OBJECTIVE:To provide reference for cultivating high-level comprehensive medical talents with high quality. METHODS:Based on the market and social needs,the teaching reform was conducted from the concepts of educational ideas, modes,curriculum system,contents,management and other aspects. RESULTS:In order to adapt to the needs of society and era, it should establish large education educational ideas to cultivate student's independent ability to obtain knowledge and self-develop-ment to make people change into community basic services and service and dedicate society with modes of cultivating inter-disci-plinary talents,including combination of prduction and study,foundation strengthening,professional expanding,penetration of sci-ence and technology and combination of arts and science;generally optimize curriculum system with theprinciple of precise defini-tion,clear classification,and optimized combination based on market and social needs;and update contents timely and teaching materials;the teaching management should be changed from closed off management of the past to the external management which dominated by the market assessment. CONCLUSIONS:Reform of medical higher education based on the market and social needs can cultivate the talents with high quality and comprehensive medical knowledge for the social needs,which is conductive to the de-velopment of medical industry.

Objective To discuss the relationship between various T lymphocyte subsets apoptosis and disease progression in chronic antiretroviral-naive HIV/AIDS patients. Methods Thirty-six chronic antiretrovi-ral-naive HIV-infected individuals as well as 16 healthy HIV-negative controls were performed in this study. Ac-cording to the CD4~+ T cell counts, all the patients were divided three groups: < 200/μl, 200-350/μl and > 350/μl. After the peripheral blood mononuclear cells(PBMC) were isolated, T lymphocyte subpopulations were determined by the expression of CD45RO and CD27, and the apoptosis of different T cell subsets were measured by Annexin V staining, then analyzed by flow cytometry. To investigate whether the apoptosis of T cells varied with the culture time in vitro, 4 healthy controls and 4 patients were chosen as subjects, and the lev-els of cell apoptosis were analyzed at the culture time points of 0, 3, 6, 12, 24 h. Results (1)The percenta-ges of the AnnexinV expression on CD4~+ and CD8~+ T cells and all the subsets in HIV/AIDS patients were sig-nificantly higher than that in the healthy controls (P<0.05), but there were no significant differences among the three HIV-infected patient groups(P>0.05). (2) No significant correlations were observed between the levels of apoptosis of all the T cells and subsets and total CD4~+ T cell counts(P>0.05) ,nor with the HIV viral load (P>0.05). (3)As the culture time prolonged in vitro, the levels of apoptosis and necrosis of CD4~6 T cells in HIV/AIDS patients were significantly higher than those in the healthy conlrols, and the CD4~+ T cells were more susceptible to apoptosis and necrosis compared with CD8~+ T cells. Conclusion The levels of T cell apoptosis in HIV/AIDS patients was significantly higher than those in the healthy controls, at the same time, CD4~+ T cells were more susceptible to apoptosis and necrosis compared with CD8~+ T cells, but no correlation was found between the T cell apoptsis and disease progression.

Objective To study the relationship of proliferation and activation of T lymphocyte subsets and disease progression in antiretroviral-naive human immunodeficiency virus(HIV)-1-infected individuals.Methods Forty-nine antiretroviral-naive,chronically HIV-1 infected patients and 16 healthy,HIV-1 negative controls were enrolled in this study.The patients were divided into 3 groups according to their CD4+T cell counts:<200×106/L,(200-350)×106/L and>350×106/L.Peripheral blood mononuclear cells(PBMC)were isolated.T cell proliferation index was measured by Ki-67 staining.T cell activation was detected by CD38 staining.The samples were analyzed by flow cytometry.The data were compared by one-way ANOVA.Results The percentage of Ki-67+cells in CIM+T ceils was 7.92%±4.37%in CD4+T cell<200×106/L group,which was significantly higher than those 0.39%d:0.24%in control group,2.61%±2.12%in(200-350)×106/k group and 2.65%±2.13%in>350 X106/L group(F=21.961,P<0.01).The percentage of Ki-67+cells in CD8+T ceils in CD4+T cells<200×106/L group was 2.87%±1.13%,which was also much higher than those in other 3 groups(0.15%±0.90%,1.40%±1.17%,1.22%±0.80%,respectively F=19.203,P<0.01).The Ki-67'CD4'T cells and Ki-67+CD8+T cells were inversely correlated with CD4+T cell counts(r=-0.654,r=-0.539,respectively;P350×106/L group(F=14.333,F=15.412,respectively;P<0.01).The expressions of Ki-67+ on CD4+ and CD8+T cells were positively correlated with CD38 expression(r=0.527,r=0.391,respectively;P=0.002).Conclusions The proliferation and activation of T lymphoeytes are enhanced during HIV/AIDS disease progression.And T eell activation may be the result of persistent immune activation.

Objective To evaluate the feasibility and safety profile of pegylated-interferonα-2a (Peg IFNα-2a) combined with adefovir dipivoxil (ADV) in inactive hepatitis B surface antigen (HBsAg) carriers (IHC).Methods This was a single center, prospective and open-label study.IHC were divided into therapeutic group (T, 112 subjects) and control group (C, 72 subjects) according to personal willingness.Patients with hepatitis B virus (HBV) DNA<20 IU/mL were treated with Peg IFNα-2a monotherapy, and those with HBV DNA ≥20-<2 000 IU/mL were treated with Peg IFNα-2a combined with ADV.Total therapy duration was 96 weeks.For patients who achieved HBsAg seroconversion and continued consolidation treatment for 24 weeks, the treatment duration could be less than 96 weeks.t test was used for continuous variable comparison between the two groups, while chi-square test or Fisher′s exact probability method was used for counting data analysis.The related factors affecting HBsAg clearance was analyzed by univariate or multivariate logistic regression analysis.Results A total of 194 patients were enrolled with 112 in therapeutic group and 72 in control group.The HBsAg clearance rate and seroconversion rate at week 48 in therapeutic group were 30.8% (32/104) and 26.0% (27/104), respectively.The rates at week 96 increased to 45.2% (47/104) and 38.5% (40/104), respectively.The HBsAg clearance rates at weeks 48 and 96 in control group were both 1.5% (1/68).HBsAg seroconversion was not achieved in control group.The HBsAg clearance rate in treatment group was significantly higher than that in control group (χ2=39.066, P<0.01).The quantitative HBsAg levels at baseline (OR=2.313, 95%CI: 1.258-4.251, P=0.007), week 12 (OR=3.159, 95%CI: 1.826-5.466, P<0.01) and week 24 (OR=3.347, 95%CI: 2.050-5.465, P<0.01), the decline of HBsAg at week 12 (OR=5.343, 95%CI: 2.085-13.689, P<0.01), and week 24 (OR=4.855, 95%CI: 2.380-9.902, P<0.01), and alanine transaminase (ALT) elevation at week 12 (OR=3.520, 95%CI: 1.369-9.052, P=0.009) were independent predictors for HBsAg clearance.Conclusions Peg IFNα-2a-based treatment for IHC could achieve higher HBsAg clearance rate and seroconversion rate, and has a safety profile.Decline of HBsAg at week 12 and week 24 with ALT elevation at week 12 could predict a higher HBsAg clearance rate.

Objective To improve the cliniciansˊ awareness of Kluver-bucy syndrome (KBS), we retrospectively analyzed 4 cases of KBS such as clinical manifestation, MRI feature, treatment and prognosis. Methods We performed a retrospective analysis on 4 cases of KBS including general clinical data, key clinical symptoms, findings from cerebrospinal fluid and Cranial MRI examination, treatment strategy and prognosis, and literature review. Results All four patients showed KBS in the course of primary disease. The clinical symptoms of KBS mainly presented as gentle, indiscriminate dietary behavior, hypersexuality, hypermetamorphosis, hyperorality and visual agnosia. MRI Showed primary disease-associated alterations in diverse brain regions including hippocampus, the temporal lobe, the insula, the frontal lobe, and the cingulate gyrus. Three cases achieved completely clinical remission after treatment with carbamazepine,fluoxetine and antipsychotic drugs. One patientˊs symptoms disappeared spontaneously and no recurrence of symptoms was observed in the following 6~12 months. Conclusion Bulimia is often the first symptom of KBS. Cranial MRI is the characteristic of the primary disease and has great diagnostic value. Treatment with antiepileptic and antipsychotics can achieve favorable prognosis.

Viral Protein R (Vpr) is an accessory protein of HIV-1 that increases the infectivity of HIV-1, activates latent viruses, and acts with other accessory proteins. A number of studies have demonstrated the important role of Vpr in the pathogenesis of HIV-1 related neurological diseases. Vpr can disrupt the integrity of the blood-brain barrier, induce neuronal apoptosis, and may be an important causative agent of AIDS dementia syndrome. However, the exact mechanism is still unknown. This review elaborates the neurotoxic effects of HIV-1 Vpr.

Objective: To observe the changes of liver function, virology and serology and the safety of drug withdrawal in pregnant women who are chronic hepatitis B virus (HBV) carriers. Methods: A prospective clinical cohort was established to enroll pregnant women who are chronic HBV carriers and they were divided into the nucleoside/nucleotide analogs (NAs) intervention group and the non-NAs intervention group according to patients' wishes. Liver function, HBV DNA and HBV serological markers were detected at gestation, postpartum 6 weeks, 12 weeks, 24 weeks, 36 weeks and 48 weeks. Results: 351 patients were enrolled, 320 in the NAs intervention group and 31 in the non-NAs intervention group. The proportion of postpartum hepatitis flares in both groups was higher than that in pregnancy (39.4% vs 12.5%, P < 0.001; 38.7% vs 3.2%, P = 0.001). Six weeks postpartum was the peak period of hepatitis flares, and 96.0% (121/126) of the hepatitis flares occurred within 24 weeks postpartum. At 6 weeks postpartum, there were 6 cases of alanine aminotransferase (ALT) ≥ 10 times upper limit of normal (ULN) in the NAs intervention group. The rate of the hepatitis flare after drug withdrawal was 16.7% (34/203). Conclusion Regardless of the presence or absence of NAs intervention, pregnant women who are chronic HBV carriers have a certain proportion of hepatitis flares during pregnancy and postpartum, and the hepatitis flare even have a tendency to be severe. Therefore, drug withdrawal after delivery is not always safe, which requires close observation and classification. At 6 weeks postpartum, the incidence of hepatitis flares was high, and those who meet the treatment indications can get better therapeutic effects if given appropriate treatment. The vast majority (96%) of postpartum hepatitis flares occur within 24 weeks, so it is recommended to follow up to at least 24 weeks postpartum after discontinuation.

Objective: To analyze the therapeutic effect on HBeAg-negative chronic hepatitis B patients treated with Peg-IFNα-2a combined with NAs to obtain the influencing factors for predicting HBsAg clearance. Methods: A retrospective study was conducted to investigate the effect of pegylated interferon alpha-2a combined with nucleoside analogues (lamivudine/adefovir dipivoxil) on HBeAg-negative chronic hepatitis B. The treatment course was 96 weeks. Patients were followed up 120 weeks after the treatment. HBsAg clearance at 120 weeks was taken as the objective of the study. Logistic regression and receiver operating characteristic curve analysis screened the related factors affecting HBsAg clearance. χ ² test was used to compare count data. Results: 111 patients were treated with pegylated interferon alpha-2a combined with nucleoside analogues, and 107 patients completed the scheduled course of treatment and follow-up. HBsAg clearance rate at120 week was 29.0% (31/107). The influencing factors for analysis were: (1) gender had no effect on HBsAg clearance rate; age and baseline levels of HBV DNA and alanine aminotransferase had no significant effect on HBsAg clearance; low baseline level of HBsAg (< 3.023 lgIU/ml) was beneficial to HBsAg clearance. The area under the working characteristic curve of the subjects was 0.746, the positive predictive value was 44.4%, and the negative predictive value was 86.8%. (2) HBsAg quantification or decline in 24 weeks and 48 weeks of treatment had a good predictive effect on HBsAg clearance, and the 48 weeks predicted value was higher than 24 weeks. When the HBsAg quantification was≤2.070 lgIU/ml at 48 weeks, the area under the receiver operating characteristic curve was 0.931, the positive predictive value was 52.8%, and the negative predictive value was 94.4%. When HBsAg decreased from baseline to≥0.991 lgIU/ml, the area under the receiver operating characteristic curve was 0.888, the positive predictive value was 50.8%, and the negative predictive value was 97.9%. (3) The analysis of HBsAg subgroup levels at 48 weeks suggested that the "interval analysis" can forecast HBsAg clearance more exactly than "nodal analysis" .The final HBsAg clearance rate of 100 IU/ml < HBsAg≤1 000 IU/ml, 10 IU/ml < HBsAg≤100 IU/ml and HBsAg≤10 IU/ml groups reached 6.7%, 31.8% and 67.7%, respectively. (4) The ALT abnormal group in the course of treatment obtained a higher HBsAg clearance rate (48.0%, 12/25). Conclusion 96-weeks long-term treatment with pegylated interferon-alpha -alpha-2a combined with nucleoside analogues for HBeAg-negative chronic hepatitis B has a good predictive value for HBsAg clearance at baseline and during treatment. The "interval level" of HBsAg at 48-weeks is more accurate in predicting HBsAg clearance, suggesting that HBeAg-negative chronic hepatitis B patients with low HBsAg levels at 48-weeks are the advantageous populations with HBsAg clearance. These patients are worthy of prolonged treatment to pursue "clinical cure".

Objective:To analyze the distribution of ages at the interhospital transfer of outborn very preterm infants in China and to compare their perinatal characteristics and outcomes at discharge and neonatal intensive care unit (NICU) treatment.Methods:A total of 3 405 outborn very premature infants with a gestational age of 24-31 +6 weeks who were transferred to the NICUs of the Chinese Neonatal Network (CHNN) in 2019 were included in this retrospective study. According to the age at transfer, they were divided into three groups: early transfer (≤1 d), delayed transfer (>1-7 d) and late transfer (>7 d) groups. Analysis of variance, t-test, Chi-square test (Bonferroni correction), Kruskal-Wallis test and Wilcoxon rank-sum test were used to compare the general clinical condition, treatment, and outcomes at discharge among the three groups. Results:The median gestational age was 29.7 weeks (28.3-31.0 weeks) and the average birth weight was (1 321.0 ± 316.5) g for these 3 405 infants. There were 2 031 patients (59.6%) in the early transfer group, 406 (11.9%) in the delayed transfer group and 968 (28.4%) in the late transfer group. Infants who received continuous positive airway pressure ventilation and tracheal intubation in the delivery room accounted for 8.4% (237/2 806) and 32.9% (924/2 805), respectively. A total of 62.7% (1 569/2 504) of the mothers received antenatal glucocorticoid therapy and the ratio in the early transfer group was 68.7% (1 121/1 631), which was higher than that in the delayed transfer group [56.1% (152/271), χ2=16.78, P<0.017] and the late transfer group [49.2% (296/602), χ2=72.56, P<0.017]. The total mortality rate of very premature infants was 12.7% (431/3 405), and the mortality rates in the early, delayed and late transfer groups were 12.4% (252/2 031), 16.3% (66/406) and 11.7% (113/968), respectively ( χ2=5.72, P=0.057). The incidences of severe intraventricular hemorrhage, late-onset sepsis, necrotizing enterocolitis, and bronchopulmonary dysplasia at the corrected gestational age of 36 weeks or discharge were all higher in the delayed and late transfer groups than in the early transfer group, respectively. The incidences of retinopathy of prematurity, retinopathy of prematurity requiring treatment and bronchopulmonary dysplasia at the corrected gestational age of 36 weeks or discharge in the late transfer group were significantly higher than that in the delayed transfer group (Bonferroni correction, all P<0.017). In the late transfer group, the median age of very premature infants at discharge was 66.0 d (51.0-86.0 d), and the corrected gestational age at discharge was 38.9 weeks (37.1-41.2 weeks), and both were greater than those in the early transfer [48.0 d (37.0-64.0 d), Z=260.83; 36.9 weeks (35.7-38.3 weeks), Z=294.32] and delayed transfer groups [52.0 d (41.0-64.0 d), Z=81.49; 37.4 weeks (36.1-38.7 weeks), Z=75.97] (all P<0.017). Conclusions:Many very premature infants need to be transferred to higher-level hospitals after birth. The later the very premature infants are transferred, the higher the incidence of complications will be. It is suggested that intrauterine or early postnatal transport may improve the prognosis of very premature infants.

Background and objective A great individual differences to chemotherapeutic effects existed in the patient with advanced lung cancer. How to choose the optimum regimens to achieve the individuation and maximum effect of chemotherapy for lung cancer is worth exploring. hTe study was designed to examine the effect of ex vitro chemo-sensitivity assay in xeno-free culture of autologous malignant effusion cells from patients with advanced lung adenocarcinoma.Methods hTe 50 treatment-naive patients with lung adenocarcinoma complicated with malignant pleural or pericardial effusions were enrolled. Effusions of all cases had been controlled by closed drainage and 300 mL-500 mL of which were retained under sterile condition from 25 cases (Chemo-sensitivity group). Primary malignant effusion cells were isolated from autologous effusions of the patients. hTen, xeno-free culture (average 11 days) were intervened with 8 chemotherapeutic drugs commonly used in clinical practice and were determined by CCK-8 assay. Optimum regimens were selected for chemotherapy based on the results of chemosensitivity test. As a contrast, chemotherapy regimens for the other 25 patients (Control group) were on the basis of physician’s clinical experience.Results Atfer four cycles of chemotherapy, in Chemo-sensitivity group, 17 (68.0%) cases were determined for partial response (PR), 5 (20.0%) cases for stable disease (SD), and the objective response rate (ORR) was 68.0%, the disease control rate (DCR) was 88.0%. Meanwhile, in Control group, 9 (36.0%) cases were determined for PR, 7 (28.0%) cases for SD, and, the ORR was 36.0%, the DCR was 64.0%. hTere were signiifcant differences between the two groups in ORR and DCR (P<0.05). To the end of follow-up, there were 21 cases of death in Chemo-sensitivity group as well as 22 cases in Control group. hTe mean progression-free survival (PFS) in Chemo-sensitivity group and Control group respec-tively were 10.0 months and 5.8 months, and the mean overall survival (OS) in the two groups were 30.2 months and 21.2 months respectively. hTere were also signiifcant differences between the two groups in PFS and OS (P<0.05). Furthermore, the adverse reactions in both groups were mild and controllable.Conclusion Xeno-free culture of autologous malignant effu-sion cells from patients with advanced lung adenocarcinoma andex vitro chemo-sensitivity assay are beneifcial to the rational choices of chemotherapeutic agents used in patients with lung adenocarcinoma complicated with malignant effusions, which is a worthy trial in personalized cell culture for individualized cancer therapy and further studies.