Objective To assess the post-licensure safety and immunogenicity of freeze-dried live attenuated hepatitis A vaccine(H_2 strain) in order to popularize it as an immunization program vaccine.Methods Totally 5 000 healthy infants and young children aged 18-24 months were injected with single dose of freeze-dried live attenuated hepatitis A vaccine, and the adverse events of 0-14 d after vaccination were monitored. Among them, 200 cases were selected into immunogenic subgroups, and the serum hepatitis A virus(HAV) specific IgG antibody(anti-HAV IgG) was measured 8 weeks before and after immunization.Results A total of 5 000 participants completed inoculation, and 4 999 participants completed safety observation, among which, 424 cases of adverse reactions were reported, and the incidence of solicited adverse reactions was 8. 48%. The common local solicited adverse reactions were redness, tenderness, itching, rash and swelling at the inoculation site, while the systemic adverse reactions were mainly fever and anorexia. The severity was mainly grade 1-2, and no serious adverse events related to the vaccine occurred. Among 200 immunogenic subgroups, 188 participants were included in the per protocol set(PPS), the seroconversion rate of anti-HAV IgG antibody was 98. 91% [95% confidence interval(CI): 96. 11%-99. 87%], with a geometric mean titer(GMT) of 83. 67 mIU/mL(95% CI: 77. 05-90. 85 mIU/mL).Conclusion A single dose freeze-dried live attenuated hepatitis A vaccine(H_2 strain) presents good safety and immunogenicity for infants and young children aged 18-24 months.

Angelman syndrome is a neurodevelopmental disorder characterized by developmental delay, intellectual disability, dyskinesia, speech impairment, pleasant expression, epilepsy and abnormal electroencephalogram.The early symptoms of this disease are not typical, and attention should be paid to identification.In this article, the recent advances in clinical, ubiquitin-protein ligase E3A gene, genetic characteristics, genetic counseling and the treatment strategies of Angelman syndrome will be reviewed.

In the paper,we will deeply research sorts of ethical problems in medical genetics and their origins through a view of the human dual evolutions,and bring forward the viewpoint that any ethical problem can be originated from the conflict between human biological evolution and cultural evolution.Based on fully reasoning the relation between ethical problems in medical genetics and human evolution,the authors put forward a series of corresponding strategies to solve the ethical problems in medical genetics.

Objective To establish immortalized bone marrow mesenchymal stem cells (BMSCs) from SD rats in vitro for further research on the characteristics and clinical application of BMSCs.Methods By using L ipo-fectamine TM 2000 -mediated gene transfection, plasmid pCMVSV40T/PUR containing the simian virus 40 large T antigene gene (SV40Tag) was transfected into BMSCs.BMSCs were screened by puromycin and then cultured on an extended scale.Their cell morphology and growth conditions were observed.Growth curve of cells was graphed.The expression of SV40Tag in transfected cells was identified by enzyme digestion method for the detection of tumor forma-tion.Results The growth rate of the experimental group of BMSCs after the 7th generation was significantly higher than that of the control group.No tumorigenicity was found in BMSCs after the 7th generation.Conclusion In vitro, the immortalized BMSCs by pCMVSV40T/PUR can provide basis on a large scale for its application in clinic and sci-entific research.

Objective To explore the changes of the internal structure and research topics of oncology from 2005 to 2014,and offer reference for the development of the related studies and research policies. Methods The articles published in 203 journals in the area of oncologyfrom 2005 to 2014 included by JCR were chosen.Firstly,we cleaned the author keywords using the TDA software.After that,we standardized and categorized the keywords according to the Medical Subject Headings (MeSH)manually.In the end,we builted the co-occurrence matrixes of high-frequency words in three stages:2005—2007,2008—2010 and 2011 —2014, and drew the evolution maps and strategic diagrams of each stage to analyze the changes of the internal structure and research topics of oncology.Results While the word frequence increasing rapidly,the main keywords reduced gradually from 2005 to 2014.The traditional treatments such as chemotherapy and radiotherapy,the diagnostic and the epidemiological investigation were the core subject of oncology.With the screening of neoplasms,the research on the cell physiological phenomena and the genetic phenomena gained vigorous expan-sion.Breast neoplasms,the topic whose deep exploration also led the development of other topics,has always been the hard nut as well as the hot topic of the oncology.During this period,researches on the screening of neo-plasms and the genetic phenomena were developed rapidly.Conclusion The content of oncology will be more thoroughly with some merge,division,development,declining and perishing of the internal themes occurred as well.The boundaries among the sub-structure are becoming more and more blurred and the screening of neo-plasms and the genetic phenomena has gradually become the dominant trend in general practices.

Objective To develop and verify a quantitative real-time PCR method for determination of the content of host cell DNA residues in severe acute respiratory symptom coronavirus 2(SARS-CoV-2) inactivated vaccine(Vero cells),in order to better control the safety of products.Methods DNA was extracted from inactivated SARS-CoV-2 vaccine(Vero cells) bulk by magnetic bead separation method,and the DNA residues of host cells were quantitatively analyzed by probetype PCR.The linear range,repeatability,intermediate precision,quantitative limit,specificity,durability and accuracy of the developed method were verified,and the host cell DNA re sidues of 5 batches of inactivated SARS-CoV-2 vaccine(Vero cells)were determined by this method.Results DNA standard curve showed good linearity in the range of 300～0.003 pg/μL(each R~2> 0.99);Relative standard deviations(RSD) of repeatability and intermediate precision verification were less than 20%;The quantitative limit was 0.001 pg/μL;Sample dilution and purified liquid dilution had no interference to detection;The results of 60 min incubation at 53,55,57 ℃ and 56,60,64 min incubation at 55 ℃ showed no significant difference;The recoveries of accuracy verification were 79%～83%,RSD <5%.This method had good adaptability in detecting DNA residues in the bulk of inactivated SARS-CoV-2 vaccine(Vero cells).Conclusion The quantitative realtime PCR method for determination of host cell DNA residues in inactivated SARS-CoV-2 vaccine(Vero cells) has been successfully developed,of which the linearity and range,repeatability,intermediate precision,quantitative limit,specificity,durability and accuracy meet the acceptable standards,and are suitable for the detection and quality control of host cell DNA residues in inactivated SARS-CoV-2 vaccine(Vero cells).

Objective To analyze the epidemiological characteristics of measles in Jilin Province from 2013 to 2020.Methods Through the measles surveillance system of China Disease Prevention and Control Information System,a national health security information project,the measles incidence data of Jilin Province from 2013 to 2022 were collected,the measles incidence and incidence characteristics were analyzed by descriptive epidemiological method,while the virus was isolated and the genotype was identified at the same time.Results From 2013 to 2022,3 202 measles cases were reported in Jilin Province,and the reported incidence rates were 0. 57/100 000,9. 88/100 000,0. 71/100 000,0. 32/100 000,0. 12/100 000,0. 13/100 000,0. 13/100 000,0. 05/100 000,0. 05/100 000 and 0. 06/100 000,respectively.By age group,people aged 0 ～ 1,2 ～ 6,7 ～ 18,19 ～ 29,30 ～ 49 and over 50 years accounted for 42. 19%,10. 31%,6. 28%,14. 52%,24. 83% and 1. 87% of all the reported incidence cases,respectively,while among cases aged less than8 months,8 ～ 12 months,2 ～ 18 years and over 19 years,98. 49%,71. 34%,33. 33% and 39. 77% had no vaccination history,respectively. From 2013 to 2018,a total of 44 measles virus strains were obtained in the measles laboratory of Jilin Province,except for one vaccine strain A genotype,the rest were all H1a genotype,and no measles virus strain was obtained since 2019.Conclusion From 2013 to 2022,the reported incidence of measles in Jilin Province showed a downward trend year by year,while there is still a need to maintain the coverage of two doses of vaccination of measles containing vaccine. At the same time,adult measles vaccination should be strengthened,and the sensitivity of surveillance system should be improved to prevent measles outbreaks.

ObjectiveTo develop and verify a multiplex real-time RT-PCR assay for simultaneous identification of human parainfluenza virus type 1(HPIV1),type 2(HPIV2)and type 3(HPIV3).MethodsThe whole genome sequences of HPIV1,HPIV2 and HPIV3 were downloaded from the database for alignment analysis,and the conserved regions were selected. Specific primers and probes were designed for the three viruses respectively to develop a multiplex real-time RTPCR assay with human ribonuclease P(RNase P)as theinternal quality control. The method was verified for the sensitivity,specificity and precision and used to detect 192 clinical samples.ResultsAfter optimization,the multiplex real-time RTPCR reaction system was determined to be 30 μL,including 10 × NeoscriptRTase/UNG Multi mix 3 μL,5 × Neoscript RT Premix Multi Buffer 6 μL,upstream and downstream primers of HPIV1,HPIV2 and HPIV3(100 μmol/L)0. 1 μL respectively,HPIV1,HPIV2,HPIV3 probes(100 μmol/L)0. 05 μL respectively,RNase P upstream and downstream primers(50 μmol/L)0. 06 μL respectively,RNase P probe(50 μmol/L)0. 03 μL respectively,template 15 μL,and ddH2O supplemented to 30 μL. The reaction conditions were 50 ℃ 20 min,95 ℃ 3 min and 45 cycles of 95 ℃ 15 s and54 ℃ 30 s. Fluorescence signals were collected during annealing in each cycle. The minimum detection limits of HPIV1,HPIV2 and HPIV3 were all 500 copies/mL by the multiplex real-time RT-PCR assay;The method showed no cross-reaction with influenza A virus,influenza B virus,respiratory syncytial virus andnovel coronaviruses. The coefficients of variation(CVs)in intra-and inter-groups of the recombinant plasmid standard mixture with three different concentrations were all less than 3%. HPIV1,HPIV2 and HPIV3 were detected in 192 clinical samples,and the positive rates were7. 81%,0. 05% and 3. 1%,respectively.ConclusionThe multiplex real-time RT-PCR assay for detection of HPIV1,HPIV2 and HPIV3 developed in this study has good sensitivity,specificity and precision,which has a high clinical application prospect in the field of rapid diagnosis and identification of HPIV.

Objective:To investigate the effect of shoulder girdle strengthening exercise combined with acupuncture and rehabilitation exercise on the recovery of stroke patients with hemiplegic shoulder pain.Method:Eighty-six stroke patients with hemiplegic shoulder pain who received treatment in the Department of Neurology of Ningbo No. 6 Hospital from January 2017 to December 2019 were included in this study. They were randomly assigned to undergo rehabilitation exercise and acupuncture (control group, n = 41) or shoulder girdle strengthening exercise combined with acupuncture and rehabilitation exercise (observation group, n = 45) for 8 successive weeks. The recovery of limb function, activities of daily living and shoulder pain were evaluated. Results:After intervention, the Visual Analogue Scale score in the observation group was significantly lower than that in the control group [(1.14 ± 0.48) points vs. (3.01 ± 0.62) points, t = 15.530, P < 0.05]. The Fugl-Meyer assessment score in the observation group was significantly higher than that in the control group [(42.68 ± 5.46) points vs. (30.78 ± 4.93) points, t = 10.622, P < 0.05]. The modified Barthel index in the observation group was significantly higher than that in the control group [(82.75 ± 8.93) vs. (71.48 ± 9.06), t = 5.801, all P < 0.05]. Conclusion:Shoulder girdle strengthening exercise combined with acupuncture and rehabilitation exercise can help improve patient’s ability of daily living and strengthen limb function. This treatment method is of great clinical significance and worthy of clinical popularization.

With the development of Semaglutide Injection(Ozempic~?)and Rybelsus~?,also known as(Semaglutide Tablets?),the original research drugs have been listed in China,and domestic biopharmaceutical companies are developing an increasing number of Semaglutide biosimilar drugs according to the biosimilar drug pathway. This paper reviews the current status of registration and research and development of original research drugs and biologically similar drugs of Semaglutide both domestically and internationally,analyzes the challenges and related technical requirements in quality research and quality similarity evaluation of Semaglutide,and combines the evaluation practice to analyze and explore common problems in pharmaceutical evaluation of Semaglutide biologically similar drugs,in order to provide reference for the pharmaceutical development and evaluation of such biologically similar drugs.