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Review Article Open Access
The World Health Organization System for Reporting Pancreaticobiliary Cytopathology: Standardized Categories and Practical Approaches to Pancreatic Lesions
Minhua Wang, Maria D. Lozano, Guoping Cai
Published online September 25, 2024
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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Illuminating and Instructive Clinical Case Open Access
Virological Response to Lamivudine and Tenofovir Treatment in a Mono-infected Chronic Hepatitis B Patient with Potential Tenofovir Resistance: A Case Report
Monica Dahiya, Teresa Tai, Trana Hussaini, Gordon Ritchie, Nancy Matic, Eric M. Yoshida, Christopher F. Lowe
Published online December 12, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00248
Abstract
Few cases of tenofovir resistance have been reported, and the appropriate treatment for such cases remains unclear. We aimed to share a case of a chronic hepatitis B mono-infected [...] Read more.

Few cases of tenofovir resistance have been reported, and the appropriate treatment for such cases remains unclear. We aimed to share a case of a chronic hepatitis B mono-infected patient with potential tenofovir resistance who required combined lamivudine and tenofovir therapy to achieve adequate viral suppression. The patient’s viral load (plasma) was monitored using the cobas® hepatitis B virus Test on the cobas® 6800 system. Hepatitis B antiviral drug resistance (AVDR) mutations were assessed by amplicon-based sequencing. Plasma was extracted using the MagNa Pure 24 system, and polymerase chain reaction targeting the polymerase gene (860bp) was performed. Sequencing was conducted on GridION R10.4.1 flow cells, and the resulting FASTQ files were analyzed using DeepChek®-HBV Software. We describe a female patient in her 60s with chronic hepatitis B who was e-antigen positive. She met treatment criteria in May 2020, when her alanine transaminase levels were 1.5 times above the upper limit of normal. She was initially started on entecavir but had to switch to tenofovir alafenamide in June 2020 due to a rash. Despite three years of tenofovir therapy, her viral load remained unsuppressed. AVDR testing identified two suspected tenofovir resistance mutations (V191I and A317S). Since no mutations associated with lamivudine resistance were detected, the patient was treated with a combination of lamivudine and tenofovir, achieving viral suppression after four months. Although rare, tenofovir resistance should be considered in patients with persistent viremia despite long-term therapy. AVDR sequencing facilitated the detection of potential tenofovir resistance and guided treatment decisions, leading to successful viral suppression in this case.

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Original Article Open Access
Isolation and Screening of Endophytes from Sarcandra glabra to Increase the Content of Isofraxidin
Yuxin Chen, Tianqing Huang, Fei Li, Ehu Liu
Published online August 23, 2024
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2024.00012
Abstract
Isofraxidin, an important coumarin compound found in the medicinal plant Sarcandra glabra, is reported to have anti-inflammatory activity. However, its natural concentration is [...] Read more.

Isofraxidin, an important coumarin compound found in the medicinal plant Sarcandra glabra, is reported to have anti-inflammatory activity. However, its natural concentration is insufficient to meet the existing demand for this valuable molecule. Therefore, biotechnological approaches are necessary to enhance the isofraxidin content.

Endophytes were isolated from the roots, stems, and leaves of Sarcandra glabra and fermented with Sarcandra glabra, respectively. The target strains capable of increasing isofraxidin content were screened using high-performance liquid chromatography. Their genes were amplified, and the polymerase chain reaction products were sequenced. BLAST analysis was used to compare the sequences with those in GenBank, and a phylogenetic tree was constructed for species identification.

Fifteen endophytic bacteria and six endophytic fungi were isolated from the roots, stems, and leaves of Sarcandra glabra. Among them, Enterobacter, Bacillus wiedmannii, Trametes versicolor from the roots, and Diaporthe celeris and Diaporthe hongkongensis from the leaves increased the isofraxidin content in Sarcandra glabra. The isofraxidin content in Sarcandra glabra fermented by endophytes Enterobacter, Bacillus wiedmannii, Trametes versicolor, Diaporthe celeris, and Diaporthe hongkongensis was 1.37, 1.27, 1.11, 1.40, and 1.16 times higher than in the blank samples, respectively.

The fermentation of Sarcandra glabra with specific endophytes can increase its isofraxidin content. These findings provide preliminary scientific evidence for the potential of using microorganisms to enhance the quality of traditional Chinese medicine.

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Illuminating and Instructive Clinical Case Open Access
Significant Response to Palbociclib Plus Lenvatinib as Second-line Treatment for CDKN2A/2B Deletion Intrahepatic Cholangiocarcinoma: A Case Report
Kai Liu, Ziyue Huang, Lijin Zhao, Haitao Zhao
Published online January 2, 2025
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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Hypothesis Open Access
Expansion of Intact Sensory-motor Territories in Proximal Neuraxial Lesions using Peripheral Nerve-muscle Weeding Interventions
Subramanya Adiga
Published online May 29, 2024
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2023.00020
Abstract
Following complete peripheral nerve injury, collateral sprouting (CS) by adjacent nerves causes concentric shrinkage of the insensate area. Such take-over of insensate territory [...] Read more.

Following complete peripheral nerve injury, collateral sprouting (CS) by adjacent nerves causes concentric shrinkage of the insensate area. Such take-over of insensate territory is unknown in proximal lesions such as stroke, spinal cord injury, and cauda equina syndrome, as peripheral nerves supplying insensate territories still maintain continuity from the cell body in the dorsal root ganglion (DRG) to the skin innervation territory. This preserved distal continuity opposes territory take-over by the expansion of adjacent sensate territories; sectioning peripheral nerves in insensate territories distal to DRGs disconnects nerve cell bodies from their skin territory, thus facilitating sensate territory expansion of adjacent nerves. Similar motor system applications in paralyzed territories include lower motor neurone lesioning and fasciectomies, facilitating motor territory expansion of adjacent nerves through CS. A search for evidence of previous conception of these hypotheses was conducted in the literature, using a combination of relevant terms from three categories (proximal neuraxial lesions, nerve-muscle interventions, collateral sprouting); however, this yielded no pertinent results, suggesting that these concepts are novel. Observations from the literature on peripheral nerve injury indicate a sound scientific basis for these hypotheses. Therefore, the suggested “weeding” interventions are likely to succeed in minimizing neurological deficits and improving patients’ quality of life. Various interventions to expand sensory/motor territories are considered; these include nerve lesioning distal to DRGs and removing fascial barriers between innervated and paralyzed muscles. Experience from such interventions will help expand our understanding of the speed and extent of CS-mediated neurological recovery as well as brain’s plastic abilities in reorienting after such procedures.

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Review Article Open Access
Feasibility and Advantages of Designing Proteolysis Targeting Chimeras Targeting Peroxisome Proliferator-activated Receptors for Cancer Treatment
Sihan Zhang, Zhipeng Yao, Na Zeng, Zheng Liu, Qidong Xia, Shaogang Wang
Published online July 25, 2024
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2023.00022
Abstract
Peroxisome proliferator-activated receptors (PPARs) participate in the fatty acid oxidation, the homeostasis of lipid and glucose metabolism, the regulation of insulin sensitivity, [...] Read more.

Peroxisome proliferator-activated receptors (PPARs) participate in the fatty acid oxidation, the homeostasis of lipid and glucose metabolism, the regulation of insulin sensitivity, and numerous metabolic processes, making them novel and important therapeutic targets for cancer treatment. However, PPARs manifest dual functions, wherein their activation and inhibition engender diverse outcomes in different types of tumors. The specificity of drugs for tumors is also a challenge when targeting PPARs. In recent years, proteolysis targeting chimeras (PROTACs) have gained significant attention in the field of cancer therapy, demonstrating potent therapeutic potential in both basic and clinical research. Furthermore, heterobifunctional molecules derived from PROTACs have ventured into domains that extend beyond protein degradation. Currently, there are no developed PPAR-targeting PROTACs. Therefore, our review delves into various aspects, including the dual roles of PPARs, known inhibitors, agonists, ligands, and co-crystal structures, and explores the feasibility and advantages of PPAR-targeting PROTACs and other heterobifunctional molecules in cancer therapy.

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Review Article Open Access
Current Status and Future Perspectives on Early Detection and Diagnosis of Colorectal Cancer in China
Zhongxue Han, Qingzhou Kong, Yanqing Li
Published online December 23, 2024
Cancer Screening and Prevention. doi:10.14218/CSP.2024.00023
Abstract
Colorectal cancer (CRC) is the second most commonly diagnosed cancer in China. Early detection and diagnosis of CRC are essential for improving survival rates. However, socioeconomic [...] Read more.

Colorectal cancer (CRC) is the second most commonly diagnosed cancer in China. Early detection and diagnosis of CRC are essential for improving survival rates. However, socioeconomic factors such as regional disparities, economic conditions, and varying levels of awareness impact the uptake of screening programs. Recently, rapid advancements in non-invasive tests, including high-quality fecal immunochemical tests and the emergence of stool and blood biomarkers for CRC, have facilitated improvements in early detection and diagnosis. Additionally, image-enhanced endoscopy, a group of advanced imaging technologies, has been developed to assist in the early identification of colorectal lesions, including narrow band imaging and linked-color imaging. The emergence of artificial intelligence also offers promising opportunities to improve early diagnosis and treatment of CRC. This review mainly introduces screening technologies and the current status of CRC screening in China, provides an overview of CRC early detection and diagnosis, and discusses the limitations and future prospects.

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Original Article Open Access
Effect of Lianhua Qingwen on Depression and Anxiety in COVID-19 Patients with Asymptomatic or Mild Symptoms
Ming Ruan, Jingjing Zhang, Wei Zhang, Changsheng Sheng, Rongsheng Wang, Jingyan Tian, Weirong Zhu, Huailin Gao
Published online June 25, 2024
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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Commentary Open Access
Original Article Open Access
Molecular Profiling Using Next-generation Sequencing of Sufficient Endobronchial Ultrasound-guided Transbronchial Needle Aspiration and Liquid Biopsy Samples in Patients with Advanced Lung Cancer
Kayla Brice, Candice Arline, Luis E. Raez, Katerine Dumais, Mark Block
Published online September 25, 2024
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2024.00021
Abstract
Tumor molecular analysis using next-generation sequencing (NGS) is the standard of care for guiding lung cancer treatment. Endobronchial ultrasound-guided transbronchial needle [...] Read more.

Tumor molecular analysis using next-generation sequencing (NGS) is the standard of care for guiding lung cancer treatment. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive technique used to sample mediastinal lymph nodes for diagnosing and staging lung cancer. This study aimed to determine if EBUS-TBNA provided adequate tissue samples for NGS.

We evaluated EBUS-TBNA samples from adult advanced non-small cell lung cancer patients who had both EBUS-TBNA and liquid biopsy samples analyzed by NGS between July 1, 2015 and June 30, 2021. Additionally, we compared the results with those from liquid biopsies performed on these patients.

Among the 44 evaluated patients, 43% were male, with a median age of 66 years at diagnosis. Seventy-five percent were smokers, 79.5% were White, 6.8% were Black, and 9.1% were Asian. EBUS-TBNA samples were sufficient for NGS in 95.5% of cases. The median turnaround time for EBUS-TBNA NGS was 38.5 days compared with eight days for NGS in liquid biopsies. Actionable genetic aberrations were detected in 71% of patients.

Our findings demonstrated that EBUS-TBNA provided sufficient tissue for identifying actionable genetic aberrations in patients with advanced non-small cell lung cancer.

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