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The previous observational studies could not overcome the effects of confounding variables and reverse causality. We aimed to determine whether there is a causal relationship between systemic lupus erythematosus and osteoporosis in East Asian and European populations, respectively, by two-sample Mendelian Randomization analysis. We obtained and downloaded data from publicly available genome-wide association study databases and analyses for East Asian and European populations, including systemic lupus erythematosus (SLE), osteoporosis (OP), multisite bone mineral density (BMD), and OP with fracture. After screening for instrumental single-nucleotide polymorphisms (SNPs) significantly correlated to SLE, the inverse-variance weighted (IVW) method was used for calculating the ratio and 95% confidence interval, besides utilizing MR-Egger, weighted median, and weighted mode to assess the robustness of the primary outcome. Moreover, multiple analyses, including MR-PRESSO, MR-Egger intercept, Cochran's Q test, as well as "leave-one-out" sensitivity, were used for evaluating horizontal pleiotropy, heterogeneity, and stability. Finally, we exchanged exposure and outcome and performed a reverse MR analysis. IVW (OR = 1.05, 95% CI = 1.01–1.09, P = 0.009) indicated a significant positive correlation between genetically predicted SLE and OP in East Asians. Furthermore, neither heterogeneity nor horizontal pleiotropy was observed. In Europe, there was no significant genetically predicted causal relation between SLE and OP. Bi-directional MR analysis showed no reverse causality between SLE and OP. In the East Asian population, genetically predicted SLE may have had a positive causal relationship with OP. In Europe, there is insufficient evidence for a potential causal relation between SLE and OP or BMD and fracture, and the correlations currently observed may be attributed to a variety of confounder variables. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the safety and efficacy of neoadjuvant tislelizumab combined with chemoradiotherapy in patients with resectable esophageal squamous cell cancer. It also investigates the changes in immune markers after treatment. This is an open-label, single-arm, single-institution phase 2 clinical trial. A total of 21 patients with newly diagnosed resectable esophageal cancer (cT1-2N+ / cT3-4aN0-3 M0) received 2 cycles of tislelizumab (200mg every 3 weeks for 2 cycles) concurrent with chemoradiotherapy. Radical esophagectomy was conducted within 4-6 weeks after neoadjuvant therapy. Baseline and pre-surgery PET/CT scans were performed to assess treatment response. Primary endpoints included pathological response rate (pCR) and major pathological response rate (MPR), the secondary endpoints were disease free survival and safety. Exploratory endpoints include molecular imaging research and immunological markers alterations in tumor microenvironment and circulating to further explore the factors affecting the efficacy of neoadjuvant therapy for esophageal cancer. A total of 21 patients were enrolled, and all received neoadjuvant tislelizumab combined with chemoradiotherapy, with 19 patients underwent radical esophagectomy. One patient underwent radical chemoradiotherapy due to lymph node metastases after neoadjuvant therapy. One patient died of pneumonia before surgery. Among 19 patients who underwent surgery, R0 was 100% (19/19),10 achieved pCR (52.6%), and 14 achieved MPR (73.7%). Most of treatment-related adverse event (TRAE) were grade 1-2. Grade ≥3 TRAEs included 1 anemia, 1 leukopenia, 1 neutropenia, 1 liver damage, 1 thrombocytopenia, and 1 elevated cardiac troponin T. A significant reduction in SUVmax of tumor was observed in both pCR and no-pCR patients after treatment. And SUVmax in no-pCR patients tended to be higher than pCR patients. Following neoadjuvant treatment, a significant increase of CD4+ T cells, CD8+ T cells, and memory T cells was observed within the TME. Patients with pCR had significant increase in the infiltration of CD4+ T cells, CD8+ T cells, and CD4+ Tm cells in tumor area. And significant increase in circulating CD4+ T cells, CD4+ effector memory T cells, and M1 macrophages was found after treatment. Moreover, a notably higher presence of CD4+ Tem cells and DC cells is observed in patients achieving pCR. Neoadjuvant tislelizumab combined with chemoradiotherapy for locally advanced ESCC has promising efficacy and good safety and enhances tumor immune infiltration and immunologic memory. [ABSTRACT FROM AUTHOR]

This paper was attempted to investigate the microstructure degradation and low cycle fatigue (LCF) performance of a serviced K465 Ni‐based superalloy turbine blade. LCF tests were carried out with small‐scale plate specimens sampled from the blades. Relationship between residual LCF life and microstructure state was estimated. The results indicate that the coarsening of γ/γ′ phases was the most significant microstructure degradation mode for the serviced blades. Both the γ matrix width and the γ′ precipitate diameter increased with the increase of service duration, while the γ′ precipitate volume fraction slightly decreased. The most severe microstructure degradation occurred at the leading edge along the chord direction, particularly at 50–70 % airfoil spans. The residual LCF life exhibited an accelerated decrease characteristic as increases of microstructure degradation degree. The coarsened microstructure diminished shear resistance of the superalloy, which resulted in additional accumulated inelastic deformation and a corresponding reduction in LCF life. Highlights: Service induced microstructure evolution and LCF life decay of a blade were investigated.Coarsening was identified as the main degradation form of γ/γ' phases in serviced blade.Accelerated decrease of residual LCF life was identified as increases of coarsening.Reduced plastic deformation resistance owing to coarsening is crucial to decay LCF life. [ABSTRACT FROM AUTHOR]

Currently, 68Ga-NOTA TATE is the most studied somatostatin receptor (SSR)- targeted PET imaging agent in neuroblastoma (NB). However, the value of 18F-labeled NOTA TATE remains unclear in children with neuroblastoma. We compared two groups of neuroblastoma patients, one group undergoing 18F-NOTA TATE PET/CT and the other undergoing 18F-FDG PET/CT, to explore the value of predicting short-term outcomes in children. We collected 46 children diagnosed with NB between 2022 and 2023 who underwent 18F-NOTA TATE PET/CT (23 cases) or 18F-FDG PET/CT (23 cases) before receiving treatment at our hospital. The metabolic tumor volume (MTV) was derived from these ROIs using a fixed SUV threshold of ≥40% of SUVmax. The software MIM automatically generated variables including SUVmax, SUVmean, MTV, total lesion SSR (TL-SSR). STL-SSR represents the sum of all soft tissue TL-SSRs. We performed immunohistochemical staining, including NSE, LDH, SSTR2 on the tumor tissue and then performed a semi-quantitative pathological scoring. Imaging evaluation was performed according to the International Neuroblastoma Response Criteria after 4-5 cycles of chemotherapy. Patients with CR or PR were classified as good responders and patients with SD or PD were classified as poor responders. Receiver operating characteristic curve analysis was used to assess the relationships between disease response and PET/CT variables. Correlations between PET variables and associated immunohistochemical markers were assessed using Spearman's rank test. The median age of patients of TATE was 3 (2,4 years and FDG groups was (1,3 years). Out of the TATE patients, 9 were classified as good responders and 14 as poor responders. In contrast, in the FDG group, 14 patients were classified as good responders and 9 as poor responders. Immunohistochemical staining was performed in a total of 15 patients with pathological tissue. In the TATE group, SSTR2 staining was positively correlated with PET/CT uptake variables (SUVmean and SUVmax; both p<0.05). In the FDG group, all variables showed no significant difference with the immunohistochemical staining values (all p <0.05). There were differences in SUVmean and SUVmax between the two groups (p=0.029, p=0.003, respectively). In our cohort, SUVmean of 18F-NOTA TATE PET/CT can predict NB short-term outcome, (area=0.792, p=0.018, 95%CI:0.582∼1.000). All variables of 18F-FDG PET/CT showed no significance in predicting. 18F-NOTA TATE PET/CT could visualize SSTR2 expression in NB compared to18F-FDG PET/CT. Our results suggest that SUVmean of baseline 18F-NOTA TATE PET/CT could predict short-term outcome in children with NB, superior to 18F-FDG PET/CT. [ABSTRACT FROM AUTHOR]