Liver cirrhosis recompensation refers to the process in which patients with decompensated cirrhosis achieve the disappearance of decompensated complications and restoration of liver function and clinical phenotype to a compensated state after etiological treatment or symptomatic treatment. In recent years， with effective control of the etiology of cirrhosis and treatment or prevention of decompensated complications， the clinical significance of recompensation has gained increasing attention. This article elaborates on recompensation from the aspects of definition， diagnostic criteria， influencing factors， mechanisms affecting long-term prognosis， and clinical management strategies， and with reference to the latest research evidence， this article also discusses the core value of recompensation in improving quality of life and reducing the risk of end-stage events， in order to provide a basis for optimizing the comprehensive management of liver cirrhosis.

Objective:To explore the effect of nursing scheme based on self-regulation theory (SRT) on self-efficacy and quality of life of patients with chronic pancreatitis, and to provide basis for better promoting patients′ rehabilitation.Methods:Using a non-random historical control study, 55 patients with chronic pancreatitis admitted to The Fifth Affiliated Hospital of Southern Medical University from November 2021 to October 2022 were classified as the control group, and 55 patients with chronic pancreatitis admitted from November 2022 to October 2023 were classified as the research group. The control group received routine nursing intervention, while the research group received SRT-based nursing intervention. Both groups received a 3-month intervention. The General Self-Efficacy Scale, Exercise of Self-Care Agency Scale, Self Rated Abilities for Health Practices Scale, and Gastrointestinal Quality of Life Index were used to evaluate the self-efficacy, self-care ability, health behavior, and quality of life of two groups before and after the intervention, and statistical comparisons were made.Results:Both groups of patients completed the study. There were 28 males and 27 females in the control group. The age was (45.33 ± 12.26) years old. There were 30 males and 25 females in the research group. The age was (45.48 ± 12.61) years old. After the intervention, the score of the self-efficacy in the research group was (29.32 ± 2.88) points, which was higher than that in the control group (19.28 ± 1.95) points, the difference was significant ( t=21.41, P<0.05). The scores of self-care skills, self-responsibility, self-concept, health knowledge and the total score of the self-care ability in the research group were (35.32 ± 2.31), (22.85 ± 1.42), (25.88 ± 1.93), (64.32 ± 5.22), (148.34 ± 8.33) points respectively. They were all higher than those of the control group (28.66 ± 1.77), (17.22 ± 1.23), (18.67 ± 1.86), (60.08 ± 4.52), (124.56 ± 8.92) points. The differences were significant ( t values were 4.55-22.23, all P<0.05). The scores of exercise, nutrition, health responsibility, psychological comfort and the total score of the health behavior in the research group were (25.58 ± 1.41), (25.02 ± 2.03), (24.31 ± 2.34), (25.16 ± 1.63), (100.05 ± 7.36) points respectively. They were all higher than those of the control group (22.31 ± 2.03), (20.15 ± 2.82), (20.16 ± 2.89), (21.15 ± 2.17), (83.79 ± 7.84) points. The differences were significant ( t values were 8.28-11.21, all P<0.05). The scores of social activity, psychological state, physiological function, self-conscious symptoms and the total score of the quality of life in the research group were (16.78 ± 1.26), (17.03 ± 1.85), (22.43 ± 1.96), (17.09 ± 0.88), (73.41 ± 4.22) points respectively. They were all higher than those of the control group (15.32 ± 1.15), (15.34 ± 1.76), (20.86 ± 1.59), (16.03 ± 0.75), (67.52 ± 4.18) points. The differences were significant ( t values were 4.61-7.35, all P<0.05). Conclusions:SRT-based nursing scheme can effectively improve the self-efficacy and self-care ability of patients with chronic pancreatitis, and improve their health behavior and quality of life.

Objective:To evaluate the long-term outcomes and predictors of coronary atherosclerotic lesions deemed functionally non-ischemic (quantitative flow ratio(QFR)>0.80) and deferred from intervention.Methods:This study is a post-hoc analysis of the FAVOR Ⅲ China trial, which enrolled 3 825 patients with stable or unstable angina pectoris or with myocardial infarction occurring at least 72 hours prior to screening, between December 5, 2018 and January 9, 2020 from 26 research centers in China. Coronary vessels with QFR>0.80 and without interventional treatment were analyzed in this study. The primary endpoint was 3-year target vessel revascularization. Vessels with revascularization (revascularized group) during follow-up were matched 1∶1 using propensity score matching to comparable vessels without revascularization (non-revascularized group). Multivariate Cox regression analysis was used to identify the risk factors for target vessel revascularization (TVR).Results:A total of 6 212 functionally negative vessels with deferred intervention were included in the final analysis, among which 153 vessels (2.5%) underwent TVR during a 3-year follow-up. Prior to propensity score matching, 6 059 vessels comprised the non-revascularized group. At the vessel level, compared to the non-revascularized group, the revascularized group exhibited a significantly higher proportion of males (79.1% (121/153) vs. 70.2% (4 253/6 059), P=0.018), higher body mass index ((25.6±4.0) kg/m2 vs. (24.3±5.2) kg/m2, P=0.003), and a higher prevalence of hypertension (73.9% (113/153) vs. 65.1% (3 944/6 059), P=0.025). And 152 pairs of vessels were successfully matched. Multivariate Cox regression analysis identified in-stent restenosis lesions ( HR=2.59, 95% CI 1.28-5.23, P=0.008) as an independent risk factor for target vessel revascularization. Conclusions:Coronary lesions classified as functionally non-ischemic at baseline are not entirely stable and may progress to lesions that requiring revascularization over time. In-stent restenosis emerges as a critical independent predictor of revascularization.

Objective:Investigate the impact of calcification on the long-term outcomes of patients with coronary chronic total occlusion (CTO) after percutaneous coronary intervention (PCI).Methods:A retrospective cohort study was conducted. Patients who underwent PCI and had at least one CTO lesion at Fuwai Hospital between January 2010 and December 2013 were consecutively enrolled. Calcification was evaluated by coronary angiography, and patients were divided into two groups: moderate/severe calcification group and non/mild calcification group. Clinical follow-up was completed up to 5 years. Incidence of PCI-related complications and immediate procedural outcomes were compared between two groups, and the primary endpoint was the target lesion failure (TLF) at 5 years after PCI. Clinical follow-up endpoint events were analyzed using Kaplan-Meier survival analysis with log-rank test, and Cox multivariate regression model was used to evaluate the relationship between calcification and TLF.Results:The study included 2 659 CTO patients with an age of (57.2±10.5) years, of whom 442 (16.6%) were female, and among whom 13.5% (360/2 659) had moderate/severe calcification. Compared with the non/mild calcification group, the moderate/severe calcification group had a higher incidence of PCI-related complications (43.2% (156/361) vs. 32.5% (772/2 374), P<0.001) and procedural failure (34.3% (124/361) vs. 24.3% (577/2 374), P<0.001). Additionally, the moderate/severe calcification group showed a higher risk of the primary endpoint event (TLF) during the 5-year follow-up (19.8% vs. 15.3%, log-rank P=0.028). Higher incidence of cardiac death was observed in moderate/severe calcification group (5.7% vs. 2.7%, log-rank P=0.003). Cox multivariate regression analysis revealed that moderate/severe calcified plaques remained an independent risk factor for 5-year TLF after CTO-PCI ( HR=1.34, 95% CI: 1.01-1.79, P=0.043). Conclusion:Compared with CTO patients with non/mild calcification, those with moderate/severe calcification have higher procedural failure and complication rates, as well as poorer long-term prognosis, mainly due to an increase in cardiac death.

Perfluorobutyric acid (PFBA) is a representative short-chain compound of per- and polyfluoroalkyl substances (PFAS), which is widely used in fluorochemical manufacturing, food packaging, and outdoor textile processing industries. PFBA primarily enters into the human body via oral intake, inhalation, and dermal exposure and can be efficiently metabolized. PFBA exhibits cytotoxicity by disrupting cell proliferation, inducing oxidative stress, and disturbing lipid metabolism, thereby impairing cellular homeostasis. In addition, PFBA can induce abnormal activation of peroxisome proliferator-activated receptor α-dependent and/or independent pathways, leading to lipid metabolism disorders and subsequent liver injury. Animal studies have demonstrated that PFBA exposure alters renal biochemical parameters and induces epidermal inflammation, abnormal keratinization, and even necrosis, suggesting potential nephrotoxicity and dermal toxicity. PFBA is capable of crossing the placental barrier, and PFBA levels in umbilical cord blood have been negatively correlated with insulin and insulin-like growth factor 1. Moreover, plasma PFBA levels in patients infected with coronavirus disease 2019 have been associated with infection severity, indicating potential reproductive, developmental, and immunotoxic effects. At present, systematic occupational and environmental exposure monitoring data for PFBA remain limited, the toxic mechanisms in certain target organs have not been fully elucidated, and the molecular regulatory networks underlying reproductive and immune toxicity remain unclear. Future research should focus on improving PFBA monitoring strategies, strengthening studies on PFBA occupational exposure detection methods, toxic effects and mechanisms, and refining occupational risk assessment systems, to provide a scientific basis for establishing occupational exposure limits, optimizing risk management strategies, and safeguarding public health.

Bio-mineralization has emerged as a promising strategy to enhance vaccine immunogenicity. This study optimized the calcium phosphate (CaP) mineralization process of foot-and-mouth disease virus-like particles (FMD VLPs) to achieve high mineralization efficiency and scalability. Key parameters, including concentrations of Ca²⁺, HPO₄^2-, NaCl, and VLPs, as well as stirring speed, were systematically optimized. Stability of the scaled-up reaction system and immunogenicity of the mineralized vaccine were evaluated. Optimal conditions [25.50 mmol/L Ca(NO₃)₂, 15 mmol/L Na₂HPO₄, 300 mmol/L NaCl, 0.75 mg/mL VLPs, and 1 500 r/min] yielded CaP-mineralized VLPs (VLPs-CaP) with high mineralization efficiency, uniform morphology, and a favorable particle size. Scaling up the reaction by 25 folds maintained consistent mineralization efficiency and particle characteristics. Immunization in mice demonstrated that VLPs-CaP induced higher titers of specific antibodies and neutralizing antibodies than unmineralized VLPs (P < 0.05). Higher IgG2a/IgG1 ratio and enhanced IFN-γ secretion (P < 0.05) further indicated robust cellular immune responses. We establish a stable and scalable protocol for VLPs-CaP, providing a theoretical and technical foundation for developing high-efficacy VLPs-CaP vaccines.
Vaccines, Virus-Like Particle/immunology* ; Immunogenicity, Vaccine ; Calcium Phosphates/chemistry* ; Foot-and-Mouth Disease Virus ; Biomineralization ; Particle Size ; Animals ; Mice ; Antibodies, Neutralizing/blood* ; Antibodies, Viral/blood* ; Immunity, Cellular

Objective To explore the nephrotoxic effects of exposure to perfluorobutanoic acid (PFBA) and its mechanism in mice, with a particular focus on analyzing the changes in kidney metabolism and their potential implications. Methods The specific pathogen free C57BL/6 mice were randomly divided into control group, low-dose group, and high-dose group, with 10 mice in each group. Mice in the three groups received intragastric administration of PFBA solution at doses of 0, 35 and 350 mg/kg body weight, once per day for seven consecutive days. The histopathological changes of kidneys of mice in these three groups were evaluated. Metabolomic profiling of mouse kidneys was performed using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Differentially accumulated metabolites (DAMs) were identified based on the Human Metabolome Database, and related metabolic pathways were analyzed through MetaboAnalyst 6.0 and Kyoto Encyclopedia of Genes and Genomes (KEGG). Results Histopathological analysis of kidneys showed that the renal pelvis mucosa of mice in the low-dose group presented focal mild inflammatory changes without marked structural damage, whereas mice in the high-dose group showed severe inflammation and partial destruction of renal structure. The kidney coefficient of mice in both low-dose group and the high-dose group decreased (both P<0.05), and the Paller scores of renal tissues increased (both P<0.05) compared with that in the control group. The Paller score of mouse renal tissue in the high-dose group was higher than that in the low-dose group (P<0.05). Metabolomic profiling identified 46 DAMs (26 upregulated, 20 downregulated) in the low-dose group and 104 DAMs (54 upregulated, 50 downregulated) in the high-dose group, with 26 shared DAMs between the two dose groups. KEGG pathway analysis revealed that DAMs were mainly involved in metabolic pathways such as glycerophospholipid metabolism, glycerolipid metabolism, sphingolipid and steroid hormone synthesis. Conclusion Acute exposure to PFBA can cause kidney injury in mice. Lipid metabolism pathways such as glycerophospholipid and sphingolipid metabolism is involved in the development of acute renal toxicity of PFBA.

Objective To investigate the protective effect of β-glucan(BG)against intestinal ischemia reperfusion(II/R)injury by regulating the secretion of glucagon-like peptide-1(GLP-1).Methods Male C57BL/6 mice(6～8 weeks old)were subjected,and finally,the experiments had sham group,II/R group,II/R+BG group(0.1 mg/mL BG in drinking water for 2 weeks before modeling),II/R+liraglutide(LLT,GLP-1 analogue)group(0.2 μg/g LLT injected every 12 hours for 3 consecutive days before modeling),and II/R+BG+Ex9-39(GLP-1 R antagonist)group(intraperitoneal injection of 2 μg/g Ex9-39 1 h before modeling).After modeling,HE staining was used to observe intestinal morphological changes,and RT-qPCR and Western blotting were employed to evaluate the molecules(Occludin,ZO-1 and Claudin-1)related to intestinal barrier damage.The effect of 0.1 mg/mL BG treatment on the GLP-1 level in the serum and intestinal tissues of normal mice was determined with ELISA and immunofluorescence assay,respectively,and RT-PCR for the molecules related to GLP-1 expression(Gcg,Pcsk1/2,GIP and Foxa2).The effects of LLT and Ex9-39 pretreatment on intestinal morphology and intestinal barrier damage were also determined by morphological observation and expression levels of related molecules.Results II/R induced significant decreases in the mRNA levels of Occludin,ZO-1 and Claudin-1 and increase in Chiu's score when compared with sham control mice(P＜0.05).While,the mRNA levels of the 3 molecules were obviously higher and the Chiu's score was lower in the II/R+BG group than the II/R group(P＜0.05).BG pretreatment induced notably enhanced secretion of GLP-1 in the serum and intestinal tract of normal mice,and improved the mRNA expression of GLP-1-related molecules(P＜0.05).The intervention of GLP-1 analogue LLT could attenuate the II/R damage and decreased Chiu's score,with statistical difference in comparison with the II/R group(P＜0.05).GLP-1 receptor antagonist Ex9-39 reversed the protective effects of BG pretreatment against II/R damage,with notably differences in the expression of Occludin,ZO-1 and Claudin-1 and Chiu's score(P＜0.05).Conclusion BG can attenuate intestinal mucosal and functional injury after II/R by promoting intestinal GLP-1 secretion.

Objective To analyze the diversity and composition changes of gut fungal communities between patients with chronic kidney disease(CKD)and healthy controls.Methods A total of 8 CKD patients admitted in Department of Nephrology of our hospital,and another 5 age-and gender-matched healthy individuals were recruited in this study.Fresh fecal samples were collected from the CKD patients and healthy controls.ITS DNA sequencing was employed to determine the composition of intestinal fungi,and then bioinformatics analysis was applied to compare the differences in fungal community diversity,structure,and function between the 2 groups.Results There were no statistical differences between the 2 groups in terms of age,gender composition,BMI,and so forth.The results of Alpha diversity assessment showed statistical differences were observed in Simpson index and Shannon index in the intestinal fungi between the 2 groups(P＜0.01).So was in the Beta diversity between them(P＜0.01).The relative abundance of Candida was increased significantly(P＜0.01),while those of Cladosporium and Penicillium were decreased in the CKD group(P＜0.05).LEfSe analysis revealed that Candida was significantly enriched in CKD patients,whereas Cladosporium and Penicillium were significantly lower in abundance when compared to the healthy control group.Conclusion The composition of intestinal fungi in CKD patients is different from that in healthy individuals,exhibiting characteristic changes.Dysfunction of gut fungal flora may promote the progression of CKD.Regulating gut fungi and restoring gut microbiota homeostasis may become a new strategy for CKD treatment.

OBJECTIVES: The purinergic receptor P2X2 (P2RX2) encodes an ATP-gated ion channel permeable to Na⁺, K⁺, and especially Ca²⁺. Loss-of-function mutations in P2RX2 are known to cause autosomal dominant nonsyndromic deafness 41 (DFNA41), which manifests as high-frequency hearing loss, accelerated presbycusis, and increased susceptibility to noise-induced damage. Zebrafish, owing to their small size, rapid development, high fecundity, transparent embryos, and high gene conservation with humans, provide an ideal model for studying human diseases and developmental mechanisms. This study aims to generate a p2rx2 knockout zebrafish model using CRISPR/Cas9 gene editing system to investigate the effect of p2rx2 deficiency on the auditory system, providing a basis for understanding P2RX2-related hearing loss and developing gene therapy strategies. METHODS: Two CRISPR targets (sgRNA1 and sgRNA2) spaced 47 bp apart were designed within the zebrafish p2rx2 gene. Synthesized sgRNAs and Cas9 protein were microinjected into single-cell stage Tübingen (TU)-strain zebrafish embryos. PCR and gel electrophoresis verified editing efficiency at 36 hours post-fertilization (hpf). Surviving embryos were raised to adulthood (F0), tail-clipped, genotyped, and screened for positive mosaics. F1 heterozygotes were generated by outcrossing, and F2 homozygous mutants were obtained by intercrossing. Polymerase chain reaction (PCR) combined with sequencing verified mutation type and heritability. At 5 days post-fertilization (dpf), YO-PRO-1 staining was used to examine hair cell morphology and count in lateral line neuromasts and the otolith region. Auditory evoked potential (AEP) thresholds at 600, 800, 1 000, and 2 000 Hz were measured in nine 4-month-old wild type and mutant zebrafish per group. RESULTS: A stable p2rx2 knockout zebrafish line was successfully established. Sequencing revealed a 66 bp insertion at the first target site introducing a premature stop codon (TAA), leading to early termination of protein translation and loss of function. Embryos developed normally with no gross malformations. At 5 dpf, mutants exhibited significantly reduced hair cell density in the otolith region compared with wild type, although lateral line neuromasts were unaffected. AEP testing showed significantly elevated auditory thresholds at all 4 frequencies in homozygous mutants compared with wild type (all P<0.001), indicating reduced hearing sensitivity. CONCLUSIONS We successfully generated a p2rx2 loss-of-function zebrafish model using CRISPR/Cas9 technology. p2rx2 deficiency caused hair cell defects in the otolith region and increased auditory thresholds across frequencies, indicating its key role in maintaining zebrafish auditory hair cell function and hearing perception. The phenotype's restriction to the otolith region suggests tissue-specific roles of p2rx2 in sensory organs. This model provides a valuable tool for elucidating the molecular mechanisms of P2RX2-related hearing loss and for screening otoprotective drugs and developing gene therapies.
Animals ; Zebrafish/genetics* ; Receptors, Purinergic P2X2/deficiency* ; CRISPR-Cas Systems/genetics* ; Gene Knockout Techniques ; Phenotype ; Zebrafish Proteins/genetics* ; Disease Models, Animal