Since 1988,our school has been enrolling in increasing numbers students in 7-year programs of clinical medicine and stomatology. During the period, we have accumulated some experience, which can be embodied in five major points. On this basis, we have, starting from this year, enrolled students working on doctoral degree in 8-year programs with candidates who have completed 4-year undergraduate programs of science and engineering, designed to further intensify reforms in medical education programs.

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.

Complicated characteristic of facial modality acquisition and measurement is commonly needed in clinical environment.Two different methods were compared, one method was acquisition two-dimensional character based on the principle of machine vision with a charge-coupled device (CCD) capturing image, and another method was acquisition three-dimensional character based on the technology of Reverse Engineering with laser scanning capturing image. The principle, composition of the system, calibration and characteristics of different method are analyzed. Two-dimensional and three-dimensional facial data of thirty undergraduates was used to compare different methods. The application and restriction of different methods are concluded. The conclusion of this paper provided a reference for face plastic surgery, facial paralysis, facial surgical evaluation and rehabilitation design.

Objective: Expression of Bcl\|2 and Bax oncoproteins was tested in laryngeal squamous cell carcinoma (LSCC) in order to find the relationship between the two genes and LSCC, and to explrore their clinical significance by retrospectively study of pathological and clinical doouments. Methods: Immunohistochemical S\|P method was emioyed in testing the expression of Bcl\|2 and Bax oncoproteins in 74 patients with LSCC, 24 laryngeal atypical hyperplasis (LAH) and 24 laryngeal normal membrane (LNM). Results: Bcl\|2 oncoprotein was mainly expressed in cytoplasm of epithelium cells and a small part of cell membrances were stained, appearing brow or yellow, granular distribution.There were no expression in the cell nuclear and stroma. Bax oncoprotein was expressed in cytoplasm and cell membrane and there were a little expression in stroma, appearing light brown and yellow, granular distribution. Bax was less stained than Bcl\|2. The positive expression percentages of Bcl\|2 oncoprotein in LSCC, LAH, LNM tissues were 59.46%,66.67% and 20.83% respectively. The Bcl\|2 expressions in LSCC, LAH tissues were significantly higher than that in LNM (P＜0.05); The positive expression percentages of Bax oncoprotein in these three groups were 56.76%, 50.0% and 66.67% respectively which were no significant difference. The results of Spearman correlated analysis showed that expression of Bcl\|2 and Bax oncoproteins had no obvious correlations with pathological grade, clinical stage and metastasis of lymph node. Both were correlated only with smoking. Conclusions: The imbalance of Bcl\|2/Bax mainly induced by the high expression of Bcl\|2 oncoprotein played an important role in the development of LSCC and LAH, Bcl\|2 may act as a reference index in judging the biological speciality of LSCC; Expressions of Bcl\|2 and Bax oncoprotein had obvious corelation with smoking in LSCC, indicating Bcl\|2 and Bax genes may be a target of carcinogenic substance in tobacco; Expression of Bcl\|2 oncoprotein was blocked may be an important part in studying gene therapy for the future.

Objective To evaluate the association between the polymorphisms of BT-H4 gene and the risk of breast cancer, a case-control study was conducted in the population of Heilongjiang province, China. Methods We genotyped the single nucleotide polymorphisms of rs10754339, rs10801935 and rs3738414 in B7-H4 gene by PCR-RFLP in a Chinese population consisting of 287 breast cancer cases and 305 controls matched for age and sex, tagged all common haplotypes (frequency ≥ 1%), and analyzed the differences between patients and normal controls. Results Our data indicated that in rs10754339, the frequencies of G allele, AA genotype and AG genotype were significantly different between patients and controls (P=0.030, OR 1.359, 95 % CI 1.030-1.794; P=0.018, OR 0.671, 95 % CI 0.482-0.935; P=0.029, OR 1.455, 95 % CI 1.038-2.038, respectively). In rs3738414, the frequencies of A allele, GG genotype and AG genotype were significantly different between patients and controls (P=0.0008, OR 0.604, 95 % CI 0.455-0.803; P=0.001, OR 1.804, 95 % CI 1.289-2.253; P=0.005, OR 0.612, 95 % CI 0.435-0.862). The frequencies of AAA haplotype and GAG haplotype were significantly different between patients and controls (P=0.0015, OR 0.614, 95 % CI 0.456-0.828; P=0.0003, OR 1.954, 95 % CI 1.363-2.803). Conclusion Polymorphisms of B7-H4 gene appear to be associated with breast cancer in the population of Heilongjiang province, China.

Objective To assess the left ventricular synchronization and global systolic function in patients with implanted dual-chamber (DDD) mode cardiac pacemakers by real-time three-dimensional echocardiography(RT-3DE). Methods Left ventricular systolic synchronization and global function were evaluated in 20 patients with implanted DDD mode cardiac pacemakers and 20 normal people by RT-3DE. The left ventricular end-diastolic volume (LEDV), end-systolic volume ( LESV), stroke volume (SV), left ventricular ejection fraction (LVEF), the mean value of time from the start of electrocardiographic QRS wave to the point of minimal systolic volume (Tmean) of the 17 segments and those standard deviation(T-SD),the maximal difference of time among all 17 segments(Tmax) were obtained by RT-3DE. Results Compared with control group, LESV was significantly increased,SV, LVEF were significantly decreased and T-SD,Tmax were significantly prolonged (P <0.01 ). There were no differences in LEDV and Tmean between the two groups (P>0.05). In patients group,LVEF correlated closely with T-SD (r =-0.674, P<0.05) and Tmax (r = - 0. 634, P < 0. 05). Conclusions There were left ventrieular systolic asychronization and global systolic dysfunction in patients with implanted dual-chamber (DDD) mode cardiac pacemakers,which could be assessed by RT-3DE.

Objective To evaluate vitamin D status in middle-aged subjects in Beijing and explore the correlation between serum 25-hydroxyvitamin D[25(OH)D] levels and dyslipidemia.Methods A total of 448 individuals over 40 years old were enrolled in the cross-sectional survey.The general information,blood biochemical and lipid profiles and serum 25 (OH) D levels were collected.The subjects were either divided into two groups (the dyslipidemia group and the non-dyslipidemia group) based on the lipid levels,or four groups according to quartiles of 25 (OH) D levels.The association between 25 (OH) D levels and dyslipidemia risk was analyzed by a logistic regression analysis.Results A total of 234 cases were in dyslipidemia group,which accounted for 52.23％ of the subjects.The serum 25 (OH) D levels were significantly lower in the dyslipidemia group than in the non-dyslipidemia group both in men and in women (all P ＜ 0.05).The median serum 25 (OH) D level in the total subjects was 15.7 (12.2,20.1) μg/L with 91.1％ subjects of serum 25 (OH) D level ＜ 30 μg/L.The proportion of subjects with dyslipidemia (high TC,high TG,high LDL-C,or low HDL-C) increased with the decrease of 25 (OH) D level quartiles (P ＜0.05).After adjustment of confounding factors,the logistic regression analysis showed that subjects in the lowest 25 (OH) D quartile group had 143％ higher risks for dyslipidemia than those in the highest quartile group.Conclusion These findings indicate that 25 (OH) D insufficiency is highly prevalent among middleaged individuals and it may be associated with the risk of dyslipidemia.

Objective To analyze the outcome of patients receiving intrauterine insemination with husband sperm,in order to evaluate the effect of relative factors on pregnancy rate after intrauterine insemination. Methods Ninety-eight infertile couples who received intrauterine insemination in the Affiliated Hospital of Nantong University from March 2013 to May 2014 were selected as our subjects and 181 cycles were included. The information including clinical factors including maternal age,infertile time,infertile causes, ovulation induction protocol,time of insemination and postwash total motitle sperm(TMS)and pregnancy rate were recorded. Results (1)Totally 26 patients received clinical pregnancies,and clinical pregnancy rate(CPR) was 14. 36% per cycle. With age increase pregnancy rate decreased( χ2 = 1. 654 9,P = 0. 647).(2)The pregnancy rate of the patients was the same within the infertile time( χ2 = 1. 588 5,P = 0. 662).(3)The pregnancy rate of the patients with secondary infertility was lower than that of the patients with primary infertility,but there was no significant difference(χ2 = 0. 923 3,P = 0. 337).(4)The pregnancy rate of ovulation induction cycles was lower than that of nature cycles,but there was no significant difference(χ2 = 2. 222 0,P= 0. 136).(5)Postwash TMS was showed the same trend(χ2 = 0. 643 4,P = 0. 422). Conclusion In terms of intrauterine insemination with husband sperm,age,infertile time,infertile types,ovulation induction protocol and posrwash TMS can affect pregnancy rate,and the effects of various factors should be considered comprehensively in the process of therapy.

BACKGROUND:CTLA-4Ig as a tolerance-induction agent is a potential strategy in graft-versus-host disease prevention. OBJECTIVE:To investigate the efficacy of CTLA4Ig-gene-modified bone marrow stromal cels mediated by adenovirus to induce T-cel tolerance of haploidentical donors. METHODS: The bone marrow stromal cels isolated culture from the bone marrow of HLA haploidentical donors were transfected by recombinant adenovirus encoding CTLA4IgcDNA (AdCTLA4Ig) at a multiplicity of infection=50 for 72 hours. The expression rate and the location of CTLA4Ig in the transfected cels were detected by fluorescence microscope after immunofluorescence staining. CTLA4Ig-modified bone marrow stromal cels (2×104, 4×104and 8×104) were respectively co-cultured with 105 T cels from the peripheral blood of HLA haploidentical donors and 105 peripheral blood mononuclear cels from recipients. The proliferative inhibition rate was determined by MTT assay, and the level of interleukin-2 in the supernatant was detected by ELISA. The bone marrow mononuclear cels (1×105/wel) were co-cultured with CTLA4Ig-modified bone marrow stromal cel layers constructed in 6-wel plates. The number of bone marrow mononuclear cels and colony-forming unit-granulocyte macrophages were calculated after 5-day culture. RESULTS AND CONCLUSION: The expression rate of CTLA4Ig at the multiplicity of infection=50 was as high as 85%, and the immunofluorescence signals of CTLA4Ig were distributed unevenly in the cytoplasm. The inhibition rates of 2×104, 4×104, and 8×104 CTLA4Ig-modified bone marrow stromal cels on proliferation of T cels were higher than that of untransfected cels. The levels of interluekin-2 in the corresponding cel groups were significantly lower than that in the untransfected cels (P < 0.05). At 5 days of culture, there was no significant difference in the number of bone marrow mononuclear cels and colony-forming unit-granulocyte macrophages between the transfected and untransfected cel groups (P > 0.05). These findings indicate that CTLA4Ig-modified bone marrow stromal cels mediated by adenovirus can induce immune tolerance of T-lymphocyte from HLA haploidentical donors in vitro.

Objective In this study ,we investigated the apoptosis of hair cell in the cochlea of age -related hearing loss(AHL) generated by ENU mutagenesis ,and to study a pan caspase inhibitor (z-VAD -FMK) which is to protect the cochlea hair cells from hearing loss induced by age-related hearing loss(AHL) .Methods Through z-VAD-FMK intraperitoneal injection and round window membrane (RWM) drug were delivered into the Cdh23 nmf308 nmf/nmf mice 5(postnatal days 2 -32) inner ear .ResuIts The results showed that the nmf308 mice with progressive hair cell loss along a base to apex gradient with age-related hearing loss .The cochlear OHCs reduced from 5% ~10% at 1 month to 100% at 3 month in the basal region .Substantial amounts of TUNEL -positive OHCs nuclei appeared at 1 month age ,and activated caspase-3 labeling demonstrated that most OHCs appeared at 2 months age .These suggested that DNA single strand break was attributed primarily to apoptosis of cochlear le_sions ,whereas in the later stage of lesion ,the expansion led to activation of caspase-3 activity reduced with further progression of nuclear condensation in age-related hearing loss .ConcIusion The addition of a pan caspase inhibitor (z -VAD -FMK ) significantly protected the cochlea against the hair cell loss induced by apoptosis .Our study showed that aspase inhibitor ,Z-VAD-FMK appeared to play a prominent role in age-related hearing loss media_ted hair cell death loss induced by apoptosis .Our study showed that aspase inhibitor ,Z-VAD -FMK appeared to play a prominent role in age-related hearing loss mediated hair cell death .