BackgroundSeveral prospective and randomized trials support immune checkpoint inhibitors (ICIs) as an emerging component of standard definitive treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). The key uncertainty has shifted from whether ICIs have antitumor activity to how they should be incorporated into multimodality therapy, including therapeutic modality, treatment timing, chemotherapy backbone, treatment duration, and agent selection.MethodsWe performed a pooled analysis of seven prospective trials enrolling 1,788 patients with LA-NPC, with data retrieved through December 2025. ICI-based regimens were evaluated across four prespecified dimensions: therapeutic modality, immunotherapy timing, chemotherapy backbone, and individual ICI agent. The protocol was registered with PROSPERO (CRD420261293069).ResultsSeven prospective trials involving 1788 patients were included. ICI-containing strategies were associated with high pooled survival estimates, including 3-year overall survival (OS) of 96.4% and 3-year failure-free survival (FFS) of 88.2%. Exploratory strategy-level analyses suggested clinically relevant differences across ICI integration approaches. In the neoadjuvant setting, chemoimmunotherapy plus antiangiogenic therapy showed the highest complete response (CR) estimate (26.5%) but also the highest grade 3 or higher treatment-related adverse event estimate (65.3%); ICI monotherapy showed limited neoadjuvant activity, with a CR estimate of 1.0%. For treatment sequencing, neoadjuvant-adjuvant ICI administration showed favorable long-term disease-control estimates, including 3-year locoregional recurrence-free survival of 96.0% and 3-year OS of 99.0%, whereas full-course neoadjuvant-concurrent-adjuvant ICI administration was associated with the lowest progressive disease estimate (0.2%). Chemotherapy backbone also appeared relevant: modified taxane-platinum-fluoropyrimidine showed a higher neoadjuvant CR estimate than gemcitabine-cisplatin (31.4% vs 13.7%). At the agent level, camrelizumab-based regimens achieved neoadjuvant objective response of 100.0%, although with a higher immune-related adverse event estimate (81.8%); toripalimab-based regimens showed 3-year OS of 97.0% with a lower overall immune-related adverse event estimate (53.6%).ConclusionICI-containing strategies showed favorable current survival estimates and measurable tumor activity in LA-NPC; however, their clinical relevance appears to vary according to how ICIs are integrated into multimodality treatment. Given that several strategy-level estimates were based on few heterogeneous studies and relatively short follow-up, these findings should be viewed as hypothesis-generating and used to inform treatment optimization and future randomized, biomarker-informed trials, rather than to identify a single preferred ICI strategy.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420261293069, identifier CRD420261293069.

Peroxiredoxin 3 (PRDX3), a key mitochondrial redox enzyme, has been implicated in malignant tumor initiation and development. However, the its biological function and clinical relevance remain unclear. Here, we performed a systematic pan-cancer analysis of PRDX3 across 33 cancers using The Cancer Genome Atlas database, examining its expression patterns, gene alterations and mutations, methylation, subcellular localization, signaling pathways, tumor microenvironment, immune infiltration, and associations with clinical outcomes. We further validated the biological function role of PRDX3 in kidney clear cell carcinoma (KIRC) through reverse transcription quantitative polymerase chain reaction, Western blotting, Transwell assays, and scratch assays. PRDX3 was differentially expressed in cancers, and its expression appeared to be influenced by copy number variation and methylation status. PRDX3 levels were significantly associated with patient prognosis in multiple tumor types, suggesting context-dependent roles in tumor biology. Functional analyses indicated that PRDX3 may affect tumor progression through programs related to cell-cycle regulation, metabolism, and redox processes. In KIRC models, PRDX3 overexpression suppressed malignant phenotypes and was accompanied by changes in PPAR signaling pathway. Collectively, our results support PRDX3 as potential prognostic biomarker and suggest a tumor-suppressive role in KIRC, although further mechanistic and in vivo validation is warranted.

BACKGROUND:Heart rate variability (HRV) represents efferent vagus nerve activity, which is suggested to be related to fundamental mechanisms of tumorigenesis and to be a predictor of prognosis in various cancers. Therefore, this study hypothesized that HRV monitoring could predict perioperative complication (PC) in colorectal cancer (CRC) patients. AIM:To investigate the prognostic value of HRV in hospitalized CRC patients. METHODS:The observational studies included 87 patients who underwent CRC surgical procedures under enhanced recovery after surgery programs in a first-class hospital. The HRV parameters were compared between the PC group and the non PC (NPC) group from preoperative day 1 to postoperative day (Pod) 3. In addition, inflammatory biomarkers and nutritional indicators were also analyzed. RESULTS:The complication rate was 14.9%. HRV was markedly abnormal after surgery, especially in the PC group. The frequency-domain parameters (including pNN50) and time-domain parameters [including high-frequency (HF)] of HRV were significantly different between the two groups postoperatively. The pNN50 was significantly greater at Pod1 in the PC group than that in the NPC group and returned to baseline at Pod2, suggesting that patients with complications exhibited autonomic nerve dysfunction in the early postoperative period. In the PC group, HFs were also enhanced from Pod1 and were significantly higher than in the NPC group; inflammatory biomarkers were significantly elevated at Pod2 and Pod3; the levels of nutritional indicators were significantly lower at Pod1 and Pod2; and the white blood cell count was slightly elevated at Pod3. CONCLUSION:HRV is independently associated with postoperative complications in patients with CRC. Abnormal HRV could predicted an increased risk of postoperative complications in CRC patients. Continuous HRV could be used to monitor complications in patients with CRC during the perioperative period.

Aseptic loosening and periprosthetic osteolysis driven by wear particles are major causes of total joint arthroplasty (TJA) failure. Investigating the upstream mechanisms of osteoblast ferroptosis in periprosthetic osteolysis is essential for developing therapeutic strategies to lengthen the lifespan of artificial joints. Titanium nanoparticle (TN)-induced osteolysis models were established in vivo and in vitro. Bone parameters including bone mineral density, bone volume, bone volume to tissue volume ratio, and total porosity were measured by micro-CT in mice. Commercial kits were applied to test the levels of glutathione, malondialdehyde, and iron. BODIPY 581/591 C11 staining was used to detect lipid peroxidation. ChIP and dual-luciferase reporter assay were utilized to investigate the interaction among TCF4 protein and YTHDF1 promoter region. RIP was employed to detect the relationship between YTHDF1 and GPX4 or SLC7A11 mRNAs. Our findings revealed a marked enhancement of ferroptosis in clinical synovial tissues surrounding implants and TN-induced periprosthetic osteolysis models both in vitro and in vivo. Ferroptosis inhibitors significantly attenuated TN-induced osteolysis. TCF4 and YTHDF1 were both downregulated in TN-induced osteolysis, and overexpression of them improved bone microarchitecture and alleviated osteoblast ferroptosis. TCF4 bound to the promoter region of YTHDF1 to transcriptionally upregulate its expression, which subsequently promoted translation of GPX4 and SLC7A11 mRNAs. Finally, the activation of Wnt/β-catenin pathway boosted TCF4/YTHDF1 axis, and restrained osteoblast ferroptosis in osteolysis. TCF4 targeted the promoter region of m6A reader YTHDF1 to promote its transcription, thereby reducing osteoblast ferroptosis in TN-induced periprosthetic osteolysis by promoting the translation of GPX4 and SLC7A11.

Introduction The survival rate of patients with intrahepatic cholangiocarcinoma (ICC) is extremely low mainly because of its high metastatic characteristic, pushing us to explore effective targets inhibiting the metastasis of ICC. Objectives To explore potential therapeutical targets to restrict the metastasis of ICC. Methods The potential targets were screened via RNA sequencing and verified in cells and tissues. The prognostic value of TMEM158 was explored in ICC patients. The abilities of TMEM158 on affecting the metastasis of ICC were detected in cells and mice models. The cell actin skeleton stiffness was measured by phalloidin staining. The effect of TMEM158 on lactic acid (LA) generation was explored via metabolic flow and relative mechanism was detected by co-immunoprecipitation and immunofluorescence. The relationship between HIF-1A and TMEM158 was explored by dual luciferase reporter gene experiment. Results TMEM158 was identified as a potential candidate over-expressed in ICC, especially with metastasis, that is linked to reduced overall survival. Besides, functional studies indicated that TMEM158 silencing inhibits ICC metastasis in vivo and in vitro through decreasing cell actin skeleton stiffness of ICC cells, and visa versa. Moreover, mechanically, lactic acid (LA) is validated as the bridge connecting TMEM158 and skeleton stiffness and TMEM158 induces the generation of LA via interaction with and activating Ras protein and subsequently enhancing glucose transporter 3 (Glut3) mediated glycolysis in ICC cells. Finally, HIF-1A directly targets the promoter region of TMEM158 and thus increases its level in ICC. Conclusion TMEM158 reduced the actin skeleton stiffness of ICC cells through activating Ras protein mediated generation of LA, which finally results in enhanced metastasis of ICC. Our work provides a preclinical evidence of concept for TMEM158 as a novel candidate inhibiting the metastasis of ICC.

Osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) facilitated by mechanical loading is a promising therapy for disuse osteoporosis (DOP), however, it is difficult to implement mechanical loading for a majority of patients. Our study aims to identify circ-ITCH-mediated novel approach to facilitate osteogenic differentiation in DOP. A rat DOP model and human BM-MSCs under microgravity condition were generated as in vivo and in vitro models of DOP, respectively. The bone mineral density (BMD) and bone parameters were examined in rats. The histological changes of bones and mineralization were monitored by H E, Alcian blue and Alizarin red S staining. Co-IP was employed to examine the ubiquitination of HOXC10 and the interaction between HOXC10 and BRCA1. The direct associations among circ-ITCH, IGFBP2 and BRCA1 mRNA were assessed by RIP, FISH and RNA pull-down assays. Circ-ITCH was downregulated in rat model of DOP and BM-MSCs under microgravity stimulation. Circ-ITCH overexpression promoted osteogenic differentiation in BM-MSCs under microgravity condition. The altered bone parameters, such as BMD, trabecular number (Tb.N), trabecular separation (Tb.Sp), trabecular thickness (Tb.Th), and bone microstructure in DOP rats were rescued by circ-ITCH overexpression. Mechanistically, circ-ITCH enhanced the ubiquitination degradation of HOXC10 through enhancing BRCA1 mRNA stability. Circ-ITCH directly bound to IGF2BP2 protein to stabilize BRCA1 mRNA via m6A modification, thus facilitating osteogenic differentiation in BM-MSCs under microgravity condition. Circ-ITCH stabilized BRCA1 mRNA via IGF2BP2-mediated m6A modification, thereby facilitating the ubiquitination degradation of HOXC10 to promote osteogenic differentiation in DOP.

Acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy. Cytarabine (Ara-C)-based chemotherapy is the primary treatment for AML, but currently known prognostic risk stratification factors cannot fully explain the individual differences in outcome of patients. In this article, we reported that patients with homozygous GLI1 rs2228224 mutation (AA genotype) had a significantly lower complete remission rate than those with GG wild type (54.17

Background Late-onset seborrhoeic dermatitis seriously affects patients' quality of life. Studies have shown an association between air pollution and other inflammatory skin diseases. However, associations between air pollution exposures and the incidence of late-onset seborrhoeic dermatitis have not been elucidated.Objectives To investigate air pollution's role in the incidence of late-onset seborrhoeic dermatitis.Methods We engaged a prospective cohort analysis utilizing the UK Biobank database. Exposure data spanning various years for specific air pollutants, namely particulate matter [PM; with an aerodynamic diameter of <= 2.5 mu m (PM2.5), between 2.5 and 10 mu m (PM2.5-10), <= 10 mu m (PM10)] along with nitrogen oxides (NO plus NO2, denoted NOx) and NO2, were incorporated. Through a composite air pollution score constructed from five pollutants and employing Cox proportional hazards models, the relationship between air pollution and seborrhoeic dermatitis was delineated.Results Our examination of 193 995 participants identified 3363 cases of seborrhoeic dermatitis. Higher concentrations of specific pollutants, particularly in the upper quartile (Q4), were significantly linked to an elevated risk of seborrhoeic dermatitis. Notably, PM2.5, PM10, NO2 and NOx exhibited hazard ratios of 1.11, 1.15, 1.22 and 1.15, respectively. The correlation was further solidified with a positive association between air pollution score increments and onset of seborrhoeic dermatitis. Intriguingly, this association was accentuated in certain demographics, including younger men, socioeconomically deprived people, smokers, daily alcohol consumers, and those engaging in regular physical activity.Conclusions Our findings revealed that air pollution exposures were associated with incidence of late-onset seborrhoeic dermatitis. These results emphasize the importance of preventing environmental air pollution exposures to mitigate the risk of developing the condition. Our study provides evidence that specific air pollutants (particulate matter with an aerodynamic diameter of <= 2.5 mu m, between 2.5 and 10 mu m and <= 10 mu m, as well as nitrogen oxides) are significantly associated with an increased risk of late-onset seborrhoeic dermatitis. The results highlight the heightened risk of seborrhoeic dermatitis in certain demographics, including younger men, socioeconomically deprived individuals, smokers, alcohol consumers and physically active people.

Purpose: The study comprehensively evaluated the prognostic roles of the platelet -to -lymphocyte ratio (PLR), neutrophil-tolymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), basophil-to-lymphocyte ratio (BLR), and eosinophil-to-lymphocyte ratio (ELR) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Patients and Methods: Six hundred and nineteen patients with AECOPD and 300 healthy volunteers were retrospectively included into the study. The clinical characteristics of the patients with AECOPD and the complete blood counts (CBCs) of the healthy volunteers were collected. The associations of PLR, NLR, MLR, BLR, and ELR with airflow limitation, hospital length of stay (LOS), C -reactive protein (CRP), and in -hospital mortality in patients with AECOPD were analyzed. Results: Compared with the healthy volunteers, PLR, NLR, MLR, BLR, and ELR were all elevated in COPD patients under stable condition. PLR, NLR, MLR, and BLR were further elevated while ELR was lowered during exacerbation. In the patients with AECOPD, PLR, NLR, and MLR were positively correlated with hospital LOS as well as CRP. In contrast, ELR was negatively correlated with hospital LOS as well as CRP. Elevated PLR, NLR, and MLR were all associated with more severe airflow limitation in AECOPD. Elevated PLR, NLR, and MLR were all associated with increased in -hospital mortality while elevated ELR was associated with decreased in -hospital mortality. Binary logistic regression analysis showed that smoking history, FEV1% predicted, pneumonia, pulmonary heart disease (PHD), uric acid (UA), albumin, and MLR were significant independent predictors ofin-hospital mortality. These predictors along with ELR were used to construct a nomogram for predicting in -hospital mortality in AECOPD. The nomogram had a C -index of 0.850 (95% CI: 0.799-0.901), and the calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) further demonstrated its good predictive value and clinical applicability. Conclusion: In summary, PLR, NLR, MLR, and ELR served as useful biomarkers in patients with AECOPD.

Background Interferons (IFNs) are essential for activating an effective immune response and play a central role in immunotherapy-mediated immune cell reactivation for tumor regression. Type III IFN (λ), related to type I IFN (α), plays a crucial role in infections, autoimmunity, and cancer. However, the direct effects of IFN-λ on the tumor immune microenvironment have not been thoroughly investigated.Methods We used mouse MB49 bladder tumor models, constructed a retroviral vector expressing mouse IFN-λ3, and transduced tumor cells to evaluate the antitumor action of IFN-λ3 in immune-proficient tumors and T cell-deficient tumors. Furthermore, human bladder cancer samples (cohort 1, n=15) were used for immunohistochemistry and multiplex immunoflurescence analysis to assess the expression pattern of IFN-λ3 in human bladder cancer and correlate it with immune cells’ infiltration. Immunohistochemistry analysis was performed in neoadjuvant immunotherapy cohort (cohort 2, n=20) to assess the correlation between IFN-λ3 expression and the pathological complete response rate.Results In immune-proficient tumors, ectopic Ifnl3 expression in tumor cells significantly increased the infiltration of cytotoxic CD8+ T cells, Th1 cells, natural killer cells, proinflammatory macrophages, and dendritic cells, but reduced neutrophil infiltration. Transcriptomic analyses revealed significant upregulation of many genes associated with effective immune response, including lymphocyte recruitment, activation, and phagocytosis, consistent with increased antitumor immune infiltrates and tumor inhibition. Furthermore, IFN-λ3 activity sensitized immune-proficient tumors to anti-PD-1/PD-L1 blockade. In T cell-deficient tumors, increased Ly6G–Ly6C+I-A/I-E+ macrophages still enhanced tumor cell phagocytosis in Ifnl3 overexpressing tumors. IFN-λ3 is expressed by tumor and stromal cells in human bladder cancer, and high IFN-λ3 expression was positively associated with effector immune infiltrates and the efficacy of immune checkpoint blockade therapy.Conclusions Our study indicated that IFN-λ3 enables macrophage-mediated phagocytosis and antitumor immune responses and suggests a rationale for using Type III IFN as a predictive biomarker and potential immunotherapeutic candidate for bladder cancer.

The data that support the findings of this study are available from the corresponding author upon reasonable request.

As a crucial component of solar radiation, the association between exposure to ambient ultraviolet (UV) radiation and acne remains unclear.

BackgroundThe associations between single risk factors and incident rosacea have been reported, but the effects of social risk factors from multiple domains coupled remain less studied. ObjectivesTo quantify the influence of social determinants on rosacea comprehensively and investigate associations between the polysocial risk score (PsRS) with the risks of incident rosacea. MethodsThis was a prospective cohort study of government employees undertaken from January 2018 to December 2021 among participants aged >20 from five cities in Hunan province of China. At baseline, information was collected by a questionnaire and participants were involved in an examination of the skin. Dermatologists with certification confirmed the diagnosis of rosacea. The skin health status of participants was reassessed every year since the enrolment of study during the follow-up period. The PsRS was determined using the nine social determinants of health from three social risk domains (namely socioeconomic status, psychosocial factors, and living environment). Incident rosacea was estimated using binary logistic regression models adjusted for possible confounding variables. ResultsAmong the 3,773 participants who completed at least two consecutive skin examinations, there were 2,993 participants included in the primary analyses. With 7,457 person-years of total follow-up, we detected 69 incident rosacea cases. After adjustment for major confounders, participants in the group with high social risk had significantly raised risks of incident rosacea with the adjusted odds ratio (aOR) being 2.42 (95% CI 1.06, 5.55), compared to those in low social risk group. ConclusionOur findings suggest that a higher PsRS was associated with an elevated risk of incident rosacea in our study population.

BackgroundImmune checkpoint blockade (ICB) and anti-angiogenic drug combination has prolonged the survival of patients with advanced renal cell carcinoma (RCC). However, not all patients receive clinical benefits from this intervention. In this study, we aimed to establish a promising immune-related prognostic model to stratify the patients responding to ICB and anti-angiogenic drug combination and facilitate the development of personalized therapies for patients with RCC.Materials and methodsBased on clinical annotations and RNA-sequencing (RNA-seq) data of 407 patients with advanced RCC from the IMmotion151 cohort, nine immune-associated differentially expressed genes (DEGs) between responders and non-responders to atezolizumab (anti-programmed death-ligand 1 antibody) plus bevacizumab (anti-vascular endothelial growth factor antibody) treatment were identified via weighted gene co-expression network analysis. We also conducted single-sample gene set enrichment analysis to develop a novel immune-related risk score (IRS) model and further estimate the prognosis of patients with RCC by predicting their sensitivity to chemotherapy and responsiveness to immunotherapy. IRS model was further validated using the JAVELIN Renal 101 cohort, the E-MTAB-3218 cohort, the IMvigor210 and GSE78220 cohort. Predictive significance of the IRS model for advanced RCC was assessed using receiver operating characteristic curves.ResultsThe IRS model was constructed using nine immune-associated DEGs: SPINK5, SEMA3E, ROBO2, BMP5, ORM1, CRP, CTSE, PMCH and CCL3L1. Advanced RCC patients with high IRS had a high risk of undesirable clinical outcomes (hazard ratio = 1.91; 95% confidence interval = 1.43–2.55; P < 0.0001). Transcriptome analysis revealed that the IRS-low group exhibited significantly high expression levels of CD8+ T effectors, antigen-processing machinery, and immune checkpoints, whereas the epithelial–mesenchymal transition pathway was enriched in the IRS-high group. IRS model effectively differentiated the responders from non-responders to ICB combined with angiogenesis blockade therapy or immunotherapy alone, with area under the curve values of 0.822 in the IMmotion151 cohort, 0.751 in the JAVELIN Renal 101 cohort, and 0.776 in the E-MTAB-3218 cohort.ConclusionIRS model is a reliable and robust immune signature that can be used for patient selection to optimize the efficacy of ICB plus anti-angiogenic drug therapies in patients with advanced RCC.

Keratin-15 (KRT15) participates in the tumorigenesis of several cancers, especially in urinary tract carcinomas by regulating basal urothelial cell malignant proliferation and differentiation. This study intended to explore the association of KRT15 with tumor features and survival in renal cell carcinoma (RCC) patients. Totally, 210 RCC patients receiving surgical resection were retrospectively enrolled, and then, KRT15 was detected by immunohistochemistry (IHC) assay in the tumor and adjacent tissues. IHC score of KRT15 was increased in tumor tissues versus adjacent tissues (P < 0.001). Meanwhile, KRT15 was associated with RCC occurring in the left kidney (P = 0.024), tumor size > 10 cm (P = 0.035), higher N stage (P = 0.048), and higher tumor-node-metastasis (TNM) stage (P = 0.029). Additionally, high KRT15 (IHC score > 3) estimated poor disease-free survival (DFS) (P = 0.008) and overall survival (OS) (P = 0.011). In addition, multivariate regression analysis revealed that high KRT15 [hazard ratio (HR) = 1.719, P = 0.023], higher pathological grade (HR = 1.847, P < 0.001), and higher N stage (HR = 3.447, P < 0.001) were independently related to poor DFS; high KRT15 (HR = 1.796, P = 0.034), eastern cooperative oncology group performance status score (1 vs. 0) (HR = 1.734, P = 0.037), higher pathological grade (HR = 2.045, P < 0.001), and higher N stage (HR = 3.966, P < 0.001) were independently linked to unsatisfactory OS. Furthermore, data from Gene Expression Profiling Interactive Analysis suggested that KRT15 was linked to poor DFS (P = 0.037) and OS (P < 0.001); data from THE HUMAN PROTEIN ATLAS revealed that KRT15 was associated with shorter OS (P < 0.001) in RCC patients. In conclusion, KRT15 is increased in tumor tissues, and correlates with higher tumor stage and larger tumor size, along with poor prognosis for RCC.

Cytarabine (Ara-C) plays an irreplaceable role in the treatment of acute myeloid leukemia (AML). However, there are significant differences in efficacy among patients. Our previous studies found that E2F1 rs3213150 polymorphism was associated with remission rate of Ara-C chemotherapy, but the specific mechanism is not clear. This study aimed to further confirm the correlation between E2F1 rs3213150 polymorphism and Ara-C resistance and prognosis in AML patients, and to provide valuable information for elucidating the molecular mechanisms involved. Methods: Rs3213150 genotyping was performed in 922 AML patients by Sanger sequencing, and the effects of different genotypes on chemosensitivity and prognosis were analyzed by Logistic regression and Cox regression. Meanwhile, a prediction model of Ara-C chemotherapy resistance was established. The impact of rs3213150 polymorphism on E2F1 expression level was determined by luciferase reporter gene assay, and differentially expressed genes between patients with different genotypes were identified by RNA sequencing. Results: Compared with rs3213150 G allele carriers, patients with AA genotype had more obvious Ara-C resistance (41.94% vs. 27.94%, P = 0.002), shorter overall survival (529 d vs. 644 d, P = 0.008) and disease-free survival (519 d vs. 556 d, P = 0.023). Rs3213150G > A mutation resulted in decreased E2F1 expression. Conclusion: E2F1 rs3213150 polymorphism influences the chemosensitivity and prognosis of Ara-C in Chinese AML patients.

Venous thromboembolism (VTE) consists of deep vein thrombosis (DVT) and pulmonary embolism (PE). Rivaroxaban is a direct oral anticoagulant (DOAC) inhibiting activated coagulation factor X (FXa), and exerts several advantages in the treatment of VTE compared to conventional therapy. However, the efficacy and safety of rivaroxaban in elderly patients with VTE was still poorly understood. The study was carried out using an observational and non-interventional approach. A total of 576 patients aged ≥ 60 years with newly diagnosed VTE were included in the study. All patients received rivaroxaban with recommended treatment duration of ≥ 3 months for secondary prevention. In addition, 535 elderly patients with various diseases except VTE were included in the study in a retrospective and randomized way. The total bleeding rate was 12.2

Herpes zoster (HZ) brings a significant economic burden. The HZ vaccine was introduced in China for the first time in 2020, and there is a lack of up-to-date information on the hospitalization costs and characteristics prior to vaccination. This study aimed to describe the characteristics and economic burden of HZ inpatients in Hunan Province, China, and analyze the factors influencing the length of stay (LOS) and costs. This was a retrospective study and we extracted information from the Chinese National Health Statistics Network Reporting System on HZ inpatients in Hunan Province, China from 2017 to 2019. Spatial join tools and Global or Local Moran's Index were used for the geographic analysis of hospitalized HZ incidence. Multivariate linear regression models were used to analyze the factors influencing LOS and costs. There were 44,311 HZ inpatients included in this study, incurring a total of $31,857,734 medical costs. These patients had a median LOS of 8 days and a median expenditure of $573.47. Older age, more comorbidities, and the presence of complications with nervous system involved were all significantly associated with longer LOS and higher costs. HZ infection resulted in a large direct medical cost and heavy disease burden, especially in patients with advanced age or underlying medical conditions. The HZ vaccine has the potential to effectively reduce the disease burden and should be widely popularized especially among high-risk groups.

BackgroundDespite of growing evidence on gastrointestinal comorbidities of rosacea, there was a lack of literatures regarding the role of diet on rosacea.ObjectivesTo investigate the relationship between adherence to a Mediterranean-like diet pattern and the risk of incident rosacea.MethodsThis was a prospective cohort study of government employees aged >20 years conducted between January 2018 and December 2021 from five cities of Hunan province of China. At baseline, participants completed a food frequency questionnaire and participated in a skin examination. Presence of rosacea was determined by certified dermatologists. Subsequent skin examinations during follow-up were performed every one-year interval since the entry of the study. The Mediterranean diet score (MDS) was generated based on seven food groups (whole grains, red meats, fish, raw vegetables, legumes, fruits and nuts). Binary logistic regression models adjusted for potential confounders were used to estimate risks for incident rosacea.ResultsOf the 3,773 participants who completed at least two consecutive skin examinations, 3,496 were eligible for primary analyses. With a total follow-up of 8,668 person-years, we identified 83 incident rosacea cases. After full adjustments for covariates, the MDS was associated a decreased risk of incident rosacea (aOR: 0.84, 95% CI: 0.72, 0.99; Ptrend = 0.037 for 1-point increment of MDS). In subgroup analyses by body mass index (BMI), this inverse association was consistently observed in the lowest and medium tertiles of BMI (<24.5 kg/m2), but not in the highest tertile of BMI (≥24.5 kg/m2), with a significant interaction effect (P < 0.001).ConclusionsOur results suggested that adherence to a Mediterranean-like diet pattern might reduce the risk of incident rosacea among non-overweight individuals.

Background: Bladder cancer (BCa) is the leading reason for death among genitourinary malignancies. RNA modifications in tumors closely link to the immune microenvironment. Our study aimed to propose a promising model associated with the "writer" enzymes of five primary RNA adenosine modifications (including m(6)A, m(6)A(m), m(1)A, APA, and A-to-I editing), thus characterizing the clinical outcome, immune landscape and therapeutic efficacy of BCa.Methods: Unsupervised clustering was employed to categorize BCa into different RNA modification patterns based on gene expression profiles of 34 RNA modification "writers". The RNA modification "writers" score (RMS) signature composed of RNA phenotype-associated differentially expressed genes (DEGs) was established using the least absolute shrinkage and selection operator (LASSO), which was evaluated in meta-GEO (including eight independent GEO datasets) training cohort and the TCGA-BLCA validation cohort. The hub genes in the RMS model were determined via weighted gene co-expression network analysis (WGCNA) and were further validated using human specimen. The potential applicability of the RMS model in predicting the therapeutic responsiveness was assessed through the Genomics of Drug Sensitivity in Cancer database and multiple immunotherapy datasets.Results: Two distinct RNA modification patterns were determined among 1,410 BCa samples from a meta-GEO cohort, showing radically varying clinical outcomes and biological characteristics. The RMS model comprising 14 RNA modification phenotype-associated prognostic DEGs positively correlated with the unsatisfactory outcome of BCa patients in meta-GEO training cohort (HR = 3.00, 95% CI = 2.19-4.12) and TCGA-BLCA validation cohort (HR = 1.53, 95% CI = 1.13-2.09). The infiltration of immunosuppressive cells and the activation of EMT, angiogenesis, IL-6/JAK/STAT3 signaling were markedly enriched in RMS-high group. A nomogram exhibited high prognostic prediction accuracy, with a concordance index of 0.785. The therapeutic effect of chemotherapeutic agents and antibody-drug conjugates was significantly different between RMS-low and -high groups. The combination of the RMS model and conventional characteristics (TMB, TNB and PD-L1) achieved an optimal AUC value of 0.828 in differentiating responders from non-responders to immunotherapy.Conclusion: We conferred the first landscape of five forms of RNA modifications in BCa and emphasized the excellent power of an RNA modifications-related model in evaluating BCa prognosis and immune landscape.