Cement and zeolite stabilization/solidification of heavy metal-contaminated sediments: 841-Day leaching characteristics, mechanisms, and microstructure.

The long-term effectiveness of stabilized/solidified sediments (S/S sediments) is increasingly attracting attention. This study investigated the long-term leaching characteristics and mechanisms of S/S sediment through an 841-day tank leaching test, considering the influence of cement content, curing time, and zeolite. The results indicate significant correlations among pH, heavy metals, TN, NH3-N, and COD. The specimens with 6 % cement cured for 30 days (C6(30)) demonstrated considerable heavy metal stabilization, with stabilization rates for Cr, Ni, Cu, Zn, As, and Pb reaching 99.81 %, 99.06 %, 98.93 %, 99.61 %, 97.58 %, and 99.97 %, respectively. Compared to C6(30), partial replacement of cement with 10 % zeolite (C5 + Z0.5(30)) not only more effectively stabilized heavy metals except As, but also reduced the release of COD and NH3-N by 4.23 % and 10.04 %, respectively. However, there was a risk of TN, NH3-N, and COD exceeding permissible limits during long-term leaching. Microscopic analysis results suggested that hydration products and low porosity contributed to stabilization of heavy metals. Leaching mechanisms was revealed that surface wash-off controls the leaching of Cr and Pb, while diffusion controls the leaching of Ni, Cu, Zn, As, COD, TN, and NH3-N. Considering stabilization performance, cost and carbon emissions, C5 + Z0.5(30) is an effective strategy for reducing long-term environmental risks of S/S sediments.

Mid-term outcomes of different treatments of internal iliac artery in endovascular aneurysm repair.

OBJECTIVE: To evaluate the mid-term outcomes of different treatment strategies for the internal iliac artery (IIA) during EVAR. METHODS: This was a retrospective study. All patients undergoing EVAR, who required treatment of at least one side of IIA from January 2013 to July 2022 in a single center, were included. According to the different treatment strategies for IIA, the patients were divided into UP (unilateral preservation), BP (bilateral preservation) and BE (bilateral embolization) groups. The primary outcomes included buttock claudication, bowel ischemia and iliac-related reintervention. Then patients who underwent IIA reconstruction were divided into IPG (iliac parallel stent graft) and IBG (iliac branch stent graft) groups according to the reconstruction technique. The primary outcomes included endoleak, iliac branch occlusion and iliac-related reintervention. RESULTS: A total of 237 patients were included, including 167 in the UP group, 9 in the BP group and 61 in the BE group. The mean follow-up time was 39.0 ± 27.7, 50.0 ± 22.1 and 25.8 ± 18.9 months in UP, BP and BE groups, respectively. Thirty cases (12.7%) of buttock claudication occurred, and it was significantly higher in the BE group than the UP group (26.2% vs. 7.8%, p < 0.001). There were no significant differences in the other follow-up outcomes among three groups. The K-M analysis indicated that the patients in the BE group had a lower survival rate than those in the other two groups (p = 0.024). 24 patients underwent IIA reconstruction, including 8 in the IPG group and 16 in the IBG group. The endoleak in the IBG group was significantly lower than that in the IPG group (0% vs. 25.0%, p = 0.041). The iliac-related reintervention, iliac occlusion and mortality were similar between the two groups. CONCLUSION: Overall it is beneficial for patients to preserve at least one side of IIA during EVAR as much as possible. Compared with IPG, IBG might be more applicable for IIA reconstruction.

Rare case of spontaneous duodeno-colic fistula.

A 48-year-old woman presented to the outpatient clinic with a 4-month history of alternating diarrhea and constipation with bloating. Physical examination revealed a body mass index of 22.89 kg/m², normal development, and no tenderness or rebound tenderness in the abdomen. The patient has maintained a stable body size since birth, with a previously healthy status and no history of abdominal surgery or trauma. Endoscopic examination revealed an abnormal channel between the posterior wall of the duodenal bulb to the hepatic flexure of the colon. The patient was managed with conservative treatment, including acid suppression and modulation of the gut microbiota, and was closely monitored. Surgical intervention would only be considered in the event of severe symptoms or complications. Over a five-month follow-up period, the patient's symptoms improved.

Stent Graft-Induced High Wall Stress Promoted Aortic Wall Failure and Aortic Wall Injurious Complications After TEVAR: A Study of Numerical Simulation and Bioinformatics Analysis Based on Pig Models.

OBJECTIVES: Stent graft-related aortic injury is a major complication after thoracic endovascular aortic repair (TEVAR) and seriously affects patient prognosis. However, the distribution characteristics of aortic wall stress under the action of stent grafts and the mechanism of abnormal wall stress leading to aortic wall injury and adverse remodeling were unclear. The aim of this study was to explore the potential mechanisms of high wall stress on the structural and functional alterations of the aortic wall by combining animal experiments, numerical simulations, and bioinformatics. METHODS: We observed stent graft-induced aortic injury by performing fenestrated TEVAR in 6 pigs, and quantitatively analyzed and visualized the stress distribution of the aortic wall under the stent graft through numerical simulation. Hematoxylin and eosin (HE) staining, Masson's trichrome staining, Verhoeff's Van Gieson (EVG) staining, and immunostaining were used to evaluate pathological changes in the aorta. Based on the numerical simulation results, the corresponding high-stress and low-stress regions of the aortic wall were subjected to bulk-RNA sequencing, and hub genes were identified by bioinformatics analysis. RESULTS: Stent grafts were successfully implanted in 5 pigs. In all computational models, we found that obvious deformation and characteristic maximum stress concentration occurred on the side of the greater curve of the aortic arch in contact with the stent graft tip, and the high wall stress concentration areas were highly consistent with the obvious pathological injury area. Subsequent pathological analysis revealed that high wall stress-induced confusion and fragmentation of elastic fibers, collagen deposition, loss and phenotypic switching of vascular smooth muscle cells, and increased inflammatory responses. Gene expression profiles of the aortic wall under different wall stress conditions were described for the first time, and the hub genes (TGFB1, CDH5, DCN, ITGA5, ITGB3, and WT1) that may be involved in regulating the aortic injury and remodeling process in response to high wall stress stimulation were identified. CONCLUSIONS: This study revealed a panoramic view of stent graft-associated high wall stress-induced aortic wall injury through technical approaches of multiple dimensions. Understanding these biomechanical features and hub genes is pivotal for advancing our comprehension of the complications associated with aortic injury after TEVAR and facilitating the development of future therapeutic interventions. CLINICAL IMPACT: This study revealed a panoramic view of stent graft-associated high wall stress-induced aortic wall injury through technical approaches of multiple dimensions. The biomechanical distribution characteristics of the aortic wall, the secondary pathological injury and the alteration of gene expression profile under the action of stent graft were comprehensively revealed by animal experiments for the first time. This will advance clinicians' comprehension of complications associated with aortic injury after TEVAR, provide a new biomechanical perspective for the rational preoperative planning of TEVAR and the management of postoperative complications, and facilitate the development of future therapeutic interventions and stent graft device designs.

Neoadjuvant everolimus in renal angiomyolipoma with or without tuberous sclerosis complex: Results from a multicenter, retrospective study.

OBJECTIVES: To assess the efficacy and safety of preoperative neoadjuvant everolimus in renal angiomyolipomas (AML) patients with or without Tuberous Sclerosis Complex (TSC). MATERIALS AND METHODS: This multi-institutional retrospective study enrolled renal AML patients who underwent partial nephrectomy (PN) or total nephrectomy after receiving at least 1 month of pre-operative everolimus. Imaging evaluations were collected before and after treatment, along with demographic, surgical, and follow-up information. The primary outcome was tumor volume reduction of ≥25%, with additional outcomes including recurrence, perioperative outcomes, renal function, and safety. RESULTS: From January 2015 to July 2022, 68 renal AML patients were studied-41 with TSC and 27 without. During everolimus treatment, 61.0% (25/41) of TSC patients and 44.4% (12/27) of non-TSC patients achieved tumor reduction of ≥25%. Additionally, 41.5% (17/41) of TSC patients and 18.5% (5/27) of non-TSC patients achieved a ≥ 50% reduction. Three TSC patients and 1 non-TSC patient discontinued treatment due to side-effects. Most patients (92.7% TSC, 85.2% non-TSC) underwent PN. After everolimus treatment, the necessary total nephrectomy decreased to 41.2% (7/17) from baseline. Postoperatively, 1 grade 3 and 3 grade 2 complications occurred, with no grade 4 or 5 complications. After a median follow-up of 24 months, only 1 TSC patient recurred with a diameter >3 cm. Retrospective nature is the major limitation of this study. CONCLUSION: Everolimus was effective and well-tolerated in neoadjuvant treatment for renal AML, especially in TSC patients. This neoadjuvant combination strategy of everolimus and PN could effectively controls recurrence and preserves renal function.

Predictors for thoracic aortic growth in patients with type B aortic dissection after thoracic endovascular aortic repair.

OBJECTIVE: To identify independent predictors of thoracic aortic growth in patients with type B aortic dissection (TBAD) undergoing thoracic endovascular aortic repair (TEVAR). METHODS: A retrospective analysis of the patients undergoing TEVAR for TBAD or intramural hematoma (IMH) from April 2014 to April 2023 was performed. The baseline morphological data of TBAD was established through computed tomography angiography (CTA) before discharge. Patients were divided into two groups based on aortic growth: growth and no growth. Aortic growth defined as an increase ≥5 mm in thoracic maximal aortic diameter during any serial follow-up CTA measurement. Logistic regression following propensity score matching (PSM) was used to identify independent predictors for aortic growth. Receiver operating characteristic curve and cutoff value of independent predictors were calculated. Linear regression was used to establish a correlation between anatomical variables and follow-up aortic diameter. RESULTS: A total of 145 patients with TBAD (n = 122) or IMH (n = 23) undergoing TEVAR were included, with a male of 83.4% and a mean age of 56 ± 14.1 years. Patients in growth group and no growth group was 26 (17.9%) and 119 (80.1%), respectively. After using PSM method, matched regression analysis showed residual maximal tear diameter (OR = 0.889, 95% CI 0.830-0.952, p = 0.001) and follow-up aortic diameter (OR = 0.977, 95% CI 0.965-0.989, p < 0.001) were independent predictors for aortic growth. The cutoff value was 8.55 mm for residual tear diameter and 40.65 mm for follow-up maximal aortic diameter. The residual maximal tear diameter showed a linear correlation with follow-up aortic diameter (DW = 1.74, R2 = 6.2%, p = 0.033). CONCLUSIONS: This study suggested that residual maximal tear diameter >8.55 mm and follow-up aortic diameter >40.65 mm could predict aortic growth in patients with TBAD undergoing TEVAR.

Low expression of selenoprotein S induces oxidative damage in cartilages.

Low levels of the indispensable trace element selenium (Se) can cause oxidative stress and disrupt environmental homeostasis in humans and animals. Selenoprotein S (Selenos), of which Se is a key component, is a member of the selenoprotein family involved in various biological processes. This study aimed to investigate whether low-level SELENOS gene expression can induce oxidative stress and decrease the antioxidative capacity of chondrocytes. Compared with control cells, SELENOS-knockdown ATDC5 cells showed substantially higher dihydroethidium, reactive oxygen species and malondialdehyde levels, and lower superoxide dismutase (SOD) expression. Knockout of the gene in C57BL/6 mice increased the 8-hydroxy-2-deoxyguanosine level considerably and decreased SOD expression in cartilages relative to the levels in wild-type mice. The results showed that the increased nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling mediated by low-level SELENOS expression was involved in oxidative damage. The proliferative zone of the cartilage growth plate of SELENOS-knockout mice was shortened, suggesting cartilage differentiation dysfunction. In conclusion, this study confirmed that low-level Selenos expression plays a role in oxidative stress in cartilages.

Diaphragm dysfunction is found in patients with chronic painful temporomandibular disorder: A case-control study.

Aim: To determine whether patients with chronic painful temporomandibular disorder (TMD) had abnormal diaphragm function compared to healthy controls and to explore the correlation between diaphragm contractility, psychological status, and pain characteristics. Methods: A single-blinded, case-control study was conducted involving 23 chronic painful TMD patients and 22 healthy volunteers. The examination and diagnosis were performed according to the Diagnostic Criteria for Temporomandibular Disorders, and questionnaires were used to evaluate pain, depression, anxiety, and physical symptoms status. B-mode ultrasound was used to measure diaphragm thickness and contractility. The sonographer responsible for measuring the diaphragm was blinded to group membership. Results: 1. Depression, anxiety, and physical symptoms scores were significantly higher in the patients than in the controls (p < 0.05). 2. The Interference Score of pain was significantly correlated with depression and physical symptoms (p < 0.01). 3. Bilateral diaphragm contractility was significantly smaller in the patients than in the controls (right: P = 0.003; left: P = 0.001). 3. There was no correlation between diaphragm contractility on the left and right sides in the patients (r = -0.112, P = 0.611), while there was a positive correlation in the control group (r = 0.638, P = 0.001). 4. No correlation was found between the degree of diaphragm contractility, psychological status, and pain scores. Conclusions: 1. Patients with chronic painful TMD have worse psychological status, including depression, anxiety, and physical symptoms. 2. Patients with chronic painful TMD have a smaller degree of bilateral diaphragm contractility and more significant left-right incongruity, which indicated that diaphragm dysfunction may be correlated with chronic painful temporomandibular disorder.

Serum and Urine Metabolic Fingerprints Characterize Renal Cell Carcinoma for Classification, Early Diagnosis, and Prognosis.

Renal cell carcinoma (RCC) is a substantial pathology of the urinary system with a growing prevalence rate. However, current clinical methods have limitations for managing RCC due to the heterogeneity manifestations of the disease. Metabolic analyses are regarded as a preferred noninvasive approach in clinics, which can substantially benefit the characterization of RCC. This study constructs a nanoparticle-enhanced laser desorption ionization mass spectrometry (NELDI MS) to analyze metabolic fingerprints of renal tumors (n = 456) and healthy controls (n = 200). The classification models yielded the areas under curves (AUC) of 0.938 (95% confidence interval (CI), 0.884-0.967) for distinguishing renal tumors from healthy controls, 0.850 for differentiating malignant from benign tumors (95% CI, 0.821-0.915), and 0.925-0.932 for classifying subtypes of RCC (95% CI, 0.821-0.915). For the early stage of RCC subtypes, the averaged diagnostic sensitivity of 90.5% and specificity of 91.3% in the test set is achieved. Metabolic biomarkers are identified as the potential indicator for subtype diagnosis (p < 0.05). To validate the prognostic performance, a predictive model for RCC participants and achieve the prediction of disease (p = 0.003) is constructed. The study provides a promising prospect for applying metabolic analytical tools for RCC characterization.

Neoadjuvant toripalimab combined with axitinib in patients with locally advanced clear cell renal cell carcinoma: a single-arm, phase II trial.

BACKGROUND: A combination of axitinib and immune checkpoint inhibitors (ICIs) demonstrated promising efficacy in the treatment of advanced renal cell carcinoma (RCC). This study aims to prospectively evaluate the safety, efficacy, and biomarkers of neoadjuvant toripalimab plus axitinib in non-metastatic clear cell RCC. METHODS: This is a single-institution, single-arm phase II clinical trial. Patients with non-metastatic biopsy-proven clear cell RCC (T2-T3N0-1M0) are enrolled. Patients will receive axitinib 5 mg twice daily combined with toripalimab 240 mg every 3 weeks (three cycles) for up to 12 weeks. Patients then will receive partial (PN) or radical nephrectomy (RN) after neoadjuvant therapy. The primary endpoint is objective response rate (ORR). Secondary endpoints include disease-free survival, safety, and perioperative complication rate. Predictive biomarkers are involved in exploratory analysis. RESULTS: A total of 20 patients were enrolled in the study, with 19 of them undergoing surgery. One patient declined surgery. The primary endpoint ORR was 45%. The posterior distribution of πORR had a mean of 0.44 (95% credible intervals: 0.24-0.64), meeting the predefined primary endpoint with an ORR of 32%. Tumor shrinkage was observed in 95% of patients prior to nephrectomy. Furthermore, four patients achieved a pathological complete response. Grade ≥3 adverse events occurred in 25% of patients, including hypertension, hyperglycemia, glutamic pyruvic transaminase/glutamic oxaloacetic transaminase (ALT/AST) increase, and proteinuria. Postoperatively, one grade 4a and eight grade 1-2 complications were noted. In comparison to patients with stable disease, responders exhibited significant differences in immune factors such as Arginase 1(ARG1), Melanoma antigen (MAGEs), Dendritic Cell (DC), TNF Superfamily Member 13 (TNFSF13), Apelin Receptor (APLNR), and C-C Motif Chemokine Ligand 3 Like 1 (CCL3-L1). The limitation of this trial was the small sample size. CONCLUSION: Neoadjuvant toripalimab combined with axitinib shows encouraging activity and acceptable toxicity in locally advanced clear cell RCC and warrants further study. TRIAL REGISTRATION NUMBER: clinicaltrials.gov, NCT04118855.

Expert-Based Narrative Review on Contemporary Use of an Off-The-Shelf Multibranched Endograft for Endovascular Treatment of Thoracoabdominal Aortic Aneurysms: Device Design, Anatomical Suitability, Technical Tips, Perioperative Care, Clinical Applications, and Real-World Experience.

Advanced endovascular techniques, such as fenestrated stent grafts, are nowadays available that permit minimally invasive treatment of complex abdominal aortic aneurysms. However, thoracoabdominal aortic aneurysm patients have anatomic limitations to fenestrated stent-grafts given a large lumen, that is, the gap between the endograft and the inner aortic wall. This has led to the development of branched endovascular aneurysm repair as the ideal option for such patients. The Zenith t-Branch multibranched endograft (Cook Medical, Bloomington, IN), which has been commercially available in Europe to treat thoracoabdominal aortic aneurysm since June 2012, represents a feasible off-the-shelf alternative for treatment of such pathologies, especially in the urgent setting, for patients who cannot wait the time required for manufacturing and delivery of custom-made endografts. The device's anatomical suitability should be considered, especially for female patients with smaller iliofemoral vessels. Several tips may help deal with particularly complex scenarios (such as, for instance, in case of narrow inner aortic lumens or when treating patients with failure of prior endovascular aneurysm repair), and a broad array of techniques and devices must be available to ensure technical and clinical success. Despite promising early outcomes, concerns remain particularly regarding the risk for spinal cord ischemia and further assessment of long-term durability is needed, including the rate of target vessel instability and need for secondary interventions. As the published evidence mainly comes from retrospective registries, it is likely that reported outcomes may suffer from an intrinsic bias as most procedures reported to date have been carried out at high-volume aortic centers. Nonetheless, with the never-ceasing adoption of new and refined techniques, outcomes are expected to ameliorate.

Mendelian randomization evidence based on European ancestry for the causal effects of leukocyte telomere length on prostate cancer.

BACKGROUND: Several lines of evidence suggest that leukocyte telomere length (LTL) can affect the development of prostate cancer (PC). METHODS: Here, we employed single nucleoside polymorphisms (SNPs) as instrumental variables (IVs) for LTL (n = 472,174) and conducted Mendelian randomization analysis to estimate their causal impact on PCs (79,148 patients/61,106 controls and 6311 patients/88,902 controls). RESULTS: Every 1-s.d extension of LTL increased the risk of PCs by 34%. Additionally, the analysis of candidate mediators between LTL and PCs via two-step Mendelian randomization revealed that among the 23 candidates, Alzheimer's disease, liver iron content, sex hormone binding global levels, naive CD4-CD8-T cell% T cell, and circulating leptin levels played substantial mediating roles. There is no robust evidence to support the reverse causal relationship between LTL and the selected mediators of PCs. Adjusting for the former four mediators, rather than adjusting for circulating leptin levels, decreased the impact of LTL on PCs. CONCLUSION: This study provides potential intervention measures for preventing LTL-induced PCs.

Evaluation of the impact of prospective payment systems on cholecystectomy: A systematic review and meta-analysis.

This systematic review and meta-analysis aimed to evaluate the impact of prospective payment systems (PPSs) on cholecystectomy. A comprehensive literature review was conducted, examining studies published until December 2023. The review process focused on identifying research across major databases that reported critical outcomes such as length of stay (LOS), mortality, complications, admissions, readmissions, and costs following PPS for cholecystectomy. The studies were specifically selected for their relevance to the impact of PPS or the transition from fee-for-service (FFS) to PPS. The study analyzed six papers, with three eligible for meta-analysis, to assess the impact of the shift from FFS to PPS in laparoscopic and open cholecystectomy procedures. Our findings indicated no significant changes in LOS and mortality rates following the transition from FFS to PPS. Complication rates varied and were influenced by the diagnosis-related group categorization and surgeon cost profiles under episode-based payment. There was a slight increase in admissions and readmissions, and mixed effects on hospital costs and financial margins, suggesting varied responses to PPS for cholecystectomy procedures. The impact of PPS on cholecystectomy is nuanced and varies across different aspects of healthcare delivery. Our findings indicate a need for adaptable, patient-centered PPS models that balance economic efficiency with high-quality patient care. The study emphasizes the importance of considering specific surgical procedures and patient demographics in healthcare payment reforms.

Calcium saccharate/DUSP6 suppresses renal cell carcinoma glycolytic metabolism and boosts sunitinib efficacy via the ERK-AKT pathway.

Current therapeutic options for renal cell carcinoma (RCC) are very limited, which is largely due to inadequate comprehension of molecular pathological mechanisms as well as RCC's resistance to chemotherapy. Dual-specificity phosphatase 6 (DUSP6) has been associated with numerous human diseases. However, its role in RCC is not well understood. Here, we show that diminished DUSP6 expression is linked to RCC progression and unfavorable prognosis. Mechanistically, DUSP6 serves as a tumor suppressor in RCC by intervening the TAF10 and BSCL2 via the ERK-AKT pathway. Further, DUSP6 is also transcriptionally regulated by HNF-4a. Moreover, docking experiments have indicated that DUSP6 expression is enhanced when bound by Calcium saccharate, which also inhibits RCC cell proliferation, metabolic rewiring, and sunitinib resistance. In conclusion, our study identifies Calcium saccharate as a prospective pharmacological therapeutic approach for RCC.

Effects of various living-low and training-high modes with distinct training prescriptions on sea-level performance: A network meta-analysis.

This study aimed to separately compare and rank the effect of various living-low and training-high (LLTH) modes on aerobic and anaerobic performances in athletes, focusing on training intensity, modality, and volume, through network meta-analysis. We systematically searched PubMed, Web of Science, Embase, EBSCO, and Cochrane from their inception date to June 30, 2023. Based on the hypoxic training modality and the intensity and duration of work intervals, LLTH was divided into intermittent hypoxic exposure, continuous hypoxic training, repeated sprint training in hypoxia (RSH; work interval: 5-10 s and rest interval: approximately 30 s), interval sprint training in hypoxia (ISH; work interval: 15-30 s), short-duration high-intensity interval training (s-IHT; short work interval: 1-2 min), long-duration high-intensity interval training (l-IHT; long work interval: > 5 min), and continuous and interval training under hypoxia. A meta-analysis was conducted to determine the standardized mean differences (SMDs) among the effects of various hypoxic interventions on aerobic and anaerobic performances. From 2,072 originally identified titles, 56 studies were included in the analysis. The pooled data from 53 studies showed that only l-IHT (SMDs: 0.78 [95% credible interval; CrI, 0.52-1.05]) and RSH (SMDs: 0.30 [95% CrI, 0.10-0.50]) compared with normoxic training effectively improved athletes' aerobic performance. Furthermore, the pooled data from 29 studies revealed that active intermittent hypoxic training compared with normoxic training can effectively improve anaerobic performance, with SMDs ranging from 0.97 (95% CrI, 0.12-1.81) for l-IHT to 0.32 (95% CrI, 0.05-0.59) for RSH. When adopting a program for LLTH, sufficient duration and work intensity intervals are key to achieving optimal improvements in athletes' overall performance, regardless of the potential improvement in aerobic or anaerobic performance. Nevertheless, it is essential to acknowledge that this study incorporated merely one study on the improvement of anaerobic performance by l-IHT, undermining the credibility of the results. Accordingly, more related studies are needed in the future to provide evidence-based support. It seems difficult to achieve beneficial adaptive changes in performance with intermittent passive hypoxic exposure and continuous low-intensity hypoxic training.

Fumarate induces LncRNA-MIR4435-2HG to regulate glutamine metabolism remodeling and promote the development of FH-deficient renal cell carcinoma.

Fumarate hydratase (FH) deficient renal cell carcinoma (RCC) is a type of tumor with definite metabolic disorder, but the mechanism of metabolic remodeling is still unclear. LncRNA was reported to closely correlate with cancer metabolism, however the biological role of LncRNA in the development of progression of FH-deficent RCC was not well studied either. FH-deficient RCC samples were collected in my hospital and used for RNA-sequencing and Mass spectrometry analysis. FH-deficient RCC cell line UOK262 and control pFH cells were used for in vitro experiments, including proliferation assay, transwell assay, western-blot, mass spectrometry and so on. PDX mouse model was used for further drug inhibition experiments in vivo. In this study, we analyzed the profiles of LncRNA and mRNA in FH-deficienct RCC samples, and we found that the LncRNA-MIR4435-2GH was specifically highly expressed in FH-deficient RCC compared with ccRCC. In vitro experiments demonstrated that MIR4435-2HG was regulated by Fumarate through histone demethylation, and the deletion of this gene could inhibit glutamine metabolism. RNA-pulldown experiments showed that MIR4435-2HG specifically binds to STAT1, which can transcriptionally activate GLS1. GLS1 inhibitor CB-839 could significantly suppress tumor growth in PDX tumor models. This study analyzed the molecular mechanism of MIR4435-2HG in regulating metabolic remodeling of FH-deficient RCC in clinical samples, cells and animal models by combining transcriptional and metabolic methods. We found that that GLS1 was a therapeutic target for this tumor, and MIR4435-2HG can be used as a drug sensitivity marker.

Midterm Outcomes of Multicenter Castor Single-Branch Stent Graft Use in the Treatment of Thoracic Aortic Diseases.

PURPOSE: The aim of this study was to evaluate the midterm efficacy and safety of a single-branch Castor stent graft in the treatment of thoracic aortic disease. MATERIALS AND METHODS: Clinical data of 106 patients with thoracic aortic disease treated with Castor single-branch stent graft at 3 centers were collected between May 2018 and June 2023. The indicators included technical success, stent-related complication, reintervention, retrograde dissection, endoleak, distal stent graft-induced entry (dSINE), branch patency, and mortality. The outcomes of the Castor stent graft for multibranch reconstruction above the arch was also analyzed. RESULTS: The technical success was 98.1% (104/106), while the surgical success was 93.4% (99/106). The reintervention was 2.8% (3/106), consisting of a case of retrograde type A dissection, an endoleak, and a dSINE. The retrograde dissection was 1.9% (2/106), while type I endoleak was 1.9% (2/106). The new dSINE was 2.8% (3/106), and the branch patency rate was 100%. The mortality was 1.9% (2/106). The mean follow-up time was 29.1±17.7 months. The 2-year post-surgery cumulative survival rate was 91.0%±3.1%, while the cumulative branch patency rate was 96.2%±2.2%. In addition, the cumulative freedom from stent-related reintervention rate was 93.2%±2.8%. A comparison showed no significant difference in the stent-related complication, branch patency, endoleak, reintervention, and mortality when the proximal end of the Castor stent graft was anchored to zones 1 or 2 of the aorta. CONCLUSION: Castor single-branch stent graft showed favorable early and midterm outcomes in the treatment of thoracic aortic disease. In addition, it was feasible to combine Castor stent graft with other advanced techniques for multibranch aortic arch reconstruction. CLINICAL IMPACT: The Castor single-branch stent graft was approval by the Chinese Food and Drug Administration in 2017. However, there were few studies on the mid-term outcomes for thoracic aortic disease after launching, which mainly focused on small single-center retrospective study. In the study, we assessed the mid-term outcomes of Castor stent graft through multi-center cases, Castor stent graft combined with other advanced techniques (such as fenestration and hybrid) for multi-branch reconstruction of aortic arch were also conducted. We found Castor single-branch stent graft showed favorable early and mid-term outcomes in the treatment of thoracic aortic disease. Additionally, it was feasible to combine Castor stent graft with other advanced technique for multi-branch aortic arch reconstruction. As an off-the-shelf branched stent graft with a wide range of models, it could be also used in most emergent situation. The Castor stent graft was expected to become more widely used in the future.

Extracellular vesicles related gene HSPH1 exerts anti-tumor effects in prostate cancer via promoting the stress response of CD8 + T cells.

BACKGROUND: T cell stress response state (TSTR), as a novel immune concept previous studies have proposed, has not yet been explored in prostate cancer (PC). As a type of cellular efflux, exosomes play important roles in the occurrence and development of PC. METHOD: Here, we conducted a combined analysis on extracellular vesicle related genes (EVRGs) in PC using data from single-cell RNA (scRNA), spatial transcriptome (ST), and bulk RNA sequencing. RESULT: Preliminary findings have revealed that heat shock protein family H (Hsp110) member 1 (HSPH1) possesses two identities, one being EVRGs and the other being a member of the heat shock protein family involved in TSTR, which may promote the differentiation of conventional T cells towards Th1 or Th2 cells through the pathway of IL2-MYC-IL2RA, thereby promoting the increase of CD8 + T cells in the tumor area, especially in the invasive zone, and inhibiting the invasion of PCs. We also notice the negative response of HSPH1 + CD8 + T cell related genes in immune checkpoint blockade (ICB). Western blot (WB) and droplet digital Polymerase Chain Reaction (ddPCR) demonstrated that the mRNA and protein levels of HSPH1 in EVs of PCs were significantly higher than those in adjacent tissues. CONCLUSION: Results above indicate the potential of HSPH1 as a critical therapeutic target in PC.

Comparative efficacy of concurrent training types on lower limb strength and muscular hypertrophy: A systematic review and network meta-analysis.

Objective: This study aims to compare, through quantitative analysis, the effectiveness of different endurance training types on increasing lower limb strength and muscle cross-sectional area (MCSA) in concurrent training. Methods: This systematic literature search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) [PROSPERO ID: CRD42023396886]. Web of Science, SportDiscuss, Pubmed, Cochrane, and Scopus were systematically searched from their inception date to October 20, 2023. Results: A total of 40 studies (841 participants) were included in this meta-analysis. MCSA analysis showed that, compared to resistance training alone, concurrent high-intensity interval running training and resistance training and concurrent moderate-intensity continuous cycling training and resistance training were more effective (SMD = 0.15, 95% CI = -0.46 to 0.76, and SMD = 0.07, 95% CI = -0.24 to 0.38 respectively), while other modalities of concurrent training not. Lower body maximal strength analysis showed that all modalities of concurrent training were inferior to resistance training alone, but concurrent high-intensity interval training and resistance training showed an advantage in four different concurrent training modalities (SMD = -0.08, 95% CI = -0.25 to 0.08). For explosive strength, only concurrent high-intensity interval training and resistance training was superior to resistance training (SMD = 0.06, 95% CI = -0.21 to 0.33). Conclusion: Different endurance training types have an impact on the effectiveness of concurrent training, particularly on lower limb strength. Adopting high-intensity interval running as the endurance training type in concurrent training can effectively minimize the adverse effects on lower limb strength and MCSA.

Hyperhomocysteinemia may aggravate abdominal aortic aneurysm formation by up-regulating RASSF2.

Abdominal aortic aneurysm (AAA) is a fatal cardiovascular disorder with high mortality and morbidity rates. To date, no drug has shown to significantly alleviate the risk of AAA. Previous studies have indicated that hyperhomocysteinemia (HHcy) significantly increases the incidence of AAA by disrupting endothelial cell homeostasis; however, the potential molecular mechanisms require clarification. Herein, we aimed to integrate transcriptomics analysis and molecular biology experiments to explore the potential molecular targets by which HHcy may increase the incidence of AAA. We integrated two AAA data profiles (GSE57691 and GSE7084) based on previously published microarray ribonucleic acid sequencing (RNAseq) data from the GEO database. Additionally, 500 µM homocysteine-treated human aorta endothelium cells microarray dataset (GSE175748) was downloaded and processed. Subsequently, single-cell RNA-seq profiles of the aortic aneurysms (GSE155468) were downloaded, scaled, and processed for further analysis. The microarray profiles analysis demonstrated that the Ras association domain family member 2 (RASSF2) and interleukin (IL)-1ß are potentially the target genes involved in the HHcy-mediated aggravation of AAA formation. Single-cell RNAseq analysis revealed that RASSF2 might impair endothelial cell function by increasing inflammatory cell infiltration to participate in AAA formation. Finally, we conducted reverse transcription quantitative polymerase chain reaction and immunofluorescence analysis to validate the up-regulated mRNA expression of RASSF2 (p = 0.008) and IL-1ß (p = 0.002) in AAA tissue compared to control tissue. Immunofluorescence staining revealed overexpression of RASSF2 protein in AAA tissue sections compared to control tissue (p = 0.037). Co-localization of RASSF2 and the aortic endothelium cell marker, CD31, was observed in tissue sections, indicating the potential involvement of RASSF2 in aortic endothelial cells. To summarise, our preliminary study revealed that HHcy may worsen AAA formation by up-regulating the expression of RASSF2 and IL-1ß in aortic endothelium cells.