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The systemic immune-inflammation index (SII) is a cost-efficient indicator for carcinoma prognosis. However, its utility in urothelial carcinoma (UC) prognosis is disputed. This meta-analysis aims to assess SII's prognostic value in UC. A thorough search of databases including PubMed, Web of Science, Embase, Cochrane Library, and Scopus, was conducted to find studies until January 11, 2023. Eligibility criteria were applied to select studies. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted from selected studies and compiled in a meta-analysis to gauge SII's association with survival outcomes such as overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and progression-free survival (PFS). This analysis includes 19 studies with 12505 UC patients. It was found that high SII significantly correlated with worse OS in UC patients (HR 1.430, 95% CI 1.237-1.653, P<0.001). High SII values also linked with poorer CSS (HR 1.913, 95% CI 1.473-2.485, P<0.001), RFS (HR 1.240, 95% CI 1.097-1.403, P=0.001), and PFS (HR 1.844, 95% CI 1.488-2.284, P<0.001) compared to low SII values. Subgroup analysis revealed SII's consistent prognostic value in UC across races, carcinoma types, sample sizes, and SII cut-off values, suggesting its potential as a prognostic indicator in UC patients. Current evidence suggests SII as a promising, cost-efficient predictor in UC patients. This meta-analysis indicates SII's potential as a valuable prognostic tool in UC patients. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=307643, identifier CRD42022307643.

Quantitative data were expressed as the mean ± standard deviation (SD) or median (25th percentile, 75th percentile) and analyzed using appropriate statistical tests such as t test, one-way analysis of variance (ANOVA), Mann–Whitney U test, or Kruskal–Wallis H test. Clinical and laboratory data are shown in Supplementary Table 1, http://links.lww.com/CM9/C129, and no significant among-group differences were observed in age and sex. A significant increase in the concentration of DcR3 protein secreted extracellularly inhibits the expression of mRNA, intracellular protein, and membrane protein by negative feedback. [6] MSU crystals form complexes with cluster of differentiation (CD)14 and bind to TLRs on macrophages to result rapidly activation of the IκB kinase complex, leading to IκBα phosphorylation, degradation, and detachment from NF-κB. The degradation of IκBα exposes the nuclear localization signaling region of NF-κB, promoting NF-κB phosphorylation and nuclear transcription.

Background The aim of this study was to investigate the applicable safety and biomechanical stability of iliosacral triangular osteosynthesis (ITO) through 3D modeling and finite element (FE) analysis. Methods Pelvic CT imaging data from 100 cases were imported into Mimics software for the construction of 3D pelvic models. The S2-alar-iliac (S2AI) screws and S2 sacroiliac screws were placed in the S2 segment with optimal distribution and their compatibility rate on the S2 safe channel was observed and analyzed. In the FE model, the posterior pelvic ring was fixed with two transsacral screws (TTS), triangular osteosynthesis (TO) and ITO, respectively. Four different loading methods were implemented in sequence to simulate the force in standing, flexion, right bending, and left twisting, respectively. The relative displacement and change in relative displacement of the three fixing methods were recorded and analyzed. Results The theoretical compatibility rate of S2AI screw and S2 sacroiliac screw in S2 segment was 94%, of which 100% were in males and 88% in females. In the FE model, in terms of overall relative displacement, TTS group showed the smallest relative displacement, the ITO group showed the second smallest, and the TO group the largest relative displacement. The change in relative displacement of the TTS group displayed the smaller fluctuations in motion. The change in relative displacement of the TO group under right bending and left twisting displayed larger fluctuations, while the ITO group under flexion displayed larger fluctuations. Conclusions The simultaneous placement of S2AI screw and S2 sacroiliac screw in the S2 segment is theoretically safe. Although the biomechanical stability of ITO is slightly lower than TTS, it is better than TO, and can be used as a new method for the treatment of posterior pelvic ring injuries.

Interleukin-6 (IL-6) is a pleiotropic cytokine, with specific effects depending on the immune microenvironment. Extensive research has confirmed the pathological roles of the IL-6/JAK2/STAT1/3 signaling pathway in inflammation, autoimmunity, and cancer, as well as its involvement in the pathogenesis of various rheumatic diseases. However, the role and impact of IL-6 as an upstream regulator of the JAK2-STAT1/3 pathway in gout have seldom been reported. This study explores the influence and role of upstream IL-6 in regulating the JAK2-STAT1/3 signaling pathway on gout inflammation, offering new insights for targeted therapeutic interventions and drug development in gout management. Clinical data and peripheral blood specimens were collected from gout patients and healthy individuals. In vitro and in vivo models of acute gout inflammation were established by stimulating PBMCs, THP-1 cells, and mice with MSU crystals. IL-6 expression was manipulated using IL-6 agonists and IL-6 knockout (KO) mouse technology to investigate the role and impact of the IL-6-mediated JAK2-STAT1/3 signaling pathway in gout models. RT-qPCR, WB, and ELISA were utilized to assess gene and protein expression levels. Paw swelling in mice was measured using a caliper gauge, while HE and IHC staining were conducted to evaluate the inflammatory status of mouse paw pad synovial tissues and detect the positive expression of relevant proteins. Serum IL-6 protein expression levels were significantly elevated in patients with gouty arthritis (GA) compared to healthy individuals, with multifactor logistic regression revealing an odds ratio (OR) of 2.175 for IL-6. In GA patients, mRNA expression of IL-6, JAK2, STAT1/3, and IL-1β was notably lower in the gout group compared to the healthy control (HC) group. Moreover, IL-6, JAK2, STAT1/3, p-JAK2, p-STAT1/3, and IL-1β proteins were markedly higher in the acute gout (AG) group compared to the intercritical gout (IG) and HC groups. Within the IG group, IL-6, JAK2, STAT3, and IL-1β proteins were significantly elevated compared to the HC group, whereas STAT1, p-JAK2, and p-STAT1/3 proteins were significantly lower. The expression of IL-6 protein and JAK2 mRNA showed positive correlations with certain inflammatory markers. In the 2h human blood in vitro gout inflammation model, expressions of IL-1β, IL-6, JAK2 mRNA, and IL-1β, IL-6, JAK2, STAT1/3, p-JAK2, p-STAT1/3 proteins were significantly higher compared to both the blank control and PBS-negative control groups. In the acute gout THP-1 cell model, The 6-hour model group showed significantly higher levels of IL-1β, IL-6, JAK2, STAT1/3 mRNA, and corresponding proteins, including their phosphorylated forms, compared to the blank control group. Additionally, treatment with an IL-6 agonist further increased these expression levels compared to the untreated model group. In the acute gout mouse model, IL-6 KO mice exhibited significantly reduced footpad swelling and swelling index compared to wild-type (WT) mice. HE staining revealed decreased inflammatory cell infiltration in IL-6 KO mice. Furthermore, Compared to 12-hour gout model WT mice, IL-1β, IL-6, JAK2, STAT1/3 mRNA, protein expression, and phosphorylated protein levels were notably decreased in IL-6 KO mice. IHC staining showed reduced positive expression of p-JAK2 and p-STAT1/3 in IL-6 KO mice. At the 24-hour mark, IL-6 mRNA and protein expression levels did not differ significantly between IL-6 KO and WT mice; however, IL-1β mRNA and protein expression, as well as JAK2 and STAT3 mRNA expression, were reduced in IL-6 KO mice, while STAT1 mRNA expression remained similar. IL-6 emerges as a potential risk factor for acute gout attacks, with its involvement in the JAK2-STAT1/3 signaling pathway contributing to the inflammation and pathogenesis process of acute gout through positive feedback mechanisms.

Objective Reconstruction of soft tissue defects in the foot and ankle remains challenging. This study was performed to investigate the technical points and clinical effects of a double-pedicle propeller flap for repair of foot and ankle soft tissue defects. Methods We used five fresh calf specimens to investigate the anatomical and operative aspects of a double-pedicle propeller flap. Eighteen patients with soft tissue defects in the foot and ankle subsequently underwent defect repair with double-pedicle propeller flaps. Results The anatomical study showed that the peroneal artery perforators and the sural nerve bundle (two blood supply systems) provided the theoretical anatomical basis for the double-pedicle propeller flap. The relative positions of the peroneal artery perforators and the sural nerve bundle differ according to the peroneal artery perforating level. Flap rotation in different directions can reduce or prevent the pedicles from compressing each other. All flaps survived, and three flaps developed local epidermal necrosis at the proximal end; these flaps healed after 1 to 2 weeks of dressing changes. The other 15 patients healed well. Conclusions The double-pedicle propeller flap can enhance the blood supply and venous return in the “big paddle” region of the flap, reducing the distal necrosis rate.

Background Five different sacral fracture fixation methods were compared using finite element (FE) analysis to study their biomechanical characteristics. Methods Denis type I sacral fractures were created by FE modeling. Five different fixation methods for the posterior pelvic ring were simulated: sacroiliac screw (SIS), lumbopelvic fixation (LPF), transiliac internal fixator (TIFI), S2-alar-iliac (S2AI) screw and S1 pedicle screw fixation (S2AI-S1) and S2AI screw and contralateral S1 pedicle screw fixation (S2AI-CS1). Four different loading methods were implemented in sequence to simulate the force in standing, flexion, right bending and left twisting, respectively. Vertical stiffness, relative displacement and change in relative displacement were recorded and analyzed. Results As predicted by the FE model, the vertical stiffness of the five groups in descending order was S2AI-S1, SIS, S2AI-CS1, LPF and TIFI. In terms of relative displacement, groups S2AI-S1 and S2AI-CS1 displayed a lower mean relative displacement, although group S2AI-CS1 exhibited greater displacement in the upper sacrum than group S2AI-S1. Group SIS displayed a moderate mean relative displacement, although the displacement of the upper sacrum was smaller than the corresponding displacement in group S2AI-CS1, while groups LPF and TIFI displayed larger mean relative displacements. Finally, in terms of change in relative displacement, groups TIFI and LPF displayed the greatest fluctuations in their motion, while groups SIS, S2AI-S1 and S2AI-CS1 displayed smaller fluctuations. Conclusion Compared with SIS, unilateral LPF and TIFI, group S2AI-S1 displayed the greatest biomechanical stability of the Denis type I sacral fracture FE models. When the S1 pedicle screw insertion point on the affected side is damaged, S2AI-CS1 can be used as an appropriate alternative to S2AI-S1.

Objective: To compare the fixation stability of the lag screw with a undercut thread design for the dynamic hip screw (DHS) system versus the lag screw with the conventional buttress thread. Methods: The lag screws with the undercut thread (a flat crest feature, a tip-facing undercut feature) and buttress thread were both manufactured. Fixation stability was investigated using cyclic compressive biomechanical testing on custom osteoporotic femoral head sawbone. The forces required for the same vertical displacement in the two types of lag screw were collected to evaluate the resistance to migration. Varus angle was measured on X-ray images to assess the ability in preventing varus collapse. Finite element analysis (FEA) was performed to analyze the stress and strain distribution at the bone-screw interface of the two types of lag screws. Results: The biomechanical test demonstrated that the force required to achieve the same vertical displacement of the lag screw with the undercut thread was significantly larger than the lag screw with conventional buttress thread ( p < 0.05). The average varus angles generated by the undercut and buttress threads were 3.38 ± 0.51° and 5.76 ± 0.38°, respectively ( p < 0.05). The FEA revealed that the region of high-stress concentration in the bone surrounding the undercut thread was smaller than that surrounding the buttress thread. Conclusion: The proposed DHS system lag screw with the undercut thread had higher migration resistance and superior fixation stability than the lag screw with the conventional buttress thread.

Rheumatoid arthritis (RA) is an enduring, progressive autoimmune disorder. Abnormal activation of fibroblast-like synoviocytes (FLSs) has been proposed as the initiating factor for inflammation of the synovium and bone destruction. Neutrophil extracellular traps (NETs), which are web-like structures composed of DNA, histones, and granule proteins, are involved in the development of RA in multiple aspects. Pyroptosis, gasdermin-mediated inflammatory programmed cell death, plays a vital function in the etiopathogenesis of RA. However, the exact mechanism underlying NETs-induced pyroptosis in FLSs of RA and its impact on cellular pathogenic behavior remain undefined. In this study, we demonstrated that gasdermin E (GSDME) expression was upregulated in RA plasma and synoviums, which was positively correlated with the elevated cell-free DNA (cfDNA) and citrullinated histone 3 (Cit H3) levels in the plasma. Additionally, in vitro experiments have shown that NETs triggered caspase 3/GSDME-mediated pyroptosis in RA-FLSs, characterized by decreased cell viability, cell membrane blebbing, and rupture, as well as increased levels of pyroptosis-related proteins and pro-inflammatory cytokines. Again, silencing GSDME significantly inhibited pyroptosis and suppressed the migration, invasion, and secretion of pro-inflammatory cytokines in RA-FLSs. Furthermore, we also found that the nuclear factor-kappa B (NF-κB) pathway, serving as an upstream mechanism, was involved in FLS pyroptosis. In conclusion, our investigation indicated that NETs could induce RA-FLS pyroptosis and facilitate phenotypic transformation through targeting the NF-κB/caspase 3/GSDME axis. This is the first to explore the crucial role of NETs-induced FLS pyroptosis in the progression of RA, providing novel targets for the clinical management of refractory RA.

BackgroundMammalian STE20-like kinase 1 (MST1) is involved in the occurrence of cancer and autoimmune diseases by regulating cell proliferation, differentiation, apoptosis and other functions. However, its role and downstream targets in rheumatoid arthritis (RA) remain unclear.MethodsThe model of RA fibroblast-like synoviocytes (RA-FLSs) overexpressing MST1 was constructed by lentiviral transfection in vitro and analyzed the effects of MST1 on apoptosis, migration, invasion, and inflammation of RA-FLSs. The effect of MST1 on joint synovial membrane inflammation and bone destruction was observed in vivo by establishing a rat model of arthritis with complete Freund’s adjuvant.ResultsMST1 is down-regulated in RA-FLSs, and up-regulation of MST1 inhibits the survival, migration, invasion and inflammation of RA-FLSs. Mechanistically, MST1 inhibits SIRT3/mTOR-signaling pathway, inducing decreased mitochondrial autophagy and increased mitochondrial fission, resulting in mitochondrial morphological abnormalities and dysfunction, and ultimately increased apoptosis. We have observed that activation of MST1 alleviates synovial inflammation and bone erosion in vivo.ConclusionsMST1 reduces the survival, migration, invasion and inflammation of FLSs by inhibiting the SIRT3/mTOR axis to reduce mitochondrial autophagy and promote mitochondrial division, thereby achieving the potential role of relieving rheumatoid arthritis.

With the increasing advancement in shale exploration and development, the complex pore structure and organic-rich characteristics of shale have gradually become the focus of rock physics models. This study combined digital core technology to obtain detailed information on the shale mineral composition, content, pore and crack contents, and composition. The isotropic self-compatible approximation (SCA) model was used to couple the shale minerals and hard pores to construct a brittle mineral framework. The VRH model was used to mix kerogen and clay, and the SCA-DEM (differential equivalent medium) model was used to add organic pores to construct a clay organic matter mineral framework. The anisotropic SCA model treated the clay organic matter mineral framework as an inclusion added to the brittle mineral framework to construct the shale mineral framework. The Eshelby–Cheng model was used to add fracture to the mineral framework and establish a physical shale model. This model was used to optimize the selection of sensitive elastic parameters for physical properties such as brittle mineral and kerogen content, fracture density, and porosity, and the optimization results were combined to construct an explanatory quantity template. In addition, according to actual data from a study area in southwestern China, we combined to the interpretation chart established by the model to perform isotropic inversion. Then, we analyzed and interpreted the brittleness index and total organic carbon content of the reservoir and predicted the sweet spot area of the shale reservoir.