1.Association between inflammatory factors and breast cancer: a Mendelian randomization study
SONG Wenfu ; GUAN Xutao ; WANG Bing ; SUN Shiling ; LI Yingying
Journal of Preventive Medicine 2024;36(8):714-717,722
Objective:
To examine the causal relationship between inflammatory factors and breast cancer using two-sample Mendelian randomization (MR) approach, so as to provide the basis for the prevention and treatment of breast cancer.
Methods:
Data of 91 inflammatory cytokines (n=14 824) and 5 subtypes of breast cancer (n=247 173) were collected from genome-wide association studies (GWAS). Single nucleotide polymorphism (SNP) associated with 91 inflammatory factors were selected as instrumental variables. MR analyses were performed using the inverse-variance weighted (IVW) method with inflammatory factors as exposure factors and breast cancer as outcome variables. The risk of type I error and the effect of multiple testing were reduced using the FDR correction method. The stability and reliability of the results were verified using Steiger test of directionality, MR-Egger regression, MR-PRESSO test and leave-one out method.
Results:
Twenty-three inflammatory factors, including β nerve growth factor, interleukin-5, cystatin D and C-X-C chemokine ligand 1 were statistically associated with breast cancer (all P<0.05). After FDR adjustment, only evaluated abundance of oncostatin-M was found to be statistically associated with an increased risk of Basal-like (triple-negative) breast cancer (OR=1.186, 95%CI: 1.081-1.302, P=0.001, q=0.029), and the other 22 inflammatory factors had a high risk of type I error (all q>0.1). The sensitivity analysis indicated that the results were robust. No instrumental variables were found to have a significant impact on the results, which could exclude the influence of heterogeneity, horizontal pleiotropy, and reverse causality on the outcome.
Conclusion
The increased abundance of oncostatin-M may increase the risk of Basal-like (triple-negative) breast cancer.
2.Role and mechanism of human Kupffer cells in liver allo-geneic transplantation
Changxi ZHANG ; Wenbiao XIE ; Xutao LIN ; Fan ZHANG ; Qinghai GUAN ; Qiangpu CHEN
Chinese Journal of Hepatobiliary Surgery 2010;16(7):520-523
Objective To explore the possible role and mechanism of the Kupffer cells (KCs) in liver allo-geneic transplantation at the early stage. Methods In vitro cell contact coculture system was established. Culture supernatants were collected respectively on the 1st, 2nd, 4th, 6th d after cocul-ture and the KCs and PBMCs were harvested on the 6th day after culture. The expression of HLA-G on the membrane of the KCs and PBMCs was detected with immunochemistry. Nitrate reduction test was used to determine the concentration of nitric oxide. IFN-γ, IL-10, TGF-β1 cytokine levels in the supernatants were also measured with ELISA. The proliferation of lymphocytes was evaluated with MTT. Results six days later, no HLA-G molecules were detected on the membrane of the KCs and PBMCs. In the experimental group containing KCs, the levels of NO, IL-10 and TGF-β1 was signifi-cantly increased(P<0. 05), while the levels of IFN-γ was relatively lower(P<0. 05) as compared to the experimental group without KCs. No IL-10 and IFN-γ were detected in the control group, and on-ly few NO and TGF-β1 was found in the control group with KCs. MTT test showed that the value of optical density was lower in the experimental group with KCs than that in any other group(P<0. 05).Conclusion No HLA-G is expressed on the membrane of KCs and PBMCs after contact coculture.KCs may participate in regulating production of NO and Th2/Th3-like cytokines and suppressing the proliferation of lymphocytes, through which KCs probably take part in inducing immunotolerance of liver transplantation in early stage.
3.Effects of reinfusion of external drained bile and pancreatic juice on the outcome of pancreaticoduodenectomy
Changxi ZHANG ; Xutao LIN ; Qinghai GUAN ; Fan ZHANG ; Xingyuan ZHANG ; Qian HUANG ; Kun OU ; Qiangpu CHEN
Chinese Journal of Digestive Surgery 2011;10(5):351-355
Objective To investigate the effect of reinfusion of drained bile and pancreatic juice on the outcome of pancreaticoduodenectomy (PD).Methods The clinical data of 51 patients who received PD at the Affiliated Hospital of Binzhou Medical College from June 2005 to March 2009 were retrospectively analyzed.Nineteen patients received external drainage of bile and pancreatic juice ( ED group) and the other 32 patients received external drainage and intraintestinal administration of autologous bile and pancreatic juice (ID group).The daily volume of output of bile and pancreatic juice,intraoperative condition,tolerance of enteral nutrition,liver function and nutritional parameters of the 2 groups were detected.All data were analyzed by using chi-square test,Fisher exact test,independent t test,Mann-Whitney U test and one-way analysis of variance.Results The pulmonary infection rate of ID group was 3% (1/32) after operation,which was significantly lower than 26% (5/19) of the ED group (P < 0.05).The output of pancreatic juice in the ID group was significantly lower than that in the ED group since postoperative day 4 ( t =7.143,9.244,8.808,7.915,6.461,14.097,15.038,P < 0.05 ).There was no significant difference in the daily output of bile between the 2 groups.The incidence of diarrhea in the ID group was 9% (3/32) after nutritional support,which was significantly lower than 37% (7/19) of ED group (P<0.05).The duration of achieving targeted enteral feeding in the ID was 3 days,which was significantly shorter than 4 days of the ED group ( U =145.000,P < 0.05 ).The levels of total bilirubin ( TBil),direct bilirubin (DBil) and indirect bilirubin (IBil) were (261 ± 108 ),( 132 + 55 ) and ( 129 + 55 ) μmol/L in the ID group,and (239 ±92),( 12A ±46) and ( 116 ±46) μmol/L in the ED group before operation.The levels of TBil,DBil and IBil were (39 ± 19),(20 ± 10) and ( 19 +9) μmol/L in the ID group,and (55 ±22),(29 ± 12) and (26 ±11 ) μmol/L in the ED group at 12 days after nutritional support.There were significant differences in the decrease of TBil,DBil and IBil between the 2 groups ( t =7.324,8.437,5.827,P < 0.05 ).The levels of serum prealbumin,retinol binding protein and transferrin were (0.261 ± 0.021 ) g/L,(34.3 ± 2.8 ) mg/L,(3.08 + 0.26 ) g/L in the ID group,and (0.263 ±0.021)g/L,(33.8 +3.5)mg/L and (3.10 +0.27)g/L in the ED group before operation.The levels of serum prealbumin,retinol binding protein and transferrin decreased significantly after operation,and then got increased 3 days after nutritional support.The levels of serum albumin,retinol binding protein and transferrin were (0.238 ±0.025)g/L,(30.7 ±2.0)mg/L,(2.78 ±0.19)g/L in the ID group,and (0.222 +0.025)g/L,(29.3 ±2.1)mg/L and (2.63 +0.21)g/L in the ED group at 12 days after nutritional support.The levels of serum albumin,retinol binding protein and transferrin in the ID group were significantly higher than those in the ED group (t=4.615,6.097,4.913,P<0.05).Conclusion Reinfusion of external drained bile and pancreatic juice after PD could enhance the tolerance of patients in early enteral nutrition,reduce incidence of pneumonia,promote decrease of serum bilirubin and improve the nutritional status.