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Objective:To investigate the correlation between serum cystatin C (CysC) and clinical and pathological features of IgA nephropathy.Methods:Four hundred and twenty-one cases of primary IgA nephropathy diagnosed by renal biopsy in Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January 2010 to January 2021 were retrospectively analyzed. According to the serum CysC level at the time of renal biopsy, the patients were divided into high serum CysC group and normal serum CysC group, and the clinical data and pathological indices of the patients were compared. Spearman correlation analysis was used to analyze the correlation between estimated glomerular filtration rate (eGFR) and serum CysC. The clinicopathological factors related to the serum CysC level were analyzed by multiple linear regression. The area under the receiver operator characteristic curve (AUC) was used to evaluate the ability of serum CysC level to predict related pathological injury.Results:The age, prevalence of hypertension, serum creatinine, urea and uric acid levels of high serum CysC group were significantly higher than those of normal serum CysC group, while the eGFR level was significantly lower than that of normal serum CysC group ( P<0.05). Spearman correlation analysis showed that serum CysC was negatively correlated with eGFR ( r=-0.744, P<0.001). In terms of pathological injury, the degree of renal tubular atrophy and renal interstitial fibrosis (T) and renal arteriole wall thickening (A) in high serum CysC group were more serious than those in normal serum CysC group ( P<0.05). Multiple linear regression analysis showed that the prevalence of hypertension, serum creatinine, urea, uric acid, T and A were correlated with serum CysC levels (standard regression coefficient β=0.048, 0.299, 0.260, 0.134, 0.195, 0.068, respectively, P<0.05). After adding serum CysC on the basis of clinical features, the prediction efficiency of renal tubular atrophy and renal interstitial fibrosis was higher (AUC were 0.829 [95% CI 0.787-0.870], 0.847 [95% CI 0.808-0.886], P<0.05). Conclusions:Patients with older age, hypertension, poor renal function and severe pathological damage are more likely to have elevated serum CysC levels. Serum CysC was related to the prevalence of hypertension, creatinine, urea, uric acid, T and A. Combined with serum CysC level can effectively improve the ability prediction of T.
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@#B7-H3 is an immune checkpoint molecule overexpressed on the surface of a variety of tumors, and is is an ideal target for tumor immunotherapy. In this study, nitrolated T cell epitope designed in the early stage of the laboratory was used to construct an epitope vaccine that can target immune checkpoint B7-H3. The vaccine can significantly inhibit tumor growth in the CT26 colon cancer model, and has a significant synergistic effect with the PD-L1 protein vaccine. B7-H3 vaccine can increase the proportion of CD4+ T cells in splenic T lymphocytes and the proportion of CD8+ T cells in tumor-infiltrating T lymphocytes, while reducing the proportion of suppressor Treg cells in tumor-infiltrating CD4+ T lymphocytes, which effectively improves tumor immunosuppressive microenvironment. Research results suggest that the B7-H3 epitope vaccine can be used as an effective tumor vaccine candidate molecule.
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OBJECTIVE@#To explore the genotype-phenotype correlation in a child with Kabuki syndrome type 1 (KS1) caused by a mosaic frameshift variant of KMT2D gene.@*METHODS@#Trio-based whole exome sequencing (WES) was carried for the patient and her parents. Candidate variant was verified by Sanger sequencing.@*RESULTS@#The proband, a 3-year-and-2-month-old Chinese girl, presented with distinctive facial features, cognitive impairment, mild developmental delay, dermatoglyphic abnormalities, minor skeletal anomalies, ventricular septal defect, and autistic behavior. Trio-based WES revealed that the proband has carried a de novo mosaic frameshit variant of the KMT2D gene, namely NM_003482.3:c.13058delG (p.Pro4353Argfs*31) (GRCh37/hg19), for which the mosaicism rate was close to 21%. The variant was unreported previously and was confirmed by Sanger sequencing. Chromosomal microarray analysis (CMA) has revealed no pathogenic or likely pathogenic copy number variations. Compared with previously reported cases, our patient has presented obvious behavior anomalies including autism, anxiety and sleep problems, which were rarely reported.@*CONCLUSION@#This study has expanded the spectrum of KMT2D gene variants, enriched the clinical phenotypes of KS1, and facilitated genetic counseling for the family.
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Female , Humans , Infant , Abnormalities, Multiple , China , DNA Copy Number Variations , DNA-Binding Proteins/genetics , Face/abnormalities , Hematologic Diseases , Neoplasm Proteins/genetics , Phenotype , Vestibular DiseasesABSTRACT
@#Human immune system(HIS)mice are usually used to evaluate the ability of tumor vaccines to induce cytotoxic T lymphocyte(CTL)effects, but they failed to accurately reflect the ability of cancer vaccines to induce humoral immune responses. In this study, human peripheral blood mononuclear cells were isolated by density gradient centrifugation and co-transplanted into NCG mice with in vitro differentiated dendritic cells(DCs)to establish a DC-HIS mouse model. In DC-HIS mice, co-transplanted antigen-presenting cells(HLA-DR+CD11c+)could colonize the spleen of model mice. Moreover, co-transplantation of DCs significantly increased the proportion of activated human CD4+ T/CD8+ T cells and B cells in HIS mice, indicating that DC-HIS mice could better mimic the human immune responses. The immunogenicity of the targeted HER2 protein vaccine(NitraTh-HER2)was evaluated using the DCs-HIS mice. The results showed that the NitraTh-HER2 vaccine was able to induce the production of HER2-specific human IgG antibodies with a significant antibody-dependent cell-mediated cytotoxicity(ADCC)effect and the lysis rate of target cell SK-BR-3 reached 47. 1%. The NitraTh-HER2 vaccine was able to produce antigen-specific CTL effect, and the lysis rate of target cell SK-BR-3 reached 14. 6%. Taken together, the DC-HIS mouse model provides an effective method for predicting the immunogenicity of human tumor vaccines.
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@#Using the genetic code extension technology, the immunogenic amino acid, p-nitrophenylalanine, was introduced into the universal T cell epitope and then fused with the fragment of the extracellular region of the immune checkpoint molecular CD47(19-140)to construct a vaccine targeting CD47. The CD47-NitraTh vaccine elicited high titer antibody in BALB/c mice, significantly inhibited CT26 colon cancer cells growth, and increased the ratio of spleen CD4+ T cells and CD8+ T cells. Meanwhile, it promoted the polarization of naï ve T cells to Th1 cells. Notably, CD47-NitraTh not only increased the proportion of tumour-infiltrating lymphocytes but also reduced the proportion of Treg cells in tumour tissues, which means that CD47-NitraTh vaccine can remodel the tumour immunosuppressive microenvironment. The results of this study suggested that CD47-NitraTh can be used as an effective tumour vaccine candidate.
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Objective To study the association, clinical presentation, and diagnosis and treatment of bile duct cancer as a late complication of biliary-enteric anastomoses for benign diseases. Methods A retrospective study was carried out on 5 patients and the medical literature was reviewed. Results They were 3 males and 2 females. The average age was ( 66. 0 ± 0. 7 ) years. The average time period was ( 14. 0 ± 6. 1 ) years after biliary-enteric anastomosis. The clinical presentations included right upper quadrant pain, fever, chills and jaundice. CA19-9, CT and MRI were valuable in diagnosis. There were two patients with distal and three patients with perihilar cholangiocarcinomas (type IIIa, n=2, and type IV, n=1). Local resection with lymphadenectomy was carried out in one patient. Another patient underwent pancreaticoduodenectomy. The remaining three patients only underwent percutaneous transhepatic cholangial drainage ( PTCD). The 2 patients who underwent surgery died of progressive tumor disease at 8 and 13 months postoperatively. The other three patients who underwent palliative biliary drainage died within 6 months of PTCD. There was no significant difference between the two types of treatment ( P ＞0. 05). Conclusions Chronic cholangitis caused by reflux and bacterial infection was properly a predisposing factor leading to late development of bile duct cancer after biliary-enteric anastomosis for benign diseases. Patients treated with biliary-enteric anastomosis should be closely monitored for late development of cholangiocarcinoma. Some procedures such as choledochoduodenostomy and jejunum interposition choledochoduodenostomy should be abandoned because of their poor outcomes and severe complications. Proper indications of biliary-enteric anastomosis should strictly be followed and the Oddi's sphincter should be protected if possible to prevent late development of bile duct cancer.
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Statins and antiplatelet drugs are the two cornerstones for the treatment of cerebrovascular disea －ses.This two drugs play a vital role in reducing platelet reactivity and inhibiting inflammation .Statins can effectively delay the progression of atherosclerosis ,reduce plaque volume and reduce the incidence of cerebrovascular diseases through multiple pathways .Clopidogrel is currently used primarily for anti －platelet aggregation .Some studies indicate that clopidogrel is also involved in the process of atherosclerosis ,but the mechanism is not clear .The anti－atheroscle－rosis effect of clopidogrel is often neglected , when statins are combined with clopidogrel .This article reviews the progress in the treatment of atherosclerotic plaque by statin combined with clopidogrel .
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Objective To investigate the improvement effect of n-3 polyunsaturated fatty acid (n-3 PUFA) on rat nonalcoholic fatty liver disease(NAFLD) induced by high fat diet.Methods Thirty Wister male rats were divided into the control group,model group and n-3 PUFA group.The high fat feeding was adopted to establish NAFLD model.After 20 weeks of experiment,7 cases were extracted from each group for detecting serum and liver total cholesterol (TC) and triacylglyceride(TG);other 3 cases were performed the liver HE staining,the levels of MCP-1,iNOS,TNF-α mRNA protein were detected by using the Real time quantitative PCR(qPCR) and Western blot.Results The TC and TG levels in serum and livers of the model group were significantly higher than those in the control group(P＜0.01),but which were evidently decreased after adding n-3 PUFA(P＜0.05).The HE staining clearly observed the rat hepatic cells fatty degeneration in the model group,while polyunsaturated fatty acid had obvious improvement effect on it.The inflammatory molecule MCP-1,iNOS,TNF-α gene expression levels in the model group were significantly higher than those in the control group(P＜0.05),while the expression levels of MCP-1,iNOS and TNF-α in the n-3PUFA group were significantly decreased compared with the model group.Conclusion High fat feeding can cause the severe fatty degeneration in rat liver,but polyunsaturated fatty acid can play obvious improvement effect.
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Objective To investigate the improvement effect of n-3 polyunsaturated fatty acid (n-3 PUFA) on rat nonalcoholic fatty liver disease(NAFLD) induced by high fat diet.Methods Thirty Wister male rats were divided into the control group,model group and n-3 PUFA group.The high fat feeding was adopted to establish NAFLD model.After 20 weeks of experiment,7 cases were extracted from each group for detecting serum and liver total cholesterol (TC) and triacylglyceride(TG);other 3 cases were performed the liver HE staining,the levels of MCP-1,iNOS,TNF-α mRNA protein were detected by using the Real time quantitative PCR(qPCR) and Western blot.Results The TC and TG levels in serum and livers of the model group were significantly higher than those in the control group(P＜0.01),but which were evidently decreased after adding n-3 PUFA(P＜0.05).The HE staining clearly observed the rat hepatic cells fatty degeneration in the model group,while polyunsaturated fatty acid had obvious improvement effect on it.The inflammatory molecule MCP-1,iNOS,TNF-α gene expression levels in the model group were significantly higher than those in the control group(P＜0.05),while the expression levels of MCP-1,iNOS and TNF-α in the n-3PUFA group were significantly decreased compared with the model group.Conclusion High fat feeding can cause the severe fatty degeneration in rat liver,but polyunsaturated fatty acid can play obvious improvement effect.
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Objective To evaluate the value of the neutrophil-lymphocyte ratio (NLR) in elderly type 2 diabetic patients (T2DM) with coronary heart disease (CHD).Methods We performed a retrospective observational study on 228 patients undergoing coronary angiography in Guizhou Provincial People's Hospital from April 2014 to July 2015.Patients were divided into three groups:the simple T2DM group (n=77),simple CHD group (n=72),and T2DM complicated with CHD group (n=79).Meanwhile,70 healthy elderly subjects served as the control group.The white blood cell count,high-sensitivity C-reactive protein (hs-CRP) and other clinical and laboratory parameters were collected,and NLR was calculated.Risk factors for CHD in T2DM patients were determined by logistic regression analysis.Multiple stepwise regression analysis was adopted to identify factors influencing NLR.Results The white blood cell count,neutrophil count,NLR and hs-CRP level in the simple T2DM,CHD,and T2DM+CHD groups were higher than in the control group [(7.48 1.81) 109/L,(7.72± 1.89) 109/L,(7.98±2.12) 109/L vs.(6.22± 1.61) 109/L;(4.49±1.38) 109/L,(4.88±1.56) 109/L,(5.35±1.40) 109/L vs.(3.52±0.84) 109/L;(2.84± 0.77),(3.07±0.79),(3.34±0.83) vs.(1.58±0.42);(2.92±0.65) mg/L,(3.20±0.86) mg/ L,(4.98±1.10) mg/L vs.(1.105±0.23) mg/L;respectively,P＜0.05 or P＜0.01].The lymphocyte count in the simple T2DM,CHD,and T2DM+CHD groups were lower than in the control group [(1.57±0.41) × 109/L,(1.58±0.40) × 109/L,(1.61±0.48) × 109/L vs.(2.22± 0.51) × 109/L,P＜0.05].NLR and hs-CRP levels in the T2DM+CHD group were higher than in the former two groups (all P＜0.05).Pearson correlation analysis showed that NLR was positively correlated with the Gensini score and hs-CRP level (r=0.7455 and 0.7792,both P＜0.01).Logistic regression analysis showed that NLR,hs-CRP levels and glycosylated hemoglobin A1c (HbA1c) were the risk factors for CHD in T2DM patients (OR=4.331,3.997 and 2.928,all P＜0.05).Multiple stepwise regression analysis showed that NLR was positively correlated with fasting plasma glucose,HbA1 c levels and systolic blood pressure (β' =0.3133,0.4720 and 0.3069,all P＜0.05).Conclusions NLR may be a valuable predictive factor for CHD in elderly T2DM patients.
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Objective To investigate the role of receptor for advanced glycation end products (RAGE)/NF-κB signaling pathway in mediating lysophosphatidylcholine (LPC)-induced TGF-β1 expression in human retinal endothelial progenitor cells (HEPCs).Methods Human retinal endothelial cells (HERCs)were transfected with siRNA for RAGE siRNA or added NF-κB in-hibitor pyrrolidine dithiocarbamate (PDTC)in the presence or absence of LPC,the expressions of TGF-β1 and RAGE genes were analyzed by qPCR and Western blot.Results LPC could increase the expression of RAGE and TGF-β1 gene in HERCs.The RAGE gene after silence could significantly decrease the expression of LPC-induced RAGE and TGF-β1 .Adding NF-κB inhibitor PDTC significantly reduced LPC-induced RAGE and TGF-β1 expression in HERCs.Conclusion RAGE/NF-κB signaling pathway plays an important role in mediating LPC induced TGF-β1 gene expression in HERCs.
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Objective To investigate the mechanism of pioglitazone preventing diabetes and the role of nuclear factor of actived T cells (NFAT) on non-obese diabetic(NOD) mice .Methods (1)Female NOD mice at 4 weeks of age were randomly divided into pioglitazone group(n=21) and control group(n=21) .The accumulative diabetes incidence was followed-up to 30 weeks of age in each group of NOD mice .(2)Pancreas were removed from NOD mice at 12 weeks of age in each group(n=15) to score insulitis se-verity by routine HE staining .IL-4 ,IFN-γand peroxisome proliferator-activated receptor γ(PPARγ) mRNA levels in spleens were tested by RT-PCR .IL-4 and IFN-γlevels in sera ,the activity of PPARγand NFATc1 nuclear protein in spleens were measured by enzyme linked immunosorbent assay (ELISA) .Results (1) At 15 weeks of age ,the diabetes incidence was 4 .76% in pioglitazone group ,and 33 .33% in control group(P0 .05) .(2) At 12 weeks of age ,the insulitis score in pioglitazone group was lower than that in control group[(1 .79 ± 0 .75) vs .(2 .38 ± 0 .66) ,P<0 .05] .(3) IFN-γ mRNA level in pioglitazone group was lower than that in control group[(0 .16 ± 0 .07) vs .(0 .53 ± 0 .26) ,P<0 .05] ,and PPARγmRNA level in pioglitazone group was higher than that in control group(0 .91 vs .0 .25 ,P<0 .05) .(4)IFN-γ level in pioglitazone group was lower than that in control group [(561 .05 ± 78 .61)pg/mL vs .(666 .43 ± 28 .42)pg/mL ,P<0 .05] .(5)At 12 weeks of age ,the spleen PPARγnuclear protein activity in pioglitazone group was higher than that in control group [(0 .05 ± 0 .01) vs .(0 .02 ± 0 .01) ,P<0 .05)] ,and NFATc1 nuclear protein activity was low-er than that in control group[(0 .23 ± 0 .04) vs .(0 .33 ± 0 .04) ,P<0 .05] .Conclusion Pioglitazone could activate PPARγ nuclear protein ,inhibit activity of NFATc1 nuclear protein ,downregulate IFN-γ,diminish Th cells deviating to Th1 ,and sequently prevents insulitis and diabetes onset in NOD mice .
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Objective To investigate the mechanism of preventing islet β-cell apoptosis in NOD mice with pioglitazone.Methods Female NOD mice at 4 weeks of age were divided into pioglitazone group ( n =21,0.02％pioglitazone was added into the feed ) and control group ( n =21,fed with regular diet).The accumulative incidence of diabetes was followed-up to 52 weeks of age in each group of NOD mice.Pancreas was removed from NOD mice at 12 weeks of age in each group ( n =15 ) to score severity of insulitis by routine H-E staining.The apoptotic β-cells in islets were observed with double-labeling technique of TUNEL in situ combined with standard sensitive avidin-biotin complex (sABC) immunohistochemical method.The spleens were taken for cell culture; IL-4 and IFN-γ levels in sera and supernatants of cultured splenocyte,the activity of PPARγ and NF-κB nuclear proteins in cultured splenocyte were measured by ELISA.Results (1)At 30 and 52 weeks of age,the respective incidences of diabetes were 57.1％ and 76.2％ in pioglitazone group,and 76.2％ and 90.5％ in control group ( all P＞0.05 ).At 15 weeks of age,the incidence became 4.8％ in pioglitazone group,and 33.3 ％ in control group ( P =0.045 ).( 2 ) At 12 weeks of age,the percentages of non infiltrated islet and peri-insulitis islet in pioglitazone group were higher than those in control group ( 14.73％ vs 5.69％,P＜0.01 ; and 26.02％ vs 15.72％,P＜0.01 ),and that of intraislet insulitis was lower than that in control group ( 59.25％ vs 78.59％,P＜0.01 ).The percentage of apoptotic β-cell in pioglitazone group was lower than that in control group( 6.17％ ±3.62％ vs 10.62％ ±4.43％,P=0.008 ).(3) In sera,IFN-γ level in pioglitazone group was lower than that in control group [( 561.05±78.61 ) vs ( 666.43 ± 28.42 ) pg/ml,P =0.045].In cultured splenocyte supernatant,the level of IFN-γ in pioglitazone group was lower than that in control group[(605.84+65.60) vs (692.20+44.98) pg/ml,P=0.041].(4) In cultured splenocyte,PPARγ nuclear protein activity in pioglitazone group was higher than that in control group ( 0.06 ± 0.01 vs 0.03 ± 0.01,P =0.013 ),and NF-κB nuclear protein activity was lower than that in control group ( 0.03 ± 0.01 vs 0.08± 0.01,P =0.001 ).Conclusions Pioglitazone activates PPARγ nuclear protein,inhibits activity of NF-κB nuclear protein,downregulates IFN-γ,diminishes differeutiation of Th cells to Th1,and subsequently prevents insulitis and β-cell apoptosis in NOD mice.
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When MR image's area is too small compared with the whole picture, the use of the current auto-window algorithms usually gets poor clarity and contrast. In order to address this problem, an improved auto-window algorithm is proposed in this paper and can solve the problem effectively and get clear and rich layers of MR images quickly and easily.
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Algorithms , Image Interpretation, Computer-Assisted , Methods , Magnetic Resonance Imaging , MethodsABSTRACT
Objective Alstr(o)m syndrome (AS) is a rare,autosomal recessive inherited disease characterized by various clinical manifestations.The aim of this study was to review the clinical characteristics and laboratory findings of AS.Methods Two cases of AS was reported.Combined with the clinical data of 7 cases of AS which had been reported in China,the clinical characteristics and laboratory findings of AS were reviewed.Results Visual disorder( median onset age:6.0 years ) and dysaudia( median onset age:10.3 years ) were found in 9 patients,short stature and obesity in 8 patients,acanthosis nigricans in 7 patients,diabetes mellitus( median onset age:14.5 years) in 6 patients,and heart disease in 4 patients; hyperuricemia was detected in 6 patients,hepatic dysfunction and hypertriglyceridemia in 5 patients.Conclusions Visual disorder was the first presentation in patients with AS.Deafness,obesity,diabetes,and short stature were common.These findings were helpful in making an early and accurate diagnosis and appropriate treatment.
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Objective To explore the clinical correlation of coronary heart disease with diabetes.Method From January 2005 to December 2008,268 patients were enrolled and randomly divided into the study group(Coronary Heart Disease combined with Diabetes)and the control group(Coronary Heart Disease).Blood pressure,hyperlipemia,degree of vasculopathy and chief heart incident was compared.Result The rate of blood pressure,hyperlipemia and chief heart incident in the control group were significantly lower than the study group(P＜0.05).The incidence rates of multi-branches lesions in the control group were significantly lower than the study group(P＜0.05).The incidence rates of single-branches lesions in the study group were significantly lower than the control group(P＜0.05).Conclusion Active measures should be taken to prevent diabetes and control the risk factors like blood sugar,blood fat,blood pressure,weight and so on in order to prevent the attack of coronary artery diseases.
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Objective To investigate the renoprotective effect of reduced glutathione on streptozotocin-induced diabetic rats and its possible mechanism.Methods Streptozotocin-induced diabetic rats received aminoguanidine(50 mg?kg~(-1)?d~(-1)) and reduced glutathione 400 mg?kg~(-1)?d~(-1) intraperitoneally respectively or synchronously for(8 weeks.) The expression of TGF-?1 mRNA and protein in renal cortex were determined by reverse transcription polymerase chain reaction(RT-PCR) and immunohistochemistry respectively.The mean glomerular area(MGA) and volume(MGV) were measured by image analysis system.The changes of creatinine clearance rate(Ccr),the kidney weight/body weight ratio and the urinary albumin excretion rate(UAER) were determined.Results By the end of 8 weeks,the Ccr,UAER,MGA,MGV,kidney weight/body weight ratio,the contents of TGF-?1 mRNA in renal cortex were increased significantly in DM groups compared with the blank control group(P