Zhenjiang City Fourth People's Hospital

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.

Given the increasing use of targeted therapies in clinical practice, we aimed to determine the clinically actionable safety profiles of second-line tyrosine kinase inhibitors (TKIs) in advanced hepatocellular carcinoma (HCC) by analysing adverse drug reactions (ADRs) reported in the WHO-VigiAccess database. Retrospective descriptive analysis of ADR reports for cabozantinib and regorafenib in advanced HCC after first-line failure. Data included patient demographics, geographic distribution, system organ classes (SOCs) and preferred terms (PTs) (MedDRA v24.0). Chi-squared tests were used to compare patient characteristics; head-to-head disproportionality analysis [reporting odds ratio (ROR)] was performed for gastrointestinal (GI) disorders. A total of 51,404 reports were analysed (cabozantinib: 33,846; regorafenib: 17,558). Cabozantinib exhibited a significantly higher proportion of GI disorders (87.2% vs. 60.3%; P<0.001) and higher GI-related ROR [1.31; 95% confidence interval (CI): 1.29-1.33] than regorafenib (0.73; 95% CI: 0.71-0.74). Diarrhoea was the most frequent ADR with cabozantinib (23.7%), whereas fatigue dominated regorafenib reports (16.3%). Death-related ADRs were similar (cabozantinib 6.36%; regorafenib 5.96%). Cabozantinib carries a disproportionately higher risk of severe GI toxicity compared with regorafenib. Clinicians should consider prophylactic anti-diarrhoeal therapy, routine liver-function monitoring, and early dose modifications when initiating cabozantinib, especially in male patients aged 45-64 years. These data supported personalized second-line TKI selection after first-line failure.

ETS1 and FLI1 exhibit distinct roles in immunoregulation and autoimmune pathogenesis. Previous transethnic genome-wide meta-analyses incorporating our Han Chinese population established significant associations between ETS1 single-nucleotide polymorphisms (SNPs) and susceptibility to primary biliary cholangitis (PBC). In our earlier genome-wide association study (GWAS), ten SNPs within the ETS1 and FLI1 loci demonstrated modest yet suggestive associations with PBC susceptibility in the Han Chinese population. To validate these putative risk loci, we conducted an independent replication study of rs10893900 and rs2246290 using a separate Han Chinese PBC cohort. A meta-analysis combining data from two stages identified rs10893900 as a genome-wide significant variant (P = 4.55 × 10-8, OR = 1.19, 95% CI = 1.12-1.27). Subsequent functional characterization identified rs10893900 as a susceptibility-associated functional variant. Based on the literature review, we summarized ETS1 variants' susceptibility to human autoimmune diseases, including SLE, RA, and PBC, and evaluated these variants in silico analysis. Importantly, our research implicates the importance of ETS1 involving JAK-STAT signaling pathway, expanding the understanding of pathological mechanisms of PBC.

ObjectiveThis study sought to comprehensively evaluate the safety profile of tremelimumab and durvalumab in patients with hepatocellular carcinoma (HCC) by examining adverse drug reaction (ADR) documented in the Food and Drug Administration’s Adverse Event Reporting System (FAERS) database.MethodsData from the FAERS database spanning from the first quarter of 2004 to the first quarter of 2025 were extracted, filtered, and standardized. The Reporting Odds Ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) method were utilized to analyze the signal strength and identify potential ADRs.ResultsA total of 574 cases and 1,021 ADR reports were identified. Gastrointestinal disorders (15.65%, n = 188), hepatobiliary disorders (12.16%, n = 146), and general disorders and administration site conditions (11.74%, n = 141) emerged as the most frequently reported categories by system organ class (SOC). Death, diarrhea, and malignant neoplasm progression were identified as the three most common preferred terms (PT) based on reporting frequency. Immune-mediated ADRs with elevated ROR and BCPNN values were prevalent across multiple systems, particularly within the gastrointestinal (528.22, 9.03), hepatic (863.82, 9.70), cardiac (365.24, 8.49), endocrine (321.26, 8.31), and dermatological (744.71, 9.51) domains.ConclusionThe study underscored the intricate safety profile of tremelimumab and durvalumab in HCC patients, characterized predominantly by immune-mediated toxicities and significant gastrointestinal and hepatobiliary risks. Utilization of drugs necessitated meticulous patient selection and a multidisciplinary management approach to optimize patient outcomes and mitigate ADRs.

Portal vein tumor thrombus is an important indicator of poor prognosis in patients with hepatocellular carcinoma. Transarterial chemoembolization is recommended as the standard first-line therapy for unresectable hepatocellular carcinoma. Portal vein stent placement is a safe and effective therapy for promptly restoring flow and relieving portal hypertension caused by tumor thrombus. To assess the clinical significance of transarterial chemoembolization plus stent placement for the treatment of hepatocellular carcinoma with main portal vein tumor thrombosis. We searched English and Chinese databases, assessed the quality of the included studies, analyzed the characteristic data, tested heterogeneity, explored heterogeneity, and tested publication bias. In total, eight clinical controlled trials were included. The results showed that the pressure in the main portal vein after stent placement was significantly lower than that with no stent placement. The cumulative stent patency and survival rates at 6 and 12 months were lower in the transarterial chemoembolization + stent placement group than in the transarterial chemoembolization + stent placement + brachytherapy/radiotherapy group. The survival rates of patients treated with transarterial chemoembolization + stent placement for 6 and 12 months were higher than those of patients treated with transarterial chemoembolization alone. For Chinese patients with hepatocellular carcinoma with main portal vein tumor thrombosis, transarterial chemoembolization plus stenting is effective. Transarterial chemoembolization + stent placement is more effective than transarterial chemoembolization alone. Transarterial chemoembolization + stent placement + brachytherapy/radiotherapy is more effective than transarterial chemoembolization + stenting.

To investigate the correlation between 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3) and the inflammatory activation of polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) in acute myocardial infarction (AMI), and to evaluate the effect of intervention targeting PFKFB3 on the inflammatory activation of PMN-MDSC during AMI. (1) Clinical trial section: a observational study was conducted. The patients with acute coronary syndrome (ACS) admitted to Zhenjiang Fourth People's Hospital were enrolled, and they were divided into AMI group and non-AMI group according to clinical diagnosis. The peripheral venous blood of the two groups was collected to detect the proportion of PMN-MDSC, and the expression of PFKFB3 gene in mononuclear cells was detected by real-time quantitative polymerase chain reaction (RT-qPCR). (2) Basic experiment section: a total of 30 male C57 mice (aged 6-8 weeks) were divided into normal control group (n = 5), Sham group (n = 5), AMI model group (n = 10) and PFKFB3 inhibitor PKF-15 intervention group (n = 10) according to random number table method. The AMI model of mice was reproduced by left anterior descending coronary artery (LADCA) ligation, and the mice in the Sham group did not attach the artery after thoracotomy. The PKF-15 intervention group was intraperitoneally injected with PKF-15 (20 μg/g) at the same time of LADCA ligation. Normal control mice did not receive any treatment. Peripheral venous blood and myocardial tissue of mice were collected 24 hours after modeling. Both the circulating PMN-MDSC ratio and the infiltration of PMN-MDSC in myocardial tissue were detected. After staining with hematoxylin-eosin (HE), the degree of inflammatory damage in mouse myocardial tissue was observed under light microscopy. PMN-MDSC were isolated from mice with flow cytometry, and the gene expressions of PFKFB3 and inflammatory factors were measured by RT-qPCR. (1) Clinical trial section: the circulating PMN-MDSC ratio of patients in the AMI group (n = 25) was significantly higher than that in the non-AMI group [n = 20; (8.53±0.96)% vs. (1.13±0.39)%, P < 0.01], and PFKFB3 gene expression in the peripheral blood mononuclear cells was also increased (2-ΔΔCt: 1.18±0.19 vs. 0.96±0.16, P < 0.01). Pearson correlation analysis showed that circulating PMN-MDSC ratio was positively correlated with PFKFB3 gene expression in mononuclear cells in AMI patients (r = 0.608, P = 0.001). (2) Basic experimental section: the circulating PMN-MDSC ratio and the infiltration of PMN-MDSC in myocardial tissue of AMI mice were significantly higher than those in the normal control group and Sham group. PFK-15 intervention could reduce the ratio of PMN-MDSC in the peripheral blood and myocardial tissue of AMI mice [(26.33±5.27)% vs. (75.12±5.02)% in peripheral blood, (20.87±2.97)% vs. (35.28±4.36)% in myocardial tissue, both P < 0.01]. Under light microscopy, the myocardial cells in the AMI modal group were disordered and a large number of inflammatory cells infiltrated. PFK-15 intervention could maintain a normal arrangement of cardiomyocytes and reduce the infiltration of inflammatory cells. The gene expression levels of PFKFB3 in the peripheral blood and myocardial tissue as well as the inflammatory factors in the myocardial tissue of AMI mice were significantly higher than those in the normal control group and Sham group. PKF-15 intervention could effectively reduce the gene expression levels of PFKFB3 in the peripheral blood and myocardial tissue as well as the inflammatory factors in the myocardial tissue of AMI mice [PFKFB3 mRNA (2-ΔΔCt): 1.01±0.09 vs. 1.40±0.12 in peripheral blood, 0.95±0.09 vs. 1.47±0.10 in myocardial tissue; myocardial tissue tumor necrosis factor-α (TNF-α) mRNA (2-ΔΔCt) was 14.55±3.99 vs. 29.66±3.90, interleukin-1β (IL-1β) mRNA (2-ΔΔCt) was 8.72±1.35 vs. 18.53±2.43, IL-6 mRNA (2-ΔΔCt) was 11.87±2.97 vs. 19.82±4.32, all P < 0.01]. The activation of PFKFB3 is closely related to the inflammatory activation of PMN-MDSC during AMI. Inhibition of PFKFB3 activity can inhibit the inflammatory activation of PMN-MDSC and reduce myocardial inflammatory injury.

This paper aims to explore the appropriate treatment plan for cervical spinal cord injury. Retrospective analysis of the treatment of 30 patients with cervical spinal cord injury in our hospital was carried out, with 15 patients treated with anterior cervical decompression and internal fixation as the study group, and 15 patients treated with posterior cervical decompression and internal fixation as the control group. There was no significant difference in postoperative and follow-up Japanese Orthopaedic Association (JOA) scores, and the incidence of postoperative complications between the two groups. The blood loss and the improvement of cervical lordosis in the study group were better than those in the control group. For patients with cervical spinal cord injury, both anterior and posterior decompression and internal fixation can achieve good clinical results, but anterior decompression and internal fixation can better maintain cervical lordosis and reduce blood loss.