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BACKGROUND:Diabetic nephropathy is an important cause of end-stage renal disease,and intestinal barrier damage plays an important role in the occurrence and development of diabetic nephropathy. OBJECTIVE:To observe the protective effect of human umbilical cord mesenchymal stem cells on the intestinal barrier in rats with diabetic nephropathy. METHODS:Thirty 8-week-old male SD rats were randomly assigned to healthy control group,model group and human umbilical cord mesenchymal stem cell group,with 10 rats in each group.Rats in the human umbilical cord mesenchymal stem cell group were injected with 1×106 human umbilical cord mesenchymal stem cells through the tail vein once a week for 4 weeks after the model establishment of diabetic nephropathy.Rats in the healthy control group and the model group were injected with an equal volume of PBS at the same time.1 week after the last injection,the histomorphological changes in the kidney and colon were observed under a light microscope.The expressions of ZO-1 and Occludin in the colon tissue of rats were detected by immunohistochemistry.Serum D-lactic acid and lipopolysaccharide levels were detected by ELISA.In addition,the distribution of human umbilical cord mesenchymal stem cells labeled with DiR dye in rats was observed by in vivo imaging system.The expression of human mesenchymal stem cell surface marker antigens CD44 and CD90 in colon tissue was detected by immunohistochemistry. RESULTS AND CONCLUSION:(1)Compared with the model group,human umbilical cord mesenchymal stem cell transplantation significantly inhibited the increase of urea nitrogen,serum creatinine,24-hour urine protein level and urinary albumin/creatinine ratio in diabetic nephropathy rats(all P<0.05).(2)The expression of human mesenchymal stem cell surface markers CD44 and CD90 was found in the colon of diabetic nephropathy rats.(3)Compared with the healthy control group,the expression levels of tight junction proteins Occludin and ZO-1 in the colon tissue of the model group were significantly reduced,while the expressions of Occludin and ZO-1 were significantly increased after treatment with human umbilical cord mesenchymal stem cells.(4)Compared with the model group,human umbilical cord mesenchymal stem cell transplantation significantly reduced serum D-lactic acid and lipopolysaccharide levels in diabetic nephropathy rats.(5)The results suggest that human umbilical cord mesenchymal stem cells may protect the intestinal barrier function by enhancing the expression of intestinal tight junction proteins in diabetic nephropathy rats.
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Objective:To study the structure and diversity of intestinal flora in IgA nephropathy (IgAN) patients, and to explore the correlation of intestinal microorganisms with clinical indicators and renal pathology.Methods:Fifteen IgAN patients in the First Affiliated Hospital of Baotou Medical College from May 2020 to September 2020 were retrospectively enrolled as IgAN group, and 8 healthy families and 7 health checkups were enrolled as healthy control group. Illumina high-throughput sequencing technology was performed for DNA sequencing in the 16S rDNA-V4 region of all bacteria in the feces sample. QIIME 2 was used to process and analyze original sequence, compared with Greengenes (V138) database. The DADA2 software was called to denoise the data, which was equivalent to a 100% similarity cluster (OTU was a 97% similarity cluster). PCoA was used to analyze the structure and diversity of intestinal flora. Spearman correlation or Pearson correlation analysis was used to analyze the correlation of differential flora with renal pathology and clinical indicators.Results:(1) The intestinal microbial β diversity in IgAN patients was significantly different from that in healthy controls ( P=0.010). (2) Compared with the healthy control group, the numbers of intestinal flora species in IgAN group were significantly increased in 1 phylum, 3 families and 22 genus. At the levels from phylum to family, the species numbers of Firmicutes and Ruminococcaceae in IgAN patients reduced than those in healthy controls and the species numbers of Chloroflexi, Gaiellaceae, Staphylococcaceae and Family-XⅢ in IgAN patients increased than those in healthy controls (all P<0.05). At the genus level, compared with the healthy controls, the species number of Subdoligranulum in IgAN patients was significantly reduced ( P=0.020), and the species number of Ruminococcus- gnavus- group was significantly increased ( P=0.004). (3) At the phylum level of the species number, Firmicutes in IgAN patients was positively correlated to albumin (ALB) ( r=0.637, P=0.037) and IgG ( r=0.452, P=0.046), Gemmatimonadetes was negatively correlated to serum creatinine ( r=-0.453, P=0.045), Verrucomicrobia was negatively correlated to IgM ( r=-0.450, P=0.046), and Patescibacteria was positively correlated to IgA ( r=0.469, P=0.037). At the genus level of the species number, Ruminococcus- gnavus- group ( r=-0.614, P=0.004) and Megamonas ( r=-0.451, P=0.042) were negatively correlated to ALB; Subdoligranulum was positively correlated to ALB ( r=0.563, P=0.009); Dialister was negatively correlated to C3 ( r=-0.427, P=0.041) and was positively correlated to IgA ( r=0.434, P=0.035); Veillonella was positively correlated to estimated glomerular filtration rate ( r=0.452, P=0.043). The species numbers of Eisenbergiella ( r=-0.850, P=0.007), Holdemania ( r=-0.845, P=0.008), Flavonifractor ( r=-0.845, P=0.008), and Ruminiclostridium- 9 ( r=-0.845, P=0.008) were negatively correlated to glomerulosclerosis or adhesion (S) of Oxford classification; the species number of Fusicatenibacter was negatively correlated to mesangial hypercellularity ( r=-0.845, P=0.008); the number of Coprococcus- 2 was positively correlated to S ( r=0.738, P=0.037) and tubular atrophy or interstitial fibrosis ( r=0.756, P=0.030). (4) Random forest model was built with Ruminococcus- gnavus- group and Subdoligranulum, after fitting the area under the receiver operating characteristic curve was 0.927. Conclusions:The intestinal flora of IgAN patients is different from that in healthy subjects. Changes of intestinal flora in IgAN patients are related to clinical indicators and renal pathology. In particular, Ruminococcus- gnavus- group and Subdoligranulum may play an important role in IgAN.
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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.
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Objective To explore the influencing factors of the vaginal birth after cesarean section (VBAC), and establish a model for predicting the risk of trial of the trial of labor after cesarean section (TOLAC). Methods From January 2016 to December 2018, total 694 pregnant women who underwent TOLAC in Northwest Women's and Children's Hospital were retrospectively analyzed. Those cases were divided into two groups according to the mode of delivery: the VBAC group and the failed TOLAC group. At the same time, 700 cases in the elective repeat cesarean section (ERCS) group were randomly selected as control group. The influencing factors of VBAC were analyzed by univariate and multivariate logistic regression, and the pregnancy outcomes between the three groups were compared. Results (1) The VBAC rate was 76.1% (528/694) and 166 women underwent the failed TOLAC (23.9%, 166/694). (2) Univariate analysis found that, the pre-pregnancy body mass index (BMI) [(22.0±3.0),(23.3±2.7) kg/m2], the previous vaginal delivery history [10.4%(55/528),3.6%(6/166)], the cervical score (5.2±1.9,4.3±1.6) and the neonatal birth weight [(3 315 ± 468), (3 484 ± 274) g] of the VBAC group were significantly different from the failed TOLAC group (P<0.05). (3) The comparison of pregnancy outcomes: the neonatal birth weight was (3 315± 468) g, and the intrapartum hemorrhage volume was (255 ± 121) ml in the VBAC group, which were significantly lower than those in the failed TOLAC group [intrapartum hemorrhage (325 ± 173) ml] and the ERCS group [(3 572±344) g, (281±125) ml], there were statistically significant differences in the comparison among the three groups (all P<0.05). Two cases of bladder injury occurred during cesarean section in the TOLAC failure group (1.2%,2/166). The rates of the blood transfusion, puerperal infection, 5-minute Apgar score and neonatal ICU admission among the three groups were no statistically significantly different (all P>0.05). There was no maternal or perinatal death. (4) Multivariate logistic regression analysis showed that the delivery age of pregnant women ( OR=0.92, 95% CI : 0.87-0.98), pre-pregnancy BMI ( OR=0.92, 95% CI :0.86-0.98), vaginal delivery history ( OR=3.31, 95% CI : 1.35-8.01), cervical score ( OR=1.29, 95% CI :1.13-1.42) and the birth weight of the neonates <3 300 g ( OR=3.15, 95% CI : 2.02-4.90) were independent influencing factors for VBAC. The area under curve of the receiver operating characteristic curve was 0.74. Conclusions The influencing factors of VBAC are delivery age, pre-pregnancy BMI, vaginal delivery history, cervical score and neonatal birth weight <3 300 g. The adequate individualized management and assessment of the TOLAC may be helpful to improve the VBAC rate.
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Objective To study the incidence and risk factors of new foot ulcer among diabetic patients on peritoneal dialysis.Methods This is a single-center prospective cohort study.Clinically-stable diabetic patients on peritoneal dialysis in our renal division were recruited from January 2014 to June 2014.Baseline data including general information,biochemistry data,dialysis adequacy,the dorsalis pedis artery pulse,clinical symptoms of diabetic foot and ankle brachial index were recorded.All patients were followed till to Dec 31,2015.The outcomes consisted of new foot ulcer,amputation due to foot ulcer or gangrene,and lower limb vascular blood supply revascularization.Results Totally 108 patients were recruited and followed up the average time (17.7±5.6) months.Among 108 patients,16 cases had a history of diabetic foot ulcer,and 1 case had amputation.During the follow-up,11 cases (10.2％) had new foot ulcer,3 cases (2.8％) had amputation due to foot ulcers or gangrene,and 8 cases (7.4％) had lower limb vascular blood supply revascularization.A total of 13 cases (12％) had composite end points with 81.3 times/1000 patients of incidence.Univariate and multivariate Cox regression models showed that the history of foot ulcer was the only independent risk factors for new foot ulcers-related composite end points.Conclusion The incidence of new foot ulcer-related composite end points was 12％,which could be independently predicted by the history of diabetic foot ulcer.
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Objective To study the incidence and risk factors of new foot ulcer among diabetic patients on peritoneal dialysis.Methods This is a single-center prospective cohort study.Clinically-stable diabetic patients on peritoneal dialysis in our renal division were recruited from January 2014 to June 2014.Baseline data including general information,biochemistry data,dialysis adequacy,the dorsalis pedis artery pulse,clinical symptoms of diabetic foot and ankle brachial index were recorded.All patients were followed till to Dec 31,2015.The outcomes consisted of new foot ulcer,amputation due to foot ulcer or gangrene,and lower limb vascular blood supply revascularization.Results Totally 108 patients were recruited and followed up the average time (17.7±5.6) months.Among 108 patients,16 cases had a history of diabetic foot ulcer,and 1 case had amputation.During the follow-up,11 cases (10.2％) had new foot ulcer,3 cases (2.8％) had amputation due to foot ulcers or gangrene,and 8 cases (7.4％) had lower limb vascular blood supply revascularization.A total of 13 cases (12％) had composite end points with 81.3 times/1000 patients of incidence.Univariate and multivariate Cox regression models showed that the history of foot ulcer was the only independent risk factors for new foot ulcers-related composite end points.Conclusion The incidence of new foot ulcer-related composite end points was 12％,which could be independently predicted by the history of diabetic foot ulcer.
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Objective Toanalyzedrugfreeforpatientswithseverementalillnessandfollow-upof82cases, inordertoprovidebasisforthedivisionoffreedelivery.Methods 82severementalillnesspatientswhowereincon-formity with the conditions of rescue,were given free drug and followed up for 2 years.Before the admission and fol-lowed up for 2 years,the social function evaluation(SDSS)and compliance were evaluated,the recurrence rate was compared.Results Comparisonofcompliance:beforetheadmission,thecompletecompliancein33cases,thepartial compliance in 27 cases,22 cases of non-compliance;After 2 years follow-up,the complete compliance in 52 cases, the partial compliance in 21 cases,9 cases of non-compliance.The difference was statistically significant(u=3.34, P<0.01).Comparison of social function:social withdrawal:before the admission (1.32 ±0.75)points,after 2 years follow-up (0.96 ±0.34)points,the difference was statistically significant(t=3.93,P<0.001 );Family activities:before the admission (1.44 ±0.69)points,after 2 years follow-up (0.87 ±0.31)points,the difference was statisti-cally significant (t=6.78,P<0.001);Personal care:before the admission (1.29 ±0.68)points,after 2 years follow-up (0.95 ±0.62)points,the difference was statistically significant(t=3.33,P<0.001);Interest in the outside world:before the admission (1.23 ±0.63)points,after 2 years follow-up (0.97 ±0.41)points,the difference was statistically significant(t=3.05,P<0.025);The total score:before the admission (15.42 ±7.23)points,after 2 years follow-up (9.56 ±6.89)points,the difference was statistically significant(t=5.28,P<0.001).Compari-son of the recurrence rate:2 years before the admission,the recurrence in 33 cases (40.2%),after 2 years follow-up the recurrence in 15 cases(18.3%),the difference was statistically significant (χ2 =10.64,P<0.001).Conclusion Drug free for patients with severe mental illness and follow-up can improve the social function and the implementation of free administration of patients with severe mental illness,and reduce the recurrence rate and improve compliance.
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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.
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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.
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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.
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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