[Reversal effect of peptide-modified chitosan tetramethylpyrazine nanoparticles on multidrug resistance in tumor cells].

To prepare peptide-modified chitosan tetramethylprazine nanoparticles(FGF-CS-TMP-NPS) and investigate its reversal effect on multidrug resistance in tumor cells. The pEGF-CS-TMP-NPs were prepared by ion crosslinking method, and their physicochemical properties were investigated. Western blot was used to detect the expression levels of epidermal growth factor receptor(EGFR)(MCF-7, MCF-7/ADR, K562 and K562/ADR) and drug-resistant related protein P-gp. MCF-7/ADR and K562/ADR were selected as cell models. The cytotoxicity of pEGF-CS-TMP-NPs, the multiple of cell resistance to adriamycin, the reversal resistance index of pEGF-CS-TMP-NPs to doxorubicin and the sensitization of pEGF-CS-TMP-NPs to doxorubicin were detected by MTT assay. After MCF-7/ADR and K562/ADR were treated with pEGF-CS-TMP-NPs, the expression changes of P-gp were detected by Western blot. The encapsulation efficiency and drug loading of pEGF-CS-TMP-NPs were 37.66%± 0.53% and 3.25%± 0.34% respectively in HPLC. The nanoparticles showed an average particle size of(150.50±9.3) nm, polymer dispersity index of(0.059±0.007) and Zeta potential of(19.30±2.02) mV as detected by laser particle size analyzer. The nanoparticles were spherical and well dispersed under transmission electron microscope. Western blot results showed that EGFR was positively expressed in MCF-7 and MCF-7/ADR cells, while negatively expressed in K562 and K562/ADR cells. P-gp was highly expressed in MCF-7/ADR and K562/ADR, while negatively expressed in MCF-7 and K562. pEGF-CS-TMP-NPs had a weak effect on MCF-7/ADR and K562/ADR. The adriamycin resistance of MCF-7/ADR cells was 108.36 times, and that of K562/ADR cells was more than 100 times. When IC_(85) of pEGF-CS-TMP-NPs was used as the administration concentration, the reversion index of MCF-7/ADR and K562/ADR cells was 3.68 and 1.87, respectively. pEGF-CS-TMP-NPs could enhance the sensitivity of adriamycin to MCF-7/ADR cells in a positive correlation with the concentration, and the sensitivity was significantly higher than that of K562/ADR cells. Western blot results showed that the expression level of P-gp in MCF-7/ADR cells decreased significantly after treatment with pEGF-CS-TMP-NPs, while the expression level of P-gp in K562/ADR cells did not change significantly. Experimental results show that pEGF-CS-TMP-NPs have an active targeting effect on MCF-7/ADR cells with high EGFR expression, and can effectively reverse the multidrug resistance of MCF-7/ADR cells. Active targeting effect is related to the peptides modification of nanoparticles, and the mechanism of reversing tumor MDR may be achieved by down-regulating the expression level of P-gp.

Management of immunosuppressive drugs in HIV-positive solid organ transplant recipients / 器官移植

The application of combination antiretroviral therapy (cART) has significantly prolonged the life expectancy of patients infected with human immunodeficiency virus (HIV). However, viral infection and adverse reactions of cART drugs make patients more prone to organ failure. Solid organ transplantation has become a standard treatment for HIV-infected patients with end-stage organ failure. Nevertheless, among HIV-positive soild organ transplant recipients, multiple problems remain to be resolved, such as increased incidence of graft rejection, increased infection risk, drug toxicity and drug interaction between cART therapy and immunosuppressive drugs, etc. It is extremely challenging to deliver appropriate management for HIV-positive soild organ transplant recipients. Therefore, the application of immune induction therapy, calcineurin inhibitors, mammalian target of rapamycin (mTOR) inhibitors and other immunosuppressive drugs in HIV-positive soild organ transplant recipients was reviewed, aiming to provide reference for subsequent management of immunosuppression in HIV-positive soild organ transplant recipients.

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 progress on determination of intracellular concentration of immunosuppressant / 器官移植

Currently, extracellular concentration measurement is the major approach of therapeutic drug monitoring (TDM) of clinical immunosuppressant in organ transplantation. Its correlation with the efficacy of immunosuppressant remains elusive. With widespread application of liquid chromatography, the detection technology of intracellular concentration of immunosuppressant is gradually mature. Theoretically, it may more accurately reflect the efficacy of immunosuppressant due to that the level of drug exposure in target cells can be directly measured. In this article, the history and present situation of the determination of intracellular concentration of immunosuppressant were summarized, and the association between the determination methods of intracellular concentration of immunosuppressant and drug efficacy was emphatically analyzed. Detection of intracellular concentration of immunosuppressant possesses better application value in clinical practice, which is worthy of promotion in clinical settings.

Reversal effect of peptide-modified chitosan tetramethylpyrazine nanoparticles on multidrug resistance in tumor cells / 中国中药杂志

To prepare peptide-modified chitosan tetramethylprazine nanoparticles(FGF-CS-TMP-NPS) and investigate its reversal effect on multidrug resistance in tumor cells. The pEGF-CS-TMP-NPs were prepared by ion crosslinking method, and their physicochemical properties were investigated. Western blot was used to detect the expression levels of epidermal growth factor receptor(EGFR)(MCF-7, MCF-7/ADR, K562 and K562/ADR) and drug-resistant related protein P-gp. MCF-7/ADR and K562/ADR were selected as cell models. The cytotoxicity of pEGF-CS-TMP-NPs, the multiple of cell resistance to adriamycin, the reversal resistance index of pEGF-CS-TMP-NPs to doxorubicin and the sensitization of pEGF-CS-TMP-NPs to doxorubicin were detected by MTT assay. After MCF-7/ADR and K562/ADR were treated with pEGF-CS-TMP-NPs, the expression changes of P-gp were detected by Western blot. The encapsulation efficiency and drug loading of pEGF-CS-TMP-NPs were 37.66%± 0.53% and 3.25%± 0.34% respectively in HPLC. The nanoparticles showed an average particle size of(150.50±9.3) nm, polymer dispersity index of(0.059±0.007) and Zeta potential of(19.30±2.02) mV as detected by laser particle size analyzer. The nanoparticles were spherical and well dispersed under transmission electron microscope. Western blot results showed that EGFR was positively expressed in MCF-7 and MCF-7/ADR cells, while negatively expressed in K562 and K562/ADR cells. P-gp was highly expressed in MCF-7/ADR and K562/ADR, while negatively expressed in MCF-7 and K562. pEGF-CS-TMP-NPs had a weak effect on MCF-7/ADR and K562/ADR. The adriamycin resistance of MCF-7/ADR cells was 108.36 times, and that of K562/ADR cells was more than 100 times. When IC_(85) of pEGF-CS-TMP-NPs was used as the administration concentration, the reversion index of MCF-7/ADR and K562/ADR cells was 3.68 and 1.87, respectively. pEGF-CS-TMP-NPs could enhance the sensitivity of adriamycin to MCF-7/ADR cells in a positive correlation with the concentration, and the sensitivity was significantly higher than that of K562/ADR cells. Western blot results showed that the expression level of P-gp in MCF-7/ADR cells decreased significantly after treatment with pEGF-CS-TMP-NPs, while the expression level of P-gp in K562/ADR cells did not change significantly. Experimental results show that pEGF-CS-TMP-NPs have an active targeting effect on MCF-7/ADR cells with high EGFR expression, and can effectively reverse the multidrug resistance of MCF-7/ADR cells. Active targeting effect is related to the peptides modification of nanoparticles, and the mechanism of reversing tumor MDR may be achieved by down-regulating the expression level of P-gp.

Novel tumor metastasis suppressorgene LASS2/TMSG1 S248A mutant promotes invasion of prostate cancer cells through increasing ATP6V0C expression / 北京大学学报(医学版)

OBJECTIVE@#LASS2/TMSG1 gene is a novel tumor metastasis suppressor gene cloned from human prostate cancer cell line PC-3M in 1999 by Department of Pathology,Peking University of Basic Medical Sciences. It was found out that protein encoded by LASS2/TMSG1 could interact with the c subunit of vacuolar-ATPase (ATP6V0C). In this study, we explored the effect of LASS2/TMSG1 and its mutants on proliferation, migration and invasion of human prostate cancer cells and its molecular mechanism.@*METHODS@#We constructed four LASS2/TMSG1 mutants and stably transfected the variants to human prostate cancer cell line PC-3M-1E8 cell with high metastatic potential. The stable transfectants were identified by qPCR and Western blot through analyzing the expression of LASS2/TMSG1 and ATP6V0C, the cell biology functions of LASS2/TMSG1 and its four mutants were studied using growth curve,MTT assay, soft agar colony formation assay, wound migration assay, Matrigel invasion study and flow cytometry. Furthermore, immunofluorescence was used to analysis the interaction of LASS2/ TMSG1 mutants and ATP6V0C.@*RESULTS@#LASS2/TMSG1 mRNA and protein in LASS2/TMSG1 group and Mut1-Mut4 groups were higher than that in Vector group; Western blot showed that ATP6V0C protein in LASS2/TMSG1 wild group was lower than that in Vector group, but ATP6V0C protein in LASS2/TMSG1 S248A group was obviously higher than that in Vector group. MTT test and growth curve assay showed growth ability in LASS2/TMSG1 S248A group was increasing compared with other groups from day 5. Soft Agar colony formation experiment showed anchor independent growth ability in LASS2/TMSG1 S248A group was higher than those in the other groups (P<0.05), Cell migrations (from 35.3%±3.2% to 70.3%±3%) in LASS2/TMSG1 S248A group was increasing compared with LASS2/TMSG1 wild group (P<0.01), and more cells passed through Matrigel in LASS2/TMSG1 S248A group compared with LASS2/TMSG1 wild group (from 50±3.2 to 203±6.5, P<0.01), the apoptosis rate in LASS2/TMSG1 S248A group was obviously higher than that in LASS2/TMSG1 wild group (from 7% to 15.1%, P<0.05), and the G0/G1 ratio in LASS2/TMSG1 S248A group was obviously higher than that in LASS2/TMSG1 wild group (from 51.0% to 85.4%). Furthermore, double immunofluorescent staining observed the colocalization between ATP6V0C and LASS2/TMSG1 protein and its mutations, the expression of ATP6V0C in LASS2/TMSG1 S248A group increased significantly compared with the other groups.@*CONCLUSION@#LASS2/TMSG1 S248A promotes proliferation, migration and invasion of prostate cancer cells through increasing ATP6V0C expression, suggesting that aa248-250 is an important function site for LASS2/TMSG1 in invasion suppression of prostate cancer cells.

Molecular typing and antibiotic resistance of Shigella isolated from 2011 to 2014 in Shandong Province / 中华疾病控制杂志

Objective To study the characteristics and epidemic trend of Shigella in Shandong province through the analysis of serotype, virulence genes, molecular typing and drug sensitivity. Methods The serotype was classified using the method of slide agglutination. Polymerase chain reaction (PCR) was used to amplify the related virulence genes. The molecular typing was carried out by pulsed field gel electrophoresis (PFGE), and the antibiotic sensitivity of the strains was determined by micro-broth dilution method. Results The main serogroups of 44 Shigella strains were Shigella flexneri (54.55%) and Shigella sonnei (43.18%). The carrying rates of ipaH, Set1, Sen and ial were 100%, 43.18%, 56.82% and 50.00%, respectively. By PFGE typing, the strains of Shigella flexneri were divided into 18 patterns with a low similarity. The strains of Shigella sonnei were divided into 14 patterns, and the similarity of 89.47% of the strains was more than 90%. 44 strains of Shigella had different levels of resistance to 14 of the 15 antibiotics. 93.18% of the strains were multidrug resistant. Conclusion The Shigella in Shandong province is dominated by serogroups of Shigella flexneri and Shigella sonnei, with high virulence gene carrying rate, clustering distribution and severe antibiotic resistance. It is necessary to strengthen the monitoring on serotype, traceability and antibiotic resistance of Shigella in Shandong province.

Regulation of transplantation of human umbilical cord blood derived mesenchymal stem cells on secretion of neural biochemistry marker after traumatic brain injury in rats / 生物医学工程学杂志

This research was to study the regulation of intravenous administration of human umbilical cord blood mesenchymal stem cells (HUCBMSCs) on secretion of neural specific protein in rats after traumatic brain injury (TBI), and to explore its mechanisms promoting the recovery of neurological function. The TBI models of rats were established. We then injected HUCBMSCs, labelled by Brdu (5-bromo-2-deoxyuridine), into the TBI rats via the tail vein using modified Feeney free-falling method. The levels of neural biochemical indicators (serum S100β protein, NSE, LDH, CK) of rats were detected in shamed group, injury group and HUCBMSCs-transplanted group. And the morphological changes of brain tissue of rats in the three groups were observed by using HE staining under light microscope. During the whole experiment no immunosuppressant was used for the four groups. From the research, transplant-related death of the rats was not found in transplantation group. In the injury group, rises were found in contents of serum S100β protein, NSE, LDH, CK in the early stage after the rats were injured, which were much higher than those in shamed group at correspondent time point (P < 0.01). In HUCBMSCs-transplanted group, although these biochemistry indexes were found rising for a short period in the early stage, along with the time, these indexes were obviously lower than in those injury group (P < 0.05). Under light microscopy pathological changes of rats in HUCBMSCs-transplanted group were much slighter than those in injury group. It was well concluded that in the situation of no immuno-suppressants, the intravenous-injected HUCBMSCs could reduce the secretion of serum S100β protein, NSE, LDH, CK, promote the repair of tissue injury effectively, and promote the functional recovery of neurons.

Determination of Ruthenium, Rhodium, Palladium, Iridium and Platinum in Copper-Nickel Sulfide Ores by Bismuth-Antimony Fire Assay / 分析化学

A bismuth-antimony fire assay method for the preconcentration of ruthenium, rhodium, palladium, iridium and platinum in copper-nickel sulfide ores was developed. 40. 0 g bismuth trioxide, 25. 0 g boric acid, 10. 0 g sodium carbonate and 1. 00 g starch were mixed with 10. 0 g sample in a 120 mL porcelain bowl, which was put in a furnace at 850 ℃. After 20 min the temperature was raised to 1000 ℃ and held for another 40 min, and then the bowl was taken out, with the slag poured, which left the bismuth button to air cooling. A two-step cupellation procedure was developed. During the first step, the bismuth button was cupellated in a magnesia cupel until its diameter reached 5 mm or so, then it was transferred to a crucible cover containing 20 g melting antimony and kept cupellating, at last a bead with a diameter of 1 mm was obtained. The bead was microwave-digested, after cooling down to room temperature, the solvent of which was transferred to a volumetric flask and diluted to 10 ml with water. Pt and Pd were analyzed by inductively coupled plasma-atomic emission spectrometry ( ICP-AES), while 99 Ru, 103 Rh, 191 Ir were analyzed by inductively coupled plasma-mass spectrometry (ICP-MS), with 115 In, 185 Re as internal standard. RSD (n = 12) of the analysis results of five platinum group elements ( PGEs) in standard reference material GBW07196 ranged from 7. 04% to 9. 48% . Under the condition of 10 g sample, the detection limits (ng / g) for PGEs are 0. 027 for Ru, 0. 016 for Rh, 0. 11 for Pd, 0. 10 for Ir and 0. 11 for Pt. The method was applied to the determination of PGEs in GBW07194, GBW07195, GBW07196 with satisfactory results.

Molecular characteristics and antibiotic resistance of Vibrio cholerae O139 in Shandong province / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the molecular epidemiological characteristics and antibiotic resistance profiles of Vibrio cholerae O139 in Shandong province.</p><p><b>METHODS</b>A total of 13 strains of V. cholerae O139 (9 clinical strains and 4 environmental strains) isolated from cholera epidemics in Shandong province since 1997 were recovered and confirmed with serum agglutination and biochemical reaction. Pulsed-field gel electrophoresis (PFGE) was carried out for molecular subtyping. Virulence genes and drug resistance related genes were detected by PCR. Antibiotic susceptibility tests were performed using micro-broth dilution method.</p><p><b>RESULTS</b>Thirteen strains of V. cholerae O139 were differentiated into seven pulsetypes. One clinical strain and two environmental strains isolated from Jining in 2013 were clustered into the pulsetype namely KZGN11O139. CN0077, and an identical PFGE pattern of KZGN11O139. CN0002 was found among three clinical strains from Jinan in 2005, Jining in 2005 and Heze in 2009. Other pulsotypes were unique in China and found only in Shandong province. Because of deletion of ctxAB and tcpI, the PFGE patterns of two strains isolated from Yantai in 2000 and 2004 were different from other 11 strains which harbored ctxAB, tcpA, tcpI, rtxA, hlyA and toxR. All strains contained one or more drug resistance related genes such as intI 1, intI 4 and sxt, and were resistant to two kinds of antibiotics at least. Among the 12 kinds of antibiotics, the resistant ratioes to kamamycin, trimethoprim-sulfamethoxazole, ampicillin and gentamicin were 11/13, 9/13, 7/13 and 7/13, respectively.</p><p><b>CONCLUSION</b>Molecular subtyping indicates possible epidemiological links among V.cholerae O139 in Shandong province, and almost all strains were toxigenic and drug resistant.</p>

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.

Influence of P-glycoprotein inhibitor on the amphotericin B transport across the blood brain barrier / 中华传染病杂志

Objective To determine the influence of P-glycoprotein (P-gp) inhibitor on the blood brain barrier (BBB) transport of amphotericin B (AmB)..Methods An in-vitro BBB model was established with brain capillary endothelia cells (BCEC). AmB was chosen as the test drug and verapamil was chosen as the inhibitor of P-gp.Cellular uptake of AmB at different time points and with series of verapamil concentrations were performed respectively after the determination of appropriate incubation time and drug dosage by the cytotoxicity assay. The AmB concentrations of series of samples were detected using high performance liquid chromatography (HPLC) method. One-way ANOVA analysis and Bonferroni test were used for data analysis.Results The cellular transport of AmB was accumulated as the time prolonged.The inhibitor group had a significant higher cellular uptake levelsof AmBat the time point of 90 min (t=6.753,P=0.001),120 min (t=3.574,P=0.016) and 150 min (t=4.759,P=0.005) as compared with the control group.The AmB cellular uptake level increased significantly when BCEC were incubated with verapamil of 2 μmol/L (P=0.000),5 μmol/L (P=0.014),10 μmol/L (P=0.000),50 μmol/L (P=0.014),75 μmol/L (P=0.000) and 100 tμmol/L (P=0.000),respectively,compared with the control group.Conclusion The P-gp inhibitor verapamil can enhance the cellular uptake of AmB which indicates that P-gp is involved in the BBP transport of AmB.

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.

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.

Effect of butylphthalide on H2S content and the expression of NR2B in the hippocampus of alcohol dependence rats / 中华行为医学与脑科学杂志

Objective To investigate the effect of butylphthalide (NBP) on H2S content and the expression of NR2B in the hippocampus of alcohol dependence rats. Methods A total of 84 SD male rats were randomly divided into 6 groups. Except for the normal group, other groups were subjected to alcohol solution with concentration of 6% ( V/V) for 28 d. Drug intervention began at the 14th day,and rats in the low,medium,high dose group were treated with NBP with a different concentration. Erden abstinence scoring was used to evaluate the rats withdrawal symptom. H2S content was measured in one side of hippocampus and CBS activity was tested in the other side of hippocampus. Hippocampus of 3 rats from each group was used to investigate NR2B mRNA level. Results Withdrawal symptom score ( 12.27 ± 1. 19),H2S content(30. 25 ±8.82), CBS activity (72. 44 ±7. 46) and NR2B mRNA expression( 19. 47 ±0. 86) in medium dose NBP group rats were lower than withdrawal symptom score(14.09 ±2.21) ,H2S content(44. 50 ±6. 65) , CBS activity(79. 06 ±4. 57) and NR2B mRNA expression (29. 13 ±1.39) in experimental control group (P<0.05). Withdrawal symptom score(12. 18 ±1.08) ,H2S content(33.00 ±5.38) ,CBS activity(67. 81 ±9. 37) and NR2B mRNA expression(23. 12 ± 1. 86) in high dose NBP group rats were lower than experimental control group (P < 0. 05). Conclusion NBP can reduce withdrawal symptoms of alcohol dependence rats,may be related to decreased expression of H2S/CBS system, and NR2B mRNA expression.

Antibiotic resistance and molecular typing of Listeria monocytogenes from foods in Shandong province from 2009 to 2010 / 中华预防医学杂志

<p><b>OBJECTIVE</b>To know the antibiotic resistance and molecular characteristics of Listeria monocytogenes in Shandong province and to study the relationship between antibiotic resistance phenotypes and genome types.</p><p><b>METHODS</b>From 2009 to 2010, a total of 80 Listeria monocytogenes isolates were collected from raw meat, cooked meat, aquatic products and other foods in 6 cities of Shandong province. The antibiotic susceptibility was measured by broth microdilution method, PFGE was performed for molecular typing and the relationship between antimicrobial resistance and PFGE patterns was analyzed.</p><p><b>RESULTS</b>16.25% (13/80) of the isolates were drug-resistant. Imipenem resistance was the most prevalent (12.50%, 10/80), followed by tetracycline and doxycycline (3.75%, 3/80 and 2.50%, 2/80). A total of the 80 isolates were subtyped into 9 antibiotic resistance patterns and 34 PFGE types which were largely dominated by the type 17 and 29. Antibiotic resistance pattern A corresponded to 79.41% (27/34) of PFGE types.</p><p><b>CONCLUSION</b>The antibiotic resistance of Listeria monocytogenes in Shandong province is serious from 2009 to 2010 and there is no correlation between PFGE types and antibiotic resistance patterns.</p>

Improved renal function in advanced renal cell carcinoma patient by targeted therapy / 中华泌尿外科杂志

Objective To report and analyze the renal function improvement in a case with ad-vanced bilateral renal cell carcinoma after targeted therapy. Methods The patient was a 60-year-old man who complained of lower back pain for 1 month. Ultrasound and CT scan detected bilateral renal masses, left lesion was 11.0 cm×9.4 cm×8.5 cm, and the right one was 3.5 cm×4.3 cm×4.1 cm. X-ray examination showed metastatic lesions in liver and lower right lung. GFR was 20.39 ml/min of left kidney, 25.40 ml/min of right kidney. The renal biopsy confirmed renal clear cell carcinoma. Sorafenib was administrated 400 mg twice or once daily for 12 weeks. Results After the targeted therapy, the decreased bilateral kidney tumor sizes were identified by CT scan. There was liquid nec-rosis in the tumor, and no new metastatic lesion detected. The kidney function was improved as well. The total GFR increased to 71.38 ml/min. Left kidney GFR increased to 31.57 ml/min, right kidney GFR increased to 39.81 ml/min, respectively. Conclusion Targeted therapy could improve renal function in advanced renal cell carcinoma cases by controlling tumor development.

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,

Clinical diagnosis and treatment of BK virus infection in renal transplant recipients / 中华器官移植杂志

Objective To investigate the prevalence of BK virus(BKV) infection in renal transplant recipients and the methods for its clinical diagnosis and treatment.Methods The urine and blood samples of 64 renal transplant recipients were taken for the BKV cytological and PCR tests.Five clinical factors were investigated to find the etiologic risks of BKV infection in renal transplant recipients.Four BKV infected recipients received experimental treatment.Results The occurrence of urine decoy cell,BKV viruria and viremia in all patients was(28.7 %),(17.2 %) and(6.3 %),respectively.The occurrence of urine decoy cell in serum creatinine(SCR) level elevated recipients was higher than that in SCR stable recipients(P=(0.04)).No significant relationships were found between the five clinical factors(gender,age,induction therapy,acute rejection episode,renal function after transplantation) and the occurrence of urine decoy cell,viruria and viremia.Ganciclovir treatment showed effective in four BKV infected recipients.Conclusions BKV monitoring is necessary for those recipients with evaluated SCR levels after renal transplantation.BKV viremia test can be used as a screening test.The efficacy of ganciclovir in the treatment of BKV infection should be further investigated.