1.Identification of key genes and pathways in minimal change disease by bioinformatics analysis
Yaping FANG ; Yan MI ; Caili WANG
Chinese Journal of Nephrology 2021;37(2):130-136
Objective:To identify the differentially expressed genes and pathways of minimal change disease (MCD) by bioinformatics analysis, and to explore the pathogenesis of MCD.Methods:The gene expression omnibus (GEO) under the National Center for Biotechnology Information (NCBI) platform of the United States was used, and the data chips GSE104948 and GSE104954 containing MCD information were selected. The data set contained the gene expression array data of 19 cases of MCD renal biopsy tissue and 36 cases of normal renal tissue. The online tool GEO2R was used to analyze data and screen differentially expressed genes, and DAVID 6.8 database was used to perform GO and KEGG functional enrichment analysis of differentially expressed genes and network analysis of genes involved in metabolic pathways. The String 11.0 database and Cytoscape 3.7.2 software were used to analyze the relationship between MCD differentially expressed genes and perform visual analysis. At the same time, the CytoHubba plug-in was used to analyze the degree of association of protein interaction networks and screen key expressed genes.Results:A total of 302 highly expressed differentially expressed genes were identified by online tool GEO2R. GO analysis showed that the products of these differential genes were mostly located in the extracellular matrix, exosomes, pernucleus and other regions, exerting cell adhesion molecule binding, deoxycytidine deaminase activity, protein homodimerization activity, 2'-5'-oligoadenylic acid synthase activity and other functions, as well as participating in the formation of extracellular matrix, cell lysis, cell apoptosis, inflammatory response, immune response and other biological processes. KEGG analysis showed that differentially expressed genes were enriched in local adhesion, NOD-like receptor and other signal pathways. Combining the results of GO analysis and Cyto Hubba analysis, the PYCARD gene was screened out as the key gene that induced the inflammatory response in MCD kidney. Conclusions:The inflammatory response may be involved in the occurrence and development of MCD, and the PYCARD gene may be a key gene in the induction of inflammatory response in MCD.
2.Study on relationship between polymorphism of TNF-?and IgA nephropathy of Han nationality Chinese in inner Mongolia Autonomous Region
Cheng WANG ; Caili WANG ; Lijun GAO ; Tianlin JU ; Wenbin QIN
Chinese Journal of Clinical Laboratory Science 2006;0(03):-
Objective To study the relationship of tumor necrosis factor beta (TNF-?) polymorphism with human IgA nephropathy of Chinese Han nationality in Inner Mongolia Autonomous Region. Methods The A→G single base mutation polymorphism in TNF-?1096 locus were analyzed among 80 normal controls and 79 IgA nephropathy patients by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results The genotype frequencies of TNF?* 1/1 and TNF?* 2/2 in IgA nephropathy patients were significantly higher than that in normal controls (x1/12=5.58,P
3.Impact of endoscopic sphincterotomy and bile duct exploration with open surgery on inflammatory response and immune function
Lan FANG ; Chaoliang LI ; Bin WANG ; Caili LI ; Zequn SUN
Chinese Journal of Digestive Endoscopy 2012;29(10):577-580
Objective To evaluate the impact of endoscopic sphincterotomy (EST) and bile duct exploration with open surgery on immune function and inflammatory response.Methods Fifty-one patients with choledocholithiasis were divided into endoscopy group ( EG,n =24) and laparotomy group ( LG,n =27 ) according to the patients' will from June 2010 to February 2012.Procalcitonin( PCT),C-reactive protein (CRP),immunoglobulins (IgA 、lgG 、IgM ) and T lymphocyte (CD4、CD8 ) of peripheral blood were examined preoperatively and on the 1st,3rd and 5th day postoperatively.Results Compared with preoperative levels,postoperative levels of serum PCT and CRP were higher in both groups (P <0.01 ),but on the 3rd day after the operation,the changes of PCT and CRP levels in the two groups were not significantly different ( P > 0.05 ).Postoperative levels of serum immunoglobulins of two groups were lower than preoperative levels (P < 0.01 ),but the IgA and IgM levels in EG were significantly higher than those in the LG (P < 0.05),and IgG levels in the two groups were not significantly different after surgery ( P > 0.05 ).Compared with preoperative levels,postoperative levels of CD4,CD8 and CD4/CD8 ratio in EG were only slightly decreased (P > 0.05 ),and returned to the preoperative levels on the 5th day postoperatively,but postoperative levels of these variables in LG were decreased significantly ( P < 0.05).Postoperative levels of CD4,CD8 and CD4/CD8 ration of the two groups were significantly different (P < 0.05).Conclusion Both EST and bile duct exploration with open surgery can inhibit immune function and induce inflammation,but the procedure of EST,which may mainly affect humoral immune function,has impact on immune function less intensely.
4.Association of MYH9 gene single nucleotide polymorphism with clinic,pathology and prognosis of IgA nephropathy patients among Han nationality population in Inner Mongolia
Caili WANG ; Yuanqing TIAN ; Liping LIU ; Niya JIA ; Lei NAN
Chinese Journal of Nephrology 2012;(10):780-784
Objective To study the association of MYH9 gene single nucleotide polymorphism (SNP) with clinical manifestation,pathology and prognosis of IgA nephropathy (IgAN) patients of Han nationality population in Inner Mongolia Autonomous Region.Method One hundred and forty-eight IgAN patients proven by biopsy were enrolled in the study.Fifty-six patients were followed up for 1-97 months.DNA was extracted from the peripheral blood of above patients.PCR restriction fragment length polymorphism (RFLP) assay was used to detect the single nucleotide polymorphisms of MYH9 gene Rs3752462,Rs4821480 sites.Association of different genotypes with clinical features,pathology and prognosis im patients with IgA nephropathy was examined.Result (1) Rs3752462 site was consistent with Hardy-Weinberg equilibrium,while Rs4821480 site did not meet the Hardy-Weinberg equilibrium.(2) IgAN patients with MYH9 gene Rs3752462 site TF genotype had lower systolic blood pressure as compared to those with CC +CT genotype (P<0.05).There were significant differences in systolic blood pressure,diastolic blood pressure and age between patients with Rs4821480 site GG genotype and patients with TT or GT genotype (P<0.05).There were no significant differences in Scr,Ccr,plasma albumin,hemoglobin,microscopic hematuria,proteinuria,pathological HASS classification,pathological lesion among Rs4821480 site GG,TT,GT genotypes.(3) Kaplan-Meier survival analysis revealed the time from renal biopsy to renal function decline was shorted in patients with Rs3752462 site CC genotype and Rs4821480 site TT genotype.Conclusions C allele of MYH9 gene Rs3752462 site is an independent risk factor of high blood pressure damage in IgAN patients.Polymorphism of 3 genotypes of MYH9 gene Rs4821480 site is associated to the prognosis of patients.Carrying Rs3752462 site C allele and Rs4821480 site T allele may affect the prognosis of patients.
5.Inflammatory and immune responses in a rat model of intermittent hypoxia-emphysema
Shuangyu HAN ; Caili LI ; Jing FENG ; Yubao WANG
Tianjin Medical Journal 2016;44(1):14-18
Objective To develop anoverlap syndrome (OS)rat model by intermittent hypoxia (IH) exposure on the base of pre-existing emphysema, and to explore its characters of severe systemic inflammation and immune responses. Methods Sixty Wistar rats were put into four groups:control group, IH group, emphysema group and overlap (emphysema+IH) group. The peripheral blood samples were collected for detecting apoptosis of CD3+CD4+,CD3+CD8+T lymphocytes and neutrophils (PMN). Tumor necrosis factor (TNF)-αand interleukin (IL)-6 were evaluated by ELISA. The bronchoalveolar la-vage fluid (BALF) was taken to calculate the ratio of macrophages, neutrophils and lymphocytes under light microscope. Tis-sue blocks of lung, liver, pancreas, and right carotid artery were taken for pathologic scoring. Results The apoptotic rates of PMN and CD3 +CD8 +T cells were significantly lower in overlap group than those of other three groups (P<0.05). Pro-in-flammatory factor IL-6, TNF-αand peripheral blood CD3 +CD4 +T cell apoptosis were the highest in overlap group com-pared to those of other three groups (P<0.05). The ratio of PMN and macrophages in BALF were significantly higher in em-physema group than those of other three groups (P<0.05) and the pathology scores of lung, liver, pancreas, the ratio of carot-id artery intima-media thickness of whole thickness of vascular were significantly higher in overlap group than those of other three groups (P < 0.05).Conclusion In rat model of intermittent hypoxia-emphysema there are more serious systemic multi-organ inflammation and immune responses.
6.Mice with focal segmental glomerular sclerosis are induced by adriamycin and its mechanism
Yaqin KANG ; Caili WANG ; Yan MI ; Dandan ZHOU
Chinese Journal of Nephrology 2016;32(8):617-622
Objective To establish adriamycin-induced focal segmental glomerular sclerosis(FSGS) mice model,and observe the expressions of and relation between oxidative stress and p38 MAPK signal pathway in renal injury.Methods Eight-week-old male Balb/c mice were randomly divided into FSGS group (n=20) and control group (n=20).In FSGS group mice were intravenously injected with a single dose of adriamycin (0.01 rag/g),and mice in control group were received saline with the same dose.At day 3,7,14,22 and 32,urine protein-to-urine creatinine ratio (P/C) was detected.At day 22 and 32,serum creatinine,blood urea nitrogen,nitric oxide (NO) and reactive oxygen species (ROS) in blood and urine,and ROS in kidney tissues were detected;changes of pathological morphology in renal tissue were analyzed by HE stain;the expressions of NF-κB,CD36,IL-13,BAX and Bcl-2 mRNA were detected by real time quantitative PCR;the expressions of NF-κB,p-p38 and p-ERK1/2 protein were detected by Western blotting.Results Compared with that in control group,P/C was gradually increasing in FSGS group,and peaked at day 22 (P < 0.05).At day 22 and 32,mice had higher creatinine,serum creatinine,urea nitrogen,ROS and NO in FSGS group than those in control group (all P < 0.05).There were mild hyperplasia of mesangial cells and mesangial matrix,segment with moderate exacerbations,podocytes with significant proliferation,and the capillary loops of the stenosed in the glomerular in FSGS group at day 32.Compared with those in control group,the mRNA expression of NF-κB,BAX,IL-13 and CD36,and the protein expressions of NF-κB and p-p38 MAPK were gradually increased in FSGS group,all showed statistical differences at day 32 (all P< 0.05);the expression of p-ERK1/2 was increased at day 22 (P < 0.05) but was reduced at day 32 (P < 0.05).Conclusions Adriamycin has induced FSGS in mice successfully,which may through oxidative stress activating p38,up-regulating NF-κB,increasing the inflammatory cytokines and inducing apoptosis pathways.
7.Investigation and analysis of the gastrointestinal symptoms in patients with chronic obstructive pulmonary disease
Caili LI ; Yue LIU ; Zequn SUN ; Bin WANG
Chinese Journal of Postgraduates of Medicine 2014;37(16):8-11
Objective To investigate the gastrointestinal symptoms in patients with chronic obstructive pulmonary disease (COPD) and explore its possible reasons.Methods Thirty-six patients with stable COPD were divided into mild group [21 cases,forced expiratory volume in first second (FEV1) measured values/predictive values ≥50%] and severe group (15 cases,FEV1 measured values/predictive values < 50%) according to the pulmonary function.Replacement of 19 healthy volunteers as control group.The patients and volunteers completed the Gastrointestinal Symptom Rating Scales (GSRS) scores and received electrogastrography,the plasma vasoactive intestinal peptide (VIP) and intestinal fatty acid binding protein (Ⅰ-FABP) were detected.Results The GSRS scores in severe group and mild group was higher than that in control group[(17.73 ± 4.64),(14.29 ± 5.44) scores vs.(8.00 ± 2.29) scores],and severe group was higher than that in mild group,there was significant difference (P < 0.05).The percentage of normal slow waves of fasting and postprandial,the percentage of bradygastria in severe group and mild group were lower than those in control group,there were significant differences(P < 0.05).The level of VIP in severe group was lower than that in mild group and control group [(36.07 ± 9.22) μ g/L vs.(44.16 ± 7.88),(46.53 ± 4.54) μ g/L],the level of I-FABP was higher than that in mild group and control group [(35.80 ± 11.69) μ g/L vs.(27.40 ±9.53),(23.58 ±8.18) μg/L],there was significant difference (P <0.05),but there was no significant difference between mild group and control group (P > 0.05).Conclusion The patients with COPD are accompanied with serious gastrointestinal symptoms and gastric dysrhythmia,severe COPD can be associated with VIP decrease and Ⅰ-FABP rise in peripheral blood.
8.Effect of Simo Decoction on Gastrointestinal Motility in Patients with Chronic Obstructive Pulmonary Disease
Caili LL ; Yue LLU ; Yongshun ZHANG ; Zequn SUN ; Bin WANG
Chinese Journal of Gastroenterology 2015;(5):283-286
Background:Gastrointestinal dysmotility is frequently seen in patients with chronic obstructive pulmonary disease ( COPD). Simo Decoction is used for promoting gastrointestinal motility in clinical practice. Aims:To study the effect of Simo Decoction on gastrointestinal symptoms and motility in patients with COPD. Methods:Thirty-six patients with stable COPD in Shiyan Renmin Hospital from Sep. 2012 to Jun. 2013 were enrolled and received a 28-day course treatment of Simo Decoction oral solution,19 healthy volunteers were served as controls. All subjects were assessed with gastrointestinal symptom rating scale(GSRS). Electrogastrography was performed and levels of vasoactive intestinal peptide(VIP)and intestinal fatty acid-binding protein( I-FABP)in peripheral blood were measured. Patients with COPD were re-examined for the above-mentioned parameters after treated with Simo Decoction. Results:The baseline GSRS score and serum I-FABP level in COPD patients were significantly increased as compared with controls(P<0. 05),while the baseline serum VIP level,as well as the fasting and postprandial normal gastric slow wave percentage in COPD patients were significantly decreased(P <0. 05). After 28-day course of Simo Decoction treatment,all these parameters in COPD patients were improved as compared with those before treatment(P<0. 05),serum levels of VIP,I-FABP and normal gastric slow wave percentage were similar to those of controls. Conclusions:Simo Decoction can ameliorate the gastrointestinal symptoms and dysmotility in patients with COPD. The regulatory effect of Simo Decoction on gastrointestinal motility might be bidirectional.
9.Association between polymorphisms in non-muscle myosin heavy chain 9 gene and hypertension susceptibility in chronic kidney disease patients
Liping LIU ; Yanhui ZHANG ; Junying FAN ; Caili WANG
Chinese Journal of Nephrology 2013;29(9):665-669
Objective To explore the association between polymorphisms in non-muscle myosin heavy chain 9 gene (MYH9) and hypertension susceptibility in chronic kidney disease (CKD)patients.Methods Five hundred and ninety-five persons,including 301 patients with CKD and 294 healthy controls,were enrolled in the study.Two single nucleotide polymorphisms (SNPs) (rs3752462,rs4821480) were genotyped by TaqMan assay or a restriction fragment length polymorphism assay for a further case-control study.The discrepancies of the patients'quantitive traits (including age,sex,systolic and diastolic blood pressure,frequency of different primary diseases and using different kinds of antihypertensive drugs) among different genotypes of the two MYH9 SNPs were analyzed.Meanwhile,the association between polymorphisms in MYH9 and hypertension susceptibility in CKD patients were analyzed in the rs3752462 site.Results The systolic blood pressure of CT genotype patients [(147.94± 27.40) mm Hg] was significantly higher than that of C C genotype patients [(136.43 ± 19.09)mm Hg] by single factor analysis of variance (P < 0.05).The frequency of using all kinds of antihypertensive drugs for CC genotype patients (7.4%) was lower than that of TT (43.9%) and CT (48.7%) genotype patients (P < 0.05).After correcting the age factor,the result of Logistic regression analysis showed that CC genotype was a protective factor of systolic blood pressure increasing.The probability of high blood pressure for CT genotype patients with CKD was 0.175 times than that of CC genotype (95% CI 0.071,0.431).Conclusions The CKD patients who carry the rs3752462 site CC genotype of MYH9 gene are not prone to high blood pressure.Polymorphism of MYH9 gene rs3752462 site is associated with systolic blood pressure in CKD patients.It may indicate that allele C mutation for T can lead to the increase in systolic blood pressure.
10.The clinical pharmacokinetics and bioequivalence of benzoylmetronidazole capsules
Jianshi LOU ; Jianjie JIAO ; Hongrong WANG ; Caili ZHANG
Chinese Pharmacological Bulletin 1987;0(01):-
AIM To compare the pharmacokinetics and bioequivalence of between capsule and solution of benzoylmetronidazole. METHODS Ten chinese healthy male volunteers in a randomized 2-way crossover study were given a single oral dose 960 mg capsule(test) and solution (control) respectively. The serum concentrations of metronidazole, one of the metabolites of benzoylmetronidazole, was measured by high performance liquid chromatography. RESULTS The serum concentration-time curves appeared one-compartment open model. The results of the capsule and the solution of benzoylmetronidazole showed that T max (5.10?1.60) h and (3.12?0.90) h; C max (5.32?0.87) mg?L -1 and (6.51?1.25) mg?L -1 ; T 12 (10.56?1.75) h and (10.16?1.65) h; AUC (106.96?19.62) mg?h -1 ?L -1 and (113.59?19.84) mg?h?L -1 . CONCLUTION No significant difference appears in the pharmacokinetic parameters between the two formulations except of T max and C max ( P