Cholera toxin B subunit(CTB)can enhance antigen presentation and promote T cell pro-liferation,B cell differentiation and B cell isotype conversion.Moreover,woodchuck hepatitis virus post transcriptional regulatory element(WPRE)can enhance gene expression efficiency by optimi-zing RNA polyadenylation,denuclearization and/or translation.In order to construct porcine epi-demic diarrhea virus like particles(VLPs)chimerized with CTB and WPRE and evaluate their im-munogenicity,the G Ⅱ type PEDV S gene,combined with the elements promoting the protein ex-pression and enhancing immune effects,was synthesized by the company and cloned into pET32a(+).Af-ter double enzyme digestion and gel recovery,the gene named as TSCW was cloned into pFastBacl to construct the recombinant plasmid pFastBac-TSCW.pFastBac-TSCW was further transformed into DH10Bac competent cells to obtain recombinant bacmid Bacmid-TSCW.Subsequently,the Bacmid-TSCW was transfected into sf9 cells to obtain recombinant baculovirus BV-TSCW.After co-infection of BV-TSCW and BV-M into sf9 cells,viral like particles VLP-TSCW was obtained and used to immunize mice to evaluate its immunogenicity.The results showed that the recombi-nant plasmid pFastBac-TSCW and bacmid Bacmid-TSCW were successfully constructed.After transfection of sf9 cells with recombinant baculovirus,significant cytopathic effects were observed.PCR and Western blot results showed that the recombinant baculoviruses existed stably in sf9 cells and the target proteins was also expressed stably.In addition,the electron microscopy results showed that BV-TSCW and BV-M successfully assembled into viral like particles VLP-TSCW.Furthermore,ELISA results indicated that VLP-TSCW induced high level specific antibodies.The above results laid the foundation for further optimization,design and development of PEDV VLPs subunit vaccines.

Cholera toxin B subunit(CTB)can enhance antigen presentation and promote T cell pro-liferation,B cell differentiation and B cell isotype conversion.Moreover,woodchuck hepatitis virus post transcriptional regulatory element(WPRE)can enhance gene expression efficiency by optimi-zing RNA polyadenylation,denuclearization and/or translation.In order to construct porcine epi-demic diarrhea virus like particles(VLPs)chimerized with CTB and WPRE and evaluate their im-munogenicity,the G Ⅱ type PEDV S gene,combined with the elements promoting the protein ex-pression and enhancing immune effects,was synthesized by the company and cloned into pET32a(+).Af-ter double enzyme digestion and gel recovery,the gene named as TSCW was cloned into pFastBacl to construct the recombinant plasmid pFastBac-TSCW.pFastBac-TSCW was further transformed into DH10Bac competent cells to obtain recombinant bacmid Bacmid-TSCW.Subsequently,the Bacmid-TSCW was transfected into sf9 cells to obtain recombinant baculovirus BV-TSCW.After co-infection of BV-TSCW and BV-M into sf9 cells,viral like particles VLP-TSCW was obtained and used to immunize mice to evaluate its immunogenicity.The results showed that the recombi-nant plasmid pFastBac-TSCW and bacmid Bacmid-TSCW were successfully constructed.After transfection of sf9 cells with recombinant baculovirus,significant cytopathic effects were observed.PCR and Western blot results showed that the recombinant baculoviruses existed stably in sf9 cells and the target proteins was also expressed stably.In addition,the electron microscopy results showed that BV-TSCW and BV-M successfully assembled into viral like particles VLP-TSCW.Furthermore,ELISA results indicated that VLP-TSCW induced high level specific antibodies.The above results laid the foundation for further optimization,design and development of PEDV VLPs subunit vaccines.

T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain(TIGIT)is a transmembrane glycoprotein expressed on the surface of immune cells.TIGIT expression is up-regulated in blad-der cancer and will have an important impact on bladder cancer development and poor prognosis.Immunotherapy that blocks TIGIT signaling is expected to improve the prognosis of bladder cancer.With further research,TIGIT is likely to become a target for bladder cancer diagnosis and treatment.This article reviews the structure,immuno-modulatory effect and the research progress of TIGIT in bladder cancer.

Recent advancements in the field of medical artificial intelligence (AI) have led to the widespread adoption of foundational and large language models. This review paper explores their applications within medical AI, introducing a novel classification framework that categorizes them as disease-specific, general-domain, and multi-modal models. The paper also addresses key challenges such as data acquisition and augmentation, including issues related to data volume, annotation, multi-modal fusion, and privacy concerns. Additionally, it discusses the evaluation, validation, limitations, and regulation of medical AI models, emphasizing their transformative potential in healthcare. The importance of continuous improvement, data security, standardized evaluations, and collaborative approaches is highlighted to ensure the responsible and effective integration of AI into clinical applications.

Objective: A meta-analysis of locus-based genome-wide association studies recently identified a relationship between AXIN1 and Parkinson’s disease (PD). Few studies of Asian populations, however, have reported such a genetic association. The influences of rs13337493, rs758033, and rs2361988, three PD-associated genetic variants of AXIN1, were investigated in the present study because AXIN1 is related to Wnt/β-catenin signaling. Methods: A total of 2,418 individuals were enrolled in our Taiwanese cohort for analysis of the genotypic and allelic frequency. Polymerase chain reaction–restriction fragment length polymorphism analysis was employed for rs13337493 genotyping, and the Agena MassARRAY platform (Agena Bioscience, San Diego, CA, USA) was used for rs758033 and rs2361988 genotyping in 672 patients with PD and 392 controls. Taiwan Biobank data of another 1,354 healthy controls were subjected to whole-genome sequencing performed using Illumina platforms at approximately 30× average depth. Results: Our results revealed that rs758033 {odds ratios [OR] (95% confidence interval [CI]) = 0.267 [0.064, 0.795], p = 0.014} was associated with the risk of PD, and there was a trend toward a protective effect of rs2361988 (OR [95% CI] = 0.296 [0.071, 0.884], p = 0.026) under the recessive model. The TT genotype of rs758033 (OR [95% CI] = 0.271 [0.065, 0.805], p = 0.015) and the CC genotype of rs2361988 (OR [95% CI] = 0.305 [0.073, 0.913], p = 0.031) were less common in the PD group than in the non-PD group. Conclusion Our findings indicate that the rs758033 and rs2361988 polymorphisms of AXIN1 may affect the risk of PD in the Taiwanese population.

INTRODUCTION: Singapore has the world's second most efficient healthcare system while costing less than 5% GDP. It remains unclear whether transcatheter aortic valve implantation (TAVI) is cost-effective for treating intermediate-low risk severe aortic stenosis (AS) patients in a highly efficient healthcare system. MATERIALS AND METHODS: A two-phase economic model combining decision tree and Markov model was developed to assess the costs, effectiveness, and the incremental cost-effectiveness ratio (ICER) of transfemoral (TF) TAVI versus surgical aortic valve replacement (SAVR) in intermediate-low risk patients over an 8-year time horizon. Mortality and complications rates were based on PARTNER 2 trial cohort A and Singapore life table. Costs were mainly retrieved from Singapore National University Health System database. Health utility data were obtained from Singapore population based on the EuroQol-5D (EQ-5D). A variety of sensitivity analyses were conducted. RESULTS: In base case scenario, the incremental effectiveness of TF-TAVI versus SAVR was 0.19 QALYs. The ICER of TF-TAVI was S$33,833/QALY. When time horizon was reduced to 5 years, the ICER was S$60,825/QALY; when event rates from the propensity analysis was used, the ICER was S$21,732/QALY and S$44,598/QALY over 8-year and 5-year time horizons, respectively. At a willingness to pay threshold of S$73,167/QALY, TF-TAVI had a 98.19% probability of being cost-effective after 100,000 simulations. The model was the most sensitive to the costs of TF-TAVI procedure. CONCLUSION TF-TAVI is a highly cost-effective option compared to SAVR for intermediate-low risk severe AS patients from a Singapore healthcare system perspective. Increased procedure experience, reduction in device cost, and technology advance may have further increased the cost-effectiveness of TF-TAVI per scenario analysis.

Certification ; United States

Accreditation ; Education ; Genetics ; United States

It is largely unknown whether lower urinary tract symptoms (LUTS) or acute retention of urine (AROU) is linked to shorter life expectancy in men. We conducted a multicenter, retrospective database analysis of patients undergoing transurethral resection of prostate (TURP) to study their relationships. Multivariate Cox regression analysis and Kaplan-Meier analysis with stratification to age and indication of TURP were performed. We further performed an age- and sex-matched survival analysis with the general population using data from the Census and Statistics Department of the Hong Kong Special Administrative Region (Hong Kong, China). From January 2002 to December 2012, 3496 patients undergoing TURP were included in our study, with 1764 patients in the LUTS group and 1732 patients in the AROU group. Old age, ischemic heart disease, cerebrovascular accident, and AROU were risk factors of mortality. Patients aged <70 years (adjusted hazard ratio [HR]: 1.52, 95% confidence interval [CI]: 1.11-2.09, P = 0.010) and 70-80 years (adjusted HR: 1.39, 95% CI: 1.15-1.70, P = 0.001) in the AROU group had worse survival than those in the LUTS group, but such difference was not demonstrated in patients aged >80 years. Compared to the general population, younger patients in the LUTS group appeared to have better survival (<70 years, P = 0.091; 70-80 years, P = 0.011), but younger patients in the AROU group had worse survival (<70 years, P = 0.021; 70-80 years, P = 0.003). For patients aged >80 years, survival was similar with the general population in both the LUTS and AROU groups. In conclusion, AROU at young age was associated with mortality, while early detection and management of LUTS may improve survival.
Age Factors ; Aged ; Aged, 80 and over ; Databases, Factual ; Humans ; Kaplan-Meier Estimate ; Lower Urinary Tract Symptoms ; Male ; Middle Aged ; Prostate/surgery* ; Prostatic Hyperplasia/surgery* ; Retrospective Studies ; Risk Factors ; Survival Analysis ; Transurethral Resection of Prostate/methods* ; Urinary Retention/surgery*

BACKGROUND AND OBJECTIVES: Ischemic post-conditioning (PostC) has been demonstrated as a novel strategy to harness nature's protection against myocardial ischemia-reperfusion (I/R). Hypercholesterolemia (HC) has been reported to block the effect of PostC on the heart. Angiotensin II type-1 (AT1) modulators have shown benefits in myocardial ischemia. The present study investigates the effect of a novel inhibitor of AT1, azilsartan in PostC of the heart of normocholesterolemic (NC) and HC rats. MATERIALS AND METHODS: HC was induced by the administration of high-fat diet to the animals for eight weeks. Isolated Langendorff's perfused NC and HC rat hearts were exposed to global ischemia for 30 min and reperfusion for 120 min. I/R-injury had been assessed by cardiac hemodynamic parameters, myocardial infarct size, release of tumor necrosis factor-alpha troponin I, lactate dehydrogenase, creatine kinase, nitrite in coronary effluent, thiobarbituric acid reactive species, a reduced form of glutathione, superoxide anion, and left ventricle collagen content in normal and HC rat hearts. RESULTS: Azilsartan post-treatment and six episodes of PostC (10 sec each) afforded cardioprotection against I/R-injury in normal rat hearts. PostC protection against I/R-injury was abolished in HC rat hearts. Azilsartan prevented the HC-mediated impairment of the beneficial effects of PostC in I/R-induced myocardial injury, which was inhibited by L-N⁵-(1-Iminoethyl)ornithinehydrochloride, a potent inhibitor of endothelial nitric oxide synthase (eNOS). CONCLUSION: Azilsartan treatment has attenuated the HC-induced impairment of beneficial effects of PostC in I/R-injury of rat hearts, by specifically modulating eNOS. Azilsartan may be explored further in I/R-myocardial injury, both in NC and HC conditions, with or without PostC.
Angiotensin II ; Animals ; Collagen ; Creatine Kinase ; Diet, High-Fat ; Glutathione ; Heart ; Heart Ventricles ; Hemodynamics ; Hypercholesterolemia ; Ischemia ; Ischemic Postconditioning* ; L-Lactate Dehydrogenase ; Myocardial Infarction ; Myocardial Ischemia ; Nitric Oxide Synthase Type III ; Rats ; Reperfusion ; Reperfusion Injury ; Superoxides ; Troponin I ; Tumor Necrosis Factor-alpha