Objective: To explore the role and mechanism of epiregulin (EREG) in clear cell renal cell carcinoma (ccRCC)，and to find biomarkers and therapeutic targets for ccRCC. Methods: Based on the data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases，the correlation between the expression level of EREG in ccRCC tissues and the clinical staging and survival of ccRCC patients was analyzed. The samples of 6 ccRCC cases treated in the Second Affiliated Hospital of the Air Force Medical University were collected. The expression of EREG was confirmed with immunohistochemistry and quantitative real-time polymerase chain reaction (q-PCR). The effects of EREG overexpression on the proliferation，cell cycle and apoptosis of ACHN cells were verified with CCK-8 and flow cytometry. Finally，the expressions of EREG，epidermal growth factor receptor (EGFR) and the downstream pathway proteins were detected with Western blotting. Results: Based on the databases，it was found that the expression of EREG in ccRCC samples was higher than that in adjacent tissues，and there was a positive correlation with the clinical stage. Survival analysis showed that high expression of EREG was a risk factor affecting the prognosis. The results of immunohistochemical staining and qPCR revealed that EREG was highly expressed in ccRCC. Flow cytometry showed that EREG overexpression promoted the proliferation of ACHN cells，enhanced cell cycle，and inhibited apoptosis. In addition，Western blotting suggested that EREG promoted the expressions of EREG，EGFR and the downstream proteins. Conclusion: The expression of EREG is associated with the prognosis of ccRCC patients. In vitro cell experiments have shown that it can promote the proliferation of ccRCC cells and inhibit their apoptosis，thereby leading to the progression of ccRCC. It can serve as a potential biomarker for prognosis prediction and a drug development target for ccRCC patients.

Objective To investigate the detection status and risk factors of bacterial pneumonia (BP) in elderly patients with acute ischemic stroke (AIS), and to provide evidence for the prevention and treatment of BP in elderly patients with AIS. Methods The case data of 320 elderly patients with AIS admitted to Xijing Hospital from June 2021 to June 2024 were retrospectively collected and analyzed. The distribution status of pathogenic bacteria of BP in the elderly AIS patients was statistically analyzed, and the risk factors of BP in AIS patients were explored and the predictive value was analyzed. Results Among the 320 elderly AIS patients, 57 cases (17.81%) developed BP. Multivariate logistic stepwise regression analysis showed that concurrent dysphagia [OR (95% CI) = 1.654 (1.240-2.206)], high platelet to lymphocyte ratio (PLR) [OR (95% CI) = 1.418 (1.116-1.801)], high neutrophil to lymphocyte ratio (NLR) [OR (95% CI) = 2.756 (1.197-5.360)], and acute ischemic stroke-associated pneumonia score (AIS-APS) [OR (95% CI) = 3.414 (1.574-7.405)] were independent influencing factors for BP in elderly AIS patients (P<0.05). The combination of the above four factors had the largest area under the curve (AUC) (0.866) in predicting BP in elderly AIS. Conclusion The occurrence of BP in elderly AIS patients is related to dysphagia, high level of PLR, high level of NLR, and high score of AIS-APS. It is necessary to strengthen the early identification and intervention of high-risk factors in clinical practice.

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People

BACKGROUND: Chronic kidney disease (CKD) poses a major global health challenge, often foreshadowing poor patient outcomes. The C-reactive protein to albumin ratio (CAR) serves as a pivotal biomarker, demonstrating a strong correlation with adverse outcomes in cardiovascular disease (CVD). This study sought to examine the correlation between CAR and the risk of all-cause and cardiovascular mortality in patients with CKD stages 3-5. METHODS: This study utilized data of CKD patients from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010, with follow-up to December 31, 2019. The optimal CAR cutoff value was identified utilizing the method of maximally selected rank statistics. Multivariable Cox proportional hazards regression model, restricted cubic splines (RCS) model, and subgroup analysis were employed to assess the association between CAR and mortality among CKD patients. RESULTS: During a median (with interquartile range) follow-up period of 115 (112,117) months among 2,841 CKD individuals, 1,893 deaths were observed, including 692 deaths due to CVD events. Based on the RCS analysis, a non-linear correlation was observed between CAR and mortality. Using 0.3 as the optimal CAR cutoff value, the cohort was divided into high and low groups. In the fully adjusted model, CKD patients with high CAR values exhibited an elevated risk of all-cause mortality (hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.28-1.83, P < 0.001) and cardiovascular mortality (HR 1.48, 95% CI 1.08-2.02, P = 0.014). Compared to the population aged >65 years (HR 1.32, 95% CI 0.99-1.76, P = 0.064), the risk of cardiovascular mortality was significantly higher in those aged ≤65 years (HR 2.19, 95% CI 1.18-4.09, P = 0.014) with elevated CAR levels. CONCLUSIONS A notable correlation exists between the elevation of CAR and increased all-cause and cardiovascular mortality, suggesting its potential as an independent indicator for evaluating the prognosis of patients with CKD stages 3-5.
Humans ; Renal Insufficiency, Chronic/epidemiology* ; Cardiovascular Diseases/blood* ; Male ; Female ; Middle Aged ; C-Reactive Protein/metabolism* ; Aged ; Biomarkers/blood* ; Nutrition Surveys ; Adult ; United States/epidemiology* ; Serum Albumin/analysis*

Transcranial temporal interference stimulation (tTIS) is a novel non-invasive neuromodulation technique with the potential to precisely target deep brain structures. This study explores the neural and behavioral effects of tTIS on the superior colliculus (SC), a region involved in eye movement control, in mice. Computational modeling revealed that tTIS delivers more focused stimulation to the SC than traditional transcranial alternating current stimulation. In vivo experiments, including Ca²⁺ signal recordings and eye movement tracking, showed that tTIS effectively modulates SC neural activity and induces eye movements. A significant correlation was found between stimulation frequency and saccade frequency, suggesting direct tTIS-induced modulation of SC activity. These results demonstrate the precision of tTIS in targeting deep brain regions and regulating eye movements, highlighting its potential for neuroscientific research and therapeutic applications.
Animals ; Superior Colliculi/physiology* ; Transcranial Direct Current Stimulation/methods* ; Eye Movements/physiology* ; Male ; Mice ; Mice, Inbred C57BL

ObjectiveTo investigate the application value of Qingre Huashi Sanjie enema prescription in the treatment of the patients with sequelae of pelvic inflammatory disease （syndrome of combined dampness，heat，and stasis） and the effects of this prescription on inflammatory mediators and T lymphocyte subsets. MethodThe patients with sequelae of pelvic inflammatory disease （syndrome of combined dampness，heat，and stasis） treated from May 2022 to August 2023 were included in this study and randomized into two groups （79 cases）. The control group was treated with conventional Western medicine，and the observation group was treated with Qingre Huashi Sanjie enema prescription on the basis of the therapy in the control group. Both groups were treated for 12 weeks. The serum levels of monocyte chemoattractant protein-1 （MCP-1），transforming growth factor-β₁ （TGF-β₁），and interleukin-6 （IL-6） were measured by enzyme linked immunoserbent assay （ELISA） before and after treatment in both groups. The erythrocyte sedimentation rate （ESR） and fibrinogen （FIB） were measured by an automatic blood rheology analyzer before and after treatment in both groups. The serum levels of CD4⁺，CD4⁺/CD8⁺ before and after treatment in both groups were measured by flow cytometry. The traditional Chinese medicine （TCM） symptom score and the 36-item short form survey （SF-36） score were assessed before and after treatment. The uterine artery resistance index （RI），uterine artery pulsatility index （PI），and uterine artery peak systolic velocity （PSV） were measured by Doppler before and after treatment. The clinical efficacy and the occurrence of adverse reactions were compared between the two groups. ResultAfter treatment，the levels of MCP-1，TGF-β₁，IL-6，ESR，and FIB decreased in both groups （P<0.01），and the decreases were larger in the observation group than in the control group （P<0.05，P<0.01）. After treatment，the serum levels of CD4⁺ and CD4⁺/CD8⁺ elevated in both groups （P<0.01） and the observation group had higher levels of CD4⁺ and CD4⁺/CD8⁺ than the control group （P<0.05，P<0.01）. The treatment in both groups decreased the TCM symptom score and TCM sign score and increased the SF-36 score （P<0.01），and the changes were more significant in the observation group than in the control group （P<0.05，P<0.01）. In addition，the treatment lowered RI and PI and elevated PSV （P<0.01），and the changes in these indicators were more significant in the observation group than in the control group （P<0.01）. The total response rate in the observation group was 93.67% （74/79），which was higher than that （79.75%，63/79） in the control group （χ²=6.645，P<0.05）. There was no significant difference in the occurrence of adverse reactions between the two groups. ConclusionFor the patients with sequelae of pelvic inflammatory disease （syndrome of combined dampness，heat，and stasis），Qingre Huashi Sanjie enema prescription can reduce inflammation，attenuate hypercoagulability，improve hemodynamics，and regulate the immune function，demonstrating a definite therapeutic effect.

Background::There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients.Methods::In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12.Results::At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician’s Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs. 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs. 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. Conclusion::Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.Trial registration::ClinicalTrials.gov, NCT05108766.

Background::Limited information exists regarding the impact of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection on psoriasis patients. The objective of this study was to identify clinical factors associated with the prognosis of psoriasis following SARS-CoV-2 infection.Methods::A retrospective, multicenter study was conducted between March and May 2023. Univariable and multivariable logistic regression analyses were employed to identify factors associated with coronavirus disease 2019 (COVID-19)-related psoriasis outcomes. The study included 2371 psoriasis patients from 12 clinical centers, with 2049 of them having been infected with SARS-CoV-2.Results::Among the infected groups, lower exacerbation rates were observed in individuals treated with biologics compared to those receiving traditional systemic or nonsystemic treatments (22.3% [236/1058] vs. 39.8% [92/231] vs. 37.5% [140/373], P <0.001). Psoriasis progression with lesions (adjusted odds ratio [OR] = 8.197, 95% confidence interval [95% CI] = 5.685–11.820, compared to no lesions), hypertension (adjusted OR = 1.582, 95% CI = 1.068–2.343), traditional systemic (adjusted OR = 1.887, 95% CI= 1.263–2.818), and nonsystemic treatment (adjusted OR= 1.602, 95% CI= 1.117–2.297) were found to be associated with exacerbation of psoriasis after SARS-CoV-2 infection, but not biologics (adjusted OR = 0.931, 95% CI = 0.680–1.274, compared to no treatment), according to multivariable logistic regression analysis. Conclusions::A reduced risk of psoriasis exacerbation after SARS-CoV-2 infection was observed with biologics compared to traditional systemic and nonsystemic treatments. Significant risk factors for exacerbation after infection were identified as existing psoriatic lesions and hypertension.

Migraine is a heterogeneous disease with various subtypes,and the diagnosis of migraine mainly relies on clinical criteria.The lack of specific biomarkers for objective assessment impacts the precise diagnosis,treatment selec-tion,and prognostic assessment of migraine.In recent years,great progress has been made in migraine in terms of genet-ics,biochemistry,and imaging,which provides objective indicators for the clinical diagnosis and treatment of migraine.Identifying specific,sensitive,easily detectable,and highly feasible markers in clinical practice will accelerate the early di-agnosis and precise treatment of migraine.