BACKGROUND:In consideration of the food safety and ecological safety of transgenic plants,the retention of marker genes is the primary safety issue affecting transgenic plants. OBJECTIVE:Based on the principle of immune caries prevention,our research team successfully constructed the plant anti-caries vaccine fusion gene expression vector pCAMBIA-E8-APB-DOCK8 for these two caries causing virulence factors surface protein and glucosyltransferase,which provides a basis for the research and development of transgenic plant vaccine. METHODS:In this study,the selective marker genes Km and GUS in the plant caries vaccine fusion gene expression vector pCAMBIA-E8-APB-DOCK8 were removed by DNA recombination technology through a series of steps such as DNA fragment separation,connection,transformation,clone detection,and sequencing. RESULTS AND CONCLUSION:The efficiency of marker gene removal was 99%.This study has laid a good experimental foundation for the safe production of transgenic plant vaccine against dental caries,and also provided ideas for the construction of other plant vaccine vectors.

AIM:To explore the effect of the peripheral defocus spectacle lenses and orthokeratology(OK)on the control of myopia progression and the impact on vision related quality of life in children and adolescents.METHODS:Prospective study. A total of 237 children initially diagnosed with myopia in the ophthalmology department of Huzhou Central Hospital from January 2021 to January 2022 were selected and divided into two groups according to different correction methods: peripheral defocus spectacle lenses group(105 cases, 105 eyes)and OK lens group(132 cases, 132 eyes). The Vision Related Quality of Life Questionnaire for Primary and Secondary School Students was used to follow up the both groups of myopic children, and the best corrected visual acuity(BCVA), spherical equivalent(SE), and axial length(AL)were recorded at the first visit and 1 a of follow-up.RESULTS:After wearing lenses for 1 a, both the peripheral defocus spectacle lenses group and OK lens group showed an increase in SE and AL, but there was no statistical difference between two groups(P>0.05). The changes in SE and AL in the peripheral defocus spectacle lenses group were greater than those in the OK lens group(all P=0.001). After 1 a of follow-up, in the emotional dimension scores, the peripheral defocus spectacle lenses group of children's vision-related quality of life scales scored higher than in the OK lens group(P<0.05). Compared with the baseline value, the change in the emotional dimension scores of the OK lens group was greater than that in the peripheral defocus spectacle lens group(P<0.05).CONCLUSION:OK lenses are superior to peripheral defocus spectacle lenses in controlling the progression of myopia in children and adolescents. Both correction methods can significantly improve myopic children's vision-related quality of life, with OK lenses being better at improving the emotional dimension of vision-related quality of life.

OBJECTIVE To evaluate the cost-effectiveness of clopidogrel versus aspirin monotherapy regimens for secondary prevention of ischemic stroke and to provide economic evidence and reference for clinical medication and decision-making. METHODS Based on the CAPRIE trial， a Markov model was constructed； the probabilities of risk events， health utility values， and costs of risk event management were obtained from relevant literature. The cycle length was 6 months， and the time horizon was 10 years. A discount rate of 5% per year was applied. The primary outcomes were total costs， quality-adjusted life-years （QALYs）， and incremental cost-effectiveness ratio （ICER）. Cost-utility analysis was performed for above 2 regimens by using TreeAge Pro software. The one-way sensitivity analysis， probabilistic sensitivity analysis and scenario analysis were conducted to validate the robustness of the analyses. RESULTS Compared with the aspirin regimen （325 mg/d of CAPRIE trial dose）， the ICER values of clopidogrel regimen for secondary stroke prevention for 10 years， 20 years and 30 years were 4 284.06， 4 201.20 and 3 986.78 yuan/QALY， respectively， which were E-mail：liuxiaoyanrj@sjtu.edu.cn all less than the willing-to-pay （WTP） threshold of one time 。 China’s per capita gross domestic product （GDP） in 2021. E-mail：scilwsjtu-wb@yahoo.com Compared with the aspirin regimen （clinically recommended dose in China， 100 mg/d）， the ICER values of clopidogrel regimen for stroke secondary prevention for 10 years， 20 years and 30 years were 58 238.27， 42 164.72 and 36 164.77 yuan/QALY， respectively， which were all less than WTP threshold. When comparing with aspirin regimen of 325 mg/d， results of one-way sensitivity analysis showed that the cost of clopidogrel and aspirin， probability of the first recurrence of ischemic stroke were sensitive factors of model. Results of probabilistic sensitivity analysis showed that when WTP was set at one time GDP per capita in China in 2021， clopidogrel had a probability of being cost- effective of about 66.5%. Results of scenario analysis showed that neither changing the time horizon to 10， 20 or 30 years nor using different doses of aspirin （50， 100， 150， 200 or 250 mg/d） would not alter any conclusions. CONCLUSIONS Compared with aspirin monotherapy， clopidogrel monotherapy is more cost-effective for secondary prevention of ischemic stroke.

OBJECTI VE To introduce the evaluation system for clinical value of antineoplastic agents at home and abroad ，and to provide reference for continuous improvement of clinical value-oriented antineoplastic agents development and research guideline in China. METHODS The suggestions were put forward to improve the evaluation system for clinical value of antineoplastic agents in China by consulting the relevant data of evaluation system for clinical value of antineoplastic agents at home and abroad and domestic antineoplastic agents R&D and management policies ，sort outing and analyzing comparatively their dimensions ， perspectives，target audiences ，application scope ，advantages and disadvantages. RESULTS & CONCLUSIONS Seven foreign value evaluation systems （value assessment framework of American Society of Clinical Oncology ，clinical benefit scale of European Society of Clinical Oncology ，value evaluation framework of American Institute of Clinical and Economic Evaluation ， etc.）had their own characteristics and unique advantages under different settings ；several value evaluation systems differed in the criteria for defining value ，depending on the perspective and population they focus on. The value dimensions were constantly changing dynamically in response to scientific values and social needs ，including not only safety ，efficacy and cost-effectiveness ， but also innovation ，fairness，quality of life attributes. Some evaluation systems adopted value assessment tools that followed the trend of the information age in the presentation form and assessment mode ，which promoted shared decision-making between doctors and patients. Combining the characteristics of foreign value evaluation system and the current situation of development and application of antineoplastic agents in China ，we can have a deeper understanding of drug efficacy ，safety，quality of life ，research and development cost and pricing in the future. Antineoplastic 2021-10-28） agents will have a more reasonable position to solve the unmet needs of patients from the perspectives of drug research and development， clinical application ， drug accessibility and fairness.

OBJECTIVE To compare five com monly used judgment criteria for potentially inappropriate medication （PIM）in the elderly ，and to provide reference for clinical selection of appropriate PIM evaluation tools for the elderly. METHODS From the aspects of applicable age ，content and scale characteristics ，five commonly used PIM judgment criteria for the elderly at home and abroad were analyzed and compared ，namely Beer ’s criteria ，STOPP/START v 2 criteria，ACOVE 3 criteria，PIM-Check criteria and“Judgment Criteria for Potentially Inappropriate Medication for Chinese Elderly ”（Chinese criteria ）. RESULTS The five standards both overlapped and focused in terms of scale characteristics. In each study ，the incidence of PIM was different according to different standards. Proton pump inhibitors ，diuretics，non-steroidal anti-inflammatory drugs and anticoagulants were the most frequently occurring PIM drugs for the elderly. CONCLUSIONS Combining with the specific conditions of patients and fully considering the benefits and risks of treatment ，rational selection and combination of five PIM judgment criteria ，and necessary supplements to my country ’s PIM judgment criteria ，will help clinicians and pharmacists to improve the efficacy and safety of the medication in the elderly patients.

Objective:To investigate the expression levels of CD4+ CD25+ FOXP3+ Treg cells and interleukin(IL)-10 in serum of patients with myelodysplastic syndrome (MDS) - refractory anemia (RA) and refractory hematopenia with multilineage dysplasia (RCMD), and to evaluate the effect of cyclosporine on CD4+ CD25+ FOXP3+ Treg cells in MDS patients.Methods:From January 2016 to January 2018, 25 MDS-RA and RCMD patients and 13 healthy controls were selected from people′s Hospital of Xinjiang Uygur Autonomous Region for retrospective analysis.The expression of CD4 + CD25 + Foxp3 + Treg and IL-10 in peripheral blood samples were detected by flow cytometry and enzyme-linked immunosorbent assay.The expression of CD4 + CD25 + Foxp3 + Treg and IL-10 in MDS-RA and RCMD patients before and 6 months after the treatment with CSA based immunosuppressive regimen was detected.Results:Of the 25 patients, 13 (52%) were effective and 12 (48%) were ineffective.The proportion of CD4 + CD25 + Foxp3 + Treg in CD4 + T cells of MDS group was significantly higher than that of healthy control group [(0.37 ± 0.10)% and (0.12 ± 0.06)% respectively, t= 2.02, P< 0.001]. The level of IL 10 in MDS group was significantly higher than that in healthy control group ((7.16±1.27) μg /L and (2.75 ± 1.06) μg /L, t= 2.03, P< 0.001). The ratio of CD4 + CD25 + Foxp3 + Treg cells in MDS group was lower than that in MDS Group ((0.15±0.06)% and (0.26±0.08%), t= 1.71, P< 0.001), and the level of IL 10 in MDS group was lower than that in MDS Group ((3.22±1.01) μg /L and (4.25±1.22) μg /L, t= 2.06, P= 0.030). The proportion of CD4 + CD25 + Foxp3 + Treg in peripheral blood of 25 MDS patients was positively correlated with the level of IL-10 expression ( r= 0.35, P= 0.02). Conclusion:The expression of CD4+ CD25+ FOXP3+ Treg cells and IL-10 increased in MDS patients increased, but decreased after cyclosporine treatment.

Objective To investigate treatment effects of levonorgestrel-releasing intrauterine system (LNG-IUS) for adenomyosis with severe dysmenorrhea in a prospective cohort study. Methods From December 2006 to December 2014, patients of symptomatic adenomyosis diagnosed by transvaginal ultrasound in outpatient or inpatient clinics of Peking Union Medical College Hospital were given the treatment of LNG-IUS. Before and after placement of LNG-IUS, all the patients′parameters were recorded prospectively, including symptoms and scores of dysmenorrhea, menstruation scores, biochemical indicators, physical parameters, carrying status of LNG-IUS, menstruation patterns and adverse effects. Changes of scores and patterns of pain during follow-up were analyzed. Results Totally 1 100 women meets inclusion criteria, among which 640 cases (58.18%, 640/1 100) had severe dysmeorrhea, with median follow-up period of 35 months (range 1-60 months), and accumulative carrying rate of 65% at 60 months follow-up. After placement of LNG-IUS, scores of pain and ratio of severe dysmenorrhea had decreased significantly compared with baselines (all P<0.01), the scroes of visual analog scale (VAS) were 8.1 ± 0.9, 5.5 ± 2.4, 4.6 ± 2.4, 3.3 ± 2.2, 2.2 ± 2.1, 2.2 ± 1.8, 1.4 ± 1.6 and 1.3 ± 1.3 at 0, 3, 6, 12, 24, 36, 48 and 60 months respectively. During 36 months after placement of LNG-IUS, scores of pain had improved significantly compared with preceding period (all P<0.01). We found no universal dependent factors predicting improvement of pain, which was neither relevant with simultaneous changes of menstruation patterns nor adverse effects (all P>0.05). Conclusion LNG-IUS is effective for adenomyosis of severe dysmenorrhea. Improvement of pain is independent on patients characters, menstruation patterns or adverse effects.

Objective To investigate the changes of mestruation patterns and adverse effects during the treatment of levonorgestrel-releasing intrauterine system (LNG-IUS) for symptomatic adenomyosis in a prospective cohort study. Methods From December, 2006 to December, 2014, patients of symptomatic adenomyosis diagnosed by transvaginal ultrasound in Peking Union Medical College Hospital were given LNG-IUS. Before and after placement of IUS, all patients′ parameters were recorded, including carrying status of IUS, symptoms and scores of dysmenorrhea, menstruation scores, biochemical indicators, physical parameters, menstruation patterns and adverse effects. Risk factors for changes of menstruation patterns and adverse effects, and their impact on treatment effects were analyzed. Results Totally 1 100 cases met inclusion criteria, with median age 36 years (range 20-44 years), median follow-up 35 months (range 1-108 months). During follow-up changes of menstruation patterns increased significantly with amenorrhea and shortened-menstruation being the most common manifestations. On 3, 6, 12, 24, 36, 48 and 60 months after the placement of LNG-IUS, 0, 5.8%(43/744), 6.9%(47/682), 10.1%(60/595), 17.3%(87/502), 27.2%(104/383) and 29.6%(82/277) patients achieved amenorrhea respectively (P<0.01). Total and subclassification of adverse effects decreased significantly (P<0.01). Within 12 months and >12 months after placement, abdominal pain and body weight increasing ≥5 kg/year were the most common adverse effects. Changes of menstruation patterns, total and subclassifications of adverse effects were neither dependent on patient parameters, treatment modes and treatment effects, nor could predict future LNG-IUS carrying status (all P>0.05). After taking out of LNG-IUS, most changes of menstruation and adverse effects disappeared. Conclusions During the treatment of LNG-IUS for symptomatic adenomyosis, changes of menstruation patterns increase gradually with amenorrhea and shortened-menstruation being the most common manifestations, while adverse effects decrease significantly. Changes of menstruation patterns or adverse effects neither have any risk factor nor have impact on treatment effects.

Objective To investigate treatment effects of levonorgestrel-releasing intrauterine system (LNG-IUS) for adenomyosis with menorrhea in a prospective study. Methods From December 2006 to December 2014, patients of symptomatic adenomyosis diagnosed by transvaginal ultrasound in outpatient or inpatient clinics of Peking Union Medical College Hospital were given the treatment of LNG-IUS. Before and after placement of LNG-IUS, all the patients′parameters were recorded prospectively, including scores of menstruation blood loss, carrying status of IUS, symptoms and scores of dysmenorrhea, biochemical indicators, physical parameters, menstruation patterns and adverse effects. Changes of pictorial chart scores of menstruation and distribution of anemia during follow-up were analyzed. Results Totally 1 100 women meets inclusion criteria, among which 618 cases (56.18%, 618/1 100) had severe menorrhea, with median follow-up period of 28 months (range 1-60 months), and accumulative carrying rate of 66% at 60 months follow-up. After placement of LNG-IUS, compared with baselines, pictorial chart scores and ratio of menorrhea had decreased significantly (all P<0.01), the scroes of menstruation were 157±34, 94±35, 70±33,67 ± 18, 67 ± 20, 65 ± 19, 66 ± 19, 65 ± 21 at 0, 3, 6, 12, 24, 36, 48 and 60 months respectively. During 24 months after placement of LNG-IUS, pictorial chart scores and distribution of anemia had improved significantly compared with preceding period (all P<0.01). We found no dependent factors predicting improvement of pictorial chart scores of menorrhea, which was neither relevant with simultaneous changes of menstruation patterns nor adverse effects (all P>0.05). Conclusions LNG-IUS is effective for adenomyosis of menorrhea. Improvement of menstruation blood loss is independent on patients characters, menstruation patterns or adverse effects.

BACKGROUND:Orthodontic treatment is a mechanical force for tooth to cause the remodeling of periodontal tissue, produced by the tooth movement. The main aspect of orthodontic periodontal tissue remodeling is the alveolar bone. Insulin-like growth factor is an important factor in the remodeling of periodontal tissue, which plays an important role in the growth, differentiation and growth of the cels. OBJECTIVE:To review the role of insulin-like growth factors in periodontal tissue remodeling. METHODS: A computer-based retrieval of PubMed, CNKI and Guizhou Province Digital Library Database was performed to search articles related to the role of insulin-like growth factors in periodontal tissue remodeling. The keywords were “insulin-like growth factor; periodontal tissue; remodeling” in English and Chinese, respectively. RESULTS AND CONCLUSION: Insulin like growth factor belongs to the insulin family, a kind of peptides, which can promote the migration, proliferation, differentiation, colagen and matrix synthesis and alkaline phosphatase activity of osteoblasts, fibroblasts and mesenchymal cels in the periodontal ligament. It also plays an important role in the repair of injury. During orthodontic treatment, the use of suitable orthodontic force combined with insulin-like growth factor can promote periodontal tissue remodeling, accelerate the orthodontic tooth movement and shorten the treatment time for patients.