Potential causal associations between leisure sedentary behaviors, physical activity, sleep traits, and myopia: a Mendelian randomization study.

BACKGROUND: Myopia is the most prevalent refractive error and a growing global health concern that significantly affects visual function. Researchers have recently emphasized considerably on the influence of lifestyle on myopia incidence and development. This study investigates the relationship between leisure sedentary behaviors (LSB)/physical activity (PA)/sleep traits and myopia. METHODS: LSB, PA, and sleep trait-associated genetic variants were used as instrument variables in a Mendelian randomization (MR) study to examine their causal effects on myopia. Summary genome-wide association studies (GWASs) statistical data for LSB and PA were obtained from UK Biobank, and the data of sleep traits was obtained from UK Biobank, UK Biobank and 23andMe, and FinnGen. We used summary statistics data for myopia from MRC IEU. The MR analyses was performed using the inverse variance-weighted (IVW), MR-Egger, weighted median, and MR Pleiotropy RESidual Sum and Outlier methods. RESULTS: Computer use was genetically predicted to increase the myopia risk [IVW odds ratio (OR) = 1.057; 95% confidence interval (CI), 1.038-1.078; P = 7.04 × 10- 9]. The self-reported moderate-to-vigorous physical activity (MVPA) (IVW OR = 0.962; 95% CI, 0.932-0.993; P = 1.57 × 10- 2) and television watching (IVW OR = 0.973; 95% CI, 0.961-0.985, P = 1.93 × 10- 5) were significantly associated with a lower myopia risk. However, genetically predicted sleep traits or accelerometer-measured physical activity had no significant associations with myopia. CONCLUSION: Our results indicated that computer use is a risk factor for myopia, whereas television watching and MVPA may protect against myopia. These findings shed new light on possible strategies for reducing the prevalence of myopia.

Repetitive transcranial magnetic stimulation as a therapy for post-stroke dysphagia: An overview of systematic reviews and meta-analysis.

OBJECTIVE: Post-stroke dysphagia is a common swallowing disorder that occurs after a stroke, leading to an increased risk of aspiration pneumonia and malnutrition. There is a pressing need for effective and safe interventions for its rehabilitation. This review aims to answer two key scientific questions: (1) What is the efficacy of repetitive transcranial magnetic stimulation in the rehabilitation of post-stroke dysphagia? (2) Is repetitive transcranial magnetic stimulation a safe intervention for post-stroke dysphagia? DATA SOURCES: A comprehensive search was conducted across four electronic databases: PubMed, Cochrane Library, Web of Science, and Embase. The search aimed to identify relevant studies concerning our topic of interest and was completed on 28 May 2024. REVIEW METHODS: In accordance with the PRISMA checklist, a comprehensive search of four databases was conducted, which identified 13 relevant systematic reviews. The inclusion criteria were systematic reviews that evaluated the efficacy and safety of repetitive transcranial magnetic stimulation for post-stroke dysphagia. Exclusion criteria were reviews that did not focus on post-stroke dysphagia or did not evaluate repetitive transcranial magnetic stimulation as a therapeutic intervention. The quality, bias, reporting, and overall evidence quality of these reviews were assessed using validated tools, including the AMSTAR 2 tool for assessing the methodological quality of systematic reviews, the ROBIS tool for assessing the risk of bias, and the GRADE approach for evaluating the overall quality of evidence. This rigorous approach ensures that our review provides a comprehensive and reliable overview of the current state of knowledge on the use of repetitive transcranial magnetic stimulation for post-stroke dysphagia. RESULTS: The sample sizes for the individual studies included in the systematic reviews/meta-analyses ranged from 66 to 555. The total number of participants across all studies included in the overall analyses was 752. The evidence was limited by the methodological flaws and heterogeneity of the systematic reviews. The quality of the evidence varied from high to low, with most outcomes having moderate quality. Future research should adopt more rigorous, standardized, and comprehensive designs to confirm the efficacy and safety of repetitive transcranial magnetic stimulation for post-stroke dysphagia. The main reason for downgrading the evidence quality was the small sample size and high heterogeneity of the primary studies. CONCLUSION: This overview synthesized research on repetitive transcranial magnetic stimulation for dysphagia, aiming to inform clinical and policy decisions. However, the current evidence does not conclusively establish the safety and efficacy of repetitive transcranial magnetic stimulation for post-stroke dysphagia rehabilitation. The studies reviewed varied in quality, and many were of poor quality. Therefore, while some studies suggest potential benefits of repetitive transcranial magnetic stimulation, these findings should be interpreted with caution. There is a pressing need for more rigorous, high-quality research to validate the use of repetitive transcranial magnetic stimulation for post-stroke dysphagia rehabilitation. The implications of these findings for clinical practice and policy will be clearer once we have more robust, evidence-based recommendations.

Radiological classification of the Heidelberg triangle and its application in laparoscopic pancreaticoduodenectomy for malignancies.

BACKGROUND: The TRIANGLE operation benefits patients with pancreatic cancer; however, the Heidelberg triangle, where the operation occurs, contains vessels that can impact safety, especially in laparoscopic pancreaticoduodenectomy (LPD) with the TRIANGLE operation. This study aimed to identify Heidelberg triangle vessel types and their implications in pancreaticoduodenectomy (PD). METHODS: Retrospective collection of radiographic data was performed from January 2017 to April 2023. Three-dimensional (3D) CT reconstructions were performed on patients. Vascular types in the Heidelberg triangle were classified based on named vessels crossing its interior. The impact of these types on surgical outcomes and complications in PD with the TRIANGLE operation was assessed. RESULTS: Preoperative CT reconstruction was conducted on 184 pancreatic surgery patients. The findings revealed 99 patients (53.8%) with the type I Heidelberg triangle, lacking named vessels crossing the interior. Type II (n = 85, 46.2%), with named vessels crossing the interior, was identified. Among reconstructed patients who underwent PD with the TRIANGLE operation (n = 103), they were categorized as type I (n = 57) or type II (n = 46). The results showed that LPD patients with type II had significantly higher median intraoperative blood loss (300 mL vs. 200 mL, P = 0.030) and mean examined lymph nodes (17.2 ± 7.6 vs. 13.4 ± 5.2, P = 0.019) compared to those with type I. No significant differences were found in operative time or postoperative complications. CONCLUSION: The presence of named vessels crossing the interior of the Heidelberg triangle was associated with increased intraoperative bleeding during LPD combined with the TRIANGLE operation. Therefore, targeted preoperative planning is required before the operation, thus improving the safety of the TRIANGLE operation in minimally invasive surgery.

Effect of acute pain on the association between preoperative cognitive impairment and postoperative delirium: a secondary analysis of three trials.

BACKGROUND: The association between preoperative cognitive impairment, postoperative pain, and postoperative delirium in older patients after noncardiac surgery is not known. METHODS: This was a secondary analysis of datasets from three previous studies. Patients aged ≥55 yr who underwent elective noncardiac surgery were enrolled. Preoperative cognitive impairment was defined as Mini-Mental State Examination <27. Pain intensity with movement was assessed using an 11-point numeric rating scale at 12-h intervals during the first 72 h after surgery; time-weighted average (TWA) pain score was calculated. Primary outcome was the occurrence of delirium within the first 5 postoperative days. Mediation analysis was used to investigate the relationships between cognitive impairment, pain score, and delirium. RESULTS: A total of 1497 patients were included. Prevalence of preoperative cognitive impairment was 40.3% (603/1497). Patients with cognitive impairment suffered higher TWA pain score within 72 h (4 [3-5] vs 3 [2-5], P=0.004) and more delirium within 5 days (12.9% [78/603] vs 4.9% [44/894], P<0.001) when compared with those without. Total and direct associations between cognitive impairment and delirium were (adjusted ß) 8.3% (95% confidence interval [CI], 4.8-12.0%; P<0.001) and 7.8% (95% CI, 4.4-12.0%; P<0.001), respectively. A significant indirect association with acute pain was observed between cognitive impairment and delirium (adjusted ß=0.4%; 95% CI, 0.1-1.0%; P=0.006), accounting for 4.9% of the total effect. CONCLUSIONS: The association between preoperative cognitive impairment and delirium is significantly mediated by acute pain in patients after noncardiac surgery. Considering the small effect size, clinical significance of this mediation effect requires further investigation.

Comparison of LASSO and random forest models for predicting the risk of premature coronary artery disease.

PURPOSE: With the change of lifestyle, the occurrence of coronary artery disease presents a younger trend, increasing the medical and economic burden on the family and society. To reduce the burden caused by this disease, this study applied LASSO Logistic Regression and Random Forest to establish a risk prediction model for premature coronary artery disease(PCAD) separately and compared the predictive performance of the two models. METHODS: The data are obtained from 1004 patients with coronary artery disease admitted to a third-class hospital in Liaoning Province from September 2019 to December 2021. The data from 797 patients were ultimately evaluated. The dataset of 797 patients was randomly divided into the training set (569 persons) and the validation set (228 persons) scale by 7:3. The risk prediction model was established and compared by LASSO Logistic and Random Forest. RESULT: The two models in this study showed that hyperuricemia, chronic renal disease, carotid artery atherosclerosis were important predictors of premature coronary artery disease. A result of the AUC between the two models showed statistical difference (Z = 3.47, P < 0.05). CONCLUSIONS: Random Forest has better prediction performance for PCAD and is suitable for clinical practice. It can provide an objective reference for the early screening and diagnosis of premature coronary artery disease, guide clinical decision-making and promote disease prevention.

The effect of dexmedetomidine on intraoperative blood glucose homeostasis: secondary analysis of a randomized controlled trial.

PURPOSE: To investigate the effect of dexmedetomidine on intraoperative blood glucose hemostasis in elderly patients undergoing non-cardiac major surgery. METHODS: This was secondary analysis of a randomized controlled trial. Patients in dexmedetomidine group received a loading dose dexmedetomidine (0.6 µg/kg in 10 min before anaesthesia induction) followed by a continuous infusion (0.5 µg/kg/hr) till 1 h before the end of surgery. Patients in control group received volume-matched normal saline at the same time interval. Primary outcome was the incidence of intraoperative hyperglycemia (blood glucose higher than 10 mmol/L). RESULTS: 303 patients in dexmedetomidine group and 306 patients in control group were analysed. The incidence of intraoperative hyperglycemia showed no statistical significance between dexmedetomidine group and control group (27.4% vs. 22.5%, RR = 1.22, 95%CI 0.92-1.60, P = 0.167). Median value of glycemic variation in dexmedetomidine group (2.5, IQR 1.4-3.7, mmol) was slightly lower than that in control group (2.6, IQR 1.5-4.0, mmol), P = 0.034. In multivariable logistic analysis, history of diabetes (OR 3.007, 95%CI 1.826-4.950, P < 0.001), higher baseline blood glucose (OR 1.353, 95%CI 1.174-1.560, P < 0.001) and prolonged surgery time (OR 1.197, 95%CI 1.083-1.324, P < 0.001) were independent risk factors of hyperglycaemia. CONCLUSIONS: Dexmedetomidine presented no effect on intraoperative hyperglycemia in elderly patients undergoing major non-cardiac surgery. TRIAL REGISTRATION: Present study was registered at Chinese Clinical Trial Registry on December 1, 2015 ( www.chictr.org.cn , registration number ChiCTR-IPR-15007654).

Molecular cloning and expression analysis of MyD88 and TRAF6 in Qihe crucian carp Carassius auratus.

Myeloid differentiation factor 88 (MyD88) and tumor necrosis factor receptor-associated factor 6 (TRAF6) are two critical signal transducers in toll-like receptor (TLR) pathway. In the present study, we identified and characterized the homologues of MyD88 and TRAF6 in Qihe crucian carp Carassius auratus, termed as CaMyD88 and CaTRAF6, respectively, and examined their roles during pathogenic infection. Full-length cDNA of CaMyD88 was 2463 bp, including a 191 bp 5'-untranslated region (UTR), a 1417 bp 3'-UTR, and an 855 bp open reading frame (ORF) encoding for a putative protein with 284 amino acids. Full-length cDNA of CaTRAF6 was identified to be 2555 bp, consisting of a 52 bp 5'-UTR, an 871 bp 3'-UTR, and a 1632 bp ORF encoding a protein of 543 amino acids. Deduced amino acid sequences of CaMyD88 and CaTRAF6 contained the typical domains (CaMyD88: death domain and TIR domain; CaTRAF6: one RING-type zinc finger domain, two TRAF-type zinc finger domains, one coiled-coil region, and one conserved C-terminal meprin and TRAF homology domain) as in other fish. Quantitative Real-Time PCR (qRT-PCR) analysis revealed that both CaMyD88 and CaTRAF6 were ubiquitously expressed throughout the development stages and appeared to be developmentally regulated. In addition, CaMyD88 and CaTRAF6 had a broadly distribution of expression in all examined eleven tissues of healthy fish, although the transcript levels varied among the different tissues. Moreover, it was found that mRNA expressions of CaMyD88 and CaTRAF6 were generally up-regulated after stimulation by polyI:C, flagellin, and Aeromonas hydrophila in spite of the down-regulation appeared at some time points or tissues. These results indicated that CaMyD88 and CaTRAF6 play the critical roles in the immune defense of Qihe crucian carp against pathogenic invasion. The present findings will provide the valuable information for understanding the innate immune responses of Qihe crucian carp and contribute to develop the preventive way against pathogens.

Parecoxib Supplementation to Morphine Analgesia Decreases Incidence of Delirium in Elderly Patients After Hip or Knee Replacement Surgery: A Randomized Controlled Trial.

BACKGROUND: Severe pain and high-dose opioids are both associated with increased risk of postoperative delirium. The authors investigated whether parecoxib-supplemented IV morphine analgesia could decrease the incidence of delirium in elderly patients after total hip or knee replacement surgery. METHODS: In a randomized, double-blind, 2-center trial, patients of 60 years or older who underwent elective total hip or knee replacement surgery were assigned in a 1:1 ratio to receive either parecoxib (40 mg at the end of surgery and then every 12 hours for 3 days) or placebo (normal saline). All patients received combined spinal-epidural anesthesia during surgery and IV morphine for postoperative analgesia. The primary outcome was the incidence of delirium within 5 days after surgery. RESULTS: Between January 2011 and May 2013, 620 patients were enrolled and were included in the intention-to-treat and safety analyses. The incidence of delirium was significantly reduced from 11.0% (34/310) with placebo to 6.2% (19/310) with parecoxib (relative risk 0.56, 95% confidence interval 0.33-0.96, P = .031). The severity of pain and the cumulative consumptions of morphine at 24, 48, and 72 hours after surgery were significantly lower with parecoxib than with placebo (all P < .001), although the differences were small. There was no difference in the incidence of postoperative complications between the 2 groups (12.3% [38/310] with placebo versus 11.6% [36/310] with parecoxib; P = .80). CONCLUSIONS: For low-risk elderly patients undergoing elective total hip or knee replacement surgery, multidose parecoxib supplemented to IV morphine decreased the incidence of postoperative delirium without increasing adverse events.

Meta-analysis with trial sequential analysis investigating the impact of adjunctive electroacupuncture therapy on vascular mild cognitive impairment.

BACKGROUND: To systematically collect, evaluate, and synthesize evidence from randomized controlled trials (RCTs) supporting the use of electroacupuncture (EA) as an additional treatment option for Vascular mild cognitive impairment (VaMCI), a meta-analysis was carried out. METHODS: Electronic searches of eight databases were used to locate RCTs that evaluated EA as a VaMCI adjuvant therapy. The Cochrane Risk of bias was used to assess the included trials' methodological quality. Review Manager 5.4 was used to analyze the data. Trial sequential analysis (TSA) was conducted with the trial sequential analysis program. RESULTS: There were 15 RCTs with 1033 subjects in them. Compared to conventional therapy (CT) alone, the Montreal Cognitive Assessment (SMD 0.72, 95 percent CI [0.55, 0.88]), Mini-mental State Examination (SMD 0.73, 95 percent CI [0.60, 0.87]), and activities of daily living (SMD 0.83, 95 percent CI [0.54, 1.12]) were significantly improved while EA was used in conjunction with CT. The current studies exceeded the required information size, according to trial sequential analysis (TSA), demonstrating the reliability of EA adjuvant therapy VaMCI. CONCLUSIONS: According to the pooled data, EA as an adjunct therapy for the treatment of VaMCI increases clinical efficacy. Although the TSA confirms a stable conclusion, it is encouraged to conduct studies of the highest quality standards.

Causal relationship between modifiable risk factors and knee osteoarthritis: a Mendelian randomization study.

Background: While several risk factors for knee osteoarthritis (KOA) have been recognized, the pathogenesis of KOA and the causal relationship between modifiable risk factors and KOA in genetic epidemiology remain unclear. This study aimed to determine the causal relationship between KOA and its risk factors. Methods: Data were obtained from published Genome-Wide Association study (GWAS) databases. A two-sample Mendelian randomization (MR) analysis was performed with genetic variants associated with risk factors as instrumental variables and KOA as outcome. First, inverse variance weighting was used as the main MR analysis method, and then a series of sensitivity analyses were conducted to comprehensively evaluate the causal relationship between them. Results: Univariate forward MR analysis revealed that genetically predicted hypothyroidism, hyperthyroidism/thyrotoxicosis, educational level, income level, metabolic syndrome (MS), essential hypertension, height, hot drink temperature, diet (abstaining from sugar-sweetened or wheat products), and psychological and psychiatric disorders (stress, depression, and anxiety) were causally associated with KOA. Reverse MR exhibits a causal association between KOA and educational attainment. Multivariate MR analysis adjusted for the inclusion of potential mediators, such as body mass index (BMI), smoking, alcohol consumption, and sex, exhibited some variation in causal effects. However, hyperthyroidism/thyrotoxicosis had a significant causal effect on KOA, and there was good evidence that height, hypothyroidism, educational level, psychological and psychiatric disorders (stress, depression, and anxiety), and abstaining from wheat products had an independent causal relationship. The mediating effect of BMI as a mediator was also identified. Conclusion: This study used MR to validate the causal relationship between KOA and its risk factors, providing new insights for preventing and treating KOA in clinical practice and for developing public health policies.

Toxoplasma gondii eIF-5A Modulates the Immune Response of Murine Macrophages In Vitro.

Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan that can elicit a robust immune response during infection. Macrophage cells have been shown to play an important role in the immune response against T. gondii. In our previous study, the eukaryotic translation initiation factor 5A (eIF-5A) gene of T. gondii was found to influence the invasion and replication of tachyzoites. In this study, the recombinant protein of T. gondii eIF-5A (rTgeIF-5A) was incubated with murine macrophages, and the regulatory effect of TgeIF-5A on macrophages was characterized. Immunofluorescence assay showed that TgeIF-5A was able to bind to macrophages and partially be internalized. The Toll-like receptor 4 (TLR4) level and chemotaxis of macrophages stimulated with TgeIF-5A were reduced. However, the phagocytosis and apoptosis of macrophages were amplified by TgeIF-5A. Meanwhile, the cell viability experiment indicated that TgeIF-5A can promote the viability of macrophages, and in the secretion assays, TgeIF-5A can induce the secretion of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and nitric oxide (NO) from macrophages. These findings demonstrate that eIF-5A of T. gondii can modulate the immune response of murine macrophages in vitro, which may provide a reference for further research on developing T. gondii vaccines.

Schwann cells in pancreatic cancer: Unraveling their multifaceted roles in tumorigenesis and neural interactions.

Pancreatic ductal adenocarcinoma (PDAC), characterized by heightened neural density, presents a challenging prognosis primarily due to perineural invasion. Recognized for their crucial roles in neural support and myelination, Schwann cells (SCs) significantly influence the process of tumorigenesis. This review succinctly outlines the interplay between PDAC and neural systems, positioning SCs as a nexus in the tumor-neural interface. Subsequently, it delves into the cellular origin and influencers of SCs within the pancreatic tumor microenvironment, emphasizing their multifaceted roles in tumor initiation, progression, and modulation of the neural and immune microenvironment. The discussion encompasses potential therapeutic interventions targeting SCs. Lastly, the review underscores pressing issues, advocating for sustained exploration into the diverse contributions of SCs within the intricate landscape of PDAC, with the aim of enhancing our understanding of their involvement in this complex malignancy.

Improving Delphi Process in Acupuncture Decision Making: Overall Descriptions and Quality Assessment of Delphi Reports.

Background: Clinical acupuncture decisions are highly operator-dependent and require physician-patient interactions. The Delphi method allows subjective factors such as expert experience and preference of patients to be taken into account in clinical decision making, which is particularly applicable to acupuncture. Currently, the Delphi method is widely used to support clinical decisions in acupuncture. Therefore, it is necessary to provide high-quality and complete descriptions of the Delphi process when making clinical decisions. This study aims to evaluate the quality of the Delphi process in acupuncture, facilitate its standardization and rigor for further clinical decision making in acupuncture. Methods: Articles sourced from six databases were searched systematically to assess the quality of the Delphi consensus process based on the standards for conducting and reporting Delphi studies (CREDES). Descriptive statistics and analysis were presented according to the percentage of each item. Five-score Likert scale was used to evaluate the reporting quality of four domains as well as each item in CREDES by two independent researchers, combined with ICC-value to assess the consistency. Results: A total of 37 qualified articles were included according to eligibility criteria. As for the low reporting rate, the item "External validation" was reported as the lowest positive rate at 32.43% and the item "Prevention of bias" was 48.65%. The item "Adequacy of conclusions", "Definition and attainment of consensus", and "Discussion of limitations" were reported at a positive ratio of 62.16%, 64.86%, and 67.57% individually. The average scores of the four domains based on CREDES from highest to lowest were, respectively, as follows: planning and design (68.75%), reporting (66.07%), rationale for the choice of the Delphi technique (65.54%), study conduct (45.10%). Conclusion: The reporting quality of the Delphi consensus process in acupuncture is acceptable currently, but the reporting rate on some items is still low. Further standardization, including either clearer checklists or study reports, should be developed and strengthened to guide clinical decisions in acupuncture.

The latest research progress: Active components of Traditional Chinese medicine as promising candidates for ovarian cancer therapy.

ETHNOPHARMACOLOGICAL RELEVANCE: Ovarian cancer ranks the first in the mortality of gynecological tumors. Because there are no obvious symptoms in the early stage of ovarian cancer, most patients are in the advanced stage of the disease at the time of diagnosis. The incidence of ovarian cancer is increasing year by year, and the incidence of ovarian cancer has a trend of younger age. In recent years. Traditional Chinese medicine (TCM) has a significant impact on improving the quality of life of cancer patients, reducing drug toxicity, preventing metastasis and recurrence, enhancing the efficacy of radiotherapy and chemotherapy, and prolonging survival time, so patients have benefited a lot. AIM OF THE STUDY: This review summarizes the mechanisms and molecular pathways through which active ingredients of TCM act in ovarian cancer. It explores the advantages of TCM in treating ovarian cancer. This review provides theoretical support for the use of TCM in the treatment of ovarian cancer, offering new perspectives for its clinical prevention and treatment. MATERIALS AND METHODS: This review conducted a literature search on PubMed, Web of Science, Wanfang Database, and China National Knowledge Infrastructure (CNKI) for relevant studies on TCM active ingredients in preventing ovarian cancer. The search terms included "ovarian cancer" combined with "Chinese herbal medicine," "Herbal medicine," "Traditional Chinese medicine," and "Active ingredients of Chinese medicine". Based on existing experimental and clinical research, the paper systematically summarized and analyzed the mechanisms of TCM in treating ovarian cancer. RESULTS: Active ingredients of TCM inhibit the occurrence and development of ovarian cancer through inducing tumor cell apoptosis, inhibiting tumor cell proliferation, suppressing tumor cell migration and invasion, inducing tumor cell autophagy, promoting epithelial-mesenchymal transition, and enhancing the efficacy of radiotherapy and chemotherapy drugs. Chinese medicine provides a comprehensive treatment option for ovarian cancer patients, synergizing with radiotherapy and chemotherapy drugs to enhance treatment effectiveness and introduce new hope and possibilities in clinical therapy. CONCLUSIONS: Active ingredients of TCM can inhibit the occurrence and development of ovarian cancer, but further clinical research is needed to support their application.

Efficacy of tanshinone IIA in rat models with myocardial ischemia-reperfusion injury: a systematic mini-review and meta-analysis.

Background: Myocardial ischemia-reperfusion injury (MIRI) refers to severe damage to the ischemic myocardium following the restoration of blood flow, and it is a major complication of reperfusion therapy for myocardial infarction. Notably, drugs such as metoprolol have been utilized to reduce ischemia-reperfusion injury. Tanshinone IIA is a major constituent extracted from Salvia miltiorrhiza Bunge. Recently, tanshinone IIA has been studied extensively in animal models for controlling MIRI. Therefore, we conducted a meta-analysis on the application of tanshinone IIA in rat models with MIRI to evaluate the therapeutic effects of tanshinone IIA. Methods: A comprehensive search was conducted across PubMed, Web of Science, Embase, the Cochrane Library, the China National Knowledge Infrastructure database, the Wanfang database, and the Chinese Scientific Journal Database to gather studies on tanshinone IIA intervention in rat models with MIRI.We employed SYRCLE's risk of bias tool to assess study quality. The primary outcome indicators were superoxide dismutase (SOD) and malondialdehyde (MDA). Myocardial infarction area was a secondary outcome indicator. This study was registered at PROSPERO (registration number CRD 42022344447). Results: According to the inclusion and exclusion criteria, 15 eligible studies were selected from 295 initially identified studies. In rat models with MIRI, tanshinone IIA significantly increased SOD levels while reducing MDA levels and myocardial infarction area. Moreover, the duration of myocardial ischemia influenced the effectiveness of tanshinone IIA. However, additional high-quality research studies are needed to establish the efficacy and definitive guidelines for the use of tanshinone IIA. Animal studies demonstrated that tanshinone IIA exerted a significant therapeutic effect when the ischemia duration was less than 40 minutes. Tanshinone IIA was found to be more effective when administered via intravenous, intraperitoneal, and intragastric routes at doses above 5 mg/kg. Additionally, treatment with tanshinone IIA at all stages-prior to myocardial ischemia, after ischemia but before reperfusion, prior to ischemia and after reperfusion, and after reperfusion-showed satisfactory results. Conclusions: Tanshinone IIA enhanced SOD activity and reduced MDA levels, thereby ameliorating oxidative stress damage during MIRI. Additionally, it reduced the myocardial infarction area, indicating its effectiveness in mitigating MIRI-induced damage in rats and demonstrating a myocardial protective effect. These findings contribute valuable insights for developing MIRI treatment strategies.

CD73-positive pediatric urethral mesenchymal stem-like cell-derived small extracellular vesicles stimulate angiogenesis.

Introduction: Angiogenesis plays an important role in the repair of urethral injury, and stem cells and their secretomes can promote angiogenesis. We obtained pediatric urethral mesenchymal stem-like cells (PU-MSLCs) in an earlier study. This project studied the pro-angiogenic effect of PU-MSLC-derived small extracellular vesicles (PUMSLC-sEVs) and the underlying mechanisms. Materials and methods: PUMSLCs and PUMSLC-sEVs were cultivated and identified. Then, biological methods such as the ethynyl deoxyuridine (EdU) incorporation assay, Cell Counting Kit-8 (CCK-8) assay, scratch wound assay, Transwell assay, and tube formation assay were used to study the effect of PUMSLC-sEVs on the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). We explored whether the proangiogenic effect of PUMSLC-sEVs is related to CD73 and whether adenosine (ADO, a CD73 metabolite) promoted angiogenesis. GraphPad Prism 8 software was used for data analysis. Results: We observed that PUMSLC-sEVs significantly promoted the proliferation, migration, and tube-forming abilities of HUVECs. PUMSLC-sEVs delivered CD73 molecules to HUVECs to promote angiogenesis. The angiogenic ability of HUVECs was enhanced after treatment with extracellular ADO produced by CD73, and PUMSLC-sEVs further promoted angiogenesis by activating Adenosine Receptor A2A (A2AR). Conclusions: These observations suggest that PUMSLC-sEVs promote angiogenesis, possibly through activation of the CD73/ADO/A2AR signaling axis.

Intraoperative hypotension is associated with decreased long-term survival in older patients after major noncardiac surgery: Secondary analysis of three randomized trials.

STUDY OBJECTIVE: To assess the association of intraoperative hypotension with long-term survivals in older patients after major noncardiac surgery mainly for cancer. DESIGN: A secondary analysis of databases from three randomized trials with long-term follow-up. SETTING: The underlying trials were conducted in 17 tertiary hospitals in China. PATIENTS: Patients aged 60 to 90 years who underwent major noncardiac thoracic or abdominal surgeries (≥ 2 h) in a single center were included in this analysis. EXPOSURES: Restricted cubic spline models were employed to determine the lowest mean arterial pressure (MAP) threshold that was potentially harmful for long-term survivals. Patients were arbitrarily divided into three groups according to the cumulative duration or area under the MAP threshold. The association between intraoperative hypotension exposure and long-term survivals were analyzed with the Cox proportional hazard regression models. MEASUREMENTS: Our primary endpoint was overall survival. Secondary endpoints included recurrence-free and event-free survivals. MAIN RESULTS: A total of 2664 patients (mean age 69.0 years, 34.9% female sex, 92.5% cancer surgery) were included in the final analysis. MAP < 60 mmHg was adopted as the threshold of intraoperative hypotension. Patients were divided into three groups according to duration under MAP < 60 mmHg (<1 min, 1-10 min, and > 10 min) or area under MAP <60 mmHg (< 1 mmHg⋅min, 1-30 mmHg⋅min, and > 30 mmHg⋅min). After adjusting confounders, duration under MAP < 60 mmHg for > 10 min was associated with a shortened overall survival when compared with the < 1 min patients (adjusted hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.09 to 1.57, P = 0.004); area under MAP < 60 mmHg for > 30 mmHg⋅min was associated with a shortened overall survival when compared with the < 1 mmHg⋅min patients (adjusted HR 1.40, 95% CI 1.16 to 1.68, P < 0.001). Similar associations exist between duration under MAP < 60 mmHg for > 10 min or area under MAP < 60 mmHg for > 30 mmHg⋅min and recurrence-free or event-free survivals. CONCLUSIONS: In older patients who underwent major noncardiac surgery mainly for cancer, intraoperative hypotension was associated with worse overall, recurrence-free, and event-free survivals.

TRIANGLE operation, combined with adequate adjuvant chemotherapy, can improve the prognosis of pancreatic head cancer: A retrospective study.

BACKGROUND: The TRIANGLE operation involves the removal of all tissues within the triangle bounded by the portal vein-superior mesenteric vein, celiac axis-common hepatic artery, and superior mesenteric artery to improve patient prognosis. Although previously promising in patients with locally advanced pancreatic ductal adenocarcinoma (PDAC), data are limited regarding the long-term oncological outcomes of the TRIANGLE operation among resectable PDAC patients undergoing pancreaticoduodenectomy (PD). AIM: To evaluate the safety of the TRIANGLE operation during PD and the prognosis in patients with resectable PDAC. METHODS: This retrospective cohort study included patients who underwent PD for pancreatic head cancer between January 2017 and April 2023, with or without the TRIANGLE operation. Patients were divided into the PDTRIANGLE and PDnon-TRIANGLE groups. Surgical and survival outcomes were compared between the two groups. Adequate adjuvant chemotherapy was defined as adjuvant chemotherapy ≥ 6 months. RESULTS: The PDTRIANGLE and PDnon-TRIANGLE groups included 52 and 55 patients, respectively. There were no significant differences in the baseline characteristics or perioperative indexes between the two groups. Furthermore, the recurrence rate was lower in the PDTRIANGLE group than in the PDnon-TRIANGLE group (48.1% vs 81.8%, P < 0.001), and the local recurrence rate of PDAC decreased from 37.8% to 16.0%. Multivariate Cox regression analysis revealed that PDTRIANGLE (HR = 0.424; 95%CI: 0.256-0.702; P = 0.001), adequate adjuvant chemotherapy ≥ 6 months (HR = 0.370; 95%CI: 0.222-0.618; P < 0.001) and margin status (HR = 2.255; 95%CI: 1.252-4.064; P = 0.007) were found to be independent factors for the recurrence rate. CONCLUSION: The TRIANGLE operation is safe for PDAC patients undergoing PD. Moreover, it reduces the local recurrence rate of PDAC and may improve survival in patients who receive adequate adjuvant chemotherapy.

The causal association between thyroid disease and gout: A Mendelian randomization study.

Observational studies have reported some associations between thyroid disease and gout, but the causal relationship between the 2 is not clear. We used Mendelian randomization (MR) Analysis to investigate the causal association between some thyroid diseases (autoimmune hypothyroidism, autoimmune hyperthyroidism, thyroid nodules, and thyroid cancer) and gout. GWAS data were used for analysis. The exposure factors were autoimmune hypothyroidism, autoimmune hyperthyroidism, thyroid nodules and thyroid cancer, and the outcome variables were gout. IVW, MR-Egger, Weighted median and Weighted mode were used for MR analysis. Cochran Q test MR-PRESSO and MR-Egger intercept analysis were used to detect heterogeneity and multi directivity. Autoimmune hypothyroidism has a causal effect on gout, IVW results show (OR = 1.13, 95% CI = 1.03-1.21, PFDR = 0.0336); Autoimmune hyperthyroidism has a causal effect on gout, IVW results show (OR = 1.07, 95% CI = 1.01-1.12, PFDR = 0.0314); Thyroid cancer has no causal effect on gout, IVW results show (OR = 1.03, 95% CI = 0.98-1.09, PFDR = 0.297); Thyroid nodules has no causal effect on gout, IVW results show (OR = 1.03, 95% CI = 0.98-1.08, PFDR = 0.225); Reverse MR Studies show that gout have no causal effect on the above thyroid diseases. Autoimmune hypothyroidism and autoimmune hyperthyroidism increase the risk of gout.

Potential Causal Association between Depression and Oral Diseases: A Mendelian Randomization Study.

BACKGROUND: Globally, oral diseases are common, pose an economic burden, and significantly decline the quality of life of affected individuals. Recently, researchers have substantially highlighted the effect of depression on oral disease incidence and development. In this study, we elucidated the correlation between depression and oral diseases. METHODS: Using two-sample Mendelian randomization (MR), the association between depression and the risk of 17 oral diseases was evaluated. Three methods were used to perform MR analysis: the inverse variance-weighted, weighted median, and MR-Egger methods. Furthermore, Cochran's Q test, MR-Egger intercept test, MR Pleiotropy RESidual Sum and Outlier test, and leave-one-out analysis were performed to analyze sensitivity. RESULTS: After implementing multiple test corrections, we observed that genetic susceptibility to depression was associated with an increased risk of mouth ulcers, toothache, loose teeth, bleeding gums, painful gums, chronic periodontitis, chronic tonsil and adenoid diseases, peritonsillar abscess, and excessive tooth attrition. However, a causal relationship between depression and other oral diseases was not observed. Sensitivity analysis confirmed the robustness of the results. CONCLUSIONS: We confirmed the causal relationship between depression and several oral diseases, thereby providing a novel viewpoint on the prevention and treatment of oral diseases. Our findings suggest the integration of depression control into routine clinical care to enhance the effectiveness of oral disease treatment.