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Illuminating and Instructive Clinical Case Open Access
Kai Liu, Ziyue Huang, Lijin Zhao, Haitao Zhao
Published online January 2, 2025
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00404
Abstract
Cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/2B) deletions are frequently identified in patients with biliary tract cancer; however, standard treatment options for this genetic [...] Read more.

Cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/2B) deletions are frequently identified in patients with biliary tract cancer; however, standard treatment options for this genetic alteration are lacking. Here, we present the case of a 64-year-old woman diagnosed with intrahepatic cholangiocarcinoma and hilar lymph node metastasis who underwent radical surgery. Postoperative pathology confirmed moderately differentiated adenocarcinoma. The tumor recurred during the second cycle of adjuvant chemotherapy following surgery, and the metastatic sites included the cranial region, right lung, and right adrenal gland. Genetic analysis revealed a CDKN2A/2B deletion, indicating palbociclib sensitivity. Subsequently, the patient received palbociclib plus lenvatinib as systemic therapy, along with stereotactic radiotherapy for the intracranial lesion. Notably, the right pulmonary metastasis significantly regressed after 12 months of treatment, with the complete disappearance of the intracranial tumor. However, the disease progressed at 32.2 months, with significant enlargement of the right adrenal gland metastasis and new metastasis in the right lung. The progression-free survival and overall survival were 32.2 months and 34.4 months, respectively. In conclusion, our case demonstrates that palbociclib plus lenvatinib is a promising chemotherapy-free second-line treatment for intrahepatic cholangiocarcinoma with a CDKN2A/2B deletion.

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Letter to the Editor Open Access
Sanjoy Majumder, Rutupurna Das, Annapurna Sahoo, Kunja Bihari Satapathy, Gagan Kumar Panigrahi
Published online November 11, 2024
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Gene Expression. doi:10.14218/GE.2024.00058
Original Article Open Access
Ming Ruan, Jingjing Zhang, Wei Zhang, Changsheng Sheng, Rongsheng Wang, Jingyan Tian, Weirong Zhu, Huailin Gao
Published online June 25, 2024
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Future Integrative Medicine. doi:10.14218/FIM.2023.00106
Abstract
Patients with corona virus disease 2019 (COVID-19) face not only physical strains but also significant psychological stress, highlighting the importance of addressing their mental [...] Read more.

Patients with corona virus disease 2019 (COVID-19) face not only physical strains but also significant psychological stress, highlighting the importance of addressing their mental health concerns. This study aimed to evaluate the impact of Lianhua Qingwen on the psychological well-being of asymptomatic and mildly symptomatic COVID-19 patients, providing empirical evidence to guide clinical practices.

Conducted in eight shelter hospitals in Shanghai, the study employed a cluster randomization method to allocate patients equally into either the Lianhua Qingwen group or the control group. The Lianhua Qingwen group received oral doses of four capsules or one packet of granules three times daily for 14 days. In contrast, the control group received standardized treatment according to the diagnostic and treatment plan, excluding Lianhua Qingwen. Mental health was assessed using the Self-rating Depression Scale and Self-rating Anxiety Scale, with symptom reporting on the 7th and 14th days, accompanied by nucleic acid test result screenshots. A follow-up investigation on new disease occurrence was conducted six months post-discharge.

Among the 2,652 valid questionnaire respondents, the Lianhua Qingwen group accounted for 1,665 cases, characterized by a higher proportion of females (32.7% vs. 26.9%), younger age (44.8 vs. 46.2 years), lower percentages of asymptomatic infections (27.6% vs. 38.5%), higher baseline Patient Health Questionnaire-9 scores (2.7 vs. 1.9), and higher Generalized Anxiety Disorder 7 scores (1.9 vs. 1.4). Further multivariate logistic regression analysis explored factors influencing the alleviation of depressive and anxiety symptoms during follow-up, revealing that Lianhua Qingwen use was an independent factor in reducing anxiety (odds ratio = 1.37, 95% confidence interval 1.14–1.65, p = 0.001) and depression (odds ratio = 1.42, 95% confidence interval 1.19–1.69, p < 0.0001). Lianhua Qingwen increased the likelihood of reducing anxiety by 37% and depression by 42%.

Lianhua Qingwen significantly alleviated anxiety and depression symptoms in COVID-19 patients, suggesting its potential therapeutic efficacy in mitigating these conditions.

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Original Article Open Access
Alshymaa A. Hassnine, Yasser Fouad, Zienab M. Saad, Alaa M. Mostafa, Hend M. Moness, Nehal I. Abbas, Nasr M. Osman, Wafaa Abdelghany
Published online May 29, 2024
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Gene Expression. doi:10.14218/GE.2023.00047
Abstract
Metabolic-associated fatty liver disease (MAFLD) may increase the risk of cardiovascular events. In this study, we assessed the predictive value of pentraxin 3 (PTX3) for severe [...] Read more.

Metabolic-associated fatty liver disease (MAFLD) may increase the risk of cardiovascular events. In this study, we assessed the predictive value of pentraxin 3 (PTX3) for severe fibrosis and carotid intima-media thickness (CIMT) in patients with MAFLD.

188 patients (114 with MAFLD, 74 with dual etiology MAFLD and chronic hepatitis C) were included. All participants underwent clinical history and examination, metabolic parameter assessment, serum level evaluation of PTX3, Fibrosis-4 index and nafld fibrosis score scores, abdominal ultrasound, and CIMT assessment.

The serum PTX3 was significantly elevated in patients with advanced fibrosis compared to those with mild/moderate fibrosis (1.8 vs 1.4, p = 0.006). The PTX3 level was independently associated with advanced fibrosis (odds ratio = 1.26, 95% confidence interval 1.008–1.040). In MAFLD patients, the PTX3 levels in patients with low fibrosis compared to those with advanced fibrosis were 1.4 (1–2.1) and 1.9 (1.3–3.8), respectively (p = 0.027). A significantly greater CIMT was noted in patients with elevated PTX3 levels (3.85 (3.42–4) vs 4.05 (3.7–4.67), p = 0.0001) compared to those with low PTX3 levels.

Serum PTX3 levels can accurately predict advanced fibrosis and CIMT in MAFLD patients. Thus, it could be useful for management and risk stratification.

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Letter to the Editor Open Access
David Yardeni, Asif Hitawala, Lilian Howard, Theo Heller, Meryl Waldman
Published online July 19, 2024
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00169
Case Series Open Access
Kenji Miki, Masayoshi Yamanishi, Satoko Mibayashi, Shinsaku Imashuku
Published online May 14, 2024
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Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2023.00064
Abstract
Disseminated carcinomatosis of bone marrow (DCBM) occurs mostly in stomach cancer patients; however, characterizing tumor cells morphologically and phenotypically in the bone marrow [...] Read more.

Disseminated carcinomatosis of bone marrow (DCBM) occurs mostly in stomach cancer patients; however, characterizing tumor cells morphologically and phenotypically in the bone marrow is not an easy task. In addition, among patients with DCBM, an unknown primary site (CUPS) is rarely noted despite standard clinical evaluation, imaging studies, and endoscopic findings. This study aimed to clarify the diagnosis/outcome of DCBM in elderly patients we have treated.

Here, we report eight DCBM cases. Once tumor clumps were noted in the bone marrow, we performed serum tumor markers, immunostaining of tumor cells in the bone marrow clot, or biopsy preparations. In addition, imaging studies (CT/MRI/ FDG PET-CT) were performed.

Of eight cases, two were diagnosed with DCBM/CUPS. Among the eight cases, six fatal cases had a median survival time of 2 months (ranging from <0.5 to 8 months) from DCBM detection to death or the time of this writing, while the CUPS cases were still alive at 2+ and 3+ months, respectively. The outcomes of DCBM and DCBM/CUPS, particularly in elderly patients, were dismal, and comprehensive genomic profiling could not be perform in these cases.

The use of conventional morphological/phenotypical characteristics to improve the prognosis of DCBM patients is limited. Consequently, the application of comprehensive genomic profiling is recommended to enhance diagnostic and therapeutic approaches.

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Original Article Open Access
Jeremiah Onubi, Oluwagbenga Adebayo Adeola, Patricia Eseigbe, Adesegun Elisha, Grace O Sheyin, Anyuku A George Chima
Published online September 6, 2024
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Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2024.00018
Abstract
Depression can lead to poor outcomes during antiretroviral therapy, and current evidence suggests high rates of depression among people living with human immunodeficiency virus [...] Read more.

Depression can lead to poor outcomes during antiretroviral therapy, and current evidence suggests high rates of depression among people living with human immunodeficiency virus (PLHIV), especially in low-and middle-income countries. This study was designed to investigate the sociodemographic factors associated with depression among PLHIV on antiretroviral therapy in a Nigerian cosmopolitan city.

A hospital-based, cross-sectional study was conducted among 592 consenting, randomly selected adult PLHIV receiving treatment at a university teaching hospital in Jos, Nigeria, in 2022, using the PHQ-9 questionnaire and an interviewer-administered sociodemographic questionnaire. Associated variables in univariate analysis were used in multivariable binary logistic regression to obtain adjusted odds ratios (AOR) with a significance level set at α = 0.05.

Depression was found to be highly prevalent among study participants, with 44.9% of them affected. Findings revealed that being male [AOR = 0.62; 95% confidence interval (CI): 0.42–0.92], being employed (AOR = 0.55; 95%CI: 0.31–0.97), and earning a monthly income of ₦50,000–100,000 ($65–130) (AOR = 0.49; 95% CI: 0.27–0.91) and >₦100,000–200,000(>$130–260) (AOR = 0.33; 95% CI: 0.13–0.77) were significantly associated with reduced odds of depression.

The significant association of being male, having formal employment, and earning a moderate monthly income with reduced odds of depression may have implications for policy and strategies for managing mental health issues among PLHIV in cosmopolitan areas like Jos, which face peculiar challenges such as cultural tensions, traffic congestion, and gentrification. PLHIV categories with a relatively higher likelihood of depression may benefit from targeted mental health support systems, in addition to other mental health management strategies generally available to PLHIV.

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Review Article Open Access
Willy Sandhika, Lina Patricia Gutjahr, Lusiani Tjandra
Published online June 25, 2024
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Cancer Screening and Prevention. doi:10.14218/CSP.2024.00013
Abstract
Molecular analysis of breast cancer tissue has revealed that breast cancer is not a uniform disease. Each breast cancer patient has several molecular signatures that differ from [...] Read more.

Molecular analysis of breast cancer tissue has revealed that breast cancer is not a uniform disease. Each breast cancer patient has several molecular signatures that differ from those of others. Therefore, breast cancer therapy should be personalized, depending on its molecular signatures. Breast cancer with hormonal receptors can be treated with a selective estrogen receptor modulator or selective estrogen receptor degrader therapy, while breast cancer with overexpression of human epidermal growth factor receptor 2 (HER2)-neu gene responds excellently to anti-HER2-neu therapy. For patients with advanced breast cancer that already has distant metastasis and a poor prognosis, a new agent has been discovered. The phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) inhibitor has been proven effective in treating advanced breast cancer with a PIK3CA gene mutation. This therapy can be administered to HER2-negative breast cancer patients and in combination with selective estrogen receptor degrader therapy for post-menopausal patients with positive hormonal receptors. Although this treatment is effective, it cannot be given to every advanced breast cancer patient. Before administering the treatment, a PIK3CA mutation test is compulsory. PIK3CA mutation detection in breast cancer can predict the cancer’s response to the PIK3CA inhibitor, providing information on which patients will benefit from the treatment.

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Original Article Open Access
Arshad A. Pandith, Usma Manzoor, Ina Amin, Shayaq Ul Abeer Rasool, Zahoor A. Wani, Iqbal Qasim, Saima Wani, Iqra Anwar, Shayesta Rah, Masarat Rashid, Adil Lateef, Aabida Ahmad
Published online June 12, 2024
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Gene Expression. doi:10.14218/GE.2023.00144
Abstract
HLA-G gene harbors certain polymorphic variations that can potentially impact its biological activity, and therefore, may confer a risk for recurrent pregnancy loss (RPL). This [...] Read more.

HLA-G gene harbors certain polymorphic variations that can potentially impact its biological activity, and therefore, may confer a risk for recurrent pregnancy loss (RPL). This study aimed to analyze whether HLA-G polymorphic variations (G*0103, G*0104, and G0105N) are related to the risk of RPL in women from Kashmir, North India.

A total of 200 women who suffered ≥2 RPLs and 240 healthy controls were recruited from the same geographical region. Additionally, 100 spouses of RPL affected women and 60 products of conception were evaluated. HLA-G genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method.

The variant genotype 0103:0103 in exon 2 of HLA-G was not detected. The genotype 0104/0105 was detected in 100% of RPL patients, spouses, and controls. Exon 2 and variant genotypes G*0103 in exon 2 and G*0105 in exon 3 of HLA-G were absent in our population and thus did not contribute to the etiopathogenesis of RPL. In contrast, the exon 3 HLA-G variant G*0104N was significantly more frequent in RPL patients and their spouses compared to the control group (p<0.05). The presence of the HLA-G variant genotype G*0104N (exon 3) was detected in 13% of RPL patients and 7% of their male partners, indicating a significantly higher frequency than in controls and suggesting a substantial risk for RPL (p<0.05).

This study revealed that the higher frequency of the HLA-G*0104 allele in both partners strongly predicted a substantial risk for RPL in our population.

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Original Article Open Access
Juan Deng, Kai Ding, Shuqing Liu, Fei Chen, Ru Huang, Bonan Xu, Xin Zhang, Weifen Xie
Published online December 20, 2024
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00197
Abstract
The transcription factor sex-determining region Y-related high-mobility group-box gene 9 (SOX9) plays a critical role in organ development. Although SOX9 has been implicated in [...] Read more.

The transcription factor sex-determining region Y-related high-mobility group-box gene 9 (SOX9) plays a critical role in organ development. Although SOX9 has been implicated in regulating lipid metabolism in vitro, its specific role in metabolic dysfunction-associated steatohepatitis (MASH) remains poorly understood. This study aimed to investigate the role of SOX9 in MASH pathogenesis and explored the underlying mechanisms.

MASH models were established using mice fed either a methionine- and choline-deficient (MCD) diet or a high-fat, high-fructose diet. To evaluate the effects of SOX9, hepatocyte-specific SOX9 deletion or overexpression was performed. Lipidomic analyses were conducted to assess how SOX9 influences hepatic lipid metabolism. RNA sequencing was employed to identify pathways modulated by SOX9 during MASH progression. To elucidate the mechanism further, HepG2 cells were treated with an adenosine monophosphate-activated protein kinase (AMPK) inhibitor to test whether SOX9 acts via AMPK activation.

SOX9 expression was significantly elevated in hepatocytes of MASH mice. Hepatocyte-specific SOX9 deletion exacerbated MCD-induced MASH, whereas overexpression of SOX9 mitigated high-fat, high-fructose-induced MASH. Lipidomic and RNA sequencing analyses revealed that SOX9 suppresses the expression of genes associated with lipid metabolism, inflammation, and fibrosis in MCD-fed mice. Furthermore, SOX9 deletion inhibited AMPK pathway activation, while SOX9 overexpression enhanced it. Notably, administration of an AMPK inhibitor negated the protective effects of SOX9 overexpression, leading to increased lipid accumulation in HepG2 cells.

Our findings demonstrate that SOX9 overexpression alleviates hepatic lipid accumulation in MASH by activating the AMPK pathway. These results highlight SOX9 as a promising therapeutic target for treating MASH.

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