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2023 Vol. 53, No. 11 Published: 2023-11-25   861 Comprehensive prevention and treatment strategy for patients with gastric cancer complicated with sarcopenia JIANG Zhixuan, SHAO Jiancan, GAO Zekan, ZHI Huaiqing, SHEN Qingzheng, SHEN Xian DOI: 10.3969/j.issn.2095-9400.2023.11.001 Gastric cancer and sarcopenia are both highly age-related diseases. In recent years, with the aging acceleration of the world population, the prevalence of sarcopenia and gastric cancer has continued to rise. Theincidence of sarcopenia in patients with gastric cancer is much higher than that of other malignant tumors due tothe reduction of nutrient intake. Therefore, the phenomenon of gastric cancer patients with sarcopenia has becomemore common. Sarcopenia is considered to be one of the most serious threats to the prevention and treatment ofgastric cancer in that people with sarcopenia tend to have more postoperative complications, higher incidence ofadverse drug reactions and higher risk of adverse outcomes including death. This article makes a comprehensiveanalysis of patients with gastric cancer complicated with sarcopenia from three perspectives: the diagnosis ofsarcopenia, the impact of sarcopenia on the treatment of gastric cancer, and the treatment of patients with gastric cancer complicated with sarcopenia, which may guides clinicians to better prevent and treat gastric cancer. 2023 Vol. 53 (11): 861-867 [Abstract] ( 249 ) HTML (1 KB)  PDF (1257 KB)  ( 735 ) 868 The application of thoracic vertebral cross section skeletal muscle index in the diagnosis and prognosisof sarcopenia in patients with advanced gastric cancer JIANG Zhixuan, LU Yangbin, HUANG Jianqiang, SHAO Jiancan1, GAO Zekan, ZHI Huaiqing, SHEN Qingzheng, SHEN Xian DOI: 10.3969/j.issn.2095-9400.2023.11.002 Objective: To investigate the feasibility of diagnosing sarcopenia with the skeletal muscle index (SMI) of thoracic vertebra section under computed tomography (CT), with a comparison of abdominal CT of third lumbar vertebra cross section (L3) for routine diagnosis of sarcopenia, and to analyze the influence of these indexes on postoperative survival of gastric cancer patients. Methods: A total of 1 096 patients with gastric cancer who underwent radical gastrectomy in the First Affiliated Hospital of Wenzhou Medical University from July 2014 to March 2019 were enrolled. Skeletal muscle areas (SMA) at the twelfth thoracic vertebra (T12) and L3 levels were measured on cross-sectional CT images, and SMI corresponding to the two levels and the skeletal muscle truncation corresponding to the diagnosis of sarcopenia at the T12 level were calculated. The correlation of two levels of CT image parameters and the predictive value of sarcopenia diagnosed at two levels for postoperative survival of gastric cancer were analyzed. Results: The cut-off value of SMI at the T12 level (SMI-T12) for the diagnosis of sarcopenia was 29.2 cm2/m2 in male patients with gastric cancer and 25.3 cm2/m2 in female patients. Thesensitivity, specificity, and area under the curve corresponding to the cut-off value in male patients were 79.3%,77.0% and 0.858, respectively, and for females, it was 71.0%, 61.8% and 0.737 correspondingly. Of all gastric cancer patients, 167 cases (15.2%) were diagnosed with sarcopenia at the T12 level [sarcopenia-T12 (+)] and 154 cases (14.1%) at the L3 level [sarcopenia-L3 (+)], with no statistical significant difference in the detection rate between the two groups of patients (P=0.188). COX regression analysis showed that sarcopenia-T12 (+) was an independent risk factor for overall survival (HR=1.502, 95%CI=1.159-1.948, P=0.002). Multiple linear regression analysis showed that both sarcopenia-T12 (+) and sarcopenia-L3 (+) were significantly associated with prolonged postoperative hospital stay (P=0.002, P=0.020). Conclusion: SMI at the T12 level can be applied to the diagnosis of sarcopenia, which is an independent risk factor for postoperative survival in patients with gastric cancer. 2023 Vol. 53 (11): 868-874 [Abstract] ( 196 ) HTML (1 KB)  PDF (1629 KB)  ( 641 ) 875 Midline 2 expression upregulates in gastric cancer and promotes malignant phenotype of gastric cancer cells CHEN Xietao, HU Xianjing, QIU Tianle, SHEN Xian, XUE Xiangyang DOI: 10.3969/j.issn.2095-9400.2023.11.003 Objective: To analyze the expression level of midline 2 (MID2) in gastric cancer and its effect on the prognosis of gastric cancer patients. To investigate the effect of MID2 expression on the biological phenotype of gastric cancer cells. Methods: A total of 420 tissue samples from the First Affiliated Hospital of Wenzhou Medical University after radical gastrectomy from January 2014 to December 2016 were retrospectively collected. The expression of MID2 in gastric cancer tissues and its effect on the prognosis of gastric cancer patients were evaluated by using gastric cancer tissue samples and TCGA database. Overexpression plasmids and small interfering RNAs (siRNAs) targeting MID2 genes were constructed, and the proliferation ability of gastric cancer cells was evaluated by CCK-8 experiment after transfection of gastric cancer cells while the migration and invasion ability of gastric cancer cells was evaluated by Transwell experiment. Results: The expression level of MID2 was upregulated in gastric cancer tissues (P<0.05). High MID2 expression predicted poorer overall survival (P=0.002), disease free survival (P=0.002) and progression free survival (P=0.003) in gastric cancer patients.Upregulating the expression of MID2 significantly promoted the proliferation, migration and invasion of gastric cancer cells BGC-823 and SGC-7901 (P<0.05). Knockdown MID2 could significantly inhibit the proliferation,migration and invasion of gastric cancer cells MGC-803 (P<0.05). Conclusion: The expression of MID2 in gastriccancer tissues is upregulated. High MID2 expression is associated with a poorer prognosis in patients with gastric cancer. Upregulating the expression of MID2 can significantly promote the malignant phenotype of gastric cancer cells. 2023 Vol. 53 (11): 875-880，888 [Abstract] ( 192 ) HTML (1 KB)  PDF (2139 KB)  ( 666 ) 881 Polo-like kinase 4 inhibitor Centrinone affects the proliferation and apoptosis of gastric cancer cells byregulating PI3K/AKT pathway ZHANG Liang, YANG Jiaqi, ZHANG Teming, HUANG Yingpeng, YOU Tao, NI Zhonglin. DOI: 10.3969/j.issn.2095-9400.2023.11.004 Objective: To investigate the effect of Centrinone on the proliferation, migration and apoptosis of gastric cancer cells and its anti-cancer mechanism. Methods: The expression of polo-like kinase 4 (PLK4) gene in gastric cancer and adjacent tissues and its effect on prognosis were analyzed in the TCGA database. The localization of PLK4 in gastric cancer tissues was analyzed in Human Proteome Atlas. Different gastric cancer cell lines were treated with different concentrations of Centrinone (0, 1, 2, 5 μmol/L), and the cell growth was detected by CCK8 method. Transwell chamber was used to detect the effect of Centrinone on the migration ability of AGS cells. The apoptosis of AGS cells was detected by flow cytometry. The apoptosis-related proteins such as poly ADP-ribose polymerase (PARP), Caspase 3, BCL-2, BAX, were detected by Western blot. Results: The expression of PLK4 in gastric cancer from TCGA database was significantly higher than that in para-cancer tissues (P<0.05), and was correlated with the prognosis of gastric cancer (P=0.001). Centrinone significantly inhibited the growth of AGS, BGC and SGC, and AGS was the most sensitive (IC50=1.386 μmol/L). The migration assay showed the higher the concentration of Centrinone, the less the number of gastric cancer cells migrated (P<0.05).Flow cytometry showed that the higher the concentration of Centrinone, the higher the percentage of apoptosis(P<0.05). Western blot results showed that with the increase of Centrinone concentration, the cleavage expression of apoptosis-related proteins PARP and caspase 3 increased (P<0.05), and the expression of BCL-2 decreased (P<0.05), while the protein expression of BAX did not change significantly (P>0.05). Phosphorylated protein expression levels of PI3K and AKT were significantly decreased (P<0.05). Conclusion: PLK4 inhibitor Centrinone can significantly inhibit the proliferation, migration and induce apoptosis of gastric cancer cells,possibly by inhibiting the expression of BCL-2 and regulating the PI3K/AKT signaling pathway. 2023 Vol. 53 (11): 881-888 [Abstract] ( 245 ) HTML (1 KB)  PDF (2576 KB)  ( 564 ) 889 Methyltransferase-like factor 3 is highly expressed and promotes the malignant phenotype of colon cancer XIANG Yilan, HU Yuanbo, HUANG Tingting, CHEN Xietao, CHEN Chenbin, LU Mingdong DOI: 10.3969/j.issn.2095-9400.2023.11.005 Objective: To evaluate the expression characteristics and clinical prognostic relevance of methyltransferase-like factor 3 (METTL3) in colon cancer patients, and to investigate the effect of METTL3 expression on different biological phenotypes of colon cancer cells. Methods: Comprehensive analysis of the expression differences of METTL3 gene in 1278 colon cancer tissues and 41 adjacent tissues from the TCGA database and 4 different GEO datasets. Kaplan-Meier curve was used to analyze the impact of METTL3 expression on the prognosis of colon cancer patients. A total of 481 colon cancer tissues and 59 paracancerous tissues from patients admitted to the First Affiliated Hospital of Wenzhou Medical University who underwent radical surgery between 2014 and 2018 were collected, retrospectively. Immunohistochemistry was used to determine the expression of METTL3. Small interfering RNA (siRNA) was used to knockdown the expression levels of METTL3in colon cancer cell lines DLD-1 and HCT-116. The biological function of METTL3 in colon cancer cells was evaluated by CCK-8 and Transwell assays. Results: In colon cancer tissue samples from the TCGA database and our cohort, METTL3 had significantly up-regulated expression in colon cancer tissue than that in adjacent tissues (P<0.001). The results of survival analysis showed that higher expression of METTL3 was associated with shorter overall survival (Log-rank P=0.028) and disease-free survival (Log-rank P=0.035) in colon cancer patients.Univariate and multivariate Cox analysis results showed that METTL3 could serve as an independent risk factorfor the prognosis of colon cancer patients (HR=1.335, 95%CI=1.032-1.738, P=0.030). Meanwhile, METTL3 knock-down could significantly inhibit the proliferation (P<0.01), migration, and invasion ability (P<0.01) of colon cancer cells. Conclusion: METTL3 is upregulated in colon cancer tissue and could serve as an independent factor for poor prognosis in colon cancer patients. Knocking down the expression of METTL3 could inhibit the malignant phenotype of colon cancer cells. METTL3 may be involved as a carcinogenic gene in the malignant progression of colon cancer. 2023 Vol. 53 (11): 889-895，904 [Abstract] ( 186 ) HTML (1 KB)  PDF (2813 KB)  ( 546 ) 896 The effect of MAGEA3 gene expression on the immune microenvironment of Asian patients with gastric cancer JIN Jinji, CAI Yiqi, YANG Jiaxin, CHENG Jun, WANG Pengfei DOI: 10.3969/j.issn.2095-9400.2023.11.006 Objective: To reveal the impact of MAGEA3 on the immune microenvironment of Asian gastric cancer patients through bioinformatic analysis of the gastric cancer dataset from The Asian Cancer Research Group (ACRG) for validation with clinical serum samples collected from gastric cancer patients. Methods:Altogether 300 gastric cancer patients in the ACRG GSE52254 dataset were divided as MAGEA3 high expression group and low expression group based on the median expression value. The ESTIMATE and CIBERSORT methods were then used to calculate the immune and stromal components as well as the proportions of 22 infiltrating lymphocyte subsets in both groups. The differences in immune microenvironment and immune cells between the two groups were compared, and further GSEA analysis was conducted to determine the changes in related pathways by MAGEA3. Serum samples of 86 gastric cancer patients admitted to the First Affiliated Hospital of Wenzhou Medical University from January to April 2022 were collected to detect the expression levels of MAGEA3 protein and the correlation between MAGEA3 protein and subpopulations of peripheral blood lymphocytes was verified through ELISA and flow cytometry. Results: The ESTIMATE results showed that theimmune scores and stromal scores of the MAGEA3 high expression group were significantly lower than those of the MAGEA3 low expression group (P<0.001), and Spearman analysis revealed a negative correlation between MAGEA3 expression and immune scores (r=-0.244, P<0.001) and stromal scores (r=-0.266, P<0.001). Further GSEA analysis suggested that there were pathways related to T cell activation, proliferation, macrophage activation, and immune cell regulation enriched in the MAGEA3 low expression group. The CIBERSORT results showed that in the MAGEA3 low expression group, there was more infiltration of naive B cells, plasma cells, CD8+ T cells, γδT cells, and activated NK cells, and less infiltration of macrophages M0. Clinical serum samples showed that MAGEA3 expression had significant negative correlation with CD8+ T cells (r=-0.310, P=0.004),which was consistent with the ACRG data analysis. Conclusion: The expression level of MAGEA3 may affect the immune components of the immune microenvironment of gastric cancer, revealing its potential as a target for immunotherapy and a biological marker 2023 Vol. 53 (11): 896-904 [Abstract] ( 200 ) HTML (1 KB)  PDF (2657 KB)  ( 507 ) 905 Risk factors of postoperative venous thromboembolism in patients with gastrointestinal malignancies LOU Neng, CAI Weilong, YE Guochao DOI: 10.3969/j.issn.2095-9400.2023.11.007 Objective: To investigate the risk factors of venous thromboembolism (VTE) in patients with gastrointestinal malignancies after surgery. Methods: Clinical data of 518 patients who underwent radical surgery for gastric or colorectal cancer in Huzhou Central Hospital between January 2017 and June 2020 were retrospectively collected to understand the characteristics of postoperative VTE in gastrointestinal malignancies.Patients were divided into VTE group (72 patients) and non-VTE group (446 patients) according to whether or not VTE occurred after surgery. Then clinical data were analyzed for postoperative VTE-related factors by univariate analysis, and the independent risk factors for postoperative VTE were explored by multivariate Logistic regression analysis. Results: Of the 518 patients with gastrointestinal malignancies, 72 cases developed postoperative VTE, with an incidence of 13.90%, including 53 cases with deep vein thrombosis (DVT) and 19 cases with pulmonary embolism (PE). Univariate analysis revealed that patients in the VTE group had older age,higher postoperative D-dimer levels, higher incidence of diabetes mellitus and preoperative chemotherapy than patients in the non-VTE group, and their tumor stage was later than that in the non-VTE group. VTE group had lower rate of perioperative mechanical and pharmacologic prophylaxis than non-VTE group, with significant differences (P<0.05). Multivariate analysis showed that aging (≥65 year, OR=1.781, 95%CI=1.009-3.145, P=0.046), late tumor stage (III/IV, OR=1.960, 95%CI=1.135-3.387, P=0.016) and elevated postoperative D-dimer(≥5 mg/mL, OR=2.936, 95%CI=1.542-5.591, P=0.001) were independent risk factors for postoperative VTE in patients with gastrointestinal malignancies. Perioperative mechanical prophylaxis (OR=0.528, 95%CI=0.309-0.792,P=0.018) and pharmacologic prophylaxis (OR=0.652, 95%CI=0.326-0.798, P=0.031) were protective factors for postoperative VTE. Conclusions: Risk factors for postoperative VTE in patients with gastrointestinal malignancies include aging (≥65 year), late tumor stage (III/IV) and postoperative elevated D-dimer (≥5mg/mL). 2023 Vol. 53 (11): 905-910，916 [Abstract] ( 212 ) HTML (1 KB)  PDF (1238 KB)  ( 721 ) 911 Evaluation of endoscopic submucosal dissection in the treatment of early stage colorectal cancer and high-grade intraepithelial neoplasia in the elderly HU Tingting, ZHANG Jie, JIN Yi, WU Wenzhi, SUN Xuecheng, HONG Wandong DOI: 10.3969/j.issn.2095-9400.2023.11.008 Objective: To investigate the safety and efficacy of endoscopic submucosal dissection (ESD) in the treatment of early-stage colorectal cancer and high-grade intraepithelial neoplasia (HGIN) in the elderly. Methods: Clinical data of 157 patients with early-stage colorectal cancer and HGIN who received ESD treatment in the First Affiliated Hospital of Wenzhou Medical University from January 2021 to December 2021 were retrospectively analyzed. According to age, they were divided into the elderly group (≥60 years old, 91 cases) and the young group (18-59 years old, 66 cases). The baseline characteristics, lesion characteristics, success rate of operation, the time of operation and postoperative complications were compared between the two groups. Results: With only one patient who failed in the dissection and was transferred to surgery 156 patients received successful ESD. The maximum diameter of lesions was [2.5(1.7, 3.5)cm] in the elderly group and [2.0(1.5,2.6)cm] in the young group, showing statistical difference (P<0.05). The lesions in the elderly group were more likely to occur in the rectum, with significant difference (P<0.05). The incidence of postoperative complications in the elderly group was higher than that in the young group, and the difference was statistically significant(P<0.05). There was no significant difference between the two groups in the en bloc resection rate, complete resection rate and recurrence rate (P>0.05). Conclusion: ESD is a safe and effective therapy in the treatment of early-stage colorectal cancer and HGIN in elderly patients, who need more care for their larger lesions and higher postoperative complication rate, compared with the young patients. 2023 Vol. 53 (11): 911-916 [Abstract] ( 159 ) HTML (1 KB)  PDF (1274 KB)  ( 689 ) 917 Effect of Hsa-miR-145 targeting replication protein A1 on proliferation of gastric cancer CHEN Jian, LI Liyi, ZHUGE Linmin, MA Xiang’ai, ZHU Yuesheng, YU Yaojun DOI: 10.3969/j.issn.2095-9400.2023.11.009 Objective: To investigate the effect of miRNA targeting replication protein A1(RPA1) gene in gastric cancer cells on tumor malignant biological behavior and its mechanism. Methods: Bioinformatics analysis was used to compare the expression of RPA1 gene in cancer and adjacent tissues and its correlation with the prognosis of gastric cancer patients. RNA pulldown method was used to detect the miRNA targeting the 3’UTR region of RPA1 gene in gastric cancer cells (SGC-7901); SGC-7901 cells with high expression of miR-145 were constructed. Cell proliferation was detected by MTT staining, and cell cycle phase was analyzed by flow cytometry; The targeting relationship between miR-145 and RPA1 was verified by luciferase experiment, which was further confirmed by Western blot. Results: Compared with the adjacent tissues, the expression of RPA1 gene was significantly up-regulated in gastric cancer tissues. The high expression of RPA1 gene in gastric cancer tissues was associated with worse prognosis of patients. RNA pulldown was used to detect miRNA targeting the 3’UTR region of RPA1 gene in gastric cancer cell SGC-7901. The results showed that miR-145 had the highest binding with the 3’UTR region of RPA1 gene. Then, miR-145 was selected for further research. The results of luciferase reporter gene experiment showed that the luciferase activity was lower than that in the control miRNA group (P<0.05); the Western blot results showed that the expression of RPA1 in gastric cancer cells in miR-145group was lower than that in the control miRNA group (P<0.05). MTT results showed that the proliferation ability of gastric cancer cells in miR-145 group was lower than that in control miRNA group (P<0.05); Flow cytometry showed that the G2/M phase arrest of gastric cancer cells in miR-45 group increased (P<0.05). Conclusion: The overexpression of miR-145 can significantly inhibit the proliferation of gastric cancer cell SGC-7901, and its mechanism may be related to down-regulation of RPA1 expression which blocks the cell cycle. 2023 Vol. 53 (11): 917-922 [Abstract] ( 172 ) HTML (1 KB)  PDF (1645 KB)  ( 525 ) 923 VOSviewer-based visualization analysis on research hot topics and frontiers in immunotherapy for gastric cancer CHEN Guijin, LIN Wei, ZHANG Chaohui, ZHU Bichun, ZHAO Lihong DOI: 10.3969/j.issn.2095-9400.2023.11.010 Objective: To analyze the researches on the immunotherapy for gastric cancer and explore the research hot spots and frontiers. Methods: The literature on immunotherapy for gastric cancer published between January 1, 2018 and July 6, 2023 from the science citation index expanded database was searched. Web of Science,InCite, Excel and VOSviewer were used to analyze the countries, institutions, authors and keywords, and knowledge mapping was drawn. Results: A total of 878 articles were included, and the annual publication number showed a general upward trend, with China, Japan and the United States ranking the top three in the number of articles published. The top three institutions in order were the National Cancer Center - Japan, Fudan University,and Seoul National University. The co-occurrence analysis of the core authors showed that Japanese and South Korean researchers had close collaborative relationship in this field, while Chinese researchers had loose collaborative relationship. Frequency analysis and cluster analysis of keywords showed that immune checkpoint blocking was the main immunotherapy for gastric cancer. The hot topics and frontiers were biomarkers or models predicting the prognosis and immunotherapy response in gastric cancer, immune checkpoint inhibitors, especially PD-1 inhibitors, and their combination with chemotherapy/targeted drugs. Conclusion: The immunotherapy for gastric cancer has developed rapidly in the past six years. China is the main research country of the field, and we should continue to focus on the hot topics such as the combined therapy with immunotherapy, the prediction of the efficacy and prognosis of immunotherapy. Meanwhile, China could encourage and strengthen domestic andforeign cooperation to improve the research quality and promote the development in this field. 2023 Vol. 53 (11): 923-929 [Abstract] ( 170 ) HTML (1 KB)  PDF (2165 KB)  ( 585 ) 939 Hyperuricemia and type 2 diabetes mellitus: Studies on recent advances from clinical perspectives to molecular mechanisms ZHANG Haohan, ZHANG Yihan, XU Huanbai DOI: 10.3969/j.issn.2095-9400.2023.11.014 In recent years, the incidence rate of hyperuricemia (HUA) combined with type 2 diabetes(T2DM) has increased year by year. This article reviews the clinical characteristics of HUA combined with T2DM and its possible mechanisms. Clinically, HUA combined with T2DM is more prone to complications such as renal function damage and an increased risk of death; it is more likely to develop in women; perirenal and perirenal fat thickness are both risk factors. Its possible molecular mechanisms include genetic mutation sites,immune inflammation mechanisms, signaling pathways, and others. This study provides a new perspective for the treatment of HUA combined with T2DM by using a new molecular mechanism as entry point. 2023 Vol. 53 (11): 939-942 [Abstract] ( 283 ) HTML (1 KB)  PDF (1233 KB)  ( 824 ) 943 Online construction and evaluation of major courses of preventive medicine program in independent medical colleges YU Qing, LU Lisun, ZHOU Lingling, LIU Huaqing, WU Hongmei, GAO Haitao, WANG Shuran DOI: 10.3969/j.issn.2095-9400.2023.11.015 Objective: To utilize information technology and internet resources to carry out online teaching construction and evaluation of major courses in order to meet the target needs of curriculum in medical education in the new era. Methods: A questionnaire survey was conducted on students who received online teaching of specialized courses during their study in independent medical colleges to investigate their satisfaction and acceptance with online teaching, their effective online learning duration, and approaches to online course engagement. The data obtained were analyzed and compared using corresponding statistical methods. Results: The surveyed students showed good overall satisfaction with online teaching (60.12%). There was a high acceptance of the online teaching model which was based on lectures supplemented by discussion. The factors that affect the effectiveness of online teaching ranked in order as follows: lack of classroom interaction, network facility conditions, and lack of effective communication between teachers and students (P<0.05). There was correlation between E-learning satisfaction and learning ability (P<0.05). Conclusion: It’s suggested that frontier knowledge, new technology and methods derived from course development should be incorporated into the content to update concepts. The teaching form based on the traditional teaching materials and courses should be transformed intoan integrated form with offline and online teaching based on informatization, big data and intelligent media. It’s important to enhance students’ proficiency in self-directed learning, exploratory learning and practical learning by ways to broaden students’ professional vision, create an offline-online integrated learning space, develop in-classand extra-curricular interaction, and establish a “teacher-student” growth community. 2023 Vol. 53 (11): 943-946 [Abstract] ( 148 ) HTML (1 KB)  PDF (1215 KB)  ( 348 )

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