Mechanism study of cross presentation of exogenous antigen induced by cholera toxin-like chimeric protein.

Tumor subunit vaccines have great potential in personalized cancer immunotherapy. They are usually administered with adjuvant owing to their low immunogenicity. Cholera toxin (CT) is a biological adjuvant with diverse biological functions and a long history of use. Our earlier study revealed that a CT-like chimeric protein co-delivered with murine granulocyte-macrophage colony stimulating factor (mGM-CSF) and prostate cancer antigen epitope could co-stimulate dendritic cells (DCs) and enhance cross presentation of tumor epitope. To further study the molecular mechanism of CT-like chimeric protein in cross presentation, major histocompatibility complex class I (MHC I)-restricted epitope 257-264 of ovalbumin (OVAT) was used as a model antigen peptide in this study. Recombinant A subunit and pentameric B subunit of CT protein were respectively genetically constructed and purified. Then both assembled into AB5 chimeric protein in vitro. Three different chimeric biomacromolecules containing mGM-CSF and OVAT were constructed according to the different fusion sites and whether the endoplasmic reticulum (ER) retention sequence was included. It was found that A2 domain and B subunit of CT were both available for loading epitopes and retaining GM1 affinity. The binding activity of GM1 was positively correlated with antigen endocytosis. Once internalized, DCs became mature and cross-presented antigen. KDEL helped the whole molecule to be retained in the ER, and this improved the cross presentation of antigen on MHC I molecules. In conclusion, hexameric CT-like chimeric protein with dual effects of GM1 affinity and ER retention sequence were potential in improvement of cross presentation. The results laid a foundation for designing personalized tumor vaccine based on CT-like chimeric protein molecular structure.

Key Factors Influencing the Operationalization and Effectiveness of Telemedicine Services in Henan Province, China: Cross-Sectional Analysis.

BACKGROUND: Telemedicine has demonstrated its potential in alleviating the unbalanced distribution of medical resources across different regions. Henan, a province in China with a population of approximately 100 million, is especially affected by a health care divide. The province has taken a proactive step by establishing a regional collaborative platform for telemedicine services provided by top-tier provincial hospitals. OBJECTIVE: We aim to identify the key factors that influence the current operationalization and effectiveness of telemedicine services in Henan province. The insights gained from this study will serve as valuable references for enhancing the efficient operation of telemedicine platforms in low- and middle-income regions. METHODS: We analyzed service reports from the performance management system of telemedicine services in Henan province throughout 2020. Using descriptive statistics and graphical methods, we examined key influencing factors, such as management competency; device configuration; and hospital capability, capacity, and service efficacy, across hospitals at 2 different tiers. In addition, we used generalized linear models and multiple linear regression models to identify key operational factors that significantly affect the service volume and efficacy of 2 major telemedicine services, namely teleconsultation and tele-education. RESULTS: Among the 89 tier 3 hospitals and 97 tier 2 hospitals connected to the collaborative telemedicine platform, 65 (73%) and 55 (57%), respectively, have established standardized management procedures for telemedicine services. As the primary delivery method for telemedicine services, 90% (80/89) of the tier 3 hospitals and 94% (91/97) of the tier 2 hospitals host videoconferencing consultations through professional hardware terminals rather than generic computers. Teleconsultation is the dominant service type, with an average annual service volume per institution of 173 (IQR 37-372) and 60 (IQR 14-271) teleconsultations for tier 3 and tier 2 hospitals, respectively. Key factors influencing the service volume at each hospital include available funding, management competency, the number of connected upper tiers, and the number of professional staff. After receiving teleconsultations from tier 3 (65/89, 73%) and tier 2 (61/97, 63%) hospitals, patients reported significant improvements in their medical conditions. In addition, we observed that service efficacy is positively influenced by management competency, financial incentives, the number of connected upper or lower tiers, and the involvement of participating medical professionals. CONCLUSIONS: Telemedicine has become increasingly popular in Henan province, with a notable focus on teleconsultation and tele-education services. Despite its popularity, many medical institutions, especially tier 2 hospitals, face challenges related to management competency. In addition to enhancing the effectiveness of existing telemedicine services, health care decision-makers in Henan province and other low- and middle-income regions should consider expanding the service categories, such as including remote emergency care and telesurgery, which have promise in addressing crucial health care needs in these regions.

N-Methylquinuclidinium-Based Anion Exchange Membrane with Ultrahigh Alkaline Stability.

Anion-exchange-membrane (AEM) water electrolysis is a promising technology for hydrogen production from renewable energy sources. However, the bottleneck of its development is the poor comprehensive performance of AEM, especially the stability at highly concentrated alkaline condition and temperature. Herein, a new cationic group N-methylquinuclidinium with enhanced alkaline stability is proposed and hereby a full-carbon chain poly(aryl quinuclidinium) AEM is prepared. Compared with reported AEMs, it shows ultrahigh comprehensive alkaline stability (no chemical decomposition, no decay of conductivity) in 10 m NaOH aqueous solution at 80 °C for more than 1800 h, excellent dimensional stability (swelling ratio: <10% in pure water, <2% in 10 m NaOH) in OH- form at 80 °C, high OH- conductivity (≈139.1 mS cm-1 at 80 °C), and high mechanical properties (tensile strength: 41.5 MPa, elongation at break: 50%). The water electrolyzer using the AEM exhibits a high current density (1.94 A cm-2 at 2.0 V) when assembled with nickel-alloy foam electrodes, and high durability when assembled with nickel foam electrodes.

Implementation, service effectiveness and satisfaction with teleconsultation services in China during the COVID-19 pandemic: from the Perspective of Primary Health Care Professionals.

OBJECTIVE: This study aims to evaluate satisfaction and service effectiveness of primary hospital physicians participating in the National Telemedicine Center of China during the COVID-19 period, and to identify potential improvement suggestions. METHODS: An online questionnaire was developed to assess the impact and satisfaction of teleconsultation services. A teleconsultation manager from each of the 98 hospitals randomly invited the medical staff involved in teleconsultation to complete the online questionnaire. RESULTS: A total of 379 health care professionals responded to the online questionnaire, with a mean age of 36.74 years. Out of these respondents, 95.5% had a positive attitude towards teleconsultation during the epidemic. Only 6.6% believed that teleconsultation systems were not useful in preventing and controlling the COVID-19 pandemic. Those respondents who were very satisfied with teleconsultation participated in it 1.81 times per week averagely. Factors related to satisfaction included weekly participation frequency（P=.003）, patient data quality(P=.023), equipment operation proficiency（P=.006）, audio and video clarity and smoothness（P=.004, P=.020）, environmental satisfaction（P=.032）, and incentive measures of title promotion（P=.003）. The main challenges in teleconsultation were the lack of understanding of medical staff and the public, insufficiently advanced software and hardware equipment, and the lack of optimization of service processes. CONCLUSIONS: Primary hospital doctors demonstrate high satisfaction levels, suggesting that teleconsultation could be an effective tool for patients seeking medical care in areas under lockdown during the COVID-19 pandemic. The primary barriers to teleconsultation include lack of public understanding and unadvanced equipment. These findings should inform future efforts to establish regional telemedicine programs in the post-COVID-19 era.

Ultra-Thin 2D Ionic Salt Supported with Strong Hydrogen-Bonding Assisted Ionic Interaction.

2D materials have attracted great interest since the report of graphene. However, because of the fragile stability of ultra-thin nanosheets, most studies are restricted to sheets maintained by strong covalent or coordination bonds. The research on which kind of bonds can maintain the free-standing existence of 2D nanosheets is still of great significance. Recently, 2D ionic salts are successfully synthesized on substrates, but whether 2D ionic salts can free-stand is still a problem. Herein this problem is addressed by a free-standing 2D ionic salt (thickness: ≈2 nm) exfoliated from a 4,4'-bipyridinium hydrochloride salt crystal. The stability of this 2D salt is supported by a strong NH···Cl hydrogen (H)-bonding assisted ionic interaction (17.99 kcal mol-1 ), which is verified by density functional theory calculation and natural bond orbital analysis. The salt crystal has strong air-stable radicals inside and the 2D ionic salt exhibits red fluorescence in solution and in solid-state, especially in solution the stokes shifts are very large (≈ 386 nm). This breakthrough work is not only beneficial for the construction of novel 2D materials but also for the understanding of H-bonding interactions.

Usage and perceptions of telemedicine among health care professionals in China.

OBJECTIVE: To explore health care professionals' usage and perceptions of telemedicine, including their experience, evaluation and attitude towards telemedicine, and the factors affecting their satisfaction, using intention, and willingness to recommend telemedicine. METHODS: A nationwide and web-based survey was conducted. Statistical charts were used to describe the usage and perceptions of telemedicine by health care professionals. And the ordinal logistic regression was applied to analyze the influencing factors. RESULTS: A total of 1349 valid questionnaires were collected. In the survey, 74.0 % of Chinese health care professionals used telemedicine once a week. The average duration of participating in telemedicine services lasted mainly 11-30 min (64.0 %). More than half (52.5 %) of participants' hospitals adopted fee subsidy measures, followed by the award for excellent evaluation (36.4 %). The majority (92.5 %) believed that telemedicine could reduce patient referral rates. More than 95 % were satisfied with telemedicine, were willing to continue, and would recommend telemedicine for patients, respectively. The main problems existing were: incomplete system equipment, insufficient timeliness, high costs, inability to reimburse medical insurance, non-standardized medical records, inadequate publicity, cumbersome processes and long waiting time. Ordinal logistic regression showed that too short service duration (≤10 min) could significantly reduce medical professionals' overall satisfaction, using intention and willingness to recommend (P = 0.026, P = 0.017 and P = 0.040 respectively), while the convenience of the operating system had a significant positive impact (P = 0.005, P = 0.003 and P = 0.001 respectively). And cost subsidy incentive and the promotion of professional titles could significantly enhance their overall satisfaction(P = 0.006, P = 0.030), using intention (P = 0.011, P = 0.001), and willingness to recommend (P = 0.040, P = 0.004). CONCLUSIONS: The usage of telemedicine is relatively insufficient. Most health care professionals have fairly positive opinions toward telemedicine. The most mentioned issues and expectations for telemedicine can be roughly divided into four categories: infrastructure, service process, charge and cost, and popularity. It is possible to improve their evaluation by improving system convenience, enhancing service punctuality, avoiding excessively short service duration and adopting incentive measures.

Telemedicine Is Becoming an Increasingly Popular Way to Resolve the Unequal Distribution of Healthcare Resources: Evidence From China.

Background: Few studies focused on the general situation of telemedicine in China. Objectives: The purpose of this review is to investigate telemedicine in China, from the aspects of necessity, history, scale, and operation procedure, to improve the further development and implementation of telemedicine service. Methods: A literature search for peer-reviewed studies was conducted using the primary electronic databases. Additional documents from the official websites of Chinese government departments involved telemedicine was also collected. We extracted telemedicine related information focused on China from the final retrieved materials, and the general situation of telemedicine was drawn. Results: In China, telemedicine offers a feasible solution to the unequal allocation of healthcare resources, which makes telemedicine increasingly become an important alternative to close the gap between rural and urban in the capability and quality of medical services. China initiated telemedicine in the late 1980s. In 2018, China's telemedicine network has covered more than 3,000 hospitals across the country. As of 2019, almost all of the 31 provinces and municipalities in mainland have established regional telemedicine centers, and the market size of telemedicine reached about USD 2.68 billion. Based on the telemedicine network, remote rural patients can apply for healthcare services of top-tier urban hospitals through local county-level medical institutions. Conclusions: Through improving the capacity, quality, and efficiency of healthcare in underserved areas, and reducing the unequal distribution of medical resources, telemedicine can help solve the problems of the difficulty and high cost to access to medical services in China.

DigestPath: A benchmark dataset with challenge review for the pathological detection and segmentation of digestive-system.

Examination of pathological images is the golden standard for diagnosing and screening many kinds of cancers. Multiple datasets, benchmarks, and challenges have been released in recent years, resulting in significant improvements in computer-aided diagnosis (CAD) of related diseases. However, few existing works focus on the digestive system. We released two well-annotated benchmark datasets and organized challenges for the digestive-system pathological cell detection and tissue segmentation, in conjunction with the International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI). This paper first introduces the two released datasets, i.e., signet ring cell detection and colonoscopy tissue segmentation, with the descriptions of data collection, annotation, and potential uses. We also report the set-up, evaluation metrics, and top-performing methods and results of two challenge tasks for cell detection and tissue segmentation. In particular, the challenge received 234 effective submissions from 32 participating teams, where top-performing teams developed advancing approaches and tools for the CAD of digestive pathology. To the best of our knowledge, these are the first released publicly available datasets with corresponding challenges for the digestive-system pathological detection and segmentation. The related datasets and results provide new opportunities for the research and application of digestive pathology.

A potential delivery system based on cholera toxin: A macromolecule carrier with multiple activities.

Macromolecular drugs are widely thought to be one of the most promising fields, but there are still many problems, especially with regard to drug delivery. Drug delivery systems are focused on loading efficiency without loss of activity, effective cellular internalization, anti-degradation, target ability, etc. New directions for macromolecular drugs delivery systems are not only to retain the activity of drugs, but bring new bioactivity to carry out dual benefits. Cholera toxin (CT) from Vibrio cholerae is one of such delivery systems and plays a potential role in delivering macromolecular drugs. After released from V. cholerae in the intestine, the B subunit of CT binds to the ganglioside GM1 on intestinal cells, and then the toxin gains access into the intestine. CT has potential as a "vaccine adjuvant-delivery system" (VADS) and is able to bring antigens and serve as adjuvants to induce specific immunity. In addition, it has been well used in the field of mucosal drug delivery and neural targeting. However, native CT is toxic, which restricts its practical application. There are several CT-based proteins with reduced virulence and reserved or even enhanced adjuvant activity under research. In this review, we comprehensively summarize the preparation strategy, advantages, applications and corresponding deficiencies of CT-based proteins. CT is focused on a delivery system when delivering macromolecular cargos such as active protein/peptide and antigen/antigen peptide. CT-based drug delivery system deserves further study due to their superiority.

Construction and Application of an Intelligent Response System for COVID-19 Voice Consultation in China: A Retrospective Study.

Background: The outbreak of novel coronavirus disease 2019 (COVID-19) has led to tremendous individuals visit medical institutions for healthcare services. Public gatherings and close contact in clinics and emergency departments may increase the exposure and cross-infection of COVID-19. Objectives: The purpose of this study was to develop and deploy an intelligent response system for COVID-19 voice consultation, to provide suggestions of response measures based on actual information of users, and screen COVID-19 suspected cases. Methods: Based on the requirements analysis of business, user, and function, the physical architecture, system architecture, and core algorithms are designed and implemented. The system operation process is designed according to guidance documents of the National Health Commission and the actual experience of prevention, diagnosis and treatment of COVID-19. Both qualitative (system construction) and quantitative (system application) data from the real-world healthcare service of the system were retrospectively collected and analyzed. Results: The system realizes the functions, such as remote deployment and operations, fast operation procedure adjustment, and multi-dimensional statistical report capability. The performance of the machine-learning model used to develop the system is better than others, with the lowest Character Error Rate (CER) 8.13%. As of September 24, 2020, the system has received 12,264 times incoming calls and provided a total of 11,788 COVID-19-related consultation services for the public. Approximately 85.2% of the users are from Henan Province and followed by Beijing (2.5%). Of all the incoming calls, China Mobile contributes the largest proportion (66%), while China Unicom and China Telecom are accounted for 23% and 11%. For the time that users access the system, there is a peak period in the morning (08:00-10:00) and afternoon (14:00-16:00), respectively. Conclusions: The intelligent response system has achieved appreciable practical implementation effects. Our findings reveal that the provision of inquiry services through an intelligent voice consultation system may play a role in optimizing the allocation of healthcare resources, improving the efficiency of medical services, saving medical expenses, and protecting vulnerable groups.

Application of Telemedicine Services Based on a Regional Telemedicine Platform in China From 2014 to 2020: Longitudinal Trend Analysis.

BACKGROUND: Telemedicine that combines information technology and health care augments the operational model of traditional medical services and brings new opportunities to the medical field. China promotes telemedicine with great efforts, and its practices in the deployment of telemedicine platforms and delivery of services have become important references for the research and development in this field. OBJECTIVE: Our work described in this paper focuses on a regional telemedicine platform that was built in 2014. We analyzed the system design scheme and remote consultations that were conducted via the system to understand the deployment and service delivery processes of a representative telemedicine platform in China. METHODS: We collected information on remote consultations conducted from 2015 to 2020 via the regional telemedicine platform that employs a centralized architectural system model. We used graphs and statistical methods to describe the changing trends of service volume of remote consultation, geographical and demographic distribution of patients, and waiting time and duration of consultations. The factors that affect consultation duration and patient referral were analyzed by multivariable linear regression models and binary logistic regression models, respectively. The attitudes toward telemedicine of 225 medical practitioners and 225 patients were collected using the snowball sampling method. RESULTS: The regional telemedicine platform covers all levels of medical institutions and hospitals in all 18 cities of Henan Province as well as some interprovince hospitals. From 2015 to 2020, 103,957 remote medical consultations were conducted via the platform with an annual increasing rate of 0.64%. A total of 86.64% (90,069/103,957) of medical institutions (as clients) that applied for remote consultations were tier 1 or 2 and from less-developed regions; 65.65% (68,243/103,945) of patients who applied for remote consultations were aged over 50 years. The numbers of consultations were high for departments focusing in the treatment of chronic diseases such as neurology, respiratory medicine, and oncology. The invited experts were mainly experienced doctors with senior professional titles. Year of consultation, tier of hospital, consultation department, and necessity of patient referral were the main factors affecting the duration of consultations. In surveys, we found that 60.4% (136/225) of medical practitioners and 53.8% (121/225) of patients had high satisfaction and believed that telemedicine is of vital importance for the treatment of illness. CONCLUSIONS: The development of telemedicine in China shows a growing trend and provides great benefits especially to medical institutions located in less developed regions and senior citizens who have less mobility. Cases of remote consultations are mainly for chronic diseases. At present, the importance and necessity of telemedicine are well recognized by both patients and medical practitioners. However, the waiting time needs to be further reduced to improve the efficiency of remote medical services.

Effectiveness of a Cloud-Based Telepathology System in China: Large-Sample Observational Study.

BACKGROUND: Whole-slide imaging allows the entire slide to be viewed in a manner that simulates microscopy; therefore, it is widely used in telepathology. However, managing the large digital files needed for whole-slide imaging is difficult. To solve this problem, we set up the Chinese National Cloud-Based Telepathology System (CNCTPS). CNCTPS has been running for more than 4 years and has accumulated a large amount of data. OBJECTIVE: The main purpose of this study was to comprehensively evaluate the effectiveness of the CNCTPS based on a large sample. The evaluation indicators included service volume, turnaround time, diagnosis accuracy, and economic benefits. METHODS: Details of 23,167 cases submitted to the CNCTPS from January 2016 to December 2019 were collected to analyze the service volume, turnaround time, and economic benefits. A total of 564 patients who visited the First Affiliated Hospital of Zhengzhou University and obtained final diagnoses were followed up to analyze the diagnostic accuracy of the CNCTPS. RESULTS: From 2016 to 2019, the service volume of the CNCTPS increased from 2335 to 9240, and the number of participating hospitals increased from 60 to 74. Consultation requests from county-level hospitals accounted for 86.57% (20,287/23,167). A total of 17,495 of 23,167 cases (75.52%) were confirmed, including 12,088 benign lesions, 5217 malignant lesions, and 190 borderline lesions. Of the cases, 3.85% (893/23,167) failed to be diagnosed for reasons such as poor slice quality and incomplete sampling. The median turnaround time was 16.93 hours and was shortened yearly (between 2018 and 2019: adjusted P=.01; other groups: adjusted P<.001); 82.88% cases were diagnosed in 48 hours. There was a discrepancy between the diagnosis and final diagnosis for 11 cases, including 4 false-positive cases and 7 false-negative cases. The sensitivity and specificity were 97.66% and 98.49%, respectively. The diagnostic accuracy of the system was 98.05%, with no statistical difference from the final diagnosis in the hospital (P=.55). By using this system, a total of US $300,000 was saved for patients every year. CONCLUSIONS: The novel cloud-based telepathology system has the potential to relieve the shortage of pathologists in primary hospitals. It can also simultaneously reduce medical costs for patients in China. It should, therefore, be further promoted to enhance the efficiency, quantity, and quality of telepathology diagnoses.

Co-delivery of PSMA antigen epitope and mGM-CSF with a cholera toxin-like chimeric protein suppressed prostate tumor growth via activating dendritic cells and promoting CTL responses.

Subunit vaccines derived from tumor antigens play a role in tumor therapy because of their unique advantages. However, because of the weak immunogenicity of peptides in subunit vaccines, it is difficult to trigger an effective cytotoxic T lymphocyte (CTL) response, which is critical for cancer therapy. A requirement for the activation of CTL cells by exogenous antigens is the stimulation of antigen presenting cells (APC) with the help of adjuvants and cross-presentation to T lymphocytes. Standard nonconjugated adjuvant-peptide mixtures do not ensure co-targeting of the antigen and the adjuvant to the same APC, which limits the effects of adjuvants. In this study, a fusion protein consisting of murine granulocyte-macrophage colony stimulating factor (mGM-CSF) fused with CTA2 (A2 subunit of cholera toxin) was generated and assembled with CTB-PSMA624-632 (prostate specific membrane antigen (PSMA) peptide 624-632 fused to CTB) to obtain a cholera toxin-like protein. The chimeric protein retained the biological activity of mGM-CSF and had stronger GM1 binding activity than (CTB-PSMA624-632)5. C57BL/6J mice immunized with the CT-like chimeric protein exhibited delayed tumor growth following challenge with human PSMA-EGFP-expressing RM-1 cells. Experiment results showed that the CT-like chimeric protein could induce the maturation of DC cells and improve CTL responses. Overall, these results indicate that the nasal administration of a CT-like chimeric protein vaccine results in the development of effective immunity against prostate tumor cells and might be useful for future clinical anti-tumoral applications.

Implementation and Application of Telemedicine in China: Cross-Sectional Study.

BACKGROUND: Telemedicine has been used widely in China and has benefited a large number of patients, but little is known about the overall development of telemedicine. OBJECTIVE: The aim of this study was to perform a national survey to identify the overall implementation and application of telemedicine in Chinese tertiary hospitals and provide a scientific basis for the successful expansion of telemedicine in the future. METHODS: The method of probability proportionate to size sampling was adopted to collect data from 161 tertiary hospitals in 29 provinces, autonomous regions, and municipalities. Charts and statistical tests were applied to compare the development of telemedicine, including management, network, data storage, software and hardware equipment, and application of telemedicine. Ordinal logistic regression was used to analyze the relationship between these factors and telemedicine service effect. RESULTS: Approximately 93.8% (151/161) of the tertiary hospitals carried out telemedicine services in business-to-business mode. The most widely used type of telemedicine network was the virtual private network with a usage rate of 55.3% (89/161). Only a few tertiary hospitals did not establish data security and cybersecurity measures. Of the 161 hospitals that took part in the survey, 100 (62.1%) conducted remote videoconferencing supported by hardware instead of software. The top 5 telemedicine services implemented in the hospitals were teleconsultation, remote education, telediagnosis of medical images, tele-electrocardiography, and telepathology, with coverage rates of 86.3% (139/161), 57.1% (92/161), 49.7% (80/161), 37.9% (61/161), and 33.5% (54/161), respectively. The average annual service volume of teleconsultation reached 714 cases per hospital. Teleconsultation and telediagnosis were the core charging services. Multivariate analysis indicated that the adoption of direct-to-consumer mode (P=.003), support from scientific research funds (P=.01), charging for services (P<.001), number of medical professionals (P=.04), network type (P=.02), sharing data with other hospitals (P=.04), and expertise level (P=.03) were related to the effect of teleconsultation. Direct-to-consumer mode (P=.01), research funding (P=.01), charging for services (P=.01), establishment of professional management departments (P=.04), and 15 or more instances of remote education every month (P=.01) were found to significantly influence the effect of remote education. CONCLUSIONS: A variety of telemedicine services have been implemented in tertiary hospitals in China with a promising prospect, but the sustainability and further standardization of telemedicine in China are still far from accomplished.

Impact of the Internet on Medical Decisions of Chinese Adults: Longitudinal Data Analysis.

BACKGROUND: The internet has caused the explosive growth of medical information and has greatly improved the availability of medical knowledge. This makes the internet one of the main ways for residents to obtain medical information and knowledge before seeking medical treatment. However, little has been researched on how the internet affects medical decisions. OBJECTIVE: The purpose of this study was to explore the associations between internet behaviors and medical decisions among Chinese adults aged 18 or over, including whether to go to the hospital and which level of medical institution to choose. METHODS: With the adult residents (≥18 years old) in 12 regions including urban and rural areas taken as the research objects, the differences in medical choices of adults with various characteristics were analyzed, and generalized linear mixed models were adopted to analyze the longitudinal data of the China Health Nutrition Survey from 2006 to 2015. RESULTS: Adult groups with different ages, genders, education levels, regions, places of residence, severities of illness and injury, years of suffering from hypertension, and history of chronic diseases showed diverse medical decisions, and the differences were statistically significant (P<.05). After controlling for these potential confounding factors and taking self-care as the reference, the probability of Chinese adults who participated in online browsing activities selecting hospital care was 0.82 (95% CI 0.69-0.98; P=.03) times that of residents who did not participate in online browsing activities. In terms of medical institution choices, adults who participated in online browsing activities were 1.86 (95% CI 1.35-2.58; P<.001) times more likely to opt for municipal medical treatment than primary care. However, the effect of online browsing on the selection probability of county-level hospitals was not significant compared with primary hospitals (P=.59). Robust analysis verified that accessing the internet had a similar effect on Chinese adults' medical decisions. CONCLUSIONS: Chinese adults who use the internet are a little less likely to go to the hospital than self-care. The internet has broken down the barriers to obtain knowledge of common diseases and thus has a slight substitution effect of self-care on hospital care. Internet use may increase the probability of adults going to municipal hospitals. The rising tendency of visiting high-level medical institutions may be consequently exacerbated due to knowledge monopoly of severe and complicated diseases that is difficult to eliminate, and the increase in inconsistent and incomplete medical information online will blur the residents' cognitive boundary of common diseases and severe diseases. Exploring the substantive impact of the internet on medical decision making is of great significance for further rational planning and utilization of the internet, in order to guide patients to appropriate medical institution.

An in vitro and in vivo study of the brain-targeting effects of an epidermal growth factor-functionalized cholera toxin-like chimeric protein.

The development of neuroprotective drugs has proven to be extremely difficult because of the blood-brain barrier. Intranasal administration is thought to transport the drug from the nasal cavity along the olfactory and trigeminal nerves to the brain, thus bypassing the blood-brain barrier. However, macromolecular protein drugs have low delivery efficiency via this route in general. We hypothesized that an innocuous cholera toxin-like chimeric protein could better enhance the efficiency of protein delivery through the intranasal route. To test this hypothesis, we designed an enhanced green fluorescent protein (EGFP) chimera to evaluate the effect of the cholera toxin (CT) as a carrier for drug delivery into the brain. Then, the EGFP was replaced with epidermal growth factor (EGF) in the chimeric protein, and the therapeutic effect of the new chimeric protein was studied in an LPS-induced neuritis mouse model. The results suggest that the CT-like chimeric protein can bypass the blood-brain barrier and enter the brain in approximately 30 min. This EGF chimeric protein can effectively protect the spatial cognitive ability of and confer anti-anxiety protection to mice. The results indicate that cholera toxin-like chimeric proteins are potential tools for effectively delivering macromodecular drugs into the brain through intranasal administration.

Design and Application of a Telemedicine System Jointly Driven by Videoconferencing and Data Exchange: Practical Experience from Henan Province, China.

Background and Objectives: There are a few problems restraining the effective operation of telemedicine in China. On the basis of practices of the Henan Province Telemedicine Center of China (HTCC), the purpose of this study was to design a telemedicine system jointly driven by videoconferencing and data exchange to address the issues limiting the further development and implementation of telemedicine. Methods: Based on service-oriented architecture, the organizational design of the telemedicine system was gradually refined from top to bottom to complete its hierarchical layout. Technologies including multiprotocol stack adaptation, self-adaptive multilink network transmission, information exchange of heterogeneous medical systems, and open application system architecture were also used to construct the system. Results: The telemedicine system realizes the integration of videoconferencing, data acquisition and exchange of heterogeneous medical information systems, and the actual applications and expansion of telemedicine services. The HTCC currently covers more than 500 telemedicine centers, workstations, and service points, forming a five-level "province-city-county-township-village" telemedicine network linkage. The HTCC handles nearly 30,000 teleconsultation cases per year, helping patients save about ¥120 million Chinese Yuan RMB (approximately US $17.5 million). Conclusions: The proposed telemedicine system achieves satisfactory operation effects, along with social and economic benefits. It has the potential to increase the coverage of medical resources in remote regions, and it can play a role in solving other problems facing telemedicine development in China. The findings also inform measures for further improvement in telemedicine's implementation effects, service quality, and application scope in China and globally.

A novel approach to determine two optimal cut-points of a continuous predictor with a U-shaped relationship to hazard ratio in survival data: simulation and application.

BACKGROUND: In clinical and epidemiological researches, continuous predictors are often discretized into categorical variables for classification of patients. When the relationship between a continuous predictor and log relative hazards is U-shaped in survival data, there is a lack of a satisfying solution to find optimal cut-points to discretize the continuous predictor. In this study, we propose a novel approach named optimal equal-HR method to discretize a continuous variable that has a U-shaped relationship with log relative hazards in survival data. METHODS: The main idea of the optimal equal-HR method is to find two optimal cut-points that have equal log relative hazard values and result in Cox models with minimum AIC value. An R package 'CutpointsOEHR' has been developed for easy implementation of the optimal equal-HR method. A Monte Carlo simulation study was carried out to investigate the performance of the optimal equal-HR method. In the simulation process, different censoring proportions, baseline hazard functions and asymmetry levels of U-shaped relationships were chosen. To compare the optimal equal-HR method with other common approaches, the predictive performance of Cox models with variables discretized by different cut-points was assessed. RESULTS: Simulation results showed that in asymmetric U-shape scenarios the optimal equal-HR method had better performance than the median split method, the upper and lower quantiles method, and the minimum p-value method regarding discrimination ability and overall performance of Cox models. The optimal equal-HR method was applied to a real dataset of small cell lung cancer. The real data example demonstrated that the optimal equal-HR method could provide clinical meaningful cut-points and had good predictive performance in Cox models. CONCLUSIONS: In general, the optimal equal-HR method is recommended to discretize a continuous predictor with right-censored outcomes if the predictor has an asymmetric U-shaped relationship with log relative hazards based on Cox regression models.