First People's Hospital of Yunnan Province

Pulmonary hypertension (PH) is a progressive disease marked by pulmonary arterial remodeling and right ventricular dysfunction. The molecular mechanisms driving this remodeling, particularly ECM (extracellular matrix)-mediated processes, remain poorly understood. This study investigates THBS4 (thrombospondin-4), an ECM glycoprotein, as a key regulator of pulmonary vascular remodeling in pulmonary hypertension. Whole-transcriptomic analysis was conducted on pulmonary arteries from rat models of pulmonary hypertension induced by hypoxia, hypoxia-SUGEN, and monocrotaline. THBS4 expression was measured in these models and in serum and lung tissue from patients with pulmonary arterial hypertension. The role of HIF-1α (hypoxia-inducible factor 1-alpha), SMAD2, and p38 MAPK (mitogen-activated protein kinase) signaling pathways in regulating THBS4 was explored. Functional assays assessed THBS4's impact on pulmonary artery smooth muscle cells. In vivo, THBS4 silencing was performed to evaluate its effect on vascular remodeling and right ventricular hypertrophy. THBS4 was upregulated in pulmonary arteries across all pulmonary hypertension models, with expression correlating with disease severity. Elevated THBS4 levels were observed in pulmonary arterial hypertension patient serum and lung tissue. Hypoxia-induced THBS4 expression was mediated by HIF-1α, while TGF (transforming growth factor)-β1 stimulation enhanced THBS4 via SMAD2 and p38 MAPK pathways. THBS4 promoted pulmonary artery smooth muscle cell proliferation, phenotypic modulation, and ECM remodeling. In vivo silencing of THBS4 attenuated pulmonary vascular remodeling and right ventricular hypertrophy. Our findings identify THBS4 as a central regulator in a self-reinforcing THBS4-TGF-β/SMAD2 signaling axis driving pulmonary vascular remodeling. Targeting THBS4 represents a promising therapeutic strategy to mitigate pathological vascular remodeling in pulmonary hypertension.

Thrombosis underlies many life-threatening cardio-cerebrovascular diseases. Although existing anticoagulants are effective in treating thrombotic diseases, their application is limited due to the concern of bleeding. New anticoagulants that preserve hemostasis have significant clinical importance. Herein, a novel galactosylated glycosaminoglycan, with unique sequence and sulfate substitutions, was isolated from the snail Camaena cicatricose (CCG). Administration of CCG effectively inhibited thrombus formation in a rat venous thrombosis model, which is positively correlated with its ex vivo anticoagulant activity (APTT prolongation), with much lower bleeding risk compared with heparins. It is also effective in preventing thrombosis in the rat arterial-venous shunt model and endotoxin-treated mice. CCG inhibited coagulation by selectively targeting iFXase enzyme complex (FIXa-FVIIIa), in an antithrombin (AT)-independent manner. CCG can bind to FIXa with high affinity and decrease the affinity of FIXa-FVIIIa, with no effect on the FIXa activity. Compared with heparins, it cannot bind to AT and exhibits high selectivity for iFXase inhibition, consistent with its absence of the specific heparin pentasaccharide sequence. Overall, the snail galactosed glycosaminoglycan inhibits thrombosis without affecting hemostasis via disrupting iFXase (FIXa-FVIIIa). CCG may represent a promising candidate for thrombosis treatment without increased bleeding risk.

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.

Endoscopic retrograde appendicitis therapy (ERAT) and its visually enhanced technique (Endoscopic direct appendicitis therapy, EDAT) represent a novel minimally invasive approach, offering advantages such as high-definition real-time visualization and precise intervention. This article reports a case of a 49-year-old male with acute appendicitis accompanied by an early abscess. CT findings suggested appendicitis with abscess formation, while EDAT exploration confirmed perforation at the appendiceal tip along with adjacent fecalith impaction, further verified by contrast imaging. During the procedure, the fecalith was extracted via EDAT, followed by irrigation of the purulent cavity and placement of a modified 7 Fr × 7 cm pancreatic stent for drainage. The patient experienced immediate symptom relief postoperatively, with serial follow-up CT scans on the procedure day, 3rd, and 7th postoperative days demonstrating gradual abscess resolution and normalized inflammatory markers, leading to discharge on day 3. A subsequent 3-month telephone follow-up revealed no recurrence of abdominal pain. This case illustrates that EDAT/ERAT can provide integrated diagnosis and definitive management for complicated appendicitis, avoiding the trauma associated with surgical intervention and offering valuable clinical insights.

ABSTRACT Aims Cirrhosis alters blood lipid profiles, yet how these changes differ according to disease etiology and respond to transjugular intrahepatic portosystemic shunt (TIPS) remains unclear. This preliminary study aimed to characterize lipid profile patterns across common cirrhosis types and evaluate their changes after TIPS. Methods In this retrospective study of 278 cirrhotic patients who underwent TIPS between January 2014 and December 2023, total cholesterol (TC), triglycerides (TG), high‑density lipoprotein cholesterol (HDL‑C), and low‑density lipoprotein cholesterol (LDL‑C) were analyzed before the procedure and during follow‑up periods of 1–3 months and 3–6 months post‑procedure. Patients were stratified by etiology (viral, alcoholic, autoimmune, cryptogenic) and Child‑Pugh grade. Multivariable analyses—including linear mixed‑effects models for longitudinal lipid changes, bidirectional stepwise linear regression, and LASSO regression with cross‑validation—were performed to identify factors influencing post‑TIPS lipid profile recovery. Results Lipid profiles varied significantly by cirrhosis etiology. Patients with cirrhosis due to autoimmune liver disease had the highest levels of TC (3.15 [2.65–4.03] mmol/L), HDL‑C (0.93 [0.73–1.06] mmol/L), and LDL‑C (1.68 [1.50–2.44] mmol/L), whereas viral cirrhosis showed the lowest TG levels (0.72 [0.60–0.93] mmol/L) and alcoholic cirrhosis had the lowest HDL‑C (0.64 [0.56–0.91] mmol/L) (all inter‑group p < 0.05). A significant declining trend was observed in TC, HDL‑C, and LDL‑C with worsening Child‑Pugh class (all p for trend < 0.05). After TIPS, HDL‑C increased progressively from 0.82 [0.63–1.01] mmol/L to 1.16 [0.98–1.33] mmol/L ( p for trend < 0.001). In contrast, TC, TG, and LDL‑C initially decreased at 1–3 months (TC: from 3.03 [2.63–3.67] mmol/L to 2.65 [2.13–3.32] mmol/L; TG: from 0.88 [0.65–1.21] mmol/L to 0.61 [0.51–0.80] mmol/L; LDL‑C: from 1.73 [1.36–2.11] mmol/L to 1.19 [0.97–1.57] mmol/L; all p < 0.05) and partially recovered by 3–6 months. TC, HDL‑C, and LDL‑C were positively correlated with albumin ( r = 0.470, p = 0.003; r = 0.470, p = 0.004; and r = 0.450, p = 0.006, respectively) and negatively correlated with albumin–bilirubin (ALBI) scores ( r = −0.600, p < 0.001; r = −0.490, p = 0.003; and r = −0.540, p < 0.001, respectively). In addition, TC and LDL‑C were negatively correlated with model for end‑stage liver disease (MELD) ( r = −0.410, p = 0.013; and r = −0.430, p = 0.008, respectively). Importantly, moderate‑to‑severe ascites independently predicted impaired recovery of TC ( β = −0.990, p = 0.016), TG ( β = −0.340, p = 0.002), and LDL‑C ( β = −0.710, p = 0.008) after TIPS. Conclusion Cirrhosis etiology and severity differentially shape lipid profiles. TIPS improves lipid profiles (particularly HDL‐C) in association with hepatic synthetic function. Ascites impairs post‐TIPS lipid recovery.

With the intensification of population aging and the increasing incidence of neurological diseases, the demand for precise and intelligent control technology in hand rehabilitation robots has become more urgent. Traditional control methods struggle to effectively capture the dynamic temporal features of hand movements, especially in scenarios where there are modal differences between hand function data of healthy individuals and stroke patients, leading to insufficient control accuracy and poor generalization. This paper focuses on hand rehabilitation robot control technology and proposes the C-GAP model. By designing a cross-modal attention mechanism, the model realizes feature collaboration of multi-source data such as electromyography (EMG), force, and joint angles. It relies on Stacked Gated Recurrent Units to accurately extract the temporal dynamic patterns of typical hand functional movements, such as grasping, pinching, and wrist rotation. In combination with an adaptive PID controller, the model optimizes force-controlled trajectories in rehabilitation training, forming a complete control scheme tailored to hand rehabilitation scenarios. Experimental validation shows that the model performs stably in classifying typical hand functional movements and dynamic control on the Ninapro DB5 (healthy hand function multimodal data) and MUSED-I (stroke patient hand function unimodal data) datasets, effectively adapting to rehabilitation training needs under different hand function states. The research provides technical support for the precise perception and control of sequential movements in hand rehabilitation robots, contributing to enhancing the specificity and safety of rehabilitation training. It has practical significance for promoting the application of recurrent neural networks in the field of rehabilitation robot control.

ABSTRACT Aims The tolerance of patients with compensated hepatitis B cirrhosis to interferon (IFN) therapy remains controversial. Therefore, this study aimed to evaluate the safety of pegylated interferon‐alpha in chronic hepatitis B (CHB) patients with compensatory cirrhosis. Methods Data from two prospective cohorts (the OASIS Project and CHESS 2306) from January 2018 to January 2024 were synthesized and analyzed. Patients with Child‐Pugh Class A hepatitis B cirrhosis who received IFN‐based therapy ( n = 920) were included. The control groups included patients with compensated hepatitis B receiving nucleos(t)ide analog (Nuc) monotherapy ( n = 714) and patients without cirrhosis receiving IFN‐based therapy ( n = 4111), respectively. Propensity score matching was used to control for confounding factors; 566 versus 566 cases were analyzed among patients with cirrhosis treated with IFN‐based therapy or Nuc monotherapy, and 785 versus 785 cases were analyzed among patients with and without cirrhosis treated with IFN‐based therapy. Primary outcomes included decompensation events, and secondary outcomes included severe adverse events, overall adverse events, and treatment‐related hospitalizations or deaths. Results In patients with hepatitis B virus‐related cirrhosis, the incidence of decompensation events was similar between IFN‐based therapy and Nuc monotherapy (6/566 [1.1%] vs. 3/566 [0.5%], p = 0.506). No hospitalizations or deaths were associated with adverse events during the observation period (48 weeks). The incidences of severe adverse events were similar in patients with cirrhosis under IFN‐based therapy or Nuc monotherapy (severe neutropenia: 1/450 [0.2%] vs. 0/378 [0], p = 0.999; severe thrombocytopenia: 4/435 [0.9%] vs. 0/296 [0], p = 0.153; severe alanine aminotransferase level elevation: 1/523 [0.2%] vs. 1/458 [0.2%], p = 0.999; and severe total bilirubin [TBIL] level elevation: 5/419 [1.2%] vs. 3/385 [0.8%], p = 0.727). The incidences of severe adverse events were similar between patients with and without cirrhosis receiving IFN‐based therapy, except that severe TBIL level elevation was more frequent in patients with cirrhosis who already had mildly to moderately elevated TBIL levels at baseline than in those without (6/153 [3.9%] vs. 0/118 [0], p = 0.040). Conclusion IFN‐based therapy demonstrates favorable safety in Child‐Pugh A compensated cirrhosis. It did not increase decompensation events or severe adverse events compared to Nuc monotherapy, and adverse event profiles were largely similar between cirrhotic and non‐cirrhotic patients, except for a higher risk of severe hyperbilirubinemia in those with pre‐existing TBIL elevation. ClinicalTrials.gov identifier: NCT04896255. Chinese Clinical Trial Registry number: ChiCTR2500107592.