1.Impact of colorectal cancer laparoscopic and open surgery on immune function
Wenbo NIU ; Chaoxi ZHOU ; Juan ZHANG ; Guangquan AN ; Yueming YU ; Guiying WANG
Chinese Journal of Immunology 2015;(5):670-673
Objective:To analyze the impact of colorectal cancer laparoscopic and open surgery on immune function.Methods:85 patients from January 2010 to December 2013 due to surgical treatment of colorectal cancer hospitalized in our department were randomly divided into experimental and control groups.The experimental group underwent laparoscopic surgery, the control group underwent laparotomy.The peripheral blood lymphocyte subsets, immunoglobulins, CRP and IL-6 levels, NO and ROS levels were compared in two groups of patients before and after one day,seven days of surgery.Results: The postoperative CD3,CD4,CD4/CD8 level after one day and seven days of surgery was significantly lower than before surgery, CD8 was significantly higher than before surgery,P<0.05.The postoperative CD3, CD4, CD4/CD8 level after one day and seven days in the experimental group were significantly higher,CD8 was significantly lower than the control group,P<0.05.The postoperative IL-6,CRP levels after one day and seven days of surgery were significantly higher than before surgery,IgG,IgM and IgA were significantly lower than before surgery,P<0.05.The postoperative IL-6,CRP levels after one day and seven days of surgery in the experimental group were significantly lower than the control group,IgG,IgM and IgA were significantly higher,P<0.05.The NO and ROS levels after one day and seven days of surgery in the control group were significantly higher than the preoperative and postoperative period the experimental group,P<0.05.The NO and ROS levels after one day and seven days of surgery in the experimental group were no significant difference,P>0.05.Conclusion:Compared to open surgery,laparoscopic treatment of colorectal cancer has a protective and smaller effect for the body′s immune func-tion.
2.Bioinformatics analysis of microRNAs differently expressed in major depression disorder
Huimin FAN ; Wenbo WU ; Wei NIU ; Xinyang SUN ; Aifang ZHONG ; Lin ZHAO ; Liyi ZHANG
Chinese Journal of Behavioral Medicine and Brain Science 2015;24(5):418-422
Objective To predict the target genes and function of has-miR-26b,has-miR-1972,has-miR4485,has-miR-4498,and has-miR-4743 by bioinformatics analysis,and provide the theoretical basis for the further research.Methods The targets of the five microRNAs were predicted by Target Scan,miRBD,and DIANA-microT-CDS,and the result were analyzed by gene ontology and pathway analysis using FunNet.Results 734 predicted targets were obtained by finding the intersected genes of Target Scan,miRBD,and DIANA-microT-CDS.GO analysis showed that biological processes regulated by the differentially expressed microRNAs included diverse terms,among which some terms (e.g.,central nervous system development,neuron differentiation,axonogenesis,synaptic transmission,learning,and memory,etc.) had direct relationship with the central nervous system and brain functions.The pathway analysis showed that a significant enrichment in several pathways related to neuronal brain function,such as axon guidance,glutamatergic synapse,Wnt signaling pathway,mTOR signaling pathway,VEGF signaling pathway,etc.Among the five microRNAs,has-miR-26b,has-miR-1972,has-miR-4498 might have more important regulatory functions.Conclusion Bioinformatic analysis indicates that has-miR-26b,has-miR-1972,has-miR-4485,has-miR-4498,and has-miR-4743 are closely related to the mechanism and pathogenesis of major depressive disorder.
3.Propofol inhibits glycolysis and tumor progression in lung cancer through GLUT4
Wenbo WANG ; Haixin BAI ; Tan ZHANG ; Li NIU
Practical Oncology Journal 2024;38(2):104-111
Objective The objective of this study was to investigate the effects of propofol on glycolysis of lung cancer,and to further explore its potential mechanism of inhibiting glycolysis in lung cancer through glucose transporter 4(GLUT4).Methods Human lung cancer A549 cells and mouse lung cancer LLC cells were cultured,and the experimental groups were set as the blank control group(Control group)and propofol(10μmol/L)group(Propofol group).The CCK-8 assay was used to detect cell viability;Immunofluorescence(IF)was used to detect the expression of Ki-67 in lung cancer cells and A549 cell xenografts.Extracellular acidi-fication rate(ECAR)and mitochondrial oxygen consumption(OCR)assays were used to detect the cellular metabolic levels;ELISA was used to detect the cell lactate and pyruvate content;Molecular docking experiments were used to detect the binding ability of GLUT4 with propofol using CB-Dock online tool;The glucose uptake kit was used to detect glucose uptake;Western blot was used to detect the expression of GLUT4,HK2,and PFK1 proteins in lung cancer cells.Results The cell viability of A549 cells(0.661±0.052)and LLC cells(0.632±0.033)in the propofol group was significantly inhibited by 10 μmol/L of propofol in lung cancer cells(P<0.001).Compared with the control group,the average fluorescence intensity of Ki-67 in A549 and LLC positive cells(0.663±0.064 and 0.540±0.070)was significantly suppressed(P<0.001).The ELISA results showed that compared with the control group,the levels of lactate and pyruvate in the propofol group decreased(P<0.001),and under the action of propofol,the glucose uptake ability of cells decreased(P<0.001).Molecular docking experiments using the CB-Dock online tool showed that GLUT4 had the strongest binding force with propofol.The results of Western blot showed a decrease in the expression of GLUT4 and its downstream HK2 and PFK1 pro-teins.After transient transfection and knockdown of GLUT4,cellular lactate(P<0.001)and pyruvate content(P<0.01)decreased,glu-cose uptake capacity reduced,and the inhibitory effect of propofol on glycolysis disappeared.In A549 cell xenografts,the weight of xenografts in the propofol group was significantly smaller than that of the model group(P<0.001).Compared with the model group,the lactate content and pyruvate content decreased in the propofol group(P<0.001).Conclusion Propofol can inhibit the proliferation of lung cancer cells and the progression of A549 cell xenografts in bearing mice by inhibiting the glycolysis of lung cancer cells,and its mechanism may be related to the targeted effect of GLUT4 on the glycolysis of lung cancer cells.
4.Correlation of expression level of lncRNA in peripheral blood mononuclear cells, chronic stress in childhood and cognitive dysfunction in schizophrenia patients
Lingming KONG ; Xiaoli ZHU ; Wei NIU ; Shengdong CHEN ; Liyi ZHANG ; Wenbo WU
Chinese Journal of Behavioral Medicine and Brain Science 2021;30(11):1005-1010
Objective:To explore the effects of expression level of long noncoding RNA (lncRNA) in peripheral blood mononuclear cells (PBMCs), chronic stress in childhood on cognitive function for providing scientific basis of prevention, intervention and rehabilitation of cognitive impairment in schizophrenia patients.Methods:Quantitative real-time PCR (qPCR) was used to screen lncRNA expression in peripheral blood mononuclear cells (PBMCs) of 100 schizophrenic patients who was recruited by convenient sampling, and all the patients were assessed by Montreal cognitive assessment-Beijing version (MoCA) and childhood chronic stress questionnaire (CCSQ). Mann-Whitney test, t-test, correlation analysis and regression analysis were employed for data processing. Results:The ΔCt values of NONHSAT089447(5.07), NONHSAT041499(8.56) were higher ( Z=-2.38, -2.07, P<0.05) and scores of all three CCSQ dimensions were lower in higher MoCA goup than those in lower MOCA group (peer bullying: 42.36±11.13 vs 50.84±9.09, abuse and neglect: 55.08±14.22 vs 69.56±13.45, adverse life events: 47.64±12.21 vs 55.80±13.92, t=-2.20--3.70, P<0.05 or 0.01). The ΔCt value of NONHSAT089447, NONHSAT041499 positively correlated with scores of visuospatial-executive, language, abstraction and delayed recall ( r=0.43-0.75, P<0.01). All three CCSQ dimensions negatively correlated with scores of visuospatial-executive, attention, language, abstract thinking and delayed recall ( r=-0.40--0.62, P<0.05 or 0.01). Multiple regression analysis showed that the ΔCt valueof NONHSAT089447, abuse and neglect in childhood significantly predicted the total score of MOCA, which could explained 31.9% of variation ( t=4.31, 5.89, P=0.007, 0.001). The ΔCt value of NONHSAT089447, NONHSAT041499 negatively correlated with peer bullying, abuse and neglect in childhood ( r=-0.39--0.53, all P<0.01). Conclusion:There are correlation in NONHSAT089447, NONHSAT041499 and chronic stress in childhood in patients with schizophrenia, which can jointly predict their cognitive function.
5.Treatment strategies for colorectal cancer patients in tumor hospitals under the background of corona virus disease 2019
Xuhua HU ; Wenbo NIU ; Jianfeng ZHANG ; Baokun LI ; Bin YU ; Zhenya ZHANG ; Chaoxi ZHOU ; Xuena ZHANG ; Yang GAO ; Guiying WANG
Chinese Journal of Gastrointestinal Surgery 2020;23(3):201-208
In December 2019, a new outbreak of corona virus disease 2019 began to occur. Its pathogen is 2019-nCoV, which has the characteristics of strong infectivity and general susceptibility. The current situation of prevention and control of new coronavirus pneumonia is severe. In this context, as front-line medical workers bearing important responsibilities and pressure, while through strict management strategy, we can minimize the risk of infection exposure. By summarizing the research progress and guidelines in recent years in the fields of colorectal cancer disease screening, treatment strategies (including early colorectal cancer, locally advanced colorectal cancer, obstructive colorectal cancer, metastatic colorectal cancer and the treatment of patients after neoadjuvant therapy), the choice of medication and time limit for adjuvant therapy, the protective measures for patients undergoing emergency surgery, the re-examination of postoperative patients and the protection of medical staff, etc., authors improve treatment strategies in order to provide more choices for patients to obtain the best treatment under the severe epidemic situation of new coronavirus pneumonia. Meanwhile we hope that it can also provide more timely treatment modeling schemes for colleagues.
6.Peripheral blood cell count composite score as a prognostic factor in patients with colorectal cancer
Peiyuan GUO ; Xuhua HU ; Baokun LI ; Ti LU ; Jiaming LIU ; Chaoyu WANG ; Wenbo NIU ; Guiying WANG ; Bin YU
Chinese Journal of Gastrointestinal Surgery 2024;27(9):953-965
Objective:To develop a prognostic prediction model for patients with colorectal cancer based on a peripheral blood cell composite score (PBCS) system.Methods:This retrospective observational study included patients who had primary colorectal cancer without distant metastasis, who did not undergo radiotherapy or chemotherapy before surgery, who did not receive leukocyte or platelet-raising therapy within 1 month before surgery, and whose postoperative pathology confirmed colorectal adenocarcinoma with complete tumor resection. Patients with severe anemia, infection, or hematologic diseases before surgery, as well as those with severe heart, lung, or other important organ diseases or concurrent malignant tumors, were excluded. In total, 1021 patients with colorectal cancer who underwent surgical treatment in the Department of Gastrointestinal Surgery of the Fourth Hospital of Hebei Medical University from April 2018 to April 2020 were retrospectively included as the training set (766 patients) and the internal validation set (255 patients). Additionally, using the same criteria, 215 patients with colorectal cancer who underwent surgical treatment in another treatment group from March 2015 to December 2020 were selected as the external validation set. The "surv_cutpoint" function in R software was used to analyze the optimal cut-off values of neutrophils, lymphocytes, and platelets, and a PBCS system was established based on the optimal cut-off values. The scoring rules of the PBCS system were as follows: Neutrophils and platelets below the optimal cut-off value = 1 point, otherwise 0 points; Lymphocytes above the optimal cut-off value = 1 point, otherwise 0 points. The scores of the three cell types were added together to obtain the PBCS. Univariate and multivariate Cox regression analyses were performed to explore the correlation between patients' clinicopathological features and prognosis, and a nomogram was constructed based on the Cox regression analysis to predict patients' prognosis. The accuracy of the nomogram prediction model was validated using the C-index, calibration curve, and decision curve analysis.Results:The optimal cut-off values for neutrophils, lymphocytes, and platelets were 4.40×10 9/L, 1.41×10 9/L, and 355×10 9/L, respectively. The patients were divided into high and low groups according to the optimal cut-off values of these cells. Survival curve analysis showed that a high lymphocyte count (training set: P=0.042, internal validation: P=0.010, external validation: P=0.029), low neutrophil count (training set: P=0.035, internal validation: P=0.001, external validation: P=0.024), and low platelet count (training set: P=0.041, internal validation: P=0.030, external validation: P=0.024) were associated with prolonged overall survival (OS), with statistically significant differences in all cases. Survival analysis of different PBCS groups showed that patients with a high PBCS had longer OS than those with a low PBCS ( P<0.05). Univariate and multivariate Cox regression analysis results showed that aspirin use history, vascular thrombus, neural invasion, CA19-9, N stage, operation time, M stage, and PBCS were independent factors affecting OS (all P<0.05). The PBCS was also an independent factor affecting disease-specific survival ( P<0.05), but not progression-free survival ( P>0.05). The above independent risk or protective factors were included in R software to construct a nomogram for predicting OS. The C-index (0.873), calibration curve, and decision curve analysis (threshold probability: 0.0%–75.2%) all indicated that the nomogram prediction model had good predictive performance for OS. Conclusion:This study demonstrates that the PBCS constructed based on preoperative peripheral blood levels of neutrophils, lymphocytes, and platelets is an independent factor associated with the prognosis of patients with colorectal cancer. The nomogram model constructed based on this score system exhibits good predictive efficacy for the prognosis of these patients.
7.Treatment strategies for colorectal cancer patients in tumor hospitals under the background of corona virus disease 2019
Xuhua HU ; Wenbo NIU ; Jianfeng ZHANG ; Baokun LI ; Bin YU ; Zhenya ZHANG ; Chaoxi ZHOU ; Xuena ZHANG ; Yang GAO ; Guiying WANG
Chinese Journal of Gastrointestinal Surgery 2020;23(3):201-208
In December 2019, a new outbreak of corona virus disease 2019 began to occur. Its pathogen is 2019-nCoV, which has the characteristics of strong infectivity and general susceptibility. The current situation of prevention and control of new coronavirus pneumonia is severe. In this context, as front-line medical workers bearing important responsibilities and pressure, while through strict management strategy, we can minimize the risk of infection exposure. By summarizing the research progress and guidelines in recent years in the fields of colorectal cancer disease screening, treatment strategies (including early colorectal cancer, locally advanced colorectal cancer, obstructive colorectal cancer, metastatic colorectal cancer and the treatment of patients after neoadjuvant therapy), the choice of medication and time limit for adjuvant therapy, the protective measures for patients undergoing emergency surgery, the re-examination of postoperative patients and the protection of medical staff, etc., authors improve treatment strategies in order to provide more choices for patients to obtain the best treatment under the severe epidemic situation of new coronavirus pneumonia. Meanwhile we hope that it can also provide more timely treatment modeling schemes for colleagues.
8.Peripheral blood cell count composite score as a prognostic factor in patients with colorectal cancer
Peiyuan GUO ; Xuhua HU ; Baokun LI ; Ti LU ; Jiaming LIU ; Chaoyu WANG ; Wenbo NIU ; Guiying WANG ; Bin YU
Chinese Journal of Gastrointestinal Surgery 2024;27(9):953-965
Objective:To develop a prognostic prediction model for patients with colorectal cancer based on a peripheral blood cell composite score (PBCS) system.Methods:This retrospective observational study included patients who had primary colorectal cancer without distant metastasis, who did not undergo radiotherapy or chemotherapy before surgery, who did not receive leukocyte or platelet-raising therapy within 1 month before surgery, and whose postoperative pathology confirmed colorectal adenocarcinoma with complete tumor resection. Patients with severe anemia, infection, or hematologic diseases before surgery, as well as those with severe heart, lung, or other important organ diseases or concurrent malignant tumors, were excluded. In total, 1021 patients with colorectal cancer who underwent surgical treatment in the Department of Gastrointestinal Surgery of the Fourth Hospital of Hebei Medical University from April 2018 to April 2020 were retrospectively included as the training set (766 patients) and the internal validation set (255 patients). Additionally, using the same criteria, 215 patients with colorectal cancer who underwent surgical treatment in another treatment group from March 2015 to December 2020 were selected as the external validation set. The "surv_cutpoint" function in R software was used to analyze the optimal cut-off values of neutrophils, lymphocytes, and platelets, and a PBCS system was established based on the optimal cut-off values. The scoring rules of the PBCS system were as follows: Neutrophils and platelets below the optimal cut-off value = 1 point, otherwise 0 points; Lymphocytes above the optimal cut-off value = 1 point, otherwise 0 points. The scores of the three cell types were added together to obtain the PBCS. Univariate and multivariate Cox regression analyses were performed to explore the correlation between patients' clinicopathological features and prognosis, and a nomogram was constructed based on the Cox regression analysis to predict patients' prognosis. The accuracy of the nomogram prediction model was validated using the C-index, calibration curve, and decision curve analysis.Results:The optimal cut-off values for neutrophils, lymphocytes, and platelets were 4.40×10 9/L, 1.41×10 9/L, and 355×10 9/L, respectively. The patients were divided into high and low groups according to the optimal cut-off values of these cells. Survival curve analysis showed that a high lymphocyte count (training set: P=0.042, internal validation: P=0.010, external validation: P=0.029), low neutrophil count (training set: P=0.035, internal validation: P=0.001, external validation: P=0.024), and low platelet count (training set: P=0.041, internal validation: P=0.030, external validation: P=0.024) were associated with prolonged overall survival (OS), with statistically significant differences in all cases. Survival analysis of different PBCS groups showed that patients with a high PBCS had longer OS than those with a low PBCS ( P<0.05). Univariate and multivariate Cox regression analysis results showed that aspirin use history, vascular thrombus, neural invasion, CA19-9, N stage, operation time, M stage, and PBCS were independent factors affecting OS (all P<0.05). The PBCS was also an independent factor affecting disease-specific survival ( P<0.05), but not progression-free survival ( P>0.05). The above independent risk or protective factors were included in R software to construct a nomogram for predicting OS. The C-index (0.873), calibration curve, and decision curve analysis (threshold probability: 0.0%–75.2%) all indicated that the nomogram prediction model had good predictive performance for OS. Conclusion:This study demonstrates that the PBCS constructed based on preoperative peripheral blood levels of neutrophils, lymphocytes, and platelets is an independent factor associated with the prognosis of patients with colorectal cancer. The nomogram model constructed based on this score system exhibits good predictive efficacy for the prognosis of these patients.
9.Meta analysis of detection rate of human adenovirus among different patients in China
Dandan NIU ; Zhen ZHU ; Wenbo XU ; Ying WANG
Chinese Journal of Experimental and Clinical Virology 2020;34(3):316-321
Objective:Human adenovirus(HAdV) can cause a variety of diseases, and sometimes leads to outbreaks of respiratory diseases, this study determines to understand the detection status of human adenovirus in the pathogenic spectrum of different diseases.Methods:This study conducted Meta analysis on the detection rate of human adenovirus in 284 studies that met the inclusion criteria and included heterogeneity test, pooling rate by random effect model, Meta regression, sensitivity analysis and publication bias analysis.Results:The detection rate varied greatly and heterogeneity of 284 studies was relatively large. Different method were used to reduce or analyze the heterogeneity: the total detection rate by random effect model was 4.21% (95% CI: 3.80%~4.66%); the detection rates of each subgroup were gastrointestinal diseases 5.06% (95% CI: 4.22%~6.06%), respiratory diseases 3.97% (95% CI: 3.53%~4.46%), children 4.50% (95% CI: 4.06%~4.99%), adults 2.09% (95% CI: 1.22%~3.56%), antigen test 1.94% (95% CI: 1.64%~2.30%), nucleic acid test 5.82% (95% CI: 5.21%~6.49%), serum test 5.60% (95% CI: 4.17%~7.48%), eastern 3.67% (95% CI: 3.18%~4.24%), central 6.07% (95% CI: 5.20%~7.08%), western 5.00% (95% CI: 4.03%~6.18%), ≤1 000 sample size 6.10% (95% CI: 5.39%~6.91%), > 1 000 sample size 2.66% (95% CI: 2.32%~3.05%); the significant factors of Meta regression analysis were disease type, age, detection method, research area, sample size and adjusted R2=37.15%. Conclusions:This study suggests that the Meta analysis needs to be improved to conduct pooling detection rate like HAdV with great heterogeneity. Different disease types, age, detection method, research area, sample size account for part of the resources for heterogeneity.
10.Clinicopathological characteristics of type 2 diabetes mellitus complicated with colorectal cancer
Zihan HAN ; Jiajia CHEN ; Nan FENG ; Pengfei NIU ; Can SONG ; Zhaoya GAO ; Qingkun GAO ; Dengbo JI ; Wenbo WANG ; Fuming LEI ; Jin GU
Chinese Journal of Gastrointestinal Surgery 2019;22(10):966-971
Objective To analyze the clinicopathological features of type 2 diabetes mellitus complicated with colorectal cancer (DCRC). Methods A case?control study was conducted. Inclusion criteria: (1) hospitalized patients receiving fibrocolonoscopy; (2) adenocarcinoma and mucinous adenocarcinoma diagnosed by pathology; (3) with preoperative cTNM clinical staging; (4) colorectal cancer patients undergoing surgical treatment; (5) with postoperative pTNM staging; (6) no smoking or drinking habits. Exclusion criteria: (1) familial adenomatous polyposis (FAP); (2) Lynch syndrome; (3) carcinoma of anal canal and perianal carcinoma; (4) multiple primary cancer; (5) with serious cardiocerebrovascular diseases or multiple organ failure. Clinicopathlogical data of 32 DCRC patients who were diagnosed and treated in Peking University Shougang Hospital from December 2017 to December 2018 were retrospectively collected and analyzed. Forty nondiabetic colorectal cancer (CRC) patients during the same period were selected as control group according to the sex ratio and the age difference less than 5 years. Student′s t test and χ2 test were used to compare the difference between the two groups in baseline clinicopathological data, clinical test results, tumor markers and infiltration status of T cells in tumor immune microenvironment. Results Among 32 DCRC patients, 24 were males and 8 were females with a mean age of (63.0±1.7) years; among 40 CRC patients, 30 were males and 10 were females with a mean age of (60.5 ± 1.6) years. The duration of diabetes mellitus in DCRC patients (from the diagnosis of diabetes mellitus to the diagnosis of colorectal cancer) was (9.2±1.3) years. The body mass index (BMI) of DCRC group was significantly higher than that of CRC group [(24.8±0.6) kg/m2 vs. (23.2±0.4) kg/m2, t=2.372, P=0.020]. There were no significant differences in other baseline data (sex, age, primary site of tumor, R0 resection rate, pathological stage, pathological type, differentiation degree of tumor, preoperative intestinal obstruction) between the two groups (all P>0.05). Serum triglyceride level in DCRC group was higher than that in CRC group [(2.1 ± 0.2) mmol/L vs. (1.5 ± 0.1) mmol/L, t=3.085, P=0.003], while hemoglobin [(120.3±5.2) g/L vs. (132.7±2.8) g/L, t=-2.224, P=0.029], anti? thrombin III [(94.2±3.7)% vs. (103.5±2.4)%, t=-2.197, P=0.031], and red blood cell count [(4.2±0.1)×1012/L vs. (4.5±0.1)×1012L, t=-2.055, P=0.044] were all lower than those in CRC group. The preoperative carcinoembryonic antigen (CEA) level in DCRC group was higher than that in CRC group [(50.3±21.8) μg/L vs. (5.6±1.0) μg/L, t=2.339, P=0.022]. There were no significant differences in preoperative levels of other four tumor molecular markers (CA199, CA242, CA724 and CA125) between the two groups (all P>0.05). The expression of Foxp3 [specific markers of CD4+, CD25+ regulatory T cells (Treg)] in DCRC group was higher than that in CRC group [(82.7±6.2) cell/ HPF vs. (62.6±4.9) cell/HPF, t=2.586, P=0.012]. There were no significant differences in the infiltration of CD4, CD8, PD?1 and PD?L1 positive cells between two groups (all P>0.05).Conclusions The average diabetic history of DCRC patients is nearly 10 years. They have higher BMI and serum CEA level, and more Treg cell infiltration in the tumor. Close attention should be paid to these patients in clinical practice.