Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

Cardiovascular disease (CVD), chronic kidney disease (CKD), and metabolic disorders are the 3 major chronic diseases threatening human health, which are closely related and often coexist, significantly increasing the difficulty of disease management. In response, the American Heart Association (AHA) proposed a novel disease concept of “cardiovascular-kidney-metabolic (CKM) syndrome” in October 2023, which has triggered widespread concern about the co-treatment of heart and kidney diseases and the prevention and treatment of metabolic disorders around the world. This review posits that effectively managing CKM syndrome requires a new and multidimensional paradigm for diagnosis and risk prediction that integrates biological insights, advanced technology and social determinants of health (SDoH). We argue that the core pathological driver is a “metabolic toxic environment”, fueled by adipose tissue dysfunction and characterized by a vicious cycle of systemic inflammation and oxidative stress, which forms a common pathway to multi-organ injury. The at-risk population is defined not only by biological characteristics but also significantly impacted by adverse SDoH, which can elevate the risk of advanced CKM by a factor of 1.18 to 3.50, underscoring the critical need for equity in screening and care strategies. This review systematically charts the progression of diagnostic technologies. In diagnostics, we highlight a crucial shift from single-marker assessments to comprehensive multi-marker panels. The synergistic application of traditional biomarkers like NT-proBNP (reflecting cardiac stress) and UACR (indicating kidney damage) with emerging indicators such as systemic immune-inflammation index (SII) and Klotho protein facilitates a holistic evaluation of multi-organ health. Furthermore, this paper explores the pivotal role of non-invasive monitoring technologies in detecting subclinical disease. Techniques like multi-wavelength photoplethysmography (PPG) and impedance cardiography (ICG) provide a real-time window into microcirculatory and hemodynamic status, enabling the identification of early, often asymptomatic, functional abnormalities that precede overt organ failure. In imaging, progress is marked by a move towards precise, quantitative evaluation, exemplified by artificial intelligence-powered quantitative computed tomography (AI-QCT). By integrating AI-QCT with clinical risk factors, the predictive accuracy for cardiovascular events within 6 months significantly improves, with the area under the curve (AUC) increasing from 0.637 to 0.688, demonstrating its potential for reclassifying risk in CKM stage 3. In the domain of risk prediction, we trace the evolution from traditional statistical tools to next-generation models. The new PREVENT equation represents a major advancement by incorporating key kidney function markers (eGFR, UACR), which can enhance the detection rate of CKD in primary care by 20%-30%. However, we contend that the future lies in dynamic, machine learning-based models. Algorithms such as XGBoost have achieved an AUC of 0.82 for predicting 365-day cardiovascular events, while deep learning models like KFDeep have demonstrated exceptional performance in predicting kidney failure risk with an AUC of 0.946. Unlike static calculators, these AI-driven tools can process complex, multimodal data and continuously update risk profiles, paving the way for truly personalized and proactive medicine. In conclusion, this review advocates for a paradigm shift toward a holistic and technologically advanced framework for CKM management. Future efforts must focus on the deep integration of multimodal data, the development of novel AI-driven biomarkers, the implementation of refined SDoH-informed interventions, and the promotion of interdisciplinary collaboration to construct an efficient, equitable, and effective system for CKM screening and intervention.

AIM To establish an UPLC-MS/MS method for simultaneous content determination of protocatechuic acid,epicatechin,chlorogenic acid,quercitrin,gaultherin and gaultheroside A in Gaultheria leucocarpa var.yunnanensis.METHODS The analysis was performed on a 40℃thermostatic Waters BEH C18 column(100 mm×2.1 mm,1.7 μm),with the mobile phase comprising of water(containing 0.1%formic acid)-acetonitrile(containing 0.1%formic acid)flowing at 0.3 mL/min in a gradient elution manner,and electron spray inoization source was adopted in positive and negative ion scanning with multiple reaction monitoring(MRM)mode.Hierarchical cluster analysis(HCA)and principal component analysis(PCA)was used to screen important components that affect the quality of medicinal materials.RESULTS Six constituents showed good linear relationships within their own ranges(R2≥0.998 2),whose average recoveries were 98.76%-101.88%with the RSDs of 1.0%-2.5%.The constituents of G.leucocarpa in the roots and aerial parts were quite different.Gaultherin,epicatechin and protocatechuic acid may be the quality mark constituents of G.leucocarpa.CONCLUSION This accurate and efficient method can be used for the quality control of G.leucocarpa.

Objective To investigate the relationship between uric acid metabolism and brain injury following cardiopulmonary bypass(CPB)in rats.Methods Healthy male SD rats were randomly assigned to either a Sham group or a CPB group,each comprising 12 rats.The Sham group only underwent vascular puncture and did not perform CPB conversion,while the CPB group was subjected to a CPB procedure with a perfusion duration of 110 min,and the brain tissue was collected post-procedure.Microdialysate was collected 1 h before and after CPB initiation.Apoptosis in the paraventricular nucleus(PVN)was assessed using TUNEL staining,and the expression of Bax mRNA in cerebral cortex and hypothalamus was determined via real-time quantitative PCR.Apoptosis-related protein expression was analyzed by Western blotting.Differentially expressed genes(DEGs)were identified through RNA-sequencing between brain tissues of two groups,and Gene Ontology(GO)analysis was performed to identify enriched pathways among the DEGs.Protein-protein interaction(PPI)networks were constructed using String and Cytoscape softwares to identify key genes.Liquid chromatography tandem mass spectrometry(LC-MS/MS)was employed to analyze differential metabolites in the PVN before and after CPB,with Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis constructed subsequently.Uric acid levels in the hypothalamus was measured using a uric acid assay kit,and the expression of key enzymes of uric acid metabolism[xanthine reductase(XDH),adenosine deaminase(ADA)]and uric acid transporter[organic anion transporter family protein 1(OAT1),organic anion transporter family protein 3(OAT3),ATP-binding cassette transporter subfamily G member 2(ABCG2),glucose transporter 9(GLUT9)]genes in the hypothalamus was evaluated by real-time quantitative PCR.Results Real-time quantitative PCR revealed a significant upregulation of Bax mRNA in the cerebral cortex and hypothalamus of CPB group compared to Sham group(P<0.05).TUNEL staining indicated a significantly higher apoptosis rate of cells in PVN region in CPB group than that in Sham group(19.0%±5.0%vs.7.6%±0.8%,P=0.01).Western blotting showed a significantly increased Bcl-2/Bax ratio in the hypothalamus of CPB group compared to Sham group(P<0.05).A total of 2829 DEGs were identified between Sham group and CPB group,with 1374 upregulated genes and 1455 downregulated genes.Uric acid metabolism-related pathways were predominantly enriched in purine nucleoside metabolism and biosynthesis,purine nucleoside monophosphate metabolism,purine nucleoside triphosphate metabolism,purine ribonucleotide metabolism and biosynthesis,purine ribonucleoside monophosphate metabolism and biosynthesis,purine ribonucleoside triphosphate metabolism and biosynthesis,and reaction to purine compounds.Eighteen differential metabolites were identified in the microdialysate,with 13 upregulated and 5 downregulated metabolites.KEGG enrichment analysis identified 7 significantly enriched metabolic pathways,among which the nicotinate and nicotinamide metabolism pathways were closely related to uric acid metabolism.Both RNA-sequencing and LC-MS/MS analysis suggested alterations in uric acid metabolism in CPB groups.Post-CPB,uric acid concentration in the hypothalamic tissue significantly increased(P<0.01),and the expression of XDH and ADA mRNA in the hypothalamus were significantly increased(P<0.05),while the expression of ABCG2,OAT1,OAT3 and GLUT9 mRNA significantly decreased(P<0.001).Conclusion Uric acid metabolism in brain is altered during CPB,which may be an important mechanism for brain injury following CPB.

Heart failure with preserved ejection fraction(HFpEF)is a highly heterogeneous systemic condition and represents the predominant form of heart heart failure(HF)worldwide.Current pharmacotherapies for HFpEF are limited and lack specific targeted drugs.Recent studies suggest that non-pharmacological strategies serve as adjuncts to conventional pharmacological treatment,offering improvements in symptoms,quality of life,and reducing the risk of rehospitalization for HF in patients with HFpEF.These strategies include CD34 stem cell transplantation,the greater splanchnic nerve ablation,atrial septal shunting,atrial pacing,myocardial contractility modulation,left ventricular expander,baroreceptor stimulation,and others.This review comprehensively summarizes the latest clinical evidence on non-pharmacological treatments for HFpEF,with the aim of advancing the understanding of treatment strategies for this condition.

Objective To investigate the association between auditory processing and problem behaviors in preschool children,as well as the mediating role of executive function.Methods A total of 2 342 preschool children were selected from 7 kindergartens in Nanjing,China from June to August 2021.They were evaluated using Preschool Auditory Processing Assessment Scale,Conners Parent Symptom Questionnaire,and Behavior Rating Inventory of Executive Functioning-Preschool version.Children with different demographic features were compared in the scores and the abnormality rates of auditory processing,problem behaviors,and executive function.The influencing factors of the total scores of auditory processing,problem behaviors,and executive function were evaluated using multiple linear regression analysis.Whether executive function was a mediating factor between auditory processing and executive function was examined.Results Sex and grade were the main influencing factors for the total score of auditory processing(P<0.05),and sex,grade,parental education level,and family economic status were the main influencing factors for the total scores of problem behaviors and executive function(P<0.05).The auditory processing score(rs= 0.458,P<0.05)and problem behavior score(rs=0.185,P<0.05)were significantly positively correlated with the executive function score,and the auditory processing score was significantly positively correlated with the problem behavior score(rs=0.423,P<0.05).Executive function played a partial mediating role between auditory processing and problem behaviors,and the mediating effect accounted for 33.44% of the total effect.Conclusions Auditory processing can directly affect the problem behaviors of preschool children and indirectly affect problem behaviors through executive function.[Chinese Journal of Contemporary Pediatrics,2024,26(2):174-180]

Purpose: During the COVID-19 pandemic, nurses have faced many professional and ethical dilemmas and challenges along with bearing physical, mental, and emotional stress resulting from worrying about themselves or their family being infected and stigmatized. This stress can potentially lead to burnout and resignation. Professional resilience is crucial for nurses to cope with these adverse situations. This study aimed to investigate the process by which nurses adapt, change, and overcome challenges during the COVID-19 pandemic and ultimately demonstrate professional resilience. Methods: Descriptive phenomenology was applied. Semi-structured interviews were conducted with 11 nurses working in COVID-19 wards and intensive care units to collect data. Giorgi's phenomenological analysis method was employed. Results: Based on the interview responses, four major themes were identified: 1) balancing patient care, self-protection, and passing on experience; 2) providing timely pandemic team resources and social support; 3) nurses' perseverance amid social discourse and constrained lives; and 4) selfless dedication shaping nursing's pinnacle experiences. Conclusions In the face of a sudden pandemic, frontline nurses play a critical role in maintaining medical capacity. Consequently, they must balance their families, lives, and work while adapting to the impact of the pandemic and changing practices and procedures based on the development of the pandemic and policy demands. The study findings provide insights into the challenges and emotional experiences encountered by nurses during a sudden pandemic outbreak and can serve as a reference for developing strategies to help nurses overcome these challenges and enhance their professional resilience.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.