Clinical application and pharmacokinetic study of nanocarriers in drug delivery system / 药学学报

Nanotechnology has shown obvious advantages in the field of medical treatment and diagnosis. Through the encapsulation of nano carriers, drugs not only enhance the therapeutic effect and reduce toxic and side effects, but also become intelligent responsive targeted drug systems through the modification on the surface of nano carriers. However, due to the obstacles in relevant basic research, production conditions, cost, clinical trials, and the lack of pharmacokinetic research on various drug loading systems, few nano systems have been used in therapy. In order to solve the above problems, this paper reviewed and analyzed the research progress of nano carriers in drug delivery, including their auxiliary role and characteristics, types and functions, pharmacokinetics, application prospects and challenges.

Correlation of tumor necrosis factor-β and interleukin-1 gene cluster polymorphism with susceptibility to bacteremia in patients undergoing kidney transplantation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Bacteremia remains a significant cause of morbidity and mortality after kidney transplantation. This study was conducted to investigate whether the polymorphisms of tumor necrosis factor (TNF)-β, interleukin (IL)-1β, and IL-1 receptor antagonist (IL-1ra) gene predicted the susceptibility to bacteremia within the first 6 months after kidney transplantation.</p><p><b>METHODS</b>Subjects comprised 82 infected kidney transplant recipients and 60 non-infected kidney transplant recipients. Bacteremia was diagnosed in 16 of the 82 infected recipients. Genomic DNA from these 142 kidney transplant recipients was extracted from peripheral blood leukocytes. Regions containing the NcoI polymorphic site at position +252 of TNF-β gene and the AvaI polymorphic site at position -511 of IL-1β gene were amplified by polymerase chain reaction (PCR) and subsequently digested with NcoI and AvaI restriction enzymes, respectively. The polymorphic regions within intron 2 of IL-1ra gene containing variable numbers of a tandem repeat (VNTR) of 86 base pairs were amplified by PCR.</p><p><b>RESULTS</b>Genotypic and allelic frequencies were similar between infected recipients and non-infected ones. Individual locus analysis showed that recipient TNF-β and IL-1ra gene polymorphisms were not associated with the presence of bacteremia (P = 0.684 and P = 0.567, respectively). However, genotype analysis revealed that recipient IL-1β-511CC genotype was strongly associated with susceptibility to develop bacteremia (P = 0.003). Recipient IL-1β-511CC genotype (odds ratio 5.242, 95% confidence intervals 1.645-16.706, P = 0.005) independently predicted the risk for bacteremia within the first 6 months after kidney transplantation.</p><p><b>CONCLUSIONS</b>These findings indicate a critical role of IL-1β gene polymorphisms in susceptibility to bacteremia after kidney transplantation, which may be useful to screen for patients at higher risk for post-transplant bacteremias. Thus, the identified individuals can benefit from preventive treatment and a less potent immunosuppressive regimen.</p>

Pattern of lymph node metastasis and extent of lymphadenectomy for distal gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To analyze lymph node (LN) metastasis patterns and determine the appropriate extent of LN dissection in distal-third gastric cancer.</p><p><b>METHODS</b>Clinical data of 545 patients with distal third gastric cancer undergoing radical operation in the Fujian Provincial Hospital between 2001 and 2010 were analyzed retrospectively. The metastasis rate for each LN station was analyzed stratified by the depth of tumor invasion.</p><p><b>RESULTS</b>The incidence of LN metastasis in this cohort was 38.2% (208/545). LN metastasis rate in mucosal cancer was 2.0% (2/99) and involved LNs were limited to station 1 LN stations. LN metastasis rate in submucosal cancer was 18.9% (18/95), significantly higher than that in mucosal cancer (P<0.01). The metastasis rates to groups No.7, 8 and 9 in station 2 were 5.3% (5/94), 3.2% (3/94), and 1.1% (1/89) respectively. In addition, 3 cases (3.2%) had metastasis in station 2 outside the range of groups 7, 8 and 9 including groups No.1, 11p and 12. Gastric cancer invading the muscularis propria or deeper layers showed an significant increased rate of metastasis (P<0.01).</p><p><b>CONCLUSION</b>D1 dissection seems to be sufficient for mucosal cancer. Standard D2 dissection should be performed for cancers of the muscularis propria or deeper. For submucosal cancer, an extended D1+ dissection is required for complete removal of metastatic nodes.</p>

Analysis of prognostic factors in lymph node-negative advanced gastric cancer patients / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the prognostic factors of lymph node-negative advanced gastric cancer patients in order to guide adjunctive therapy and surveillance tragedy.</p><p><b>METHODS</b>A total of 236 advanced gastric cancer patients with no less than 12 retrieved lymph nodes and without lymph node metastasis from Fujian Provincial Hospital between 1998 and 2008 were collected retrospectively. Univariate and multivariate prognostic analysis were performed.</p><p><b>RESULTS</b>Two hundred and twenty-four patients(94.9%) were followed up and 5-year overall and disease-free survival rates were 75.2% and 66.4% respectively. Univariate prognostic analysis showed that depth of infiltration, Lauren histotype and retrieved lymph nodes were associated with 5-year overall survival(all P<0.05). Multivariate prognostic analysis testified that depth of infiltration was independent prognostic predictor(P<0.05). Recurrent rates of T2 and T3 patients were 5.8%(8/138) and 14.0%(12/86),5-year overall survival rates were 82.5% and 59.0%, 5-year disease-free survival rates were 70.4% and 52.2% respectively. These differences were all statistically significant (all P<0.05).</p><p><b>CONCLUSIONS</b>T2N0 gastric cancer patients have a better prognosis than T3N0 patients. Depth of infiltration should be considered to stratify lymph node-negative gastric cancer patients for an adjunctive treatment and follow-up scheduling.</p>

Analysis of antibiotics treatment in 86 cases of liver transplant recipients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To analyze the characteristic of bacterial infections, and the relationship between antibiotics treatment and bacterial infections after liver transplantation, and to prevent antibiotic-resistant bacterial infections.</p><p><b>METHODS</b>86 liver transplant recipients were retrospected. Different indexes including limited daily dose, the frequency of medication, drug use index were used to evaluate the rationality of the use of antibiotics, three-dimensional test was used to explore extended-spectrum beta-lactamase and AmpC enzyme of Gram-negative bacteria.</p><p><b>RESULTS</b>The major pathogens of infection after liver transplantation were Enterococcus faecalis, Enterobacter cloacae, fungi and E. coli. Pre-operative antibiotic utilization rate was 83.7%, it was mainly a single use of antibiotics; After- operative antibiotic usage was 100.0%, it was mainly joint use of two or three antibiotics; The top 3 antibiotics used were cephalosporins, the combined enzyme inhibitors and penicillin. Antibiotics with drug utilization index (DUI) more than 1.1 included ampicillin and Lalin proxy. 43.3% and 31.8% of Gram -Negative bacteria produced ESBLs and AmpC, respectively, while 21.3% Gram -Negative bacteria produced two enzymes.</p><p><b>CONCLUSION</b>There is high incidence of bacterial infections after liver transplantation. The use of antibiotics is high dose, high-frequency and reasonable; High resistance of bacterial infections was prone to develop and the prevention of the high resistance of bacterial infections is very important.</p>

Longbixiao capsule reduces expressions of TGF-beta1 and Smoothelin in human prostatic stromal cells cultured in vitro / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the effects of the Chinese herbal medicine of Longbixiao (LBX) Capsule on the expressions of TGF-beta1 and Smoothelin in human prostatic stromal cells cultured in vitro.</p><p><b>METHODS</b>Blood serum medicated with LBX was incubated with the stromal cells isolated from men with benign prostatic hyperplasia (BPH) and cultured in vitro. The mRNA expression levels of TGF-beta1 and Smoothelin were detected by real-time RT-PCR and other relevant techniques.</p><p><b>RESULTS</b>In the high and low concentration groups, the gene relative expressions of TGF-beta1 were (0.158 +/- 0.020) and (0.169 +/- 0.020) , while those of Smoothelin were (0.035 +/- 0.007) and (0.036 +/- 0.007) respectively, both significantly decreased in comparison with the control group(P < 0.01).</p><p><b>CONCLUSION</b>LBX reduces the mRNA expressions of TGF-beta1 and Smoothelin in human prostatic stromal cells and can be used in the treatment of BPH.</p>

Cefoxitin disk diffusion test in the detection of MRS heterogenic drug-resistant strains / 中南大学学报(医学版)

OBJECTIVE@#To evaluate the reliability and clinical practicability of cefoxitin disk diffusion test in the detection of methicillin-resistant staphylococcus (MRS) heterogenic drug-resistant strains.@*METHODS@#Three hundred and ten strains of staphylococcus isolated from clinics were detected by the oxacillin disk diffusion test, the cefoxitin disk diffusion test as well as the oxacillin agar dilution test according to the standard operation procedures of NCCLS, and the detection of mecA gene of staphylococcus was used as a criterion. The sensitivities and specitivities of the 4 methods were compared.@*RESULTS@#By the detection of mecA gene, the ratio for MRSA was 57.1%(113/198) and the ratio for MRCNS was 62.5%(70/112). Both the sensitivity and specificity of cefoxitin disk diffusion test in the detection of MRS were 100%, and those in the detection of MRCNS were 98.6% and 100%.@*CONCLUSION@#Cefoxitin disk diffusion test is reliable, simple and convenient, and it can be used as a conventional method for the detection of MRS in clinical laboratories.

Effect of CagA(+) helicobacter pylori strain on the expression of connexin 43 and cell proliferation in BGC-823 cells / 中南大学学报(医学版)

OBJECTIVE@#To determine the effect of CagA(+) Helicobacter pylori(H.pylori)strain and anti-H.pylori drugs on the expression of connexin 43(Cx43) and cell proliferation of BGC-823 cells in vitro,and to investigate the relation between the changes of Cx43 expression, cell proliferation of BGC-823 cells and CagA(+)H.pylori.@*METHODS@#BGC-823 cells were co-cultured with CagA(+) H.pylori strain(NCTC J99) or CagA(-) H.pylori strain(NCTC 12908)at bacteria/cells ratio of 20:1,100:1 and 500:1 for 24 hours and 48 hours respectively. anti-H.pylori drugs was given in the group co-cultured at bacteria/cells ratio of 100:1 after 16 hours. In the control group, BGC-823 cells were cultured for 24 hours and 48 hours respectively,but without H.pylori or antij H.pylori drugs. Immunocytochemical SABC method and the image analysis of the computer were applied to detect the changes of Cx43 expression in BGC-823 cells. The cell proliferation was examined by methyl tetrazolium (MTT) method.@*RESULTS@#(1)The expression of Cx43 in the control group after cultivation for 48 hours was higher than that for 24 hours (P0.05). Cx43 expression in the groups co-cultured with CagA(-) H.pylori strain at the ratio of 100:1 and 500:1 was lower than that in the control group, and Cx43 expression at the ratio of 500:1 was lower than that at the ratio of 20:1 for 24 hours and 48 hours. Cx43 expression increased after the intervention with anti-H.pylori drugs for 48 hours. (2) In the groups co-cultured with CagA(+)H.pylori strain, the optical density value of MTT indicated that the cell proliferation at the bacteria/cells ratio of 100:1 was higher than that in the control group, but no significant difference was found in other two groups co-cultured for 24 hours. After co-culturing for 48 hours, the cell proliferation at the bacteria/cells ratio of 20:1 and 100:1 was significantly accelerated, while the cell proliferation at 500:1 was inhibited. In the groups co-cultured with CagA(-) H.pylori strain,there was no change in the cell proliferation. Intervention with anti-H.pylori drugs could suppress the cell proliferation.@*CONCLUSION@#CagA(+) H.pylori can down-regulate the expression of Cx43 in BGC-823 cells,which is related to the reaction time and the density of H.pylori. Low density of CagA(+)H.pylori suspensions can accelerate the proliferation of BGC-823 cells, while high density can suppress the cell proliferation. The CagA(-) H.pylori has no effect on the cell proliferation. Intervention with anti-H.pylori drugs can up-regulate the expression of Cx43,and suppress the cell proliferation of BGC-823 cells.

Antibiotic resistance of Helicobacter pylori / 中南大学学报(医学版)

OBJECTIVE@#To examine the infection and bacteria resistance of Helicobacter pylori (H.pylori) to clarithromycin and furazolidone,to determine whether the antibiotic resistance is primary or secondary, and to decide if a new H.pylori infection plays a role in eradication failures.@*METHODS@#Twenty one H.pylori had been isolated from human biopsy specimens, and antimicrobial susceptibility testing was performed. DNA fingerprints were generated using random amplification polymorphic DNA (RAPD) to determine the identity of H.pylori before and after the eradication therapy.@*RESULTS@#Eight bacteria resisted against clarithromycin, and one against furazolidone, with the resistant rates 38.1% and 4.8% respectively. The number of primary antibiotic resistance, secondary resistance and new infection was 1 for each.@*CONCLUSION@#Resistance to clarithromycin is more common compared with that to furazolidone. Development of primary and secondary resistance to clarithromycin occurs as a rule in eradication failures. New H.pylori infection plays a role in eradication failures.

Distribution of pathogen and resistance of nosocomial infections in the intensive care units / 中南大学学报(医学版)

OBJECTIVE@#To determine the distribution of pathogens and their characteristics of drug susceptibility originating from nosocomial infections in the intensive care units (ICU), and to provide evidence for clinical anti-infection treatments.@*METHODS@#Retrospective analysis to the pathogens and their drug susceptibility characteristics was carried out. These pathogens were isolated from the samples that came from patients infected in the ICU from 2002 to 2004.@*RESULTS@#The main nosocomial infective pathogens in the ICU were gram negative bacilli (48.2%), and the next ones were gram positive bacteria (43.3%) and fungus (8.5%). The most common gram negative bacilli were Pseudomonas aeruginosa and Escherichia coli; while for gram positive bacteria, the main bacterin were Staphylococcus aureus. The gram negative bacilli could resist 4 or more than 4 antibiotics, and the rate for resistance exceeded 40%. Similarly, oxacillin resistance staphylococcus could resist 7 antibiotics, and the rate was over 50%. The detective rates of ESBLs and AmpC enzymes produced by Escherichia coli and K. peumoniae were 34.0% & 30.7% and 13.2% & 23.1%, respectively. The rate for oxacillin resistance staphylococcus was 66.3%, and there was relative high resistance rate ( > 55%) for most antibiotics: There was statistical difference, compared with that of non-resistant strains.@*CONCLUSION@#Though gram positive coccus still play an important role, most infections are caused by gram negative bacilli of nosocomial infections in the ICU. The antibiotics resistant rate of all bacteria has been rising gradually. It shows strong resistance and multi-drug resistance. The most importment cause for resistance of gram negative bacilli is that the bacteria can produce ESBLs and AmpC enzymes. The antibiotic resistant rate for oxacillin resistance staphylococcus is really high.

Pathogenic characters of infected bacteria after liver transplantation / 中南大学学报(医学版)

OBJECTIVE@#To analyze the main pathogens of infection after the liver transplantation and their antibiotic resistant patterns.@*METHODS@#The main pathogens of infection after the liver transplantation were retrospectively analyzed. Using 3-dimensional tests, ESBLs (extended-spectrum beta-lactamase), and AmpC were detected among the Gram negative bacilli. beta-Lactamase and Van gene in Enterococcus were determined by the standard agar dilution susceptibility tests and Nitrocefin respectively.@*RESULTS@#The main infected strains were Enterococcus faecalis (15.0%), Enterobacter cloacae (13.9%), fungus (13.3%), and Escherichia coli (10.7%) after the liver transplantation. Among them, 32.4% of Enterobacter cloacae and 36.8% of Escherichia coli produced ESBLs; 33.8% of Enterobacter cloacae and 10.5% of Escherichia coli. produced AmpC beta-lactamases. The detectable rate of VanA gene in Enterococcusfaecalis and Enterococcus faecium was 7.5% and 11.1%; VanB was 3.8% and 7.4%; VanC was 1.3% and 0, respectively.@*CONCLUSION@#The infection mainly occurs in the intestinal tract after the liver transplantation. The production of ESBLs and AmpC beta-lactamases is the main mechanism of antibiotic resistance. The increased detectable rate of vancomycin-resistant Enterococcus should be paid attention to.

Clinical significance of expression of PSA, hK2, PSMA in the peripheral blood of patients with prostate cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To find sensitive and specific micro-metastic markers for prostate cancer.</p><p><b>METHODS</b>Using nested reverse transcription-PCR, we examined the expression of PSA, hK2 and PSMA mRNA in peripheral blood mononuclear cells of 51 patients with prostate cancer, 33 patients with benign prostate hyperplasia (BPH) and 32 normal young people.</p><p><b>RESULTS</b>The expression rates of PSA, hK2 and PSMA mRNA were 52.9%, 43.1% and 64.7%, respectively in prostate cancer group, and 6.2%, 7.7% and 4.6%, respectively in control group (BPH patients and normal young people) with statistical significance (P < 0.01). Although the expression rate of PSA and hK2 mRNA increased with cancer progression, there was no statistical significance among patients in different stages. The expression rate of PSMA mRNA was higher than that of PSA and hK2 mRNA in each clinical stage.</p><p><b>CONCLUSION</b>PSMA mRNA expression detected by nested RT-PCR is of greater value for the diagnosis, therapy choice and prognostic evaluation of prostate cancer patients.</p>

Effects of NMDA receptor on glucocorticoid receptor mRNA levels in hippocampus of rats after scald burn stress / 第三军医大学学报

Objective To investigate the changes of glucocorticoid receptor (GR) gene expression in the hippocampus of rats following scald burn stress and the role of N methyl D aspartate (NMDA) receptor in this change. Methods Adult male Wistar rats inflicted with 30% TBSA full thickness scalding were applied as severe scalding stress model. GR mRNA levels in the hippocampus were detected with RT PCR. Results A significant decrease of GR mRNA levels was observed in the hippocampus 2 h after the scalding stress. The decrease could be inhibited when MK 801, an NMDA receptor antagonist, was administered prior to stress, and be augmented with the administration of NMDA, an NMDA receptor agonist, but not be affected by normal saline. Conclusion NMDA receptors are involved in the scalding stress induced down regulation of GR gene expression in the rat hippocampus.