Jiangxi Chest Hospital

Chronic spontaneous urticaria (CSU) poses a significant burden on both patient and caregiver. Currently treatments for CSU are inadequate for some patients. TLL-018, an oral TYK2/JAK1 inhibitor, is under investigation for CSU treatment. To evaluate the efficacy and safety of TLL-018 for treating moderate-to-severe CSU in patients who had an inadequate response to antihistamines. In this multicenter, double-blind, randomized, placebo-controlled, parallel-group pilot study (NCT05373355), patients with CSU who showed an inadequate response to antihistamines received either 10 mg or 30 mg of TLL-018, or placebo orally twice daily. After 4 weeks, patients on placebo were switched to 20 mg of TLL-018, and continuing treatment for an additional 8 weeks. The primary endpoint was safety, while secondary endpoints included efficacy measures, such as weekly Urticaria Activity Score (UAS7) ≤ 6, UAS7 = 0, and a Dermatology Life Quality Index of 0 or 1 at weeks 4 and 12. The study involved of 41 patients. At week 4, the ANCOVA versus change from placebo of UAS7/weekly Itch Severity Score/weekly Hive Severity Score were -11.5/-8.0/-3.8 in the 10-mg groups and -16.0/-9.0/-7.0 in the 30-mg groups. At week 12, the percentages achieving UAS7 ≤ 6 and UAS7 = 0 were 53.8%/38.5%, 71.4%/64.3%, and 61.5%/53.8% in the placebo-to-20 mg, the 10-mg, and the 30-mg TLL-018 groups, respectively. Common treatment-emergent adverse events included elevated serum creatine kinase and blood lipid levels, hyperglycemia, and urinary occult blood. TLL-018 was well-tolerated and effective in treating moderate-to-severe CSU in patients who had an inadequate response to antihistamines.

In response to the limitations of traditional therapies for immune and infectious skin diseases in terms of tissue penetration, cost, and drug resistance, nanobodies derived from camelids and containing only a single heavy chain variable domain have shown significant advantages: their small molecular weight ensures excellent skin penetration ability, the extended CDR3 domain enables precise targeting of hidden epitopes, and they have excellent stability (tolerance to extreme pH, temperature, protease) and low-cost production potential. In the treatment of immune skin diseases, nanobodies effectively synergistically block key inflammatory pathways through multivalent/multispecific design, demonstrating deep therapeutic effects beyond some traditional therapies in areas such as psoriasis, atopic dermatitis, and hidradenitis suppurativa. In the field of infectious skin diseases, it effectively blocks the process of pathogen infection by efficiently neutralizing key virulence factors (such as invasion proteins, adhesion factors, toxins) of viruses, bacteria, fungi, and parasites, and has the potential to serve as a highly specific diagnostic tool. Future research and development will focus on multi-target optimization, artificial intelligence assisted design, new transdermal/long-acting delivery systems, and precision medicine strategies, promoting nanobodies as an efficient and precise solution to revolutionize the treatment of skin diseases.

Perianal herpes simplex virus (HSV) infection represents a rarely reported clinical variant that is frequently misdiagnosed. We present a case of perianal HSV in a patient with a history of renal transplantation and type 2 diabetes mellitus. Following a previous diagnosis of perianal eczema, the patient’s cutaneous lesions slowly worsened despite treatment with topical corticosteroids. Notably, the presence of well-demarcated superficial erosions, combined with immunosuppressive conditions including diabetes mellitus and renal transplantation, prompted targeted HSV screening which confirmed the diagnosis. This case underscores the importance of considering HSV testing in patients presenting with atypical perianal eruptions.

The rapid development of deep learning has promoted its application in disease diagnosis, treatment, and prognosis prediction. Medical imaging plays a crucial role in the management of rifampicin-resistant tuberculosis/multidrug-resistant tuberculosis (RR-TB/MDR-TB). In particular, chest computed tomography (CT) scans offer detailed lung images that can reveal subtle features. In this study, we propose a Convolutional Neural Network-Long Short-Term Memory (CNN-LSTM) model to predict treatment outcomes in RR-TB/MDR-TB patients, aiming to support clinicians in timely adjustment of therapeutic strategies and improving treatment success. The model integrates CNN for image feature extraction with LSTM for sequential analysis of patient monitoring data, including two types of immune detection indicators (T-cell subsets and peripheral blood tuberculosis-related CD161-positive cells). Transfer learning with weight initialization was applied to enhance model performance, and three backbone architectures (DenseNet201 + ABC, ResNet-50 + ABC, CheXNet + ABC) were compared to assess their impact on predictive accuracy. Experimental results demonstrated that the CNN-LSTM model with DenseNet201 + ABC as the backbone achieved the highest accuracy in predicting subsequent treatment indicators. These findings demonstrated the feasibility and effectiveness of using CNN-LSTM for treatment outcome prediction in RR-TB/MDR-TB, and highlighted its potential to assist clinicians in precision-tailoring treatment plans, thereby improving therapeutic efficacy and offering both theoretical and practical value in healthcare.

The permanent metallic occluders used for atrial septal defect (ASD) closure are associated with risks of late complications and may impede access to the left atrium. Bioresorbable occluders have the potential to address these limitations but have yet to be validated in randomized clinical trials. To evaluate whether a bioresorbable occluder is noninferior to a metallic occluder based on its efficacy and safety for transcatheter ASD closure. This multicenter, noninferiority, open-label randomized clinical trial included participants with secundum ASD. Enrollment occurred from May 8, 2021, to August 3, 2022, at 10 hospital sites in China. The 2-year follow-up period ended in September 2024. Participants were randomized in a 1:1 ratio to receive a bioresorbable occluder (n = 116) or a metallic occluder (n = 114). The primary outcome was the success rate of ASD closure at 6 months (closure success was defined as procedural success with a residual shunt diameter of ≤2 mm, which was assessed using transthoracic echocardiography). At the 2-year follow-up, the occluder groups were compared regarding the success of ASD closure and the device-related adverse events. The degradation profile of the bioresorbable occluder was assessed at 2 years. Of the 230 participants randomized, implantation was not attempted in 1 participant in the bioresorbable occluder group due to a small femoral vein, leaving 229 (median age, 14.1 years [IQR, 7.0 to 37.3 years]; 68% were female). At 6 months, the success rate of ASD closure was 96.5% (111 of 115 patients) for the bioresorbable occluder group vs 97.4% (111 of 114 patients) for the metallic occluder group (between-group difference, -0.8 percentage points [95% CI, -5.0 to 3.7]; P < .001 for noninferiority). At 2 years, there were no statistically significant between-group differences in ASD closure success (94.8% [109/115] in the bioresorbable occluder group vs 96.5% [110/114] in the metallic occluder group; P = .75), or in device-related adverse events (2.6% [3/115] vs 3.5% [4/114], respectively; P = .72). The rate of degradation at 2 years was approximately 99.8% for the bioresorbable occluder. A bioresorbable occluder is noninferior to a metallic occluder for ASD closure, with near-complete degradation by 2 years. These findings suggest that a bioresorbable occluder could be a valuable addition to the options for transcatheter ASD closure. chictr.org.cn Identifier: ChiCTR2100044408.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) overlap syndrome, characterized by extensive epidermal necrosis, represents a life-threatening severe dermatological disorder.Therapeutic agents and regimens for this condition include high-dose glucocorticoids, intravenous immunoglobulin (IVIG), plasma exchange, immunosuppressants, and TNF-α inhibitors. A study demonstrates that JAK/STAT hyperactivation—characterized by interferon signature enrichment, STAT1 phosphorylation in keratinocytes/macrophages, and subsequent GBP1/WARS1-mediated cytotoxicity—drives epidermal detachment in TEN. JAK inhibitors (including JAK1-selective agents) suppressed this pathway in murine models and achieved rapid resolution in seven TEN patients.Recent clinical studies have demonstrated the therapeutic efficacy of JAK inhibitors in SJS/TEN management. In this context, we present the case of a 54-year-old woman who presented to the hospital with a 6-day history of rapidly worsening erythema, accompanied by a 4-day history of blistering and erosion. The patient received treatment with methylprednisolone (40 mg/day, weight: 49 kg) and upadacitinib (15 mg/day for 2 weeks). Combination therapy achieves rapid disease control by halting the progression of cutaneous necrosis while enabling accelerated glucocorticoid tapering. This case underscores that the combination therapy of upadacitinib and methylprednisolone can offer a promising approach for the SJS/TEN overlap syndrome.

Proteasome 26S subunit non-ATPase 12 (PSMD12), a critical subunit of the proteasome system, is essential for maintaining protein homeostasis. However, its role in hepatocellular carcinoma (HCC) remains underexplored. Bioinformatics analysis, immunohistochemistry, Western blotting, and qRT-PCR confirmed the upregulation of PSMD12 in HCC tissues compared to normal liver tissues, with this overexpression correlating with poor patient prognosis. Functional assays revealed that PSMD12 knockdown suppressed HCC cell proliferation and migration, inducing G2/M phase cell cycle arrest. In contrast, PSMD12 overexpression promoted these malignant behaviors. Mechanistically, PSMD12 interacts with cyclin-dependent kinase 1 (CDK1), preventing its degradation through deubiquitination, thereby accelerating HCC progression by enhancing cell cycle progression. These findings underscore PSMD12’s role in HCC and highlight its potential as both a prognostic biomarker and therapeutic target, providing new insights into the molecular mechanisms driving HCC progression.

Tuberculosis (TB) diagnostics urgently require non-sputum biomarkers to address the limitations of conventional methods in distinguishing active TB (ATB) from latent infection (LTBI), healthy controls (HCs), and TB-mimicking diseases (ODs, other diseases). Transcriptomic data from GSE83456 and GSE152532 were combined to form the selection dataset. Marker genes were identified from differentially expressed autophagy-related genes using a Random Forest classifier. The optimal gene signature was selected based on optimal performance through a linear Support Vector Machine (SVM) classifier with cross-validation. The signature was subsequently evaluated in six independent evaluation datasets and validated using whole blood samples collected from 70 participants. We identified a novel four-gene autophagy-related signature (CASP1, FAS, TRIM5, C5) in the selection dataset. This signature demonstrated robust diagnostic accuracy across multiple evaluation datasets: Area Under the Curve (AUC) 0.83-0.98 for ATB vs. LTBI and 0.82-0.94 for ATB vs. HCs. Crucially, it maintained high specificity (AUC 0.89-0.90) against ODs. RT-qPCR validation in whole blood samples confirmed elevated expression in ATB, while an SVM model achieved promising differentiation (AUC 0.86 for ATB vs. LTBI and AUC 0.99 for ATB vs. HCs). Our findings yielded a four-gene signature in whole blood that is robustly diagnostic for ATB, validated across multiple evaluation datasets and clinical samples. The autophagy-driven specificity and PCR-compatible design of this signature offer a blood-based, cost-effective strategy to enhance TB detection, addressing WHO-aligned diagnostic needs.

To explore the clinical value of transcatheter arterial chemoembolization (TACE) using a temperature-sensitive liquid embolic agent for the interventional treatment of primary hepatocellular carcinoma. The clinical data and follow-up results sourced from the First Affiliated Hospital of Fujian Medical University were retrospectively analyzed from February 2023 to May 2023. Clinical efficacy was assessed through follow-up imaging using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1. In addition, adverse reactions and adverse events were observed and classified using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTC) version 3.0. Among the 11 patients analyzed in this study, a total of 41 lesions were identified. The average maximum diameter of the lesions was 3.55 ± 1.88 cm (range: 1.70 cm-6.60 cm). One month postoperatively, the efficacy assessment revealed complete response (CR) in 1 case, partial response (PR) in 9 cases, stable disease (SD) in 1 case, and progression in 0 case. The objective response rate (CR + PR) was 90.91%, and the disease control rate (CR + PR + SD) was 100%. Postoperative adverse reactions were mostly of grade 1-2, including abdominal pain, bloating, fever, nausea, and vomiting. The use of temperature-sensitive liquid embolic agents loaded with lobaplatin for chemoembolization in the treatment of unresectable primary liver cancer is a safe and effective therapeutic modality.