Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

Objective:To analyze the epidemiological characteristics of a cluster of 5 confirmed COVID-19 cases related with the transmission in incubation period of initial case, and find out the infection source and transmission chain.Methods:According to "The Prevention and Control Protocol for Coronavirus Disease 2019 (Third Edition)" issued by the National Health Commission, a field epidemiological survey was conducted for the 5 cases in January 2020. Nasopharyngeal swabs and sputum samples were collected from them for the detection of 2019-nCoV by real time RT-PCR. Multi prevention and control measures were taken, such as tracking and screening close contacts, medical isolation observation, investigating the epidemiological link, analyzing transmission chain.Results:Case 1, who had common environmental exposure with other COVID-19 cases, got sick on 20 January, 2020 and was confirmed on 1 February. Case 2 became symptomatic on 22 January and was confirmed on 27 January. Case 3 got sick on 25 January and was confirmed on 30 January. Case 4 had illness onset on 20 January and was confirmed on 1 February. Case 5 got sick on 23 January and was confirmed on 31 January. Among the 5 cases, case 2 died and the illness of other cases were effectively controlled. After exclusion of other common exposure factors, case 1 had a 6-hour meeting with case 2 and case 3 on 19 January. Case 2 and case 3 might be infected by case 1 during the incubation period. It is the key point for epidemiological investigation.Conclusion:The epidemiological investigation indicates that the transmission might occur in the incubation period of COVID-19 case, close attention should be paid to it in future COVID-19 prevention and control.

Objective To explore the relationship between nutrition status and activity of daily livingof elders in nursing homes and the mediating effect of physical activity. Methods From Apr to Sep in 2016,320 elders in nursing homes were selected and were surveyed using the standardized tools. The mediating effects were analyzed with PROCESS. Results The scores of elders′ nutrition status, physical function and activities of daily living were (11.88±2.27), (3.61±3.51), (79.13±26.00) points, respectively. And there were 66.9％ elders suffering from activities of living life impaired. The nutrition status were significantly positive correlated with physical function and activities of daily living of elders, and the physical function were significantly positive correlated with activities of daily living of elders. The physical function partly mediated the association between nutrition status and activities of daily living, and the effect was reached to 39.1％. Conclusions The elders′activities of daily life was poor in nursing home in China. The physical function partly mediated the association between nutrition status and activities of daily living. The related departments could combine the long time and short time plans targeting at improving of nutrition status and physical function respectively, to enhance the outcomes of elders in nursing homes.

Objective To explore the immune-microenvironment of the retinas at different stages of retinal degeneration in Royal College of Surgeon (RCS) rats. Methods RCS-rdy--P+(RCS) rats at early stage (P20), middle stage (P40) and late stage (P60) were involved,12 rats at each post-natal day,RCS-rdy+-P+rats severed as control. Relative concentrations of rat cytokines in rat retina homogenate were detected by using Bio-Plex Suspension Array System. Relative expressions of interleukin-2 (IL-2),C-C motif ligand 2 (CCL2),chemokine (C-X-C motif) ligand 9 (CXCL9),CXCL10,CXCL11 and interferon-γ(IFN-γ) mRNA in rat retina were analyzed by real-time PCR. Expressions of IFN-γ and immune cells surface marker CD4,CD8 and CD161 in the retinas were detected by immunohistochemical staining. Percentage of IFN-γ positive T lymphocytes and natural killer(NK) cells in rat retina were analyzed by flow cytometry. The concentrations of IFN-γ in rat retina homogenate were evaluated by enzyme-linked immunosorbent assay ( ELISA ). The use and care of the animals complied with Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission. Results Lymphocytes related cytokines and chemokines mRNA expression levels in the RCS rat retinas showed increase trends with the extension of time. The expression levels of IL-2,CCL2,CXCL9,CXCL10,CXCL11 and IFN-γ mRNA in P60 RCS rat retinas were significantly increased than those in the P20 RCS rat retinas and the control rat retinas (all at P<0.05).The positive rates of CD4,CD8 and CD161 cells in the retinas of P60 RCS rats was (9.09±0.89)%, (18.77±0.38)% and (9.41±0.38)% ,respectively. The proportion of IFN-γ positive cells in the retinas of P60 RCS rats was (8.29±0.27)%,which was significantly higher than that of the control rats ([0.28±0.02]%),with a significant difference between them (t=29.03,P=0.00). CD4+,CD8+and CD161+lymphocytes were mainly distributed in the retinas of P60 RCS rats, and the expressions of IFN-γ were co-located with lymphocyte surface markers. There were significant differences in the concentrations of IFN-γ in the retinas of RCS rats and control rats at different day ages (Fgroup=16.49,P<0.01; Ftime=21.05,P<0.01),the concentration of IFN-γ in retinas of P60 RCS rats was significantly higher than that of P20 RCS rats, P40 RCS rats and control rats, and the differences were statistically significant ( all at P<0.05). Conclusions Along with the process of retinal degeneration,immune privilege balance in the retinas is disrupted, the expressions of lymphocytes related chemokines and cytokines are elevated. Lymphocytes infiltration and activation are appeared in the retina highly activated at the late stage of RP, leading to the significant up-regulation of inflammatory cytokine IFN-γ in microenvironment, which indicates that lymphocytes mediated immune response may take part in retinal degeneration.

Objective To investigate students' experiences of learning achieved through the flipped classroom based on Massive Open Online Course(MOOC). Methods Qualitative study in which data were gathered from semi-structured and in-depth interviews conducted with 8 key students from the flipped classroom. The interviews were analyzed using Nancy′s phenomenology 7-step analysis method. Results Four themes emerged from the interviews: personalized learning, active learning, cooperative learning, and the critical role of teacher. Conclusions Overall, our research highlights the efficacy of MOOC-based flipped classroom. The implementation of the flipped classroom in this study improved personalized, active, and cooperative learning, and promoted the positive teacher-student relationship. Further research is needed to continue the investigation into maintaining students′ learning initiatives, controlling teach-learning progression,and strengthening formative evaluation.

In order to investigate the molecular evolution and spatio-temporal migration of Getah viruses (GETV) isolated around the world,the nucleotide and deduced amino acid sequence of GETVs were analyzed and phylogenetic trees were constructed by using informatics software including ClustalX1.83,MegaAlign,GeneDOC and Mega6.0.The Bayesian Stochastic Search Variable Selection (BSSVS) program in the BEAST v 1.8.1 software package was used to analyze the spatial dynamics of the Getah virus.Results showed that the full-length of Getah virus E2 gene consists of 1 266 nueleotides,encoding 422 amino acids.And the homology of nucleotide and amino acid were 94.5％ 100％ and 96.4％ 100％ respectively.The molecular evolution analysis revealed that there were no species and geographical distribution difference existing among GETV host animals (e.g.horses and pigs) and vectors (e.g.mosquitoes).Bioinformatics analysis showed that GETV originated in Malaysia,then it was spread to Japan,China,South Korea,Mongolia,Russia,etc.GETV E2 gene was relatively stable since GETV was first isolated in 1955.The differences of species and geographical distribution did not exist among GETV host animals and vectors,and the virus has spread from tropical regions to Eurasian continent.Thus,strengthening the detection and monitoring of GETV and its infections in humans and livestock is critical.

Objective: To investigate the distribution patterns of arboviruses in Yunnan province near the China-Laos-Myanmar border, China, and to provide evidence for prevention and control of arboviruses diseases. Methods: Mosquito samples were collected in Daluo county of Xishuangbanna Dai Autonomous Prefecture and Zhengdong county of Pu’er city in Yunnan province, 2012. Viruses were isolated from the samples by tissue culture, positive isolates were identified by RT-PCR with arbovirus species-specific primers, for further sequencing and phylogenetic analysis. Results: A total of 17 species of mosquitoes from 6 genera were collected. A total of 24 strains of viruses were isolated from the mosquito pools and identified as Tembusu virus (TMUV) (2 strains), Japanese encephalitis virus (JEV) (3 strains), Getah virus (GETV) (2 strains), Banna virus (BAV) (4 strains), Densovirus (DNV) (9 strains) and Nam Dinh virus (NDiV) (3 strains). Conclusions The China-Laos-Myanmar border of Yunnan province is rich in species of mosquitoes and arboviruses.

Immunoglobulin (Ig) is considered a part of the innate immune system and cooperates with the complementary system as the first line of defense. In this study, a monoclonal antibody (MAb) direct against the light chain of goose Ig (GoIgCL) was generated, characterized and identified in various immunoassays to detect goose Ig. An immunoaffinity chromatography column prepared with this MAb was used to separate the goose Ig from sera. After being conjugated with horseradish peroxidase (HRP), this MAb was used as the secondary antibody to evaluate the goose-specific antibody. In addition, this MAb distinguished and localized the SIg+ lymphocytes from peripheral blood lymphocytes. MAb against GoIgCL may be good candidate to detect or purify goose Ig under various conditions and as a powerful tool for humoral immunity research on goose.

BACKGROUND:Existing evidence has shown that xenogeneic bone derived graft materials have the ability to repair bone defects, but little report is on the comparison of composition of xenogeneic bone and human bone.
OBJECTIVE:To analyze the chemical composition, mineral phase, calcium and phosphorus contents, total protein contents, and appearance of the cancel ous bones of the tibia from pig, bovine and human.
METHODS:Cancel ous bones of the tibia from pig, Banna miniature pig, bovine, young and old people were cut into bone particles of 0.5 cm×0.5 cm×0.5 cm. After degreasing or drying treatment, chemical composition, mineral phase, calcium and phosphorus contents, total protein contents of bone particles were detected using Fourier transform infrared spectroscopy, X-ray diffraction, plasma emission spectroscopy, scanning electron microscopy, and Kjeldahl method, respectively. Nano Measurer 1.2 and Photoshop cs6 were used to measure pore diameter and porosity rate based on the results of scanning electron microscope.
RESULTS AND CONCLUSION:The main inorganic phase of five kinds of cancel ous bones was hydroxyapatite and the main chemical composition was phosphate and carbonate. The calcium content of the bovine cancel ous bonewas lower than that of the other cancel ous bones (P<0.05) and the phosphorus content of the cacel ous bone of young man was higher than that of the pig and bovine cancel ous bones (P<0.01). The total protein content in the cancel ous bones of normal pig and Banna miniature pig was higher than that in the other three kinds of cancel ous bones (P<0.05). The pore diameter of five kinds of cancel ous bones was 400 to 600μm and the porosity rate was 60%to 70%. Moreover, the porosity rate of the bovine cancel ous bone was the highest. Therefore, we conclude that there are some certain differences in the organic and inorganic components of the pig or bovine cancel ous bones as compared with humans.