Moxibustion Regulates the BRG1/Nrf2/HO-1 Pathway by Inhibiting MicroRNA-222-3p to Prevent Oxidative Stress in Intestinal Epithelial Cells in Ulcerative Colitis and Colitis-Associated Colorectal Cancer.

Oxidative stress is crucial in ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC). Intestinal epithelial cells (IECs) are an important component of the intestinal barrier. In previous studies, we have demonstrated that suppressing microRNA-222-3p (miR-222-3p) can protect against oxidative stress in IECs, which ameliorates colonic injuries in UC mice and prevents the conversion of UC to CAC. In this case, we hope to explore whether moxibustion can alleviate UC and CAC by inhibiting miR-222-3p based on mouse models of UC and CAC. After herb-partitioned moxibustion (HPM) intervention, the disease activity index (DAI) and colon macroscopic damage index (CMDI) were significantly reduced in UC mice, and the number and volume of intestinal tumors were decreased considerably in CAC mice. Meanwhile, we found that HPM suppressed miR-222-3p expression and upregulated the mRNA and protein expression of Brahma-related gene 1 (BRG1), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), while inhibiting Kelch-like ECH-associated protein 1 (Keap1) expression in IECs of UC and CAC mice. With changes in reactive oxygen species (ROS), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and inflammatory cytokines interleukin (IL)-1ß and tumor necrosis factor (TNF)-α), we verified that HPM protects against oxidative stress and inflammation in IECs of UC and CAC mice. The effect of HPM was inhibited in miR-222-3p overexpression mice, further demonstrating that the protective effect of HPM on UC and CAC mice was through inhibiting miR-222-3p. In summary, HPM regulates the BRG1/Nrf2/HO-1 pathway by inhibiting miR-222-3p to attenuate oxidative stress in IECs in UC and CAC.

Electroacupuncture for mild-to-moderate dry eye: study protocol for a multicentre, randomised, single-blind, sham-controlled trial.

INTRODUCTION: Dry eye (DE) is a multifactorial ocular surface disease causing considerable medical, social and financial implications. Currently, there is no recognised long-term, effective treatment to alleviate DE. Clinical evidence shows that electroacupuncture (EA) can improve DE symptoms, tear secretion and tear film stability, but it remains controversial whether it is just a placebo effect. We aim to provide solid clinical evidence for the EA treatment of DE. METHODS AND ANALYSIS: This is a multicentre, randomised, sham-controlled trial. A total of 168 patients with DE will be enrolled and randomly assigned to EA or sham EA groups to receive 4-week consecutive treatments and follow-up for 24 weeks. The primary outcome is the change in the non-invasive tear break-up time (NIBUT) from baseline to week 4. The secondary outcomes include tear meniscus height, the Schirmer I test, corneal and conjunctival sensation, the ocular surface disease index, corneal fluorescein staining, the numerical rating scale and the Chinese DE-related quality of life scale. ETHICS AND DISSEMINATION: The trial protocol and informed consent were approved by the Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine (identifier: 2021-119), Shanghai Eye Disease Prevention and Treatment Center (identifier: 2022SQ003) and Eye and ENT Hospital of Fudan University (identifier: 2022014). TRIAL REGISTRATION NUMBER: NCT05552820.

Prevalence of dry eye during the COVID-19 pandemic: A systematic review and meta-analysis.

OBJECTIVE: During the COVID-19 pandemic, many people devoted longer time to screen viewing due to the need for study, work, and online social activities, instead of outdoor activities, which may have led to an increase in dry eye symptoms. This study aimed to evaluate the prevalence of dry eye during the COVID-19 pandemic. METHODS: PubMed, Cochrane Library, Embase, and Web of Science were searched from January 1, 2020 to October 20, 2022. Cross-sectional surveys on dry eye prevalence conducted after January 1, 2020 were included. Two review authors independently performed data extraction and assessed study quality. The random-effects model was used to analyze the prevalence of dry eye, and the odds ratio was used to assess the strength of the association between variables. Subgroup analysis was performed to detect heterogeneity, the leave-one-out method for sensitivity analysis, and the Egger test for publication bias. RESULTS: A total of eleven studies with 15692 individuals met the eligibility criteria. The prevalence of dry eye during the COVID-19 pandemic was 61.0% (95%CI: 51.8%-70.2%) globally and 56.7% (95%CI: 45.3%-68.1%) in Asia. The prevalence of dry eye had significant differences in sex and visual display time, with higher prevalence among females and visual display time of more than 4 hours per day. Subgroup analysis was performed based on diagnostic tools, study population, and average age. A significant difference was found in diagnostic tools, but no significant change in heterogeneity (P<0.05). The leave-one-out method showed stable results, and the Egger test identified no significant publication bias. CONCLUSION: The prevalence of dry eye during the COVID-19 pandemic is significantly higher than before, and a higher prevalence is found among females and those having a visual display time of more than 4 hours per day.

Sedative-sparing effect of acupuncture in gastrointestinal endoscopy: systematic review and meta-analysis.

Objective: This study aimed to perform a systematic review and meta-analysis to identify the efficacy of acupuncture therapy (including manual acupuncture and electroacupuncture) performed before or during gastrointestinal endoscopy with propofol as the main sedative, compared with placebo, sham acupuncture, or no additional treatment other than the same sedation. Methods: A systematic search was performed through PubMed, Embase, Web of Science, Cochrane Library, Chinese Biomedical Databases (CBM), Wanfang database, China National Knowledge Infrastructure (CNKI), SinoMed, and Chinese Scientific Journal Database (VIP) to collect randomized controlled trials published before 5 November 2022. Bias assessment of the included RCTs was performed according to Version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2). Stata16.0 software was used to perform statistical analysis, sensitivity analysis, and publication bias analysis. The primary outcome was sedative consumption, and the secondary outcomes included the incidence of adverse events and wake-up time. Results: A total of 10 studies with 1331 participants were included. The results showed that sedative consumption [mean difference (MD) = -29.32, 95% CI (-36.13, -22.50), P < 0.001], wake-up time [MD = -3.87, 95% CI (-5.43, -2.31), P < 0.001] and the incidence of adverse events including hypotension, nausea and vomiting, and coughing (P < 0.05) were significantly lower in the intervention group than in the control group. Conclusion: Acupuncture combined with sedation reduces sedative consumption and wake-up time compared with sedation alone in gastrointestinal endoscopy; this combined approach allows patients to regain consciousness more quickly after examination and lower the risk of adverse effects. However, with the limited quantity and quality of relevant clinical studies, caution must be applied until more high-quality clinical studies verify and refine the conclusions. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?, identifier: CRD42022370422.

Suppression of microRNA-222-3p ameliorates ulcerative colitis and colitis-associated colorectal cancer to protect against oxidative stress via targeting BRG1 to activate Nrf2/HO-1 signaling pathway.

Oxidative stress is an important pathogenic factor in ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC), further impairing the entire colon. Intestinal epithelial cells (IECs) are crucial components of innate immunity and play an important role in maintaining intestinal barrier function. Recent studies have indicated that microRNA-222-3p (miR-222-3p) is increased in colon of UC and colorectal cancer (CRC) patients, and miR-222-3p is a crucial regulator of oxidative stress. However, whether miR-222-3p influences IEC oxidative stress in UC and CAC remains unknown. This study investigated the effect of miR-222-3p on the regulation of IEC oxidative stress in UC and CAC. An in vitro inflammation model was established in NCM460 colonic cells, mouse UC and CAC models were established in vivo, and IECs were isolated. The biological role and mechanism of miR-222-3p-mediated oxidative stress in UC and CAC were determined. We demonstrated that miR-222-3p expression was notably increased in dextran sulfate sodium (DSS)-induced NCM460 cells and IECs from UC and CAC mice. In vitro, these results showed that the downregulation of miR-222-3p reduced oxidative stress, caspase-3 activity, IL-1ß and TNF-α in DSS-induced NCM460 cells. We further identified BRG1 as the target gene of miR-222-3p, and downregulating miR-222-3p alleviated DSS-induced oxidative injury via promoting BRG1-mediated activation Nrf2/HO-1 signaling in NCM460 cells. The in vivo results demonstrated that inhibiting miR-222-3p in IECs significantly relieved oxidative stress and inflammation in the damaged colons of UC and CAC mice, as evidenced by decreases in ROS, MDA, IL-1ß and TNF-α levels and increases in GSH-Px levels. Our study further demonstrated that inhibiting miR-222-3p in IECs attenuated oxidative damage by targeting BRG1 to activate the Nrf2/HO-1 signaling. In summary, inhibiting miR-222-3p in IECs attenuates oxidative stress by targeting BRG1 to activate the Nrf2/HO-1 signaling, thereby reducing colonic inflammation and tumorigenesis.

Effects of electroacupuncture on dry eye: A pilot randomized controlled trial.

PURPOSE: The purpose of the study was to assess the efficacy of electroacupuncture on dry eye (DE). METHODS: Eighty-four DE patients were randomly assigned to receive electroacupuncture (EAG) three times a week or 0.1% sodium hyaluronate artificial tears (ATG) four times per day for 4 weeks. The primary outcomes were non-invasive tear film breakup time (NIBUT) and tear meniscus height (TMH). The secondary outcomes included the ocular surface disease index (OSDI), Schirmer I test (SIT), corneal sodium fluorescein staining (CFS) score, corneal topography descriptors surface asymmetry index (SAI) and surface regularity index (SRI), corneal sensitivity, 36-item Short-form Health Survey (SF-36) score and Hospital Anxiety and Depression Scale (HADS) score. All outcomes were assessed at Week 0 (baseline), Week 4 (after-treatment) and Week 8 (follow-up). RESULTS: Between-group comparisons showed significant differences in the changes in NIBUT (Week 4, p = 0.003; Week 8, p = 0.008), TMH (Week 4, p = 0.014; Week 8, p = 0.009), OSDI (Week 4, p = 0.029; Week 8, p = 0.022), CFS score (Week 8, p = 0.036) and SF-36 role-physical score (Week 4, p = 0.010), favouring EAG. Mean changes in SIT, SAI, SRI, corneal sensitivity and HADS scores were statistically equal between the two groups (all p > 0.05). Treatment with electroacupuncture was well-tolerated and showed minimal adverse events. CONCLUSIONS: Compared with artificial tears, electroacupuncture shows superior efficacy in improving tear film stability and symptoms of DE.

The efficacy of acupuncture with Lingguibafa acupoint selection in the treatment of insomnia: A PRISMA-compliant meta-analysis.

BACKGROUND: As a major public health problem, insomnia has garnered much attention. Acupuncture, with dialectical acupoint selection (DAS), has been proved to be effective for insomnia, but there is no evidence of evidence-based medicine to prove the efficacy of Lingguibafa acupoint selection (LAS) for insomnia. This study is to evaluate the clinical efficacy of acupuncture with LAS in patient with insomnia. METHODS: The PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, Weipu Database for Chinese Technical Periodicals, Chinese Biomedical Database, and Wanfang Database were systematically searched from the inception dates to December 18, 2021. Randomized controlled trials of acupuncture with LAS versus acupuncture with DAS or acupuncture with LAS plus DAS versus acupuncture with DAS in patient with insomnia were included. Two review authors independently performed the data extraction and assessed study quality. A meta-analysis was performed using random-effects models to calculate relative risk and weighted mean difference for categorical and continuous variables, respectively. The primary efficacy outcome was improvement on Pittsburgh Sleep Quality Index (PSQI). Secondary outcomes included insomnia severity index, Epworth sleepiness scale, Hamilton anxiety scale, Hamilton Depression Scale (HAMD), and total effective rate. RESULTS: A total of 7 trials with 468 patients fulfilled the selection criteria. The pooled results indicated that acupuncture with LAS plus DAS could reduce PSQI score by 2.08 (1.60 after excluding heterogeneity) compared to acupuncture with DAS. Acupuncture with LAS plus DAS had high reliability in sleep quality, sleep latency, sleep time and daytime function, but showed no significant effect on sleep disorder and hypnotic drug. For total effective rate, acupuncture with LAS plus DAS or acupuncture with LAS was better than acupuncture with DAS, but the conclusion was less credible. CONCLUSION: Acupuncture with LAS is significantly associated with improvements in several sleep parameters, primarily evident on the PSQI score. Nevertheless, considering the poor methodological quality, trials employing appropriate randomization concealment and blinding based on a larger sample size are needed in the future.

LncRNA-miRNA-mRNA Network Analysis Reveals the Potential Biomarkers in Crohn's Disease Rats Treated with Herb-Partitioned Moxibustion.

Background: Long noncoding RNA (lncRNA) is receiving growing attention in Crohn's disease (CD). However, the mechanism by which herb-partitioned moxibustion (HPM) regulates the expression and functions of lncRNAs in CD rats is still unclear. The aim of our study is to identify lncRNA-miRNA-mRNA network potential biological functions in CD. Methods: RNA sequencing and microRNA (miRNA) sequencing were carried out to analyze lncRNA, miRNA and mRNA expression profiles among the CD rats, normal control rats, and CD rats after HPM treatment and constructed the potential related lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) networks. Then, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, protein-protein interaction (PPI) analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to explore potentially important genes in ceRNA networks. Results: A total of 189 lncRNAs, 32 miRNAs and 463 mRNAs were determined as differentially expressed (DE) genes in CD rats compared to normal control rats, and 161 lncRNAs, 12 miRNAs and 130 mRNAs were identified as remarkably DE genes in CD rats after HPM treatment compared to CD rats. GO analysis indicated that the target genes were most enriched in cAMP and in KEGG pathway analysis the main pathways included adipocytokine, PPAR, AMPK, FoxO and PI3K-Akt signaling pathway. Finally, qRT-PCR results confirmed that lncRNA LOC102550026 sponged miRNA-34c-5p to regulate the intestinal immune inflammatory response by targeting Pck1. Conclusion: By constructing a ceRNA network with lncRNA-miRNA-mRNA, PCR verification, and KEGG analysis, we revealed that LOC102550026/miRNA-34c-5p/Pck1 axis and adipocytokine, PPAR, AMPK, FoxO, and PI3K-Akt signaling pathways might regulate the intestinal immune-inflammatory response, and HPM may regulate the lncRNA LOC102550026/miR-34c-5p/Pck1 axis and adipocytokine, PPAR, AMPK, FoxO, and PI3K-Akt signaling pathways, thus improving intestinal inflammation in CD. These findings may be novel potential targets in CD.