Advances and applications of quantitative systems pharmacology modeling and virtual clinical trials in modern drug development / 药学学报

Quantitative systems pharmacology (QSP) modeling is an emerging computational medicine approach with growing applications and significance in modern drug development. QSP models are generally formulated based on multiscale disease mechanisms and drug-target interactions, which makes them capable of integrating multimodal data from the preclinical and clinical space. This also enables them to generate quantitative characterization of the dynamic disease progression as well as high-throughput predictions of drug-induced efficacy and toxicity signals. Therefore, QSP modeling and model-based virtual clinical trials have been widely implemented to guide drug development, in scenarios such as target identification and assessment, clinical trial design, evaluation of combination therapy and biomarkers, and personalized medicine. In US and Europe, QSP modeling has been developing rapidly in the past 10 years and is now an integral part of the model-informed drug development paradigm; however, in China it is still a nascent field. Here we will present a comprehensive review of the recent advancements of QSP and its impact in modern drug development through a number of case studies. This review will provide guidance for the future drug development efforts and the growth of QSP practice in China.

La evidencia científica de las consecuencias de la modernidad / Scientific evidence of the consequences of modernity

Resumen La prevalencia de diabetes tipo 2 (DT2) en México es del 14.4%. La enfermedad se caracteriza por un estado de hiperglucemia e inflamación crónica secundaria a la resistencia y la secreción inadecuada de insulina. Dentro de sus factores de riesgo destacan la obesidad, el sedentarismo, las dietas hipercalóricas y las variantes genéticas. Durante décadas, diferentes grupos de investigación básica y aplicada han trabajado de forma interdisciplinaria para ofrecer evidencia científica que ha ayudado a entender los mecanismos implicados en la fisiopatología de la DT2 en pacientes mexicanos. Sin embargo, hoy en día la urgencia de conseguir mejores propuestas de prevención y manejo del paciente con DT2 hace necesario el uso de la medicina traslacional, que integra el conocimiento científico con el uso de tecnologías innovadoras para brindar una atención integral. El presente documento describe de forma concisa y con un enfoque traslacional las implicaciones de la interacción de factores de riesgo ambientales y genéticos en el desarrollo de obesidad infantil y DT2 en México.

Abstract The prevalence of type 2 diabetes (T2D) in Mexico is 14.4%. This disease is characterized by a state of hyperglycemia and chronic inflammation secondary to inadequate insulin secretion and its resistance. Among its risk factors for metabolic diseases development, the interaction between obesity, sedentary lifestyle, hypercaloric diets and genetic variants play an important role. For decades, different basic and applied research groups have worked in an interdisciplinary way to provide scientific evidence that has helped to understand the mechanisms involved in the pathophysiology of T2D in Mexicans. However, today the urgency of the advance and better proposals for prevention and management of patients with T2D makes it necessary to use translational medicine, which integrates scientific knowledge with the use of innovative technologies to provide comprehensive health care. In this sense, the present document concisely describes, with a translational approach, the implications of the interaction of environmental and genetic risk factors in the development of childhood obesity and T2D in Mexico.

The funding system of American dentist scientist and its enlightenment / 中华医学科研管理杂志

Objective:To provide reference for the cultivation of stomatologist scientists in China by comparison and learning from the development of dental scientist training funding system in the United States.Methods:The development, training funding system and evaluation system of dental scientists in the United States were analyzed through literature review, and compared with the training of dental scientists in Chinese context.Results:The training of American dental scientists started early, and the funding system covered the whole process of dental students' learning and career choice; tailored measurements were adopted to deal with challenges and difficulties during the training process. On the other hand, the training of stomatologist scientists in China started late, the methods are diverse but uneven. In this paper, it is proposed to enhance the training by strengthening the construction of the training and funding system of stomatologist scientists, encouraging the collaboration between professional societies and colleges and universities, establishing specific funds and balancing the weight of clinical and scientific research in the teaching system.Conclusions:The funding system for the training of dental scientists in the United States can be used as a reference for optimizing the training of dental scientists in China.

Do medicine and cell biology talk to each other? A study of vocabulary similarities between fields

A close interaction between basic science and applied medicine is to be expected. Therefore, it is important to measure how far apart the field of cell biology and medicine are. Our approach to estimating the distance between these fields was to compare their vocabularies and to quantify the difference in word repertoire. We compared the vocabulary of the title and abstract of articles available in PubMed in two selected high-impact journals in each field: cell biology, medicine, and translational science. Although each journal has its own editorial policy, we showed that within each field there is a small vocabulary difference between the two journals. We developed a word similarity index that can measure how much journals share a common vocabulary. We found a high similarity index between each cell biology (91%), medical (71-74%), and translational journal (65%). In contrast, the comparison between medicine and biology journals produced low correlation values (22-36%), suggesting that their vocabularies are quite dissimilar. Translational medicine journals had medium similarity values when compared to cell biology journals (52-70%) and medicine journals (27-59%). This approach was also performed in 10-year periods to evaluate the evolution of each field. Using the "onomics" strategy presented here, we observed that differences in vocabulary of basic science and medicine have been increasing over time. Since translational medicine has an intermediate vocabulary, we confirmed that translational medicine is an efficient approach to bridge this gap.

Medicina Traslacional en el Perú, generación de políticas y mejoras basadas en la evidencia / Translational medicine in Peru, policy making and evidence-based improvement

Introducción: la investigación traslacional es una rama de la ciencia de reciente creación, su objetivo principal es la aplicación del conocimiento que se genera de las investigaciones, que no quede formando parte de la literatura gris, en el papel o para unos pocos, sino que pueda servir a la mayor cantidad posible de individuos y/o poblaciones. Objetivo: determinar los avances que se han dado a lo largo de los últimos años en la aplicación de la medicina traslacional en Perú. Métodos: se realizó una búsqueda por conveniencia en bases de datos (Google Scholar, Pubmed). Se han brindado ejemplos de cómo la investigación traslacional en Perú puede aportar en gran medida a la mejora de realidades y problemáticas específicas, esto refuerza la necesidad de que las decisiones políticas deben basarse en la medicina basada en la evidencia. Resultados: la medicina traslacional en Perú enfrenta muchas dificultades, como lo son los recursos limitados, tiempo escaso para implementar la investigación formativa, carencia de modelos pedagógicos actualizados, docentes preparados en escuelas antiguas y con capacidad limitada para la educación médica continua; obstáculos que deben de superarse para poder asegurar que la ciencia -y por ende la sociedad- progresen. Conclusiones: en Perú, el avance de la medicina traslacional ha derivado en la generación de personal de salud más capacitado que ha proporcionado los medios para el desarrollo de múltiples políticas públicas. Dichas políticas en muchos casos han terminado plasmadas en normas, reglamentos y hasta leyes en el país(AU)

Introduction: translational research is a branch of science of recent creation. Its main aim is the application of the knowledge generated by research so that it will not become grey literature printed on paper or for the use of a chosen few, but serve as many people and/or populations as possible. Objective: determine the progress made in recent years in the application of translational medicine in Peru. Methods: a convenience search was conducted in the databases Google Scholar and PubMed. Examples are offered of the way in which translational research may greatly contribute to improve specific realities and problems in Peru. This reinforces the need that political decisions be based on evidence-based medicine. Results: translational medicine is faced with many difficulties in Peru, such as limited resources, scant time to implement training research, lack of updated pedagogical models, and teachers trained in old schools and with a limited capacity for continuing medical education. These hurdles should be overcome to ensure the progress of science and therefore of society as well. Conclusions: progress of translational medicine in Peru has resulted in the training of more skilled health personnel, providing the means for the development of multiple public policies. In many cases those policies have been included in standards, regulations and even laws in the country(AU)

Perspectiva Latinoamericana del Modelo Conceptual Conocimiento en Acción de Knowledge Translation / Latin-American Perspective about the Conceptual Model Knowledge in Action of Knowledge Translation

Introducción: El vacío entre lo que se sabe y lo que se hace es complejo para la toma de decisiones ante las demandas de la práctica diaria de atención a la salud de las personas, familias y comunidades. En ese sentido, la traducción del conocimiento puede ser una estrategia de transformación del conocimiento en acción con la participación del usuario del sistema de salud. Objetivo: Reflexionar acerca del significado, las potencialidades y límites de aplicación del modelo conceptual conocimiento en acción de la estrategia de traducción del conocimiento para transferir conocimientos científicos al campo de la salud y la enfermería. Métodos: Análisis teórico-reflexivo del modelo conceptual de traducción del conocimiento en acción, editado por expertos del área de la salud, de acuerdo con la definición del Instituto Canadiense de Investigación en Salud y adoptado por la OMS y EVIPNET, con aplicación en países latinoamericanos. Esa reflexión fue dividida en tres ejes: significado; modelo conceptual y aplicación en la práctica. Conclusiones: Algunas propuestas de transformación del conocimiento en acción y justicia social han empezado a considerarse en América Latina, tanto en la política como en la práctica clínica. En el campo de la enfermería hay una creciente aplicación del modelo de traducción del conocimiento a la acción, con la utilización de diferentes enfoques de investigación para integrar a los participantes para la producción de nuevas prácticas más eficiente, efectiva, eficaz y segura(AU)

Introduction: The gap between what is known and what is done is complex for decision-making in the face of daily-practice demands of the healthcare of individuals, families and communities. In that respect, knowledge translation can be a strategy of knowledge transformation in action with the participation of the health system user. Objective: To reflect on the meaning, potentialities and limits of applying the conceptual model knowledge in action of the knowledge translation strategy to transfer scientific knowledge to the field of health and nursing. Methods: Theoretical-reflexive analysis of the conceptual model of translation of knowledge in action, edited by experts in the health area​​, in accordance with the definition of the Canadian Institutes for Health Research and adopted by WHO and EVIPNET, with application in Latin American countries. That reflection was divided into three axes: meaning, conceptual model, and application in practice. Conclusions: Some proposals for the transformation of knowledge into action and social justice have started to be considered in Latin America, both in politics and in clinical practice. In the field of nursing, there is a growing application of the model of translation of knowledge into action, with the use of different research approaches to integrate participants for the production of new practices that are more efficient, effective, and safer(AU)

Alterações cromossômicas e periostite / Chromosomal alterations and periostitis

Introdução: A periostite é uma inflamação do periósteo que pode se estender para os tecidos moles adjacentes. Há pouca informação na literatura sobre alterações genéticas nessas lesões, as quais são reparadas por intensas reações de proliferação osteoblástica e possuem curso clínico semelhante ao das osteomielites crônicas inespecíficas, que podem evoluir para neoplasias. Objetivo: análise citogenética de amostra de periostite para detecção e descrição de alterações cromossômicas, principalmente as associadas com desenvolvimento de neoplasias. Métodos: material obtido de lesão em palato de paciente, um homem de 74 anos de idade, submetido anteriormente a cirurgias de remoção de carcinoma basocelular em nariz e cavidade oral. Após a coleta, com estudo histopatológico confirmando apenas material de periostite, a amostra foi submetida à análise citogenética a partir de cultura de células e bandamento GTG. Resultados: o cariótipo composto evidenciou, como alterações clonais, monossomia dos cromossomos 10, 15, 20 e 22; trissomia do cromossomo 22; inversão do cromossomo 12 e deleção de 15q. O grande número de alterações cromossômicas estaria relacionado com a alta taxa de proliferação celular, a qual poderia induzir replicação celular desbalanceada e instabilidade genética. Há genes, envolvidos com desenvolvimento de neoplasias, localizados nos pontos de quebra das alterações estruturais encontradas nos cromossomos 12 e 15. Conclusão: foram evidenciadas várias alterações cromossômicas que refletiriam a proliferação celular local. A análise citogenética em casos de periostite poderá auxiliar na descoberta de biomarcadores de prognóstico e ser utilizada, futuramente, na rotina médica para um melhor manejo dos pacientes.

Introduction: Periostitis is an inflammation of the soft tissues adjacent to the bone that affects the periosteum. There is little information in the literature about genetic alterations in these lesions, which are repaired by intense osteoblast proliferation reactions and present a clinical course that resembles that of nonspecific chronic osteomyelitis that may progress to neoplasms. Objective: Cytogenetic analysis of periostitis sample for detection and description of chromosomal alterations, especially those associated with cancer development. Methods: Material obtained from a palate lesion of a 74-year-old man who had previously undergone surgery to remove basal cell carcinoma in the nose and oral cavity. After collection, with a histopathological study confirming only periostitis material, the sample was submitted to a cytogenetic analysis from cell culture and GTG banding. Results: The composite karyotype showed, as clonal alterations, monosomy of chromosomes 10, 15, 20, and 22; trisomy of chromosome 22; inversion of chromosome 12, and deletion of 15q. The large number of chromosomal alterations would be related to the high rate of cell proliferation, which could induce unbalanced cell replication and genetic instability. There are genes, which are involved in the development of neoplasms, mapped at the breakpoints of structural changes found on chromosomes 12 and 15. Conclusion: Several chromosomal alterations that were observed would reflect local cell proliferation. Cytogenetic analysis of periostitis may help in the discovery of prognostic biomarkers and may be used in the medical routine for better patient management in the future.

Translational research on gastric cancer: Ruijin experience / 中华胃肠外科杂志

Translational medicine refers to translating basic research achievements into the clinical application for diagnosis and treatment. There are still many issues of gastric cancer to be solved in clinical diagnosis and treatment. We need to focus on clinical questions, by means of basic research and multidisciplinary intersection approach, to further improve the overall efficacy of gastric cancer. Based on Ruijin Hospital′s translational research experiences, in this paper, the authors describe the future direction in the field of translational research, such as the etiology and pathogenesis of gastric cancer, tumor markers for early diagnosis, prediction of recurrence and metastasis, classification criteria, evaluation of chemotherapy, tumor heterogeneity, targeted therapy, immunotherapy and research platform establishment. In addition, here we share our perspective of the research on serum biomarkers, specific antibodies and improvement of drug delivery for gastric cancer.

Effect and Safety of CX-DZ-II Intelligent Electroacupuncture Therapeutic Instrument for Neck Pain Caused by Cervical Spondylos: Study Protocol for A Randomized Controlled Trial / 中国结合医学杂志

BACKGROUND@#Neck pain caused by cervical spondylosis (CS) is a chronic pain condition, with an increasingly high incidence in the general population. Electroacupuncture is a common analgesic modality that has been widely applied in neck pain treatment. However, current electroacupuncture instruments used in the clinic have low intelligence levels and obscure parameter standards. We here designed this study for assessing the effect and safety of a new, intelligent electroacupuncture instrument, the CX-DZ-II, in treating neck pain.@*METHODS@#The present study is a prospective, two-center, randomized, controlled, open-label, non-inferiority trial for CX-DZ-II on treating neck pain caused by CS. Totally 160 eligible patients will be included in this trial and randomly assigned to an experimental group and a control group in a 1:1 ratio. A semi-standard acupoint selection strategy will be employed. In the experimental group, selected acupoints will be stimulated by CX-DZ-II. Electroacupuncture treatment will be accomplished by a pre-existing electroacupuncture instrument in the control group. The duration of treatment will be 2 weeks. The primary outcome is the change of Visual Analog Scale (VAS) score after one course of treatment. The secondary outcomes include the VAS scores after each treatment, the responder rate, drug-usage rate of non-steroidal antipyretic analgesics, the rate of adverse events occurrence, and the performance of instrument.@*DISCUSSION@#This study will evaluate the effect and safety of the CX-DZ-II intelligent electroacupuncture therapeutic instrument in comparison with a pre-existing non-intelligent instrument in the treatment of neck pain caused by CS. The results will hopefully demonstrate a more optimal electroacupuncture instrument for the treatment of neck pain. (Trial registration No. gov NCT03005301).

Individualized induction of immune tolerance and regulatory T cell / 器官移植

The induction of immune tolerance is an essential component and the utmost goal in the field of organ transplantation immunity, which depends upon the recognition and presentation of transplantation antigens, the activation and response of the immune system and other immune essence. However, before successfully inducing immune tolerance, how to carry out individualized induction of immune tolerance in organ transplant recipients to optimize the combination of immunosuppressive agents and individualized treatment and achieve the ideal state of optimal prevention and treatment of immune rejection and minimal adverse reactions, remains to be further resolved by the organ transplantation practitioners. Based on the reports of international core journals, the individualized induction strategy of immune tolerance and the future prospects were reviewed in this article from the following aspects including the mechanism underlying induction of immune tolerance, realization of operational immune tolerance, novel strategy of individualized induction of immune tolerance and application of regulatory T cell in individualized immune tolerance in combination with clinical and laboratory research results of regulatory T cell in our center.

Accelerating the development of Chinese urology in clinical research by taking the advantages and making cooperation / 中华泌尿外科杂志

The clinical research is an important cornerstone of medical innovation and development.In the past decade,there have been some breakthrough achievements in the field of urological clinical research internationally.However,there is still a large gap between Chinese urological clinical research and the international level.Urologists across China should improve the clinical research to a new level of awareness,starting with the idea of patients' expectation being our concern,and making clinical research our priority.The multi-center clinical research should be the priority,involving the real-world study,prospective randomized controlled trails,translational medicine,and artificial intelligence,etc.The standardized method must be adopted and the integrity of scientific research should be concerned in the process of clinical research.The clinical research results should not only be published in the international journals,but more importantly be published in the domestic journals.The proposal of "publishing the studies on the land of our motherland" should be vigorously advocated.

Application of biomarkers in clinical development of biologics and bioanalytical strategies / 中国临床药理学与治疗学

China's biologic drug research and development is on a fast track lane. The rising cost of new drug development has not improved the success rate of drug launch, and a shift in the model of drug development is urgently needed. In order to improve the success rate, a biomarker strategy of the new drug development model has been proposed and is generally accepted. This paper reviews the research and development of new translational medicine drugs with biomarkers as the core, the application of biomarkers in the clinical study of biological drugs, biomarker biological analysis strategies, and the opportunities and challenges of biomarkers in the clinical study of biological drugs. By comparing international standards, seeking China's advantages and seeking opportunities from the research and development model of translational medicine based on biomarkers, China can make innovative drugs with global influence in the near term.

Preliminary study on the construction of national major science and technology infrastructure for translational medicine in China / 上海交通大学学报（医学版）

Objective • To explore the preliminary experience of the construction of national major science and technology infrastructure for translational medicine in China, and to provide reference for their future development. Methods • The current situation, experience and enlightenment of major science and technology infrastructure construction at home and abroad were sorted out by literature analysis, relevant recommendations were collected through expert interviews, and the preliminary experience of national major science and technology infrastructure construction for translational medicine in China was summarized. Results • The experience and enlightenment that can be used for reference from the construction of major science and technology infrastructure at home and abroad mainly included 7 aspects, i.e. high-quality team construction, device sharing, industry-academiaresearch collaboration, international cooperation, the cluster effect producing, talents cultivation and the scientific data sharing mechanism. In China, the construction of major science and technology infrastructure for translational medicine started late, and had a good try at the above first 5 aspects, but not so good at the last 2. At the same time, self-experience has been formed in taking full advantages of the supporting institutions and getting funds through multiple channels. Conclusion • The construction of national major science and technology infrastructure for translational medicine in China should learn from the development experience at home and abroad, combine our own characteristics, explore and innovate the system and mechanism, and seek new breakthroughs.

Innovación en salud en México: retos importantes y un largo camino que recorrer / Health innovation in Mexico: important challenges and a long road to walk

Resumen: La transferencia de tecnología de instituciones de investigación en salud a empresas que generen nuevos tratamientos médicos ha generado grandes beneficios para la salud pública a nivel mundial. Sin embargo, en México existen importantes rezagos en los indicadores de innovación. Hay barreras culturales, regulatorias y financieras que obstaculizan la innovación en México. Al mismo tiempo, los últimos años han visto la aparición de varias iniciativas útiles que avanzan en la dirección correcta. El presente trabajo describe la situación actual y las principales barreras y oportunidades para promover la innovación en salud y la contribución de ésta a mejoras en salud pública.

Abstract: The transfer of technology from health research institutions to businesses that develop new medical treatments has generated great benefits for public health at a global level. Mexico however, is lagging in innovation indicators. There are important cultural, regulatory, and financial barriers that limit innovation in Mexico. However recent years have seen the appearance of several useful initiatives that constitute progress in the right direction. This work provides a brief overview of the current situation of innovation in Mexico, describes the main barriers and gives recommendations that can promote health innovation in Mexico, which can contribute to improvements in public health.

Medical research model and its application in ophthalmology under the background of big data / 中华实验眼科杂志

With the rapid development of global information technology, the wide application of electronic medical record management system and the construction and operation of biological sample base platform, the research value of medical big data is increasingly valued.In recent years, as a bridge between basic medical research and clinical medical research, the progress of translational medicine has greatly shortened the space-time distance between basic and clinical medicine, and also opened up a new prospect for the application of medical big data.As a methodology of clinical medical research, epidemiology emphasizes the design, measurement and scientific evaluation methods of medical research, which plays an important role in every link of translational medical research and is an important part of translational medical research.It takes systematic epidemiology as the main research method, deeply excavates and makes full use of medical big data resources, promotes translational research and knowledge integration with the rapid development of big data, the clinical transformation of basic research results of ophthalmology has entered a new era, greatly promoting the cross integration of ophthalmology and related fields.

The exploration and practice of clinical translational medicine research for pancreatic cancer / 中华消化外科杂志

Pancreatic cancer is a digestive system malignant tumor with extremely poor prognosis.With the rapid development of science and technology,although breakthrough results has been achieved in basic research of pancreatic cancer and some achievement in surgical techniques and adjuvant treatment approach,the survival of patients with pancreatic cancer has not been significantly improved.Among them,the serious disconnection between basic research and clinical practice has led to a slow improvement in the diagnosis and therapy.As a bridge between basic research and clinical work,translational medicine can promote progress of the early detection and precision treatment of pancreatic cancer,thus providing new hope for patients with pancreatic cancer.

Promoting nursing patents and eliminating barriers to the implementation of nursing intellectual property rights / 中华医学科研管理杂志

Objective As one of the important parts of medical scientific research outcomes,the significance of nursing patents is becoming more and more prominent during recent years.However,the nursing department is the blind spot of intellectual property in most hospitals.This article tried to explore strategies to eliminate harriers to the implementation of nursing intellectual property rights in order to promote nursing patents.Methods This paper conducted systematic analysis of the problems and obstacles in the implementation and transformation of nursing patents,and proposed tailored administrative plan.Results Identified obstacle factors include personal reasons of the nursing staff,heavy daily clinical work,as well as the immature patent system and patent market in China.Accordingly,our hospital adopted several corrective measurements,for instance,improving the support for the implementation of nursing patents,strengthening the cultivation and incubation of the intellectual property of nursing staff and standardizing the patent management.Conclusions These measures have effectively im proved the awareness and enthusiasm of nurses' patent knowledge.And we have obtained the ice breaking of the transformation of nursing patents in our hospital.

Perspectives for cancer immunotherapy mediated by p19Arf plus interferon-beta gene transfer

While cancer immunotherapy has gained much deserved attention in recent years, many areas regarding the optimization of such modalities remain unexplored, including the development of novel approaches and the strategic combination of therapies that target multiple aspects of the cancer-immunity cycle. Our own work involves the use of gene transfer technology to promote cell death and immune stimulation. Such immunogenic cell death, mediated by the combined transfer of the alternate reading frame (p14ARF in humans and p19Arf in mice) and the interferon-β cDNA in our case, was shown to promote an antitumor immune response in mouse models of melanoma and lung carcinoma. With these encouraging results, we are now setting out on the road toward translational and preclinical development of our novel immunotherapeutic approach. Here, we outline the perspectives and challenges that we face, including the use of human tumor and immune cells to verify the response seen in mouse models and the incorporation of clinically relevant models, such as patient-derived xenografts and spontaneous tumors in animals. In addition, we seek to combine our immunotherapeutic approach with other treatments, such as chemotherapy or checkpoint blockade, with the goal of reducing dosage and increasing efficacy. The success of any translational research requires the cooperation of a multidisciplinary team of professionals involved in laboratory and clinical research, a relationship that is fostered at the Cancer Institute of Sao Paulo.

Super “STAR” in translational medicine: Current status and prospects of exosome-related diagnosis and treatment technologies / 第二军医大学学报

Recently, exosome has gained great attention in the field of biomedical research, especially in precision medicine-related diagnostic technology and clinical transformation of therapeutic strategies. There have been a large number of exosome-related studies involving non-invasive diagnosis of diseases, liquid biopsy of tumor, development of precision drugs and observation of clinical efficacy. Exosomes possess four biological characteristics: stable, trackable, active and real-time, which make them the key factors for the next generation “STAR” of translational medicine. Since 2014 exosomerelated studies began to show an explosive increase, and several exosome-associated patent technologies or products have appeared. This article summarizes the research history, biological characteristics and clinical exploration of exosomes, and analyzes the prospects of exosome-related technology.