Our study aims at systematically summarizing and evaluating the applications of digital intelligence technologies in the field of rare disease medical care insurance now and in the future and at constructing a conceptual framework for the digital powered mechanism for the medical care insurance for rare diseases. By using Chinese keywords of " rare disease" " medical insurance"" artificial intelligence"" prediction model"" machine learning"" big data"" algorithm" and their English equivalents, we searched the databases of PubMed, Embase, Web of Science, CNKI, Wanfang, and VIP, collected relevant literature, and decided the criteria of inclusion and exclusion. The finding of our study shows that medical care insurance mechanism of rare disease in China faces significant challenges in drug accessbility and the funding sustainability. Meanwhile, our study shows that the digital intelligence technologies have broad potential in applications-in financing, accessbility, payment, and supervision. Specifically, dynamic simulation models and big data analysis can make precise prediction of the demand for funding of medical care insurance. The machine learning algorithms improve the dynamic evaluation of drug safety and cost-effectiveness. The personalized payment models enhance the efficiency in identifying the cohort with high expenditure so as to alleviate fund expenditure pressures. The intelligent monitoring technologies can accurately detect the abnormal behaviors in funds of medical care insurance. These technologies provide systematic and scientific solutions for improving the medical care mechanism for rare diseases. Even though further investigation is needed, the digital intelligence technologies have shown remarkable potential in enhancing the flexibility, efficiency, and sustainability of the medical care insurance system and a promising future in meeting the needs of patients with rare diseases.

Objective To summarize the experience and practical value of living donor kidney harvesting in Bama miniature pigs with six gene modified. Methods The left kidney of Bama miniature pigs with six gene modified was obtained by living donor kidney harvesting technique. First, the ureter was occluded, and then the inferior vena cava and abdominal aorta were freed. During the harvesting process, the ureter, renal vein and renal artery were exposed and freed in sequence. The vascular forceps were used at the abdominal aorta and inferior vena cava, and the renal artery and vein were immediately perfused with 4℃ renal preservation solution, and stored in ice normal saline for subsequent transplantation. Simultaneously, the donor abdominal aorta and inferior vena cava gap were sutured. The operation time, blood loss, warm and cold ischemia time, postoperative complications and the survival of donors and recipients were recorded. Results The left kidney of the genetically modified pig was successfully harvested. Intraoperative bleeding was 5 mL, warm ischemia time was 45 s, and cold ischemia time was 2.5 h. Neither donor nor recipient pig received blood transfusion, and urinary function of the kidney transplanted into the recipient was recovered. The donor survived for more than 8 months after the left kidney was resected. Conclusions Living donor kidney harvesting is safe and reliable in genetically modified pigs. Branch blood vessels could be processed during kidney harvesting, which shortens the process of kidney repair and the time of cold ischemia. Living donor kidney harvesting contributes to subsequent survival of donors and other scientific researches.

This study aims at examining the application and development of digital teaching materials in the field of epidemiology, encompassing both China and international contexts. The research involved conducting search on websites and literature databases to assess the status of digital teaching materials in epidemiology, nationally and internationally. At present, in China, digital teaching materials used in epidemiology are primarily presented in the form of printed books with added QR codes, providing teaching resources such as videos and exercises. However, issues with the level of interactivity have been identified. In foreign countries, with stronger emphasis placed on personalization, interactivity, and the use of rich media technologies in the digital teaching materials, epidemiologically. Enhanced digitization regarding materials and learning outcomes is achieved through features such as real-time notes, interactive animations, and quizzes. These approaches are considered worth considering for adoption. This study provides valuable insights for the digital transformation of epidemiology education.

Neutrophil extracellular traps(NETs)are fibrous web-like structures composed of decondensed chromatin and granular proteins released by neutrophils,with the ability to capture and kill bacteria.Pathogens,such as bacteria and viruses,can trigger the formation of NETs via NETosis,a type of programmed cell death that has two distinct forms:suicidal NETosis and vital NETosis.Numerous studies have found that NETs interact with immune cells in the tumor microenvironment,where they activate macrophages,promote immunosuppressive effects of myeloid-derived suppressor cells,and coat the tumor surface to prevent cytotoxic effects of CD8+T cells and natural killer cells.Recent research has identified a substantial presence of NETs in oral squamous cell carcinoma(OSCC)tissues,indicating a complex re-lationship between NETs and OSCC development.Depending on the phenotype of neutrophils,NETs may exhibit pro-tu-mor or anti-tumor effects.For instance,NETs derived from N1-type neutrophils may exert anti-tumor effects,while TGF-β-induced NETs derived from N2-type neutrophils may exert pro-carcinogenic activity,thereby contributing to the devel-opment of oral squamous metaplasia.Furthermore,NETs likely play a role in OSCC metastasis by capturing circulating tumor cells and inducing a hypercoagulable state,thereby facilitating tumor-related thrombus formation and hematoge-nous metastasis.The involvement of NETs in the occurrence and progression of OSCC opens new avenues for anti-tumor therapy and prognostication.Inhibiting NET formation can significantly suppress the development of chemotherapy-in-duced drug resistance and reduce the risk of thrombosis in OSCC patients,thereby inhibiting tumor metastasis.Current-ly,multiple prognostic models based on NET-related genes have been constructed and validated for head and neck squa-mous cell carcinoma,indicating the potential clinical value of NETs.However,the association between NETs and OSCC treatment is still unclear,necessitating further research on its underlying mechanisms and feasibility.This article attempts to review the relationship between NETs and OSCC,aiming to provide novel perspectives for OSCC treatment.

Although blood banks based on human blood can provide blood transfusions for the wounded timely and effec-tively,scientific research has never given up on finding new blood sources due to the restrictions of human blood sources.With the application of transgenic technology and the successful breeding of gene-edited pigs,gene-edited pig blood as a po-tential source of clinical transfusion has attracted wide attention.Now there are preclinical studies showing the feasibility of transfusing gene-edited pig red blood cells into primates.This paper discusses the related research and future development of xenogeneic transfusion of porcine red blood cells by gene editing.

Objective:To investigate the protective effect of hypothermic antegrade machine perfusion against canine ischemic brain injury.Methods:Thirteen beagle dogs were divided into the mild hypothermia with perfusion group ( n=6) and normothermia with perfusion group ( n=7) according to the random number table. The model of ischemic brain injury was established by neck transection. After 1 hour of ischemic circulatory arrest, the perfusion fluid based on autologous blood was continuously perfused through bilateral common carotid artery for 6 hours. The temperature of the perfusion fluid was set at 33 ℃ in the mild hypothermia with perfusion group and 37℃ in the normothermia with perfusion group, respectively. Blood oxygen saturation was recorded at 0, 1, 2, 3, 4, 5 and 6 hours after the beginning of perfusion to evaluate the perfusate oxygen level. The perfusate was collected, and the levels of Na +, K +, Ca 2+ and glucose as well as the pH value of the perfusate were detected in the two groups. At the end of perfusion, the parietal brain tissues of 1 dog from each group were collected to evaluate the water contents of brain tissues. Nissl staining was used to evaluate the morphological integrity of the pyramidal neurons in the frontal cortex and hippocampus. Neuronal nuclei antigen (NeuN) was used to evaluate the structural and morphological integrity of pyramidal neurons. Immunofluorescence glial fibrillary acidic protein (GFAP) and ionic calcium binding adaptor molecule 1 (Iba1) were used to evaluate the integrity and activity of astrocytes and microglia fragments. Results:At 0, 1, 2, 3, 4, 5 and 6 hours of perfusion, there was no significant difference in the blood oxygen saturation or Na + concentrations between the two groups (all P>0.05); the K + concentrations in the mild hypothermia with perfusion group were (4.57±0.12)mmol/L, (4.67±0.14)mmol/L, (4.27±0.12)mmol/L, (4.45±0.10)mmol/L, (6.60±0.15)mmol/L, (7.37±0.18)mmol/L and (9.03±0.16)mmol/L, respectively, which were significantly lower than those in the normothermia with perfusion group [(4.84±0.10)mmol/L, (5.31±0.13)mmol/L, (5.44±0.24)mmol/L, (5.70±0.18)mmol/L, (7.79±0.18)mmol/L, (10.44±0.40)mmol/L, (10.40±0.41)mmol/L] (all P<0.01). At 0, 1, 2 and 3 hours of perfusion, the Ca 2+ concentrations in the mild hypothermia with perfusion group were (0.72±0.15)mmol/L, (1.55±0.16)mmol/L, (1.62±0.15)mmol/L and (1.88±0.15)mmol/L, respectively, being significantly higher than those in the normothermia with perfusion group [(0.41±0.13)mmol/L, (0.99±0.12)mmol/L, (1.29±0.13)mmol/L, (1.57±0.11)mmol/L] (all P<0.01), and no significant differences were found at other time points (all P>0.05). At 0, 1 and 2 hours of perfusion, the glucose concentrations in the mild hypothermia with perfusion group were (5.75±0.19)mmol/L, (5.17±0.15)mmol/L and (4.72±0.15)mmol/L, respectively, being significantly higher than those in the normothermia with perfusion group [(5.30±0.22)mmol/L, (4.89±0.20)mmol/L, (4.30±0.17)mmol/L] (all P<0.01), with no significant differences found at other time points (all P>0.05). At 2, 3, 4, 5 and 6 hours of perfusion, the pH values of the mild hypothermia with perfusion group were 7.32±0.06, 7.25±0.02, 7.23±0.02, 7.24±0.02 and 7.24±0.02, respectively, being significantly higher than those in the normothermia with perfusion group (7.26±0.01, 7.21±0.01, 7.17±0.02, 7.15±0.02, 7.08±0.02) ( P<0.05 or 0.01), with no significant differences at other time points (all P>0.05). The water content of brain tissues in the mild hypothermia with perfusion group was (74.9±0.4)%, which was significantly lower than (79.9±0.9)% in the normothermia with perfusion group ( P<0.01). Nissl staining showed that the pyramidal neurons in prefrontal cortex and dentate gyrus had good integrity in the mild hypothermia with perfusion group. NeuN immunofluorescence staining showed that the morphology and structure of pyramidal neuron cells in the mild hypothermia with perfusion group were better with clearly visible axons than those in the normothermia with perfusion group, whereas the cytosol was full and swollen with scarce axons in the normothermia with perfusion group. GFAP and Iba1 immunofluorescence staining showed that more structurally intact glial cells, more abnormally active cells, thickener axons and better axon integrity in all directions were found in the mild hypothermia with perfusion group than those in the normothermia with perfusion group. Conclusion:Compared with normal temperature antegrade mechanical perfusion, the mild hypothermia antegrade mechanical perfusion can protect canine brain tissue and alleviate ischemic brain injury by maintaining stable energy and oxygen supply, balancing ion homeostasis and perfusion fluid pH value, reducing tissue edema, and maintaining low metabolism of pyramidal neurons, astrocytes and microglia.

ObjectiveTo develop a questionnaire on the knowledge needs of respiratory rehabilitation training for in-service healthcare workers, and test its reliability and validity. MethodsA theoretical framework was constructed based on the contents of the respiratory rehabilitation course modules of American Association of Cardiopulmonary Rehabilitation and American Association for Respiratory Care. The first draft of the questionnaire was prepared through literature searches and analyses, semi-structured interviews, and expert group discussions. The reliability and validity of the questionnaire was tested by interviewing 17 respiratory rehabilitation professionals and 16 respiratory rehabilitation experts by correspondence, and investigating 380 cases of in-service healthcare workers engaged in respiratory rehabilitation. ResultsThe knowledge needs questionnaire of respiratory rehabilitation training for in-service healthcare workers included progress in respiratory rehabilitation, physiological basis and diagnosis of chronic lung diseases, individualized assessment and management principles of chronic lung diseases, treatment of chronic lung diseases and guideline-recommended medications, oxygen therapy, exercise assessment and exercise prescription, tobacco addiction and cessation, nutritional assessment and weight management, psychological screening and intervention, self-management and health behavior promotion, and effectiveness assessment of respiratory rehabilitation, totaling eleven dimensions and 52 items. The total Cronbach's α was 0.921, the total folded half reliability was 0.904, the total retest reliability was 0.922, and the Cronbach's α of each dimension ranged from 0.909 to 0.953; the folded half reliabilities ranged from 0.882 to 0.924, and the retest reliabilities ranged from 0.908 to 0.950. The validity of the questionnaire's content was 0.902. In exploratory factor analysis, eleven metric factors were extracted, and their cumulative variance contribution rate was 75.324%. ConclusionThe questionnaire on the knowledge needs of respiratory rehabilitation training for in-service healthcare workers is reliable and valid, and can be used to assess the knowledge needs of healthcare workers participating in in-service training in respiratory rehabilitation.

Adjusting time-dependent covariates into prediction models may help improve model performance and expand clinical applications. The methodology of handling time-dependent covariates is limited in traditional regression strategies (i.e., landmark model, joint model). For example, the number of predictors and practical situations which can be handled are restricted when using regression models. One new strategy is to use machine learning (i.e., neural networks). This review summarizes the methodology of handling time-dependent covariates in prediction models, such as applicable scenarios, strengths, and limitations, to offer methodological enlightenment for processing time-dependent covariates.

OBJECTIVE：To investigate the pharmaceutical ca re for a child with refractory Stenotrophomonas maltophilia sepsis by clinical pharmacists ，and to provide reference for the treatment of children with this disease. METHODS ：Clinical pharmacist participated in drug therapy for a child with refractory S. maltophilia sepsis. Based on the pathophysiological characteristics of the child and the PK/PD characteristics of the antimicrobials ，clinical pharmacists suggested that the anti-infection regimen should be adjusted as cefoperazone sodium and sulbactam sodium 160 mg/（kg·d），every 8 hours combined with levofloxacin 10 mg/kg， every 12 hours. For clinical manifestations of severe inflammatory reaction ， the clinical pharmacist suggested receiving methylprednisolone sodium succinate 1 mg/kg additionally ，every 12 hours，for anti-inflammatory adjuvant therapy. At the same time， clinical pharmacist provided individualized pharmaceutical care （including the detection of blood concentration of cefoperazone sodium and sulbactam sodium ，the detection of ADR and medication education of oxygen atomization ）during the treatment，and followed up the child for one year. RESULTS ：The doctors adopted the suggestions of clinical pharmacists. The sepsis was controlled ，the child ’s condition were improved and then discharged. During the follow-up ，the child did not suffered from ADR ，such as cartilage and joint injury. CONCLUSIONS ：Hypoimmunity，long stay in intensive care unit ，endotracheal intubation and malignant tumor are the high risk factors of S. maltophilia infection. The monitoring of therapeutic drugs of cefoperazone sodium and sulbactam sodium is very necessary in the treatment of severe infection in children. After weighing the advantages and disadvantages and meeting certain conditions ，children can use quinolones for anti-infection ；based on the effective anti-infection treatment ，low-dose glucocorticoid can reduce the systemic inflammatory respense in patients with sepsis.

Objective:To investigate the potential pleiotropism of cancer-related single nucleotide polymorphisms (SNPs) among Chinese population.Methods:Based on the catalogue of GWAS jointly constructed by the National Human Genome Research Institute and the European Institute of Bioinformatics, according to population origin (Chinese population and non-Chinese population) and disease traits (cancer and non-cancer traits). All SNPs found by GWAS before August 2020 were divided into four categories: cancer in Chinese population, non-cancer in Chinese population, cancer in non-Chinese population and non-cancer in non-Chinese population. The number, correlation and linkage of the four categories of SNPs were described.Results:By August 2020, a total of 196 813 SNPs from 4 096 GWAS were included in the GWAS directory. The information that SNPs refer to unknown or were not related to the disease was excluded, and 117 441 independent SNPs were finally included. There were 619 SNPs related to cancer and 9 569 SNPs related to non-cancer disease in Chinese population, respectively. There were 4 624 SNPs related to cancer and 106 448 SNPs related to non-cancer disease (trait) in non-Chinese population, respectively. Three SNPs, rs2736100, rs6983267 and rs401681, were associated with two or more types of cancer in both Chinese and non-Chinese populations. Seven SNPs, rs7705526, rs2736100, rs10993994, rs2735839, rs4430796, rs174537 and rs9271588, were associated with cancer and non-cancer diseases in both Chinese and non-Chinese populations, respectively.Conclusion:There is a potential pleiotropism of cancer-related SNPs in Chinese population.