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721
Review Article Open Access
Saurabh Dawra, Manish Manrai
Published online July 12, 2023
Gene Expression. doi:10.14218/GE.2023.00004
Abstract
Alcohol-related liver disease is a major public health problem, with a varying clinical course and often devastating consequences. Its spectrum can vary from alcohol-related fatty [...] Read more.

Alcohol-related liver disease is a major public health problem, with a varying clinical course and often devastating consequences. Its spectrum can vary from alcohol-related fatty liver, alcoholic hepatitis, cirrhosis, and hepatocellular carcinoma. Multiple environmental, genetic, socio-economic and epigenetic factors are intrinsically involved, affecting disease behavior and progression. Recent advances in genome-wide association studies have identified multiple genetic polymorphisms that may affect the pathophysiological process, and in turn, affect disease progression. Although the present understanding of this complex process remains nascent at best, there is an ardent need to incorporate available genetic markers into diagnostic and prognostic algorithms. This may pave the way for future research into targeted therapies.

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722
Review Article Open Access
Marilyn H. Silva
Published online July 12, 2023
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2023.00017
Abstract
Cannabis sativa contains phytocannabinoids that are psychoactive and neurotoxic (delta-9-tetrahydrocannabinol: Δ9THC) or nonpsychoactive and presumptively neuroprotective (cannabidiol: [...] Read more.

Cannabis sativa contains phytocannabinoids that are psychoactive and neurotoxic (delta-9-tetrahydrocannabinol: Δ9THC) or nonpsychoactive and presumptively neuroprotective (cannabidiol: CBD). Along with rising legalization, availability, and demand, the Δ9THC:CBD ratio also has increased. Cannabis legalization means that use will likely increase in pregnant or breastfeeding women, affecting all stages of brain and neurodevelopment of their offspring. Δ9THC exposure in utero or during development leads to lasting detrimental effects on behavior, cognition, locomotor activity, as well as epigenetic changes. Caution is urged with cannabis use. CBD is one of the most actively studied therapies for a broad spectrum of neurological, inflammatory, and mental diseases (e.g., Parkinson’s disease, Huntington’s disease, Alzheimer’s disease, schizophrenia) because of its efficacy, low toxicity, and availability. While data indicate that the benefits of CBD may outweigh its risks, there are indications that it poses a risk for adverse effects on neurodevelopment from in-utero exposure as well as detrimental effects on male reproduction. Therefore, there is a clear need to continue researching the effects of Δ9THC exposure as well as the optimal CBD treatment related to disease management while stressing the need to further characterize possible adverse effects.

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723
Original Article Open Access
Jianshe Yang, Qiang Wang, Siyang Zhou, Fenfen Zhang, Zhongwei Lv
Published online July 7, 2023
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2023.00009
Abstract
Traditional Chinese medicine (TCM) prescriptions are complex compositions according to certain compatibility rules to treat different diseases. Therefore, understanding the superposition, [...] Read more.

Traditional Chinese medicine (TCM) prescriptions are complex compositions according to certain compatibility rules to treat different diseases. Therefore, understanding the superposition, inhibition, and interaction between the effective components is essential. This study aimed to use modern information technology and the established TCM databases to analyze and explore the effectiveness of TCM compositions in terms of prescription and regulation.

We adopted data mining technology to analyze the composition rules and active components among the spleen and stomach prescriptions that mainly includes the core algorithms of the apriori method and the frequent pattern (FP)-growth method.

In the present work, a new algorithm was developed that uses the modified FP-tree and the head table structure, producing only the FP-tree once and the head table structure at each recursion.

The new algorithm can be used to obtain the same results as the original algorithm of frequent item set mining, but it is at least two times faster than the FP-growth method. Thereafter, it can be used to screen and preprocess other agent data as well as to create a database by using the improved algorithm, thus establishing a simulation system for effective component and computer-composing principles of TCM that is characterized by frequent item sets, association rules, and the clustering analysis algorithm and consequently undergoes analysis for the frequency of medicinal herbal ingredients, frequency of symptoms with certain compounds, medicine-sickness connection, and pharmaceutical composition clustering to determine the related effective ingredients to treat disorders of the spleen and stomach.

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724
Original Article Open Access
Caiyun Zheng, Shunmin Huang, Meimei Lin, Baohui Hong, Hengfen Dai, Jing Yang
Published online July 7, 2023
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2023.00124
Abstract
Immune-mediated liver injury is a fatal side effect of sintilimab. This study aimed to shed light on the associated risk factors and characteristics of this adverse event. The [...] Read more.

Immune-mediated liver injury is a fatal side effect of sintilimab. This study aimed to shed light on the associated risk factors and characteristics of this adverse event.

The clinical records of 772 patients treated with sintilimab were retrospectively reviewed to investigate risk factors associated with sintilimab immune-related hepatotoxicity, as well as its incidence and outcome. The Roussel Uclaf Causality Assessment Method was used to identify cases of sintilimab-induced hepatotoxicity. Furthermore, logistic regressions were performed to compare the clinical and bloodwork characteristics of patients with and without immune-mediated liver injury caused by checkpoint inhibitors.

Of the 585 patients included in the study, 71 (12.1%) developed liver injury during sintilimab use. The median RUCAM score with interquartile range was 7 (6, 8). Hypoproteinemia, dyslipidemia, and the presence of thyroid peroxidase antibodies were risk factors for sintilimab-related hepatotoxicity. A nomogram model was constructed for sintilimab-induced immune-mediated liver injury based on these risk factors, which had a C-index value of 0.713 and a good calibration curve. When applied to patients with grade ≥3 and ≥4 sintilimab-induced immune-mediated liver injury, it achieved C-index values of 0.752 and 0.811, respectively. The nomogram model also showed a good prediction potential in patients ≥65 years and males. Six of the patients with sintilimab-related hepatotoxicity showed improved liver function upon treatment with steroids.

This study demonstrated that hypoproteinemia, dyslipidemia, and the presence of thyroid peroxidase antibodies were clinically feasible prognostic biomarkers to predict liver injury in patients treated with sintilimab.

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725
Original Article Open Access
Bin-Yan Zhong, Jian-Qiang Jiang, Jun-Hui Sun, Jin-Tao Huang, Wei-Dong Wang, Qi Wang, Wen-Bin Ding, Xiao-Li Zhu, Cai-Fang Ni
Published online July 7, 2023
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2023.00099
Abstract
To validate prognostic performance of the China liver cancer (CNLC) staging system as well as to compare these parameters with those of the Barcelona Clinic Liver Cancer (BCLC) [...] Read more.

To validate prognostic performance of the China liver cancer (CNLC) staging system as well as to compare these parameters with those of the Barcelona Clinic Liver Cancer (BCLC) staging system for Chinese hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE).

This multicenter retrospective study included 1,124 patients with HCC between January 2012 and December 2020 from six Chinese hospitals. Based on overall survival (OS), the prognostic performance outcomes for the CNLC and BCLC staging systems were compared by model discrimination [C statistic and Akaike information criterion (AIC)], monotonicity of the gradient (linear trend chi-square test), homogeneity (likelihood ratio chi-square test), and calibration (calibration plots). A prospective cohort of 44 patients receiving TACE-based therapy included between January 2021 and December 2022 was used to prospectively validate the outcomes.

Median OS was 19.1 (18.2–20.0) months, with significant differences in OS between stages defined by the CNLC and BCLC observed (p<0.001). The CNLC performed better than the BCLC regarding model discrimination (C-index: 0.661 vs. 0.644; AIC: 10,583.28 vs. 10,583.72), model monotonicity of the gradient (linear trend chi-square test: 66.107 vs. 57.418; p<0.001), model homogeneity (159.2 vs. 158.7; p<0.001). Both staging systems had good model calibration. Similar results were observed in the prospective cohort.

Combining model discrimination, gradient monotonicity, homogeneity, and calibration, the CNLC performed better than the BCLC for Chinese HCC patients receiving TACE.

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726
Case Report Open Access
Jose Miguel Ingelmo Calvo, José Ruiz Cobo, Mohamed Farouk Allam
Published online July 4, 2023
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2023.00015
Abstract
Topical corticosteroids, alone or in combination with calcipotriol, a topical vitamin D analog, have proved effective in treating mild to moderate psoriasis. Topical corticosteroids, [...] Read more.

Topical corticosteroids, alone or in combination with calcipotriol, a topical vitamin D analog, have proved effective in treating mild to moderate psoriasis. Topical corticosteroids, like clobetasol propionate, have a vasoconstrictor effect on the peripheral dermal vessels, and this explains skin atrophy in psoriatic patients applying topical corticosteroids regularly for long periods. However, a new topical treatment for psoriasis has been developed and patented. The new treatment is prepared as a lotion and is composed of clobetasol, papaverine hydrochloride, spironolactone, milk-peptide-complex, and propylene glycol. A 47-year-old male presented with extensive psoriasis lesions in the elbows and back. The patient had an irrelevant past medical history and was complaining mainly of severe itching in the psoriatic lesions. The patient was advised to use our newly patented lotion once daily for one week. After 7 days of local application of the new lotion, the patient was examined in the outpatient clinic. The patient reported significant improvement in the itching sensations and remission of the scaled lesions. Comparing the lesions before and after the application of the local treatment for 7 days, it was observed that the psoriasis area severity index score had improved from 20.9 to 1.8. Further studies with larger sample sizes and longer follow-up periods are required to confirm the findings of our case report.

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727
Review Article Open Access
Anil K. Philip
Published online July 4, 2023
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2023.00034
Abstract
Dry eye disease (DED) is a prevalent ocular condition affecting a significant proportion of the global population. Characterized by disruption of tear film homeostasis, DED results [...] Read more.

Dry eye disease (DED) is a prevalent ocular condition affecting a significant proportion of the global population. Characterized by disruption of tear film homeostasis, DED results in dryness, discomfort, impaired visual clarity, and potential corneal damage. Despite its severe consequences, consistently effective treatments for DED remain elusive, leaving the majority of patients with persistent symptoms. This review aims to examine recent advancements in DED therapy, emphasizing the role of nanotechnology-based delivery systems in the development of novel treatments. By harnessing the potential of cutting-edge nanotechnology, we aspire to unveil innovative therapeutic strategies that address the unmet needs of patients with DED. Furthermore, we will discuss the current challenges, limitations, and future associated with these novel nanotechnology-based therapies for managing DED.

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728
Original Article Open Access
Quentin Binet, Audrey Loumaye, Michel P Hermans, Nicolas Lanthier
Published online June 30, 2023
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2023.00117
Abstract
Most data on liver assessment in type 2 diabetes mellitus (T2DM) patients are from retrospective cohorts with selection bias. We aimed at appraising the feasibility, results, and [...] Read more.

Most data on liver assessment in type 2 diabetes mellitus (T2DM) patients are from retrospective cohorts with selection bias. We aimed at appraising the feasibility, results, and benefits of an outpatient systematic noninvasive screening for metabolic dysfunction-associated fatty liver disease (MAFLD) severity and determinants in T2DM patients.

We conducted a 50-week cross-sectional study enrolling adult T2DM outpatients from a diabetes clinic. An algorithm based on guidelines was applied using simple bioclinical scores and, if applicable, ultrasound and/or elastometry.

Two hundred and thirteen patients were included. Mean age and body mass index were 62 years and 31 kg/m2 and 29% of patients had abnormal transaminase levels. The acceptance rate of additional liver examinations was 92%. The prevalence of MAFLD, advanced fibrosis and cirrhosis was 87%, 11%, and 4%, respectively. More than half of the cases of advanced fibrosis had not been suspected and were detected by this screening. MAFLD was associated with poor glycemic control, elevated transaminases, low HDL-C and the absence of peripheral arterial disease. Advanced fibrosis was linked to high waist circumference and excessive alcohol consumption, which should be interpreted with caution owing to the small number of patients reporting excessive consumption.

Simple bioclinical tools allowed routine triage of T2DM patients for MAFLD severity, with high adherence of high-risk patients to subsequent noninvasive exams.

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729
Review Article Open Access
Tomas Koltai, Larry Fliegel
Published online June 28, 2023
Gene Expression. doi:10.14218/GE.2023.00014
Abstract
Rapidly proliferating cancer cells exhibit a high energy demand. However, their utilization of the glycolytic pathway is inefficient, leading to a compensatory effect wherein cancer [...] Read more.

Rapidly proliferating cancer cells exhibit a high energy demand. However, their utilization of the glycolytic pathway is inefficient, leading to a compensatory effect wherein cancer cells consume ten to twenty times more glucose than normal cells. In cases where glucose availability is limited due to a poorly perfused hypoxic microenvironment, cancer cells resort to alternative energy sources, including fructose. Certain tumors have been found to rely heavily on fructose, and fructose utilization contributes to pro-tumoral signaling and increased cancer risk. Over the past 70 years, dietary fructose intake has steadily increased, resulting in a rise in obesity and metabolic syndrome, both of which elevate cancer risk. In this paper, we present compelling evidence that highlights the role of fructose and the glucose transporter GLUT5 in promoting specific types of tumors. We summarize the existing evidence and pathways through which fructose contributes to cancer metabolism, particularly in cases where glucose availability is restricted. Furthermore, we propose a hypothesis that elucidates the regulation of the lipogenic phenotype by dietary fructose intake and cellular energy status. It is important to note that the effects of fructose are context-dependent, with its tumor-promoting effects varying based on the energy status of the cell. We comprehensively analyze why targeting fructose uptake and fructolysis should be important for the management of some tumors and cancer prevention.

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730
Opinion Open Access
731
Review Article Open Access
Liang Lu, Haodong Xu
Published online June 27, 2023
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2023.00008
Abstract
The World Health Organization (WHO) recently published new guidelines for the diagnosis and classification of lung and pleural tumors. This review provides a concise overview of [...] Read more.

The World Health Organization (WHO) recently published new guidelines for the diagnosis and classification of lung and pleural tumors. This review provides a concise overview of the key updates, including discussions of histologic features and recommended terminology for small diagnostic lung samples, the revised grading system for lung adenocarcinoma with inclusion of complex glandular and filigree micropapillary patterns, and molecular features of large cell neuroendocrine carcinoma. Additionally, rare neoplasms such as bronchiolar adenoma/ciliated muconodular papillary tumor, SMARCA4-deficient undifferentiated thoracic tumor, and primary pulmonary hyalinizing clear cell carcinoma are described in terms of their diagnostic approaches and molecular features. This review also includes discussion of the diagnostic algorithm for malignant epithelioid mesothelioma.

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732
Review Article Open Access
Fei Chen, Xiaoqi Lin
Published online June 26, 2023
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2022.00035
Abstract
The Paris System for Reporting Urinary Cytology (TPS 1.0, published in 2016) is the first standardized, evidence-based reporting system established as an international reporting [...] Read more.

The Paris System for Reporting Urinary Cytology (TPS 1.0, published in 2016) is the first standardized, evidence-based reporting system established as an international reporting system for urine specimens after the International Congress of Cytology in Paris. Its primary purpose is to reduce the rate of unnecessary indeterminate diagnoses but maintain the excellent performance of urine cytology, in detecting high-grade urothelial carcinoma. The reporting system comprises six diagnostic categories, as well as each category’s diagnostic criteria, estimated risk of malignancy, and management recommendations. After six years, TPS 2.0 was applied in 2022 upon the unfolding of new data. TPS 2.0 clarifies the diagnosis categories and updates the risk of malignancy in each category and developments of molecular tests. This review provides an updated summary of TPS 2.0. Some diagnostic pitfalls and molecular tests were also discussed.

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733
Review Article Open Access
Cong He, Yan Luo, Xin-Long Wang, Can Zhang, Bei Sun
Published online June 25, 2023
Cancer Screening and Prevention. doi:10.14218/CSP.2023.00015
Abstract
Pancreatic cancer remains the most malignant type of cancer. Although immunotherapy has shown good efficacy in most solid tumors, it has a poor response in pancreatic cancer. The [...] Read more.

Pancreatic cancer remains the most malignant type of cancer. Although immunotherapy has shown good efficacy in most solid tumors, it has a poor response in pancreatic cancer. The difficulty in applying immunotherapy to pancreatic cancer lies in the fact that it is an immunologically “cold” tumor. The dense and poorly vascularized microenvironment of pancreatic cancer is not conducive to the infiltration of immune cells, making it difficult to trigger an immune response. Immunogenic cell death is a specific type of cell death that can initiate an adaptive immune response and turn a “cold” tumor into a “hot” one. In this review, we discuss the basis of immunogenic cell death and its inducers in pancreatic ductal adenocarcinoma. The key point is that the manipulation of adjuvant immunogenic cell death inducers can usually synergize with other immunotherapies. This synergetic effect allows for the combination therapy to fully utilize the immune potential of each component, overcome the immune-suppressed microenvironment of pancreatic cancer, and ultimately activate immune responses that result in tumor regression. Clinical trials of therapy based on this strategy may offer hope to patients with pancreatic cancer.

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734
Original Article Open Access
Minoo Roostaie, Ali Esmaily, Hamid Taghvaei Javanshir, Maryam Arabi, Ali Tafti, Ahmad Bereimipour, Habibollah Mahmoodzadeh, Farimah Hadjilooei, Melikasadat Hosseininejad
Published online June 25, 2023
Cancer Screening and Prevention. doi:10.14218/CSP.2023.00016
Abstract
Ovarian cancer (OvCa) is the most deadly gynecological cancer. This study aimed to determine which genes and miRNAs play an important role in OvCa. We accessed the Gene Expression [...] Read more.

Ovarian cancer (OvCa) is the most deadly gynecological cancer. This study aimed to determine which genes and miRNAs play an important role in OvCa.

We accessed the Gene Expression Omnibus database and downloaded the mRNA microarray dataset. Through the use of GEO2R, we were able to collect data on differentially expressed genes (DEGs) and microRNAs (DEMs). By querying the Enrichr database, we were able to conduct functional and pathway enrichment analysis on DEGs. STRING was used to create a network of protein–protein interactions, and Cytoscape was used to display the networks. Gene Expression Profiling Interactive Analysis and The Cancer Genome Atlas were then used to conduct overall survival and clinical data analyses of hub genes. DEM target predictions were also made using miRnet. For extracellular vesicles confirmation, Exocarta and Vesiclepedia were used.

There were a total of 1,778 DEGs found, and most of them were enriched for terms associated with the cell cycle, mitosis, and the ovulation cycle. There were 141 nodes used in the creation of the protein–protein interaction network. There were 10 genes with a lot of connections between them. Patients with OvCa had a shorter overall survival if they had high expression of four of the 10 genes tested: ATF3, ZEB1, CSF1R, and HSPA8. We found out that the protein–protein interaction network has a significant module. The cell cycle, extracellular matrix receptor, and cell invasion were among the enriched functions and pathways. In addition, we found a total of 20 DEMs. The hsa-let-7 family (hsa-let-15a-3p, hsa-let-18a-5p, and hsa-let-615-5p) may target ZEB1 because its expression is inversely correlated with that of ZEB1.

This study uncovered critical genes that represent promising therapeutic targets in the fight against OvCa.

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735
Original Article Open Access
Chengcheng Guo, Zirong Liu, Hongsheng Liu
Published online June 25, 2023
Future Integrative Medicine. doi:10.14218/FIM.2023.00001
Abstract
Hepatic ischemia-reperfusion injury (HIRI) is a key factor leading to complications and poor prognosis after hepatobiliary surgery, but its pathogenesis remains unclear. Hence, [...] Read more.

Hepatic ischemia-reperfusion injury (HIRI) is a key factor leading to complications and poor prognosis after hepatobiliary surgery, but its pathogenesis remains unclear. Hence, it is a very necessary discovery the prevention and treatment methods and pathological mechanism of HIRI.

Our animal experiments indicated that two doses of dogwood alcohol extract (DAX) at 5 g/kg and 2.5 g/kg (crude drug/mouse body mass) could significantly reduce serum alamine aminotransferase (AST) and aspartate aminotransferase (ALT) in HIRI mice. The level of these two transaminases determined the pharmacodynamic effect of DAX on HIRI. Next, we used the results of network pharmacology and transcriptome sequencing to obtain important prevention and cure target genes, and applied molecular docking to simulate receptor and ligand binding. Finally, immunohistochemical method was made use of verifying the results.

When the model group vs control group, administration group vs model group, set padj < 0.05, | log2FoldChange | >1.0 filter condition, the intersection between the obtained transcriptome sequencing data set and the network pharmacological target was only heparin-binding epidermal growth factor (HBEGF). Then DockThor online software was applied to make loganin and ursolic acid, small molecular compounds contained in DAX, form complexes with HBEGF active sites through hydrogen bonding to interfere with HIRI. Meanwhile, immunohistochemical test results showed that HBEGF expression decreased in the administration group compared with the model group (*P < 0.05).

DAX interferes with the occurrence and development of HIRI by down-regulating HBEGF. Our experimental results not only highlight the advantages of traditional Chinese medicine in treating difficult diseases, but also provide a reference for clinical exploration of new methods to prevent and treat HIRI.

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736
Systematic Review Open Access
Yingling Chen, Mark C. Hou, Yafen Hsu
Published online June 25, 2023
Future Integrative Medicine. doi:10.14218/FIM.2023.00002
Abstract
Angelica sinensis (Dang gui) has been widely used in traditional Chinese medicine (TCM) clinics and diet therapy for thousands of years. According to TCM theory, A. sinensis can [...] Read more.

Angelica sinensis (Dang gui) has been widely used in traditional Chinese medicine (TCM) clinics and diet therapy for thousands of years. According to TCM theory, A. sinensis can be used for the treatment of breast cancer. As A. sinensis has effects on estrogen, it may have an adverse effect on the prognosis of breast cancer. This article systematically reviews the literature to explore whether breast cancer patients need to avoid taking A. sinensis.

Using the search terms “breast cancer AND Dong-quai”, “breast cancer AND Angelica sinensis”, “breast cancer AND Dang gui” and “breast cancer AND Dang qui”, relevant studies were retrieved from the PubMed database up to December 31, 2022. After excluding irrelevant and repeated studies, the papers were critically reviewed by TCM physicians, and the papers were secondly screened by the impact factor and ranking of the published journals. The included papers were classified into three groups, reporting a “positive”, “negative” or “inconclusive” effect in patients with breast cancer.

A total of 22 articles were identified, which included 9, 5 and 7 positive negative and inconclusive studies, respectively. The results showed that studies advocating that A. sinensis may be safely consumed by patients with breast cancer had a higher evidence hierarchy than those that did not support consumption.

The findings implied that A. sinensis can be prescribed to patients with breast cancer in appropriate doses under TCM treatment theory.

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737
Original Article Open Access
Weichen Si
Published online June 25, 2023
Future Integrative Medicine. doi:10.14218/FIM.2022.00058
Abstract
To explore the main action targets and key pathways, along with their mechanisms of action, of Panax ginseng’s special ingredients in the treatment of ulcerative colitis using network [...] Read more.

To explore the main action targets and key pathways, along with their mechanisms of action, of Panax ginseng’s special ingredients in the treatment of ulcerative colitis using network pharmacology methods. To provide a theoretical basis for subsequent laboratory experiments and clinical trials.

The main active ingredients of Panax notoginseng were obtained through the TCMSP database and the specific ingredients were screened. The targets of Panax notoginseng-specific components were obtained from the Swiss Target Prediction database. The GeneCards, OMIM, and DisGent databases were used to obtain the targets related to ulcerative colitis. The protein interaction network (PPI) of intersecting targets was constructed using the STRING database. GO function and KEGG pathway enrichment analysis were performed in R language software. Construction of the herb-component-target-disease-KEGG pathway network was achieved using Cytoscape software.

Seven major active ingredients of Panax notoginseng were obtained, and ginsenoside f2 was found to be a special ingredient, corresponding to 16 potential targets. A search of the disease database yielded 5,536 targets for ulcerative colitis. Eight core targets were obtained by protein interaction analysis of the intersecting targets: STAT3, VEGFA, HSP90AA1, FGF2, IL2, MET, BCL2L1, and RORC, respectively. 417 entries were obtained by GO functional enrichment analysis, and 22 statistically significant pathways were obtained by KEGG enrichment analysis.

The mechanism of action of ginsenoside f2 in the treatment of ulcerative colitis features multi-target and multi-pathway interactions. The receptors may be related to STAT3, VEGFA, HSP90AA1, FGF2, IL2, MET, and other targets, and the main signaling pathways may be related to the PI3K-Akt signaling pathway, Th17 cell differentiation, and inflammatory bowel disease among others and this provides a theoretical basis for the next in-depth experimental study.

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738
Original Article Open Access
Jia-Wei Zhou, Zhen Li, Rui Ji, Pei-Zhu Wang, Ai-Jun Zhang, Kang-Kang Wu, Cheng-Xia Liu, Qiong Niu, Yan-Liu Chu, Xiu-Feng Su, Xiu-Li Zuo, Yan-Qing Li
Published online June 25, 2023
Cancer Screening and Prevention. doi:10.14218/CSP.2023.00012
Abstract
Studies on the effect of sedated endoscopy on adenoma detection rate (ADR) and advanced adenoma detection rate (AADR) remain scarce. The present study aims to determine whether [...] Read more.

Studies on the effect of sedated endoscopy on adenoma detection rate (ADR) and advanced adenoma detection rate (AADR) remain scarce. The present study aims to determine whether sedation can help improve ADR and AADR.

Colonoscopies conducted in four endoscopy centers from January 2012 to July 2019 were included to create a propensity score-matched cohort, and compare the endoscopic factors.

The colonoscopies of 216,400 cases were included. The ADR (32.24% vs. 31.63%, p < 0.05), AADR (5.59% vs. 5.39%, p < 0.05), and polyp (20.61% vs. 20.21%, p < 0.05) increased in the sedated endoscopy group, especially for flat adenomas (44.80% vs. 43.95%, p < 0.05) and adenomas of 0–5 mm (66.99% vs. 66.24%, p < 0.05). However, there was no significant difference, in terms of lesion site. Furthermore, the number of biopsies per colonoscopy was significantly higher in the sedated group (0.79 ± 0.93 vs. 0.56 ± 0.80, p < 0.001). Moreover, there was a significant increase in electronic (0.92% vs. 0.83%, p < 0.05) and chemical staining (0.57% vs. 0.45%, p < 0.001) in the sedated group.

The ADR, AADR and polyp detection rate increased for sedated colonoscopy, especially for flat adenomas and adenomas of 0–5 mm. In addition, the frequency of staining, image enhancement techniques, and number of biopsies per colonoscopy increased in sedated colonoscopy.

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739
Original Article Open Access
Guo-Xiu Ma, Yuan-Chen Wang, Yan Liu, Xiao-Tong Mao, Sheng-Han Mao, Si-Huai Xiong, Zhao-Shen Li, Li Hou, Wen-Bin Zou
Published online June 25, 2023
Cancer Screening and Prevention. doi:10.14218/CSP.2023.00022
Abstract
Pancreatic cancer (PC) is a highly malignant tumor of the digestive system with a poor prognosis. The early diagnosis and accurate screening of PC in high-risk populations are warranted [...] Read more.

Pancreatic cancer (PC) is a highly malignant tumor of the digestive system with a poor prognosis. The early diagnosis and accurate screening of PC in high-risk populations are warranted to improve the prognosis of patients. The present study aimed to evaluate the global research characteristics, hotspots, and future trends of the early screening of PC.

A comprehensive search of studies on early screening of PC in the Web of Science core database was performed between 1 January 2003 and 28 December 2022. The information, which included the study population, authorship, journal, contributing institution, country of origin, and keywords, were collected. The Excel, VOSviewer, and Citespace software were used for the bibliometric analytical processing and visualization.

A total of 581 publications were included and analyzed after the screening. For the past 20 years, the annual number of publications exhibited a fluctuating rising trend. The United States contributed more than 40% of the publications. Ralph H. Hruban was the most cited scholar. Pancreas (n = 35), World Journal of Gastroenterology (n = 24), and Pancreatology (n = 18) were the top three journals with the highest number of publications. Keywords related to liquid biopsies, such as “extracellular vesicle”, “dna”, and “circulating tumor cell”, continued to burst until 2022.

Over the past two decades, this area has been gradually gaining attention, with the number of publications rising annually. Liquid biopsy will be the future research trend. These present findings will provide the latest insight into the state of PC early screening, identifying new perspectives for further research.

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740
Review Article Open Access
Xiao-Hu Lin, Wen-Kai Zhou, Cheng-Zhong Lin, Wei Cao
Published online June 20, 2023
Cancer Screening and Prevention. doi:10.14218/CSP.2023.00006
Abstract
The transcriptional inhibitor histone methyltransferase enhancer of zeste homolog 2 (EZH2) predominantly targets genes involved in tumor suppression. EZH2 is highly expressed in [...] Read more.

The transcriptional inhibitor histone methyltransferase enhancer of zeste homolog 2 (EZH2) predominantly targets genes involved in tumor suppression. EZH2 is highly expressed in a variety of human malignancies and promotes carcinogenesis and malignant transformation. Recent research has indicated that altering the tumor microenvironment by focusing on epigenetic variables can improve antitumor immunity. Recent research has also revealed that EZH2 has pleiotropic functions in immune and malignant cells. EZH2 inhibition could be a promising strategy to improve the outcomes of current immunotherapies. Based on the role of EZH2 in the immunomodulation of both immune and tumor cells, we evaluated the effect of EZH2 on tumor immunity in this review. We also highlight improvements in combined EZH2-targeted treatment and immunotherapy.

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