Synthesis of Bridged Cycloisoxazoline Scaffolds via Rhodium-Catalyzed Coupling of Nitrones with Cyclic Carbonate.

Bridged isoxazolidines were synthesized via Rh(III)-catalyzed C-H allylation of α-aryl nitrones with 5-methylene-1,3-dioxan-2-one. The nitrone group serves as a directing group and 1,3-dipole in the C-H activation/[3 + 2] cycloaddition cascade, exhibiting excellent chemo- and stereoselectivity along with good functional group compatibility. The resulting skeletal structure was conveniently modified to produce a range of important chemical frameworks, and the protocol was applied to biologically active molecules.

MiR-590-3p Promotes the Phenotypic Switching of Vascular Smooth Muscle Cells by Targeting Lysyl Oxidase.

ABSTRACT: We investigated the clinical characteristics of patients with acute aortic dissection (AAD) and miR-590-3p levels in serum, tissue, and vascular smooth muscle cells. The effect of miR-590-3p on the vascular smooth muscle cell phenotype was assessed, and the regulation of lysyl oxidase by miR-5903p was determined. C57BL/6 mice were used to investigate the incidence of AAD and effects of miR-5903p on AAD. The miR-590-3p levels were measured in the aortae of mice, and hematoxylin and eosin staining and Masson staining were performed to identify the morphological features of the aorta. Comparative analysis revealed significant differences in clinical characteristics between patients with AAD and healthy control subjects, with most patients with AAD exhibiting concomitant hypertension and nearly 50% having atherosclerosis. Lysyl oxidase was a direct target of miR-590-3p. Lysyl oxidase overexpression inhibited switching of the vascular smooth muscle cell phenotype from contractile to synthetic, but miR-590-3p overexpression significantly reversed this change. In the mouse model, miR-590-3p upregulation increased the incidence of AAD to 93.3%, and its incidence decreased to 13.3% after miR-590-3p inhibition. Hematoxylin and eosin and Masson staining revealed that the miR-590-3p agomiR group had a greater loss of the contractile phenotype in the dissected aortic wall and an increased number of muscle fibers in the aortic wall, which contributed to thickening of the aortic wall and the formation of a false lumen in aortic dissection. miR-590-3p might be pivotal in the pathogenesis of AAD. Thus, targeting miR-590-3p or its downstream pathways could represent a therapeutic approach for AAD.

Construction and validation of a clinical differentiation model between peripheral lung cancer and solitary pulmonary tuberculosis.

OBJECTIVE: To establish and validate a clinical model for differentiating peripheral lung cancer (PLC) from solitary pulmonary tuberculosis (SP-TB) based on clinical and imaging features. MATERIALS AND METHODS: Retrospectively, 183 patients (100 PLC, 83 SP-TB) in our hospital were randomly divided into a training group and an internal validation group (ratio 7:3), and 100 patients (50 PLC, 50 SP-TB) in Sichuan Provincial People's Hospital were identified as an external validation group. The collected qualitative and quantitative variables were used to determine the independent feature variables for distinguishing between PLC and SP-TB through univariate logistic regression, multivariate logistic regression. Then, traditional logistic regression models and machine learning algorithm models (decision tree, random forest, xgboost, support vector machine, k-nearest neighbors, light gradient boosting machine) were established using the independent feature variables. The model with the highest AUC value in the internal validation group was used for subsequent analysis. The receiver operating characteristic curve (ROC), calibration curve, and decision curves analysis (DCA) were used to assess the model's discrimination, calibration, and clinical usefulness. RESULT: Age, smoking history, maximum diameter of lesion, lobulation, spiculation, calcification, and vascular convergence sign were independent characteristic variables to differentiate PLC from SP-TB. The logistic regression model had the highest AUC value of 0.878 for the internal validation group, based on which a quantitative visualization nomogram was constructed to discriminate the two diseases. The area under the ROC curve (AUC) of the model in the training, internal validation, and external validation groups were 0.915 (95 % CI: 0.866-0.965), 0.878 (95 % CI: 0.784-0.971), and 0.912 (95 % CI: 0.855-0.969), respectively, and the calibration curves fitted well. Decision curves analysis (DCA) confirmed the good clinical benefit of the model. CONCLUSION: The model constructed based on clinical and imaging features can accurately differentiate between PLC and SP-TB, providing potential value for developing reasonable clinical plans.

Performance of next-generation sequencing for diagnosis of blood infections by Klebsiella pneumoniae.

Objective: Klebsiella pneumoniae (Kp) bloodstream infections (BSI) can be a life-threatening opportunistic infection. We aimed to evaluate the diagnostic accuracy of metagenomic next-generation sequencing (mNGS) for Kp BSI. Methods: We retrospectively analyzed 72 patients suspected with bloodstream infection and mNGS Kp positive in peripheral blood, who were hospitalized in our hospital from January 2022 to January 2023. Clinical data and laboratory parameters were collected. All patients had blood drawn and other samples for blood mNGS, blood cultures (BC) and other cultures (OC). The accuracy of mNGS results was analyzed according to infection site, clinical indicators, therapeutic effect and routine culture results. The detection of pathogenic microorganisms by blood mNGS and routine culture was compared. Results: Among 72 infection patients, 29 cases (40.28%) were BC positive, 43 cases (59.72%) were other culture (OC) positive, 16 cases (22.22%) were both BC and OC positive, 56 cases were positive for both mNGS and routine culture. Among the 56 double-positive cases, mNGS and conventional cultures were completely consistent in 27 cases, partially consistent in 15 cases, and completely inconsistent in 14 cases. Using the clinical diagnosis as the reference standard, There were 51 cases consistent with the results of mNGS with Kp BSI, the clinical consistency was 70.83% (51/72). The coincidence rate of mNGS and clinical diagnosis was higher than that of BC (54.17%, 39/72), indicating a statistically significant difference between the two methods (P<0.01). Conclusions: Current evidence indicates that mNGS exhibits excellent accuracy for the diagnosis of Kp BSI. Although it cannot replace blood culture detection technology, it can be used as a supplement to provide stronger diagnostic capabilities for BSI and optimize treatment.

Effectiveness of virtual reality in cardiac rehabilitation: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Cardiovascular disease has risen sharply and causes more premature deaths than cancer, while it represents a major economic burden for healthcare systems and impacts patients' quality of life negatively. Virtual reality has captured the attention of researchers in the field of cardiac rehabilitation. However, the efficacy of virtual reality among individuals undergoing cardiac rehabilitation remains inconclusive. OBJECTIVE: To appraise research evidence on the effects of virtual reality for individuals undergoing cardiac rehabilitation. DESIGN: Systematic review and meta-analysis. METHODS: A systematic search of publications was conducted using Pubmed, Embase, Web of science, Cumulative Index to Nursing and Allied Health Literature database (CINAHL), Cochrane Central Register of Controlled trials and Physiotherapy Evidence Database (PEDro) from inception to 15 May 2022, without language restriction. The Cochrane Risk of Bias Tool was used to examine the methodological quality of the included randomized controlled studies. When feasible, a meta-analysis was performed to calculate the pooled effects using Review Manager (Version 5.4). Otherwise, narrative summaries were performed. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of the evidence. RESULTS: A total of ten studies were included. Virtual reality probably increases exercise capacity for individuals undergoing cardiac rehabilitation (the pooled mean difference 49.55, 95% confidence interval 30.59 ~ 68.52, P < 0.00001, moderate-certainty evidence) and might result in a reduction in emotional tension (mean difference -6.43, 95% confidence interval -9.02 ~ -3.84, P < 0.00001, low-certainty evidence) and intrapsychic stress (mean difference -4.25, 95% confidence interval -6.83 to -1.67, P = 0.001, low-certainty evidence). It also seemed to have a positive effect on quality of life, although meta-analysis could not be conducted to pool the results. Virtual reality might reduce depression (standardised mean difference -0.48, 95% confidence interval -0.84 ~ -0.12, P = 0.009,very low- certainty evidence), but the evidence was uncertain, with similar results of anxiety, general level of stress, external stress, total cholesterol, and low-density lipoprotein. The evidence was uncertain about the effect of virtual reality on high-density lipoprotein (mean difference -1.79, 95% confidence interval -8.96 ~ 5.38, P = 0.62, very low-certainty evidence), with similar results of triglycerides and BMI. CONCLUSIONS: Individuals undergoing cardiac rehabilitation may benefit from virtual reality since it can improve exercise capacity and psychological outcomes. More large, and well-designed studies with tailored virtual reality intervention are warranted to confirm the effects of virtual reality on individuals undergoing cardiac rehabilitation. TWEETABLE ABSTRACT: Virtual reality may benefit individuals undergoing cardiac rehabilitation since it can improve exercise capacity and psychological outcomes.