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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

HNSC exosome-derived MIAT improves cognitive disorders in rats with vascular dementia via the miR-34b-5p/CALB1 axis.

OBJECTIVE: To explore the molecular mechanism by which hippocampal neural stem cell (HNSC) exosome (exo)-derived MIAT improves cognitive disorders in rats with vascular dementia (VD). METHODS: Rat hippocampal tissues were collected, and HNSCs and hippocampal neuronal cells (HNCs) were isolated, purified, and identified. Then the exosomes (exo) of the HNSCs were extracted and identified. A VD rat model was constructed. HE staining was used to evaluate the hippocampal pathology in each group. The expressions of the RNAs in the HNSCs were intervened, and the cells were then grouped. ELISA was used to measure the of TNF-α, IL-1, and Aß1-42 expression levels. The kits were used to determine the oxidative stress factor levels. The targeting relationships among MIAT, miR-34b-5p, and CALB1 were measured using dual-luciferase assays. The MIAT expressions in exo were measured using qRT-PCR. The proliferation and apoptosis of the HNCs were determined using CCK-8 and Annexin V-FITC/PI staining, respectively. The CALB1, TH, and Bcl-2 protein expressions were determined using Western blot. The Morris water maze test was used for the spatial learning and memory testing. RESULTS: The hippocampal tissues in the model group were clearly damaged, but the pathological characteristics were significantly improved in the exo group. The exo group also showed an increased SOD level, decreased MDA and ROS levels, and down-regulated TNF-α, IL-1, and Aß1-42 expressions (all P<0.05). MiR-34b-5p had a targeting relationship with both MIAT and CALB1, and MIAT was found to be expressed in exo. The oe-MIAT-exo group and the miR-34b-5p inhibitor group showed significantly up-regulated CALB1, TH, and Bcl-2 protein expressions in the HNCs, increased cell viability, as well as reduced apoptosis, but the si-MIAT-exo group showed the opposite results (all P<0.05). The MiR-34b-5p inhibitor partially reversed the effect on the si-MIAT-exo group. The miR-34b-5p mimic group showed significantly down-regulated CALB1, TH, and Bcl-2 protein expressions in the HNCs, inhibited cell viability, as well as increased apoptosis, but the oe-CALB1 group showed the opposite results (all P<0.05). Oe-CALB1 partially reversed the effect on the miR-34b-5p mimic group. The memory and learning abilities of the rats in the oe-MIAT-exo group and the model + exo group were significantly improved but not as much as they were in the normal rats. CONCLUSION: MIAT-containing exo from HNSCs can improve cognitive disorders in VD rats via the miR-34b-5p/CALB1 axis.

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.

Effect of acupoint catgut embedding in chronic fatigue syndrome patients: A protocol for systematic review and meta-analysis.

BACKGROUND: Chronic fatigue syndrome (CFS) is a relatively complex and disabling illness with a substantial economic burden and functional impairment. Until now, many CFS patients lack appropriate healthcare. Acupoint catgut embedding is an effective and emerging alternative therapy for CFE. With this research, we endeavor to investigate the effect and safety of ACE for CFS. METHODS: Eight databases will be searched from inception to December 2020: PubMed, EMBASE, The Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chong-Qing VIP database, and Wan-fang database. We regard studies as eligible for inclusion if they were RCTs done in CFS patients, compare acupoint catgut embedding to another treatment strategy, and report fatigue changes at the end of the intervention period. Two independent reviewers complete the study selection, data extraction, and the risk of bias assessment. We assess pooled data using a random-effects model through Revman software (v.5.3) and Stata (version 15.0). ETHICS AND DISSEMINATION: Ethics approval is not required because the individual patient data will not be involved, with no privacy concerns. This systematic review and meta-analysis will provide a reference for CFS patients and clinicians on the non-drug interventions. We will publish and disseminate the results of this review in a peer-reviewed journal or relevant conference. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/7SHD9 (https://osf.io/7shd9).

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.

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.

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.

Depression and APOEε4 Status in Individuals with Subjective Cognitive Decline: A Meta-Analysis.

OBJECTIVE: To evaluate the associative role of depression and apolipoprotein E epsilon 4 allele (APOEε4) in subjective cognitive decline (SCD) and its progression to objective cognitive decline. METHODS: After literature search in electronic databases, studies were selected by following precise eligibility criteria. Meta-analyses were performed to examine the role of APOEε4 and depression in SCD or its progression to mild cognitive impairment (MCI) or dementia. RESULTS: APOEε4 positivity was not different between SCD and normal individuals but was significantly higher in individuals with SCD plus than in normal individuals [odds ratio: 2.39 (95% CI: 1.87, 3.05); p<0.00001] and in SCD converters than in non-converters [odds ratio: 5.19 (95% CI: 2.36, 11.42); p<0.00001]. Depression was significantly higher in individuals with SCD [standardized mean difference: 0.63 (0.45, 0.82); p<0.00001] and SCD plus [standardized mean difference: 0.83 (0.43, 1.22); p<0.0001] than in normal individuals. However, depression was not different between SCD and MCI or between SCD converters and non-converters. Age of SCD converters was higher than non-converters [mean difference: 2.95 years (0.58, 5.31)]. CONCLUSION: Whereas APOEε4 positivity was higher in SCD plus and SCD converters, depression was higher in SCD and SCD plus but was not different between SCD and MCI.

Effect of acupuncture versus artificial tears for dry eye disease: A protocol for systematic review and meta-analysis.

BACKGROUND: The global prevalence of dry eye disease (DED) ranged from 5% to 50%, accompanied by the yearly increasing trend and younger onset. To date artificial tear serves as a mainstay therapy for DED management. It is noteworthy that, acupuncture has been accepted for treating DED with a time-honored history in China. However, no systematic review has been updated till now, which is focusing on comparing acupuncture vs. artificial tears for DED management. METHODS: Eight databases will be searched with the language restrictions of English and Chinese from their inception to July 1, 2020. Randomized controlled trials comparing acupuncture versus artificial tears for DED treatment were enrolled. Identification, research inclusion, data extraction and assessment of the risk of bias were conducted independently by 2 or more reviewers. The primary outcomes were Schirmer I test and tear break-up time. We used Review Manager Software (v.5.3) for assessing the risk of bias and all statistical analyses. RESULTS: Based on the evidence obtained, whether the effect of acupuncture was equal to or even better than that of artificial tear therapy in the treatment of DED would be elaborated. CONCLUSION: In summary, this review would provide a relatively convincing conclusion on whether acupuncture deserves to be recommended as an adjunct treatment for DED, so as to propose some significant insights for the doctors handling with DED. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/Z28M6.