Objective:To analyze the current situation of low copper diet management in children with hepatolenticular degeneration, so as to provide reference and help for individualized low copper diet guidance.Methods:Questionnaire survey and semi-structured interview were used. In the questionnaire survey, a total of 113 parents of children with hepatolenticular degeneration who were treated in the Pediatric Outpatient Department and ward of Chinese Academy of Medical Sciences, Peking Union Medical College Hospital from August 2021 to October 2022 were selected as the research objects. And a self-designed Low Copper Diet Status Questionnaire for Children with Hepatolenticular Degeneration was used for investigation. In the semi-structured interview, the purposive sampling method was used to recruit research objects that met the inclusion criteria. When the information reached saturation, they were no longer included, and finally 16 interviewees were included. Results:The results of the questionnaire showed that the items with the lowest accuracy in the part of the low-copper diet knowledge questionnaire for parents of children with hepatolenticular degeneration were "whether the food was edible according to the amount of copper in the food, for example, if the copper content in 100 g food exceeded 0.5 mg, it was forbidden to eat" and "in the following bean food (tofu, yuba, dried bean curd, oily bean curd), which one had the highest copper content". Among the 113 children, 55 were completely managed by their parents on a low copper diet, 53 children were jointly managed with their parents on a low copper diet, and 4 children were self-managed on a low copper diet. A total of 64 children currently followed the principle of a low copper diet, only consuming a few major categories of foods with low copper content. A total of 32 children ensured a diversified diet while ensuring that the total copper content in their daily food did not exceed the standard. The themes extracted from semi-structured interviews included insufficient awareness of low copper diet among parents of affected children, concerns about their children dining outside, doubts about how to balance low copper diet and nutritional balance among parents, and hopes that medical staff could provide some assistance in low copper diet guidance.Conclusions:The management of low-copper diet in children with hepatolenticular degeneration is poor. The parents of the affected children lack knowledge about low copper diet and have many confusions, and there is an urgent need for medical personnel to provide more specific, rich and practical guidance on low copper diet.

Premature ovarian insufficiency(POI),also known as"ovarian insufficiency",has an incidence of 1％～5％.The incidence has been on the rise in recent years,seriously affecting women's physical and mental health and quality of life.At present,the cause and mechanisms of POI are still unclear,and the method and applications of model construction are also confusing.Most models have some shortcomings in pertinence and stability.The limitations greatly limit research into the clinical diagnosis and treatment of POI.This paper summarizes and discusses the etiology and pathogenesis of POI and the construction of POI animal models to provide a comprehensive reference for those studying POI.

Objective:To understand the mental health status of fathers in neonatal intensive care unit and the intervention strategies for fathers′ mental health problems.Methods:Using the scoping review method as a framework, the studies on the mental health status of fathers with NICU in PubMed, CINAHL, Embase, Web of Science, Cochrane Library, PsycINFO, CNKI, WanFang Data, VIP and CBM were searched. The included studies were summarized and analyzed. The search time was from the database establishment to 30 August 2022. The content of literature extraction included author, country, publication time, research type, sample size, research variables, research content, and research results.Results:A total of twenty-five articles were included. Among them,11 literatures reported the mental health status of fathers of children in neonatal intensive care unit. Fathers experienced both negative and positive psychological changes after admission to the neonatal intensive care unit, including anxiety, depression, post-traumatic stress disorder, stress, sadness, and post-traumatic growth. Fourteen articles involved intervention strategies for mental health problems of fathers. Intervention strategies include enhancing social support (emotional support, peer support), stress management training (written disclosure, relaxation training, mindfulness therapy), information support, family integrated care (accompanied visits, kangaroo care).Conclusions:The admission of a newborn to the intensive care unit has caused many psychological problems for the father. However, there is still a lack of intervention strategies for fathers′ mental health problems, and it is still necessary for medical staff to take corresponding intervention measures according to fathers′ needs.

Objective:To investigate the whole genome characteristics and mutation of imported 2019-nCoV and trace potential source at the genomics level, the viral genomes from the specimens of a cluster of COVID-19 cases which were imported from a freighter were directly sequenced and determined by high-throughput sequencing technology and bioinformatics analysis.Methods:Throat swab specimens from the 8 confirmed cases of COVID-19 from the same freighter were collected to perform the whole genome sequencing for 2019-nCoV using the targeted genome amplification, combined with Ion S5 next-generation sequencing (NGS) technology. Varieties of online virus analysis platforms was used to classify the viruses and analyze mutation sites in the whole genome. Phylogenetic analysis software was used to construct a phylogenetic tree for the viruses, combined with the epidemiological data of the case, to speculate about the source of the viruses.Results:Eight complete genome sequences of 2019-nCoV was successfully obtained. The complete genomes of the viruses were 29, 822-29, 865 bp in length, with the average sequencing depth of 11 928×-33 588× and the coverage of 99.73%-99.87%; the result of Pangolin classification showed that all the eight 2019-nCoV genomes belong to VOC/Delta (B.1.617.2) lineage. The result of whole genome mutation analysis showed that compared with the Wuhan reference strain, the median number of nucleotide mutations in the eight 2019-nCoV genome sequences was 35 (31 to 38), and the median number of amino acid mutations was 26 (24-28); the mutation sites were distributed in 8 gene coding regions (ORF1a, ORF1b, S, ORF3a, M, ORF7a, ORF8, N). Further analysis revealed that eight 2019-nCoV genomes contained 23 characteristic mutation sites belonging to the Delta (B.1.617.2·AY.2) variants of 2019-nCoV. Since the mutation sites among the eight 2019-nCoV genomes were not completely overlapped, and the epidemiological survey report showed that the freighter stopped at multiple ports and had personnel alternation, it was speculated that the clustered COVID-19 cases might have different origins. Phylogenetic analysis showed that all the eight 2019-nCoV genomes were on the AY.2 sub-lineage of the B. 1.617.2 lineage. This result was consistent with the result of Pangolin classification and mutation analysis.Conclusions:In this study, 8 whole genome sequences of Delta variants were obtained through NGS technology from the clustered COVID-19 cases which were imported from a freighter. The sequencing method and analysis result in this study could provide reference for the 2019-nCoV mutation analysis and tracing the source of the COVID-19 cases for the prevention and control of the COVID-19 epidemic.

OBJECTIVE To boost access to medical insurance for drugs and improve the accessibility and affordability of drugs. METHODS The current status of the application of international and domestic drug Managed Entry Agreement （MEA）were investigated through literature research method and other methods ，and analyzed comparatively from the aspects of the scope of agreement drugs ，the types of agreements and the content of the agreement ，etc. The problems existing in the application of drug MEA in China were summarized to put forward the suggestions. RESULTS & CONCLUSIONS The UK ，Australia and Italy had rich experience in the application of drug MEA ，and the operation management mechanism were complete. The scope of drugs included in MEA in these countries were relatively broad and the types of agreements were relatively diversified. In China ，drugs included in MEA were mainly oncology drugs and rare disease drugs. The types of agreements mainly included “finance-based agreements”and effect guarantee/effect-based payment in individual-level of“performance-based agreements ”. China ’s evidence collection platform was imperfect and lacked standardized process of MEA. It is suggested that stakeholders should consider increasing the types of drugs ，diversified types of agreements ，improving the accuracy and continuity of evidence collection ， establishing a standardized process for MEA.

Objective:To systematically evaluate the life experience of patients with postpartum depression.Methods:PubMed, web of science, EMBASE, Scopus, PsychINFO, the Cochrane Library, CNKI, VIP, Wanfang and China biomedical database were searched for qualitative studies on life experience of patients with postpartum depression from the establishment to January 2021. The quality of articles was evaluated by the quality evaluation standard of JBI evidence-based health care center (2016) in Australia, and the results were summarized for meta integration.Results:A total of 23 studies were included, 50 complete results were extracted, 9 new categories were summarized, and 3 integrated results were obtained. Integration result 1: negative psychological emotion experience and coping style; integration result 2: personal role change and social environment influence; integration result 3: needs and obstacles.Conclusions:To improve the public′s cognition of postpartum depression, get the understanding of relatives and the attention of medical staff; pay attention to the life experience of patients with postpartum depression, give all-round support, meet the needs of pregnant women, promote the adaptation of mother′s role, and provide reference for medical staff to give humanized intervention.

In recent years, virtual reality technology has gradually been applied to alleviate children's anxiety due to its immersive, interactive and imaginative characteristics. This article introduces the related concepts of virtual reality technology and its intervention mechanism on anxiety and the application status of virtual reality technology in alleviating preoperative anxiety, dental anxiety and anxiety in children with cancer, in order to provide reference and guidance for clinical practice.

Objective:To integrate the experience of healthy siblings of children with chronic diseases living with their sick siblings.Methods:Cochrane Library, PubMed, Embase, Web of Science, CINAHL, PsycINFO, China National Knowledge Infrastructure, Wanfang, VIP and China Biology Medicine disc were searched for qualitative research literature on life experience of siblings of children with chronic diseases. The retrieval period was from the database construction to January 5, 2022. The quality of literature was evaluated using the qualitative research quality evaluation standard of JBI Evidence-based Health Care Center in Australia (2016) and the results were integrated using the method of pooled integration.Results:A total of 18 studies were included, 32 complete results were extracted, and the similar results were summarized to obtain 9 new categories, which were integrated into 4 integrated results, respectively, the first integrating result was that the challenges and burdens faced by healthy siblings in the process of living with their sick compatriots made them physically and mentally exhausted, the second integrating result was that the family relationship and life within the family had changed since the diagnosis of the disease, the third integrating result was that healthy siblings had limited perception ability and they were eager for information support and social support, the fourth integrating result was that with the passage of time, healthy siblings continued to adjust and adapt themselves, developed coping strategies and achieved positive personal growth.Conclusions:Children suffering from chronic diseases can adversely affect the psychosocial functions of their healthy siblings. It is suggested that the government, medical and health institutions, the public and families of children with chronic diseases should pay more attention to the psychosocial needs and life challenges of healthy siblings of children with chronic diseases, help them improve their negative emotions, improve their quality of life and further promote the healthy growth of siblings.

OBJECTIVE：To investigate the activity of lycorine to the in vivo apoptosis of tumor cells in H 22-bearing mice and its mechanism. METHODS ：Kunming mice were inoculated subcutaneously with ascites of H 22 hepatoma mice in the armpit of forelimb to establish solid tumor model. After modeling ，mice were randomly divided into negative control group ，positive control group（hydroxycamptothecin 6 mg/kg），lycorine low-dose ，medium-dose and high-dose groups （10，20，40 mg/kg），with 10 mice in each group. Negative control group was given constant volume of normal saline intragastrically ，and administration groups were given relevant medicine intragastrically ，once a day ，for consecutive 7 days. After last medication ，the weight of tumor was detected and anti-tumor rate was calculated. Ascites tumor model of mice was established by intraperitoneal injection of H 22 hepatoma mice ascites ，and then were grouped with same method and given relevant medicine as above. After last medication ， survival time of mice was recorded and the life prolongation rate was calculated. The early apoptotic rate of tumor cells in mice was detected by flow cytometry. On the basis of normal control group （normal mice without tumor ），the mitochondrial membrane permeability of tumor cells in each group was investigated by Calcein AM staining. The changes of mitochondrial potential were investigated by Rhodamine 123 staining. Colorimetry and Western blot assay were adopted to detect the Caspase-3 activity and expression of apoptosis-related protein （Bcl-2，Bax，Cyt-C and Caspase- 9）. RESULTS ：Compared with negative control UN- group，the tumor weight of positive control group and lycorine PYSCT-2017208） groups were decreased significantly ，while the survival time was significantly prolonged ，and the early apoptotic rate of tumor cells was significantly increased （P＜0.05 or P＜0.01）；the anti-tumor rates were 39.41％ ， 23.36％ ， 36.50％ ， 56.93％，and life prolonga tion rates were 49.23％，29.09％， E-mail：ym913@yahoo.com.cn 50.19％，69.08％. Compared with normal control group ，the mitochondrial membrane permeability ，Caspase-3 protein activity and protein expression of Cyt-C and Caspase- 9 were significantly increased，while the mitochondrial membrane potential and Bcl- 2/Bax ratio were decreased significantly （P＜0.05 or P＜0.01）. Compared with negative control group ，mitochondrial membrane permeability and Bcl- 2/Bax ratio were decreased significantly in administration groups ，while mitochondrial permeability ，Caspase-3 protein activity and protein expression of Cyt-C and Caspase- 9 were significantly increased （P＜0.05 or P＜0.01）. CONCLUSIONS ：Lycorine can induce the apoptosis of tumor cells in H22-bearing mice ，the effects of which may be associated with opening mitochondrial membrane permeability transition pore to increase mitochondrial permeability ， decreasing mitochondrial membrane potential and up-regulating the expression of apoptosis-related proteins.

Objective: To evaluate the accuracy of a 3D-printed template used to assist the preparation of tibial tunnel in reconstruction of anterior cruciate ligament (ACL). Methods: Twenty healthy adult cadaveric knees were scanned by computed tomography(CT) and magnetic resonance imaging (MRI). The knees were from 11 males and 9 females who had died at an average age of 36 years (range, from 27 to 68 years) and from 8 left and 12 right sides. Individualized 3D reconstruction models of the knee joint were established based on their imaging data. According to the anatomic footprints of the virtual tibial tunnel, 20 individualized navigation templates were designed and printed by 3D printing. The templates were used to assisst preparation of tibial tunnels in the ACL reconstruction for the 20 cadaveric knees. After operation, CT scanning was conducted again to compare the corresponding postitions between the preoperative virtual tunnel and the postoperative actual tunnel. The positions of the tibial tunnel were described by the Tsukada method. Results: The ratio of the distance between the tunnel outlet center and the medial edge of the tibia to the distance between the median and lateral edges of the tibial plateau was 49.7%±2.1% for the preoperative virtual tibial tunnel and 48.8%±2.8% for the postoperative actural tunnel, showing no significant difference between them (t=1.971, P=0.063). The ratio of the distance between the tunnel outlet center and the anterior edge of the tibia to the distance between the anerior and posterior edges of the tibial plateau was 41.3%±1.3% for the preoperative virtual tibial tunnel and 40.3%±3.7% for the postoperative actural tunnel, showing no significant difference between them(t=1.494, P=0.152). Conclusion 3D printing can be used to design and manufacture a navigation template which can accurately assist preparation of tibial bone tunnel in ACL reconstruction.