Highlights of international frontier hot spots and new progress on renal transplantation in 2020 / 器官移植

A large quantity of studies related to renal transplantation were reviewed to extract and summarize the international frontier hot spots and difficulties, new transplantation technologies, new methods, new visions and new progress on renal transplantation in 2020.The main contents included rejection, optimization application and regulation of immunosuppression, transplant infection, malignancy after transplantation, non-invasive detection and biomarkers, donor organ preservation, repair and utilization, recurrence of renal disease after renal transplantation, multi-factors affecting long-term survival of transplant kidney, computer and artificial intelligence, etc.Strengthening the reading and thinking of literatures in the field of renal transplantation and broadening horizons in higher starting piont, combined with clinical practice of renal transplantation in China, help to promote the long-term efficacy of renal transplantation.

Research status and prospect of artificial intelligence technology in the diagnosis of urinary system tumors / 生物医学工程学杂志

With the rapid development of artificial intelligence technology, researchers have applied it to the diagnosis of various tumors in the urinary system in recent years, and have obtained many valuable research results. The article sorted the research status of artificial intelligence technology in the fields of renal tumors, bladder tumors and prostate tumors from three aspects: the number of papers, image data, and clinical tasks. The purpose is to summarize and analyze the research status and find new valuable research ideas in the future. The results show that the artificial intelligence model based on medical data such as digital imaging and pathological images is effective in completing basic diagnosis of urinary system tumors, image segmentation of tumor infiltration areas or specific organs, gene mutation prediction and prognostic effect prediction, but most of the models for the requirement of clinical application still need to be improved. On the one hand, it is necessary to further improve the detection, classification, segmentation and other performance of the core algorithm. On the other hand, it is necessary to integrate more standardized medical databases to effectively improve the diagnostic accuracy of artificial intelligence models and make it play greater clinical value.

Overview of international forefront hotspots and new progress on organ transplantation in 2019 ATC / 器官移植

In this paper, forefront hotspots in clinical and applied basis of organ transplantation as well as translational medicine during 2019 American Transplant Congress (ATC) were summarized. It involved transplantation clinical priorities and difficulties which were concerned by transplant surgeons. These hot topics included the immunological mechanisms, risk factors, prognosis evaluation and important biological markers of donor specific antibody (DSA) and antibody-mediated rejection (AMR), desensitization strategy in highly sensitized patients and progress of AMR prevention and treatment, current status and development direction of clinical immune tolerance, hotspots and prevention progress on transplantation-related infection, and brief evaluation of various donor organ mechanical perfusion methods, etc.

miR-498 inhibits A549 cell migration and invasion by down-regulating FOXM1 / 西安交通大学学报(医学版)

Objective To verify whether miR-498 can inhibit A549 cell migration and invasion by down-regulating FOXM1.Methods miR-498 mimic and miR-NC were transfected into A549 cells.Wound healing and Transwell method were employed to test the migratory ability and invasion ability of A549 cells;Western blot was used to detect the expressions of COL1A1,COL1A5 and FOXM1 in A549 cells.Luciferase assay was used to confirm whether FOXM1 is the target gene of miR-498.Results Compared with those in the control group,the expressions of COL1A1,COL1A5 and FOXM1 were decreased,and the migration and invasion abilities of A549 cells were decreased in the miR-498 group (both P<0 .01 ).The luciferase activity of the FOXM1-3′-UTR plasmid was significantly suppressed by miR-498 (P<0 .05 );over-expression of FOXM1 could reverse the effect of miR-498 on A549 cells.Conclusion miR-498 inhibits A549 cell migration and invasion by down-regulating FOXM1.

KRT19 enhances the proliferation and chemoresistance of breast cancer cells by upregulating CDK1 / 中国医师杂志

Objective To explore the role and mechanism of keratin 19 (KRT19) in breast cancer.Methods Quantitative real-time polymerase chain reaction (qRT-PCR) assay was used to determine KRT19 levles in 35 cases of breast cancer tissues and normal tissues.The correlation between KRT19 levels and clinical property of breast cancer was analyzed.Meanwhile,the expression levels of KRT19 in several breast cancer cells and mammary epithelial cell Michigan cancer foundation (MCF)-10A were evaluated by qRT-PCR assay.Over-expressed and knocked-down KRT19 in breast cancer ceils,3-(4,5-dimenthylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay was performed to detect the proliferation and chemosensitivity of these cells.The ability of forming colon of these breast cancer cells with treated KRT19 was studied via colony-forming unit assays.Western blot assay was performed to determine expression levels of ceil cycler related proteins.Results KRT19 was upregulated in breast cancer tissues comparing to normal tissues.KRT19 was positively related to tumor node metastasis (TNM) stage and distant metastasis of breast cancer.Similarly,KRT19 was highly expressed in breast cancer cells compared to mammary epithelial cell MCF-10A.The proliferation and colony-forming ability was significantly enhanced in MCF-7 cell with o,verexpressed KRT19.MTS assay showed that chemosensitivity of MCF-7 cells with overexpression of KRT19 was much more remarkably reduced than the control group.However,knocking down KRT19 in breast cancer cells MDA-MB-231 got the opposite results.Western blot assay suggested that KRT19 could obviously upregulated cyclin-dependent kinase 1 (CDK1) but not p27 expression levels.Conclusions KRT19 was upregulated in breast cancer tissues and was positively related to TNM stage and distant metastasis of breast cancer.KRT19 can significantly enhance proliferation and chemoresistance of breast cancer cells via upregulating CDK1.

Research Progress in Black Queen Cell Virus Causing Disease / 病毒学报

In nature, honeybees are the most important pollinators. They play a vital role in both protecting the diversity of natural ecosystems, and maintaining the yield-improving effects of agroecosystems. But in recent years, epidemic disease in bees has caused huge losses. Black Queen Cell Virus (BQCV) is a bee pathogen that was first reported in 1955. It mainly infects bee larvae and pupae, making their bodies turn dark and black, and causing a massive decrease in the bee population. More specifically, the virus makes the exterior of the cell walls in the larvae and pupae turn black. BQCV is a seasonal epidemic, spread by means horizontal and vertical transmission, and is often unapparent. BQCV not only infects a variety of bee species, but also spiders, centipedes and other arthropods. It can also be coinfected with other honeybee viruses. In recent years, research has shown that the Nosema intestinal parasite plays an important role in BQCV transmission and bees carrying Nosema that become infected with BQCV have increased mortality. Here we summarize current research on the incidence, prevalence, geographical distribution and transmission of BQCV.

Isolation, Identification and Analysis of the Complete Genome Sequence of Black Queen Cell Virus Strain China-JL1 / 病毒学报

Honeybee pupae were collected from Jilin apiaries and RNA was extracted for use as a tefnplate for amplification. Based on the complete genome sequences of black queen cell virus (BQCV) published on GenBank, we designed 10 pairs of primers to amplify genes by reverse transcription-polymerase chain reaction (RT-PCR). Using this approach, we have obtained the first complete genome sequence of a BQCV isolate in China. The genome of the isolated strain, named BQCV-JL1, is composed of 8358 nucleotides and shares between 86% and 93% homology with the complete genome sequences of the other six BQCV strains published on GenBank. ORF 1 of BQCV-JL1 is positioned between nucleot ides (nt) 546 and 4676 (4131 nt), while ORF 2 is located between nt 5750 and 8203. Between the two ORFs of BQCV-JL1 there is a short ORF, called ORF 3, between nt 4891 and 5433 (543 nt). The first functional gene ex- pression domain of the BQCV-JL1 strain is positioned between nt 546 and 5 429, encompassing both ORF 1 and ORF 3. There is an internal ribosome entry site (IRES) located before ORF 2, the last three bases of which are CCU (nt 5642-5644). These bases act as an initiation.codon facilitating the translation of ORF 2. The second functional gene expression domain of the BQCV-JL1 strain is located between nt positions 5642 and 8203. The BQCV-JL1 strain was found to share high sequence identity (93%) with the Hungary 10 genotype at the whole-genome level and analysis of the nucleotide and amino acid sequences revealed that the BQCV-JL1 strain also shows close genetic relationships with the South Korea strain, suggesting that both the BQCV-JL1 and South Korea strains may have migrated from European countries. BQCV-JL1 strain was different from the other 6 strains in dividing the nucleotides positions of QRF, which vqs because of the gene mutation.

Incidence and mortality of thyroid cancer in six cancer registries of Zhejiang province, 2000-2009 / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the incidence and mortality rates of thyroid cancer in Zhejiang province during 2000 to 2009.</p><p><b>METHODS</b>The data of thyroid cancer were collected from six cancer registries in Zhejiang province and the incidence and mortality rates of thyroid cancer were analysed.</p><p><b>RESULTS</b>The mean annual incidence rate of thyroid cancer in Zhejiang cancer registration areas was 6.93/100 000 during 2000 to 2009, and male/female ratio was 1: 3.43. The incidence rate was 3.62/100 000 in 2000 and it increased to 11.42/100 000 in 2009, with the annual percent change (APC) of 16.32% (95% confidence interval: 12.90%-19.85%). The mean annual mortality rate of thyroid cancer was 0.27/100 000 during 2000 to 2009, and male/female ratio was 1: 1.12. The mortality showed a rising trend without a distinct fluctuation from 2000 to 2009, the APC was 2.14% (95% confidence interval: from -7.10% to 12.30%). The incidence showed a rising trend with the increase of ages after 15 years old, and peaked at 55-60 years old. The mortality was low before 54 years old, but showed a rising trend with a distinct fluctuation after 55 years old, and peaked at 85-90 years old.</p><p><b>CONCLUSION</b>The prevention and control of risk factors for thyroid cancer in young and middle-aged people is key to decrease the incidence and mortality of thyroid cancer.</p>

Analysis of incidence and mortality of prostate cancer in cancer registration area in Zhejiang province from 2000 to 2009 / 中华泌尿外科杂志

Objective To investigate the epidemic characteristics and trends of incidence and mortality of prostate cancer in cancer registration areas in Zhejiang province from 2000 to 2009.Methods Clinical data incidence and mortality of prostate cancer were collected from 6 cancer registration areas in Zhejiang province,including Hangzhou,Jiaxing,Jiashan,Haining,Shangyu and Xianju.Crude rates,standardized rate and change trend,age-specific rates and annual percent change (APC,95％ CI) of prostate cancer were checked,sorted and analyzed in Zhejiang Cancer Center.Results The prostate cancer incidence rate from 2000 to 2009 was 9.79/100 000,age-standardized incidence rates by world standard population (ASIRW) was 6.39/100 000,and the incidence cumulative risk of males aged 0-74 was 0.72％ ; while the mortality rate was 2.73/100 000,age-standardized mortality rates by world standard population was 1.74/100 000,and the mortality cumulative risk of males aged 0-74 was 0.14％.Age-specific incidence of prostate cancer remained low before 50,years old and peaked at over 85-year-old group (130.30/100 000).Age-specific mortality of prostate cancer increased after 55,and also peaked at over 85-year-old group (81.19/100 000).The annual prostate cancer incidence rate generally grew from 1.39/100 000 (2000) to 13.89/100 000 (2009),and the APC was 14.18％ (95％ CI,9.68％-18.98％).Meanwhile,the prostate cancer mortality rate also increased from 1.52/100 000 (2000) to 3.58/100 000 (2009),and the APC was 11.83％ (95％ CI,5.69％-18.33％).Conclusion Prostate cancer incidence and mortality in Zhejiang cancer registration areas increased sharply,and the prevention and treatment of prostate cancer should be strengthened.

Incidence and mortality of brain tumor in areas with cancer registration of Zhejiang province,from 2000 to 2009 / 中华流行病学杂志

Objective To investigate the incidence and mortality of brain tumor in Zhejiang cancer registration areas from 2000 to 2009.Methods Data from 6 Cancer registration areas of Zhejiang province were collected.Number of cases,crude rates,proportions,age standardized rates,cumulate rates,cut rates,age-specific rates and annual percentage change (APC,95％ CI) of brain tumor incidence and mortality were analyzed.Results There were 5 123 new diagnosed brain tumor cases in Zhejiang cancer registration areas,accounting for 3.14％ of all the new cancer cases.The incidence rate of brain tumor was 8.53/100 000,and the standardized incidence rate by Chinese population was 5.72/100 000,ranking the 7th in cancer incidence spectrum of anatomic sites.Agespecific incidence of brain tumor increased along with age,and peaked among 70-74 age groups (24.09/100 000).The annual incidence rate of brain tumor increased from 2000 (6.87/100 000) to 2009 (8.35/ 100 000),with APC as 1.58％ (95 ％ CI:-2.17％-5.47％,no statistical significance).A total of 2 357 deaths caused by brain tunor were reported from 2000-2009,accounting for 2.47％ of all the cancer death cases.Mortality rate on brain tumor appeared to be 3.92/100 000,with the standardized mortality rate by Chinese population as 2.45/100 000,ranking the 7th in cancer mortality spectrum of anatomic sites.The age-specific mortality of brain tumor remained low among 0-39 year-olds,and reached the peak at 80-84 age groups (17.64/100 000).The annual mortality rate of brain tumor decreased from 2000 (4.30/100 000) to 2009 (3.83/100 000) with minor fluctuation,and the APC was-0.65％ (95％CI:-3.35％-2.12％,no statistical significance).Conclusion Brain tumors incidence and mortality in Zhejiang cancer registration areas were at a relatively high level.People who were at middle-age,especially above 70 years old should be the key targets for protection on this disease.Brain tumor incidence rates increased annually in Zhejiang,which should be called for attention.

Negative regulation on allograft immune response induced with up-regulated expression of IDO mediated by 3,4-DAA / 中华器官移植杂志

Objective To investigate role of N-(30,40-dimethoxycinnamonyl) anthranilic acid (3,4-DAA) in mediating the negative immune regulation by indoleamine 2,3-dioxygenase in mice skin transplantation.Method The mice skin transplant model was established.T lymphocytes were isolated from mice splenocytes,and serum was collected.ELISA was applied to detect the IL-2 and IFN-γ concentrations in culture supernates of mice spleen lymphocytes and serum.Flow cytometry was applied to examine the phenotypes of T lymphocytes and RT-PCR to analyze the IDO mRNA transcription.Results T lymphocyte proliferation was significantly decreased by 3,4-DAA and the concentrations of IL-2 and IFN-γ were apparently decreased in 3,4-DAA group as compared with those in control group.The percentages of CD3 +,CD4 + and CD8 + T lymphocytes were lower,and the percentage of CD4 + CD25 + T lymphocytes was higher in 3,4-DAA disposal group than in control group,but there was no significant difference.IDO mRNA expression showed obvious increase in 3,4-DAA group as compared with control group.Conclusion 3,4-DAA can up-regulate the IDO expression to induce the increasing metabolism of tryptophan,subsequently inhibiting T cell proliferation and showing specific property of negative immune regulation.

Observation on the effects of Kang'ai injection and Shenqifuzheng injection on liver function of patients with advanced primary liver cancer after interventional procedure / 国际中医中药杂志

Objective To investigate the effect of Kang' ai injection and Shenqifuzheng injection on liver function of patients with advanced primary liver cancer after being performed transcatheter arterial chemomembolization (TACE).Methods 120 patients with advanced primary liver cancer were randomly divided into three groups:a control group,a Kang'ai injection group,and a Shenqifuzheng injection group,with 40 patients in each group.All three groups were treated with TACE,and after TACE the control group was treated with anti-infection,inhibiting-acid,protecting-liver function and Shuganning tablets,20 ml/day.On this basis,the Kang'ai injection group was additionally injected with Kang'ai injection,40ml/day,and Shenqifuzheng injection group was additionally injected with Shenqifuzheng injection,250ml/day.All three groups were treated for 15 days.Liver function was tested and compared at the 3rd day,the 7th day and 14th day after TACE in all three groups.Results At the 14th day after TACE,ALT,AST,TBiL,and TBA of the Kang' ai group and Senqifuzheng group [(40.35 ± 10.10) μmol/L、(37.52 ± 10.57) μmol/L、(40.13 ± 8.36) μmol/L、(45.19 ± 19.65) μmol/L in Senqifuzheng group; (40.11 ±7.31) μmol/L,(34.99±9.38) μmol/L,(32.15±6.58) μmol/L,(40.75 ± 6.79) μmol/L in Kang'ai group] were greatly improved than the control group [(61.28 ± 13.38) μmol/L,(57.53 ± 13.36) μmol/L,(68.69± 7.25) μmol/L,(67.75 ± 17.88) μmol/L],with statistical significance (P＜ 0.01).Conclusion Kang'ai injiection and Shenqifuzhcng injection both can reduce liver function damage caused by TACE,thus they can be used together with TACE for treating advanced primary liver cancer.

Intravenous immunoglobin for treating pneumonia following kidney transplantation / 中华器官移植杂志

Objective To investigate the adjunctive therapeutic effects and safety of intravenous immunoglobin (IVIG) for treating pneumonia following kidney transplantation.Methods Sixteen cases of pulmonary infection after kidney transplantation were divided into two groups.Twenty-eight cases were subjected to IVIG therapy (0.2 g·kg-1 ·day-1) for 7-10 days besides the standard specific anti-bacterial,anti-fungal,and anti-virus treatment and regular immunosuppressive regimen with dose adjustment (IVIG group),and the control group was only treated with standard specific anti-pathogen therapy.The incidence and mortality ofsevere pulmonary infection,levels of serum IgG,T lymphocyte subsets,and creatinine in the two groups were observed.Results The effective power of IVIG group and control group was 100 ％ and 93.75 ％ (P＜0.05).The incidence of severe pneumonia in IVIG and control groups was 0 and 12.5％,respectively (P＜0.05),with the mortality being 0 and 6.25％,respectively (P＜ 0.05).The levels of serum IgG were significantly increased in IVIG group as compared with that before treatment and in control group.There were no significant adverse reactions associated with IVIG infusion.Conclusion As an adjunctive therapy,IVIG treatment for pulmonary infection can reduce the incidence of severe pulmonary infection and mortality after kidney transplantation,further increase the survival rate of patients after kidney transplantation.

Long term survival improved by optimization of immunosuppression strategy in renal transplant ecepients: a single center experience / 中华器官移植杂志

Objective To investigate the influence of immunosuppression strategy optimization on the outcomes of the renal transplant recipients in the last decades. Methods Data from 404 renal transplant recipients from Jan. 1st, 2001 to Dec. 31st, 2010 were analyzed retrospectively. The patients were divided into early transplant group (n = 260) and late transplant group (n= 144). The change of immunosuppression strategy included a low dose antithymoglobin (ATG) induction, a quick corticosteroid reduction and mycophenolate mofetil therapeutic monitoring with calcineurin inhibitor minimization. Recipients' gender,age, donor type, induction therapy, immunosuppression regime, occurrences of biopsy-proven acute rejection (BPAR), severe pulmonary infection and patient/allograft survival were compared between groups. A Cox regression model was used to investigate the factors that influenced the allograft survival. Results The follow-up rate was 98. 3 % in this study. The median follow-up period was 65 month (1-112 months). The proportion of ATG induction in late transplant group was significantly higher than in early transplant group (78. 5 % versus 31. 9 %, P<0. 01). The severe pulmonary infection rate was lower in late transplant group, while the BPAR rate was comparable between two groups. The allograft survival rate was significantly higher in late transplant group. Severe pulmonary infection was correlated with patient/allograft survival in Cox regression model. Conclusion The improvement of outcome in renal transplant recipients in our center is related to the optimization of immunosuppression strategy that reduces the severe pulmonary infection rate with no increase in BPAR.

Important trials of targeted therapy in patients with advanced gastric carcinoma / 国际肿瘤学杂志

The conventional treatment options for advanced gastric carcinoma patients remain unsatisfactory in terms of response rate and overall survival benefit. Targeted therapy plus systemic chemotherapy now becomes a new promising therapeutic option. In this review we profiled important trials of international multicenter phase Ⅲ clinical studies in patients with advanced gastric carcinoma, including ToCA trial, EXPAND trial, LOGIC trial, AVAGAST trial, REAL3 trial, and granite-1 trial. These trials warrant the role of molecular targeted therapy in patients with advanced gastric carcinoma.

Protective effects of sinomenine on renal ischemia/reperfusion injury in mice / 中华器官移植杂志

Objective To evaluate the protective effect of sinomenine (SIN) on renal ischemia/reperfusion (I/R) in mice. Methods In the experiment one, 12 C57BL/6 mice were randomly divided into 2 groups: SIN group (mice were injected with 200 mg/kg SIN by tail vein) and control group (mice were injected with equal volume of saline). Six and 24 hs later, the serum was collected and the contents of alanine aminotransferase (ALT) and creatinine (SCr) were determined. In the experiment two, C57BL/6 mice were randomly divided into 3 groups: sham-operated (SO) group, SIN group (mice were injected with 200 mg/kg sinomenine just before ischemia induction) and saline group (mice were injected with equal volume of saline at the same time). At the 6th h after reperfusion, the sera and renal samples subject to IR injury were collected. The SCr and BUN levels in serum were determined and renal histological changes were also examined. The apoptosis of renal tubular epithelial cells was measured by using terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assay. The infiltration of F4/80 positive macrophages was measured by using immunohistochemistry and that of neutrophils with myeloperoxidase (MPO) kits. The mRNA expression of tumor necrosis factor (TNF)-α, chemokine CXC ligand (CXCL)-10, intercellular adhesion molecule (ICAM)-1 and IL-17 was detected by using real-time reverse transcription PCR. The activation of transcription factor NF-κB was measured by using Western blotting. Results In the experiment one, there was no significant difference in ALT and SCr between the two groups at 6 or 24 h. In the experiment two,levels of SCr and BUN were lower in SIN group (P＜0. 05 or P＜0. 01 ), histological damage was milder (P＜0. 01 ), and apoptosis rate of renal tubular epithelial cells apoptosis was lower than in saline group (P＜0. 05). The infiltration of macrophages, neutrophils and the mRNA expression of TNF-α, CXCL-10, ICAM-1 and IL-17 in the renal tissue in SIN group were reduced as compared with saline group (P＜0. 05 or P＜0. 01 ). The activation of NF-κB in SIN group was significantly downregulated as compared with saline group. Conclusion SIN can ameliorate the renal IR injury without hepatic or renal toxicity, which is associated with inhibition of acute inflammatory response induced by reperfusion.

Influence of the concentration of silver nanoparticles on the proliferation behavior of human umbilical vein endothelial cell and human umbilical artery smooth muscle cells / 生物医学工程学杂志

The proliferation difference between Human Umbilical Vein Endothelial Cells (HUVEC) and Human Umbilical Artery Smooth Muscle Cells (HUASMC) in response to the concentration of silver nanoparticles was investigated via MTT, BCA and FCM tests. The obtained experimental data were statistically analyzed and discussed in order to know the causation of the proliferation difference. The results show there is significant difference in proliferation between HUVEC and HUASMC corresponding to the concentration of silver nanoparticles, and such difference can be attributed to the varied adhesion shape and apoptosis of the cells being influenced by nano-Ag content and Fetal bovine serum (FBS) content in culture medium.

Construction and identification of recombinant human cytomegalovirus with ganciclovir-resistance associated mutations in UL97 gene / 中华传染病杂志

Objective To construct drug-resistant variant recombinant human cytomegalovirus (rHCMV)and identify drug susceptibility by phenotypic and genotypic assays.Methods The UL97 fragments containing Pine I recongnition site and resistant mutation were introduced by site-directed mutagenesis using gene splicing by overlap extension polymerase chain reaction(PCR),and blended with human cytomegalo-virus(HCMV)standard strain ADl 69 genomic DNA proportionally,then the DNA mixture were transfected into MRC-5 fibroblasts by the vector of liposomes.HCMV-PP65 antigen was detected by indirect-immunofluorescent assay to verify rHCMV infection of MRC-5 fibroblasts.When the eytopathic effect(CPE)of homologous recombinant virus reached 100%,the virus was harvested.The purified target virus was screened by plague with different concentrations of ganciclovir(GCV)and the recombinant virus was identified by plague reduction test and DNA sequencing of drug-resistant genes(UL97 and UL54).Results The UL97 fragments containing intended mutations for transfection were constructed successfully.After cotransfected with AD169DNA mixture for 7 days,rHCMV formed cytopathology was obviously visible,which was verified as rHCMV infected focus by HCMV-PP65 antigen test.The UL97 genotypic analysis of recombinant virus obtained by cloning was as expected.No mutation was found by UL54 gene sequencing.The GCV susceptibility of rHCMV positive clone was 15 μmol/L (50% inhibiting concentration),which was 12-fold of standard AD169 strain and was drug-resistant phenotype.Conclusions The rHCMV containing intended mutations is constructed successfully by cotransfeetion into MRC-5 cells and the recombinant virus strain is obtained by GCV screening and plaque purifying.The establishment of this method provides technique platform for identifications of new drug-resistant mutations of HCMV during anti-viral therapy.

Multidrug resistance 1 gene polymorphism affects early mycophenolate mofetil exposure in Chinese renal transplant recipients / 中华器官移植杂志

Objective To investigate the relationship between the polymorphism of human multidrug resistance 1 gene(MDR1)polymorphism and early MMF pharmacokinetics.Methods Twenty-eight Chinese primary renal transplant recipients were emrolled.On day 14 post-transplant,patients took the MMF orally on fast.Whole blood samples(2 ml)were obtained at the following time points:predose(G0)and 0.5,1,1.5,2,4,6,8,10 and 12 h(C0.5,C1,C1.5,G2,C4,C6,C8,C10,C12,respectively)postdose during the dosing interval.The MPA plasrna concentration was assayed by high performance liquid chromatography (HPLC).Pharmacokinetie parameters were determined by WINNOLIN 3.1.Three major single nucleotide polymorphisrrls(SNP),C1236 T,G2677 T/A,C3435 T of MDR1 were analyzed by PCR-RFLP.Pharmacokinetie parameters of MPA were compared between different MDR1 genotype and haplotype groups.Ailele frenqueneis were also compared in high(MPA area under concentratation-time curve 0～12 h,frequencies of 1236 TT,2677 TT/AA,3435 TT in three major MDR1 SNP positions,exons 12,21 and 26,were 0.368,0.184 and 0.211,respectively.MPA AUC was significantly higher in 1236 TT group than in 1236 CC/CT group(65.36±11.51 vs 53.33±13.77,P=0.032).On C1236 T SNP,TT genotype frequency showed significant difference between MPA high and low exposure groups(66.7%vs 15.4%,P=0.013,OR=2.526).T allele frequency was marginally higher in MPA high exposure group than that in low exposure group(83.3%vs 53.3%,P=0.072).Conclusion TT genotype on 1236 of MDR1 indicates a risk of early high exposure to MPA in Chinese renal transplant patients given by oral MMF,

Microemulsificated CsA C_2 monitoring of Neoral in elderly Chinese renal transplant recipients / 中华器官移植杂志

(0.05). The CsA dosage and C 2 concentrations were lower in group II than in group I.Conclusion Neoral C 2 monitoring are beneficial to clinical outcomes in elderly Chinese renal transplant recipients and C 2 (concentration) is lower in elderly recipients than in young ones.