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AIM: In order to bridge the gap between pharmacogenomic research and its clinical application, we propose the concept of genetic electronic identity, named "GeneFace", and developed an electronic information system which integrated "drug-gene" interactions and recommendations for personalized medicine. METHODS: Based on the self-developed Precision Medicine knowledgebase, which concludes drug directions, guidelines or important literatures with high level of evidence, we developed GeneFace with Java-based open-resource application framework Spring Boot, further developed a mobile App with cross-platform framework Uni-APP. RESULTS: The App includes six modules: genetic testing appointment, genetic knowledge introduction, individualized medication advice, medication records, Geneface interpretation, and Precision Medicine knowledgebase. By detecting the genotype of more than 300 gene loci upon first use, users import the results to form a personal "drug-gene identity card". Then scan or enter the drug name in "GeneFace", the App would automatically give corresponding medication recommendations, including: risks for possible adverse drug reactions, risks for reducing the efficacy or even ineffectiveness, and possibility for dose adjustment, etc., which increase the safety of clinical drug use. People can obtain pharmacogenomics knowledge and basic drug information in the "GeneFace" app. CONCLUSION: Development as a digital therapeutic product, the expanded application of GeneFace can rapidly promote clinical applications of basic pharmacogenomics research and significantly improve drug use safety, which creating a new model for accelerating the clinical application of personalized medicine.
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The complement system is a part of the innate immune system, playing an important role in protecting hosts from pathogens.Many researches showed that complements were strongly associated with a wide spectrum of glomerulonephritis, such as IgA nephropathy, membranous nephropathy, post infectious glomerulonephritis, membranoproliferative glomerulonephritis, C 3 nephropathy, focal segmental glomerulosclerosis, lupus nephritis, and ANCA induced renal vasculitis.Various factors may induce abnormal activation or dysregulation of the local or systemic complement system, resulting in further kidney injury.Selective blocking of the complement cascades could protect the kidney.Further investigations are needed to fully understand the mechanism of complement, and targeting complement could be considered a novel therapeutic method in refractory renal diseases.
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IgA nephropathy(IgAN)is the most common primary glomerulonephritis in children and adolescents.It is an important cause of chronic kidney disease and end stage renal disease.The pathogenesis of IgAN has not been fully elucidated and it is thought to be associated with a multi-hit hypothesis, namely, increased levels of galactose-deficient IgA1(Gd-IgA1)(Hit 1); production of auto-antibodies directed against Gd-IgA1(Hit 2); formation of Gd-IgA1-containing immune complexes(Hit 3); the deposition of immune complexes in the glomerular mesangium resulting in glomerular injury(Hit 4). Gd-IgA1 is regarded as the initiator of the pathogenesis of IgAN.Core 1, β1, 3-galactosyltransferase(C1GALT1)is a key enzyme in the process of O-glycosylation of IgA.The reduction in the activity and/or gene expression of C1GALT1 is closely related to Gd-IgA1.This review will illustrate the role of C1GALT1 in the pathogenesis, diagnosis, treatment and prognosis of IgAN to provide molecular strategies for the clinical practice.
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Minimal change nephrotic syndrome (MCNS) is the most common nephrotic syndrome among children.Although the details of pathogenesis remain unknown, it is widely considered that upregulated expression of T lymphocyte cell cytokines contributes to the initiation of MCNS.Moreover, studies had revealed that altered number and function disorder of B lymphocyte cells could change the functions of antigen presentation, participating in the onset of MCNS by affecting the function of T lymphocyte cells.Recently, CD80 has emerged as a popular research topic which exerts its effects via the change of podocytes morphology, thereby affecting the glomerular permeability.However, neither immune disorder nor podocyte dysfunction is poorly demonstrated to be associated with the pathogenesis of MCNS, the hypothesis such as "a 'two hit disorder" and "γδT cells exacerbate podocyte injury via the CD28/B7-1-phosphor-SRC kinase pathway" are raised.In the current review, we summarized the related investigations to help us to understand the mechanisms and pathogenesis of MCNS.
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The cultivation of research ability can promote eight-year medical students to explore the uncharted academic fields and solve complex clinical problems. One of the firts pilot universities to provide eight-year programs, Xiangya Medical College of Central South University builds on its profound experience in medical education, and establishes a curriculum structure aiming at improving the students' research ability. In the general education stage, cross-disciplinary courses are set up. In the core medical education stage, basic medical innovation experiment extracurricular research courses are set up, and a two-year overseas exchange program is set up in the postgraduate training stage. Different evaluation methods are also designed to meet the specific needs in each stage. This program has achieved preliminary effects.
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As one of the first pilot eight-year clinical medicine education institutions, Xiangya School of Medicine has already put it into practice for almost 12 years. After years exploring and reforming, its cultivating plan has already been built up. This paper will make a brief comparative analysis between 2004 version and 2012 version in cultivating objectives, model and characteristics, demonstrated the development and reform of its eight-year program education, shown its features such as strengthening the basic knowledge, emphasizing the clinical skills, cultivating the capabilities, and broadening the international perspectives, and attempt to contact the residency and research training, in order to provide the reference for the eight-year program education reform.
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Primary nephrotic syndrome(PNS) is a common kidney disease. However,its mechanisms remain unclear,and immunity might to play an important role in PNS. This article will review the pathology from cellular immunity,humoral immunity and the immunity involved in podocytes. It is useful for further understand-ing,and it may help guide the diagnosis,prognosis and therapeutic strategies.
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Objective To explore the role of nuclear translational factor homeobox A13(HOXA13)gene in epithelial - to - mesenchymal transition(EMT)induced by human serum albumin(HSA)overload in human renal tu-bular epithelial(HKC)cells. Methods HKC cells were treated with different concentrations of HSA(ranging from 0 - 30 g/ L)for 48 h or 20 g/ L HSA for different times(ranging from 0 - 72 h)in vitro. The protein expressions of cy-tokeratin(CK),Vimentin,and HOXA13 protein in HKC cells were detected by using Western blot respectively. Mean-while,liposome - mediated DNA transfection was used to transfect the HOXA13 gene into HKC cells before HSA treat-ment,and the expressions of CK,Vimentin and HOXA13 protein in HKC cells were also detected by using Western blot. Results (1)The protein expression of CK decreased but Vimentin increased after HKC cells were exposed to HSA,which was in a concentration - and time - dependent manner.(2)Expression of HOXA13 was down - regulated by HSA in a dose - and time - dependent manner,and the expressions of HOXA13 protein in HKC in 5 g/ L,10 g/ L, 20 g/ L,30 g/ L group were 58. 24%(P = 0. 005),44. 73%(P = 0. 003),38. 40%(P = 0. 033)and 24. 83%(P =0. 011)respectively as compared with 0 g/ L group. Likewise,the protein expressions of HOXA13 in 24 h,48 h,72 h group were 52. 00%(P = 0. 023),46. 83%(P = 0. 008)and 35. 10%(P = 0. 034)respectively as compared with 0 h group.(3)There was a positive correlation between the levels of HOXA13 protein expression and CK protein expression (r = 0. 86,P = 0. 005),while the relationship between the levels of HOXA13 protein expression and Vimentin protein expression was negative(r = - 0. 94,P = 0. 002).(4)Up - regulated expression of HOXA13 in HKC cells by lipo-fectamine transfection alleviated the degree of EMT induced by HSA significantly. The expression of Vimentin decreased by 35. 34%(P = 0. 005)while the expression of CK increased 360. 00% - fold(P = 0. 005),compared with that of untransfected HKC cells. Conclusion EMT induced by HSA in HKC cells may play a role through HOXA13.
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Central South University began to implement the eight-year medical education in 2004, and has accumulated rich experience in the pre-medical education through continuous reform and improvement. Since 2012, Central South University has made a series of reformation, which is more conducive to the all-round development of medical students , on the pre-medical education . Through adding freshman courses, humanities courses, bilingual teaching courses, and applying aca-demic adviser institution, early scientific research training and open courses during the pre-medical education, Central South University has exercised and strengthened students' scientific research ability, the humanistic quality, English level, and made the pre-medical comprehensive examination for the shunt selection of students. Thus Central South University has improved the eight-year medical students' comprehensive quality, and provided an example of the reformation for medical education.
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The incidence of acute kidney injury(AKI) in neonate is not low,it occurs in many cases such as ischemic-hypoxic injury,infection,administration of nephrotoxicity drugs and urinary tract obstruction,of which perinatal asphyxia ranked first in China.Due to the severe food security crisis,the occurrence of urinary tract obstruction is rising in recent years.The child health care should pay attention to prevent and screen this kind of disease for the high risk group.The diagnosis of AKI is difficult for newborn because serum creatinine and urine are hard to make a definite boundary.So study of early markers of AKI seems to be of great importance,of which neutrophil gelatinase associated lipocalin and cystatin C are research focuses,treatments should aim at solving primary disease such as ischemic,and so on.Renal replacement therapy is recommended when it comes to severe cases,but mortality still remains high,corresponding to severe primary disease and complications.
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Objective To research Henoch-Schonlein purpura purpura (HSP) and renal pathology in children.Methods 31 hospitalized HSP children that with normal urine routine and accepted renal biopsy in our hospital.Results There were different levels of kidney pathological damage in this group of 31 cases,the results of light microscope were from grade Ⅱ to grade Ⅵ The proportion was grade Ⅱ(35.48％,11 of 31),grade Ⅲ (54.83％,17 of 31),and grade Ⅳ,Ⅴ and Ⅵ (each 1 case of 31,3.23％ ).lmmunofluorescence pathology results were showed as following:merely IgA depositional (48.38％,15 of 31 ),IgA + IgG depositional ( 19.36％,6 of 31 ),IgA + IgM depositional ( 19.36％,6of 31 ),IgA + igG + IgM depositional ( 12.90％,4 of 31 ).Microalbuminuria had been founded in 14 cases,and the microalbuminuria level of 10 cases were higher than normal value( 10 of 14,71.43％ ).Conclusions HSP children had renal pathologic dysfunction,even the urine routine were normal,and the detection of urine microalbumin was a significant marker in the early stage.
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ObjectiveTo explore the mechanism of Montelukast combined with Huang Qi Huai in the treatment of asthma.MethodsForty male Sprague-Dawley (SD) rats were chosen and randomly divided into five groups:control group (Control),model group (Model),Montelukast group (MK),Huang Qi Huai group (H),Montelukast + Huang Qi Huai group (MK + H),each group has 8 rats.The other four groups except the control group were built to chronic rat asthma model.The treatment groups were administered intragastrically with Montelukast,Huang Qi Huai and Montelukast + Huang Qi Huai respectively.All animals were sacrificod; plasma and bronchoalveolar lavage fluid (BALF) and superior lobe of right lung tissues were collected.Superior lobes of right lung tissues were used to measure the expression of IL-17 in lung tissue by immunohistochemistry.The airway inflammation was analyzed by histochemistry staining with H.E.Total cells score and differential score in BALF were counted.The levels of IL-17 in the plasma and BALF were measured by Enzyme-linked immunosorbent assay (ELISA).ResultsCompared with the control group,the degree of inflammatory cell around the airway in the model group were significantly higher (P ＜ 0.05).Compared with group model,the degree of inflammatory cell around the airway in the Group MK,group H and group MK + H were significantly ameliorated ( P ＜0.05).Compared with Group MK,the degree of inflammatory cell around the airway in group MK + H was significantly ameliorated ( P ＜O.05),the expression of IL-17 in lung tissues was significantly lower ( P ＜0.05),the numbers of total cells and the concentration of IL-17 in plasma and BALF were decreased too ( P ＜0.05).Correlation analysis showed that the level of IL-17 in the plasma and BALF was positively correlated with the level of IL-17 in the lung tissue( P ＜ 0.05 ).ConclusionsCombined Huang Qi Huai adjuvant Montelukast treatment of asthmatic rat further reduced the concentration of IL-17 in the plasma and BALF,reduced the expression of IL-17 in lung tissue,improved the airway inflammation.Down regulation the expression of IL-17 was probably one of the mechanisms of anti-inflammatory.
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As we know more and more about asthma pathogenesis and chronic inflammatory disorder mechanism,and additional immunomodulator options become available.Studies have suggested that Th2 cell differentiation increases,and Th1 cell differentiation reduces in asthma.Therefore,it becomes an important immunotherapy method to modulate the Th1/Th2 response by promoting Th1 cytokines and inhibiting Th2 cytokines.At present,the use of immunomodulator such as anti-IgE antibody,anti-IL-5 agents,CpG oligodeoxynucleotides,imiquimod,bacterial extracts,Chinese medicine in asthma has already made some progress,and besidse it demonstrate great efficacy in clinical.
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Objective To investigate the effect and possible mechanism of bone marrow stem cell mobilized by stem cell factor (SCF) with granulocyte colony-stimulating factor(G-CSF)on renal peritubular capillary, fibrosis and renal function in unilateral ureteral obstruction (UUO) rats. Methods One hundred and twenty eight healthy male Wistar rats were randomly divided into four groups: Sham group, SCF-G group, UUO group and UUO+SCF-G group. Eight rats of each group were randomly selected and killed on the 5th, 14th, 21st and 28th day. Serum creatinine, CD34 positive cells and factor Ⅷ positive cells in renal interstitium, histopathologic lesion scores of interstitial fibrosis and interstitial pathology in kidney were measured. The mRNA expression of vascular endothelial growth factor (VEGF). and thrombospondin-1 (TSP-1) in the renal cortex was detected. Results (1) The renal interstitial fibrosis anti the loss of peritubular capillary were observed in UUO group after two weeks. (2) The number of bone marrow stem cells homing to renal interstitium in UUO +SCF-G group was significantly higher than that in UUO and Sham groups (P<0.05). (3) The loss of peritubular capillary in UUO+SCF-G group appeared later than that in UUO group (P<0.05). (4) The interstitial fibrosis and tubule injury was milder in UUO+SCF-G group than that in UUO group (P<0.05). (5) The decrease of VEGF mRNA expression of renal cortex in UUO +SCF-G group was seen later than that in UUO group. VEGF mRNA expression in UUO+SCF-G group was higher than that in UUO group. (6) The increase of TSP-1 mRNA expression of renal cortex in UUO+SCF-G group was seen later than that in UUO group. TSP-1 mRNA expression in UUO+SCF-G group was lower than that in UUO group (P<0.05). (7) In UUO and UUO+SCF-G groups, peritubular capillary index was negatively correlated with serum creatinine, interstitial fibrosis and interstitial lesion scores. VEGF mRNA expression of renal cortex was positively correlated with peritubular capillary index, and TSP-1 mRNA expression of renal cortex was positively correlated with peritubular capillary index. Conclusions (1)The loss of peritubular capillary is found in UUO group, and is correlated with interstitial fibrosis and interstitial lesion. (2) Application of SCF with G-CSF can effectively motivate stem cells to injured renal tissue, contribute to decrease the loss of peritubular capillary, lessen interstitial fibrosis and interstitial lesion, and ameliorate renal function. (3) Application of SCF with G-CSF can up-regulate VEGF mRNA expression and down-regulate TSP-1 mRNA expression, which may contribute to promote the repair of endothelial cells and protect peritubular capillary.
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Objecfive To detect the functional repair of metanephric mesenchymal cells (MMCs) transplantation in adriamycin (ADR)-induced glomerulopathy rats. Methods A total of 90 Sprague-Dawley female rats were randomly divided into three groups:ADR group (n=40,rats were injected via the tail vein with O.25 mg ADR/100 g body weight on days 1 and 21),ADR- MMCs group(n=40,rats were injected via the tail vein with 5×10~6-7×10~6 MMCs 8 weeks after the second ADR administration),control(n=10).All the rats were scarified 8 weeks after MMCsinjection.Pathology and collagen IV expression in renal tissue were examined.Moreover,matrix metalloproteinases 2 (MMP-2) and matrix metallopmteinases 9 (MMP-9) expression in the renal tissue were also detected with immunohistochemistry,and quantity analysis of protein and gene was further demonstrated with Westem blot and RT-PCR analysis,respectively. Results There were no significant differences in tubulointerstitial injury score and glomerulosclerosis degree between ADR group and ADR-MMCs group(P>0.05).Compared with ADR group,collagen Ⅳ and MMP-2 expression decreased, MMP-9 expression incrased in renal tissue of ADR-MMCs group, and the difference was significant (P<0.05). Conclusion MMCs transplantation may have potentially therapeutic effect on renal tissue fibrosis of adriamyein-induced glomerulopathy in rats, and the signaling pathways of MMPs appear to be involved in these processes.
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BACKGROUND:Stem cell transplantation provides a new approach to treat chronic renal disease.Specific marking and in vivo tracing of stern cells are the basis of studies in this field.However,the marking methods appropriate for all cells remain uncertain.OBJECTIVE:To observe the in vivo location and differentiation of 4',6-diamidino-2-phenylindole (DAPI) and green fluorescence protein (GFP)-Iabeled cells in adriamycin nephrosis rats so as to explore an efficient labeling and tracing method for metanephric mesenchymal cells (MMCs) derived from embryonic rats.DESIGN,TIME AND SETTING:Grouping comparative observation was performed at the Second Xiangya Hospital of Central South University from April to December 2007.MATERIALS:A total of 60 female SD rats,weighing 180-220 g,of dean grade,were used to establish models of adriamycin nephrosis.METHODS:DAPI and MMCs infected with GFP and DAPI were respectively injected into addamycin nephrosis via the tail vein.DAPI and GFP distribution in the frozen sections was detected at 1,3,and 5 weeks,postoperatively.In addition,GFP expression in renal tissues was detected by ABC immunoenzymatic staining method.MAIN OUTCOME MEASURES:DAPI and GFP-labeled Cell grafts in adriamycin nephrosis rats were compared.The changes of GFP-transfected MMCs at different time points were observed.RESULTS:DAPI positive cells were observed in tubular structures after 1 weeks of injection of DAPI-labeled cells and DAPI alone,and remained existing at 5 weeks,but the florescence was reduced with time.GFP-transfected MMCs were able to survive and integrate into tubular structures after 1 week,and remained existing at 5 weeks.Moreover,the fluorescence was not reduced.ABC immunoanzymatic staining showed that only a few GFP-positive MMCs appeared in glomerular tufts,and mainly distributed in cytoplasm.Semi-quantitative evaluation of GFP show that the positive cell rate in rats with early application was greater than that with advanced application,and the positive rate was increased with time.CONCLUSION:Liposome mediated GFP gene transfer was an efficient labeling in vitro and suitable tracing method for cell differentiation experiment in vivo,suitable for short-term tracing and observation of transplanted cells.
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ObjectiveTo evaluate the nephroprotective effects of transplanting metanephric mesenchymal cells (MMCs) into the renal subcaspsule of rats with acute tubular necrosis (ATN) induced by gentamicin. MethodsMMCs were expanded in culture and immunocytochemistry was used to characterize the cells. After gentamicin-induced ATN, fluorescence-labeled cells were transplanted and traced in kidney tissues by fluorescence microscopy. Serum creatinine (Scr) and N-acetyl-b-D-glucosaminidase (NAG) were tested. Kidney pathology was studied by hematoxylin-eosin staining. Apoptosis was examined by the TUNEL assay. Ki-67 and Bcl-2 expression was examined by immunohistochemistry. ResultsMMCs were expanded in culture and the phenotype of the cells was vimentin-positive and keratin-negative. Compared with other ATN groups, in the MMCs-treated group, Scr and NAG clearly decreased[14d Scr: (101.38±20.46) μmol/L vs (248.78±23.15), (252.98±33.52), (229.08±18.18) μmol/L;NAG: (14.83±7.74) U/L vs (33.33±14.88), (29.62±10.54), (30.22±10.94) U/L, P<0.05, respectively];the histopathoiogic lesion scores were lower (P<0.05);the Ki-67 antibody and apoptosis of renal tubular epithelial cells were improved or reduced respectively;the expression of Bcl-2 protein was up-regulated (P<0.05). ConclusionThe subcapsular transplantation of MMCs can ameliorate renal function and repair kidney injury.
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A homozygous A to G transition (AGT to GGT) in codon 16 of growth hormone receptor (GHR) gene was found in one patient with idiopathic short stature(ISS), resulting in an amino acid change(Ser16Gly). This may be a novel GHR gene mutation; and another novel Arg43Gln GHR gene polymorphism was found in Chinese people.
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Comparing traditional lecture-based learning and problem-based learning(PBL) in medical education,PBL simulates real life clinical situation,focuses on competencies training of clinical reasoning and decision-making,and makes students learn how to learn.This article illustrates the process,critical factors,and some cognitive bias in PBL operation.It demonstrates the pure core of PBL and the practicability in China.
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Objective To explore the relationship between the pathological classification and clinical manifestations of lupus nephritis(LN)in children by renal biopsy and laboratory examination. Methods Renal biopsy and routine laboratory tests were performed in 35 cases of LN . The pathological classification of LN was made according to the criteria of WHO1982. Results Type Ⅳ of LN was most common(37.4%), and type Ⅴ(31.7%) and type Ⅲ(20.0%) were next. Type Ⅳ and type Ⅴ usually appeared as nephritic syndrome, while Type Ⅱ and Ⅲ mainly appeared as nephritis syndrome. The frequency of hypertension and renal dysfuction was the highest in type Ⅳ. Generally the renal interstitial injury of LN was mild, but that of type IV of LN was relatively obvious. There was a positive correlation between serum creatinine level and the degree of renal interstitial injury. Conclusion Lupus nephritis in childhood possessed some features in renal pathological change and clinical manifestations. Renal biopsy was important to diagnosis, treatment and prognosis evaluation of lupus nephritis.