Zhejiang Chinese Medical University

Aim This study aimed to (1) investigate the current status of social isolation, stigma, and return‐to‐work readiness among young and middle‐aged patients with stroke and (2) explore the relationship among the three variables and construct a mediation model to test the mediating role of social isolation in the relationship between stigma and return‐to‐work readiness. Design A cross‐sectional descriptive study. Methods Data collection was conducted among patients 18–60 years of age (N = 154) who visited for the management of stroke. Participants completed a questionnaire measuring social isolation, stigma, and return‐to‐work readiness. The analysis of data and effect of mediation was tested by the PROCESS for SPSS 25.0. This study was reported following the STROBE guidelines. Results Stroke stigma was a significant predictor of social isolation (B = 0.0.68, SE = 0.02, t = 27.89, p < 0.000), with a confidence interval (LLCI = 0.63, ULCI = 0.73) excluding zero. Stigma was a significant predictor (c′ = −0.140, SE = 0.066, p = 0.035 < 0.05, 95% CI [−0.270, −0.010]) of return‐to‐work readiness. Social isolation partially mediated the relationship between stigma and return‐to‐work readiness, with a mediation effect of −0.207, accounting for 59.67% of the total effect. Patient or Public Contribution This study was informed by young and middle‐aged stroke survivors who contributed critical data through their participation. While patients were not directly involved in study design or analysis, their lived experiences with stigma and social isolation during post‐stroke rehabilitation provided essential context for interpreting the mediation mechanisms. The findings illuminate actionable pathways to enhance return‐to‐work readiness, offering healthcare providers strategies to address psychosocial barriers in vocational rehabilitation programmes.

Eosinophilic fasciitis is a rare connective tissue disease characterized by increased levels of peripheral blood eosinophils and infiltration in the myofascia. The diagnosis of eosinophilic fasciitis is primarily based on clinical manifestations, laboratory tests, and pathological biopsy, with the exclusion of other possible causes of fasciitis and eosinophil increase. Herein, we report a case of postnatal eosinophilic fasciitis occurring in a woman in her 20s, who developed the condition in her right forearm. The patient, who was postpartum, showed considerable recovery after conservative treatment with the corticosteroid prednisone.

This study investigated resveratrol impact on oral squamous cell carcinoma (OSCC) via the NORAD/IGF2BP2/PDK1 pathway. CAL-27, SCC-25, and KB cell lines were used to evaluate cell proliferation, cell cycle arrest, and protein expression. Key molecular markers were assessed using Western blot, RNA interference, and functional assays. Resveratrol inhibited the growth of CAL-27, KB, and SCC-25 cancer cell lines in a dose-dependent manner, with IC50 values of 70, 145, and 125 μg/mL, respectively (P < 0.01). In CAL-27 cells, 50 μg/mL resveratrol induced G2/M arrest (P < 0.05); 100 μg/mL caused S and G2/M phase arrest (P < 0.01). Thirteen proteins changed significantly: cPKCα and Notch4 were upregulated, while p-ERK, p-PDK1, p-Cdc2, p-RB, NORAD, IGF2BP2, CDK2, Cdc2P34, Cyclin E, 14–3-3beta, and XIAP were downregulated. si-NORAD groups showed lower CAL-27 proliferation than control. IGF2BP2 silencing reduced proliferation to 69.13% in HSC3 and 74.01% in CAL-27 (P < 0.001) and decreased invasion to 72.85% and 52.44% (P < 0.001). PDK1 overexpression enhanced the proliferation and migration of hypopharyngeal cancer cells. Resveratrol inhibits OSCC proliferation, particularly in CAL-27 cells. It affects NORAD, IGF2BP2, and PDK1 pathways, altering cell cycle protein expression and causing S and G2/M phase arrest.

Background This study analyzes the trends in the burden of chronic kidney disease due to type 2 diabetes (CKD‐T2D) in China from 1990 to 2021, evaluates variations in risk factors, and projects the disease burden through 2036. Method Estimates of prevalence, incidence, mortality, and disability‐adjusted life years (DALYs) for CKD‐T2D were retrieved along with their 95% uncertainty intervals (UIs). Age‐period‐cohort analysis was used to assess burden trends from 1990 to 2021, identify risk factor population attributable fractions (PAFs), and project the burden through 2036. Results In 2021, there were 20 911 520 CKD‐T2D cases in China, with an age‐standardized prevalence rate (ASPR) of 1053.92 per 100 000, an incidence rate (ASIR) of 23.07, an age‐standardized mortality rate (ASMR) of 5.72, and an age‐standardized DALY rate (ASDR) of 122.15. Although the overall burden showed a slow decline from 1990 to 2021, incidence continued to rise. The 2021 data revealed a marked age effect, with the burden rising with age. Period effects also contributed to an increased risk, with metabolic risk factors such as high fasting plasma glucose and BMI contributing the most. Projections suggest a decline in mortality and DALYs by 2036, while incidence will keep increasing. Conclusion Despite declines in ASMR and ASDR, CKD‐T2D incidence and cases continue to rise, especially among males and the elderly. This increasing burden is driven by aging and metabolic risk factors. Early screening, education, and risk management are essential for addressing CKD‐T2D in China.

Introduction Periprosthetic femoral fracture (PPFF) is a serious complication following hip arthroplasty. The objective of this study was to determine the risk factors for PPFF following hip arthroplasty from existing studies. Methods A comprehensive systematic search was performed in 4 databases: Pubmed, Embase, Web of Science, and Cochrane Library. The last search was carried out on 26th July 2024. We focused on identifying risk factors for PPFF following hip arthroplasty. Study eligibility required PPFF as an outcome and reporting of associated risk factors. Quality assessment was performed using the Newcastle-Ottawa Scale (NOS), with evidence certainty evaluated via Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). Meta-analyses employed both fixed-effect and random-effects models to pool odds ratios for identified risk factors. Results Out of 1553 articles, 36 studies published between 2006 and 2024 were included. Risk factors associated with increased incidence of PPFF ranges from very Low to High. High-quality evidence supported the use of uncemented stems (Odds Ratio [OR]: 3.36, 95% Confidence Interval [95% CI]: 3.02–3.74), major teaching hospital (OR: 2.04, 95% CI: 1.37–3.05). Moderate-quality evidence: female gender (OR: 1.60, 95% CI: 1.43–1.78), morbid obesity (OR: 1.44, 95% CI: 1.01–2.16), higher Deyo-Charlson index (OR: 1.44, 95% CI: 1.18–1.77), rheumatoid arthritis (OR: 1.89, 95% CI: 1.16–3.06), femoral Dorr type C (OR: 4.23, 95% CI: 2.82–6.33). Low evidence: age > 70 years (OR: 1.67, 95% CI: 1.19–2.34), revision hip arthroplasty (OR: 2.60, 95% CI: 1.59–4.27). BMI > 30 and history of hip surgery are not the risk (very low). Diagonized as osteoarthritis before surgery is a protective factor (OR:0.51, 95%CI: 0.40–0.65, quality = High). Conclusion This meta-analysis provided some low-to-high evidence about the risk of PPFF following hip arthroplasty. It’s recommended that clinicians consider these risk factors when evaluating patients for hip arthroplasty and take steps to mitigate their impact, like optimizing patients health preoperatively, using cemented stems, and monitoring high-risk patients closely.

Background Primary Sjögren’s syndrome (pSS) manifests a spectrum of neuropsychological symptoms, primarily cognitive impairment, but the mechanism of central nervous system damage remains unclear. This study sought to analyze differences in the static and dynamic fractional amplitude of low-frequency fluctuation (fALFF) and region homogeneity (ReHo) between pSS patients and healthy controls (HCs), aiming to elucidate regional brain function alterations and investigate underlying mechanisms. Methods Using stringent inclusion and exclusion criteria, 68 pSS patients and 69 HCs were assessed, including rs-fMRI, neuropsychological assessments, and laboratory tests. Static fALFF (sfALFF), static ReHo (sReHo), dynamic fALFF (dfALFF), and dynamic ReHo (dReHo) were calculated separately using two-sample t-tests to identify differences in brain regions between the two groups. Correlations between these regions and disease duration, laboratory indicators, and neuropsychological test scores were also examined. Results Static index analysis revealed increased sfALFF in the right supplementary motor area in pSS patients, with significant decreases in sReHo in the left orbital media frontal gyrus, left caudate nucleus, and right precuneus lobe. Dynamic index analysis showed significant increases in dfALFF in the left supplementary motor area and dReHo in the right dorsolateral superior frontal gyrus. Furthermore, sReHo in the right precuneus lobe negatively correlated with NCT-A scores (P = 0.005), and dReHo in the right dorsolateral superior frontal gyrus negatively correlated with DST scores (P = 0.007). Conclusion PSS patients experience notable changes in regional brain function, as evidenced by alterations in both static and dynamic brain indicators. Integrating these metrics provides a holistic view of the brain function alterations in pSS patients.

Background In critically ill elderly patients, malnutrition is a common comorbidity. The Geriatric Nutritional Risk Index (GNRI) is a straightforward tool for evaluating the nutritional status of elderly individuals. The association between GNRI score and unfavorable health outcomes has been established. However, no studies have yet elucidated the relationship between GNRI score and sepsis-related acute kidney injury (S-AKI). Methods We sourced patient data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. All patients were divided into four groups based on their GNRI score using quartile analysis. The main objective of this study was to investigate the 28-day mortality rate. Secondary study outcomes were the incidence of severe AKI, length of stay in the intensive care unit, and days in the hospital. To evaluate the association between GNRI score and study outcomes, we used a Cox proportional hazards regression model and restricted cubic splines. Kaplan–Meier curves were used to compare the outcomes in each group. Results A total of 4515 elderly patients with S-AKI were included in this study. Patients were categorized into four groups according to GNRI quartile: Q1 (< 78.92), Q2 (78.92–84.88), Q3 (84.88–90.84), and Q4 (> 90.84). Overall 28-day mortality was 29.5%. Patients with a low GNRI were predominantly women, and had a low body mass index. After controlling for confounding factors, GNRI score emerged as an independent predictor of 28-day mortality among elderly patients with S-AKI (Q4 vs. Q1: hazard ratio 0.74, 95% confidence interval 0.63–0.87; p < 0.001). Restricted cubic spline analysis revealed a linear relationship between GNRI and 28-day mortality (p for non-linearity = 0.207), and this association remained consistent across all subgroup analyses. Conclusions The GNRI is an important nutritional assessment tool, and is useful in predicting the prognosis of critically ill elderly patients with S- AKI.

Background Pre-eclampsia (PE) and pregnancy hypertension (PH) are common and serious complications during pregnancy, which can lead to maternal and fetal death in severe cases. Therefore, further research on the potential therapeutic targets of PE and PH is of great significance for developing new treatment strategies. Methods This study used the summary data-based Mendelian randomization (SMR) method to analyze expression quantitative trait loci (eQTL) data from blood, aorta, and uterus with Genome-wide association studies (GWAS) data on PE and PH, exploring potential genetic loci involved in PE and PH. Since proteinuria is a clinical manifestation of PE, we also analyzed genes related to the kidney and PE. The HEIDI test was used for heterogeneity testing, and results were adjusted using FDR. The cis-eQTL data were obtained from the blood summary-level data of the eQTLGen Consortium and the aorta and uterus data from the V8 release of the GTEx eQTL summary data. The GWAS data for PE and PH were obtained from the FinnGen Documentation of R10 release. This study utilized the STROBE-MR checklist for reporting Mendelian Randomization (MR) studies. Results This study identified several potential therapeutic targets by integrating eQTL data from blood, uterus, and aorta with GWAS data for PE and PH, as well as kidney eQTL data with GWAS data for PE. Additionally, the study discovered some genes with common roles in PE and PH, offering new insights into the shared pathological mechanisms of these two conditions. These findings not only provide new clues to the pathogenesis of PE and PH but also offer crucial foundational data for the development of future therapeutic strategies. Conclusion This study revealed multiple potential therapeutic targets for PE and PH, providing new insights for basic experimental research and clinical treatment to mitigate the severe consequences of PE and PH. Clinical trial number Not applicable.

Background Osteomyelitis (OM) is a bone disease that can leave people disabled. Eukaryotic translation initiation factor (EIF5A) is involved in cell proliferation, apoptosis, differentiation, and inflammation, but the role of EIF5A in staphylococcus aureus (S. aureus)-infected OM remains unclear. Methods The mRNA and proteins were detected by qRT-PCR and western blot. Cell viability was examined by CCK8 assay. The reactive oxygen species (ROS), malondialdehyde (MDA), ferrous iron (Fe²⁺), and glutathione (GSH) levels were analyzed using the ROS, MDA, GSH, and Fe²⁺ detection kits. The levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and Interleukin-6 (IL-6) were examined using Enzyme-linked immunosorbent (ELISA) kits. The binding between FOS and promoter of EIF5A was detected by chromatin immunoprecipitation (CHIP) assay. The interaction between EIF5A and Fos proto-oncogene (FOS) was detected by dual-luciferase reporter assay. The diagnostic values of EIF5A and FOS were analyzed with blood of S. aureus-infected OM patients and healthy volunteers by ROC curve. Results The EIF5A was up-regulated in S. aureus-infected OM. EIF5A knockdown promoted cell viability in S. aureus-infected MG-63 cells and reduced ROS, MDA, and Fe²⁺ levels, and increased GSH levels. Meanwhile, silencing EIF5A could increase expression of glutathione peroxidase 4 (GPX4), and ferritin heavy chain1 (FTH1) and reduce acyl-CoA synthetase long-chain family member 4 (ACSL4) expression, and silencing EIF5A could reduce immune factors (TNF-α, IL-1β, and IL-6) levels. FOS could bind to EIF5A. Silencing FOS promoted cell viability, and increased GSH levels in S. aureus-infected MG-63 cells, but reduced ROS, MDA, and Fe²⁺ levels. Meanwhile, promoted GPX4 and FTH1 expression, inhibited ACSL4 expression, and reduced immune factor levels in S. aureus-infected MG-63 cells. Interestingly, EIF5A overexpression could weaken the actions. FOS promotes ferroptosis and inflammation via EIF5A in S. aureus-infected MG-63 cells. Besides, the EIF5A and FOS might be potential molecular diagnostic markers in the progression of OM. Conclusion FOS promotes ferroptosis and inflammation via EIF5A in S. aureus-infected OM. This study is first to report the role of FOS and EIF5A in S. aureus-infected OM, but we found that there are still some limitations in our work, such as not covering all possible types of infection, which is the focus of future research.

Background An increasing number of critically ill patients are immunocompromised. These patients are at high risk of intensive care unit (ICU) admission because of numerous complications. Acute respiratory failure due to severe community-acquired pneumonia (SCAP) is one of the leading causes of admission. Early targeted antibiotic therapy is crucial for improving the prognosis of these patients. Metagenomic next-generation sequencing (mNGS) in bronchoalveolar lavage fluid (BALF) has shown significant value in pathogen detection in recent years. However, there are few studies on summarizing pathogen profiles of SCAP in immunocompromised patients. Methods We performed a multicenter retrospective analysis of patients with SCAP in the ICU diagnosed between May 2021 to October 2024. Bronchoalveolar lavage fluid (BALF), blood, and sputum samples were collected and subjected to mNGS and conventional microbiological tests (CMTs). The pathogen profiles detected by the two methods were compared. Results In our study, compared to CMTs, mNGS increased the detection rates of mixed infections in the immunocompromised group (58.82% vs 17.96%, P < 0.05) and immunocompetent group (44.58% vs 18.72%, P < 0.05), while also reducing the rate of no pathogen detected (4.90% vs 38.73%, P < 0.05; 8.37% vs 32.76%, P < 0.05). In both groups, the proportion of positive clinical impacts (diagnosis) resulting from mNGS results exceeded 90% (96.57% vs 93.84%), and the treatment effectiveness rate in the immunocompromised group was higher than in the immunocompetent group (65.69% vs 56.40%, P < 0.05). Further analysis showed that when mNGS-guided treatment was effective, the 28-day mortality rate significantly improved in both the immunocompromised group (31.34% vs 74.29%, P < 0.05) and the immunocompetent group (42.36% vs 40.68%, P < 0.05) compared to when the treatment was ineffective. Conclusion This study indicates that ICU patients with SCAP, particularly those who are immunocompromised, are more likely to have polymicrobial infections. mNGS in BALF provides rapid and comprehensive pathogen profiling of pulmonary infections, thereby having a positive impact on both the diagnosis, treatment and prognosis of immunocompromised patients with SCAP.

An electrochemical sensor for the simultaneous detection of mangiferin (MAN) and neomangiferin (NEO) was developed using CuBTC and GO-COOH through an electroreduction method for the first time. The electrochemical properties of the CuBTC@ErGO-COOH/GCE and the electrochemical behavior of MAN and NEO on this sensor were investigated. Several factors were investigated, including the concentration of CuBTC, pH value, accumulation time and scanning rate using cyclic voltammetry. The electrochemical reaction processes of MAN and NEO on the CuBTC@ErGO-COOH/GCE were inferred. An electroanalytical method was developed for the simultaneous detection of MAN and NEO using linear sweep voltammetry, allowing for precise and sensitive quantification of both compounds. The electrode reaction processes of MAN and NEO on the CuBTC@ErGO-COOH/GCE were both determined to be diffusion-controlled. The linear ranges for MAN and NEO were established from 0.1 ∼ 8 μM, with the detection limits of 8.1 nM and 17 nM (S/N = 3), respectively. The sensor demonstrated good repeatability, reproducibility, stability and anti-interference ability. Furthermore, it was successfully applied to the simultaneous detection of MAN and NEO in urine and serum samples with satisfactory recovery.

Chronic pain, a hallmark symptom of rheumatoid arthritis (RA), is strongly linked to central sensitization driven by spinal glial cell activation. Despite its clinical significance, the precise mechanisms remain unclear. Recent findings highlight the crucial role of interactions between circulating monocytes and central nervous system glial cells in chronic pain associated with autoimmune conditions. Our study focuses on CD4 ⁺ T-cell infiltration into the spinal dorsal horn (SDH) after collagen-induced arthritis (CIA) immunization. Immunohistochemistry results indicate that CD4 ⁺ T cells are critical in initiating arthritic pain. Intrathecal injection of CD4 ⁺ T cells in naïve mice induced glial activation and pain-like behaviors, while neutralizing antibodies suppressed these effects. Elevated phosphorylation of collapsin response mediator protein 2 (CRMP2) in CIA-derived CD4 ⁺ T lymphocytes was closely associated with pathological spinal infiltration. To modulate CRMP2 phosphorylation, we used naringenin (NAR), a known CRMP2 regulator, and (S)-Lacosamide ((S)-LCM), a specific inhibitor of phosphorylated CRMP2. Both compounds reduced CD4 ⁺ T-cell infiltration into the SDH and attenuated central sensitization in CIA rats. CRMP2 conditional knockout (cKO) in CD4 ⁺ T cells significantly alleviated arthritic pain. In addition, in vitro blood brain barrier models and Transwell assays showed impaired CD4 ⁺ T-cell migration and transendothelial invasion upon cKO or treatment with NAR and (S)-LCM. These interventions also decreased the proportion of polarized CD4 ⁺ T cells in CIA-induced mice. Our research highlights the role of CRMP2 phosphorylation in CD4 ⁺ T-cell behavior, spinal infiltration, and pain modulation, suggesting potential novel therapeutic strategies for RA-associated chronic pain.

Background The application of machine learning (ML) in predicting the requirement for total knee arthroplasty (TKA) at knee osteoarthritis (KOA) patients has been acknowledged. Nonetheless, the variables employed in the development of ML models are diverse and these different approaches yield inconsistent predictive performance of models. Therefore, we conducted this systematic review and meta-analysis to explore the feasibility of ML in identifying candidates for TKA. Method This study was conducted based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. This study was registered on the international prospective register of systematic reviews registration database website, PROSPERO, with a unique ID: CRD 42023443948. The study subjects were patients diagnosed with KOA. Relevant studies were searched through PubMed, Web of Science, Cochrane, and Embase until September 15, 2024. The c-index was used as the outcome measure. The risk of bias in the primary study was assessed by Prediction model Risk of Bias Assessment Tool (PROBAST). Random or fixed effects were used for the meta-analysis. Results A total of 13 articles were included in this study, but only 11 articles with 25 models were eligible for the meta-analysis. ML models in the included studies were classified based on the source of variables, including clinical features, radiomics, and the combination of clinical features and radiomics. In the training set, the c-index was 0.713 (0.628 – 0.799) for clinical features, 0.841 (0.777 – 0.904) for radiomics, and 0.844 (0.815 – 0.873) for the combination of clinical features and radiomics. In the validation set, the c-index for ML models based on clinical features, radiomics, and the combination of clinical features and radiomics was 0.656 (0.526 – 0.786), 0.861 (0.806 – 0.916), and 0.831 (0.799 – 0.863), respectively. Conclusion The results of this meta-analysis highlighted that the ML model is feasible in identifying candidates for TKA. X-ray-based ML models exhibit the best predictive performance among the models. However, there is currently a lack of high-level research available for clinical application. Furthermore, the accuracy of ML models in identifying candidates for TKA is significantly limited by the quality of modeling parameters and database architecture. Therefore, constructing a more targeted and professional database is imperative to promote the development and clinical application of ML models.