1.A novel nomogram-based model to predict the postoperative overall survival in patients with gastric and colorectal cancer
Siwen WANG ; Kangjing XU ; Xuejin GAO ; Tingting GAO ; Guangming SUN ; Yaqin XIAO ; Haoyang WANG ; Chenghao ZENG ; Deshuai SONG ; Yupeng ZHANG ; Lingli HUANG ; Bo LIAN ; Jianjiao CHEN ; Dong GUO ; Zhenyi JIA ; Yong WANG ; Fangyou GONG ; Junde ZHOU ; Zhigang XUE ; Zhida CHEN ; Gang LI ; Mengbin LI ; Wei ZHAO ; Yanbing ZHOU ; Huanlong QIN ; Xiaoting WU ; Kunhua WANG ; Qiang CHI ; Jianchun YU ; Yun TANG ; Guoli LI ; Li ZHANG ; Xinying WANG
Chinese Journal of Clinical Nutrition 2024;32(3):138-149
		                        		
		                        			
		                        			Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.
		                        		
		                        		
		                        		
		                        	
2.Effect of right stellate ganglion block on acute lung injury induced by hind limb ischemia-reperfusion in rats
Huanlong GAO ; Yadong ZHANG ; Nan XIN ; Haitao TIAN ; Yanli WANG
Chinese Journal of Anesthesiology 2024;44(6):694-697
		                        		
		                        			
		                        			Objective:To evaluate the effect of the right stellate ganglion block (SGB) on the acute lung injury induced by hind limb ischemia-reperfusion (I/R) in rats.Methods:Twenty-seven SPF healthy male Sprague-Dawley rats, aged 7-8 weeks, weighing 200-250 g, were divided into 3 groups ( n=9 each) by the random number table method: sham operation group (Sham group), hind limb I/R group (I/R group) and right SGB+ hind limb I/R group (SGB+ I/R group). The right hind limb I/R injury model was developed in anesthetized rats in I/R and SGB+ I/R groups, and the right SGB was performed with 0.2% ropivacaine 0.5 ml before the right hind limb ischemia in SGB+ I/R group. The pathological changes of lung tissues were observed with a light microscope, the wet/dry lung weight ratio, PaO 2 and PaCO 2 were determined, and the oxygenation index was calculated. The concentrations of serum malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were determined using enzyme-linked immunosorbent assay. Results:Compared with Sham group, the wet/dry lung weight ratio, PaO 2, oxygenation index, and GSH-Px concentrations were significantly decreased, and the concentrations of serum MDA were increased in I/R and SGB+ I/R groups ( P<0.05). Compared with I/R group, the wet/dry lung weight ratio, PaO 2, oxygenation index, and GSH-Px concentrations were significantly increased, the concentrations of serum MDA were decreased ( P<0.05), and the pathological changes of lung tissues were significantly attenuated in SGB+ I/R group. There was no significant difference in PaCO 2 among the 3 groups ( P>0.05). Conclusions:The right SGB can alleviate the acute lung injury induced by hind limb I/R, and the mechanism may be related to the inhibition of oxidative stress responses in rats.
		                        		
		                        		
		                        		
		                        	
3.Research progress on characteristics of gastrointestinal flora in patients with Crohn's disease and the efficacy of fecal microbiota transplantation
Kai XIA ; Renyuan GAO ; Huanlong QIN ; Lu YIN
Chinese Journal of Clinical Nutrition 2021;29(2):109-113
		                        		
		                        			
		                        			Crohn's disease (CD) is a chronic nonspecific inflammatory bowel disease that can involve the whole digestive tract. At present, the pathogenesis is believed to be mainly related to environment, genetics and intestinal microecology changes. Compared with healthy people, CD patients demonstrate different degrees of flora imbalance in the digestive tract, and the flora composition varies across different regions. In recent years, reconstruction of gastrointestinal microecological balance has become the focus of research. Fecal microbiota transplantation as a new treatment strategy has been gradually applied in clinical practice. Here we reviewed the changes of flora across different regions of digestive tract in patients with CD and the relevant pathogenic mechanism, as well as the progress of fecal microbiota transplantation in the treatment of CD.
		                        		
		                        		
		                        		
		                        	
4.Effects of probiotics on the intestinal microecological abnormalities and colorectal cancer of mice induced by high-fat diet
Jide HE ; Cheng KONG ; Renyuan GAO ; Fang YIN ; Yang ZHANG ; Huanlong QIN
Chinese Journal of Gastrointestinal Surgery 2020;23(Z1):77-85
		                        		
		                        			
		                        			Objective:To establish the mice colorectal cancer (CRC) model induced by AOM/DSS with the intervention of high fat diet and probiotics, and to explore the potential mechanism of probiotics intervention in regulating intestinal flora disturbance and antitumor efficiency.Methods:Forty 8-week-old male C57BL/6J mice were randomly divided into 4 groups with 10 mice in each group: HFD group, HDF with probiotics intervention (HFD+P) group, normal diet (ND) group, normal diet with probiotics intervention (ND+P) group. The probiotic groups were administered with probiotics preparation by gavage. During the experiment, AOM/DSS was used to induce mouse colorectal cancer model. The mouse body weight was regularly recorded and the body status was evaluated weekly. High-throughput 16S rDNA sequencing was used to analyze the changes of fecal flora in bacterial structure before and after cancer induction. At the end of the experiment, intestinal tissues of mice were collected and the epididymis adipose mass (EAM) and tumor burden were recorded. The Alpha diversity index was used to analyze the abundance and diversity of the intestinal flora (higher chaol index means higher abundance of bacteria and greater Simpson index means lower diversity in flora structure). The Beta diversity index was used to analyze the significance of the difference in the distribution of intestinal flora among the four groups (When R>0, the difference in the distribution of bacteria among the groups is greater than the difference within the group).Results:After 15 weeks of experiment, the body weight of mice in HFD group, HFD+P group, ND group and ND+P group was (33.70±0.52) g, (28.70±0.32) g, (25.90±0.34) g and (25.60±0.40) g, whose difference was statistically significant ( F=700.89, P<0.01). The body weight of HFD group was higher than that of ND group and HFD+P group while the body weight of HFD+P group was still higher than that of ND group, and the differences were statistically significant (all P<0.017). The average EAM of HFD group, HFD+P group, ND group and ND+P group was (1.36±0.15) g, (0.67±0.08) g, (0.58±0.10) g and (0.54±0.05) g, whose difference was statistically significant ( F=114.03, P<0.01). Pairwise comparisons showed that EAM in HFD group was higher than that in ND group and HFD+P group respectively, with statistically significant difference (both P<0.01), while average EAM of HFD+P group was similar to ND group ( P=0.09). Under the diet intervention, the Chao1 index of HFD group, HFD+P group, ND group and ND+P group was 217.62, 235.32, 301.51 and 305.71 respectively, and the Simpson index was 0.93, 0.89, 0.91 and 0.90. At the same time, the Anosim analysis of Beta diversity analysis showed that the difference in the flora distribution among four groups was greater than the difference with in each group with statistically significant difference ( R=0.655, P=0.001). Species abundance analysis revealed that, compared with ND group, at phylum level, HFD group had a higher proportion of Bacteroides phylum and Firmicutes phylum in the intestinal flora and lower proportion of Verrucomicrobia; at genus level, the proportion of Bacteroides and Oscillibacter in HFD group was higher while the proportion of Akkermansia and Alloprevotella was lower. After the intervention of probiotics, the flora mentioned above was improved significantly except for Alloprevotella. The average number of tumor in HFD group, HFD+P group, ND group and ND+P group was 4.63±1.19, 2.33±0.52, 2.56±0.73 and 2.38±0.52 with statistically significant difference ( F=14.92, P<0.01). Conclusion:Probiotics therapy can reduce obesity and flora imbalance caused by HFD and reduce the incidence of CRC by regulating intestinal flora disturbance.
		                        		
		                        		
		                        		
		                        	
5.Effects of probiotics on the intestinal microecological abnormalities and colorectal cancer of mice induced by high-fat diet
Jide HE ; Cheng KONG ; Renyuan GAO ; Fang YIN ; Yang ZHANG ; Huanlong QIN
Chinese Journal of Gastrointestinal Surgery 2020;23(Z1):77-85
		                        		
		                        			
		                        			Objective:To establish the mice colorectal cancer (CRC) model induced by AOM/DSS with the intervention of high fat diet and probiotics, and to explore the potential mechanism of probiotics intervention in regulating intestinal flora disturbance and antitumor efficiency.Methods:Forty 8-week-old male C57BL/6J mice were randomly divided into 4 groups with 10 mice in each group: HFD group, HDF with probiotics intervention (HFD+P) group, normal diet (ND) group, normal diet with probiotics intervention (ND+P) group. The probiotic groups were administered with probiotics preparation by gavage. During the experiment, AOM/DSS was used to induce mouse colorectal cancer model. The mouse body weight was regularly recorded and the body status was evaluated weekly. High-throughput 16S rDNA sequencing was used to analyze the changes of fecal flora in bacterial structure before and after cancer induction. At the end of the experiment, intestinal tissues of mice were collected and the epididymis adipose mass (EAM) and tumor burden were recorded. The Alpha diversity index was used to analyze the abundance and diversity of the intestinal flora (higher chaol index means higher abundance of bacteria and greater Simpson index means lower diversity in flora structure). The Beta diversity index was used to analyze the significance of the difference in the distribution of intestinal flora among the four groups (When R>0, the difference in the distribution of bacteria among the groups is greater than the difference within the group).Results:After 15 weeks of experiment, the body weight of mice in HFD group, HFD+P group, ND group and ND+P group was (33.70±0.52) g, (28.70±0.32) g, (25.90±0.34) g and (25.60±0.40) g, whose difference was statistically significant ( F=700.89, P<0.01). The body weight of HFD group was higher than that of ND group and HFD+P group while the body weight of HFD+P group was still higher than that of ND group, and the differences were statistically significant (all P<0.017). The average EAM of HFD group, HFD+P group, ND group and ND+P group was (1.36±0.15) g, (0.67±0.08) g, (0.58±0.10) g and (0.54±0.05) g, whose difference was statistically significant ( F=114.03, P<0.01). Pairwise comparisons showed that EAM in HFD group was higher than that in ND group and HFD+P group respectively, with statistically significant difference (both P<0.01), while average EAM of HFD+P group was similar to ND group ( P=0.09). Under the diet intervention, the Chao1 index of HFD group, HFD+P group, ND group and ND+P group was 217.62, 235.32, 301.51 and 305.71 respectively, and the Simpson index was 0.93, 0.89, 0.91 and 0.90. At the same time, the Anosim analysis of Beta diversity analysis showed that the difference in the flora distribution among four groups was greater than the difference with in each group with statistically significant difference ( R=0.655, P=0.001). Species abundance analysis revealed that, compared with ND group, at phylum level, HFD group had a higher proportion of Bacteroides phylum and Firmicutes phylum in the intestinal flora and lower proportion of Verrucomicrobia; at genus level, the proportion of Bacteroides and Oscillibacter in HFD group was higher while the proportion of Akkermansia and Alloprevotella was lower. After the intervention of probiotics, the flora mentioned above was improved significantly except for Alloprevotella. The average number of tumor in HFD group, HFD+P group, ND group and ND+P group was 4.63±1.19, 2.33±0.52, 2.56±0.73 and 2.38±0.52 with statistically significant difference ( F=14.92, P<0.01). Conclusion:Probiotics therapy can reduce obesity and flora imbalance caused by HFD and reduce the incidence of CRC by regulating intestinal flora disturbance.
		                        		
		                        		
		                        		
		                        	
6.Value of the methylation status of SDC2 and SFRP2 for colorectal cancer screening
Yu BAI ; Jing LIU ; Qian KANG ; Yushu CHEN ; Meicong WANG ; Peng JIN ; Yiqun MI ; Renyuan GAO ; Huanlong QIN ; Zhaoshen LI ; Nan QIN ; Jianqiu SHENG
Chinese Journal of Digestive Endoscopy 2019;36(6):427-432
		                        		
		                        			
		                        			Objective To explore the value of methylation of SDC2 and SFRP2 genes promoter in fecal DNA for colorectal cancer ( CRC) screening. Methods All stool samples were enrolled from Changhai Hospital of Naval Medical University, the Tenth People' s Hospital of Tongji University and the Seventh Medical Center of Chinese People's Liberation Army General Hospital. A total of 500 stool samples collected from March 2018 to December 2018 were allocated to CRC group ( 132 CRCs ) , adenoma group ( 38 advanced adenomas), healthy group (152 healthy individuals), interferential group (178 cases of benign colorectal disease or other non-colorectal tumors) and negative group (330 cases composed of healthy group and interferential group ) . The promoter methylation of fecal SDC2 and SFRP2 genes was detected by methylation-specific PCR (MSP) and compared with single gene methylation and the fecal immunochemical tests ( FIT) to evaluate its sensitivity and specificity. Results The stool sample analysis showed that the sensitivity of combined detection of SDC2 and SFRP2 in CRC group was 97. 73% ( 129/132 ) , which was significantly higher than those of the single gene SDC2 test [ 70. 45% ( 93/132) , P=0. 000] , single SFRP2 test [81. 82% (108/132), P=0. 000] and FIT [69. 70% (92/132), P=0. 000]. In adenoma group, the sensitivity of combined detection of SDC2 and SFRP2 was 57. 89% (22/38), which was significantly higher than those of the single gene SDC2 test [ 15. 79% ( 6/38 ) , P= 0. 000 ] and FIT [ 21. 05% ( 8/38 ) , P=0. 021] , with no significant difference compared with that of SFRP2 test [ 47. 37% ( 18/38) , P=0. 358] . In healthy group, the specificity of combined detection of SDC2 and SFRP2 was 98. 68% (150/152), with no significant difference compared with those of single gene SDC2 test [ 100. 00%( 152/152) , P=0. 156] , single SFRP2 test [98. 68% (150/152), P=1. 000] or FIT [95. 39% (145/152), P=0. 091]. Specificities of combined detection of two genes in interferential and negative groups were 90. 45% ( 161/178) and 94. 24%( 311/330) , which were significantly higher than 73. 03%( 130/178, P=0. 000) and 83. 33%( 275/330, P=0. 000) of FIT, respectively. Conclusion The combined detection test of methylation of SDC2 and SFRP2 is superior to single gene test, whose sensitivity of CRC and aggressive adenoma and specificity of distinguishing benign and malignant lesions are higher than FIT, which has potential application value.
		                        		
		                        		
		                        		
		                        	
7.Effect of synbioties on the intestinal microbiota in patients with chronic functional constipation
Linsheng HUANG ; Xuebing YAN ; Hao LI ; Renyuan GAO ; Tongyi SHEN ; Huanlong QIN
Chinese Journal of Clinical Nutrition 2018;26(4):228-234
		                        		
		                        			
		                        			Objective To investigate the beneficial role of synbiotics in the intestinal microbiota of patients with chronic functional constipation (CFC).Methods According to the inclusion and exclusion criteria,6 patients with CFC were enrolled with their fresh fecal samples collected,after a continuous treatment of one month their fresh fecal samples collected again.Meanwhile,6 healthy volunteers were enrolled as the control group with their fresh fecal samples collected.All samples were transported with ice and stored in -80 ℃ refrigerator,and were analyzed by metagenomics sequencing.Results After 4 weeks of symbiotic treatment,the intestinal microbiota had changed in species in patients with CFC.Bacteria of Escherichia_ coli,Clostridium_ sp._ SS2/1 and Clostridium_ sp._ 7_ 3_ 54FAA,which were rich in the people with constipation,decreased in abundance after the treatment.Bacteria of Lactobacillus_ oris and Bifidobacterium _ animalis,which were rich in the healthy people,increased in content after the treatment.Bacteria of Veillonella_ parvula,Veillonella_ sp._ 6_ 1_ 27,Veillonella_ sp._ 3 _ 1_ 44 which were rich in the healthy people,decreased in content after the treatment.LEfSe analysis showed that Parabacteroides distaso nis,Escherichia_ coli and Enterobacter-cloacae were the specific species of the three groups respectively.Conclusion Synbiotics can change the intestinal microbiota showing therapeutic effect,thus can be used as a novel clinical treatment method.
		                        		
		                        		
		                        		
		                        	
8.Structural difference of gut microbiota in obese patients with or without acanthosis nigricans
Cuiling ZHU ; Renyuan GAO ; Hao LI ; Huanlong QIN ; Shen QU
Chinese Journal of Clinical Nutrition 2017;25(2):104-110
		                        		
		                        			
		                        			Objective To investigate the distribution of gut microbiota in obese patients with or without acanthosis nigricans .Methods Totally 131 obese patients and 25 healthy participants were divided into three groups:the obesity with acanthosis nigricans (AN) group (n=59), the simple obesity (OB) group (n=79), and the control (CON) group (n=25).The fresh stool samples were collected , and the clinical and biochemistry markers were measured .Pyrosequencing technology was performed based on the 16s rRNA of fecal samples to identify and analyze the distribution pattern of gut microbiota in each group .Results The AN group had signifi-cantly higher body mass index [ (37.45 ±5.12) kg/m2 vs.(33.34 ±2.54) kg/m2 vs. (20.35 ±1.68) kg/m2, P=0.045, P<0.001], insulin [32.77 (25.18) mU/L vs.20.73 (9.30) mU/L vs.8.70 (6.18) mU/L, P<0.001, P<0.001], insulin resistance [7.78 (6.87) vs.4.71 (2.88) vs.1.81 (1.40), P<0.001, P<0.001], and interleukin (IL) -6 [ (3.64 ±2.23) ng/L vs.(2.71 ±0.78) ng/L vs.(2.17 ±0.86) ng/L, P=0.040, P=0.009] levels than OB and CON groups compared with OB and CON groups , AN group had sig-nificantly decreased diversity of bacterial flora ( P=0.015 , P=0.001 ) , while no significant difference was observed in the abundance of bacterial flora .At the phylum level , the composition of flora among these three groups was similar, mainly including bacteroidetes , firmicutes, proteobacteria, and actinomycetes.Although the proportions of main bacteria flora were different , the difference was not statistically significant .At the genus level, the bacteria flora in AN and OB groups were primarily composed of Bacteroides, Megamonas, Faecalibac-terium and Escherichia-Shigella.In addition, compared to OB and CON groups , AN group had significantly lower proportion of Ruminococcus ( P=0.023 , P=0.043 , respectively ) and higher proportion of Veillonella (P=0.048, P=0.043, respectively).Furthermore, the proportion of Weissella was higher in AN and OB groups than in CON group ( P=0.045 , P=0.025 ) .Conclusion Obese patients with AN have more severe in-sulin resistance and inflammation status than those with simple obesity , and the distribution feature of gut micro-biota also differ between these two patient populations .
		                        		
		                        		
		                        		
		                        	
9.Research progress on application of microecological agents in treatment of gut diseases
Renyuan GAO ; Leiming HONG ; Mingming YIN ; Huanlong QIN
Chinese Journal of Clinical Nutrition 2015;23(5):308-312
		                        		
		                        			
		                        			Gut microbiota is one of the complicated eco-systems in human body.A large amount of bacteria colonize in the healthy human intestine, which not only play a variety of biological functions, but also are associated with various diseases.By adding microecological agents (probiotics, prebiotics, and synbiotics), we are able to improve the gut microbiota structure and reduce the related carcinogenic metabolites, and also to improve the clinical manifestations of certain diseases.Therefore, it is meaningful to apply microecological agents (probiotics, prebiotics, and synbiotics) both in healthy population and patients.We reviewed the researches on microecological aspect of gut microbiota-related diseases, aiming to shed some light on fully understanding and popularizing of the application of microecological agents among different populations.
		                        		
		                        		
		                        		
		                        	
10.Effect of high-fat diet on 1,2-dimethylhydrazine-induced colon tumors
Wen WU ; Qingchao ZHU ; Yongzhi YANG ; Chenzhang SHI ; Renyuan GAO ; Huanlong QIN
Chinese Journal of Clinical Nutrition 2014;22(3):171-177
		                        		
		                        			
		                        			Objective To explore the effect of fat on 1,2-dimethylhydrazine (DMH)-induced colon tumors.Methods A total of 50 7-week-old male Wistar rats were further divided into four groups:standard diet feed control group (n =10),standard diet feed plus DMH-induced tumor group (SDT,n =15),high-fat diet feed control group (n =10) and high-fat diet feed plus DMH-induced tumor group (HFDT,n =15).Rats were killed 18 weeks later,and enzyme-linked immunosorbent assay was used to detect serum triglyeeride,tumor necrosis factor (TNF-α),and colonic TNF-α,interleukin-6.After the intestinal tracts were removed,the location,amount,and size of the tumors were observed.The pathological changes of the tissue sections were observed,and the distributions of TNF-α and Ki-67 in the normal tissues and tumors were detected by immunohistochemistry.Results Upon the completion of the study,the mortality rate of rats was 20.00% in the SDT group and 26.67% in the HFDT group,the tumor formation rate was 75.00% in the SDT group and 81.82% in the HFDT group,and the tumor-bearing rate was 117% in the SDT group and 191% in the HFDT group.No statistical significance difference between the two groups in mortality rate,tumor formation rate (P =0.545) and tumor bearing rate (x2 =1.343,P =0.247).The average tumor volume was significantly different between the standard diet feed control group and high-fat diet feed control group (28.57% vs 66.67%,P =0.030).Also,the serum triglyceride and TNF-α levels significantly differed between the SDT group and HFDT group [TG (1.39 ± 0.31) mmol/L and TNF-α (124.80 ± 21.69) ng/L in the HFDT group and TG (0.46 ±0.20) mmol/L and TNF-α (85.83 ± 17.45) ng/L in the SDT group] (P =0.000).The expressions of TNF-α,IL-6,and Ki-67 in colonic mucosa were significantly higher in the high-fat diet feed control group than in the standard diet feed control group [TNF-α:(6.22 ± 0.63) ng/g vs (2.33 ± 0.44) ng/g,P=0.020; IL-6:(13.50±0.67) ng/gvs (7.31 ±0.41) ng/g,P=0.000; and Ki-67:40% vs 10%,P =0.028].The Ki-67 expression rate was 90.48% in the HFDT group,compared to 50% in the SDT group (P =0.015).Conclusions High-fat diet can increase the serum triglyceride and TNF-α levels in rats,upregulate the expressions of TNF-α,IL-6 and Ki-67,and thus promote inflammation and cell proliferation,and ultimately affect the tumor formation and development.However,the effect of fat on DMH-induced colon tumors warrants further studies.
		                        		
		                        		
		                        		
		                        	
            
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