Beijing Hua Xin Hospital

Holt-Oram syndrome, also known as atrio-digital syndrome, is a rare autosomal dominant genetic disorder primarily characterized by upper limb malformations and congenital heart defects, associated with mutations in the TBX5 gene. Diagnosis is typically based on clinical presentation, and the prognosis for affected individuals is closely related to the severity of cardiac involvement. Our study aims to highlight some key features of Holt-Oram syndrome to improve the level of clinical diagnosis. We collected 11 patients with clinical features strongly suggestive of Holt-Oram Syndrome at the First Affiliated Hospital of Tsinghua University from January 2010 to January 2025. These patients exhibited both limb malformations and cardiac abnormalities. We then analyzed the characteristics of their diseases. The skeletal abnormalities and cardiac defects presented in diverse forms among the 11 patients. Among the congenital heart diseases, atrial septal defect (ASD) was the most common, accounting for 80% of cases. However, some patients presented with severe conditions such as tetralogy of Fallot or Ebstein's anomaly. Regarding upper limb malformations, the most frequent finding was triphalangeal thumb (8/10 patients), but thumb hypoplasia or aplasia and radial bone abnormalities were also observed. The predominant cardiac structural abnormality in this group of patients was atrial septal defect. Upper limb malformations were predominantly characterized by polydactyly or syndactyly. However, arrhythmias appeared to be mainly supraventricular tachycardia, and upper limb involvement did not seem to show a clear left-sided predominance. The prognosis following cardiac corrective surgery was favorable. Nevertheless, for this condition, emphasis should be placed on prevention.

Human disease network (HDN) analysis, which jointly considers a large number of diseases and focuses on their interconnections, is getting increasingly popular and can shed important insight not possessed by individual-disease-based analysis. Multiple network analysis techniques have been developed for HDNs, although new developments are still strongly needed. In this article we adopt latent space modeling, which has proven powerful in other network analysis contexts and offers unique, insightful interpretations, but has been limitedly applied in HDN analysis. Different from some other types of network analysis and some other HDN analyses (such as gene-centric ones), in this article we pay unique attention to modeling temporal variations. For this purpose, a penalization approach is developed, which can identify time regions with constant network structures (that correspond to ignorable changes) as well as those with smooth variations. The statistical and computational properties are rigorously established. With Medicare data—one of the most powerful medical claims databases—we analyze the admission records of 133 million hospital inpatient treatments from January 2008 to December 2019. Sensible findings are made on disease interconnections and clustering structures. Additionally, the temporal variations, which have not been revealed in the literature, are found to be interpretable. The analysis can provide a new way for connecting and grouping diseases and assist in understanding and planning medical resources.

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.

BackgroundCirrhosis, particularly HBV-induced, poses a significant global health burden. This study compares immune cell landscapes in HBV and non-viral cirrhosis using single-cell RNA sequencing (scRNA-seq) to elucidate distinct immune mechanisms driving disease progression.MethodsLiver tissues from HBV cirrhosis patients and healthy controls were analyzed via scRNA-seq. Public single-cell and spatial transcriptomics data were integrated to map immune cell populations. Computational analyses included differential expression, pathway enrichment (KEGG/GO), and cell–cell communication (CellChat).ResultsHBV cirrhosis exhibited expanded Macrophage-PLCG2 (anti-inflammatory) and CD8 + T-FABP5 subsets, while Macrophage-CD5L, CD4 + T-ANXA1, CD4 + T-CCR6, and NK-FCER1G were reduced. Pathway analysis linked Macrophage-PLCG2 to Rap1 signaling, whereas Macrophage-CD5L associated with lysosomal pathways. Spatial analysis revealed myeloid-T cell colocalization in HBV cirrhosis. Enhanced HLA-E/KLRK1 signaling between myeloid and NK cells was identified in HBV cases (p < 0.05).ConclusionThis study delineates immune cell heterogeneity between HBV and non-viral cirrhosis, highlighting potential therapeutic targets like Macrophage-PLCG2 and CD8 + T-FABP5. Findings underscore the role of immune dysregulation in HBV cirrhosis progression.

Abstract Aim Positive coronary remodeling closely related to plaque burden is an independent risk factor for poor long-term prognosis in patients with coronary heart disease. This study aims to investigate the association of insulin resistance (IR) and positive coronary remodeling and plaque burden in patients with acute coronary syndrome (ACS). Methods This study retrospectively analyzed patients with ACS who underwent intravascular ultrasound (IVUS)-guided revascularization in our hospital from December 2020 to December 2021. The homeostasis model assessment insulin resistance index (HOMA-IR) was assessed by the homeostasis model, and a HOMA-IR value greater than 2.5 was defined as IR positive. The lesion site, the proximal and distal ends of the lesion, and the external elastic membrane (EEM) and lumens were assessed by IVUS. The remodeling index was calculated by the formula (EEM at the lesion/mean value of EEM at the proximal and distal reference sites of the lesion). The definition of remodeling index greater than 1.05 is positive remodeling; remodeling index &lt; 0.95 is negative remodeling; 0.95 ≤ remodeling index ≤ 1.05 is intermediate state. Plaque burden, defined as (vessel area-lumen area)/vessel area, is automatically calculated by the IVUS analysis system and presented in the report. Results In strict accordance with the inclusion and exclusion criteria, a total of 98 ACS patients were included in this study, including a total of 111 target lesions assessed by IVUS. Preliminary analysis found that the plaque burden (70.91 ± 11.49 vs 66.03 ± 13.04, p = 0.040) and remodeling index (1.02 ± 0.32 vs 0.88 ± 0.28, p = 0.018) of the IR-positive group were significantly higher than those of the insulin resistance-negative group. Further analysis found that the IR-positive group had a relatively high rate of positive remodeling (43.4% vs 15.5%) and a relatively low rate of negative remodeling (47.2% vs 58.6%) and intermediate state (9.4% vs 25.9). In univariate regression analysis, glycosylated hemoglobin (hemoglobin A1c, HbA1c) ( OR = 0.694, 95% CI 0.508 to 0.946, p = 0.021) was associated with IR ( OR = 4.174, 95% CI 1.706 to 10.211, p = 0.002) It is closely related to positive coronary remodeling. After further adjusting for age, gender, HbA1c, and other confounding factors by multivariate regression analysis, IR was still an independent risk factor for positive coronary remodeling ( OR = 3.611, 95%CI 1.431 to 9.111, p = 0.007). Receiver operating characteristic curve assessment found that HOMA-IR predicted moderate positive coronary remodeling (AUC 0.656, 95%CI 0.542 to 0.771, p = 0.0074). By calculating the Youden index, it was found that the prediction power was the best when the HOMA-IR was 2.44, with a sensitivity and specificity of 63.3% and 71.9%, respectively. Conclusions IR positivity assessed by HOMA-IR was independently associated with positive coronary remodeling in ACS patients. However, its power to predict positive coronary remodeling in ACS patients is relatively low. IR positivity was significantly associated with plaque burden at the most severe coronary stenosis in ACS patients.

Peroxisome proliferator-activated receptors (PPARs) play critical roles in metabolic regulation, inflammation, and cellular differentiation. Recent studies have revealed their significant involvement in a spectrum of kidney diseases, including chronic kidney disease (CKD), acute kidney injury (AKI), diabetic kidney disease (DKD), renal cell carcinoma, lupus nephritis, and autosomal dominant polycystic kidney disease. In this narrative review, we summarize current insights into the roles and mechanisms of PPARs in kidney pathophysiology and evaluate the efficacy of PPAR-targeted therapies in both animal models and clinical studies. Collectively, our analysis highlights the therapeutic potential of PPARs as promising molecular targets for renal disorders, particularly CKD, AKI, and DKD. However, important challenges remain for clinical translation, including dose-dependent adverse effects and the lack of renal-specific drug delivery, both of which highlight the need for safer and more targeted PPAR modulators.

Diabetes mellitus (DM), a globally prevalent metabolic disease, affects the nervous system through multiple mechanisms, leading to cranial neuropathies. Tolosa-Hunt syndrome (THS) is a rare disorder that, when occurring in diabetic patients, may present with clinical manifestations that overlap with diabetic cranial neuropathy (DCN), increasing the risk of misdiagnosis and delaying corticosteroid treatment. This study aims to systematically analyze the clinical characteristics of THS in diabetic patients and explore optimal management strategies. This study conducted a retrospective analysis, integrating data from previously published cases and cases diagnosed at our center. Inclusion criteria were based on the diagnostic standards for THS outlined in the ICHD-3, while cases with other potential causes of headache and ophthalmoplegia were excluded. Data collected included baseline characteristics, clinical manifestations, treatment regimens, and therapeutic outcomes. Statistical analysis was performed using Fisher's exact test, t-test, and Wilcoxon rank-sum test. A total of 19 cases of diabetes-associated THS were included (11 males, 8 females), with males presenting at a significantly younger age than females (P = 0.041). All patients experienced severe headaches, 89.47% had ptosis, 94.73% exhibited ophthalmoplegia, and 15.79% presented with facial sensory disturbances. Eight patients were initially misdiagnosed with DCN and received neurotrophic therapy without improvement, but they responded rapidly to corticosteroid treatment. All patients showed significant symptom improvement within six days of corticosteroid administration. Methylprednisolone and dexamethasone demonstrated therapeutic effects comparable to prednisone, though symptom resolution was slightly delayed in the prednisone group. The clinical features of diabetes-associated THS include severe headache, ptosis, and ophthalmoplegia, which can be easily confused with DCN. Corticosteroid therapy demonstrated high efficacy in this cohort. Clinicians should consider the possibility of THS in diabetic patients presenting with ptosis and ophthalmoplegia to avoid misdiagnosis and ensure timely corticosteroid treatment, thereby improving patient outcomes.

Severe disabling attacks neuromyelitis optica spectrum disorders (NMOSD) severely affect patients’ quality of daily life and life safety. This retrospective study enrolled consecutive Chinese patients suffering from NMOSD who visited the China-Japan Friendship Hospital (Beijing, China) between October, 2010 and February, 2023. Correlation analysis was used to perform feature selection. The prediction model was constructed using the support vector machine (SVM) and extreme gradient boosting (XGBoost) algorithm. A total of 356 patients (mean [SD] age, 34.45[15.22] years) and 1291 NMOSD attacks were eligible for this study. ON and age were positively and linearly correlated, and TM and age were negatively and linearly correlated. Throbbing headache and neuralgia showed a significant linear relationship with disabling episodes, and circumventricular organ- area postrema syndrome (CVO-APS) showed a significant linear relationship with disabling episodes only in a few cases. We select top three high correlation variable (HCV) for predicting ON and TM models. Then, we constructed prediction models based on the XGBoost using age as a feature, and HCV and warning symptoms (WS) as features respectively. The ML models showed reasonable predictive performance for ON (Age + WS: AUC, 0.809; Age + HCV: AUC, 0.787) and TM (Age + WS : AUC, 0.817; Age + HCV: AUC, 0.854) We also constructed the first prediction model about severe NMOSD attacks using XGBoost and SVM. Among them, the fundamental model incorporated the 16 features with AUC of Xgboost: 0.830 and SVM: 0.775. On the basis of the fundamental model, we also incorporated the results of nadir and remission the expanded disability status scale (EDSS) or visual outcome scale (VOS) from the last time attack as features to construct 12 optimized models. As a whole, the optimized models showed higher predictive performance for severe attack. The AUC for the model adding the nadir EDSS scores as features were XGBoost: 0.862, SVM: 0.741, adding the nadir VOS scores as features were XGBoost: 0.870, SVM: 0.723, adding the remission EDSS scores as features were XGBoost: 0884, SVM: 0.806, adding the remission VOS scores as features were XGBoost: 0.9998, SVM: 0.700, adding both nadir and remission EDSS scores as features were XGBoost: 0.899, SVM: 0.794, adding both nadir and remission VOS scores as features were XGBoost: 0.905 and SVM: 0.705. This study innovatively identified associations between disabling attacks of NMOSD and age, warning symptoms and developed an easy-to-use, less costly and less invasive machine learning model for predicting NMOSD disabling attack symptoms and severe attacks.