = 1.93, 95 % CI 1.33-2.80, P < 0.001; homozygous model: OR = 1.35, 95% CI 1.02-1.79, P = 0.038; heterozygous model: OR = 2.04, 95% CI 1.36-3.07, P = 0.001; respectively), especially for the polymorphisms rs2234693 and rs9340799. Furthermore, we found significant correlations of ESR2 genetic polymorphisms with the risk of PD (allele model: OR = 1.78, 95% CI 1.19-2.67, P = 0.005; recessive model: OR = 1.93, 95% CI 1.15-3.27, P = 0.014; homozygous model: OR = 1.77, 95% CI 1.09-2.89, P = 0.022; heterozygous model: OR = 1.88, 95% CI 1.08-3.27, P = 0.025; respectively), especially for the rs1256049 polymorphism. Our meta-analysis suggests that genetic polymorphisms in VDR, ESR1 and ESR2 genes may contribute to increased risks for PD.

Theaflavin-3,3'-Digallate Protects Liver and Kidney Functions in Diabetic Rats by Up-Regulating Circ-ITCH and Nrf2 Signaling Pathway.

Theaflavin-3,3'-digallate (TFDG) in black tea has a strong antioxidant capacity. However, its effect on diabetic liver and kidney injury and the underlying mechanisms remain unclear. In the present study, our findings indicated that TFDG administration effectively lowers the fasting blood glucose and serum lipid concentrations and enhances the functionality and cellular architecture of the liver and kidney in rats with diabetes. The data also showed that TFDG mitigates oxidative harm in the liver and kidney of rats afflicted with diabetes. Additionally, metformin combined with TFDG was significantly more effective in reducing blood glucose and oxidative stress. Further studies suggested that TFDG upregulates the Nrf2 signal pathway and circ-ITCH (hsa_circ_0001141) expression. Silencing of circ-ITCH by transfection of the interfering plasmid apparently reduces the effects of TFDG on the Nrf2 signal pathway and oxidative stress in high-glucose-treated hepatic and renal cells. In conclusion, the present study highlights the great potential of TFDG in ameliorating diabetic liver and kidney injury by up-regulating circ-ITCH to promote the Nrf2 signal pathway and provides a potential option for the prevention and treatment of diabetic complications.

Folate intake and risk of colorectal cancer: a systematic review and up-to-date meta-analysis of prospective studies.

PURPOSE: Colorectal cancer is one of the most commonly diagnosed and deadly cancers worldwide. Epidemiological studies on the relationship between folate intake and the risk of colorectal cancer have reported inconsistent findings since folate fortification in the USA. For this situation, we conducted a large number of data analyses to study the relationship between folate intake and colorectal cancer risk. METHODS: PubMed and EMBASE databases were used to search the literature systematically. Eligible studies were reviewed and meta-analyzed to assess the relationship. RESULTS: A total of 24 cohort studies involving 37 280 patients and 6 165 894 individuals were included. The results showed that high folate intake was associated with a reduced risk of colorectal cancer. The combined relative risk (RR) for the highest intake compared with the lowest was 0.88 [95% confidence interval (CI), 0.83-0.92, P = 10 -4 ). Further studies indicated that the increase of folate intake may decrease the risk of colorectal cancer in people with medium or high alcohol consumption (RR = 0.97, 95% CI: 0.96-0.99, P = 0.008; RR = 0.95, 95% CI: 0.92-0.98, P = 0.003), but not in non-drinkers (RR = 1.00, 95% CI: 0.98-1.02, P = 0.827). Next, high folate intake may decrease the risk of colon cancer (RR = 0.86, 95% CI: 0.81-0.92, P = 10 -4 ) but not rectal cancer (RR = 0.92, 95% CI: 0.84-1.02, P = 0.112). Additionally, the result that high folate intake may decrease the risk of colorectal cancer was observed in the USA and Europe but not in other regions. CONCLUSION: High folate intake may be protective against colon cancer, particularly in people with middle or high alcohol consumption, but it still needs to be further confirmed.

Study on the Specific Expression of Infrared Radiation Temperature on the Body Surface of Acupoint in Rats with Chronic Myocardial Ischemic Injury.

BACKGROUND: Infrared thermal imaging technology was used to observe the changes in infrared radiation temperature at acupoints in rats caused by chronic myocardial ischemia injury. OBJECTIVE: This study aims to compare the difference of body surface infrared radiation temperature information of three groups of acupoints: bilateral Neiguan (PC6), bilateral Yanglingquan (GB33), and bilateral Sham Acupoints (SA) in the pathological state of myocardial ischemia injury, and to explore the relationship between acupoints and viscera state. METHODS: SPF adult Wistar male rats (n = 20) were randomly divided into a control (CTL; n = 10) and an isoproterenol group (ISO; n = 10). Chronic myocardial injury was induced in rats by subcutaneous injection of isoproterenol hydrochloride for 14 d. On the second day after the establishment of the model, the serum levels of cardiac troponin (cTnI) and creatine kinase isoenzyme (CK-MB) were measured by enzyme-linked immunosorbent assay (ELISA). The morphological changes of the myocardial tissue in the two groups were observed by hematoxylin-eosin (HE) staining and their pathological scores were evaluated, which was then used to determine the myocardial ischemic injury. Two days before and after the establishment of the model, the electrocardiograms (ECG) of the two groups of rats were recorded by the (ECG) data acquisition system, and the infrared thermal imaging platform was used to detect the temperature of the six acupoints. RESULTS: 1. After subcutaneous injection of isoproterenol hydrochloride for 14 days, the ST segment of the ECG decreased in the ISO group compared with that of the CTL group; 2. Myocardial tissue injury was serious in the ISO group compared to the CTL group; 3. Serum cTn-I and CK-MB were significantly increased (P <0 01) in the ISO group, compared to that in the CTL group; 4. The infrared radiation temperature on the body surface of bilateral Neiguan (PC6) acupoints decreased significantly in the ISO group, compared to that of the CTL group. CONCLUSION: Infrared thermal imaging technology can be used to detect the changes in the energy state of acupoints. Chronic myocardial ischemic injury can cause a decrease in IR temperature on the body surface of bilateral Neiguan (PC6) acupoints, suggesting that visceral diseases can lead to changes in the energy metabolism of acupoints.

Eriodictyol inhibits breast carcinogenesis by targeting circ_0007503 and repressing PI3K/Akt pathway.

BACKGROUND: Eriodictyol in citrus fruits, Eriodictyon californicum and several Chinese herbal medicines shows great promise for chronic disease prevention, including cancers. However, its role in chemopreventive activities against breast carcinogenesis is unknown. PURPOSE: In the present study, we investigated the chemopreventive effect and the underlying mechanism of eriodictyol on carcinogens-induced breast carcinogenesis in vivo and in vitro. METHODS: The carcinogenic transformation in MCF10A cells was induced by the environmental carcinogens in vitro. The chemopreventive effect in vivo was evaluated by using the experimental model of 1-methyl-1-nitrosourea (MNU)-induced mammary tumorigenesis in rats. The activation of the PI3K/Akt pathway was detected by western blot assay; the levels of circular RNAs (circRNAs) were measured by qRT-PCR. RESULTS: First, eriodictyol significantly reduces cells viability and induces apoptosis in breast cancer cells in a dose-dependent manner in vitro (P < 0.05). Next, eriodictyol could effectively suppress environmental carcinogens-induced acquisition of carcinogenic properties in human breast epithelial cell MCF10A (P < 0.05). In vivo, eriodictyol administration reduces the incidence of mammary tumor by 50% in carcinogen-treated female rats (P < 0.05). Further study revealed that eriodictyol represses the PI3K/Akt signaling pathway and down-regulates the level of circ_0007503 in breast cancer cells and in breast carcinogenesis (P < 0.01). When the effect of eriodictyol on circ_0007503 was blocked by transfection of a circ_0007503 over-expression plasmid, the cytotoxic effects and the suppression of the PI3K/Akt pathway of eriodictyol in breast cancer cells were significantly reduced (P < 0.05). CONCLUSION: Our data indicated that eriodictyol could effectively suppress breast carcinogenesis in vitro and in vivoThe mechanism may be attributed to targeting circ_0007503 and inhibiting PI3K/Akt pathway.

Electroacupuncture at PC6 (Neiguan) Attenuates Angina Pectoris in Rats with Myocardial Ischemia-Reperfusion Injury Through Regulating the Alternative Splicing of the Major Inhibitory Neurotransmitter Receptor GABRG2.

Angina pectoris is the most common manifestation of coronary heart disease, causing suffering in patients. Electroacupuncture at PC6 can effectively alleviate angina by regulating the expression of genes, whether the alternative splicing (AS) of genes is affected by acupuncture is still unknown. We established a rat model of myocardial ischemia-reperfusion by coronary artery ligation and confirmed electroacupuncture alleviated the abnormal discharge caused by angina pectoris measured in EMG electromyograms. Analysis of the GSE61840 dataset established that AS events were altered after I/R and regulated by electroacupuncture. I/R decreased the expression of splicing factor Nova1 while electroacupuncture rescued it. Further experiments in dorsal root ganglion cells showed Nova1 regulated the AS of the GABRG2, specifically on its exon 9 where an important phosphorylation site is present. In vivo, results also showed that electroacupuncture can restore AS of GABRG2. Our results proved that electroacupuncture alleviates angina results by regulating alternative splicing.

Tai Chi and other mind-body interventions for cancer-related fatigue: an updated systematic review and network meta-analyses protocol.

INTRODUCTION: Fatigue is one of the most common symptoms in patients with cancer and is responsible for a reduced quality of life. There is a strong evidence base for mind-body interventions (MBIs) to manage cancer-related fatigue (CRF). However, the efficacy of Tai Chi and other MBIs in the treatment of CRF remains controversial. METHODS AND ANALYSIS: We will perform a systematic review and network meta-analyses (NMAs) that aim to assess the effects of Tai Chi and other MBIs in patients with CRF. The following databases will be searched from their inception to 1 August 2021: PubMed, EMBASE, Scopus, OVID, Web of Science, Cochrane Central Register of Controlled Trials, the China National Knowledge Infrastructure, China Science and Technology Journal Database, Chinese Biomedical Database and Wan Fang Digital Journals. We will include randomised controlled trials that compare MBIs with no treatment, placebo and usual care in the treatment of CRF. The primary outcome will be changes in the fatigue state as evaluated by validated scales. We will perform a Bayesian NMA to analyse all the evidence for each outcome. The surface under the cumulative ranking curve and the mean ranks will be used to rank the various treatments. We will assess the quality of evidence contributing to network estimates of outcomes using the Grading of Recommendations Assessment, Development and Evaluation system framework. ETHICS AND DISSEMINATION: This NMAs will be disseminated through publication in a peer-reviewed journal. Since no individual patient data will be involved in the review, ethics approval and concerns about privacy are not needed. PROSPERO REGISTRATION NUMBER: CRD42021244999.

Effectiveness and safety of acupuncture for angina pectoris: An overview of systematic reviews.

Background: The number of systematic reviews meta-analyses (SRs/MAs) on the effectiveness of acupuncture for angina pectoris (AP) is increasing. Due to the inconsistent conclusions and unknown quality of these SRs/MAs, this overview aimed to systematically evaluate and synthesize the existing SRs/MAs, attempting to provide more reliable evidence for the effectiveness and safety of acupuncture in the treatment of AP. Methods: SRs/MAs were searched via eight databases from inception to March 14, 2022. The risk of bias was evaluated using the Risk of Bias in Systematic reviews (ROBIS) tool. The quality of the methodology, reporting, and evidence were assessed by the Assess Systematic Reviews 2 (AMSTAR-2), the Preferred Reporting Item for Systematic Review and Meta-analysis for Acupuncture (PRISMA-A), and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system, respectively. Results: Sixteen SRs/MAs were included and fifteen SRs/MAs were considered being of critically low quality according to AMSTAR-2. Only three SRs/MAs were rated at low risk of bias. No study reported all the items listed in the PRISMA-A checklist. No high-quality evidence with GRADE assessment was found. With the low-quality evidence, acupuncture combined with other interventions was superior to monotherapy (medications or Chinese medicine) in the angina symptom and electrocardiogram recovery. No adverse effects owing to acupuncture were reported. Conclusions: Owing to the lack of high-quality evidence provided by the current SRs/MAs, the effectiveness of acupuncture for AP still warrants further proof. Further researches with more critical design and methodology are needed for providing more convincing evidence. Registration: This review was registered at PROSPERO (www.crd.york.ac.uk/prospero/): CRD42021219367.

Downregulation of lncRNA Miat contributes to the protective effect of electroacupuncture against myocardial fibrosis.

BACKGROUND: Myocardial fibrosis changes the structure of myocardium, leads to cardiac dysfunction and induces arrhythmia and cardiac ischemia, threatening patients' lives. Electroacupuncture at PC6 (Neiguan) was previously found to inhibit myocardial fibrosis. Long non-coding RNAs (lncRNAs) play a variety of regulatory functions in myocardial fibrosis, but whether electroacupuncture can inhibit myocardial fibrosis by regulating lncRNA has rarely been reported. METHODS: In this study, we constructed myocardial fibrosis rat models using isoproterenol (ISO) and treated rats with electroacupuncture at PC6 point and non-point as control. Hematoxylin-eosin, Masson and Sirius Red staining were performed to assess the pathological changes and collagen deposition. The expression of fibrosis-related markers in rat myocardial tissue were detected by RT-qPCR and Western blot. Miat, an important long non-coding RNA, was selected to study the regulation of myocardial fibrosis by electroacupuncture at the transcriptional and post-transcriptional levels. In post-transcriptional level, we explored the myocardial fibrosis regulation effect of Miat on the sponge effect of miR-133a-3p. At the transcriptional level, we studied the formation of heterodimer PPARG-RXRA complex and promotion of the TGF-ß1 transcription. RESULTS: Miat was overexpressed by ISO injection in rats. We found that Miat can play a dual regulatory role in myocardial fibrosis. Miat can sponge miR-133a-3p in an Ago2-dependent manner, reduce the binding of miR-133a-3p target to the 3'UTR region of CTGF mRNA and improve the protein expression level of CTGF. In addition, it can also directly bind with PPARG protein, inhibit the formation of heterodimer PPARG-RXRA complex and then promote the transcription of TGF-ß1. Electroacupuncture at PC6 point, but not at non-points, can reduce the expression of Miat, thus inhibiting the expression of CTGF and TGF-ß1 and inhibiting myocardial fibrosis. CONCLUSION: We revealed that electroacupuncture at PC6 point can inhibit the process of myocardial fibrosis by reducing the expression of lncRNA Miat, which is a potential therapeutic method for myocardial fibrosis.

Preemptive analgesia using selective cyclooxygenase-2 inhibitors alleviates postoperative pain in patients undergoing total knee arthroplasty: A protocol for PRISMA guided meta-analysis of randomized controlled trials.

BACKGROUND: The postoperative pain associated with total knee arthroplasty (TKA) is severe for most patients. The analgesic efficacy and safety of preoperative use of selective cyclooxygenase-2 (COX-2) inhibitors for patients undergoing TKA are unclear. OBJECTIVES: We conducted a systematic review and meta-analysis to assess whether the use of selective COX-2 inhibitors before TKA decreases the postoperative pain intensity. METHODS: Data sources: The PubMed, Embase, EBSCO, Web of Science, and Cochrane Controlled Register of Trials databases from inception to January 2020. STUDY ELIGIBILITY CRITERIA: All randomized controlled trials (RCTs) in which the intervention treatment was preoperative selective COX-2 vs placebo in patients undergoing TKA and that had at least one of the quantitative outcomes mentioned in the following section of this paper were included. Letters, review articles, case reports, editorials, animal experimental studies, and retrospective studies were excluded. INTERVENTIONS: All RCTs in which the intervention treatment was preoperative selective COX-2 vs placebo in patients undergoing TKA. STUDY APPRAISAL AND SYNTHESIS METHODS: The quality of the RCTs was quantified using the Newcastle-Ottawa quality assessment scale. RevMan 5.3 software was used for the meta-analysis. RESULTS: Six RCTs that had enrolled a total of 574 patients were included in the meta-analysis. The visual analog scale pain score at rest was significantly different between the experimental group and control group at 24 hours (P < .05) and 72 hours (P < .05) postoperatively. The experimental group exhibited a significant visual analog scale pain score during flexion at 24 hours postoperatively (P < .05), and it was not different at 72 hours postoperatively (P = .08). There was a significant difference in opioid consumption (P < .05), but there was no difference in the operation time (P = .24) or postoperative nausea/vomiting (P = .64) between the groups. CONCLUSION: The efficacy of preoperative administration of selective COX-2 inhibitors to reduce postoperative pain and opioid consumption after TKA is validated. SYSTEMATIC REVIEW REGISTRATION NUMBER: INPLASY202090101.