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Original Article Open Access
Shuyun Huang, Jianchun Guo, Bukun Zhu, Siwen Ye, Wei Zhang
Published online June 1, 2026
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Gastroenterology & Hepatology Research. doi:10.14218/GHR.2026.00002
Abstract
Primary biliary cholangitis (PBC) significantly impairs health-related quality of life (HRQL), yet the impact of disease stage and fatigue on HRQL and psychological status remains [...] Read more.

Primary biliary cholangitis (PBC) significantly impairs health-related quality of life (HRQL), yet the impact of disease stage and fatigue on HRQL and psychological status remains insufficiently quantified. This study aimed to investigate differences in HRQL across disease stages and the impact of fatigue in patients with PBC.

This cross-sectional study recruited 219 patients with PBC from two Chinese tertiary hospitals (2011–2024). After excluding one preclinical case, 218 patients were analyzed. Quality of life was assessed using the validated Chinese versions of the SF-36 and Chronic Liver Disease Questionnaire (CLDQ); psychological status was assessed using the Self-Rating Anxiety Scale and Self-Rating Depression Scale. Between-group differences were quantified by mean differences (MDs) and odds ratios (ORs) with 95% confidence intervals (CIs). Baseline characteristics were balanced across stages (all P > 0.05).

Of the 218 patients (90.4% female; mean age, 57.2 ± 10.3 years), 41 were in the clinical stage, 75 in the fibrosis stage, and 102 in the cirrhosis stage. SF-36 scores were lowest in the cirrhosis stage (e.g., Physical Functioning MD, 17.26; 95% CI, 6.93–27.59 vs. clinical stage), with similar declines in CLDQ domains. Anxiety was highest in the clinical stage (58.5%; OR vs. cirrhosis, 4.13; 95% CI, 1.92–8.92), whereas depression was highest in the cirrhosis stage (55.9%; OR vs. clinical stage, 4.50; 95% CI, 1.95–10.38). Fatigue prevalence was 66.1% and increased with disease stage. Patients with fatigue had lower SF-36 scores in Physical Functioning, Bodily Pain, Vitality, Mental Health, and Physical Component Summary (e.g., Physical Component Summary MD, 38.22; 95% CI, 10.41–66.02).

HRQL declines progressively with PBC stage. Fatigue is strongly associated with impaired HRQL and is closely interrelated with anxiety and depression. Stage-specific psychological patterns suggest the need for tailored supportive interventions.

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Letter to the Editor Open Access
Shumeng Shen, Wenhao Wang, Zhengwei Huang
Published online April 28, 2026
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Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2026.00003
Mini Review Open Access
Siyao Zeng, Zhipeng Yao, Yue Li, Junbo Zheng, Hongliang Wang
Published online June 11, 2026
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Journal of Translational Critical Care Medicine. doi:10.14218/JTCCM.2026.00005
Abstract
Ulinastatin, a broad-spectrum serine protease inhibitor widely used in Asia, has attracted increasing interest for its potential role in critical care. This review summarizes current [...] Read more.

Ulinastatin, a broad-spectrum serine protease inhibitor widely used in Asia, has attracted increasing interest for its potential role in critical care. This review summarizes current evidence on its efficacy and safety in acute pancreatitis, severe acute pancreatitis, sepsis, acute respiratory distress syndrome, and perioperative management in cardiac surgery with cardiopulmonary bypass. Meta-analyses suggest that ulinastatin may improve outcomes by reducing mortality, shortening intensive care unit and hospital stays, and attenuating inflammatory responses. In severe acute pancreatitis, its use has been associated with reduced mortality and shorter hospitalization. In sepsis and septic shock, ulinastatin appears to lower all-cause mortality, decrease organ dysfunction scores, and reduce inflammatory markers. Evidence in acute respiratory distress syndrome indicates improvements in the oxygenation index and possible mortality reduction. Perioperative administration during cardiac surgery may mitigate postoperative inflammation and shorten the duration of mechanical ventilation. Despite these encouraging findings, most available studies originate from Asia and are limited by small sample sizes, heterogeneous designs, and inconsistent dosing regimens, which restrict generalizability and prevent standardized recommendations. Additionally, although ulinastatin demonstrates a favorable safety profile with a low incidence of adverse drug reactions, long-term and multinational pharmacovigilance data remain limited. Well-designed international, multicenter randomized controlled trials are required to clarify optimal dosing strategies, confirm clinical efficacy across diverse populations, and determine its independent effects compared with combination therapies. Overall, ulinastatin shows promise as a potential adjunctive therapy in critical care through modulation of inflammation and organ protection, but broader global adoption will depend on higher-quality evidence addressing current methodological gaps.

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Review Article Open Access
Danzhu Zhao, George Y. Wu
Published online July 2, 2026
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2026.00173
Abstract
Nitric oxide (NO) is a crucial regulator of hepatic and systemic vascular tone. Abnormal distribution of NO in various anatomical locations is a pathogenetic characteristic of portal [...] Read more.

Nitric oxide (NO) is a crucial regulator of hepatic and systemic vascular tone. Abnormal distribution of NO in various anatomical locations is a pathogenetic characteristic of portal hypertension. Under normal portal pressure conditions, liver sinusoidal endothelial cells produce NO, which promotes both vasodilation and hepatic stellate cell relaxation. In portal hypertension, endothelial dysfunction, imbalance of asymmetric dimethylarginine levels, and production of superoxide result in impaired intrahepatic NO availability, leading to activation and contraction of hepatic stellate cells and worsening portal hypertension. Excess extrahepatic NO levels in the splanchnic vasculature result in systemic vasodilation, hyperdynamic circulation, and collateral vascular formation, worsening portal pressure. Abnormal clearance and production of NO can lead to extrahepatic complications, including hepatorenal syndrome and hepatopulmonary syndrome. Therapies including statins, phosphodiesterase-5 inhibitors, and midodrine have been developed to restore NO homeostasis but have achieved only partial success in modulating NO production, bioavailability, and distribution. The aim of this review is to update the understanding of the mechanisms and effects of NO dysregulation in cirrhosis as they relate to current and future therapeutic options.

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Reviewer Acknowledgement Open Access
Editorial Office of Exploratory Research and Hypothesis in Medicine
Published online December 30, 2025
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Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2025.000RA
Original Article Open Access
Yaqin Zhang, Fengxin Chen, Shuojie Wang, Xin Wei, Shiyu Wang, Linmei Yao, Zixuan Gao, Wen Deng, Minghui Li
Published online July 9, 2026
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2026.00093
Abstract
The impact of baseline liver fibrosis severity on the effectiveness of pegylated interferon (Peg-IFN) combined with nucleos(t)ide analogs (NAs) in the treatment of hepatitis B e [...] Read more.

The impact of baseline liver fibrosis severity on the effectiveness of pegylated interferon (Peg-IFN) combined with nucleos(t)ide analogs (NAs) in the treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) has not been fully clarified. This study aimed to investigate whether the effectiveness of this combination therapy differed according to the severity of baseline liver fibrosis.

A total of 172 HBeAg-positive CHB patients receiving Peg-IFN plus NAs were stratified according to non-invasive fibrosis markers (aspartate aminotransferase-to-platelet ratio index [APRI] and fibrosis-4 index [FIB-4]) into three groups: no significant fibrosis (n = 75), significant fibrosis (n = 70), and advanced fibrosis/cirrhosis (n = 27). The primary outcome was the HBeAg clearance rate at 24 months of treatment. Secondary outcomes included the hepatitis B surface antigen (HBsAg) clearance rate, the rate of HBsAg level decline > 1.0 log10, virological response, and improvement in non-invasive fibrosis indices.

At 24 months, HBsAg clearance and complete virological response rates were comparable across the three groups. Cumulative HBeAg clearance rates differed significantly (log-rank P = 0.027): 16.00%, 30.00%, and 40.74% in the three groups, respectively, with Group 3 higher than Groups 1 and 2. Multivariate analysis identified a significantly higher likelihood of HBeAg clearance in Group 3 versus Group 1 (adjusted odds ratio = 6.373, 95% confidence interval: 1.288–31.531, P = 0.023). Additionally, analysis of liver fibrosis outcomes showed that patients with more severe baseline fibrosis had a higher proportion of improvement in non-invasive fibrosis indices, with 95.00% in Group 3, while 42.98% of the overall cohort achieved fibrosis improvement.

Baseline fibrosis severity is associated with higher HBeAg clearance and greater improvement in non-invasive fibrosis indices during Peg-IFN plus NAs therapy in HBeAg-positive CHB.

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Original Article Open Access
Huan Wang, Juanfang Zhang, Xuan Tan, Li Sun, Lianlian Qu, Yuxin Zhan, Sisi Zhang, Danfeng Li, Qiong He, Xiaomei Wei, Hailan Peng
Published online June 29, 2026
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Neurosurgical Subspecialties. doi:10.14218/NSSS.2026.00007
Abstract
Given that hemodynamic fluctuations acutely escalate the risk of devastating rebleeding and secondary neurological deficits in unsecured ruptured intracranial aneurysms, this study [...] Read more.

Given that hemodynamic fluctuations acutely escalate the risk of devastating rebleeding and secondary neurological deficits in unsecured ruptured intracranial aneurysms, this study aimed to synthesize the best available evidence for blood pressure management in this population and to provide an evidence-based foundation for clinical nursing practice.

A systematic search was conducted in domestic and international databases and relevant websites for evidence pertaining to blood pressure management in patients with ruptured intracranial aneurysms, including clinical practices, guidelines, expert consensuses, evidence summaries, and systematic reviews/meta-analyses. The search period covered database inception up to June 2025. Two researchers independently performed literature quality assessments and evidence extraction, with particular attention to nursing-relevant evidence on hemodynamic monitoring, bedside assessment, complication prevention, fluid management, and follow-up coordination.

A total of 17 studies were included, comprising 11 guidelines, 4 expert consensuses, and 2 clinical decision entries. The synthesized evidence yielded 32 recommendations, structured into 6 core clinical domains: personnel and environmental configuration, individualized blood pressure targeting, precision hemodynamic monitoring, complication prevention, fluid therapy strategy, and longitudinal follow-up protocols. These recommendations further clarified key nursing responsibilities in triage coordination, continuous blood pressure surveillance, neurological assessment, delayed cerebral ischemia surveillance, fluid balance monitoring, and long-term follow-up.

Blood pressure management in patients with ruptured intracranial aneurysms should be individualized and multidisciplinary. The synthesized evidence highlights key nursing priorities in hemodynamic monitoring, delayed cerebral ischemia surveillance, fluid management, and follow-up coordination, and may inform standardized clinical nursing protocols.

Full article
Original Article Open Access
Wei Huang, Yanmin Pang, Wenmei Zhao, Liang’e Xia, Luting Wang, Yingde Nong, Kai Xiao, Yichong Ning
Published online June 29, 2026
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Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2025.00077
Abstract
Apatinib has been shown to be efficacious in the treatment of gallbladder cancer. However, the underlying mechanisms remain unclear. This study aimed to explore pathways related [...] Read more.

Apatinib has been shown to be efficacious in the treatment of gallbladder cancer. However, the underlying mechanisms remain unclear. This study aimed to explore pathways related to the antitumor effects of apatinib at the cellular level in gallbladder cancer.

NOZ and GBC-SD gallbladder cancer cells were treated with apatinib at concentrations of 0 μM, 10 μM, or 20 μM. The effect of apatinib on the proliferation of these cells was assessed using MTT and colony formation assays, and the effects of apatinib on cell cycle progression and DNA synthesis were evaluated using flow cytometry. Clinical cancer tissue samples, along with paired adjacent normal tissue samples, were obtained from 10 patients with gallbladder cancer. Immunohistochemistry, western blotting, and quantitative real-time polymerase chain reaction analyses were conducted to elucidate molecular changes induced by apatinib treatment.

Treatment with 20 μM apatinib significantly inhibited the expression of phosphorylated (p)-vascular endothelial growth factor receptor 2 (VEGFR2), p-AKT, and histone deacetylase 1 (HDAC1). Additionally, apatinib treatment led to upregulated expression of p-cyclin-dependent kinase 1, p21, and Bax, and downregulated expression of cell division cycle 25B, B-cell lymphoma 2, Snail, and Slug. Apatinib decelerated DNA replication and induced cell cycle arrest at the G2/M phase, consequently suppressing the proliferation of gallbladder cancer cells.

Apatinib inhibits the proliferation of gallbladder cancer cells, and the mechanism involves VEGFR2/AKT, HDAC1, and downstream genes. These findings provide a basis for further investigation into the molecular mechanisms underlying the inhibitory effect of apatinib in gallbladder cancer.

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Original Article Open Access
Ruoyu Wang, Zhang Wang
Published online June 26, 2026
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Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2026.00007
Abstract
Observational studies have shown that educational attainment is associated with the risk of myopia, but the causality of this relationship is unclear. The aim of the present study [...] Read more.

Observational studies have shown that educational attainment is associated with the risk of myopia, but the causality of this relationship is unclear. The aim of the present study was to investigate the causal association between educational attainment and myopia.

Using publicly available data from genome-wide association studies, single nucleotide polymorphisms associated with educational attainment (college/university completion and years of education) were selected as instrumental variables. Causal associations with myopia risk were examined using two-sample Mendelian randomization (MR) analyses. Sensitivity analyses were conducted to assess the robustness of the results in terms of violations of MR assumptions.

The inverse variance–weighted analysis revealed potential causal associations of college/university completion (odds ratio (OR) = 1.102; 95% confidence interval (CI): 1.085–1.119; P < 0.001) and years of education (OR = 1.009; 95% CI: 1.007–1.010; P < 0.001) with myopia risk. MR-Egger and weighted median methods yielded similar results for both educational attainment measures.

MR evidence supports a potential causal association between educational attainment and myopia. This evidence highlights the need for careful management of myopia risk in individuals with higher educational attainment.

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Original Article Open Access
Xiaoyue Shi, Wei Cao, Chenran Wang, Jiaxin Xie, Zilin Luo, Xiaolu Chen, Zeming Guo, Yixuan Qin, Yu Wang, Xuesi Dong, Fei Wang, Ni Li
Published online June 29, 2026
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Cancer Screening and Prevention. doi:10.14218/CSP.2026.00038
Abstract
Bladder cancer (BC) remains a major public health concern in China, but comprehensive and up-to-date assessments of its burden and temporal patterns remain limited. This study aimed [...] Read more.

Bladder cancer (BC) remains a major public health concern in China, but comprehensive and up-to-date assessments of its burden and temporal patterns remain limited. This study aimed to systematically evaluate the current burden, temporal trends, and future projections of BC in China using data from the Global Burden of Disease Study 2023.

Data on BC incidence, mortality, disability-adjusted life years, and risk-attributable mortality in China from 1990 to 2023 were extracted from the Global Burden of Disease Study 2023. Temporal trends were assessed using Joinpoint regression, with a maximum of six joinpoints allowed, to estimate annual percentage changes and average annual percentage changes. Age-period-cohort models based on log-linear Poisson regression were used to examine age, period, and cohort effects. Bayesian age-period-cohort models were then applied to project incidence and mortality rates to 2030 while accounting for age-period-cohort effects and demographic changes.

From 1990 to 2023, crude incidence, mortality, and disability-adjusted life year rates increased, whereas age-standardized rates generally declined (average annual percentage changes = −0.32%, −1.31%, and −1.62%, respectively). Recent upward trends were nevertheless observed across all three indicators, particularly for incidence and mortality during 2020–2023 (annual percentage changes = 5.05% and 4.39%, respectively). Local drifts were negative in most age groups but approached or exceeded zero in the oldest groups. The incidence local drift was 0.35% (95% confidence interval [CI]: −0.07%, 0.78%) in the 85–89-year age group and 0.64% (95% CI: −0.31%, 1.61%) in the 90–94-year age group, whereas the corresponding mortality local drifts were −0.70% (95% CI: −0.97%, −0.43%) and −0.18% (95% CI: −0.72%, 0.36%), respectively. Compared with the reference period (2004–2008), the relative risks for incidence and mortality in 2019–2023 were 0.95 (95% CI: 0.91–0.98) and 0.75 (95% CI: 0.71–0.78), respectively. Compared with the reference cohort (1951–1956), earlier birth cohorts had elevated risks; in the 1901–1906 cohort, the relative risks were 1.13 (95% CI: 0.82, 1.57) for incidence and 2.10 (95% CI: 1.75, 2.52) for mortality. During 2024–2030, both crude incidence and crude mortality rates were projected to increase further.

Despite long-term declines in age-standardized rates, BC remains a substantial burden in China, and recent upward trends warrant attention. These findings support targeted primary prevention and risk-stratified early-detection strategies for high-risk populations.

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