Small interfering RNAs (siRNAs) are an emerging class of RNA interference (RNAi) therapeutics with unique pharmacokinetic properties. Five siRNA drugs based on two delivery systems have been approved, and an increasing number of siRNA drugs have already moved to the clinical study phase. Physiologically-based pharmacokinetic (PBPK) modeling is a useful tool and has been demonstrated to have wide ranging utility in drug development and regulatory review. However, PBPK modeling is still in its infancy in guiding the development of siRNA-based drugs in the context of its widespread use in small and large molecule areas. This article reviews the pharmacokinetic profiles of siRNA drugs, outlines the current state of PBPK model building in siRNA drug development, and describes the key parameters required for model building. This article provides insights into the future applications of PBPK models and for optimizing the key parameters when building the model for siRNA drug development.

Objective To study a new method of correcting flaring ear. Methods Auricular cartilage was slited from posterior auricula. On Gibson's principle of cartilage distortion antero-lateral cartilage membrane was scarified in order of the involute interpolation of anthelix and cartilage membrance was ground. Then the cartilage outside the slited line was put behind the cartilage inside the slited line. Finally,cartilage was operated with Mustarde's mattres suture. Results 12 patients with flaring ear ( 14 ears) were corrected with this operating method and appearance of corrected ears were very good after operation. Following up for 6-18 months, no one recurred. Conclusion Otoplasty of slited cartilage is an effective method of correcting flaring ear.

Objective To assess the impact of preoperative ureteral stenting on outcome of flexible ureteroscopic lithotripsy . Methods The clinic data of flexible ureteroscope lithotripsy were analyzed retrospectively .All 52 eligible patients were divided into three group :goup A(no preoperative ureteral stenting );group B (preoperative ureteral stenting for 3-10 days);group C(preopera‐tive ureteral stenting for two weeks or more ) .The application of ureteral access sheath ,operation time ,stone free rates ,hospital stays ,complications were compared among the three groups .Results There were no significant differences in aging ,gender ,stone size , distribution ,average hospitalization days ,postoperative complications among the three groups (P>0 .05) .There were significantly differ‐ences between group A and group B ,group C(P<0 .05) ,and there were no difference between group B and group C (P>0 .05) on the suc‐cess rate of indwelling ureteral access sheath ,average operation time ,stone free rate .Conclusion Preoperative ureteral stenting could en‐hance the success rate of indwelling ureteral access sheath ,shorten the operation time ,improve the stone free rate .There was similar out‐come of flexible ureteroscopic lithotripsy between preoperative ureteral stenting for 3-10 days and two weeks or more .

AIM:To construct eukaryotic expression vector expressing double shRNA sections targeting Survivin gene.METHODS: Eukaryotic expression vector expressing double shRNA sections targeting Survivin gene were designed and chemically synthesized.They were directionally inserted into plasmid pGenesil-1 with respectively U6 promoter and termination code,the common green fluorescence protein(EGFP) gene and Neo gene. In this way,the vector of pGenesil-1 shRNA containing 2 sections of Survivin shRNA were constructed and they were transfected into the pancreatic cancer cell Bx-PC3.Transfection was detected by fluorescence microscope.The inhibition expression of Survivin mRNA was measured by RT-PCR.RESULTS: HE1 and HE2 plasmids were identified by the biocatalyst cut which confirmed the exactitude and were analyzed by the sequence analysis which verified the perfect clone plasmid inserted by them.CONCLUSION: A eukaryotic expression vector of double short hairpin RNA for Survivin gene is successfully constructed.The pancreatic cancer cells Bx-PC3 succeed to be transfected and expression of Survivin mRNA is inhibited obviously.

Objective: To study the preventive actions of ganoderma lucidum polysaccharide(GLP) against kidney damage induced by cisplatin. Methods : Female Wistar rats were randomly divided into normal saline(NS) group, cisplatin(CDDP) group, GLP group, CDDP+GLP group. The changes of Scr, BUN, MDA, SOD were measured and renal structure was observed after 5 days by injecting drugs. Results : The contents of serum Scr and BUN of CDDP group were significantly highter than that of NS group. The activity of RBC SOD reduced and the contents of serum MDA increased. The contents of renocortical tissue MDA increased and the activity of SOD declined in renocortical tissue. The contents of serum Scr and BUN of GLP+CDDP group were significantly lower than that of CDDP group. The activity of RBC SOD increased and the contents of serum MDA declined. The concents of renocortical tissue MDA declined and the activity of SOD increased in renocortical tissue. The pathological slice indicated that renal structure was significantly improved. Conclusion : GLP may reduce cisplatin nephrotoxicity and its mechanism may be correlative with that GLP inhibited the blood and renocortical tissue lipid peroxidation increasing.

Background Clinical researches showed that antimicrobial-resistance of bacterium is gradually serious.It is very important to master pathogen distribution and antimicrobial susceptibility after eye surgery.Objective This study was to investigate the distribution and drug sensitivity of pathogenic bacteria from ocular operative infection in 3-year duration to provide a reference for reasonable selection of antibiotics.Methods Sixtyfive positive specimens were obtained from 65 patients due to postoperative infection in Department of Ophthalmology of Shenzhou Hospital and Shengjing Hospital from 2009 January through 2011 December.The pathogenic bacteria were isolated and then the drug sensitivity test of conventional antibiotics was performed.Results Among the 65 ophthalmic specimens,35 strains of Gram-positive bacteria were isolated with the constituent ratio 53.8％,and 15 strains of Gram-negative bacteria accounted for 23.1％.Fungus was found in 15 cases with the constituent ratio 23.1％.Staphylococcus epidermidis accounted for 42.9％ in Gram-positive bacteria,and Pseudomonas aeruginosa accounted for 33.3％ in Gram-negative bacteria.Aspergillus was the main component of fungus,which accounted for 60.0％ of the proportion 3 strains of methicillin-resistant Staphylococcus aureus (MRSA) in 8 strains of Staphylococcus aureus,but no vancomycin-resistant Enterococcus (VRE) and vancomycin-resistant Staphylococcus (VRS) were seen.The in vitro drug sensitivity test showed that the main Gram-positive bacteria,Staphylococcus epidermidis and Staphylococcus aureus,were sensitive to linezolid,vancomycin,levofloxacin and ciprofloxacin with the sensitive rates ＞50.0％,and these bacteria were lowly sensitive to penicillin and erythromycin with the sensitive rates ≤30.0％.Pseudomonas aeruginosa appeared to be the main Gram-negative bacteria,showing a sensitive rate ≥ 80.0％ to tobramycin,amikacin,ceftazidime,cefepime,cefoperazone/sulbactam,piperacillin/tazobactam,imipenem and meropenem.Conclusions Staphylococcus epidermidis,Staphylococcus aureus,Pseudomonas aeruginosa and Aspergillus are primary pathogens in ocular infection after operation.Antibiotics such as penicillin,erythromycin,levofloxacin,cefotaxime seem to be relatively high resistant to eye infection.To choose sensitive antibiotics timely and reasonably is a key to the prevention and control of ocular infection after operation.

Objective To investigate the expressions of claudin-5 and claudin-10 in colorectal carcinoma(CRC) and its significance.Methods Pathological verified 50 colorectal tissue (CRT),25 colorectal adenoma (CRA),25 non lymph node metastasis CRC (non-LNM CRC) and 25 lymph node metastasis CRC (LNM CRC) were detected for the expression of claudin-5 and claudin-10 by immunohistochemical SP(streptavidin perdcidase) method.Results The positive expression rate of Claudin-5 was 82%,76%,68% in CRT,CRA,CRC,respectively.The positive expression rate of claudin-5 in different groups was not significantly different(X~2 =2.638,P＞0.05).claudin-5 expression was correlated with LNM (P＜0.05),but was not correlated with gender,age,tumor,location,differentiation,tumor diameter and serous membrane invasion(P＞0.05).The positive expression rate of claudin-10 was 54%,56%,72% in CRT,CRA,CRC,respectively.The positive expression rate of claudin-10 in different groups was not significantly different(X~2 = 3.839,P＞0.05).claudin-10 expression was correlated with tumor diameter,serous membrane invasion and LNM (P＜0.05),but was not correlated with gender,age,location and differentiation (P＞0.05).There was no significant correlation between claudin-5 expression and claudin-10 expression in CRC (r = 0.050,P = 0.732).Conclusions claudin-5 and clandin-10 are expressed in CRT,CRA,and CRC.They are not involved in CRC occurrence,claudin-5 and clandin-10 abnormally expressions are significantly associated with the incidence of LNM.Meanwhile,claudin-10 expression is correlated with tumor diameter and serous membrane invasion.There was no significant correlation between claudin-5 expression and claudin-10 expression in CRC.

Objective To construct pseudotyped retroviral vector MuLV/VSV-G and transfer it into rabbit smooth muscle cells (SMC) in order to provide a high-efficiency vector for SMC gene transfer. Methods We constructed pseudotyped retroviral vector MuLV/VSV-G containing the previously reported gene lacZ, determined the titer, and determined the efficiency of gene transfer into SMC mediated by pseudotyped retroviral vector MuLV/VSV-G. Finally the transfer efficiency was compared with that by MuLV. Results MuLV/VSV-G vector was constructed. The titer of the vector was 6-7.8×10~6CFU, the transfer efficiency was (92±12)% by using MuLV/VSV-G vector and (24±5)% by MuLV vector. Conclusion Pseudotyped retroviral vector MuLV/VSV-G which was constructed successfully is a kind of high-efficiency gene transfer vector in smooth muscle cells.

BACKGROUND: Smooth muscle cells (SMCs) proliferation and transmigration and platelet activation cause thrombogenesis and lead to grafted vessel restenosis. Nitric oxide (NO) can inhibit the above-mentioned biological responses, but whether endothelial nitric oxide synthase (eNOS) gene transfection can inhibit the neointimal hyperplasia in graft seeded with SMCs remains uncertain.OBJECTIVE: This study was designed to further investigate the effect of eNOS gene transfection on neointimal hyperplasia in the grafts seeded with SMCs.DESIGN, TIME AND SETTING: This study, a repeated observation and measurement experiment, was performed at the Central Laboratory and Laboratory of Molecular Biology of Xi'an Jiaotong University Medical College from April 2006 to May 2007.MATERIALS: One 1-month-old New Zealand rabbit was used to acquire SMCs. Another 18 adult New Zealand rabbits were randomly divided into 3 groups (n=6).In normal control group,the vessel graft with no SMCs were transplanted; In SMC/lacZ group, the vessel grafts with SMCs transfected with lacZ were transplanted;In SMC/eNOS group,the vessel grafts with SMCs seeded with eNOS were transplanted.METHODS: Rabbit SMCs were transduced with pseudotyped retroviral vectors, Murine leukemia virus/vesicular stomatitis virus G glycoprotein, carrying genes coding for eNOS or lacZ gene. The SMCs then were seeded on the vessel grafts and implanted into the rabbit abdominal aorta using vessel bypass transplantation.MAIN OUTCOME MEASURES: Nitric oxide (NO) content in the supernatant of cells transfected with eNOS and lacZ gene was detected by citrulline method. The grafts were stained with X-gal to visualize the seeded cells: the seeded SMCs were stained blue,while eNOS were stained red. The thickness of the neointima on a graft was measured with a microscope.RESULTS: Eighteen rabbits were all included in the final analysis. NO content in the SMC/eNOS group was significantly higher than that in the normal control group (P<0.05). The SMCs transfected with lacZ gene showed blue after X-gal staining under the inverted microscope. Thirty days after implantation, there was no difference in neointimal thickness between normal grafts and grafts seeded with eNOS or lacZ transduced SMCs (P>0.05).100 days after implantation,the neointimal thickness on grafts seeded with eNOS transduced SMCs was similar to that of unseeded grafts (P>0.05 ), but was significantly thinner than that on grafts seeded with SMCs transduced with only lacZ gene (P<0.05).CONCLUSION: eNOS gene transfection inhibits nenintimal hyperplasia in the vessel graft seeded with SMCs.

OBJECTIVETo explore the correlation between electronic bronchus mirror and Chinese medical syndrome typing of Mycoplasma pneumonia children.

METHODSTotally 198 Mycoplasma pneumonia children inpatients were assigned to three syndrome types according to Chinese medical syndrome typing and self-formulated typing standards of electronic bronchus mirror, i.e., Fei-qi accumulation of damp and heat syndrome, Fei-qi accumulation of toxicity and heat syndrome, deficient vital qi leading to lingering of pathogen syndrome. The correlation between electronic bronchus mirror and Chinese medical syndrome typing was explored.

RESULTSAs for comparison between electronic bronchus mirror and Chinese medical syndrome typing, Kappa value (K^) was 0.645 and Spearman coefficient correlation (r) was 0.653 (P < 0.01) for Fei-qi accumulation of damp and heat syndrome; K^ was 0.724 and r(s) was 0.727 (P < 0.01) for Fei-qi accumulation of toxicity and heat syndrome; K^ was 0.506 and r(s) was 0.515 (P < 0.01) for deficient vital qi leading to lingering of pathogen syndrome.

CONCLUSIONChinese medical syndrome typing of Mycoplasma pneumonia children was moderately in line with inspection typing under electronic bronchoscope with significant correlation.