OBJECTIVE:To study the pharmacokinetics of oral single dose adefovir dipivoxil(ADV) tablet in Chinese healthy volunteers.METHODS:The study was a randomized,open,three-way crossover study.Twelve healthy volunteers were randomly assigned to receive single oral dose of 5 mg(Group A),10mg(Group B) or 30 mg(Group C) ADV tablets in three weeks.The plasma concentrations of ADV were determined by LC/MS/MS method.The pharmacokinetic parameters were computed.RESULTS:The main pharmacokinetic parameters in Group A,B and C were as follows:Cmax were(11.4? 3.7),(25.4? 8.2) and(76.3? 23.0) ng? mL-1;tmax were(1.69? 1.41),(0.90? 0.56) and(0.94? 0.50) h;AUC0～ t were(102.7? 51.7),(235.0? 82.3) and(715.4? 267.6) ng? h.mL-1;AUC0～ ∞ were(168.7? 30.7),(266.2? 83.7) and(741.5? 273.9) ng? h? mL-1,respectively.CONCLUSION:ADV tablets had a rapid absorption in healthy volunteers and the Cmax and AUC of adefovir tablets were directly correlated to doses.It is safe for healthy volunteers to take ADV tablets at a dose of 5～30mg.

To study the kinetics in vivo of a Hantaan virus DNA vaccine, we constructed a fusion DNA vaccine,pEGFP/S, by cloning the S segment of Hantavirus into the vector, pEGFP-C1, which encodes Green fluorescent protein EGFP. In this report, we provide evidence that pEGFP/S was distributed and persistently expressed for more than 60 days in several organs after inoculation. Our findings suggest that the persistent immune responses induced by a Hantaan virus DNA vaccine are likely due to the plasmid pEGFP/S deposited in vivo, which acts as a booster immunization.

To evaluate the efficacy of Tuina and Chinese patent drug Shuxuetong injection in preventing patients undergoing total knee arthroplasty from deep venous thrombosis and in functional rehabilitation.

Objective To investigate the safety , feasibility , and clinical application value of digital sub-traction angiography ( DSA) -guided insertion of totally implantable venous access port ( TIVAP) in patients with digestive system cancer .Methods We retrospectively analyzed the data of 15 digestive system cancer patients who were inserted with TIVAP under DSA guidance between April 2013 and January 2016, recorded the TIVAP-related complications and indwelling time, and investigated the patients’satisfaction about TIVAP.Paired rank sum test was used for the differences in patients’quality of life before and after the insertion of TIVAP.Results Of the 15 digestive system cancer patients , operation success rate of TIVAP insertion was 100%, with the success rate of venipuncture on first attempt being 100%.The incidence of complication was 6.67% ( 1/15 ) , which was manifested as pull feeling at the neck occurring in the eighth month after insertion .The indwelling time of TIVAP was from 2 to 28 months, with a median value of 9 months.Patients’satisfaction rate of TIVAP was 86.67%(13/15).The proportion of patients with a good quality of life was 100%(15/15), statically signifi-cantly higher than that before the insertion [46.67%(7/15), Z=-3.416, P=0.000).Conclusions TIVAP insertion under DSA guidance in digestive system cancer patients is safe and feasible , with few complications and fair patient satisfaction .It may improve the patient ’s quality of life , worthy of clinical application .

Objective To study the therapeutic effect of estrogenic equol (Eq) on mustard gas-caused skin wounds and the possible mechanism. Methods A rabbit skin wound model was established by contaminating the hip skin with mustard gas (0. 5 mg/cm2). The contaminated wound was treated externally with different concentrations (10, 50, and 100 μmol/L) of Eq for a week, and the changes of the wound were observed macroscopically. Wound specimens were collected for histopathological evaluation. Cell apoptosis and DNA cycle changes were analyzed by flow cytometry. Levels of IL-6 and TNF-α in the contaminated wound specimens were detected. Results The scores of erythema, edema, erosion and necrosis of the contaminated wounds in the treatment groups were significantly lower than those in the control group 120 h after mustard gas exposure (P<0. 05). The scores for changes of histopathological inflammation and necrosis were significantly lower in the 50 μtmol/L Eq treatment group than those in the control group 168 h after mustard gas exposure (P<0. 05). The results of flow cytometry showed that the proportion of apoptotic cells in the control group was significantly higher than those in the treatment groups 168 h after mustard gas exposure (P<0. 05), and the proportion of cells in DNA (S+G2-M) phase in the treatment groups was significantly higher than that in the control group (P<0. 05). The levels of IL-6 and TNF-α in the treatment groups were significantly lower than those in the control group 168 h after mustard gas exposure (P<0. 05). Conclusion Eq can promote healing of mustard gas-caused local skin damaged by inhibiting inflammatory response and cell apoptosis and enhancing cell proliferation.

Objective To investigate the prognostic value of preoperative neutrophil lymphocyte ratio (NLR) in patients with gastrointestinal stromal tumors (GIST).Methods The clinical-pathological data from 85 GIST cases were collected from the Second Affiliated Hospital of Wenzhou Medical University and retrospectively analyzed from June 2009 to December 2013.According to the exclusion criteria,79 cases were enrolled.Preoperative neutrophil and lymphocyte count was collected and NLR was calculated.According to the receiver operating characteristic (ROC) curve of NLR,GIST patients were divided into low NLR group (NLR ＜ 2.30) and high NLR group (NLR ≥ 2.30).Clinic-pathological features and five year disease free survival (DFS) were compared between the two groups.Results There was a statistical significant difference in tumor size and tumor risk between high NLR group and low NLR group (respectively,x2 =9.517,12.411,all P ＜ 0.05).Univariate analysis showed that the five year disease free survival rate of low NLR and high NLR group were 78％ and 32％ (x2 =18.749,P =0.000).By multivariate analysis a high NLR was identified as an independent risk factor of poorer prognosis for patients with GISTs (RR:3.516,95％CI:1.453-8.506,P=0.005).Conclusion A high preoperative NLR is an independent risk factor for the prognosis of GISTs.

Objective To evaluate the effect of CYP3A5 genetic polymorphisms on tacrolimus (Tac) concentration/dosing and other clinical outcomes in a pilot cohort of 113 Chinese HTx recipients.Methods Association between CYP3A5 genetic variants and blood dose-adjusted trough concentrations (C0/D) of Tac at 1st month at the beginning of the immunosuppressive therapy was evaluated in cohorts of 113 patients,then at 1st,3rd,6th,and 12th months after transplantation in 41 patients who received Tac-based immunosuppressive therapy and never changed within one year after transplantation,respectively.In addition,we also evaluated the association between CYP3A5 genetic variants and other clinical outcomes,such as the classifications of endomyocardial biopsy and longterm prognosis.Results The CYP3A5 wild homozygote (* 1/* 1),mutant homozygote (* 3/* 3),and mutant heterozygote (* 1/* 3) occurred in 5,34 and 74 recipients respectively.The gene mutation rate of CYP3A5 in this cohort of Chinese HTx recipients was 80.5 ％ and the homozygous proportion was 65.5％.Compared with CYP3A5 expressors (* 1/* 1 or * 1/* 3),CYP3A5 nonexpressors (* 3/* 3) had a higher Tac C0/D at 1st month (47.34 ± 11.40 vs.116.11 ± 42.40 vs.293.70 ± 171.20,P =0.000),as well as other studied time points (3rd month:98.32 ± 39.43 vs.292.07 ± 141.08,P=0.003;6th month:90.00 ± 21.31 vs.341.68 ± 165.02,P =0.002;and 12th month:96.02 ± 29.33 vs.339.23 ± 162.30,P =0.018);and might have a lower classification of endomyocardial biopsy at 1st month (1.43 ± 0.73 vs.1.50 ± 0.58,P =0.867),3rd month (1.55 ±1.00 vs.2.00 ± 1.73,P =0.512),and 6th month (1.36 ± 0.84 vs.2.33 ± 1.53,P =0.132);as well as a higher mortality due to acute organ rejection (10％ vs.0,P =0.244) and all-cause mortality (20％ vs.9.7％,P =0.580).Conclusion In Chinese HTx recipients,the frequency of this * 3 allele is lower than that has been reported in the white population.The determinations of CYP3A5 genetypes in heart transplant recipients are helpful to guide the individualized Tac regimens.

Objective To evaluate mortality associated with simultaneous bilateral or staged bilateral TKA, and better understand the risks involved in the simultaneous versus staged bilateral procedures.Methods A systematic review was conducted, following an a priori protocol, according to the methods recommended by the Cochrane Musculoskeletal Group in the Cochrane Collaboration. Eligible studies were identified in PubMed (1990-2010), OVID MEDLINE (1990-2010), and the Cochrane library, concerning postoperative complications of bilateral or staged bilateral total knee arthroplasty. All of the English-language abstracts were obtained, and retrieval words including bilateral total knee arthroplasty, staged total knee arthroplasty, and total knee arthroplasty, etc. An extensive analysis was then performed to identify articles fulfilling the inclusion criteria for the study. The details of the reported data were extracted and evaluated by two reviewers independently. Data analyses were conducted with Stata 10.0. Results Six studies met our inclusion criteria for review. The combined results showed that the prevalence of mortality[OR=2.925, 95% CI (2.352, 3.638)], mortality 30 days postoperatively[OR=5.078, 95% CI (2.192, 1 1.763)]and mortality in 70 years or older patients[OR=4.087, 95% CI (1.947, 8.582)]were statistically higher in the population that had undergone simultaneous TKA compared with staged TKA. Conclusion Compared with staged bilateral TKA, simultaneous bilateral TKA might carries a higher potential risk of postoperative mortality. Patients should be aware of this information when deciding whether to proceed with simultaneous bilateral TKA. Further well-designed and large-scale randomized controlled trials are required to confirm these findings.

AIMTo determine the effect of piperazinyl estrone, a new estrogen derivative, on bone turnover, bone mass and uteri in ovariectomized rats.

METHODSFemale Sprague-Dawley rats were ovariectomized (OVX) or sham operated (sham) at the age of 3 months and treated with estrone (E) at 0.75 mg.kg-1.d-1, or with piperazinyl estrone (P-E) at 1 or 10 mg.kg-1.d-1, orally, for 3 months. At the time of death, the uterine weight was measured. Bone histomorphometric analysis of proximal tibial metaphyses (PTM) was performed in undecalcified sections.

RESULTSBone histomorphometric data showed that the percent trabecular area (% Tb.Ar) of OVX rats with bone high turnover was significantly decreased. The uteri were atrophied. The percent trabecular area (% Tb.Ar) of estrone treated group was increased in decreasing bone turnover manner. But the size and weight of uteri in this group were increased vs OVX group. The bone loss induced by OVX was preserved by P-E treatment, but the mechanism of maintaining bone is different from that of E-treated rats. P-E treatment in low dose did not decrease any bone formation indices, such as percent labeling perimeter, bone formation rate per bone volume (BFR/BV), except bone mineral apposition rate (MAR) compared with E-treated group, and maintained them at OVX level. The uteri were found to be in atrophy compared with the match dose (0.75 mg) of E-treated OVX rats. But rats treated with high dose of P-E showed the same change like E-treated group.

CONCLUSIONThe finding of this study shows that lower dosage of piperazinyl estrone has effect on preventing the bone losses in OVX rats, while the bone formation and the uterus are not affected, thus supporting the hypothesis that piperazinyl estrone has the potential to prevent postmenopausal bone loss in women with less side effects.

Animals ; Atrophy ; prevention & control ; Bone Density ; Estradiol Congeners ; pharmacology ; therapeutic use ; Estrone ; analogs & derivatives ; pharmacology ; therapeutic use ; Female ; Organ Size ; drug effects ; Osteogenesis ; drug effects ; Osteoporosis ; prevention & control ; Ovariectomy ; Rats ; Rats, Sprague-Dawley ; Uterus ; pathology

ObjectiveTo explore the electrophysiological mechanisms of the schizophrenic patients with aggressive or violent behaviors.MethodsAccess the aggressive behaviors of schizophrenic patients being treated in hospitals or clinics with the revised MOAS in accordance with the ICD-10 diagnostic criteria,and sort the qualified patients into two groups:the group of aggressive or violent schizophrenia (Aggressive Group,n=70) and the group of non-aggressive or non-violent schizophrenia ( Non-Aggressive Group,n =65 ) ; 60 age- and gendermatched healthy people were collected as Healthy Group.P300 tests were carried out on patients in these three groups with the MEB-9200 Nicolet Bravo Instrument by the Nihon Kohden Corporation.Results ( 1 ) latency P3a of the Aggressive Group on Cz point exceeded that of the Non-Aggressive Group (P =0.01 ),and that of the Non-Aggressive Group exceeded that of the Healthy Group.All these disparities were of statistical significance (P ＜0.01 ).Latency P3a of the Aggressive Group on Fz point exceeds that of the Non-Aggressive Group,and that of the Non-Aggressive Group exceeded that of Healthy Group.All these disparities are also of stafistical significance (P＜0.01).(2)N2' amplitude of the Aggressive Group on Cz point was higher than those of the Non-Aggressive Group and the Healthy Group.This disparity was of statistical significance(P ＜ 0.05 ) and the disparity between the Non-Aggressive Group and the Healthy Group did not have statistical significance (P =0.985 ).ConclusionCharacteristic electrophysiological changes exist in the event-related potentials P300 of schizophrenic patients with aggressive or violent behaviors.