Based on the translational research measurement and backtracking model put forward in this paper,it takes the new drug approved to enter into the market by American FDA from 2006-2015 as the fundamental data to measure the knowledge relations among new drug products-core patent-scientific paper-fund assistance,and puts forward the policies and suggestions for promoting innovation of pharmaceutical products in China.

Hepatocellular carcinoma (HCC)is a common malignant tumor in the world,and surgical resection and liver transplantation are two radical treatment modalities,but only 10%-20%of all patients can receive such treatments.In recent years,local therapies including radiofrequency ablation,microwave ablation,cryoablation,and the irreversible electroporation ablation which appeared recently have gradu-ally become the alternative therapies for the patients who are unable to undergo surgery.In addition to local tumor growth control and im-provement in survival outcomes,the ablation technology also helps to downgrade tumor for secondary resection.This article focuses on the re-search progress in radiofrequency ablation alone and in combination with other therapies in the treatment of HCC,compares radiofrequency ablation with other local ablative therapies,and briefly introduces the application of intelligent navigation technology in adjuvant ablation. With the development of medical imaging and progress in related fields,the ablation technology will be widely applied in clinical practice in the future.

Objective To evaluate the effect of naringenin on KIM-1 expression in rats with renal interstitial fibrosis caused by unilateral ureteral obstruction(UUO).Methods 24 SD male rats were randomly divided into Sham group,UUO group and naringe-nin group(Nar group),respectively.Rats in UUO group and Nar group got UUO to establish renal interstitial fibrosis models. Rats in Sham group only free but not ligated and cut ureters.Rats were administered saline and naringenin 25 mg/(kg·d)for 14 days.Then,24 h urine samples were collected before the rats were killed,and KIM-1 in these samples were measured by ELISA. Specimens were obtained from obstructive renal,the pathological change of renal tubule and interstitial were observe by HE and Masson staining.Moreover,the tubulointerstitial damage index was scored and the expression of KIM-1 in renal tissue was examined by immunohistochemical staining.Results Compared with Sham group,the tubulointerstitial damage index of UUO group significantly increased(P <0.05),contents of KIM-1 in urine and renal tissues also significantly increased(P <0.05).Com-pared with UUO group,the tubulointerstitial damage index score of Nar group alleviated(P <0.01),contents of KIM-1 in urine and renal tissues also reduced(P <0.05 ).Correlation analysis showed that there was positive correlation between KIM-1 in urine and renal tissues and TDI(r=0.862,0.866,P <0.01).Conclusion Naringenin can relieve renal interstitial fibrosis and reduce the content of KIM-1.

Objective To promote the development of precision medicine and gene sequencing technologies in China by analyzing the innovation situation in gene sequencing technologies.Methods An innovation situation research analysis frame was established with scientific literature and patent information as its basic data.The innovation situation in gene sequencing technologies was analyzed in aspects of scientific research and technical R & D.Results The research on gene sequencing technologies and technical R & D were focused on tumor diagnosis and treatment,plant gene sequencing,identification of HIV and gastrointestinal flora.Single cell genome amplification technology has greatly promoted the development of gene sequencing technologies.Conclusion The level of gene sequencing technologies and technical R & D in China is approaching to that in the world.

Purpose To establish a golden hamster model of intrahepatic cholangiocarcinoma (ICC) using BOP [N-nitrosobis (2-oxo-propyl) amine] and to explore the protein expression of Wisp-1,β-catenin, TGF-β1 and Smad4 in ICC and their relationship with the tumorigenesis. Methods 57 female golden hamsters aged 8 to 9 weeks (39 in experimental group, 18 in control group), the experi-mental animals were subjected to subcutaneous injection of BOP, the control group was injected with saline. The liver was removed and paraffin sections were prepared for histopathological observation. The protein expression of Wisp-1,β-catenin, TGF-β1 and Smad4 was detected by immunohistochemistry (IHC) in these blocks. Results Most of the animals in the experimental group (29/39) developed ICC, part of the animal (8/39) developed bile duct dysplasia, 1 developed focal bile duct hyperplasia, and 1 was not found bile duct hyperplasia. The positive expression rates of four protein markers in ICC, bile duct dysplasia and normal intrahepatic bile duct tissues were Wisp-1,79. 3%, 87. 5% and 5. 0%,β-catenin, 96. 6%, 100. 0% and 15. 0%, Smad4, 96. 6%, 100. 0% and 25. 0%, TGF-β1, 62. 1%, 12. 5% and 5. 0%, respectively. The positive expression rates of Wisp-1, beta-catenin and Smad4 protein in both the ICC and the tissue of bile duct dysplasia were higher than that of normal intrahepatic bile duct tissue ( P<0. 001 ) , The positive ex-pression of TGF-β1 in the ICC tissue was higher than that of normal intrahepatic bile duct tissue and bile duct dysplasia (P<0. 001). Conclusions The study showed that BOP can induce a golden hamster model of ICC and provides a reliable animal model for the study of ICC. The high expression of Wisp-1,β-catenin, TGF-β1 and Smad4 in BOP-induced intrahepatic cholangiocarcinoma is closely re-lated to occurrence, development and infiltration of ICC.

Analyzed in this paper are the methods and their operability and efficiency for assessing the impact of papers on clinical research in view of evidence-based medicine, including citation analysis based on the clinical practice guidelines and evidence-based medicine database and comparative analysis of clinical trials registry data-base, with the model for assessing the impact of papers on clinical research in view of evidence-based medicine proposed.

Objective Through the analysis of the special thromboelastography (TEG) graphics to improve the ability of analysis and identification the TEG and provide more valuable results for clinical practice.Methods This study is a retrospective study.Retrospectively analysis of 15 430 cases of TEG results from People's Liberation Army General Hospital,using the parametrs as reaction time (R),the clotting time (K),the solidification angle (Angle),the maximum amplitude (MA),the percentage of blood clot dissolution (EPL),the rate of 30 minutes clot amplitudereduce (LY30),the coagulation index (CI) and other parameters to analyze the hyperfibrinolysis group,the heparin graphics group,the secondary activation of fibrin group,the platelet function group and the anti-platelet drug monitoring group.Results In the hyperfibrinolysis group,the EPL value,LY30 value and CI value of primary hyperfibrinolysis group was 19.3,19.3 and 0.4 respectively and the secondary hyperthyroidism group was 11.6,11.6 and 3.2 respectively.In the heprin application graphic group,R value of CKH group was shorter than that of CK group (10.9 vs.50.8),R value of CKH group was longer than that of CK group (12.2 vs.15.7).In fiber protein secondary activation graphics groups,the MA value of the first time detection was 35.2,then replacing the channel repetition MA value was 34.7 in true functional fiber protein secondary activation group.For the pseudo fiber protein secondary activation group the first time detection MA value was 73.4,then replacing the channel repetition MA value was 20.0.The MA value of platelet function reduce group and hyperfunction group was 21.6 and 79.2 respectively in platelet function group.In anti-platelet drug monitoring group,the inhibition rate of adenosine diphosphate (ADP) of ADP inhibitor (clopidogrel) ineffective group was 10.9％ ; And the inhibition rate of arachidonic acid (AA)of AA metabolic pathway inhibitor (aspirin) ineffective group was 7.5％.Conclusions The correct judgment on the abnormal thromboelastography graphics is helpful to ensure the accuracy of the results andto reduce the occurrence of adverse events.

Objective To analyse the clinical characteristics,gene mutation and enzymatic activity of αgalactosidase A(α-GalA)in a 15-year-old male patient with typical Fabry disease,whose mother was without any clinical manifestations.Methods Clinical features and laboratory data were collected from the patient and his mother.Genomie DNA was extracted from peripheral blood of the patient.his mother,and a healthy control subject.Seven exons of the GLA gene were amplified by PCR.PCR products were purified.cloned into T vector,and then sequenced.The enzymatic activity of α-GalA Was measured by fluorimetrie substrate assay. Results DNA sequencing results showed that a missense mutation of 10036-10038delAAG in exon 7 WaS identified in the patient,resulting in the replacement of 374 lysine and 375 glyeine by arginine,which Was not previously reported.The patient Was a hemizygote with gene mutation,his mother WaS a heterozygote carrying gene mutation,and the healthy control without mutation.α-GalA enzymatic activity assay showed that the enzymatic activity of the patient with GLA gene mutation was only 50%of the healthy control subject,while the enzymatic activity of the patient's mother Was about 70%of the heahhy control SObject.Conclusiolls Detecting GLA gene mutation and α-GalA enzymatic activity in patients with Fabry disease who have been clinically diagnosed seelns to be helpful in finding other patients in the family and in further understanding the molecular pathogenesis of that disease.

Objective:To explore the intervention effect of proteasome inhibitor MG132 in rats with collagen-induced arthritis(CIA),which resembles human rheumatoid arthritis(RA).Methods:Forty-eight female SD rats were randomly divided into three groups,including blank control group,CIA model group and MG132-treated group.There were sixteen rats in each group.Rats in CIA model group and MG132-treated model group were injected with type Ⅱ collagen to established CIA rats.21 days after the initial immunization,the rats in the MG132-treated model group were injected subcutaneously with 1 mg/kg MG132 once daily for 2 weeks.42 days after the initial immunization,the change of paw-swelling and the arthritis scores were determined.The synovial pathology examination was performed with HE staining.The 20S proteasome activity in synovial tissue was measured by fluorescence substrate assay.The expression of NF-κB/p65,IκBα in synovial tissue were analyzed by Western blot.Results:Proteasome inhibitor MG132 significantly attenuated the severity of arthritis and histopathological changes in CIA rats.Compared with the blank control group,the 20S proteasome activity was increased significantly in the CIA model group(P<0.05),and decreased after injection of MG132.Compared with CIA rats,the expression of NF-κB/p65 significantly decreased in rats treated with MG132(P<0.01).Compared with the blank control group,the expression of IκBα protein decreased in CIA model group.After injected with MG132,the protein was significantly increased(P<0.01).Conclusion:The proteasome inhibitor MG132 may attenuates the severity of arthritis and histopathological changes in CIA rats.These effects may be mediated through the inhibition of NF-κB activity.

OBJECTIVE:To study the pharmacokinetic characteristics of Puerarin solid self-microemulsion capsules in rats in vi-vo. METHODS:The rats were randomly divided into two groups with 18 rats in each group. They were given Puerarin solid self-mi-croemulsion capsules(S-SMEDDS capsules)and commercially available Yufeng ningxin tablet,with the dose of 158.15 mg/kg puer-arin. The 0.2 ml blood samples were collected from tail vein 0,5,10,20,40,60,90,120,180,240,360,480,600 min after medication,respectively. The blood concentration of puerarin was determined by HPLC,and pharmacokinetic parameters and rela-tive bioavailability were calculated by using 3p87 software. RESULTS:The metabolism of puerarin was one-compartment model in rats. Pharmacokinetic parameters of S-SMEDDS capsules and Yufeng ningxin tablet were as follows as cmax of (1.032 0 ± 0.020 6) and(0.587 3±0.011 7)μg/ml,t1/2ke of(116.431 4±2.166 0)and(88.222 6±1.752 4)min,AUC0-t of(261.532 2±1.464 0)and (102.835 5±1.957 4)μg·min/ml. Relative bioavailability was 238.77%. CONCLUSIONS:Compared with Yufeng ningxin tablet, S-SMEDDS capsules are absorbed more completely and removed faster.