Beijing Ditan Hospital

Community-acquired pneumonia (CAP), particularly severe CAP (SCAP), poses a significant clinical challenge with high mortality. MicroRNAs, including miR-342-3p, have been implicated in various pulmonary diseases, suggesting a potential role in SCAP. To examine the expression, functional mechanisms, and clinical relevance of miR-342-3p in SCAP. Bioinformatic analysis was performed on two independent GEO datasets (GSE196399 and GSE136390). Serum miR-342-3p levels were measured in a clinical cohort of 109 SCAP patients and 109 healthy controls by RT-qPCR, and its correlation with clinical prognosis was analyzed. An in vitro pneumonia model was established using LPS-stimulated MRC-5 cells. Gain-of-function experiments of miR-342-3p were achieved through mimic transfection. MiR-342-3p's involvement in inflammation, cytotoxicity, and pyroptosis was assessed via ELISA, western blot, CCK-8, and LDH assays. The interaction between miR-342-3p and EP300 was confirmed by dual-luciferase reporter and RNA pull-down assays, and its functional role was confirmed through rescue experiments. The downregulation of miR-342-3p in SCAP patient serum correlated with increased mortality. In vitro, miR-342-3p overexpression reduced LPS-induced inflammation and pyroptosis. Bioinformatics analysis confirmed that histone acetyltransferase EP300 is a candidate target gene for miR-342-3p. Mechanistically, miR-342-3p directly targeted and negatively regulated EP300. Overexpression of EP300 abolished the anti-inflammatory and anti-pyroptotic effects of miR-342-3p through the activation of NF-κB p65. MiR-342-3p acts as a protective factor in SCAP by targeting EP300 to inhibit inflammation and pyroptosis. These results indicate the potential of miR-342-3p as a biomarker and therapeutic target in SCAP.

To compare the efficacy and safety of BIC/FTC/TAF versus EFV+3TC + TDF for rapid ART initiation in late-presenting (CD4 < 200 cells/µL) people with HIV in the real world. This retrospective cohort included 366 ART-naïve adults at Beijing Ditan Hospital (2021–2024). Patients were stratified by opportunistic infection (OI) status and initiated on either BIC/FTC/TAF or EFV+3TC + TDF. The primary endpoint was virological suppression (HIV-1 RNA < 50 copies/mL) at Week 48. At Week 48, virological suppression rates were significantly higher with BIC/FTC/TAF versus EFV+3TC + TDF in both patients without OIs (92.4% vs. 62.5%) and with OIs (92.3% vs. 55.9%). Treatment retention was also superior with BIC/FTC/TAF (94.1% vs. 62.3%). Kaplan-Meier analysis confirmed a higher cumulative probability of maintaining suppression with BIC/FTC/TAF (96.7% vs. 80.4%, log-rank p < 0.001). Pre-treatment drug resistance in NNRTIs was present in 11.6% of the EFV group and 1.4% of the BIC group. Acquired resistance emerged only in the EFV group (10.8% by Week 24). CD4 + T-cell counts in both groups increased. BIC/FTC/TAF was associated with early, stable increases in creatinine and lipids, while EFV+3TC + TDF showed a marked triglyceride rise. In this real-world cohort of late-presenting people with HIV, BIC/FTC/TAF demonstrated superior virological efficacy, treatment retention, and resistance profile over EFV+3TC + TDF, supporting its use in rapid ART initiation.

BackgroundMass-forming (MF) type is the most common, accounting for 57.1–83.6% of intrahepatic cholangiocarcinoma (ICC), with a poor prognosis. Transarterial chemoembolization (TACE) can induce necrosis of tumor cells, induce the release of tumor antigens, enhance the immune response of tumor-specific CD8+ T cells, and regulate the proliferation of Treg cells. However, real-world data directly comparing TACE combined with programmed cell death protein-1 (PD-1) versus programmed death ligand-1 (PD-L1) inhibitors in MF-ICC are lacking. Therefore, we aimed to evaluate the efficacy and safety between the different immune checkpoint inhibitors (ICIs) (PD-1/PD-L1 inhibitors) in MF-ICC, and to explore prognosis-related clinical factors and preliminary immune mechanisms underlying this combined therapy.MethodsA total of 50 patients with MF-ICC who underwent TACE combined with ICIs at Beijing Friendship Hospital and Beijing Ditan Hospital from May 2020 to December 2024 were retrospectively enrolled. Least absolute shrinkage and selection operator (LASSO) regression was used to screen the risk factors of overall survival (OS). Survival was estimated using the Kaplan-Meier method and compared by the log-rank test. Univariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between treatment regimen and survival. In parallel, we analyzed dynamic changes in immune cells before and after ICI treatment using the single-cell RNA sequencing dataset GSE208205 and further validated these findings by flow cytometry.ResultsThe median overall survival (mOS) and median progression-free survival (mPFS) for TACE-PD-L1 followed by therapy were 18 and 13 months, which were significantly longer than those with TACE-PD-1 sequential therapy (mOS: 12 months, HR: 0.42, 95% CI: 0.17–1.03, P=0.047; mPFS: 8 months, HR: 0.29, 95% CI: 0.12–0.73, P=0.006). In exploratory multivariable analysis, pre-treatment monocyte-to-lymphocyte ratio (MLR), Child-Pugh classification, total bilirubin (TBIL), and alanine aminotransferase (ALT) emerged as potential prognosis-related factors for OS. Single-cell analysis showed that CD4+ T and CD8+ T cells were markedly increased after treatment, while circulating tumor cells and vascular endothelial cells were decreased. This was further validated by the flow cytometry. Moreover, regardless of treatment status, ICC patients in the PD-L1 groups exhibited higher levels of CD4+ and CD8+ T cells compared to the PD-1 group, whereas B cells were lower in the PD-L1 group than in the PD-1 group.ConclusionsTACE combined with PD-L1 inhibitors was associated with longer survival than TACE combined with PD-1 inhibitors in patients with mass-forming ICC. The immune system, particularly lymphocytes, plays a critical role in the efficacy of combination therapy. In addition, several baseline inflammation- and liver function-related factors (MLR, Child-Pugh class, TBIL, ALT) were associated with OS in exploratory analyses.

To investigate the clinical characteristics and imaging features of patients with spontaneous pneumomediastinum (SPM) and conduct a literature review to provide reference strategies for the diagnosis and treatment of the affected population. A retrospective analysis was conducted on patients diagnosed with SPM via chest computed tomography (CT) at our Hospital from January 2022 to December 2023. General information, clinical manifestations, and imaging findings were collected and analyzed. Relevant domestic and international literature was reviewed, and a comparative analysis was performed. A total of 40 patients were included in this study. Acute retrosternal pain was the most common symptom (45.0%), followed by varying degrees of dyspnea, shortness of breath, and chest tightness (25.0%), persistent coughing (17.5%), and discomfort or pain in the neck and throat (5%). The Macklin effect was observed in 38 patients, characterized by varying degrees of gas accumulation around the mediastinum near the pulmonary hilum. After three days of treatment, the symptoms resolved, and follow-up chest CT scans indicated absorption of mediastinal gas. Patients showed improvement and were discharged. The clinical manifestations of SPM are complex and diverse, making it prone to clinical misdiagnosis or delayed diagnosis, which may hinder timely treatment. Chest CT is instrumental in the accurate diagnosis of mild mediastinal emphysema. A comprehensive evaluation, incorporating patient complaints and clinical symptoms with chest CT findings, is essential for accurate diagnosis.

Postpartum hemorrhage (PPH) remains the leading cause of maternal mortality and a common obstetric complication. Rapid onset and severity can lead to hemorrhagic shock and fatal outcomes if not promptly managed. Major causes include uterine atony, placental abnormalities, birth canal trauma, and coagulation disorders. This study proposes a risk prediction model for PPH based on a Deep Belief Network (DBN), using relevant risk factors as input features. To address limitations from random initialization in the DBN, an improved Particle Swarm Optimization (IPSO) algorithm—featuring adaptive inertia weight and learning factors—was introduced to optimize network parameters. The optimized model, referred to as IDBN, was applied to predict PPH risk levels more accurately and efficiently. The results demonstrate the superior performance of the IDBN method, which achieved the highest accuracy and F1 score among all models evaluated. This approach offers a novel, data-driven method for early PPH risk identification and clinical intervention.

BackgroundThe Hedgehog signaling pathway is involved in the carcinogenesis and development of hepatocellular carcinoma(HCC); however, few studies on the prognostic model of the Hedgehog signaling pathway have been found.MethodsFirst, we selected 56 Hedgehog signaling pathway-related genes from the UALCAN database and used the DESeq2 method to screen out differentially expressed genes in HCC and normal liver samples. Validation was performed using quantitative real-time PCR (qRT-PCR) of HCC and normal tissues. Second, the differentially expressed genes were analyzed using Cox and Lasso regression, and a five-gene prognostic risk model was established. Risk scores were divided into high-risk and low-risk groups, and their correlation with clinical indicators and immunity was analyzed. Univariate and multivariate regression analyses were performed for risk scores. Finally, a comparative functional enrichment analysis was conducted to delineate the biological pathway disparities between the high- and low-risk groups. The effectiveness of the model was validated using the ICGC database.ResultsThe prognostic risk model of five genes(BMP2,CSNK1D,CSNK1E, ZIC2, and PRKACB) was obtained after screening 56 Hedgehog signaling pathway-related genes. Risk scores emerged as robust independent predictors of overall survival through univariate and multivariate analyses, independent of other clinicopathological parameters, in TCGA and ICGC cohorts. A significant correlation was observed between risk scores and immune microenvironment characteristics, including immune cell infiltration and immune checkpoint expression levels. qRT-PCR analysis confirmed that the expression of the five genes in the prognostic model was higher in HCC tissues than in normal tissues. Moreover, some functional pathways were identified in the high-risk group in the low-risk group.ConclusionsWe developed a novel five-gene prognostic model centered on Hedgehog signaling pathway-related genes, which holds potential as a valuable prognostic tool for HCC and may provide guidance for immunotherapy selection.