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Case Report Open Access
Weiguang Qiao, Qiling Liang, Fachao Zhi
Published online November 12, 2024
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Cancer Screening and Prevention. doi:10.14218/CSP.2024.00005S
Abstract
Achalasia is a rare esophageal motility disorder characterized by the inability of the lower esophageal sphincter to relax and the absence of normal esophageal peristalsis. This [...] Read more.

Achalasia is a rare esophageal motility disorder characterized by the inability of the lower esophageal sphincter to relax and the absence of normal esophageal peristalsis. This condition leads to difficulties in swallowing (dysphagia), regurgitation of food, and chest pain. Clinical observations suggest an association between achalasia and esophageal tumors, as achalasia can increase the risk of developing esophageal cancer. We explore the pathophysiology of achalasia, its clinical manifestations, and the associated risk of esophageal malignancies, supported by recent research and clinical evidence, including specific case studies.

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Review Article Open Access
Minhua Wang, Maria D. Lozano, Guoping Cai
Published online September 25, 2024
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Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2024.00034
Abstract
The World Health Organization System for Reporting Pancreaticobiliary Cytopathology introduces a seven-tier category system to standardize terminology and nomenclature. This system [...] Read more.

The World Health Organization System for Reporting Pancreaticobiliary Cytopathology introduces a seven-tier category system to standardize terminology and nomenclature. This system includes the following categories: Insufficient/non-diagnostic, benign/negative for malignancy, atypia, pancreaticobiliary neoplasm low-risk/grade, pancreaticobiliary neoplasm high-risk/grade, suspicious for malignancy, and malignant categories. Adopting a standardized reporting scheme facilitates consistent diagnostic criteria among pathologists, thereby reducing report variability and enhancing communication with the clinical team for optimal patient management. The report also highlights the role of critical ancillary tests in improving diagnostic accuracy for pancreatic lesions and discusses practical approaches to managing solid and cystic pancreatic lesions.

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Original Article Open Access
Jiayu Liu, Guangyong Wu, Bo Liu, Jingru Zhou, Cungang Fan, Donliang Wang, Bo Hei, Fang Li, Jia Ouyang, Zhi Liu, Qingpei Hao, Ruen Liu
Published online December 4, 2024
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Neurosurgical Subspecialties. doi:10.14218/NSSS.2024.00003
Abstract
Atypical trigeminal neuralgia (ATN) is a chronic pain condition characterized by persistent facial pain that does not respond well to conventional medical treatments, often leading [...] Read more.

Atypical trigeminal neuralgia (ATN) is a chronic pain condition characterized by persistent facial pain that does not respond well to conventional medical treatments, often leading to significant impairment in quality of life. This study examined the clinical characteristics and surgical outcomes of microvascular decompression combined with nerve combing in patients with ATN.

We conducted a retrospective analysis of surgical techniques, clinical data, and treatment outcomes in 40 patients from January 2009 to January 2018. Pain levels and patient prognoses were assessed using the Visual Analog Scale and the Barrow Neurological Institute (BNI) pain score. Dynamic monitoring of arterial blood pressure was performed, and levels of total adrenaline, norepinephrine, and dopamine were measured before and during the nerve combing procedure.

During surgery, veins combined with arachnoid adhesions and arachnoid adhesions alone were observed compressing the trigeminal nerve in seven patients (17.50%) and 33 patients (82.50%), respectively. Immediate postoperative BNI scores indicated excellent outcomes (P = 2) in 30 patients (75.00%) and good outcomes (P = 3) in four patients (10.00%). Long-term postoperative BNI scores showed excellent outcomes (P = 2) in 25 patients (62.50%) and good outcomes (P = 3) in seven patients (17.50%). All patients experienced an increase in arterial blood pressure during nerve combing, and the mean levels of adrenaline and norepinephrine before combing showed significant improvement (P < 0.05).

Microvascular decompression combined with nerve combing achieves favorable results in treating ATN. Long-term trigeminal nerve compression and central sensitization may contribute to the etiology in these patients.

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Original Article Open Access
Regina Oshins, Zhiguang Huo, Zachary Greenberg, Virginia Clark, Sergio Duarte, Huiping Zhou, Jesse West, Mei He, Mark Brantly, Nazli Khodayari
Published online November 19, 2024
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00253
Abstract
Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder associated with liver disease, ranging from fibrosis to hepatocellular carcinoma. The disease remains asymptomatic until [...] Read more.

Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder associated with liver disease, ranging from fibrosis to hepatocellular carcinoma. The disease remains asymptomatic until its final stages when liver transplantation is the only available therapy. Biomarkers offer an advantage for disease evaluation. The presence of microRNAs (miRNAs) in plasma extracellular vesicles (EVs) presents a noninvasive approach to assess the molecular signatures of the disease. In this study, we aimed to identify miRNA biomarkers to distinguish molecular signatures of the liver disease associated with AATD in AATD individuals.

Using small RNA sequencing and qPCR, we examined plasma EV miRNAs in healthy controls (n = 20) and AATD patients (n = 17). We compared the EV miRNAs of AATD individuals with and without liver disease, developing an approach for detecting liver disease. A set of miRNAs identified in the AATD testing cohort was validated in a separate cohort of AATD patients (n = 45).

We identified differential expression of 178 EV miRNAs in the plasma of the AATD testing cohort compared to controls. We categorized AATD individuals into those with and without liver disease, identifying 39 differentially expressed miRNAs. Six miRNAs were selected to test their ability to discriminate liver disease in AATD. These were validated for their specificity and sensitivity in an independent cohort of 45 AATD individuals. Our logistic model established composite scores with three- and four-miRNA combinations, achieving areas under the curve of 0.737 and 0.751, respectively, for predicting AATD liver disease.

We introduce plasma EV-derived miRNAs as potential biomarkers for evaluating AATD liver disease. Plasma EV-associated miRNAs may represent a molecular signature of AATD liver disease and could serve as valuable tools for its detection and monitoring.

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Original Article Open Access
Xieer Liang, Qiaoqiao Chen, Hong Tang, Yujuan Guan, Minfeng Liang, Peng Hu, Wen Xie, Huiying Rao, Junqi Niu, Liang Chen, Li Yan, Xiaowei Chen, Xiaohe Li, Yulin Zhao, Oliver Lenz, Michael Biermer, Jinlin Hou
Published online February 24, 2025
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00313
Abstract
Large-scale data on the hepatitis D virus (HDV)/hepatitis B virus (HBV) co-infection rate is needed to estimate the current epidemiology of HDV in China. This study aimed to estimate [...] Read more.

Large-scale data on the hepatitis D virus (HDV)/hepatitis B virus (HBV) co-infection rate is needed to estimate the current epidemiology of HDV in China. This study aimed to estimate the current epidemiology of HDV.

Patients with chronic HBV infection, with documented serum hepatitis B surface antigen (HBsAg) positivity for more than six months, were enrolled across China. Blood samples were collected at baseline for central evaluations of HDV antibody and HBsAg quantification. Assessments for antibodies of hepatitis A virus, hepatitis C virus, hepatitis E virus, and human immunodeficiency virus, as well as HDV RNA quantification, were performed in patients who tested positive for HDV antibodies.

Of the 5,044 enrolled patients between September 24, 2021, and December 28, 2022, 4,936 patients were included in the analysis. The mean age (±standard deviation) was 42.9 ± 9.9 years, and 69.8% of patients were male. The mean alanine aminotransferase level was 34 ± 58 U/L, and 1,509 (30.6%) patients were hepatitis B e antigen-positive. The mean (standard deviation) HBsAg level at baseline was 3,535 ± 11,292 IU/mL among 4,842 patients who were HBsAg positive. The rate of HBV infection and HDV antibody positivity was 0.24% (95% confidence interval: 0.1–0.4%), and only one patient was HDV RNA positive.

The prevalence of HDV antibody positivity was 0.24% in Chinese patients with chronic HBV infection, and only one patient with both anti-HDV antibody and HDV RNA positivity was observed in this study.

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Original Article Open Access
Naweed Mohammad, Regina Oshins, Tongjun Gu, Virginia Clark, Jorge Lascano, Naziheh Assarzadegan, George Marek, Mark Brantly, Nazli Khodayari
Published online September 14, 2024
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00201
Abstract
Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder characterized by the misfolding and accumulation of the mutant variant of alpha-1 antitrypsin (AAT) within hepatocytes, [...] Read more.

Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder characterized by the misfolding and accumulation of the mutant variant of alpha-1 antitrypsin (AAT) within hepatocytes, which limits its access to the circulation and exposes the lungs to protease-mediated tissue damage. This results in progressive liver disease secondary to AAT polymerization and accumulation, and chronic obstructive pulmonary disease (COPD) due to deficient levels of AAT within the lungs. Our goal was to characterize the unique effects of COPD secondary to AATD on liver disease and gene expression.

A subcohort of AATD individuals with COPD (n = 33) and AATD individuals without COPD (n = 14) were evaluated in this study from our previously reported cross-sectional cohort. We used immunohistochemistry to assess the AATD liver phenotype, and RNA sequencing to explore liver transcriptomics. We observed a distinct transcriptomic profile in liver tissues from AATD individuals with COPD compared to those without.

A total of 339 genes were differentially expressed. Canonical pathways related to fibrosis, extracellular matrix remodeling, collagen deposition, hepatocellular damage, and inflammation were significantly upregulated in the livers of AATD individuals with COPD. Histopathological analysis also revealed higher levels of fibrosis and hepatocellular damage in these individuals.

Our data supports a relationship between the development of COPD and liver disease in AATD and introduces genes and pathways that may play a role in AATD liver disease when COPD is present. We believe addressing lung impairment and airway inflammation may be an approach to managing AATD-related liver disease.

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Original Article Open Access
Enmeng Bao, Kuanyu Wang, Dezhi Gao, Bin Luo, Ali Liu, Shibin Sun
Published online December 17, 2024
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Neurosurgical Subspecialties. doi:10.14218/NSSS.2024.00002
Abstract
The role of radiosurgery in the treatment of grade 2 meningioma remains unclear. This study aimed to evaluate the long-term outcomes of gamma knife radiosurgery (GKRS) in patients [...] Read more.

The role of radiosurgery in the treatment of grade 2 meningioma remains unclear. This study aimed to evaluate the long-term outcomes of gamma knife radiosurgery (GKRS) in patients with grade 2 meningiomas and to identify factors influencing tumor control and survival.

In this retrospective study, seventy patients underwent GKRS for grade 2 meningioma between 2007 and 2016. Tumor recurrence was categorized as local, marginal, or distant. Survival curves were estimated using the Kaplan-Meier method, while the log-rank test and Cox proportional hazards model were employed to analyze potential risk factors.

The median follow-up period was 48 months (range: 8 to 132 months). The one-year, three-year, and five-year local control rates were 92%, 73%, and 65%, respectively. The one-, three-, and three-year progression-free survival rates were 87%, 51%, and 44%, respectively. Multiple lesions and multiple prior recurrences were identified as negative predictors of marginal control and progression-free survival. Similarly, multiple lesions and marginal doses ≤13 Gy were associated with poor local control. Serious complications related to gamma knife use occurred in 4% of patients.

Our results support that GKRS is a reasonable treatment option in the management of grade 2 meningiomas. However, outfield progression remains a significant challenge, particularly in patients with multiple prior relapses and/or multiple lesions. More aggressive treatment strategies should be explored for these high-risk patients.

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Original Article Open Access
Wende Li, Wanshu Liu, Yihui Rong, Dongze Li, Bing Zhu, Shaobo Yang, Shidong Sun, Shaoli You, Yu Chen, Jun Li
Published online September 30, 2024
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00316
Abstract
Early determination of prognosis in patients with acute-on-chronic liver failure (ACLF) is crucial for optimizing treatment options and liver allocation. This study aimed to identify [...] Read more.

Early determination of prognosis in patients with acute-on-chronic liver failure (ACLF) is crucial for optimizing treatment options and liver allocation. This study aimed to identify risk factors associated with ACLF and to develop new prognostic models that accurately predict patient outcomes.

We retrospectively selected 1,952 hospitalized patients diagnosed with ACLF between January 2010 and June 2018. This cohort was used to develop new prognostic scores, which were subsequently validated in external groups.

The study included 1,386 ACLF patients and identified six independent predictors of 28-day mortality through multivariate analysis (all p < 0.05). The new score, based on a multivariate regression model, demonstrated superior predictive accuracy for both 28-day and 90-day mortalities, with Areas under the ROC curves of 0.863 and 0.853, respectively (all p < 0.05). This score can be used to stratify the risk of mortality among ACLF patients with ACLF, showing a significant difference in survival between patients categorized by the cut-off value (log-rank (Mantel–Cox) χ2 = 487.574 and 606.441, p = 0.000). Additionally, the new model exhibited good robustness in two external cohorts.

This study presents a refined prognostic model, the Model for end-stage liver disease-complication score, which accurately predicts short-term mortality in ACLF patients. This model offers a new perspective and tool for improved clinical decision-making and short-term prognostic assessment in ACLF patients.

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Original Article Open Access
Xiuxiu Deng, Hui Li, Yuru Zhong, Haibo Wang, Lixin Ke, Zhifei Wang, Alexios-Fotios A. Mentis, Yangqin Xun, Qiang Zhang, Cuncun Lu
Published online November 11, 2024
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00351
Abstract
Liver cancer is a digestive system malignancy that poses a significant public health challenge globally. This study aimed to analyze and compare the epidemiological trends of liver [...] Read more.

Liver cancer is a digestive system malignancy that poses a significant public health challenge globally. This study aimed to analyze and compare the epidemiological trends of liver cancer attributed to hepatitis B (LCHB) and alcohol use (LCAL) over the past 32 years.

Data on mortality and disability-adjusted life years for LCHB and LCAL in China, globally, and across five sociodemographic index regions were obtained from the Global Burden of Disease 2021 database and comprehensively analyzed.

In 2021, the global and Chinese death counts and disability-adjusted life years attributed to LCHB and LCAL showed substantial increases compared to 1990. China had the highest number of deaths from LCHB and LCAL among 204 countries and regions. Gender and age disparities were notable, with males and those aged 40–75 years bearing a higher burden than females and other age groups. Global age-period-cohort analysis revealed an escalating risk of death from LCHB with age, alongside a lower risk in younger cohorts and more recent periods. The mortality risk for LCAL also increased with age but exhibited distinct cohort and period effects compared to LCHB. Decomposition analysis indicated that shifts in the global burden of LCHB and LCAL were influenced by population growth, with population aging playing a crucial role in China.

A significant burden of LCHB and LCAL persists, highlighting the need for tailored prevention, screening, and control strategies to mitigate their incidence, as well as the identification of advanced therapeutics to reduce mortality.

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Review Article Open Access
Swarup K. Chakrabarti, Dhrubajyoti Chattopadhyay
Published online April 17, 2025
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Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2024.00045
Abstract
This review explores the complex interplay between the microbiome and human aging, highlighting how dysbiosis impacts host physiology and health, particularly in relation to genomic [...] Read more.

This review explores the complex interplay between the microbiome and human aging, highlighting how dysbiosis impacts host physiology and health, particularly in relation to genomic stability and telomere attrition. Recent advances in cellular and molecular biology have underscored the role of both intrinsic and extrinsic factors in human aging, with the microbiome emerging as a key determinant of host physiology and health. Dysbiosis—disruptions in microbiome composition—is linked to various age-related diseases and impacts genomic stability and telomere attrition, the progressive shortening of telomeres that limits cell division and contributes to aging. This review examines how microbiome dynamics influence aging by triggering inflammation, oxidative stress, immune dysregulation, and metabolic dysfunction, all of which affect two primary hallmarks of aging: genomic instability and telomere attrition. Understanding these interactions is essential for developing targeted interventions to restore microbiome balance and promote healthy aging, offering potential treatments to extend healthspan and alleviate aging-related diseases. The convergence of microbiome and aging research promises transformative insights and new avenues for improving global population well-being.

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