Objective: To elucidate the biological function and clinical relevance of killer cell lectin like receptor B1(KLRB1)in cervical cancer. Methods: Multi-omics approaches were employed. The Cancer Genome Atlas (TCGA) cohort: RNA-seq data from 304 cervical cancer patients were analyzed to evaluate KLRB1's association with clinical features, prognosis (Kaplan-Meier, Cox regression), and immune functions (Gene Set Variation Analysis, GSVA enrichment); single-cell transcriptomics: the GSE208653 dataset [tumor, high-grade squamous intraepithelial lesion(HSIL), and healthy tissues] was processed via Seurat for clustering and t-distributed stochastic neighbor embedding (t-SNE) visualization; clinical validation: flow cytometry quantified KLRB1 expression on peripheral T/NK cells in 37 cervical cancer patients, 37 HSIL patients, and 20 healthy controls, correlated with FIGO stage and other parameters. Results: High KLRB1 expression correlated with improved overall survival (OS, P=0.001 2) and recurrence-free survival (RFS, P=0.015 0). Expression was reduced in advanced stages (FIGO Ⅲ-Ⅳ) and lymph node metastasis (P < 0.01). KLRB1 positively correlated with T/NK cells activation pathways (P < 0.001), and tumor-infiltrating/peripheral blood T/NK cells showed lower KLRB1 in cancer versus HSIL/healthy control groups (P < 0.001). Stage-specific patterns were observed: early-stage patients (FIGO Ⅰ-Ⅱ) exhibited higher KLRB1 on NK cells and CD8+ T cells (P < 0.05), while no significant associations were found with histology or menopause. Conclusion: KLRB1 is a protective immune biomarker in cervical cancer. Its downregulation indicates immune exhaustion and poor prognosis, while its stage-specific expression patterns in NK and CD8+ T cells inform personalized immunotherapeutic strategies targeting the tumor microenvironment.
Objective: To identify differentially expressed miRNAs in the peripheral blood of individuals with unipolar depressive spectrum disorders, and examine the relationships between these miRNAs and the severity of depression and stress-related events. Methods: A total of 73 participants were recruited, comprising 16 healthy controls, 17 individuals with subsyndromal depression, 20 individuals with mild depression, and 20 individuals with major depressive disorder. Samples of peripheral blood were obtained and miRNA sequencing was performed. RT-qPCR was used to select and validate differentially expressed miRNAs. The correlation between the miRNA expression and the results of Hamilton Depression Rating Scale-17 items (HAMD-17), Hamilton Anxiety Scale (HAMA), Life Events Scale (LES), and Adverse Childhood Experiences International Questionnaire (ACE-IQ) were analyzed. Results: Sixteen of the 95 miRNAs that were shown to be differentially expressed among groups (P < 0.05) by sequencing were confirmed by RT-qPCR. Thirteen miRNAs remained significantly differentially expressed after controlling for age and gender. Let-7a-5p and let-7b-5p showed substantial negative associations (|r| > 0.6, P < 0.01) with HAMD-17 and HAMA total scores. Negative LES showed a positive correlation with miR-30a-5p (rs=0.244, P < 0.05). Let-7a-5p expression and ACE-IQ scores showed a modest negative correlation (r=-0.264, P < 0.05). Conclusion: miR-30a-5p and peripheral blood let-7 family members may be useful biomarkers for unipolar depressive spectrum disorders, with expression alterations being associated with stress exposure and the severity of depression.
Objective: To investigate the prognostic value of the age-adjusted Charlson comorbidity index (aCCI) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) requiring endotracheal intubation, and to evaluate the independent associations of individual comorbidities with 28-day in-hospital mortality. Methods: This retrospective cohort study was conducted using the Medical Information Mart for Intensive Care Ⅳ (MIMIC-Ⅳ) database and included 2 270 intubated patients with AECOPD. In addition, 72 intubated patients with AECOPD treated at Zhongshan Hospital (Xiamen), Fudan University, between Jan 2021 and Feb 2026 were retrospectively enrolled as an external validation cohort. The primary outcome was 28-day in-hospital mortality. Cox proportional hazards regression was used to assess the association between aCCI and mortality risk, as well as examine the independent effects of individual comorbidities. The optimal aCCI cut-off was determined by X-tile for stratified survival comparisons. An aCCI-only model and a combined model were further developed; discrimination was evaluated using the receiver operating characteristic (ROC) curve and the area under the curve (AUC), while calibration and clinical net benefit were assessed using calibration plots and decision curve analysis, with further validation in the external cohort. Results: The 28-day in-hospital mortality rate was 27.14% (616/2 270). In multivariable analysis, aCCI was an independent risk factor for 28-day in-hospital mortality (adjusted hazard ratio, aHR=1.08). Among individual comorbidities, severe liver disease (aHR=1.56), renal disease (aHR=1.24), and metastatic solid tumor (aHR=1.70) were associated with a higher mortality risk (all P < 0.05). Using an aCCI cut-off of 10, the high comorbidity-burden group (aCCI > 10) had a significantly higher risk of 28-day in-hospital mortality than the low-burden group (aCCI≤10) (hazard ratio, HR=1.91, P < 0.001). Regarding predictive performance, the aCCI-only model yielded an AUC of 0.65, whereas the combined model incorporating aCCI, pulse oxygen saturation (SpO2), lactate, base excess (BE), and the Sequential Organ Failure Assessment (SOFA) score achieved an AUC of 0.73, with a significant improvement (P < 0.001). The combined model achieved an AUC of 0.75 in the external validation cohort, showed good calibration in both the derivation and validation cohorts, and provided higher net benefit across a wide range of threshold probabilities. Conclusion: Comorbidity burden is independently associated with 28-day in-hospital mortality in intubated patients with AECOPD, and aCCI may serve as a rapid tool for risk stratification. Incorporating lactate, SOFA score, and SpO2 alongside aCCI may further improve identification of high-risk patients and inform early individualized management.
Objective: To investigate the prevalence of loneliness among community-dwelling elders in Shanghai and analyze its relationship with health-related quality of life. Methods: We conducted face-to-face investigations on the healthy aging surveillance cohort established by the project team in 2 central urban areas, 2 suburban areas, and 2 rural areas of Shanghai from Aug to Dec 2024. The UCLA 3-item Loneliness Scale (UCLA-3) and the EuroQol Five-dimensional Five-level Questionnaire (EQ-5D-5L) were utilized to collect data on loneliness and health-related quality of life. Intergroup comparison of loneliness was conducted using the χ2 test or Fisher's exact test. The student's t test and One-way ANOVA analysis were used to compare the differences in health utility values and visual analogue scale (VAS) scores across different subgroups of the elderly population. Based on the data characteristics, Spearman correlation analysis, Tobit regression, and ordinary least squares (OLS) regression models were used to examine the association between loneliness and health-related quality of life. Results: A total of 1 978 community-dwelling elders aged 60 and above were included. The mean UCLA-3 score was 3.42±0.95. Overall, 19.8% reported mild-to-moderate or severe loneliness, with a significantly higher detection rate among those living alone than among those who did not (45.0% vs. 17.0%, χ2=88.82, P < 0.001). Loneliness showed significant negative correlations with utility scores (r=-0.23, P < 0.001) and VAS (r=-0.15, P < 0.001). After adjusting for demographic characteristics, health behaviors, and psychosocial adaptation factors, these associations remained robust (utility scores, β=-0.08, P < 0.001; VAS, β=-1.34, P < 0.001). Perceived economic pressure, multimorbidity, physical inactivity, lack of family interaction, sleep disturbances, and low subjective well-being also showed consistent statistical associations with health-related quality of life in the multivariable models (all P < 0.05). Conclusion: Nearly 20% of the community-dwelling elders in Shanghai suffer from loneliness, which is significantly associated with poorer health-related quality of life.
Objective: To investigate the association between comprehensive lifestyle and the risk of developing chronic disease multimorbidity in a general population, based on the Shanghai Suburban Adult Cohort and Biobank (SSACB). Methods: A case-control study was performed within the SSACB cohort. Subjects free of chronic diseases at baseline were enrolled. The outcomes of chronic disease multimorbidity were tracked by linking the databases of regional medical records and disease management. Baseline data of the SSACB cohort were collected from Apr 2016 to Dec 2019, with follow-up conducted from baseline through Dec 2023 for this study. Participants newly diagnosed with chronic disease multimorbidity during follow-up were assigned to the case group, and individuals without chronic diseases in the cohort were matched 1∶1 to the cases by sex, age and other factors to form the control group. Exposure to common lifestyle factors and anthropometric indicators at baseline were compared between the two groups, and the assigned values for these factors were summed to derive a comprehensive unhealthy lifestyle score. Logistic regression models were used to analyze the associations of each single lifestyle factor and the comprehensive unhealthy lifestyle score with chronic disease multimorbidity, respectively. Results: A total of 6 894 participants were included in the analysis, and the results showed that sedentary time > 4 h/d (OR=1.200, 95%CI: 1.075-1.339, P=0.001), moderate sleep quality (OR=1.210, 95%CI: 1.063-1.378, P=0.004) and poor sleep quality (OR=1.438, 95%CI: 1.082-1.911, P=0.012), BMI≥28.0 kg/m2 (OR=1.374, 95%CI: 1.089-1.734, P=0.008), central obesity (OR=1.485, 95%CI: 1.268-1.739, P < 0.001) and pre-central obesity status (OR=1.154, 95%CI: 1.012-1.317, P=0.033) were risk factors for chronic disease multimorbidity. The mean of comprehensive unhealthy lifestyle score was higher in the case group (5.70±2.26) than in the control group (5.35±2.18) (t=6.522, P < 0.001). Each 1-point increment in the score was associated with an 8.6% increased risk of chronic disease multimorbidity (OR=1.086, 95%CI: 1.061-1.112, P < 0.001). Conclusion: Prolonged daily sedentary time, moderate sleep quality and poor sleep quality, BMI≥28.0 kg/m2, central obesity and pre-central obesity status were independent risk factors for chronic disease multimorbidity. A combination of unhealthy lifestyle factors was associated with an increased risk of chronic disease multimorbidity.
Objective: We carried out a transcriptome-wide association study (TWAS) to identify susceptibility gene and potential drug targets for sensorineural hearing loss (SNHL). Methods: The TWAS was used to identify candidate genes for SNHL. The functional summary-based imputation (FUSION) was performed to validate the discoveries in single tissues. The multimarker analysis of genomic annotation (MAGMA) was used to screen the candidate genes. Additionally, summary data-based Mendelian randomization (SMR) as well as colocalization analyses were employed to further infer the causal associations. Gene enrichment analysis was conducted to provide further insight into the functional significance of these susceptibility genes. The druggability of these identified genes was assessed to find the candidate drugs. Results: A total of 22 susceptibility genes were identified by cross-tissue TWAS analysis. There were 8 genes (SPTBN1, EML6, SLC16A8, ARHGAP28, ASCC2, C2orf73, MICALL1 and GCAT) confirmed to have a significant correlation with SNHL by FUSION and MAGMA analyses. SMR and colocalization analyses further validated these susceptibility genes. These candidate genes might be associated with SNHL by regulating multiple pathways. Pyridoxal phosphate might be a candidate drug for SNHL, based on database mining and molecular docking prediction. Conclusion: A total of 8 susceptibility genes associated with SNHL risk and potential drug targets are identified, among which the association between GCAT and the marketed compound pyridoxal phosphate provides a genetic-based rationale for the drug-repurposing strategy in SNHL.
Objective: To construct an influenza transmission model for southern China and explore the role of climatic factors in influenza transmission. Methods: Influenza surveillance data from 2011 to 2019 in southern China were collected. The influenza-like illness percentage (ILI%) plus positive rate of influenza nucleic acid test was used as an indicator reflecting influenza activity intensity. Six compartment models were constructed based on different combinations of humidity, temperature, and immune duration. The period from Jan 2011 to Dec 2016 was used as the training set, and from Jan 2017 to Dec 2019 as the testing set. Structural similarity index (SSIM) was used to assess the similarity in trends between the fitted curve and the actual epidemic curve, and Brier score was used to measure how well the prediction interval effectively covers the actual outcome. Results: The SH/T/Short model incorporating specific humidity (SH), temperature, and multiple infection scenarios performed the best. In the testing set, the model's SSIM median and Brier score were 0.84 and 0.40, respectively.The model further quantified a U-shaped relationship between R0 and SH (trough interval approximately 9-13 g/kg), revealed a threshold effect of temperature on the transmission rate (critical temperature Tc approximately 20.49-24.53 ℃), and estimated an optimal immune duration of 205-510 days. Conclusion: The SH/T/Short model is the optimal compartment model for fitting influenza transmission patterns in southern China. Simultaneously incorporating specific humidity, temperature, and shorter immune duration significantly improves fitting accuracy. There is a significant U-shaped relationship between SH and influenza transmission, with both low and high SH favoring influenza spread. Temperature further affected transmission rates through a modulating effect.
Objective: To investigate the incidence of prolonged stay in the emergency rescue room among elderly patients and to identify its associated factors, so as to provide evidence for optimizing emergency care processes for elderly patients. Methods: A retrospective study was conducted involving elderly patients admitted to the emergency rescue room of a tertiary hospital from Jan to Jun 2023. Patients were divided into a prolonged-stay group and a non-prolonged-stay group according to whether the length of stay exceeded 72 hours. General demographic characteristics and visit-related information were collected, including age, sex, payment method, consultation time period, accompanying personnel, mode of arrival, primary admitting department, number of diagnoses, triage level, distribution area, diversion direction, and treatment compliance. Univariate analyses were performed to compare differences between the two groups. Variables with statistical significance were further included in a multivariable Logistic regression model to explore factors associated with prolonged stay in the emergency rescue room among elderly patients. Results: A total of 7 768 elderly patients were included, of whom 2 312 had a length of stay longer than 72 hours, yielding a prolonged stay rate of 29.7%. Univariate analysis showed that age, payment method, consultation time period, accompanying personnel, mode of arrival, primary admitting department, number of diagnoses, triage level, distribution area, diversion direction, and treatment compliance were associated with prolonged stay in the emergency rescue room (P < 0.05). Multivariable Logistic regression analysis demonstrated that age, consultation time period, mode of arrival, number of diagnoses, triage level, and treatment compliance remained significantly associated with prolonged stay after adjustment for confounding variables (P < 0.05). Conclusion: The incidence of prolonged stay in the emergency rescue room among elderly patients is relatively high, which suggests that greater attention should be paid to elderly patients who are older, have more complex conditions, or present during specific consultation time periods in future emergency management and process optimization, in order to reduce prolonged stay in emergency rescue room.
Objective: To investigate the distribution characteristics of pathogenic antigens and their correlations with IgG subtypes in patients with primary membranous nephropathy(PMN)in a single center for kidney disease research of Shanghai, and to explore the clinical significance of antigen-specific distribution patterns. Methods: Paraffin-embedded renal tissues from 220 PMN cases archived at the Department of Pathology, School of Basic Medical Sciences, Fudan University were retrospectively analyzed. Immunofluorescence and immunohistochemistry were performed to detect the expression of phospholipase A2 receptor (PLA2R), thrombospondin type-1 domain-containing 7A (THSD7A), neural epidermal growth factor-like 1 (NELL-1), and proprotein convertase subtilisin/kexin type 6 (PCSK6), along with IgG subtype analysis. Clinical and pathological data were integrated for clinicopathological evaluation. Results: PLA2R positivity was the highest(83.2%, 183/220), with IgG4 as the predominant subtype; THSD7A ranked second in positivity(7.3%, 16/220), also predominantly associated with IgG4;NELL-1 and PCSK6 exhibited low positivity rates of 1.4%(3/220)and 0.45%(1/220), respectively, both linked to IgG1;PLA2R-positive cases showed no comorbidities other than PMN; three THSD7A-positive patients developed malignancies during follow-up; one PCSK6-positive patient had a history of short-term high-dose of nonsteroidal anti-inflammatory drug use; no extrarenal diseases were observed in NELL-1-positive cases; statistically significant differences in pathological staging were observed between PLA2R- and THSD7A-positive groups (P < 0.05). Conclusion: PLA2R is the predominant pathogenic target antigen in PMN, with IgG4 as its primary autoantibody. THSD7A may be associated with malignancies or infections. Positive cases for NELL-1 and PCSK6 were rarely detected.
Objective: To investigate different dose of esketamine combined with propofol on perioperative hemodynamics in elderly patients. Methods: A randomized controlled study was conducted in 165 elderly patients (≥60 years) scheduled for elective ophthalmic surgery from Eye and ENT Hospital, Fudan University between Aug 2022 and Dec 2024. Patients were randomly divided into 3 groups: 2 mg/kg propofol+20 mL normal saline (PS group, n=55), 1 mg/kg propofol+0.50 mg/kg esketamine (PE1 group, n=55), and 1 mg/kg propofol + 0.75 mg/kg esketamine (PE2 group, n=55). The incidence of adverse events including hypotension, hypertension, tachycardia, and bradycardia was compared among the 3 groups. Trends in heart rate (HR) and mean arterial pressure (MAP) were compared at the following time points: before induction after entering the operating room (T0), 1 min after drug administration (T1), 1 min before intubation (T2), 1 min after intubation (T3), 5 min after intubation (T4), and 10 min after intubation (T5). Results: PE1 group showed a lower incidence of hypotension compared to PS group and PE2 group (all P < 0.05). There was no significant difference among the three groups in the incidence of hypertension, tachycardia and bradycardia. The MAP in PE1 group and PE2 group was higher than that in PS group at T1, T2 and T3 (all P < 0.05). Only PE2 group had a higher MAP than that in PS group (P < 0.01) at T4. There was no difference in MAP among the three groups at T5. No significant differences in MAP were observed between PE1 group and PE2 group at any time points. The HR in PE2 group was higher than that in PE1 group at T1 and T3 (all P < 0.05). The HR in PE1 group was higher than that in PS group and PE2 group at T5 (all P < 0.05). There was no statistically significant difference in HR between PE2 group and PS group at any time points. Conclusion: The combination of 0.50 mg/kg esketamine with propofol provides better maintenance of hemodynamic stability during the induction period in elderly patients.
Objective: To validate the predictive value of the improved antineutrophil cytoplasmic antibody (ANCA) renal risk score (ANCA kidney risk score, AKRiS) for the prognosis of patients with ANCA-associated glomerulonephritis (ANCA-GN). Methods: Patients diagnosed with ANCA-GN by renal biopsy at Tongji Hospital, Tongji University between Oct 2011 and Jan 2024 were retrospectively enrolled. The endpoint event was defined as end-stage renal disease (ESRD) or all-cause death. Kaplan-Meier survival analysis and Cox regression were used to evaluate the predictive value of AKRiS for the prognosis of patients with ANCA-GN. Results: A total of 34 patients were enrolled, with a median follow-up time of 16 months. Based on the AKRiS risk stratification, patients were divided into three groups, including low-risk, moderate-risk, and high/very high-risk groups. The cumulative incidence rates of the endpoint event in the low-risk, moderate-risk, and high/very high-risk groups were 26.3%, 71.4% and 100.0% respectively (χ2=13.876, P < 0.001). All patients in the high/very high-risk group reached the endpoint event within 6 months. Survival curves showed significant differences in cumulative survival rates among the three groups (χ2=19.359, P < 0.001). The cumulative survival rate of the low-risk group was significantly higher than that of the moderate-risk group (χ2=6.256, P=0.012), with 5-year cumulative survival rates of 65.4% and 28.6%, respectively. Multivariate Cox regression analysis showed that AKRiS was a key prognostic predictor for ANCA-GN patients (HR=1.125, 95%CI: 1.010-1.254, P=0.033). The area under the curve of AKRiS for predicting the endpoint event was 0.844 (95%CI: 0.706-0.982, P=0.001). Conclusion: AKRiS demonstrates high predictive value for outcomes in ANCA-GN patients, as demonstrated in our cohort.
Objective: To investigate the associations of sleep duration and sleep quality with anxiety and depression symptoms in community-dwelling elderly residents aged 60 years and above in Minhang District, Shanghai. Methods: A convenience sampling method was used to select elderly residents who participated in health examinations at Huacao Community Health Service Center in Minhang District, Shanghai from May to Jun 2023. The Pittsburgh Sleep Quality Index (PSQI), Geriatric Anxiety Inventory (GAI), and the 15-item Geriatric Depression Scale (GDS-15) were used to collect sleep, anxiety, and depression scores, respectively. Multivariate Logistic regression analysis and subgroup analysis were employed to investigate the association between sleep duration, sleep quality, and anxiety and depression. Results: A total of 1 381 community residents aged 60 years and above were included. Among them, 369 (26.7%) had poor sleep quality, 120 (8.7%) were identified with anxiety, and 274 (19.8%) with depression symptoms. Multivariate Logistic regression models revealed that after adjusting for general demographic information, social support, lifestyle, and prevalence of chronic diseases, compared with those with sleep duration ≥7 h, individuals with sleep duration ≤5 h had OR (95%CI) for anxiety and depression symptoms of 2.14 (1.20-3.83) and 2.30 (1.45-3.64). Compared with those with good sleep quality, individuals with poor sleep quality had OR (95%CI) for anxiety and depression symptoms of 4.85 (2.96-7.93) and 3.20 (2.32-4.41). Subgroup analysis by gender revealed that men with sleep duration ≤5 h had a higher risk of anxiety, while women had a higher risk of depression, with OR (95%CI) of 5.67 (1.85-17.36) and 2.55 (1.46-4.47). Poor sleep quality was associated with both anxiety and depression symptoms in both sexes, and this correlation was stronger in women, with OR (95%CI) of 5.21 (2.81-9.66) for anxiety and 4.56 (2.96-7.02) for depression. In the PSQI scale, subjective sleep quality was associated with anxiety and depression symtoms in both sexes, but the association was stronger in women. Conclusion: The impact of sleep on anxiety and depression symptoms in older community-dwelling adults is gender-specific. Older men with short sleep duration are more likely to experience anxiety, while older women are more likely to experience depression. Poor sleep quality and subjective sleep quality affect both anxiety and depression in older community-dwelling adults, with a greater impact on women.
Objective: To investigate the detection rate of pulmonary nodules and related risk factors among non-manual workers in Shanghai, so as to provide a scientific basis for the early prevention and control of lung cancer in this population. Methods: A retrospective cohort study design was employed, enrolling 19 572 non-manual workers from the Shanghai region who underwent health examinations in Shanghai Health and Medical Center from Jan to Dec 2023. The differences in the detection rates of pulmonary nodules among populations stratified by gender and age were analyzed. Based on the presence or absence of pulmonary nodules, the participants were divided into a group with nodules and a group without nodules. Demographic characteristics, physical examination findings, selected laboratory indicators, and past medical history were compared between the two groups, and a predictive model was constructed accordingly. Results: The overall detection rate of pulmonary nodules in this population was 85.89% (16 811/19 572), and the detection rate increased with age. There was no statistically significant difference in the detection rates of pulmonary nodules between genders.Univariate analysis showed that there were significant differences between the two groups in age, systolic blood pressure, total protein, albumin, fasting blood glucose, blood urea nitrogen, waist-hip ratio, history of arteriosclerosis, history of hypertension, history of tumor, history of pulmonary emphysema, history of smoking, and history of Helicobacter pylori infection (P < 0.05). However, there were no significant differences in BMI, heart rate, diastolic blood pressure, globulin, A/G, triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, creatinine, uric acid, as well as gender, history of interstitial lung disease and history of fatty liver. Multivariate logistic regression analysis identified age, high waist-to-hip ratio, history of tumors, smoking history, history of arteriosclerosis, history of hypertension, and history of Helicobacter pylori infection as independent risk factors for pulmonary nodules. The predictive model constructed based on these risk factors demonstrated limited discriminative ability (AUC=0.682, 95%CI: 0.648-0.717). Conclusion: The study population exhibited a high detection rate of pulmonary nodules, the occurrence of which was associated with multiple risk factors. The risk prediction model established using these factors demonstrated limited discriminative performance and thus requires further refinement.
Objective: To investigate the relationship between the insulin resistance marker， the triglyceride glucose index （TyG index）， and the treatment efficacy of sudden sensorineural hearing loss （SSNHL）. Methods: Data from patients with SSNHL hospitalized at the Eye and ENT Hospital，Fudan University from 2019 to 2023 were analyzed retrospectively. A multivariate linear regression model was used to assess the relationship between the TyG index and pure-tone audiometry （PTA） improvement. In addition， restricted cubic spline （RCS） analysis and subgroup analysis were conducted to explore the dose-response relationship between the TyG index and the treatment efficacy of SSNHL， as well as to identify any special populations. Results: A total of 1 306 ears （from 1 259 patients） were included in the study. Multivariable-adjusted linear regression analysis revealed a significant negative association between the TyG index and hearing gain （β=-2.90，95%CI： -5.15 to -0.64； P=0.012）. RCS analysis also confirmed a linear negative relationship between the TyG index and hearing improvement， with a P-value for nonlinearity of 0.475. Subgroup analyses did not identify any significant interactions modifying this relationship. Conclusion: The TyG index is negatively correlated with hearing improvement in patients with SSNHL.
Objective: To evaluate the efficacy of modified Bazhen Granules in treating thrombocytopenia in patients with metastatic renal cell carcinoma（mRCC） after sunitinib targeted therapy. Methods: Patients with mRCC who received sunitinib treatment in the Department of Urology， Zhongshan Hospital， Fudan University between Nov 2020 and May 2023 were randomly divided into the experimental group and the control group. The experimental group was additionally given modified Bazhen Granules prophylactically during the same period. Routine blood tests were performed regularly in both groups to evaluate the severity of thrombocytopenia. Safety and efficacy assessments were conducted periodically. Dose reduction and discontinuations of sunitinib， as well as progression-free survival （PFS）， and overall survival （OS） of patients were also recorded. Results: A total of 88 patients with mRCC were enrolled， including 43 in the experimental group and 45 in the control group. The baseline characteristics of patients in the two groups were generally comparable. After treatment， the incidence of thrombocytopenia in the experimental group was lower than that in the control group （P=0.046）， and the incidence of grade 3-4 thrombocytopenia was also lower （P=0.017）. Patients in the experimental group achieved a higher maximum tolerated dose of sunitinib（P<0.001） and better treatment efficacy （P=0.004）. No significant difference was observed in drug safety between the two groups. Conclusion: Modified Bazhen Granules is safe and effective in relieving thrombocytopenia in mRCC patients treated with sunitinib，and it can enhance the therapeutic efficacy of targeted therapy.
Objective: To determine the distribution of fungal otitis externa flora and genetic variation diversity by morphology, gene sequencing, and phylogenetic tree analysis, to clarify the distribution of fungal infection species, and to obtain relevant information on their evolution and transmission can be obtained, so as to facilitate the implementation of targeted prevention and control work as soon as possible. Methods: The external ear canal secretions of patients with fungal otitis externa were collected for culture and morphological identification, and the strains were isolated. The three gene fragments of ribosomal internal transcribed spacer (ITS), β-tubulin (BenA) and calmodulin (CaM) were amplified and sequenced by nucleic acid amplification technology, and then Basic Local Alignment Search Tool (BLAST) was used for comparison and identification. A phylogenetic evolutionary tree was constructed to accurately identify the Aspergillus strains. Results: The strains (96 strains in total) were composed of Aspergillus (80 strains, 83.33%) and Candida (16 strains, 16.67%). There were 6 main pathogenic strains, including Aspergillus terreus (53 strains, 55.21%), Candida parapsilosis (16 strains, 16.67%), Aspergillus fumigatus (10 strains, 10.42%), Aspergillus tubingensis (7 strains, 7.29%), Aspergillus niger (6 strains, 6.25%), and Aspergillus flavus (4 strains, 4.17%). Based on ITS, BenA, and CaM single genes and multigenes, 8 phylogenetic trees were constructed based on ITS, BenA, and CaM single genes and multigenes by maximum likelihood and neighbor-joining methods. Multigene evolutionary trees could more accurately distinguish Aspergillus niger from Aspergillus tubingensis than single gene evolutionary trees, revealing the diversity distribution of strains. Conclusion: Compared to morphological and gene sequencing methods, constructing phylogenetic trees more accurately identified fungal strains and obtained correct results on the distribution of the fungal community. The closeness of the phylogenetic relationship between high-proportion strains (such as Aspergillus terreus and Aspergillus fumigatus) and the standard strain reflected the genetic variation tendency of dominant strains in external auditory canal fungal infections, providing a clear direction for clinical drug research.
Objective: To translate and revise the Mental Help Seeking Attitudes Scale (MHSAS) into Chinese and evaluate its reliability and validity among urban older adults. Methods: Following international guidelines for cross-cultural translation and adaptation of instruments, the MHSAS was translated into Chinese and revised. A convenience sampling method was used to recruit participants aged 60 years and above from a community health service center and affiliated stations in Pudong New Area, Shanghai. A total of 901 questionnaires were collected, of which 787 valid responses remained after excluding those failing quality control. Item analysis, exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and reliability testing were conducted for the Chinese version of the MHSAS. Results: Item-total correlations ranged from 0.78 to 0.91, and all item scores differed significantly between high- and low-score groups (P < 0.01). EFA extracted one common factor with a cumulative variance contribution rate of 75.95%. Based on factor loadings, modification indices, and cognitive interview findings, the model was adjusted; CFA then showed good fit (χ2/DF=4.920, CFI=0.994, TLI=0.988, SRMR=0.010, RMSEA=0.071). Reliability analysis indicated that Cronbach's α was 0.96 and the Guttman split-half reliability coefficient was 0.92. Conclusion: The revised Chinese version of the MHSAS demonstrated a clear structure and good reliability and validity. It may be used as a measurement tool to assess attitudes toward seeking help from mental health professionals among urban older adults.
Invasive fungal sinusitis refers to the invasion of fungal infection from the sinuses to adjacent tissues and organs, including cavernous sinus, orbital apex, internal carotid artery, meninges, and brain parenchyma, causing serious damage of the nervous system. Invasive fungal sinusitis is more common in patients with immune dysfunction. This disease is extremely dangerous, with a poor prognosis and may even lead to death. Here we report a patient who presented with cavernous sinus-orbital apex syndrome as the first symptom. Combined the imaging examination, previous sinus surgery findings with pathological reports, the patient was diagnosed with invasive fungal sinusitis. After receiving systemic antifungal therapy, the patient's condition conversely worsened progressively, and she was treated with a third sinus operation. The tissue samples were sent for histological evaluation. Finally, the patient was diagnosed as diffuse large B-cell lymphoma (DLBCL) by histopathological and immunohistochemical analysis. The patient subsequently received chemotherapy and radiotherapy, but ultimately had a poor prognosis and died. The purpose of this case report is to enhance understanding of invasive fungal sinusitis and lymphoma of nasal sinuses.
The conventional Cox proportional hazards model relies solely on baseline information for "static" prediction, failing to incorporate the dynamic information of time-varying covariates, including disease progression, biomarker trajectories, and treatment modifications. Although independently fitted landmark models enable dynamic prediction, they are limited by low statistical efficiency and discontinuous predicted risk estimates. The presence of competing events further constrains the applicability of the classical landmark framework. The landmark supermodel is a novel approach to dynamic prediction based on stacked data structures. In complex competing risks setting, the model can be further extended to a cause-specific hazard model. Using the multiethnic cohort study (MEC) dataset under a competing risks survival analysis framework, we demonstrate the implementation of the landmark supermodel via the dynamicLM package in R. The key steps in model construction include: (1) specification of landmark time points and prediction windows; (2) stacking of datasets across landmark time points; (3) construction of covariate-by-time interaction terms; (4) fitting a cause-specific hazard model on the stacked dataset. Model evaluation based on the time-dependent AUC, Brier score, and calibration curves demonstrated that the landmark supermodel exhibits satisfactory discriminative ability and predictive accuracy in competing risks scenarios. When applied in clinical practice, individual dynamic risk trajectory curves can be generated, providing quantitative evidence to inform personalized follow-up and screening strategies.
