Yan'an University

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.

Metal–organic framework (MOF) materials exhibit significant potential for hydrogen peroxide production from aqueous solutions through piezoelectric-photocatalysis. However, the high recombination rates of photogenerated electrons (e–) and holes (h+) still pose a significant challenge. To address this issue, the NH2–SnMOF catalyst was designed. The incorporation of amino groups facilitates efficient electron transfer, thereby promoting the Sn2+/Sn4+ dynamic conversion within the SnMOF and enabling a dual-channel H2O2 production mechanism. Concurrently, the introduction of −NH2 reduces the symmetry of the SnMOF, enhances the structural polarity, generates a built-in electric field, and promotes the separation of photogenerated e– and h+. Notably, the catalyst shows remarkable H2O2 production in oxygen-saturated aqueous solution without requiring sacrificial agents. Under the influence of the piezoelectric effect, this resulted in a high H2O2 production rate of 22.38 mM·g–1·h–1, demonstrating promising potential for wastewater treatment applications. The reaction process simultaneously involves 2e– ORR and 2e– WOR, effectively utilizing both e– and h+ in the redox reactions. Theoretical calculations reveal that amino functionalization increases the adsorption energy of SnMOF, significantly lowers the ΔG value of *OOH, and promotes the activation of O2. Oxygen adsorption oxidizes Sn2+ to Sn4+, which is then reduced back to Sn2+ under electron influence. The amino group donates additional electrons to the Sn site, facilitating cyclic Sn2+/Sn4+ conversion. The synergistic mechanism between amino ligand functionalization and metal site valence state conversion (Sn2+/Sn4+) significantly enhances the performance of piezo-photocatalytic H2O2 production. This work provides a theoretical framework for advancing piezo-photocatalytic H2O2 production and expanding their applications across diverse research fields.

Ganoderma lucidum has a long-standing history of use as a medicinal mushroom, with its spore oil (GLSO) extracted from broken cell walls using CO2 supercritical extraction. However, there is a notable scarcity of experimental studies on the protective effects and underlying mechanisms of GLSO on immune function impairment. The present study aims to explore the characteristics that GLSO contributes to protecting immune functions in cyclophosphamide-induced immunocompromised mice through a multi-omics analysis approach. GLSO administration significantly improved serum hemolysin levels, macrophage phagocytosis, and NK cell activity in immunosuppressed mice. Metagenomics, metabolomic, and proteomic analyses revealed that the immune protection mediated by GLSO was associated with structural rearrangements within gut microflora and shifts in microbial diversity. Specifically, there was an increase in beneficial microorganisms and a decrease in pathogenic organisms, accompanied by various alterations in metabolites and protein expressions. The identified 5 metabolites (propionic acid, beta-glycyrrhetinic acid, 3-aminosalicylic acid, creatine, and 2-phenylacetamide) and 5 proteins (Slc9a9, Blm, Hk3, AP1M2, and J chain) might serve as potential mediators of GLSO to alleviate immune dysfunction collectively caused by CYP in immunosuppressed mice.

This study aims to compare and analyze the effects of denosumab combined with calcium and vitamin D versus calcium and vitamin D alone on bone remodeling markers and bone mineral density (BMD) in patients with osteoporotic fractures. This single-center retrospective comparative study included patients with osteoporotic fractures admitted between January 2022 and January 2024. According to the treatment regimen, patients were divided into the denosumab group (subcutaneous denosumab every 6 months plus oral calcium and vitamin D supplementation) and the calcium plus vitamin D (CaD) group (oral calcium and vitamin D supplementation only). Propensity score matching was used to balance baseline characteristics, with 60 cases in each group. Bone remodeling markers (β-isomerized C-terminal telopeptide of type I collagen [β-CTX], procollagen type I N-terminal propeptide [P1NP], bone-specific alkaline phosphatase, osteocalcin), BMD changes, and safety profiles were compared between the 2 groups before treatment, and at 6 and 12 months after treatment. After treatment, the levels of the bone resorption marker β-CTX and the bone formation marker P1NP were significantly reduced in the denosumab group, and remained significantly lower than those in the CaD group at all time points (time, group, and interaction effects all P < .001). After 12 months of treatment, BMD increases in the lumbar spine and femoral neck were 8.8% and 7.3% respectively in the denosumab group, significantly higher than in the CaD group (2.6% and 2.2%) (P < .01 for both group and interaction effects). Correlation analysis showed that in the denosumab group, the decreases in β-CTX and P1NP were significantly negatively correlated with BMD improvements in the lumbar spine and femoral neck (r = -0.33 to -0.42, P < .05). The overall incidence of adverse events did not differ significantly between the 2 groups (13.3% vs 8.3%, P > .05), and all events were mild. For patients with osteoporotic fractures, denosumab combined with calcium and vitamin D supplementation is more effective in suppressing bone turnover and improving bone mineral density than calcium and vitamin D alone, without increasing significant safety risks. Bone remodeling markers β-CTX and P1NP may serve as potential reference indicators for evaluating the therapeutic efficacy of denosumab.