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.

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.

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.

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.

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.

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.

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.

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.

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 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.

LncRNA IGFBP4-1 promotes tumor development by activating Janus kinase-signal transducer and activator of transcription pathway in bladder urothelial carcinoma: retraction.

[This retracts the article DOI: 10.7150/ijbs.46986.].

Transcranial Magnetic Stimulation as a Therapy for Migraine: An Overview of Systematic Reviews.

Introduction: This overview of systematic reviews (SRs) systematically collected, evaluated, and combined the evidence for migraine treatment with transcranial magnetic stimulation (TMS). Methods: We conducted a systematic literature search in various databases, such as PubMed, The Cochrane Library, Web of Science, Embase, the China National Knowledge Infrastructure, Wanfang, VIP, and China Biomedical Literature. Two reviewers independently assessed the methodological quality, risk of bias, reporting quality, and strength of evidence of the included studies using AMSTAR-2, ROBIS, the PRISMA checklist, and the GRADE system. Results: We performed an overview of 7 relevant SRs, of which 4 were of moderate quality and 3 were of low quality according to AMSTAR 2. All SRs had low risk of bias in Phase 1 (Assessing relevance), Domain 1 (Study eligibility criteria), and Domain 4 (Synthesis and findings) as evaluated by ROBIS. In Domain 2 (Identification and selection of studies), 4 SRs (57.1%) had low risk of bias, while in Domain 3 (data collection and study appraisal) and Risk of Bias in the Review Phase 3, 4 SRs (57.1%) had low risk of bias. The PRISMA reporting standards were generally comprehensive, but some limitations were observed in the assessments, pooled results, evidence reliability, registration and protocols, and funding sources. The GRADE levels ranged from moderate to low, with 10 outcomes of moderate quality and 6 outcomes of low quality. The main reason for the low quality of evidence was the small sample size and high heterogeneity of the available studies. Conclusion: TMS may improve migraine severity and frequency, but the evidence is limited due to methodological flaws and heterogeneity. Future studies should standardize use, assess side effects, and compare with other treatments.

SFTSV infection is associated with transient overproliferation of monoclonal lambda-type plasma cells.

The impairment of antibody-mediated immunity is a major factor associated with fatal cases of severe fever with thrombocytopenia syndrome (SFTS). By collating the clinical diagnosis reports of 30 SFTS cases, we discovered the overproliferation of monoclonal plasma cells (MCP cells, CD38+cLambda+cKappa-) in bone marrow, which has only been reported previously in multiple myeloma. The ratio of CD38+cLambda+ versus CD38+cKappa+ in SFTS cases with MCP cells was significantly higher than that in normal cases. MCP cells presented transient expression in the bone marrow, which was distinctly different from multiple myeloma. Moreover, the SFTS patients with MCP cells had higher clinical severity. Further, the overproliferation of MCP cells was also observed in SFTS virus (SFTSV)-infected mice with lethal infectious doses. Together, SFTSV infection induces transient overproliferation of monoclonal lambda-type plasma cells, which have important implications for the study of SFTSV pathogenesis, prognosis, and the rational development of therapeutics.

Effect of intraoperative dexmedetomidine on long-term survival in older patients after major noncardiac surgery: 3-year follow-up of a randomized trial.

STUDY OBJECTIVE: To assess the impact of intraoperative dexmedetomidine on long-term outcomes of older patients following major noncardiac surgery mainly for cancer. DESIGN: A long-term follow-up of patients enrolled in a randomized trial. SETTING: The initial trial was performed in a tertiary care hospital in Beijing, China. PARTICIPANTS: Patients aged 60 years or older who were scheduled for major noncardiac surgery. INTERVENTION: Participants were randomized to receive either dexmedetomidine (a loading dose of 0.6 µg/kg over 10 min, followed by a continuous infusion of 0.5 µg/kg/h until 1 h before end of surgery) or placebo during anesthesia. MEASUREMENTS: The primary endpoint was overall survival. Secondary endpoints included recurrence-free survival and event-free survival. Cox proportional hazard models were used to adjust for predefined confounding factors. Propensity score matching was employed for sensitive analysis. RESULTS: Among 620 patients who were randomized in the initial trial, 619 were included in the long-term analysis (mean age 69 years, 40% female, 77% oncological surgery). The median follow-up duration was 42 months (interquartile range 41 to 45). Overall survival did not differ between the two groups: there were 49/309 (15.9%) deaths with dexmedetomidine versus 63/310 (20.3%) with placebo (adjusted hazard ratio [HR] 0.78, 95% CI 0.53-1.13, P = 0.187). Recurrence-free survival was improved with dexmedetomidine (68/309 [22.0%] events with dexmedetomidine versus 98/310 [31.6%] with placebo; adjusted HR 0.67, 95% CI 0.49-0.92, P = 0.012). Event-free survival was also improved with dexmedetomidine (120/309 [38.8%] events with dexmedetomidine versus 145/310 [46.8%] with placebo; adjusted HR 0.78, 95% CI 0.61-1.00, P = 0.047). Results were similar after propensity-score matching and in the subgroup of cancer patients. CONCLUSIONS: In older patients having major noncardiac surgery mainly for cancer, intraoperative dexmedetomidine did not improve overall survival but was associated with improved recurrence-free and event-free survivals.

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.

Isolation and identification of a mesenchymal stem/stromal cell-like population from pediatric urethral tissue.

Mesenchymal stem cells (MSCs) are important seed cells for cell therapy and tissue engineering because of their multidirectional differentiation potential, high proliferative capacity, low immunogenicity, and immunomodulatory ability. In this study, we successfully isolated and cultured a population of mesenchymal stem-like cells from pediatric urethra (PU-MSLCs). The cells had a spindle-shaped fibroblast-like morphology, similar to MSCs derived from other tissues. The PU-MSLCs highly expressed MSC surface markers CD29, CD73, CD90, and CD105 but were negative for leukocyte common antigen CD45, and MHC class II-encoded molecule HLA-DR. After in vitro induction, the PU-MSLCs had the potential to differentiate into adipocytes, osteocytes, and chondrocytes. The PU-MSLCs maintained a normal karyotype and showed no tumorigenicity during long-term cultivation. We thus demonstrated that the mesenchymal stem/stromal cell-like population obtained from pediatric urethra tissue is capable of self-renewal and multidirectional differentiation, has promising application prospects for cell therapy and tissue engineering, and is expected to contribute to urethral tissue reconstruction.

CD73-Positive Small Extracellular Vesicles Derived From Umbilical Cord Mesenchymal Stem Cells Promote the Proliferation and Migration of Pediatric Urethral Smooth Muscle Cells Through Adenosine Pathway.

Smooth muscle cells (SMCs) are the main functional component of urethral tissue, but are difficult to proliferate in vitro. Mesenchymal stem cells (MSCs) and mesenchymal stem cell-derived small extracellular vesicles (MSC-sEV) have been shown to promote tissue repair by regulating the proliferation and migration of different types of cells. In this study, we investigated the effect of umbilical cord mesenchymal stem cell-derived sEV (UCMSC-sEV) on the proliferation and migration of pediatric urethral smooth muscle cells (PUSMCs) and the mechanism by which sEV regulates the function of PUSMCs. We observed that UCMSC-sEV can significantly promote the proliferation and migration of PUSMCs in vitro. UCMSC-sEV exerted proliferation and migration promotion effects by carrying the CD73 to PUSMCs and catalyzing the production of adenosine. Conversely, the effect of UCMSC-sEV on the proliferation and migration of PUSMCs were no longer observed with addition of the PSB12379 as a CD73 inhibitor. It was found that the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway in PUSMCs was activated by adenosine or UCMSC-sEV intervention. In summary, UCMSC-sEV promoted proliferation and migration of PUSMCs in vitro by activating CD73/adenosine signaling axis and downstream PI3K/AKT pathway. Thus, we concluded that UCMSC-sEV may be suggested as a new solution strategy for the urethral tissue repair.

Effectiveness of herb-partitioned moxibustion on the navel for pregnancy outcomes in patients with recurrent implantation failure undergoing in vitro fertilization and embryo transfer: a study protocol for a randomized controlled trial.

BACKGROUND: Recurrent implantation failure (RIF) in the majority of patients undergoing in vitro fertilization and embryo transfer (IVF-ET) is caused by various factors such as maternal age, embryo quality, endometrial receptivity (ER), and immunity. The incidence of RIF is usually between 5 and 10%. Previous studies have shown that herb-partitioned moxibustion on the navel is one of the treatment methods of acupuncture with a positive effect on pregnancy. However, its application in the treatment of RIF has not been reported. Therefore, this study aims to evaluate the effectiveness and safeness of herb-partitioned moxibustion on the navel in improving the outcome of frozen embryo transfer (FET) in patients with RIF. METHODS: This study conducts a randomized controlled trial (RCT). It is planned to recruit 210 patients undergoing RIF for FET from Affiliated Hospital of Shandong University of Traditional Chinese Medicine and randomly divide them into the treatment group and the control group in a ratio of 1:1. The patient of the treatment group will be treated with herb-partitioned moxibustion on the navel once a week for three consecutive menstrual cycles. No intervention will be used in the control group for 3 menstrual cycles. In the fourth menstrual cycle, all patients will undergo artificial cycle to prepare the endometrium for FET. The pregnancy outcomes will be recorded after a 3-month follow-up. Primary outcome will be assessed as the ongoing pregnancy rate compared with the control group. Secondary outcomes include the endometrial type, resistance index (RI), pulsatility index (PI) of the bilateral uterine artery, endometrial blood flow, serum estradiol (E2), progesterone (P), biochemical pregnancy rate, implantation rate, and clinical pregnancy rate. DISCUSSION: If the results show that the herb-partitioned moxibustion on the navel can improve IVF-ET outcomes in patients with RIF, it will be recommended in clinical practice. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) ChiCTR2100043954 . Registered on 8 July 2021.