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Case Report Open Access
Xinyu Yu, Weiming Xu
Published online February 28, 2025
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Neurosurgical Subspecialties. doi:10.14218/NSSS.2025.00001
Abstract
Balamuthia mandrillaris is a free-living amoeba that can cause granulomatous amoebic encephalitis, a lethal neurological condition in humans. This pathogen infects not only immunocompromised [...] Read more.

Balamuthia mandrillaris is a free-living amoeba that can cause granulomatous amoebic encephalitis, a lethal neurological condition in humans. This pathogen infects not only immunocompromised hosts but, more commonly, immunocompetent individuals. Balamuthia mandrillaris mainly infects the skin and nervous system. When it affects the nervous system, it can manifest as Balamuthia mandrillaris encephalitis (BAE). This article presents a case of BAE in central China, diagnosed through next-generation sequencing and histopathology. The patient is a 64-year-old male who was admitted to the Department of Neurosurgery with a one-week history of headache. Magnetic resonance imaging scans revealed a mass in the right temporal-occipital region, and postoperative pathological examination confirmed that the lesion was BAE. We will detail the clinical course of this disease in this patient, aiming to enhance clinicians’ understanding of Balamuthia mandrillaris infections.

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Case Report Open Access
Qihan Guo, Wei Xie, Andrea Fuentes, Wen Shuai
Published online May 9, 2025
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Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2025.00012
Abstract
Philadelphia chromosome-positive (Ph+) B-lymphoblastic leukemia/lymphoma (B-ALL/LBL) is an aggressive hematologic malignancy driven by the BCR::ABL1 fusion. While many cases respond [...] Read more.

Philadelphia chromosome-positive (Ph+) B-lymphoblastic leukemia/lymphoma (B-ALL/LBL) is an aggressive hematologic malignancy driven by the BCR::ABL1 fusion. While many cases respond well to treatment, some patients exhibit persistent BCR::ABL1 expression after therapy, presenting significant diagnostic challenges.

We present the case of a seven-year-old girl diagnosed with Ph+ B-ALL. Despite low percentages or negative results for blasts post-treatment, molecular and cytogenetic studies persistently detected high levels of BCR::ABL1, suggesting a high disease burden at the genetic level. This discordance supported multilineage involvement and the potential for retrospective revision of the initial diagnosis to lymphoblast crisis of chronic myeloid leukemia (LBC-CML).

Classifying such cases as de novo Ph+ B-ALL with multilineage involvement or LBC-CML is challenging, as there is currently no consensus among experts. Further studies are necessary to clarify the distinction, given the different management strategies and treatment responses between these two conditions.

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Original Article Open Access
Mingshu Gao, Jiaying Li, Yanan Zhang, Jiangtao Huang, Jiaqi Chen, Dawen Liao, Shengnan He, Qian Bi, Lele Ji, Yulu Du
Published online May 30, 2025
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00072
Abstract
Metabolic-associated steatohepatitis (MASH) is an advanced and progressive liver disease that potentially causes cirrhosis and hepatocellular carcinoma. Exercise is a crucial and [...] Read more.

Metabolic-associated steatohepatitis (MASH) is an advanced and progressive liver disease that potentially causes cirrhosis and hepatocellular carcinoma. Exercise is a crucial and effective intervention for ameliorating metabolic dysfunction-associated steatotic liver disease. This study aimed to provide a comprehensive understanding of the underlying mechanisms of MASH, which benefit a broad spectrum of MASH patients, including those who have difficulty engaging in physical activity.

We established a mouse model of MASH and selectively knocked down L-type amino acid transporter 1 and alanine-serine-cysteine transporter 2. Mice were fed a high-fat high-cholesterol diet and subjected to either short- or long-term exercise regimens. We assessed the phosphorylation and activity of branched-chain alpha-keto acid dehydrogenase (BCKDH) as well as branched-chain amino acid (BCAA) content in skeletal muscle following exercise.

Short-term exercise significantly reduced hepatic steatosis and inflammation without causing notable changes in body weight. It also enhanced BCKDH activity in skeletal muscle and decreased hepatic BCAA accumulation. Muscle-specific overexpression of BCKDH further promoted BCAA catabolism and significantly attenuated hepatic steatosis and inflammation in high-fat high-cholesterol-fed mice. In contrast, muscle-specific L-type amino acid transporter 1 knockdown, which suppresses BCAA uptake, markedly abolished these beneficial effects. Interestingly, BCKDH overexpression in muscle increased glutamine levels in both the blood and liver. Hepatic alanine-serine-cysteine transporter 2 knockdown, which inhibited glutamine uptake, lessened the protective effect of exercise on MASH. Further in vitro study revealed that glutamine derived from myocytes improved redox homeostasis and inhibited lipid accumulation in hepatocytes.

Short-term exercise enhances BCAA catabolism in skeletal muscle and promotes glutamine production, which circulates to the liver to improve redox balance and alleviate MASH.

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Review Article Open Access
Zhicheng Yang, Yongle Zhao, Honglin Chen, Han Zhang, Maoting Tan, Xianliu Li, Lingling Tao, Hongyun Zhao
Published online July 29, 2025
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00124
Abstract
Actively identifying the risk factors and predictive indicators associated with portal vein thrombosis (PVT) in liver cirrhosis (LC) can enable early diagnosis and treatment, which [...] Read more.

Actively identifying the risk factors and predictive indicators associated with portal vein thrombosis (PVT) in liver cirrhosis (LC) can enable early diagnosis and treatment, which is of great significance for prolonging the survival of patients with LC. Hemodynamic disturbances, advanced LC, vascular endothelial injury, and mutations in thrombophilic genetic factors are established risk factors for PVT-LC. Venous dilatation and decreased blood flow velocity contribute to hemodynamic disturbances. The severity of LC can be assessed by the degree of portal hypertension, liver metabolic function biomarkers, and validated liver scoring systems. Iatrogenic interventions, endotoxemia, and metabolic syndrome may induce vascular endothelial injury and hypercoagulability, the latter of which can be quantified via coagulation-anticoagulation-fibrinolysis biomarkers. Mutations in thrombophilic genetic factors, such as Factor V Leiden, MTHFR C667T, and JAK2 V617F, disrupt coagulation-anticoagulation homeostasis and predispose patients to PVT-LC. This review specifically focuses on comprehensively delineating established risk factors and predictive indicators for PVT-LC, thereby providing a theoretical foundation for the construction of clinically applicable PVT predictive models to guide early interventions and improve the prognosis. Future research should further validate the associations between recently proposed risk factors and PVT-LC, while simultaneously establishing cutoff values for indicators with robust predictive value to construct a clinically applicable PVT prediction framework.

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Case Report Open Access
Chisom Enwere, Vivien Wong, Jonathan Rieber
Published online April 23, 2025
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Journal of Translational Gastroenterology. doi:10.14218/JTG.2024.00046
Abstract
Mucinous cystic neoplasms (MCNs) are rare pancreatic lesions that often go undiagnosed due to their asymptomatic nature. Though typically benign, they can harbor malignant potential, [...] Read more.

Mucinous cystic neoplasms (MCNs) are rare pancreatic lesions that often go undiagnosed due to their asymptomatic nature. Though typically benign, they can harbor malignant potential, making early detection and treatment essential. This case report presents a 32-year-old female with intermittent epigastric pain, who was found to have a cystic lesion in the pancreatic tail, diagnosed as an MCN through endoscopic ultrasound and fine-needle aspiration. The patient underwent a spleen-sparing distal pancreatectomy, which was complicated by a peri-pancreatic abscess that required drainage. This case highlights the importance of distinguishing MCNs from other pancreatic cystic lesions, as misdiagnosis or delayed intervention can lead to adverse outcomes. It underscores the need for vigilant diagnostic imaging and individualized treatment strategies, particularly in young patients, to avoid unnecessary morbidity and ensure optimal outcomes. The report contributes to the growing understanding of MCNs, emphasizing early diagnosis, tailored surgical management, and the significance of postoperative care.

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Review Article Open Access
Nicole M. Anastasio, George Y. Wu
Published online March 14, 2025
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00315
Abstract
Extrahepatic portosystemic shunts (EPS) are abnormal connections between the portal and systemic circulations. Acquired EPS occur most commonly in adults and are usually associated [...] Read more.

Extrahepatic portosystemic shunts (EPS) are abnormal connections between the portal and systemic circulations. Acquired EPS occur most commonly in adults and are usually associated with portal hypertension due to cirrhosis. Acquired EPS cases can be further subdivided into two types: variceal (pre-existing) EPS and non-variceal EPS (NVEPS). Variceal EPS arise from originally small vessels with pre-existing dual portal and systemic drainage. Due to elevated portal pressure, these vessels dilate and undergo a reversal of flow, sending blood back to the systemic circulation. A much less common and, therefore, underappreciated subset of acquired EPS is NVEPS, which consists of aberrant connections that did not previously exist between the portal vein and large systemic vessels, usually in the presence of portal hypertension. Neoangiogenesis results in the development of abnormal anastomoses between the portal vein and other large veins, resulting in splenorenal, gastrorenal, portocaval, and mesocaval shunts. While not uncommon, they are frequently overlooked in the diagnosis and treatment of portal hypertension and can pose significant diagnostic and therapeutic challenges. Because the treatment of variceal EPS and NVEPS can differ markedly, it is important to correctly diagnose NVEPS and institute appropriate management. The aim of this article was to review acquired EPS, with particular attention to NVEPS, updating the pathogenesis, diagnosis, and treatment.

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Original Article Open Access
Xiaobo Cai, Yin Qu, Wen Xie, Yanbin Wang, Mengyu Zhao, Ling Zhang, Ying Luo, Ping Yin, Jun Cheng, Lungen Lu
Published online March 10, 2025
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00472
Abstract
Liver fibrosis is a key process in the progression of chronic liver diseases. However, there are currently no drugs specifically designed to treat liver fibrosis. Our Phase 2 trial [...] Read more.

Liver fibrosis is a key process in the progression of chronic liver diseases. However, there are currently no drugs specifically designed to treat liver fibrosis. Our Phase 2 trial of hydronidone for the treatment of chronic hepatitis B (CHB)-associated liver fibrosis showed that adding hydronidone to entecavir resulted in significant reversal of liver fibrosis. To further evaluate the efficacy of a 270 mg/day dose of hydronidone for treating liver fibrosis associated with CHB, we conducted this Phase 3 trial.

This is a 52-week, randomized (1:1), double-blind, placebo-controlled, multicenter, entecavir-based Phase 3 clinical study conducted at 44 study centers across China. Adult patients aged 18 to 65 years with significant liver fibrosis (defined as an Ishak score ≥ 3 on liver biopsy) associated with CHB were included.

The primary endpoint of the trial is to demonstrate the efficacy of fibrosis reversal, defined as a decrease in the Ishak stage score of liver fibrosis by ≥1 after 52 weeks of treatment, compared to baseline.

The results of this trial are expected to further support the antifibrotic indication for this novel drug.

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Original Article Open Access
Shankar Katekhaye, Bhagyashree Kamble, Ghaida Mustafa, James Fearnley, Anant Paradkar
Published online May 13, 2025
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Future Integrative Medicine. doi:10.14218/FIM.2025.00004
Abstract
Propolis is a resinous material produced by honeybees. Its chemical composition is highly complex and varies significantly depending on geographic region and season. This intrinsic [...] Read more.

Propolis is a resinous material produced by honeybees. Its chemical composition is highly complex and varies significantly depending on geographic region and season. This intrinsic variability presents challenges to the standardization and quality control of propolis. This study aimed to evaluate the chemical composition, total phenolic content, and antioxidant potential of propolis collected from seventeen geographical regions across Africa.

A reverse-phase high-performance liquid chromatography (RP-HPLC) method coupled with a photodiode array detector (PDA) was used for analysis of propolis samples. The flavonoid and phenolic contents of the samples were determined using colorimetric and Folin-Ciocalteu methods. Antioxidant capacity was assessed using the 2,2-diphenyl-1-picrylhydrazyl assay.

Five flavonoids (naringenin, pinocembrin, galangin, chrysin, and quercetin), one flavonoid glycoside (rutin), six phenolic acids (caffeic acid, p-coumaric acid, cinnamic acid, chlorogenic acid, ferulic acid, and gallic acid), and an aromatic ester - caffeic acid phenethyl ester were simultaneously detected and quantified using RP-HPLC with an ACE-5 C18 column (250 mm × 4.6 mm i.d., 5 µm) and PDA detector. The reference standards showed good linearity with regression coefficients (R2) ranging from 0.96 to 0.99. For precision, repeatability, and stability studies, the relative standard deviation for all reference standards was below 2.5%. The 2,2-diphenyl-1-picrylhydrazyl assay yielded EC50 values ranging from 17.6 ± 0.39 to 0.16 ± 0.001 mg/mL.

RP-HPLC method for the simultaneous quantification of thirteen reference standards will serve as a reliable tool for the standardization and quality evaluation of propolis. The flavonoid and phenolic contents are key contributors to the antioxidant activity of propolis and reflect local plant biodiversity and bee–plant interactions within the ecosystem.

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Original Article Open Access
Xiuding Zhang, Haoda Weng, Qinzhi Deng, Min Deng, Xuwei Wu, Zuxiong Huang, Shourong Liu, Rui Wu, Chunlian Ma, Yao Xu, Jianfeng Zhong, Jie Yang, Yinxia Wu, Huajiang Shen, Feng Ding, Fang Wang, Xuezhen Zhai, Chunxian Peng, Haotang Ren, Jie Jin, Xiangfei Xu, Xiaofei Li, Xiaoting Ye, Guoqing Qian, Shuilin Sun, Xuebing Yao, Haifeng Miao, Qianggu Xiao, Shaoheng Ye, Qing Zhang, Xinyi Xu, Xia Yu, Yue Yu, Yan Lan, Huilan Tu, Xianbin Xu, Xinrong Zhang, Rui Huang, Xiaohan Qian, Qiao Yang, Jifang Sheng, Yu Shi
Published online July 3, 2025
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00211
Abstract
Epidemiological data on bacterial infections in cirrhosis in China remain limited. Therefore, we aimed to conduct a multicenter study to investigate the characteristics and outcomes [...] Read more.

Epidemiological data on bacterial infections in cirrhosis in China remain limited. Therefore, we aimed to conduct a multicenter study to investigate the characteristics and outcomes of patients with cirrhosis and bacterial infections in China.

We retrospectively enrolled 1,438 hospitalized adult patients with cirrhosis and bacterial or fungal infections from 24 hospitals across China between January 2018 and September 2024. Data on demographics, clinical features, microbiology, treatment, and outcomes were collected.

A total of 1,783 infection episodes were recorded, including 1,668 first infections and 115 second infections. Most infections were community-acquired (86.6%). Pneumonia was the most common infection type (26.7%), followed by spontaneous bacterial peritonitis (19.5%) and spontaneous bacteremia (14.1%). Among 754 pathogens isolated from 620 patients, Klebsiella pneumoniae (20.1%) was nearly as common as Escherichia coli (21.7%). Multidrug-resistant (MDR) organisms accounted for 41.0% of all isolates, with extended-spectrum β-lactamase-producing Escherichia coli being the most prevalent MDR strain (8.9% of patients). Adherence to empirical antibiotic treatment guidelines from the European Association for the Study of the Liver was significantly lower in this cohort compared to the global study (21.5% vs. 61.2%, P < 0.001), accompanied by a lower clinical resolution rate (63.5% vs. 79.8%, P < 0.001).

The clinical and microbiological characteristics of bacterial infections in patients with cirrhosis in China differ substantially from those reported in other regions. These findings highlight the need for region-specific management and prevention strategies, particularly in light of the changing microbiological landscape, high MDR prevalence, and suboptimal antibiotic practices.

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Original Article Open Access
Silpa Choday, Anne Jarvis, William Graham, Paul Kang, Justin Reynolds
Published online August 1, 2025
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Journal of Translational Gastroenterology. doi:10.14218/JTG.2025.00019
Abstract
While metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with obesity, the cause of its rapidly rising prevalence is not well understood. In this study, [...] Read more.

While metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with obesity, the cause of its rapidly rising prevalence is not well understood. In this study, we aimed to examine the association between arsenic exposure and MASLD in humans.

Urinary inorganic arsenic data from the National Health and Nutrition Examination Survey, 2011–2020, were used. These were combined with death certificate data from the National Death Index of the National Center for Health Statistics to ascertain mortality rates. Weighted linear regression and chi-squared analysis were performed.

The analysis included 6,386 participants after exclusions. The mean urinary arsenic level was 5.92 µg/L in participants with MASLD versus 5.59 µg/L in those without. Alanine aminotransferase levels exhibited a statistically significant increasing trend across both continuous arsenic levels and arsenic quintiles. A statistically significant upward trend was observed for the income-to-poverty ratio and body mass index but not for education status. MASLD prevalence was highest among the white population, while an increasing trend was observed in the Hispanic population over the years (p < 0.001). The proportion of Mexican Americans increased to 12.6% in the MASLD group versus 8.09% in the non-MASLD cohort (p < 0.001). There was a statistically significant increase in the odds of MASLD across arsenic exposure levels, with individuals in the highest quintile having a 32% greater likelihood compared to those in the lowest quintile (p-trend = 0.002). The odds further increased to 55% in the highest quintile (odds ratio 1.55, 95% confidence interval: 1.19–2.03; p-trend < 0.001). MASLD was more prevalent in females than males (57.9% vs. 47.6%; p < 0.001), and the mean age increased from 46.9 years to 49.9 years (p = 0.016).

Our findings reveal a positive association between urinary arsenic exposure and MASLD, with increasing trends particularly observed among Hispanics and those with higher income-to-poverty ratios and body mass index.

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