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Methyltransferase-like 3 (METTL3) is the key subunit of methyltransferase complex responsible for catalyzing N6-methyladenosine (m6A) modification on mRNA, which is the most prevalent post-transcriptional modification in eukaryotes. In this study, we utilized online databases to analyze the association between METTL3 expression and various aspects of tumorigenesis, including gene methylation, immunity, and prognosis. Our investigation revealed that METTL3 serves as a prognostic marker and therapeutic target for liver hepatocellular carcinoma (LIHC). Through experimental studies, we observed frequent upregulation of METTL3 in LIHC tumor tissue and cells. Subsequent inhibition of METTL3 using a novel small molecule inhibitor, STM2457, significantly impeded tumor growth in LIHC cell lines, spheroids, and xenograft tumor model. Further, transcriptome and m6A sequencing of xenograft bodies unveiled that inhibition of METTL3-m6A altered genes enriched in SMAD and MAPK signaling pathways that are critical for tumorigenesis. These findings suggest that targeting METTL3 represents a promising therapeutic strategy for LIHC. [ABSTRACT FROM AUTHOR]

Background: Based on previous studies which failed to analyze important confounding variables, the association between preoperative anemia and outcomes of patients who underwent colorectal cancer (CRC) surgery has not been clearly demonstrated. This study aimed to investigate the relationship between preoperative anemia and short-term outcomes in patients with CRC. Methods: Data from a retrospective collective database of patients who underwent CRC surgery at our hospital between September 1, 2019 and September 30, 2021 were retrieved and analyzed, and the short-term postoperative outcomes of anemic (hemoglobin < 120 g dL− 1 for female, hemoglobin < 130 g dL− 1 for male) and non-anemic patients were analyzed, using a 1:1 propensity score matching (PSM) analysis. Results: After excluding some cases, the remaining 1894 patients had complete data available for analysis. The incidence of preoperative anemia was 39.8% (754/1894). Before PSM, preoperative anemia patients had a higher risk of major morbidity than non-anemia patients (27.2% vs. 23.1%, odds ratio [OR] 1.245, 95% confidence interval [CI] 1.008–1.538, P = 0.042). After PSM was performed in the cohort, 609 patients remained in the anemic and non-anemic groups. The incidence of major morbidity (25.8% vs. 24.0%, OR 1.102, 95% CI 0.849–1.429, P = 0.446) between anemic and non-anemic patients was comparable. No significant difference was found between the anemic and non-anemic groups in postoperative length of stay (8.0 [6.0–12.0] vs. 8.0 [7.0–11.0], P = 0.311). The sensitivity analysis results were in accordance with the primary outcome. Furthermore, we did not ascertain any discernible correlation between the extent of anemia and significant major morbidity. Conclusions: Compared with preoperative non-anemia, anemia status does not seem to be associated with major morbidity in patients with CRC surgery. It is noteworthy that, anemia is insufficient as a solitary risk factor and may be a better marker of poor health resulting from multiple factors. Trial registration: Registration Authority: Chinese Clinical Trial Registry; Registration number and date: ChiCTR2100049696, 08/08/2021; Principal investigator: Ting Yan; Link to trial registry: http://www.chictr.org.cn/showproj.aspx?proj=131698;. [ABSTRACT FROM AUTHOR]

Background: This study aimed to examine the treatment and prognosis of patients with type B2 + B3 thymoma and compare it with those patients with type B2 and B3 thymoma. Methods: We conducted a retrospective analysis of the results of 39 patients with type B2 + B3 thymoma, 133 patients with type B2 thymoma, and 64 patients with type B3 thymoma. The Kaplan–Meier technique was used to generate survival curves. For multivariate analysis, the Cox proportional hazard model was applied. Results: With a median follow‐up of 60 months (range: 1–128 months), the percentage of patients with tumor, node, metastasis (TNM) stage III and IV disease gradually increased from 19.5% to 25.6% to 35.9% among those with histological subtypes B2, B2 + B3, and B3, respectively, p = 0.045. Twenty‐three patients experienced recurrence or metastasis. The total 10‐year progression‐free survival (PFS) rates were 86.0% overall (85.0% in type B2, 87.2% in type B2 + B3, and 87.5% in type B3). Age, R0 resection, and Masaoka–Koga stage were found to have a significant on PFS in all patients. There was no statistically significant difference in PFS between different histotypes of thymoma, p = 0.650. PFS was predicted by R0 resection in all histotypes and by the Masaoka–Koga stage in the type B2 subgroup. Conclusion: Combining the two staging methods to guide the diagnosis and treatment of patients with B2 + B3 thymoma is recommended. R0 resection is recommended to reduce recurrence. Patients with B2 + B3 thymoma have a prognosis similar to those with a B2 thymoma or a B3 thymoma alone. [ABSTRACT FROM AUTHOR]

Background: Multiple oral insulin-sensitizing agents, such as metformin, thiazolidinediones, inositols, and berberine, have been proven safe and efficacious in improving the endocrine, metabolic, and reproductive abnormalities seen in polycystic ovary syndrome (PCOS), providing more options for healthcare providers and patients. These oral insulin sensitizers are more convenient, practical, and economic than agents that need to be injected. A comparison of the clinical effectiveness of the four different classes of oral insulin sensitizers in PCOS has not been explored, leading to clinical uncertainty about the optimal treatment pathway. The present study aims to compare the effects of oral insulin sensitizers on endocrine and metabolic profiles in women with PCOS. Methods: We identified randomized controlled trials for PCOS from a variety of databases, published from January 2005 to October 2020. Outcomes included changes in menstrual frequency, improvements in hyperandrogenism and glucolipid metabolism and adverse side effects. A random-effects network meta-analysis was performed. Results: Twenty-two trials comprising 1079 patients with PCOS were included in this study. Compared with metformin, treatment with myo-inositol + d-chiro-inositol was associated with a greater improvement in menstrual frequency (odds ratio 14.70 [95% confidence interval (CI) 2.31–93.58]). Myo-inositol + d-chiro-inositol and metformin + thiazolidinediones combination therapies were superior to respective monotherapies in reducing total testosterone levels. Thiazolidinediones, metformin + thiazolidinediones, and myo-inositol + d-chiro-inositol were associated with a lower insulin resistance index (HOMA-IR) compared with that in metformin alone (mean differences: − 0.72 [95% CI (− 1.11)–(− 0.34)] to − 0.89 [95% CI (− 1.460)–(− 0.32)]). Metformin + thiazolidinediones treatment was associated with lower triglyceride levels compared with that in metformin and thiazolidinediones monotherapy, while thiazolidinediones was superior to metformin in increasing high-density lipoprotein cholesterol and decreasing fasting plasma glucose, triglycerides, low-density lipoprotein cholesterol, and gastrointestinal adverse events. Conclusions: Ours is the first study to report that for women with PCOS, myo-inositol combined with d-chiro-inositol and metformin combined with thiazolidinediones appear superior to metformin alone in improving insulin resistance and decreasing total testosterone. Myo-inositol combined with d-chiro-inositol is particularly efficacious in menstrual recovery. Thiazolidinediones and metformin combined with thiazolidinediones improve lipid metabolism better than metformin alone. Trial registration PROSPERO CRD42020211524 Plain English summary: This study aimed to compare the effects of oral insulin sensitizers on endocrine and metabolic profiles in women with polycystic ovary syndrome (PCOS). A random-effects network meta-analysis including 22 trials was conducted. For women with PCOS, myo-inositol combined with d-chiro-inositol and metformin combined with thiazolidinediones appear superior to metformin alone in improving insulin resistance and decreasing total testosterone level. Myo-inositol combined with d-chiro-inositol is particularly efficacious in menstrual recovery. Thiazolidinediones and metformin combined with thiazolidinediones improve lipid metabolism better than metformin alone. [ABSTRACT FROM AUTHOR]

Background. In Traditional Chinese Medicine (TCM), Dahuang Danshen decoction (DD) is used to treat pancreatic fibrosis. Pancreatic fibrosis is a typical manifestation of chronic pancreatitis (CP), which affects the digestive system. The therapeutic mechanisms of DD in pancreatic fibrosis are unclear. Aim. This study aimed to investigate the regulatory mechanisms of DD on oxidative stress and endoplasmic reticulum stress in CP. Materials and Methods. Experimental rats were intraperitoneally injected with 500 mg/kg BW of diethyldithiocarbamate (DDC) twice a week for six weeks to induce CP. At the same time, DD was administered orally at daily doses of 1.37 g/kg BW, 2.74 g/kg BW, and 5.48 g/kg BW to evaluate its treatment effects on CP. After all treatments, pancreatic tissues were harvested and subjected to H&E staining. Transmission electron microscopy (TEM) was also performed to show the endoplasmic reticulum structure in the pancreatic tissues. Immunohistochemistry was used to detect the α-SMA expression level in the pancreatic tissues. Metabolomics analysis of the serum and proteomics analysis of the pancreatic tissues were performed to reveal the changes of endogenous metabolites and proteins, respectively. Concentrations of GSH, MDA, SOD, ROS, col-1, and col-3 were determined using corresponding kits. The western blotting method was used to determine the protein levels of Keap-1, HO-1, NQO1, Nrf2, GRP, JNK, and caspase 12. The pancreatic mRNA levels of NQO1, GPX1, HO-1, GST-π, GRP, JNK, and caspase 12 were also determined by quantitative PCR. The interactions between TCM components and Keap-1 were investigated by molecular docking modeling. Results. The pathohistological results demonstrated that DD could ameliorate DDC-induced CP in vivo, indicated by reduction of α-SMA, col-1, col-3, TNF-α, and IL-6. DD increased serum levels of GSH and SOD but reduced pancreatic ROS. DD decreased cytoplasmic Keap-1 and increased Nrf2 nuclear localization. Correspondingly, DD increased the expression levels of Nrf2 downstream antioxidant genes NQO1, GPX1, HO-1, and GST-π. DD also decreased ERS hallmarks caspase 12 cleavage and GRP expression. Eventually, DD inhibited PSC activation by reducing JNK phosphorylation and MMK-3/p38 expression. Molecular docking analysis showed that salvianolic acid B and emodin had a good binding affinity toward Keap-1. Conclusions. These results demonstrated that DD could ameliorate the oxidative and endoplasmic reticulum stress through releasing Nrf2 from Keap-1 binding and inducing the downstream antioxidant enzymes. As a result, DD could thwart pancreatic fibrosis by inhibiting PSCs activation, which was induced by OS and ERS through JNK and MMK3/p38 pathways. [ABSTRACT FROM AUTHOR]

Objective The purpose of this study was to review the effects of robot-assisted therapy (RT) for improving poststroke upper extremity motor impairment. Methods The PubMed, Embase, Medline, and Web of Science databases were searched from inception to April 8, 2020. Randomized controlled trials that were conducted to evaluate the effects of RT on upper extremity motor impairment poststroke and that used Fugl-Meyer assessment for upper extremity scores as an outcome were included. Two authors independently screened articles, extracted data, and assessed the methodological quality of the included studies using the Physiotherapy Evidence Database (PEDro) scale. A random-effects meta-analysis was performed to pool the effect sizes across the studies. Results Forty-one randomized controlled trials with 1916 stroke patients were included. Compared with dose-matched conventional rehabilitation, RT significantly improved the Fugl-Meyer assessment for upper extremity scores of the patients with stroke, with a small effect size (Hedges g  = 0.25; 95% CI, 0.11-0.38; I 2 = 45.9%). The subgroup analysis revealed that the effects of unilateral RT, but not that of bilateral RT, were superior to conventional rehabilitation (Hedges g  = 0.32; 95% CI, 0.15-0.50; I 2 = 55.9%). Regarding the type of robot devices, the effects of the end effector device (Hedges g  = 0.22; 95% CI, 0.09–0.36; I 2 = 35.4%), but not the exoskeleton device, were superior to conventional rehabilitation. Regarding the stroke stage, the between-group difference (ie, RT vs convention rehabilitation) was significant only for people with late subacute or chronic stroke (Hedges g  = 0.33; 95% CI, 0.16-0.50; I 2 = 34.2%). Conclusion RT might be superior to conventional rehabilitation in improving upper extremity motor impairment in people after stroke with notable upper extremity hemiplegia and limited potential for spontaneous recovery. [ABSTRACT FROM AUTHOR]

A combination of peppermint oil and caraway oil (POCO) with its unique properties has been shown clinical benefits for FD. However, the potent statistical data to confirm its effects are lacking. This meta-analysis thus aimed at evaluating the efficacy and safety of POCO compared with placebo in treating patients with FD. We searched CENTRAL, PubMed, EMBASE (Ovid), Web of Science, Google Scholar, China National Knowledge Infrastructure database, Wanfang, and VIP databases for randomized clinical trials (RCTs) up to June 2019. Dichotomous data were shown as a risk ratio (RR) with 95% confidence intervals (CIs). All data were analyzed by Review Manager 5.2 software. The search identified 382 citations, and 5 RCTs (578 participants) were included. POCO showed a statistically significant effect in global improvement of FD symptoms (RR for not much or very much improvement 0.59, 95% CI: 0.49 to 0.71, P < 0.00001 , I2 36%, NNT 3) and improvement in epigastric pain (RR 1.61, 95% CI: 1.28 to 2.03, P < 0.0001 , I2 0%, NNT 3). There were no significant differences in the total number of adverse events between POCO and placebo (NNH 40). In conclusion, this is the first meta-analysis to assess the effects of POCO in FD. POCO is an effective and safe short-term treatment for FD. However, current findings are based on smaller sample sizes and low/very low quality of the evidence. More well-designed RCTs with large sample sizes of FD patients are required. [ABSTRACT FROM AUTHOR]

Objective. To systematically assess the effects of yoga on pain, mobility, and quality of life in patients with knee osteoarthritis. Methods. Pubmed, Medline, EMBASE, the Cochrane Central Register of Controlled Trials, Physiotherapy Evidence Database (PEDro), and other sources were searched systematically in this study. Two reviewers identified eligible studies and extracted data independently. Downs and Black’s Quality Index were used to evaluate the methodological quality of the included studies. Results. A total of 9 articles (6 studies) involving 372 patients with knee osteoarthritis met the inclusion criteria. The most common yoga protocol is 40~90 minutes/session, lasting for at least 8 weeks. The effect of yoga on pain relief and function improvement could be seen after two-week intervention. Conclusion. This systematic review showed that yoga might have positive effects in relieving pain and mobility on patients with KOA, but the effects on quality of life (QOL) are unclear. Besides, more outcome measure related to mental health of yoga effects on people with KOA should be conducted. [ABSTRACT FROM AUTHOR]

Objectives: We examine the therapeutic efficacy of extended thymectomy with blood vessel resection and reconstruction in thymic carcinoma patients with great vessel invasion.Methods: In total 26 patients diagnosed as clinical stage III thymic carcinoma with severe great vessel invasion were enrolled in this retrospective study. Among these patients, 14 cases received adjuvant chemo- and radiotherapy (non-operation subgroup, NOG), the other 12 patients received extended thymectomy with vessel resection and reconstruction followed by the adjuvant treatment (operation subgroup, OG).Results: All surgical procedures went smoothly with no perioperative death. R0 resection was obtained in all surgical cases, and we also observed a lymph node metastasis rate of 38.8%. The overall survival (OS) was 34 months for the whole cohort, 48 and 26 months for the OG and NOG respectively (p = 0.013). The median disease metastasis free survival (DMFS) was 47 months for the OG and 18 months for the NOG (p = 0.019).Conclusion: Extended thymectomy with vessel resection is feasible for patients with clinical stage III thymic carcinoma. Surgery significantly improves the overall survival and the prognosis of clinical stage III thymic carcinoma. [ABSTRACT FROM AUTHOR]