Objective To explore whether PPARαtransgenic mice are more sensitive animal models in the evalua-tion of toxicity of PPARαagonists.Methods Twenty-eight 8-week old PPARαtransgenic mice (Tg) and 28 C57BL/6J mice (WT) with half males and half females were randomly divided into high dose group (400 mg/kg of clofibrate), low dose group (30 mg/kg of clofibrate) and solvent control group (10%sodium carboxymethyl cellulose ).The time of gavage administration lasted 28 days.The blood biochemistry , organ coefficient and pathological changes of the heart , liver, kid-neyweretestedafterthedrugadministration.Thegrowthofmicewasalsorecorded.Results ①Bloodbiochemistry:Com-pared with the WT male administration group , in the Tg male administration group , the levels of blood creatinine ( CREA) and aspartate aminotransferase (AST) were markedly increased (P<0.01, P<0.05).② Organ coefficient: Compared with the Tg control group, the kidney coefficients of Tg administration group were significantly increased (P<0.01,P<0.05).③Histopathology:Compared with the WT administration group , the pathological damages of liver and kidney were more serious in the Tg administration group .Conclusions Compared with C57BL/6J mouse, PPARαtransgenic mice are more sensitive in evaluation of hepatotoxicity and nephrotoxicity of PPARαagonists .It is a new animal model .

Nutrition investigations on the workers of drilling rig “Bohai 7” belong ing to Bohai Oil Company were conducted in November (winter) 1990 and June (summer) 1991, Energy consumptions of seven major and nine special actions of the offshore personnels were studied. Based on this, recommended amount of food to be taken and that of nutrients to be supplied in the daily dietary intake have been proposed for the workers on offshore drilling platforms, to improve the present improper food pattern which was characterized by high fat and low vitamin to ensure the workers health and to increase their potential adaptability to the special environment.

To construct, express and purify fusion protein containing HBcAg and HBsAg preS1 epitope peptide for the purpose of investigating a novel HBV vaccine with both prophylactic and therapeutic functions. Using DNA recombinant technology, prokaryotic expression plasmid pBTcs1 expressing HBcAg and HBsAg pre-S1 epitope peptide fusion protein was constructed. After expressed in E.coli. HB101, the production BTcs1 was purified by sucrose density gradient ultracentrifugation and identified by SDS-PAGE, SEC, Western-blot and electron microscope. The results indicated that expression plasmid pBTcs1 was constructed successfully, and 20~25 mg purified BTcs1 fusion protein was obtained from 1L LB culture. Result of DOT-BLOT indicated that the distribution of BTcs1 was mainly in 30~50% sucrose, the purity of BTcs1 was greater than 95% by SDS-PAGE and SEC analysis. BTcs1 could probe with specific antibodies at 28 kDa by Western-blot, BTcs1 could also self assemble VLP by electron microscope analysis, its diameter was 30~34 nm approximately. The present study lay a foundation for further research functions and applications of BTcs1.

Drug stability is closely related to drug safety and needs to be considered in the process of drug production, package and storage. To investigate the stability of epalrestat, a carboxylic acid derivative, a reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed in this study and applied to analyzing the degradation kinetics of epalrestat in aqueous solutions in various conditions, such as dif-ferent pH, temperatures, ionic strengths, oxidation and irradiation. The calibration curve was A=1.6 × 105C–1.3 × 103 (r=0.999) with the liner range of 0.5–24 μg/mL, the intra-day and inter-day precision was less than 2.0%, as was the repeatibility. The average accuracy for different concentrations was more than 98.5%, indicating that perfect recoveries were achieved. Degradation kinetic parameters such as degradation rate constants (k), activation energy (Ea) and shelf life (t0.9) under different conditions were calculated and discussed. The results indicated that the degradation behavior of epalrestat was pH-dependent and the stability of epalrestat decreased with the rised irradiation and ionic strength;however, it was more stable in neutral and alkaline conditions as well as lower temperatures. The results showed that the degradation kinetics of epalrestat followed first-order reaction kinetics. Furthermore, the degradation products of epalrestat under stress conditions were identified by UHPLC-PDA-MS/MS, with seven degradation products being detected and four of them being tentatively identified.

Objectives：This study was designed to investigate the regulation effect of 8-Br-cAMP （ 8-Bromo 3′ ：5′ -cyclic adenosine monophosphate） on the expression of connexin gene (Cx43) in human tongue carcinoma cell line (Tca8113) . Methods：The inhibitory effect of 8-Br-cAMP on growth of Tca8113 cell line was examined by methyl thiazolyl tetrazolium (MTT) assay. Cx43 gene expression in Tca8113 cells after treated with 8-Br-cAMP was analyzed by immunocytochemistry and flow cytometry . Results：After treated with 8-Br-cAMP(10-5 mol/L, 10-4 mol/L, 10-3 mol/L), Tca8113 cells was inhibited and the inhibition rate was increased with the concentration of 8-Br-cAMP; Immunocytochemistry showed Cx43 protein detectability and up-regulation in 8-Br-cAMP treated cells; The positive rate of Cx43 protein in Tca8113 ce1ls increased from 4.8％ to 26.5％ . There was significant difference between 8-Br-cAMP treated cells and untreated cells （ P<0.01） . Conclusion： The anti-tumor effect of 8-Br-cAMP on Tca8113 cells might be due to up-regu1ation on Cx43 gene.

Objective: To evaluate the clinical value of echocardiography in aortic valvuloplasty (AVP) in the low-age pediatric patients with congenital aortic valve stenosis. Methods: We retrospectively studied 39 low-age (at median of 23 months) patients with congenital aortic valve stenosis who received aortic valve repair in our hospital for their echocardiography information, and statistically analyzed the main indicator changes by 4 time points as pre-operation and 1 week, 1-3 months, 6-12 months after the operation respectively. Results: In our study, the bicuspid to tricuspid valve ratio was approximately at 5.5/1 and 2 patients died during peri-operative period. Compared with pre-operative time point, Doppler aortic valve peak velocity (Vmax ) and the mean aortic transvalvular pressure gradient (MPG) were reduced accordingly, for Vmax: (4.30 ± 0.73) m/s vs (2.65 ± 0.78) m/s, (2.93 ± 0.63) m/s, (3.01 ± 0.83) m/s,P<0.01, for MPG: (45.78 ± 15.19) mmHg vs (18.24 ± 10.08) mmHg, (21.01 ± 10.08) mmHg, (22.31 ± 13.41) mmHg. Compared with pre-operative time point, left ventricular ejection fractions (LVEF) were similar in 3 post-operative time points. Compared with 1 week post operative time point, left ventricular end-diastolic anteroposterior diameter (LVEDD) was increased at 6-12 months post-operative time point, the relative wall thickness (RWT) was decreased, bothP<0.05, and aorta valve regurgitation (AR) was increasedP<0.01. Pearson correlation analysis showed that aortic annulus (AA) inner diameter was positively related to LVEDD (r= 0.648,P<0.01), negatively related to Vmax (r= -0.205,P<0.05) and RWT was positively related to Vmax (r= 0.196,P<0.05). There were 6 patients with pre-operatively decreased LVEF, 1 of them died and the rest 5 with elevated LVEF at 6-12 months post-operative period,P<0.05. Conclusion: Echocardiograghy could be used as the ifrst choice of imaging method for diagnosing congenital aortic valve stenosis, it has the important role for in-operative monitoring and post-operative evaluation of AVP in relevant patients.

Objective To report the outcome of emergency repair of severe complex defect in forearm by transplantation of free flap and simultaneous functional reconstruction.Methods From Mar.1994 to Aug.2003,4 cases with severe complex defect in forearm was repaired by transplantation of free skin flap, free skin flap combined with fibula flap,or fibula osteocutaneous flap in emergency.Simultaneously the flexion and extension function were repaired by muscle transfer and/or tendon grafting,tenonectomy.Results All the cases were successful.Follow-up period ranged from 1 to 3 years postoperatively.The blood-supply,tex- ture and elasticity of transferred flaps were excellent with good bone healing.Opposition of thumb with four fin- gers was good.Sensory recovery of the hand was satisfactory.Conclusion Transplantation of free flap com- bined with simultaneous functional reconstruction is an ideal method in emergency repair of severe complex de- fect in forearm.

OBJECTIVETo investigate the augmentation effect and mechanism of all-trans retinoic acid (ATRA) on the bystander effect of herpes simplex virus thymidine kinase (HSV-TK)/ganciclovir (GCV) system in the treatment of tongue carcinoma cell line.

METHODSImmunocytochemistry and flow cytometry (FCM) were used to analyze the expression of Cx43 protein in Tca8113 cells after treated with ATRA; The bystander effect of HSV-TK/GCV system on tongue carcinoma cells before and after treatment with ATRA was detected by MTT assays. The interaction of ATRA and bystander effect was analyzed by factorial experiment.

RESULTSAfter treated by ATRA (10(-7) mol/L - 10(-5) mol/L), the expression of Cx43 protein was up-regulated in Tca8113 cells and the positive rate of Cx43 protein increased from 5.17% (before treatment) to 30.53% (10(-5) mol/L ATRA). There was significant difference between ATRA treated cells and untreated cells (P < 0.01). The bystander effect of HSV-TK/GCV system on Tca8113 cells was poor, but improved after combined with ATRA. There was cooperation effect between ATRA and bystander effect of HSV-TK/GCV (P < 0.05).

CONCLUSIONSATRA can augment the bystander effect of HSV-TK/GCV system in the treatment of tongue carcinoma cell line. The mechanism might be due to up-regulation of Cx43 gene and restore gap junction intercellular communication.

Antineoplastic Agents ; pharmacology ; Bystander Effect ; drug effects ; Cell Survival ; drug effects ; Connexin 43 ; metabolism ; Dose-Response Relationship, Drug ; Drug Synergism ; Ganciclovir ; pharmacology ; Humans ; Simplexvirus ; enzymology ; Thymidine Kinase ; genetics ; Tongue Neoplasms ; metabolism ; pathology ; therapy ; Tretinoin ; pharmacology ; Tumor Cells, Cultured ; drug effects ; metabolism

Abstract: Objective　To collect and organize malaria case data in Hubei Province from 2017 to 2021, compare and analyze the malaria epidemic characteristics on the before and after malaria elimination, and provide scientific support for Hubei Province to further optimize the comprehensive strategies to prevent re-transmission after the elimination of malaria. Methods The study was conducted by collecting the data of reported malaria cases of Hubei during 2017-2021 from the Infectious Disease Surveillance Reporting and Management System, and conducting the epidemiological characteristics of malaria on pre-elimination (2017-2019) and post-elimination (2020-2021). Results A total of 429 cases of imported malaria were reported in Hubei Province from 2017 to 2021, and the malaria epidemic showed an obvious trend of rising first and then falling. On the pre-malaria elimination, 374 malaria cases were reported, including 262 cases of P.falciparum (70.05%); on the post-malaria elimination, 55 malaria cases were reported, including 25 cases of P.falciparum (45.45%). There was a statistically significant difference in the proportion of infections caused by the four types of malaria parasites before and after the elimination of malaria (χ2=14.248, P<0.05). On the pre-malaria elimination, the peak of disease onset mainly occurred in January, July, and November; on the post-malaria elimination, the peak of disease onset mainly occurred in January to February, and December. Both before and after malaria elimination, the reported cases were mainly concentrated in Wuhan, Yichang, Huangshi, Xiangyang, Shiyan and Huanggang, but the range of cases showed a clear trend of narrowing. Before and after malaria elimination, malaria cases in Hubei Province were mainly among young and middle-aged males aged 30-49. The proportions of workers and migrant workers increased from 37.70% and 9.09% before the elimination to 50.91% and 18.18% after the elimination, respectively, with a statistically significant difference (χ2=17.839, P<0.05). The percentage of interval from onset of illness to initial diagnosis ≥ 5d decreased from 21.66% before the elimination to 10.91% after the elimination (χ2=6.448, P<0.05). The percentage of definitive diagnosis of malaria at initial diagnosis in town clinic increased from 18.18% before the elimination to 50.00% after the elimination. The proportion of malaria cases diagnosed by county-level medical institutions increased from 22.73% before the elimination to 34.55% after elimination. There was no statistically significant difference in the proportion of malaria cases diagnosed by medical institutions at all levels before and after the elimination of malaria (χ2=5.630, P>0.05). The proportion of cases with the interval between initial diagnosis and diagnosis within 24h increased from 43.85% before the elimination to 70.91% after the elimination. There was a statistically significant difference in the proportion of cases with the interval between initial diagnosis and diagnosis before and after the elimination of malaria (χ2=14.006, P<0.05). Before and after malaria elimination, all reported cases were mainly imported from African countries. Conclusions There are imported malaria cases reported every year in Hubei Province before and after the elimination of malaria, which poses a great challenge to the prevention of re-transmission. Therefore, it is necessary to strengthen the surveillance system, detect and standardize the treatment of imported malaria cases in a timely manner, conduct targeted retransmission risk surveys and assessments, and consolidate the achievements of malaria elimination.

This study was aimed to investigate the effect of recombinant human granulocyte colony-stimulating factor(G-CSF) on murine thymocyte emigration and cell cycle alteration after a sublethal dose of gamma-irradiation. Female BALB/c mice were given 6.0 Gy γ-ray total body irradiation and then randomly divided into G-CSF and control groups. Mice in the G-CSF group were injected recombinant human G-CSF 100 µg/(kg·d) subcutaneously once daily for 14 consecutive days and mice in the control group were given the same volume of phosphate buffered solution. Thymocyte cycle alteration and the proportion of apoptosis cells were detected by flow cytometry within 72 hours after irradiation. Real-time PCR was used for detection and quantitation of murine T cell receptor rearrangement excision circles (sjTREC) of the thymic cells at 30 and 60 day after the irradiation. The results showed that at 6 hour after irradiation G-CSF could significantly increase the thymic cells in G(0)/G(1) phase, G-CSF vs control: (82.0 ± 5.0)% vs (75.9 ± 2.8)% (p < 0.05), and decrease the thymic cells in S phase, G-CSF vs control: (10.2 ± 4.8)% vs (15.7 ± 2.3)% (p < 0.05), but G-CSF seemed have no evident effects on the percentage of thymic cells in G(2)/M phase. G-CSF could also protect thymocytes from apoptosis at 6 hour and 12 hour after irradiation the percentages of apoptosis cells in G-CSF group were (11.5 ± 2.4)% and (15.5 ± 3.3)%, respectively, which were significantly lower than that of the control group (16.5 ± 2.2)% and (22.6 ± 0.7)%, respectively (p < 0.05). The sjTREC copy amount was conspicuously higher in G-CSF group than that in the control at 30 day after irradiation (p < 0.01), but the preponderance disappeared 60 days later. It is concluded that G-CSF has a positive effect on the thymic cell cycle alteration to protect thymocytes from apoptosis and enhance the recent thymocyte emigration, which may contribute to the central immune reconstitution after irradiation.
Animals ; Cell Cycle ; drug effects ; radiation effects ; Female ; Gamma Rays ; adverse effects ; Granulocyte Colony-Stimulating Factor ; pharmacology ; Mice ; Mice, Inbred BALB C ; Recombinant Proteins ; pharmacology ; Thymocytes ; drug effects ; radiation effects