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Table of Content

    08 February 2022, Volume 49 Issue 2 Previous Issue    Next Issue
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    Original Articles
    Effects of exogenous AGR2 on the proliferation and invasion abilities of colon cancer cells
    Laibijiang Wusiman, Cao Bowei, Zhang Wenbin, Gao Hua
    2022, 49 (2):  73-78.  doi: 10.3760/cma.j.cn371439-20210526-00011
    Abstract ( 194 )   HTML ( 186 )   PDF (21097KB) ( 104 )   Save

    Objective To detect the expressions of anterior gradient protein 2 (AGR2) in the cultures of three colon cancer cell lines SW480, SW620 and COLO205, and to investigate the effects of different concentrations of exogenous AGR2 on the proliferation, migration and invasion abilities of SW620 cells. Methods Western blotting was used to detect the expression levels of AGR2 protein in SW480, SW620 and COLO205 colon cancer cell cultures. SW620 cells were divided into blank control group, anterior gradient protein 2 homologous human recombinant protein (rAGR2) low concentration group (100 μg/ml) and rAGR2 high concentration group (200 μg/ml), and CCK-8 assay, cell scratch assay and Transwell migration and invasion assay were used to detect the effects of different concentrations of rAGR2 on the biological behaviors of SW620 cells. Results Western blotting results showed that the expression levels of AGR2 protein in SW480, SW620 and COLO205 cells were 0.545±0.097, 0.662±0.040 and 0.882±0.156 respectively, with a statistically significant difference (F=7.46, P=0.024). The level of AGR2 protein in COLO205 cell line was significantly higher than that in SW480 and SW620 cell lines (P=0.009; P=0.047). The results of CCK-8 experiment showed that the proliferative activities of SW620 cells in the blank control group, rAGR2 low concentration group and rAGR2 high concentration group were 0.422±0.031, 0.542±0.040 and 0.574±0.033 respectively, with a statistically significant difference (F=26.35, P<0.001), and the rAGR2 low concentration group and rAGR2 high concentration group were significantly higher than the blank control group (both P<0.001). The results of cell scratching assay showed that the percentage of 36 h cell scratching area was (28.029±2.107)%, (20.642±0.983)% and (16.951±1.608)% for the three groups of cells respectively, with a statistically significant difference (F=35.85, P<0.001), the rAGR2 low concentration group was higher than the blank control group (P=0.001), and the rAGR2 high concentration group was higher than the rAGR2 low concentration group (P=0.032). The results of cell migration assay showed that the number of cells migrated in the three groups was 447.1±32.3, 513.1±55.8 and 632.4±50.3 respectively, with a statistically significant difference (F=35.62, P<0.001), the rAGR2 low concentration group was more than the blank control group (P=0.007), and the rAGR2 high concentration group was more than the rAGR2 low concentration group (P<0.001). The results of the invasion assay showed that the number of cells invaded in the three groups was 369.1±56.1, 505.1±34.4 and 579.0±71.5 respectively, with a statistically significant difference (F=32.40, P<0.001), the rAGR2 low concentration group was more than the blank control group (P<0.001), and the rAGR2 high concentration group was more than the rAGR2 low concentration group (P=0.010). Conclusion The expression of AGR2 protein varies in the extracellular fluid of different invasive colon cancer cells and increases with the invasive ability. AGR2 protein can increase the proliferation, migration and invasive abilities of colon cancer cells SW620.

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    Analysis of risk factors and prediction model establishment for early postoperative recurrence in glioma patients
    Zhu Yishuo, Cui Yujie, Liu Qi, Li Jun, Fan Yuechao
    2022, 49 (2):  79-83.  doi: 10.3760/cma.j.cn371439-20210121-00012
    Abstract ( 267 )   HTML ( 191 )   PDF (3402KB) ( 93 )   Save

    Objective To investigate the related factors of early postoperative recurrence of glioma patients and to establish a prediction model for early recurrence. Methods A total of 94 patients with pathologically diagnosed glioma treated at Affiliated Hospital of Xuzhou Medical University from August 2014 to July 2016 were retrospectively analyzed. Kaplan-Meier method was used for survival analysis and log-rank test was carried out. Cox proportional risk regression model was used to analyze the clinical factors influencing early postoperative recurrence of glioma patients, and the prediction model of early recurrence was established. Results The recurrence rates were 26.6% (25/94) and 39.4% (37/94) at 12 months and 24 months after operation, respectively. Univariate analysis showed that age (χ2=9.59, P=0.008), degree of tumor resection (χ 2=14.26, P<0.001), Karnofsky performance status (KPS) score (χ 2=19.41, P<0.001), radiochemotherapy (χ 2=5.10, P=0.024) and pathological grade (χ 2=5.83, P=0.016) were significantly associated with early postoperative recurrence in glioma patients. Multivariate Cox proportional hazards regression model analysis showed that pathological grade (OR=2.64, 95%CI: 1.75-3.97, P<0.001), degree of resection (OR=0.34, 95%CI: 0.19-0.62, P<0.001) and radiochemotherapy (OR=2.58, 95%CI: 1.34-4.99, P=0.005) were independent factors influencing early postoperative recurrence in glioma patients. The risk function model expression of early recurrence in glioma patients was h(t)=h0exp(0.970X1-1.081X2+0.949X3). X1, X2 and X3 represented pathological grade, resection degree and radiochemotherapy respectively. Conclusion High grade pathology and the absence of radiochemotherapy are independent predictors of early recurrence in glioma patients, and complete tumor resection can reduce the risk of early recurrence and improve the prognosis. The model of early recurrence prediction can provide some reference for clinical diagnosis and treatment.

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    Effects of TPF regimen and IMRT on immune function and survival prognosis of patients with advanced esophageal cancer
    Geng Hui, Hu Fengchao, Lu Hongchao, Guo Jungang, Qi Zengping
    2022, 49 (2):  84-88.  doi: 10.3760/cma.j.cn371439-20210420-00013
    Abstract ( 193 )   HTML ( 21 )   PDF (3459KB) ( 101 )   Save

    Objective To study the effects of docetaxel, cisplatin and fluorouracil (TPF) regimen simultaneous intensity modulated radiotherapy (IMRT) on immune function and survival prognosis of patients with advanced esophageal cancer. Methods A total of 93 patients with advanced esophageal cancer were screened in Hebei Veterans General Hospital from June 2015 to December 2017, and were divided into two groups using randomized envelope method. The observation group (47 cases) was given synchronous TPF regimen and IMRT, and the control group (46 cases) was given synchronous PF regimen (cisplatin combined with fluorouracil) and IMRT. Esophageal barium meal, chest and upper abdominal CT were reviewed within 1 month after treatment to assess the short-term efficacy and compare the immune function of the two groups before and after treatment. Kaplan-Meier survival curve was plotted to evaluate the long-term efficacy based on overall survival (OS). The incidence of adverse reactions in the two groups was collected to evaluate their safety. Results After treatment, the T cell subgroup CD8+ level of the observation group was higher than that of the control group [(33.55±4.46)% vs. (29.06±3.61)%, P<0.05], while CD3+[(51.29±5.22)% vs. (56.04±6.10)%, P<0.05], CD4+ [(28.27±3.63)% vs. (30.35±3.52)%, P<0.05] and CD4+/CD8+ (0.84±0.25 vs. 1.04±0.08, P<0.05) levels were lower than those of the control group. The effective rate of recent treatment in the observation group was 82.98% (39/47), while the effective rate in the control group was only 63.04% (29/46), with a statistically significant difference (χ2=4.70, P=0.030). The median OS of the observation group was 25.3 months (95%CI: 17.9-26.1), and that of the control group was 18.2 months (95%CI: 14.4-25.5), with a statistically significant difference (χ 2=3.28, P=0.038). Adverse reactions during the follow-up period of the two groups of patients were mainly nausea/vomiting, fatigue, anorexia, hematological toxicity, esophagitis and pneumonia, etc., which were mostly grade 1-2, and disappeared after symptomatic treatment or termination of treatment. Compared with the control group, the incidence of nausea/vomiting (46.81% vs. 78.26%, χ 2=9.80, P=0.002), anorexia (44.86% vs. 71.74%, χ 2=6.99, P=0.008), leukopenia (36.96% vs. 73.91%, χ 2=13.37, P<0.001) and esophagitis (61.70% vs. 82.61%, χ 2=5.05, P=0.025) adverse reactions was lower in the observation group. Conclusion TPF combined with IMRT has high efficacy and low adverse reactions, which can be used as an effective treatment to improve the survival prognosis of patients with advanced esophageal cancer.

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    Influence of preoperative Naples prognostic score on prognosis of patients with thoracic esophageal squamous cell carcinoma
    Guo Xinwei, Zhang Han, Ye Hongxun, Liu Yangchen, Ji Shengjun, Zhou Shaobing, Zhou Juying
    2022, 49 (2):  89-94.  doi: 10.3760/cma.j.cn371439-20210526-00014
    Abstract ( 263 )   HTML ( 25 )   PDF (3649KB) ( 88 )   Save

    Objective To explore the impact of preoperative Naples prognostic score (NPS) on the survival prognosis of patients with thoracic esophageal squamous cell carcinoma (ESCC). Methods From December 2014 to December 2020, a total of 134 patients who underwent radical esophagectomy in Department of Thoracic Surgery, Affiliated Taixing People's Hospital of Yangzhou University were retrospectively analyzed. The NPS was calculated by the median values of preoperative serum albumin, total cholesterol, neutrophil to lymphocyte ratio (NLR) and lymphocyte to monocyte ratio (LMR), and then the enrolled patients were divided into NPS 0 group (20 cases), NPS 1 or 2 group (62 cases) and NPS 3 or 4 group (52 cases). Kaplan-Meier method was used to calculate survival rate and survival comparison was performed by log-rank test. The univa-riate and multivariate Cox models were used to analyze the relationship between NPS and survival prognosis. Results The 1-, 3- and 5-year progression free survival (PFS) rates were 95.0%, 70.0% and 60.0% in the NPS 0 group, 66.1%, 24.2% and 24.2% in the NPS 1 or 2 group, and 48.1%, 3.8% and 1.9% in the NPS 3 or 4 group respectively, with a statistically significant difference (χ2=31.27, P<0.001). In the NPS 0 group, the 1-, 3- and 5-year overall survival (OS) rates were 100.0%, 80.0% and 70.0% respectively. In the NPS 1 or 2 group, the 1-, 3- and 5-year OS rates were 96.8%, 36.7% and 32.3% respectively, while in the NPS 3 or 4 group, the 1-, 3- and 5-year OS rates were 90.4%, 32.7% and 5.8% respectively, and there was a statistically significant difference (χ 2=29.70, P<0.001). Univariate analysis found that sex, T stage, N stage, TNM stage and NPS were closely related to PFS and OS of patients with thoracic ESCC (all P<0.05). Furthermore, multivariate Cox regression analysis showed that T stage (HR=1.46, 95%CI: 1.07-2.00, P=0.019), N stage (HR=1.34, 95%CI: 1.02-1.76, P=0.037) and NPS (set NPS 0 group as the subvariable, NPS 1 or 2 group: HR=3.35, 95%CI: 1.58-7.11, P=0.002; NPS 3 or 4 group: HR=6.15, 95%CI: 2.89-13.11, P=0.001) were independent prognostic factors for PFS. Additionally, T stage (HR=1.67, 95%CI: 1.01-2.77, P=0.046), N stage (HR=1.44, 95%CI: 1.00-2.20, P=0.048) and NPS (set NPS 0 group as the subvariable, NPS 1 or 2 group: HR=3.10, 95%CI: 1.31-7.32, P=0.010; NPS 3 or 4 group: HR=5.09, 95%CI: 2.14-12.11, P=0.001) were independent prognostic factors for OS. Conclusion Preoperative NPS plays an important role in predicting the survival prognosis of patients with thoracic ESCC.

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    Application of 192Ir brachytherapy combined with external beam radiation and biliary stent in the treatment of unresectable hilar cholangiocarcinoma
    Yang Wenbo, Xiao Li, Bi Jianqiang, Sun Yunchuan
    2022, 49 (2):  95-99.  doi: 10.3760/cma.j.cn371439-20201125-00015
    Abstract ( 216 )   HTML ( 14 )   PDF (6843KB) ( 56 )   Save

    Objective To evaluate the efficacy and safety of 192Ir brachytherapy combined with external beam radiation for the treatment of unresectable hilar cholangiocarcinoma. Methods The clinical data of 26 patients with unresectable hilar cholangiocarcinoma admitted to Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine from February 2016 to July 2018 were retrospectively analyzed. All patients received 192Ir brachytherapy combined with external beam radiation. First, percutaneous hepatobiliary stent implantation was given, followed by external beam radiotherapy (radiotherapy dose 45 Gy, 25 times), and then 192Ir brachytherapy (radiotherapy dose 20 Gy, 4 times), a total of 4 to 6 cycles of chemotherapy. The short-term and long-term efficacy were evaluated, and the Karnofsky performance status (KPS) score, CA19-9, total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST) level changes and percutaneous transhepatic biliary drainage (PTCD) tube indwelling time were analyzed. Adverse reactions were recorded according to the Radiation Therapy Oncology Group (RTOG) injury classification standard. Results Three months after the end of treatment, 4 cases (15.4%) were completely remitted, 20 cases (76.9%) were partially remitted, 2 cases (7.7%) were stable, and there was no disease progression. The objective remission rate was 92.3% (24/26). The 1-year and 2-year local control rates were 75.0% and 62.5% respectively, and the 1-year and 2-year overall survival rates were 57.7% and 26.9% respectively. The KPS score was 70.39±10.76 one month after the treatment, which was significantly higher than the 60.00±10.58 before treatment (t=-27.00, P<0.001). The levels of CA19-9 before treatment and 1 month, 2 months and 3 months after treatment were (390.88±202.62) U/ml, (322.45±204.06) U/ml, (254.00±160.49) U/ml, (182.85±124.05) U/ml, which showed a gradual decrease trend, and there was a statistically significant difference (F=126.94, P<0.001). TBIL [(250.88±80.83) μmol/L, (153.98±61.74) μmol/L, (93.45±38.12) μmol/L, (53.82±26.75) μmol/L], DBIL [(205.82±66.68) μmol/L, (133.23±58.53) μmol/L, (64.31±36.25) μmol/L, (40.55±26.16) μmol/L], ALT [(163.92±54.12) U/L, (68.23±28.86) U/L, (45.73±21.94) U/L, (32.66±12.88) U/L], AST [(177.69±58.68) U/L, (79.23±32.87) U/L, (49.77±25.45) U/L, (35.54±16.10) U/L] showed progressive decline, with statistically significant differences (F=315.60, P<0.001; F=385.30, P<0.001; F=284.24, P<0.001; F=311.80, P<0.001), and liver function was improved. The PTCD tube was removed after treatment in all patients, with a median time of 54 days (49-96 days). During the treatment, bone marrow suppression, nausea and vomiting, abdominal pain and biliary tract infection occurred. All of them improved after symptomatic treatment. No serious complications such as bile leakage and biliary hemorrhage occurred. Conclusion 192Ir brachytherapy combined with external beam radiation has a reliable curative effect in the treatment of unresectable hilar cholangiocarcinoma. It can improve the quality of life of patients, and the adverse reactions can be tolerated. It provides a feasible and safe treatment method for the clinic.

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    Efficacy and safety of teriprizumab combined with bevacizumab in the treatment of metastatic MSI-H colorectal cancer above the second line
    Lin Rongsheng, Wu Chuhai, Guo Yingmei, Wang Tao, Chen Rongbin, Liu Shaoqin, Gan Bing
    2022, 49 (2):  100-105.  doi: 10.3760/cma.j.cn371439-20210409-00016
    Abstract ( 584 )   HTML ( 29 )   PDF (4136KB) ( 122 )   Save

    Objective To observe the efficacy and safety of teriprizumab combined with bevacizumab in above the second line treatment of high-level microsatellite instability (MSI-H) type metastatic colorectal cancer (mCRC) patients. Methods From February 2019 to September 2019, 56 patients with MSI-H mCRC admitted to the Third Affiliated Hospital of Guangdong Medical University were selected and divided into control group and test group by random number table method, with 28 cases in each group. The control group was treated with bevacizumab, and the test group was treated with teriprizumab combined with bevacizumab. The objective response rate (ORR), disease control rate (DCR), progression-free survival, overall survival and incidence of adverse reactions were compared between the two groups. Results The ORR and DCR of the test group were 60.71% (17/28) and 75.00% (21/28) respectively, higher than 28.57% (8/28) and 46.63% (13/28) of the control group, with statistically significant differences (χ2=5.85, P=0.016; χ 2=4.79, P=0.029). The median progression-free survival of patients in the control group and the test group were 3.5 months and 5.8 months respectively, with a statistically significant difference (χ 2=9.83, P=0.003). The median overall survival of patients in the control group and the test group were 12.1 months and 16.2 months respectively, with a statistically significant difference (χ 2=6.13, P=0.007). There were no significant diffe-rences in the incidences of hematological reaction (17.86% vs. 14.29%, χ 2=0.13, P=0.716), cardiovascular injury (10.71% vs. 14.29%, χ 2=0.16, P=0.686), liver and kidney function injury (25.00% vs. 21.43%, χ 2=0.10, P=0.752), gastrointestinal reaction (28.57% vs. 35.71%, χ 2=0.33, P=0.567), skin and mucosal injury (7.14% vs. 10.71%, χ 2=0.35, P=0.553), nervous system disease (3.57% vs. 14.29%, χ 2=2.25, P=0.134), endocrine reaction (3.57% vs. 10.71%, χ 2=1.29, P=0.256), alopecia (14.29% vs. 17.86%, χ 2=0.13, P=0.716) and fatigue (25.00% vs. 28.57%, χ 2=0.27, P=0.605) between the control group and the test group. Conclusion The combination of teriprizumab and bevacizumab can improve the short-term and medium-long-term efficacy of patients with MSI-H mCRC, which is safe and reliable.

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    Reviews
    Clinical significance of expression of tumor immunogenic cell death related molecules
    Xu Lu, Long Jinhua, Jin Feng, Wu Weili
    2022, 49 (2):  106-110.  doi: 10.3760/cma.j.cn371439-20210607-00017
    Abstract ( 216 )   HTML ( 17 )   PDF (3684KB) ( 79 )   Save

    Tumor immunogenic cell death is a type of regulatory cell death, which is driven by stress including chemotherapy drugs, radiotherapy, oncolytic virus, nano carrier drugs and photodynamic force. It can induce specific immune response to tumor death cell antigen. The further study can provide theoretical basis and new ideas for anti-tumor immunity and clinical immunotherapy of tumor.

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    Application of PD-L1 inhibitors in the treatment of non-small cell lung cancer
    Xie Hongxia, Zuo Jinhui, Liao Dongying, Deng Renfen, Yao Yang, Jia Yingjie, Li Xiaojiang, Kong Fanming
    2022, 49 (2):  111-115.  doi: 10.3760/cma.j.cn371439-20210121-00018
    Abstract ( 201 )   HTML ( 20 )   PDF (3440KB) ( 102 )   Save

    Patients with non-small cell lung cancer (NSCLC) are treated in a variety of ways. In addition to radiotherapy, chemotherapy and targeted therapy, breakthroughs have been made in immune checkpoint inhibitors, in particular, programmed cell death 1 (PD-1) and its ligand (PD-L1) inhibitors have achieved survival benefits for NSCLC patients, and some of them have been approved as first-line drugs by the US Food and Drug Administration. Currently, commonly used PD-L1 inhibitors are atezolizumab, durvalumab and avelumab. Combination therapies include combination with chemotherapy, anti-vascular endothelial growth factor drugs, molecular targeted therapy and immunotherapy.

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    Application of the combination of stereotactic body radiation therapy and immune checkpoint inhibitors in non-small cell lung cancer
    Li Ping, Sun Xiaonan
    2022, 49 (2):  116-120.  doi: 10.3760/cma.j.cn371439-20210126-00019
    Abstract ( 196 )   HTML ( 12 )   PDF (3780KB) ( 105 )   Save

    The major treatments of non-small cell cancer (NSCLC) contain surgery, chemotherapy, radiotherapy, targeted therapy, immunotherapy and the combinations of them. Among them, stereotactic body radiation therapy (SBRT) is applied more and more extensively. Based on the immunoregulatory effects of SBRT, the combination with immune checkpoint inhibitors (ICIs) is used in all stages of NSCLC. This kind of treatment mode needs to be continuously explored to maximize the radio-immunity synergistic effect.

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    Research progress of Fusobacterium nucleatum and occurrence and development of colorectal cancer
    He Xiaokang, Tu Xian, Yao Fei, Wu Qingming
    2022, 49 (2):  121-124.  doi: 10.3760/cma.j.cn371439-20210202-00020
    Abstract ( 258 )   HTML ( 17 )   PDF (2964KB) ( 107 )   Save

    Colorectal cancer (CRC) is a common malignant tumor of the digestive tract, which seriously threatens human health. In recent years, many studies have found that Fusobacterium nucleatum (Fn) is positively related to the occurrence of CRC. In the process of CRC carcinogenesis, Fn can play an important role by inducing the expression of pro-inflammatory cytokines and triggering chronic inflammation, inhibiting the function of immune cells, inducing chemotherapy resistance, promoting the expressions of tumor genes and microRNAs and regulating glycolysis.

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