Role of myeloid-derived suppressor cells in mouse pre-sensitized cardiac transplant model.

Harness of sensitized transplantation remains a clinical challenge particularly in parallel with prolonged cold ischemia time (PCI)-mediated injury. Our present study was to test the role of myeloid-derived suppressor cells (MDSCs) in mouse pre-sensitized transplantation. Our findings revealed that CD11b+Gr1(low) MDSC was shown to have strong suppressive activity. MDSCs subsets from the tolerated mice exhibited higher suppressive capacities compared with counterparts from naive (untreated) mice. Depletion of Tregs could not affect splenic CD11b+Gr1(-low) MDSC frequency, but increase peripheral and intragraft CD11b+Gr1(-low) frequency. Intriguingly, boost of Tregs remarkably caused an increase of CD11b+Gr1(-low) frequency in the graft, peripheral blood, and spleen. Furthermore, peripheral CD11b+Gr1(-low) cells were massively accumulated at the early stage when allogeneic immune response was enhanced. Taken together, MDSCs could prevent grafts from PCI-mediated injury independent on Tregs in the pre-sensitized transplant recipients. Utilization of MDSC subset particularly CD11b+Gr1(-low) might provide a novel insight into improving graft outcome under such clinical scenarios.

Experiences and Challenges of Emerging Online Health Services Combating COVID-19 in China: Retrospective, Cross-Sectional Study of Internet Hospitals.

BACKGROUND: Internet-based online virtual health services were originally an important way for the Chinese government to resolve unmet medical service needs due to inadequate medical institutions. Its initial development was not well received. Then, the unexpected COVID-19 pandemic produced a tremendous demand for telehealth in a short time, which stimulated the explosive development of internet hospitals. The Second Affiliated Hospital of Zhejiang University (SAHZU) has taken a leading role in the construction of internet hospitals in China. The pandemic triggered the hospital to develop unique research on health service capacity under strict quarantine policies and to predict long-term trends. OBJECTIVE: This study aims to provide policy enlightenment for the construction of internet-based health services to better fight against COVID-19 and to elucidate future directions through an in-depth analysis of 2 years of online health service data gleaned from SAHZU's experiences and lessons learned. METHODS: We collected data from SAHZU Internet Hospital from November 1, 2019, to September 16, 2021. Data from over 900,000 users were analyzed with respect to demographic characteristics, demands placed on departments by user needs, new registrations, and consultation behaviors. Interrupted time series (ITS) analysis was adopted to evaluate the impact of this momentous emergency event and its long-term trends. With theme analysis and a defined 2D model, 3 investigations were conducted synchronously to determine users' authentic demands on online hospitals. RESULTS: The general profile of internet hospital users is young or middle-aged women who live in Zhejiang and surrounding provinces. The ITS model indicated that, after the intervention (the strict quarantine policies) was implemented during the outbreak, the number of internet hospital users significantly increased (ß_2=105.736, P<.001). Further, long-term waves of COVID-19 led to an increasing number of users following the outbreak (ß_3=0.167, P<.001). In theme analysis, we summarized 8 major demands by users of the SAHZU internet hospital during the national shutdown period and afterwards. Online consultations and information services were persistent and universal demands, followed by concerns about medical safety and quality, time, and cost. Users' medical behavior patterns changed from onsite to online as internet hospital demands increased. CONCLUSIONS: The pandemic has spawned the explosive growth of telehealth; as a public tertiary internet hospital, the SAHZU internet hospital is partially and irreversibly integrated into the traditional medical system. As we shared the practical examples of 1 public internet hospital in China, we put forward suggestions about the future direction of telehealth. Vital experience in the construction of internet hospitals was provided in the normalization of COVID-19 prevention and control, which can be demonstrated as a model of internet hospital management practice for other medical institutions.

A Comparison of the Development of Medical Informatics in China and That in Western Countries from 2008 to 2018: A Bibliometric Analysis of Official Journal Publications.

Objective: We focused on medical informatics journal publications rather than on conference proceedings by comparing and analyzing the data from journals and conferences from a broader perspective. The aim is to summarize the unique contributions of China to medical digitization and foster more multilevel international cooperation. Method: In February 2019, publications from 2008 to 2018 in three major English-language medical informatics journals were retrieved through Scopus, including the journals, namely, International Journal of Medical Informatics (IJMI, international community), JAMIA (United States), and Methods of Information in Medicine (MIM, Europe). Three major Chinese-language journals, namely, China Digital Medicine (CDM), Chinese Journal of Health Informatics and Management (CJHIM), and Chinese Journal of Medical Library and Information Science (CJMLIS), were searched within the major three Chinese literature databases. The datasets were preprocessed using the NLP package on Python, and a smart local moving algorithm was used as a clustering method for identifying the aforementioned journals. Result: Between 2008 and 2018, the total number of published papers and H-index of the three English-language journals was 1371 and 67 (IJMI), 1752 and 86 (JAMIA), and 637 and 35 (MIM), respectively. In the same period, the total number of published papers and H-index in the three Chinese-language journals was 6668 and 23 (CDM), 1668 and 22 (CJHIM), and 2557 and 25 (CJMLIS), respectively. IJMI, JAMIA, and MIM received submissions from 82, 59, and 62 countries/regions, respectively. By contrast, the three Chinese journals only received submissions from seven foreign countries. The proportions of authors from institutional affiliations were similar between the three English-language journals (IJMI, JAMIA, and MIM) and CJMLIS because the majority of the authors were from universities (81%, 74%, 73%, and 65.2%), followed by medical institutions (12%, 10%, 9%, and 23.4%) or research institutes (2%, 4%, 10%, and 4.3%). Furthermore, the proportions of the authors from enterprises were low (2%, 6%, 4%, and 0.3%) for all journals. However, the authors in CDM and CJHIM were mainly from medical institutions (50% and 40%), followed by universities (33% and 32%) and research institutes (3% and 4%). In addition, the proportions of enterprises were only 3% and 2%, respectively. Among the top five authors in three English-language journals (ranked in terms of the number of published papers), 100% had doctoral or master's degrees, compared with only 60% in the Chinese journals. Additionally, 28204 different keywords were extracted from the aforementioned papers, covering 275 specific high-frequency key terms. Based on these key terms, four clusters were found in the English literature-"Health and Clinical Information Systems," "Internet and Telemedicine," "Medical Data Statistical Analysis," and "EHRs and Information Management"-and three clusters were found in the Chinese literature: "Hospital Information Systems and EMR," "Library Science and Bibliometrics Analysis," and "Medical Reform Policy and Health Digitization." Only two clusters are similar, and Chinese-language journals focus more on health information in technology and industrial applications than in medical informatics basic research. Conclusion: This study provides important insights into the development of medical informatics (MI) in China and Western countries showing that the medical informatics journals of China, the United States, and Europe have distinct characteristics. Specifically, first, compared with the Western journals, the number of papers published in the journals of professional associations in the field of MI in China is large and the application value is high, but the academic influence and academic value are relatively low; second, most of the authors of the Chinese papers are from hospitals, and most of the counterparts in the Western countries are from universities. The proportion of master's or doctoral degrees in the former is also lower than that of the latter; furthermore, regarding paper themes, on the one hand, China MI has no theoretical and basic research on medical data statistics and consumer health based on the Internet and telemedicine; on the other hand, after nearly 10 years of hospital digital development, China has fully used the latecomer and application advantages in hospitals and, through extensive international cooperation, has made significant advancements in and contributions to the development of medical information.

Evaluating the Applications of Health Information Technologies in China During the Past 11 Years: Consecutive Survey Data Analysis.

BACKGROUND: To achieve universal access to medical resources, China introduced its second health care reform in 2010, with health information technologies (HIT) as an important technical support point. OBJECTIVE: This study is the first attempt to explore the unique contributions and characteristics of HIT development in Chinese hospitals from the three major aspects of hospital HIT-human resources, funding, and materials-in an all-around, multi-angled, and time-longitudinal manner, so as to serve as a reference for decision makers in China and the rest of the world when formulating HIT development strategies. METHODS: A longitudinal research method is used to analyze the results of the CHIMA Annual Survey of Hospital Information System in China carried out by a Chinese national industrial association, CHIMA, from 2007 to 2018. The development characteristics of human resources, funding, and materials of HIT in China for the past 12 years are summarized. The Bass model is used to fit and predict the popularization trend of EMR in Chinese hospitals from 2007 to 2020. RESULTS: From 2007 to 2018, the CHIMA Annual Survey interviewed 10,954 hospital CIOs across 32 administrative regions in Mainland China. Compared with 2007, as of 2018, in terms of human resources, the average full time equivalent (FTE) count in each hospital's IT center is still lower than the average level of US counterparts in 2014 (9.66 FTEs vs. 34 FTEs). The proportion of CIOs with a master's degree or above was 25.61%, showing an increase of 18.51%, among which those with computer-related backgrounds accounted for 64.75%, however, those with a medical informatics background only accounted for 3.67%. In terms of funding, the sampled hospitals' annual HIT investment increased from ¥957,700 (US $136,874) to ¥6.376 million (US $911,261), and the average investment per bed increased from ¥4,600 (US $658) to ¥8,100 (US $1158). In terms of information system construction, as of 2018, the average EMR implementation rate of the sampled hospitals exceeded the average level of their US counterparts in 2015 and their German counterparts in 2017 (85.26% vs. 83.8% vs. 68.4%, respectively). The results of the Bass prediction model show that Chinese hospitals will likely reach an adoption rate of 91.4% by 2020 (R2=0.95). CONCLUSIONS: In more than 10 years, based on this top-down approach, China's medical care industry has accepted government instructions and implemented the unified model planned by administrative intervention. With only about one-fifth of the required funding, and about one-fourth of the required human resources per hospital as compared to the US HITECH project, China's EMR coverage in 2018 exceeded the average level of its US counterparts in 2015 and German counterparts in 2017. This experience deserves further study and analysis by other countries.

The experience and challenges of healthcare-reform-driven medical consortia and Regional Health Information Technologies in China: A longitudinal study.

OBJECTIVE: To achieve universal access to medical resources-a partial goal of the second ambitious health reform since 2010-the Chinese government aimed to build a regional medical consortium and enhance the efficiency of health information exchange (HIE). We analyzed the experience of constructing a medical consortium in Chinese hospitals, which was based on regional health information technology (RHIT) promoted by HIE. METHOD: In this longitudinal study, we analyzed the results of the annual surveys that were conducted by the China Hospital Information Management Association from 2006 to 2015. The survey results mainly concerned whether hospitals should join the regional medical consortium, the methods used for sharing inter-hospital medical data, and the out-of-hospital information interaction system. The Bass diffusion model was adopted to fit and predict the proportion of Chinese hospitals joining the consortium from 2006 to 2025. RESULT: As of 2015, the survey results of 7272 hospitals were obtained. The proportion of hospitals in partnership systems increased from 3.0% in 2007 to 57.2% in 2015. There has been a rapid development in the electronic sharing of medical data between hospitals. The proportion of hospitals that relied solely on paper documents for data interaction decreased from 43.3% in 2011 to 8.0% in 2015. There was a strong positive linear correlation between hospitals joining the consortium and the accessibility of electronic medical data exchange within hospitals (r = 0.925). The proportions of hospitals that supported dual referral systems and appointments, data browsing between hospitals and regional information systems, and remote consultation services increased to 65.0%, 61.6%, and 81.9% in 2015, as compared to 18.8%, 16.8%, and 10.9% in 2011, respectively. The Bass prediction model showed that the goal of recruiting 90% of the hospitals to the consortium by 2020 will likely be achieved (adjusted R2 = 0.93). CONCLUSION: The Chinese government has applied a top-down, high-level design model to promote the rapid development of a medical consortium, in which the RHIT technologies are crucial technical enabler.

Tolerance induced by IL-6 deficient donor heart is significantly involved in myeloid-derived suppressor cells (MDSCs).

OBJECTIVES: Transplant tolerance induced by IL-6 deficient donor is supported by regulatory T cells (Tregs). However, it is unknown whether innate immunoregulatory cells such as myeloid-derived suppressor cells (MDSCs) are involved in the process. MATERIALS AND METHODS: In this study, we demonstrate the role of MDSCs by transplanting IL-6 deficient heart grafts into wild-type recipients in a murine allogeneic transplant model. RESULTS: Our data further revealed that utilization of IL-6 deficient heart grafts could cause a significant prolongation of allograft survival (Mantel-Cox Test, p = 0.001; Gehan-Breslow-Wilcoxon Test, p = 0.0016) and a remarkable increase of the frequency of CD11b + Gr1(-low) in the recipients' spleens (p = 0.0028). CONCLUSIONS: MDSCs rather than Th17 cells are closely involved in induced tolerance by IL-6 deficient donor heart. This unveiled mechanism of targeting IL-6 or its signaling pathway may provide a novel insight into preventing allograft rejection for non-sensitized transplant recipients.

Attitudes toward live and postmortem kidney donation: a survey of Chinese medical students.

OBJECTIVES: As the gap between supply and demand for donor organs is increasing, we sought to clarify the knowledge and attitudes regarding living-organ donation among Chinese medical students and analyze their incentives and influencing factors. MATERIALS AND METHODS: Data were collected from Chinese medical students using a standardized questionnaire. RESULTS: Of 320 surveyed participants, 261 participants (81.6%) said they would consider donating their live kidney organ, and 262 participants (81.9%) were willing to donate posthumously. Although 177 participants (55.7%) confirmed current regulations on posthumous organ donation, only 85 participants (26.7%) could correctly identify the regulations on live organ donation in China. Gender differences were not significantly associated with willingness to donate a kidney, whereas religion and socioeconomic status of the respondents were significantly associated with willingness to donate a live or posthumous kidney. CONCLUSIONS: Among well-informed, young, healthy, and economically well-off Chinese male and female medical students, most were willing to be live kidney donors. Religion and socioeconomic status may affect the decision-making process for organ disposition.

Biomarkers for renal transplantation: where are we?

Although surgical techniques, post-transplant care medicine, and immunosuppressants have been greatly improved, permanent acceptance of renal allograft remains a clinical challenge owing to the appearance of various influencing factors. To predict graft dysfunction, development of noninvasive biomarkers is becoming a highlighted research topic in the field of renal transplantation, which provides a possibility for physicians to give preemptive rescue treatment. From the viewpoint of diagnostic techniques, repetitive sampling is prerequisite to identify applicable biomarkers in the clinic. Early biomarkers can be used to dynamically monitor renal graft status and accurately predict transplant outcome independent of various confounders. This review highlights recent studies on the predictive value of biomarkers and methods to quantify biomarkers for monitoring kidney transplant. It is important to analyze and compare different biomarkers for living, and nonliving donors. Analysis of identified clinically relevant biomarkers will advance our understanding of distinct molecular and cellular mechanisms of transplantation and provide insight into developing novel potential approaches to induce transplant tolerance.

Gender issues in solid organ donation and transplantation.

Gender as a critical, intrinsic, non-immunologic factor plays a pivotal role in the field of transplantation. The gender of donors and recipients is involved in the entire process, including organ donation and transplant surgery. This review article aims to summarize the literature related to the role of gender in solid organ donation and transplantation and to unveil the underlying mechanism by which gender mismatch between donor and recipient impacts transplant rejection. A systematic search was conducted through PubMed by using the following key words: "gender", or "sex", and "transplant", "organ donation" for published articles. The prima facie evidence demonstrated that females are more likely to donate their organs and are less willing than males to accept transplant surgery; however, their donated liver organs will have a higher risk of graft failure compared with males. With respect to kidney, heart, and lung transplantations, the role of gender remains controversial. Results of animal studies support the negative impact of gender mismatch on allograft function. In conclusion, our present study advances the knowledge of gender issues in the field of solid organ donation and transplantation. In general, gender mismatch is not advantageous to transplant outcome, as evidenced by many aspects of biological investigations on immunogenicity of H-Y antigen to females. Therefore, gender issues should be highlighted and an a priori intervention is needed to improve graft survival in clinical practice.

Alteration of innate immunity by donor IL-6 deficiency in a presensitized heart transplant model.

Engraftment of IL-6 deficient donor into wild-type recipient could significantly improve allograft survival through T cell lineage particularly regulatory T cells (Tregs) in non-sensitized transplant host. However, its effect on innate immune responses remains uncertain. Our data revealed that donor IL-6 deficiency significantly increased infiltration of two subsets of MDSCs (CD11b+Gr1+myeloid-derived suppressor cells), CD11b+Gr1(-low) and CD11b+Gr1(-int) with strong immunosuppression activity in the transplanted graft. It resulted in a dramatic increase of CD11b+Gr1(-low) frequency and a significant decrease of the frequency of CD11b+Gr1(-high) and CD4-CD8-NK1.1+ cells in the recipient's spleen. Unexpectedly, donor IL-6 deficiency could not significantly reduce macrophage frequency irrespective of in the host's spleen or graft. Taken together, suppression of innate immune effector cells and enhanced activity of regulatory MDSCs contributed to tolerance induction by blockade of IL-6 signaling pathway. The unveiled novel mechanism of targeting IL-6 might shed light on clinical therapeutic application in preventing accelerated allograft rejection for those pre-sensitized transplant recipients.

Presensitized immune condition of host exaggerates prolonged cold ischemia-mediated injury of cardiac graft involving regulatory T cells.

BACKGROUND: The detrimental effect of prolonged cold ischemia time (PCI) on presensitized transplanted graft is conceivable, but the impact of presensitization status of recipient on PCI-mediated graft injury and inflammation is not well defined. METHODS: Allogeneic skin grafts from BALB/c donors were transplanted into C57BL/6 recipients for presensitization. Syngeneic or allogeneic heterotopic heart transplantations with PCI were performed using C57BL/6 or BALB/c donors for these recipients through different treatments. RESULTS: We revealed that PCI could not affect isograft survival but significantly shortened allograft survival in the presensitized recipients. Depletion of regulatory T cells (Tregs) starting 1 day before and after heart transplantation with anti-CD25 monoclonal antibody remarkably induced intragraft Foxp3 gene expression, worsened architecture damage and subepicardial and intramuscle inflammatory cellular infiltration, and caused a dramatic fall of intragraft CD4+/CD8+ ratio, whereas adoptive transfer of exogenous wild-type Tregs or endogenous Tregs promoted by rapamycin had a beneficial effect on preventing the infiltration of T lymphocytes and Gr-1+ neutrophils and reversed intragraft CD4+/CD8+ ratio, preserving cardiac graft architecture. However, their distinct protective mechanisms showed that rapamycin treatment mainly diminished CD4+ T-cell infiltration. Nevertheless, CD4+ still outnumbered CD8+ T cells in the graft, whereas adoptive transfer of Tregs expanded both CD4+ and CD8+ T cells, particularly CD8+ T cells. CONCLUSION: Allogeneic immunoresponses synergistically enhanced PCI effect under presensitized condition. PCI could affect subsequent immunoresponses. Tregs were closely involved in this pathophysiologic process. Our data may pave the way to use Tregs as a novel therapeutic approach to prevent PCI-mediated injury in the presensitized transplant recipients.

Introduction of modified cervical cardiac transplant model in mice.

OBJECTIVES: The murine cervical heterotopic heart transplant model was initially designed to test the immune response to third-party allografts, modified by cuff techniques. While cuff techniques simplify the execution of this procedure, cutting of the carotid artery and the external jugular vein alters the blood supply to central nervous system and makes it difficult to achieve long-term graft survival. In the present study, we describe modified techniques that preserve the continuity and function of blood vessels and improve transplant integrity. MATERIALS AND METHODS: The modified techniques in this study comprise the following aspects: (1) Preservation of the sternal head of the right sternocleidomastoid muscle, (2) use of the donor's intrathoracic inferior vena cava for anastomosis and (3) preservation of the function of the recipient's carotid artery and external jugular vein and thus, continuity of blood flow to the central nervous system. RESULTS: Stable, long-term, disease-free allograft survival has been achieved with syngeneic transplants (> 200 days), whereas allografts from fully major histocompatibility complex-mismatched donors were acutely rejected in a time similar to the traditional abdominal heterotopic heart transplant model (8.2 ± 1.3 vs 8.4 ± 1.4 days; P = .73 in the Mantel Cox test, and P = .61 in the Gehan-Breslow-Wilcoxon test). Similar alloresponses could be induced in these 2 models. CONCLUSIONS: It is possible and feasible to achieve long-term graft survival in the mouse cervical heart transplant model using the modified procedures described in the present study.

Strategies for successfully establishing a kidney transplant in a mouse model.

OBJECTIVES: Kidney transplant in mouse model is quite useful and valuable for studying transplant immunobiology. However, its technical complexity and high mortality have hindered widespread use. We sought to review and analyze the various techniques of kidney transplant in mice to prevent pitfalls and reduce complications. MATERIALS AND METHODS: We searched PubMed using the key words "kidney transplant" or "renal transplant," "mouse" or "mice," and "technique" or "model" for articles published between January 1973 and June 2010. We found a series of factors that were collected and analyzed, which may influence establishing a mouse kidney transplant model. RESULTS: A mouse kidney transplant model is practical for research. Mouse body weight, sex, animal strain, type of anesthesia, and type of flushing solution are relevant but do not determine a successful transplant. Warm and cold ischemia time should be less than 35 minutes and 2.5 hours. CONCLUSIONS: End-to-side vascular anastomosis and ureter-to-bladder or bladder-to-bladder for ureter reconstruction is preferred for establishing a kidney transplant model in mice.

A giant ganglion cyst of hip joint causing lower limb edema.

Lower limb edema caused by a giant ganglion cyst of hip joint, rather than deep venous insufficiency or lymphedema, is unusual particularly for guiding clinical practice. In this study, we present a rare case of a 76-year-old man with a 3-month history of progressive swelling of right lower extremity and 2-month history of a known inguinal mass, which was initially thought as hemangioma by using ultrasound. But, subsequent computed tomography examination and exploration surgery revealed a giant ganglion cyst compressing the right femoral vein. Resection of the cyst led to complete resolution of symptoms postoperatively. To the best of our knowledge this is a very rare case of giant ganglion cyst of hip joint origin causing lower limb edema in the literature.