Development of an interpretable machine learning model associated with heavy metals' exposure to identify coronary heart disease among US adults via SHAP: Findings of the US NHANES from 2003 to 2018.

Limited information is available on the links between heavy metals' exposure and coronary heart disease (CHD). We aim to establish an efficient and explainable machine learning (ML) model that associates heavy metals' exposure with CHD identification. Our datasets for investigating the associations between heavy metals and CHD were sourced from the US National Health and Nutrition Examination Survey (US NHANES, 2003-2018). Five ML models were established to identify CHD by heavy metals' exposure. Further, 11 discrimination characteristics were used to test the strength of the models. The optimally performing model was selected for identification. Finally, the SHapley Additive exPlanations (SHAP) tool was used for interpreting the features to visualize the selected model's decision-making capacity. In total, 12,554 participants were eligible for this study. The best performing random forest classifier (RF) based on 13 heavy metals to identify CHD was chosen (AUC: 0.827; 95%CI: 0.777-0.877; accuracy: 95.9%). SHAP values indicated that cesium (1.62), thallium (1.17), antimony (1.63), dimethylarsonic acid (0.91), barium (0.76), arsenous acid (0.79), total arsenic (0.01) in urine, and lead (3.58) and cadmium (4.66) in blood positively contributed to the model, while cobalt (-0.15), cadmium (-2.93), and uranium (-0.13) in urine negatively contributed to the model. The RF model was efficient, accurate, and robust in identifying an association between heavy metals' exposure and CHD among US NHANES 2003-2018 participants. Cesium, thallium, antimony, dimethylarsonic acid, barium, arsenous acid, and total arsenic in urine, and lead and cadmium in blood show positive relationships with CHD, while cobalt, cadmium, and uranium in urine show negative relationships with CHD.

A Large-Scale Screening Responding Sporadic Epidemic of COVID-19 in China by an Integrated Health-Care System.

Introduction: In the post-pandemic period of COVID-19, the majority of cities in China try to balance the normalization of epidemic prevention and social-economic development. However, the appearance of asymptomatic infected patients poses threats to public health, which might be infectious without clinical symptoms and only be detected by testing approaches. Methods: Along with the appearance of one symptomatic case, a regional large-scale screening program was carried out in Shenzhen City charged by a regionally integrated healthcare system. After describing the screening program, a retrospective cross-sectional study for the screening outcome and efficacy was conducted. Discussion: According to the screening results, the asymptomatic case was infectious and their close contacts should be quarantined cautiously as the close contacts of symptomatic cases. Besides, after integrating medical resources in Luohu district of Shenzhen, the medical capability of Luohu district improved greatly which could be demonstrated in inspection and organization abilities in this screening program. Conclusion: The large-scale screening contributed to preventing epidemic transmission. In the post-pandemic period, regular surveillance of asymptomatic cases and rapid response capability for emergent screening program are both crucial for the prevention and control of COVID-19 epidemic. The integrated healthcare system coordinating regional medical institutions and optimizing regional medical recourse has advantages to address public health emergencies.

Application of Traditional Chinese Medicine and Systems Pharmacology in Drug Prevention and Treatment against COVID-19.

A novel coronavirus named SARS-CoV-2 is causing the severe acute pneumonia (COVID-19) and rapid spread nationally and internationally, resulting in a major global health emergency. Chinese governments and scientists have implemented a series of rigorous measures and scientific research to prevent and control the SARS-CoV-2 infection. However, there is still no specific antiviral drug or vaccine against SARS-CoV-2. It has been proven that traditional Chinese medicine (TCM) exerts an important role in the prevention and treatment of the COVID-19 caused by SARS-CoV-2 during the outbreak. Although the therapeutic effects of these TCM formulas are attractive, the molecular mechanism of action has not been fully elucidated. An emerging strategy of systems pharmacology has been proposed to be a promising method to interpret drug action in complex biological systems and quickly screen out the bioactive compounds from TCM to treat treatment of COVID-19 caused by SARS-CoV-2. Therefore, in this study, the epidemiology, TCM therapy, and the systems pharmacology-based method for TCM are reviewed for COVID-19 to provide a perspective for the prevention and treatment of SARS-CoV-2 infection. Further efforts should be made to reduce disease burden and improve the ability to design antiviral drugs and vaccines, which will benefit the health care system, economic development and even social stability.

Integrated Healthcare Systems Response Strategies Based on the Luohu Model During the COVID-19 Epidemic in Shenzhen, China.

COVID-19 has affected primary health-care delivery in metropolitan areas. An integrated health-care system offers advantages in response to the community outbreak and transmission of highly infectious diseases. On the basis of practitioner experience with a pioneering integrated health-care system in Shenzhen, China, this article presents the following effective strategies in response to the epidemic: (1) enhance the public workforce in primary health care; (2) integrate resources to allow regional sharing and efficient use; (3) employ teams centered on general practitioners for community containment; and (4) adopt e-health and telemedicine for health-care delivery. An integrated health-care system is usually very specific to a particular regional context; however, the core strategies and mechanisms based on the Luohu model can contribute to improving the public health capacity in emergency responses; they can transform health-care delivery in the COVID-19 epidemic. The experience in Shenzhen may help other cities in enhancing and coordinating the preparedness of their health-care systems in dealing with future public health emergencies.

Systems Pharmacology-Based Method to Assess the Mechanism of Action of Weight-Loss Herbal Intervention Therapy for Obesity.

Obesity is a multi-factorial chronic disease that has become a serious, prevalent, and refractory public health challenge globally because of high rates of various complications. Traditional Chinese medicines (TCMs) as a functional food are considered to be a valuable and readily available resource for treating obesity because of their better therapeutic effects and reduced side effects. However, their "multi-compound" and "multi-target" features make it extremely difficult to interpret the potential mechanism underlying the anti-obesity effects of TCMs from a holistic perspective. An innovative systems-pharmacology approach was employed, which combined absorption, distribution, metabolism, and excretion screening and multiple target fishing, gene ontology enrichment analysis, network pharmacology, and pathway analysis to explore the potential therapeutic mechanism of weight-loss herbal intervention therapy in obesity and related diseases. The current study provides a promising approach to facilitate the development and discovery of new botanical drugs.

People-centred integrated care in urban China.

In most countries, the demand for integrated care for people with chronic diseases is increasing as the population ages. This demand requires a fundamental shift of health-care systems towards more integrated service delivery models. To achieve this shift in China, the World Health Organization, the World Bank and the Chinese government proposed a tiered health-care delivery system in accordance with a people-centred integrated care model. The approach was pioneered in Luohu district of Shenzhen city from 2015 to 2017 as a template for practice. In September 2017, China's health ministry introduced this approach to people-centred integrated care to the entire country. We describe the features of the Luohu model in relation to the core action areas and implementation strategies proposed and we summarize data from an evaluation of the first two years of the programme. We discuss the challenges faced during implementation and the lessons learnt from it for other health-care systems. We consider how to improve collaboration between institutions, how to change the population's behaviour about using community health services as the first point of contact and how to manage resources effectively to avoid budget deficits. Finally, we outline next steps of the Luohu model and its potential application to strengthen health care in other urban health-care systems.

Dans la plupart des pays, la demande de soins intégrés pour les personnes atteintes de maladies chroniques augmente à mesure que la population vieillit. Cette demande nécessite une réorientation majeure des systèmes de soins de santé vers des dispositifs de prestation de services plus intégrés. Pour effectuer cette réorientation en Chine, l'Organisation mondiale de la Santé, la Banque mondiale et le gouvernement chinois ont proposé un système de soins de santé à plusieurs niveaux selon un dispositif de soins intégrés axés sur l'être humain. Cette approche a été utilisée pour la première fois dans le district de Luohu de la ville de Shenzhen de 2015 à 2017 en tant que modèle de pratique. En septembre 2017, le ministère chinois de la Santé a appliqué à l'ensemble du pays ce dispositif de soins intégrés axés sur l'être humain. Nous décrivons les caractéristiques du modèle de Luohu par rapport aux principaux domaines d'action et aux stratégies de mise en œuvre proposées et nous résumons les données extraites d'une évaluation des deux premières années du programme. Nous examinons les difficultés rencontrées lors de la mise en œuvre et les leçons tirées de ces difficultés pour d'autres systèmes de soins de santé. Nous réfléchissons aux moyens d'améliorer la collaboration entre les institutions, de changer le comportement de la population concernant l'utilisation des services de santé des collectivités comme premier point de contact et de gérer efficacement les ressources pour éviter les déficits budgétaires. Enfin, nous décrivons les prochaines étapes à suivre dans le cadre du modèle de Luohu et son application potentielle pour renforcer les soins de santé dans d'autres systèmes urbains de soins de santé.

En la mayoría de los países, la demanda de atención integrada para las personas con enfermedades crónicas aumenta a medida que la población envejece. Esta demanda requiere un cambio fundamental de los sistemas de atención sanitaria hacia modelos de prestación de servicios más integrados. Para lograr este cambio en China, la Organización Mundial de la Salud, el Banco Mundial y el gobierno chino propusieron un sistema escalonado de prestación de servicios sanitarios de acuerdo con un modelo de atención integrada centrada en las personas. El enfoque se introdujo en el distrito de Luohu de la ciudad de Shenzhen de 2015 a 2017 como modelo para la práctica. En septiembre de 2017, el Ministerio de Salud de China introdujo este enfoque de atención integrada centrada en las personas en todo el país. Se describen las características del modelo de Luohu en relación con las áreas centrales de acción y las estrategias de implementación propuestas y se resumen los datos de una evaluación de los dos primeros años del programa. Se exponen los desafíos enfrentados durante la implementación y las lecciones aprendidas de la misma para otros sistemas de atención sanitaria. Se considera cómo mejorar la colaboración entre las instituciones, cómo cambiar el comportamiento de la población sobre el uso de los servicios sanitarios comunitarios como primer punto de contacto y cómo gestionar eficazmente los recursos para evitar déficits de presupuesto. Por último, se esbozaron los próximos pasos del modelo de Luohu y su posible aplicación para fortalecer la atención sanitaria en otros sistemas urbanos de atención sanitaria.

The Luohu Model: A Template for Integrated Urban Healthcare Systems in China.

INTRODUCTION: Emerging from the epidemiological transition and accelerated aging process, China's fragmentated healthcare systems struggle to meet the demands of the population. On Sept 1st 2017, China's National Health and Family Planning Commission encouraged all cities to learn from the Luohu model of integration adopted in Luohu as an approach to meeting these challenges. In this paper, we study the integration process, analyze the core mechanisms, and conduct preliminary evaluations of integrated policy development in the Luohu model. POLICY DEVELOPMENT: The Luohu hospital group was established in Aug 2015, consists of five district hospitals, 23 community health stations and an institute of precision medicine. The group adopted a series of professional, organizational, system, functional and normative strategies for integrated care, which was provided for the residents of Luohu, especially for the elderly population and patients with chronic conditions. According to a preliminary evaluation of the past two years, the Luohu model showed improvement in the structure and process towards integrated care. New preventive programs conducted in the hospital group resulted in changes of disease incidence. Residents were more satisfied with the Luohu model. However, spending exceeded the global budget for health insurance because of short-term increases in the demand for health care. LESSONS LEARNED: First, engagement of multiple stakeholders is essential for the design and implementation of reform. Second, organizational integration is a prerequisite for integrated care in China. Third, effective care integration requires alignment with payment reforms. Fourth, normative integration could promote collaboration in an integrated healthcare system. CONCLUSION: Core strategies and mechanisms of the Luohu model will promote integrated care in urban China and other countries facing the same challenges. However, it is necessary to study the effects of the Luohu model over the long term and continue to strive for integrated care.

[Inhibitory effect and acting mechanism of Tongxinluo on IL-1beta-mediated coronary intimal hyperplasia and 5-hydroxytryptamine-induced coronary vasospasm in small swine].

OBJECTIVE: To observe the inhibitory effect of Tongxinluo (TXL) on coronary vaso spasm in small swine in vivo, and to investigate its possible acting mechanism. METHODS: The model of coronary atherosclerosis in 16 male small swines was established by left thoracotomy after anesthesia, isolated the sections of left anterio-descending branch and proximal end of rotator branch with similar outer diameter, and encapsulated them with paper-towel holding 2.5 microg interleukin-1beta. Two weeks later, the condition of coronary vasospasm induced by catheter intra-coronary injection of 5-hydroxytryptamine (5-HT, 10 microg/kg) was observed through coronary artery contrast examination. The 12 swines with successfully formed coronary vaso spasm were randomly divided into 2 groups, the TXL group and the control group. They were fed with special diet, but TXL 1 g/(kg d) was administered additionally to the TXL group for 4 weeks. The observation on coronary vasospasm was repeated 1 week after discontinuation of TXL treatment, then the animals were sacrificed, their vascular sections enclosed with IL-1beta was taken to conduct the pathologic examination and to detect the expressions of Rho kinase mRNA and its substrate myosin- binding subunit phosphorylation (MBS-P) by RT-PCR and Western blot method. RESULTS: Coronary artery contrast showed that local coronary stenosis occurred in the 12 model swines to different extents (20% - 30%, and vascular spasm on them could be induced by 5-HT. At the time of repeating examination, 11 vascular sections in the control group still maintain their positive spasm reaction to 5-HT, but only 2 in the TXL group did so, the reaction turned to negative in 1 and 10 in the two groups respectively. Pathological examination showed that different degrees of macrophage aggregation could be found in both groups. The degree of lumen stricture and endometrial hyperplasia in the TXL group was obviously attenuated than those in the control group. The expressions of Rho kinase mRNA and MBS-P in the control group were up-regulated obviously. As compared with those in the control group, they were inhibited significantly in the TXL group, as (71.5 +/- 2.4) vs (98.2 +/- 7.7)% and 16,633 +/- 1,390 vs 25,818 +/- 4,745, respectively (all P < 0.05). CONCLUSION: TXL could obviously inhibit the coronary intimal hyperplasia mediated by IL-1beta and coronary vasospasm induced by 5-HT, one of its mechanisms is possibly the inhibition on the intracellular Rho kinase mRNA expression in the IL-1beta enclosed vascular section to decrease the level of MBS-P.