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El artículo informa acerca de la validación de un instrumento sobre la aplicación de los principios bioéticos de la corriente principialista en cada uno de los elementos de los protocolos de investigación clínica. Para ello, se realizó la valoración de un instrumento de 173 ítems por medio del método Delphi, con la colaboración de 12 expertos latinoamericanos en bioética de la investigación. El instrumento tuvo dos rondas de revisión. Al final solo se tuvieron 171 ítems, en el que se aplicaron los principios bioéticos en 208 ocasiones, de los cuales 87 (41,82%) pertenecían a Beneficencia, 63 (30,29%) a No Maleficencia, 36 (17,31%) a Justicia y 22 (10,58%) a Autonomía. En cuanto a la congruencia de los principios en general respecto de las variables de los elementos del protocolo de investigación clínica, se encontró en 189 (90,87% IC 95% 86.10 a 94.41) ocasiones, K=0.98 (0.01), p=<0.0001. Se concluye que ell instrumento validado nos brinda la opción de aplicar los principios bioéticos de la corriente principialista a cada uno de los elementos de los protocolos de investigación clínica.
The aim of this article is to report on the validation of an instrument on the application of principialist bioethical principles in each of the elements of clinical research protocols. To this end, a 173-item instrument was evaluated using the Delphi method, with the collaboration of 12 Latin American experts in research bioethics. The instrument underwent two rounds of revision. In the end there were only 171 items, in which the bioethical principles were applied 208 times, of which 87 (41.82%) belonged to Beneficence, 63 (30.29%) to Non-Maleficence, 36 (17.31%) to Justice and 22 (10.58%) to Autonomy. Regarding the congruence of the principles in general with respect to the variables of the elements of the clinical research protocol, it was found on 189 (90.87% CI 95% 86.10 to 94.41) occasions, K=0.98 (0.01), p=<0.0001. It is concluded that the validated instrument gives us the option of applying the bioethical principles of the principialist current to each of the elements of the clinical research protocols.
O objetivo deste artigo é informar acerca da validação de um instrumento sobre a aplicação dos princípios bioéticos da corrente principialista em cada um dos elementos dos protocolos de investigação clínica. Para isso, realizou-se a valoração de um instrumento de 173 itens por meio do método Delphi, com a colaboração de 12 especialistas latino-americanos em bioética da investigação. O instrumento teve duas rodadas de revisão. Ao final, analisou-se 171 itens, aos quais se aplicaram os princípios bioéticos em 208 ocasiões, dos quais 87 (41,82%) pertenciam a Beneficência, 63 (30,29%) a Não Maleficência, 36 (17,31%) a Justiça e 22 (10,58%) a Autonomia. Quanto à congruência dos princípios em geral, a respeito das variáveis dos elementos do protocolo de investigação clínica, encontrou-se em 189 (90,87% IC 95% 86.10 a 94.41) ocasiões, K=0.98 (0.01), p=<0.0001. Concluiu-se que o instrumento validado nos dá a opção de aplicar os princípios bioéticos da corrente principialista a cada um dos elementos dos protocolos de investigação clínica.
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En el cruce entre la revolución tecnológica y la educación en ciencias de la rehabilitación y del movimiento humano, la inteligencia artificial (IA) emerge como herramienta transformadora en los cursos de metodología de investigación. Este artículo destaca su potencial para optimizar la experiencia de aprendizaje y personalizar la instrucción, pero enfatiza la necesidad crucial de abordar desafíos éticos y pedagógicos. Propone orientaciones para equilibrar la innovación educativa y la responsabilidad académica, resaltando la importancia de la implementación consciente y planificada de la IA en los equipos de investigación en ciencias de la rehabilitación y del movimiento humano, garantizando así la integridad científica y ética en este campo en constante evolución.
In the intersection between technological advancements and education in rehabilitation science, artificial intelligence (AI) emerges as a transformative tool in research methodology. This article navigates the ethical and academic considerations tied to the incorporation of AI in rehabilitation and movement science courses. While acknowledging its potential to enhance learning experiences, it critically addresses the imperative to tackle ethical and pedagogical challenges. The paper offers guidance to strike a balance between educational innovation and academic responsibility. It emphasizes the need for a conscientious and planned implementation of AI, ensuring both scientific integrity and ethical adherence in this dynamically evolving field.
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Lecanemab is a new drug used to treat early Alzheimer's disease (AD) with mild cognitive impairment or mild dementia. It is a human anti-Aβ fibril monoclonal IgG1 antibody, which is injected intravenously into the patient, through the blood-brain barrier into the brain, clearing amyloid plaque, thereby slowing the rate of cognitive decline in patients and delaying disease progression. This article reviews the pharmacological studies, clinical studies, safety and limitations of lecanemab, in order to help clinical understand the current research status and existing achievements of this drug.
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AIM: To investigate and analyze the current situation and needs of clinical research nurses in China, in order to provide scientific basis for constructing a training system for research nurses, promoting standardized training, and achieving standardized management for them. METHODS:A self-made questionnaire was used to investigate 102 research nurses from nearly 70 well-known clinical trial institutions in China. The contents of the questionnaire mainly included the general information, professional experience and work content of the research nurses, the sense of accomplishment and training needs of clinical trial work. RESULTS: Among the 102 research nurses surveyed, 92.15% have a bachelor's degree or above; 53.92% of those have intermediate or higher professional titles; 74.51% of them are part-time research nurse. Among professional experiences, 19.61% have more than 10 years of clinical trial experience; 47.06%, 40.20%, and 21.17% of surveyed research nurses were authorized to participate in clinical trial drug management, sample management, and quality control; 70.59% of research nurses have a high sense of achievement in their daily work. In terms of education and training needs, clinical trial related laws and regulations, standardized training for clinical trial protocol implementation, and good clinical practice (GCP) are the three most important aspects. CONCLUSION: Clinical research nurses in China have a relatively high level of education and nursing experience, but there is still a large gap in the amount of professional full-time clinical research nurses in China. Due to the rapid development of innovative drugs and devices, as well as the urgent need to improve the clinical research system, it is necessary to establish a training, assessment, and evaluation system for research nurses that is in line with China's national conditions in order to improve the professional level of research nurses, and improve the quantity and quality of clinical trial research on innovative drugs and devices in China.
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In order to understand the status quo of ethical review of clinical research on the defecation function of patients with rectal cancer after sphincter-preserving surgery, analyze its causes and put forward corresponding suggestions, to arouse researchers’ attention to ethical review in subsequent relevant clinical studies. The ethical review of literatures related to the defecation function of patients with rectal cancer after sphincter-preserving surgery published on CNKI in recent 10 years was sorted out and summarized. The results showed that the ethical review of clinical research papers on defecation function of patients with rectal cancer after sphincter-preserving surgery was not optimistic. We should strengthen the ethical training of researchers, improve the ethical awareness of researchers, strictly implement the ethical norms of paper publication, strengthen the ethical requirements of manuscript contracts, perfect the ethical review system, and pay attention to the examination and supervision of informed consent, so as to promote the construction of ethical examination and approval norms of clinical research documents.
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For multi-center clinical research, how to ensure the quality of ethical review and improve the efficiency of ethical review through cooperation among centers is an important direction for clinical research management departments and research parties to explore. By combing and analyzing the existing pattern of multi-center ethical review at home and abroad, combining the current situation of the ethical review and management development in China, taking cancer clinical research as the breakthrough point, it was advocated to establish a cooperative review led by professional institute in domestic, on the basis of extensive and in-depth training exchanges and effective communication on the same platform, collaborative review, ensure quality and efficiency, so as to promote and implement the "mutual recognition" of ethical review. Then, this paper further put forward the concept of "whole-process linkage" in the ethical management process of multi-center clinical research, and pointed out that all research parties should clarify their responsibilities, enhance their awareness and ability, and jointly and comprehensively implement the protection of subjects among clinical researchers.
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It is the responsibility of a clinical research institution to protect the rights and interests of research subjects. For the full process supervision of clinical research projects, the construction of a Human Research Protection Program (HRPP) which is suitable to the hospital’s situation can gradually improve the ethical review quality, and provide comprehensive protection measures for participants and potential participants throughout the entire clinical research process. Combined with the characteristics of clinical research and ethical review of Traditional Chinese Medicine(TCM), this paper introduced the construction of an HRPP system that highlights TCM characteristics. At the same time, this paper systematically analyzed the division of responsibilities, communication and cooperation of different committees and departments within the HRPP system to ensure the effective operation of the entire HRPP system, improve the quality of TCM clinical research and the protection level of the HRPP system, in order to achieve the goal of promote the healthy, orderly and scientific development of clinical research.
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From January 23, 2020 to May 29, 2021, there were 17,550 clinical research registrations on the China Clinical Trial Registry Platform. The index of clinical research on COVID-19 showed 840 registrations, accounting for 4.79% (840/17 550) of the total registrations. According to the trend chart of epidemic development, 487 clinical research projects of COVID-19 registered from January 23, 2020 to March 18, 2020 were set as the early stage of epidemic discovery in the region, the following 15 months were divided into stable initial stage, stable later stage and the later stage of the first wave of domestic epidemic every five months. The proportion of COVID-19 research projects registered in each stage was 29.80%, 5.87%, 0.76% and 1.15% of all registered projects respectively. The registration ratios of COVID-19 in each clinical stage was 57.98%, 28.81%, 5.95% and 7.26% respectively. Intervention studies were 61.60% (300/487) in the early stage of the epidemic, and most of them were in biological agent and drug therapy, which were 40.49%, 50.00% and 73.77% respectively in the later stages. Stable initial stage biological agent projects decreased. Then the vaccine research program became a focused research program. Among the 58 registration projects involving vaccines, 25 were clinical trials of vaccines in different stages, with the major research units being biopharmaceutical companies. Of the 487 clinical studies registered in the early stage, 10.23%(50/487) were withdrawn, of which 38 were intervention treatment studies, most notably drug studies (17) and blood biological products (16), but they were still registered in the stable initial stage. It is necessary to reflect on the scientific and ethical nature of early COVID-19 clinical trials or research, including whether the three core values of equal respect, help to alleviate pain and fairness can be achieved. Whether the "ethics review meeting should pay special attention to the scientificity, safety, fairness, subject protection, informed consent documents and informed consent process, avoidance of conflicts of interest, etc. of clinical trials or research" has been implemented. Competent government departments at all levels and all clinical medical research institutions should organize evaluation, and then establish an effective evaluation mechanism when new clinical trials or research projects are registered in the future.
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In order to speed up the review and approval of new drugs of Traditional Chinese Medicine (TCM) in China, it is accelerating the construction of TCM registration review evidence system, which combines the theory of TCM, human experience and clinical trials, and optimizing the technical requirements for the review of and approval of new drugs of TCM based on ancient classic prescriptions, famous old Chinese medicine prescriptions, and medical institution preparations. The United States has strict requirements on the application for the marketing of herbal medicines. According to the characteristics of herbal medicines and combined with human experience, the European Union has classified registration management, reflecting the regulatory concept of inheritance and innovation. TCM has a long history of human use experience in China, its application has a scope of application, basic requirements, and it is necessary to classify and exempt the declaration materials according to the evidence grading evaluation standards. When the ethics committee reviews the research scheme of human experience of TCM, it should pay attention to the review points such as scientific basis for new drugs or prescriptions of TCM, clinical positioning, applicable population, effectiveness and safety information, research design, sample size, conflict of interest management and informed consent. Finally, Human experience is helpful to formulate the research scheme of new drugs of TCM, which can not only improve the success rate of research and development, but also reduces the cost of research and development, accelerate the marketing of new drugs of TCM, and can benefit more patients.
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It is worth pondering how to seek advantages and avoid disadvantages in stem cell clinical research and give full play to the advantages of technology for the benefit of mankind. Through the analysis of the status of stem cell clinical research, including technology and related management methods, proposed the main problems existing in stem cell research, such as the risks of technological uncertainty, ambiguity between research and treatment, over-treatment and technological innovation. Then this paper discussed the ethical and legal risks of stem cell clinical research in China, mainly related to the problems that the construction of laws and regulations is lagging behind, the regulatory challenges of administrative departments are large, the ethical awareness of researchers needs to be further improved, the principle of fairness and justice is not taken into account, the research platform construction of medical institutions is not in place and the protection system of subjects is imperfect, and the organization construction and review capacity of the ethics committee is still lacking.
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Stem cell clinical research is a hot frontier research. The ethical review of stem cell clinical research is full of challenges. Currently, clinical researches lack specific operational guidelines. Considered the related laws and regulations, and the operability of practical work, experts from the field of stem cells, such as law, ethics and management, will form a consensus on the basis of full discussion and continuous revision. It will provide reference for the operation of the ethics committee of corresponding institutions, and lay a certain foundation for the establishment of national expert consensus in the future, so as to promote the effective guidance of ethical review practice and quality evaluation of stem cell research.
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Chronic obstructive pulmonary disease （COPD） is a common disease in clinical practice. It is associated with obvious exposure to toxic particles or gases and has become the leading cause of death and disability worldwide. The pathogenesis of COPD is complex， and the oxidative stress involved in COPD plays a crucial role in the pathological process of the disease. Patients with COPD usually have high levels of oxidative stress in the lungs， which will affect the whole body for a long time， causing a variety of complications and accelerating the development of the disease. On the one hand， oxidative stress can directly damage the airway and lung tissue. On the other hand， it also drives other pathological mechanisms to jointly promote the development of disease， such as participating in inflammatory reactions and protease/anti-protease imbalance， promoting mucus secretion， accelerating cellular senescence， causing autoimmunity， and involving in genetic regulatory pathways. At present， western medicine treatment is mostly based on conventional drug treatment， and antioxidant-targeted oxidative stress is adopted， but there are still some challenges in efficacy and safety. Traditional Chinese medicine has a long history of preventing and treating COPD. In particular， Chinese herbal medicine formulas have great potential to interfere with the oxidative stress of COPD. Whether it is the modified classical traditional Chinese medicine or the new formulation developed by modern doctors， the research results reflect the multi-target and multi-channel advantages of traditional Chinese medicine treatment， and their efficacy and safety are gradually verified. This paper reviewed the literature in recent years， starting with the basic and clinical research on the intervention of traditional Chinese herbal medicine formulas on oxidative stress of COPD， so as to provide further ideas for related research on the prevention and treatment of oxidative stress of COPD by traditional Chinese medicine.
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In recent years, the vigorous development of clinical researches carried out by medical schools is inseparable from the effective participation of medical students. However, as the number and categories of clinical research projects that medical students participate in increase, medical ethics related issues gradually occur. This article sorts out the ethical issues that arose in clinical researches, in which medical students participated, analyzes the underlying causes, and proposes solutions for the above-mentioned ethical issues, aiming to provide reference for medical ethics education and research project management for medical schools.
La participación efectiva de los estudiantes de medicina ha contribuido en gran medida al desarrollo exitoso de la investigación clínica en las escuelas de medicina de China en los últimos años. Sin embargo, con el creciente número y tipos de proyectos de investigación clínica en los que participan estudiantes de medicina, las cuestiones éticas se exponen gradualmente. Este trabajo enumera las cuestiones éticas que han surgido en la participación de los estudiantes de medicina en la investigación clínica en los últimos años, analiza las causas subyacentes y propone soluciones a las cuestiones éticas mencionadas anteriormente, con el objetivo de proporcionar referencia para la enseñanza de la ética médica y la gestión de proyectos de investigación para las escuelas de medicina.
A participação efetiva dos estudantes de medicina tem contribuído muito para o próspero desenvolvimento da pesquisa clínica nas escolas médicas da China nos últimos anos. No entanto, com o aumento do número e tipos de projetos de pesquisa clínica dos quais os estudantes de medicina participam, questões relacionadas à ética e à alfabetização são gradualmente expostas. Este artigo lista as questões éticas que surgiram na participação de estudantes de medicina em pesquisas clínicas nos últimos anos, analisa as causas subjacentes e propõe soluções para as questões éticas acima mencionadas, com o objetivo de fornecer referência para o ensino de ética médica e gestão de projetos de pesquisa para escolas médicas.
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Humains , Mâle , FemelleRésumé
Patients with rare diseases frequently face unmet medical needs due to the high costs, lengthy development times, and slow approval processes for new treatments. This case study discusses innovative access alternatives for rare diseases in Brazil, focusing on early access to pabinafusp-alfa for mucopolysaccharidosis type II (MPS-II), a rare genetic lysosomal storage disease characterized by a deficiency of the enzyme iduronate-2-sulfatase. From September 2018 to March 2023, 20 Brazilian MPS-II patients received pabinafusp-alfa through a clinical research protocol. This enzyme replacement therapy (ERT) crosses the blood-brain barrier to address central nervous system manifestations unmet by existing treatments. Patients' participation in the clinical study resulted in an estimated BRL 65 million in cost savings for the public healthcare system compared to conventional ERT with idursulfase-alfa and potentially better clinical outcomes. The case study underscores the importance of innovative mechanisms in addressing patients' medical needs. Early access alternatives include: a) clinical study access, with execution/development aligned with healthcare managers and linked to future access strategies; b) regulatory-level risk-sharing, considering effectiveness uncertainties and the possibility of market withdrawal and/or reimbursement in case of negative results; and c) drug pre-delivery, with payment contingent on positive phase III clinical study outcomes. Although public-private partnerships in clinical research are underused, they could benefit all stakeholders by accelerating drug development, facilitating early patient access to innovative medicines, and generating healthcare system savings, particularly for rare diseases.
Pacientes com doenças raras frequentemente enfrentam necessidades médicas não atendidas devido aos altos custos, longos tempos de desenvolvimento e processos de aprovação lentos para novos tratamentos. Este estudo de caso discute alternativas inovadoras de acesso para doenças raras no Brasil, com foco no acesso precoce ao alfapabinafuspe para mucopolissacaridose tipo II (MPS-II), uma doença lisossômica de armazenamento genético rara, caracterizada por uma deficiência da enzima iduronato-2-sulfatase. De setembro de 2018 a março de 2023, 20 pacientes brasileiros com MPS-II receberam alfapabinafuspe por meio de pesquisa clínica. Essa terapia de reposição enzimática (TRE) atravessa a barreira hematoencefálica para tratar manifestações do sistema nervoso central não atendidas pelos tratamentos existentes. A participação dos pacientes no estudo clínico resultou em uma economia estimada de 65 milhões de reais para o sistema público de saúde, em comparação com a TRE convencional com idursulfase alfa, além de potencialmente melhores resultados clínicos. O estudo de caso destaca a importância de mecanismos inovadores no atendimento das necessidades médicas dos pacientes. As alternativas de acesso precoce incluem: a) acesso por meio de estudos clínicos, com execução/desenvolvimento alinhada aos gestores de saúde e vinculada a estratégias futuras de acesso; b) compartilhamento de risco em nível regulatório, considerando as incertezas de eficácia e a possibilidade de retirada do mercado e reembolso em caso de resultados negativos; e c) pré-entrega do medicamento, com pagamento condicionado aos resultados positivos do estudo clínico de fase III. Embora as parcerias público-privadas em pesquisa clínica sejam subutilizadas, elas poderiam beneficiar todas as partes interessadas ao acelerar o desenvolvimento de medicamentos, facilitar o acesso precoce dos pacientes a medicamentos inovadores e gerar economias para o sistema de saúde, especialmente para doenças raras.
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Mucopolysaccharidose de type II , Maladies rares , Accès aux Médicaments Essentiels et aux Technologies de la SantéRésumé
Resumo Objetivo Identificar a atuação da Fiocruz em estudos clínicos relacionados à Covid-19. Analisar as diferentes terminologias utilizadas para se referir à participação da Fiocruz. Mapear a região desses estudos. Mensurar a quantidade dos estudos aprovados nas plataformas de registro de estudos clínicos e bases ético-regulatórias. Dentre estes, analisar as características metodológicas e de boas práticas dos protocolos dos estudos intervencionais. Métodos Foram revisadas as bases de dados da Agência Nacional de Vigilância Sanitária (ANVISA), Comissão Nacional de Ética em Pesquisa (Conep), Registro Brasileiro de Ensaios Clínicos (ReBEC), ClinicalTrials.gov, International Clinical Trials Registry Platform (ICTRP), US Food and Drug Administration (FDA) e Instituto Nacional de Propriedade Industrial (INPI). Resultados Foram encontrados 53 estudos clínicos sobre Covid-19 com a participação da Fiocruz em 39 destes como instituição proponente. Dentre os 53 estudos, 19 estão em plataformas de registro. Sobre os estudos intervencionais registrados, cinco são de prevenção e nove de tratamento. A intervenção mais analisada nestes estudos foi cloroquina/hidroxicloroquina. Observou-se ainda maior concentração dos estudos clínicos na Região Sudeste, com o total de 37. Conclusão Foram analisadas algumas limitações no delineamento metodológico que podem afetar o alcance dos estudos. Espera-se que os dados obtidos sejam utilizados para orientação futura de estudos clínicos sobre Covid-19 com participação da Fiocruz.
Abstract Objective To identify Fiocruz's performance in clinical studies related to Covid-19. Analyze the different terminologies used to refer to Fiocruz participation. Map the region of these studies. Measure the number of studies approved on clinical study registration platforms and regulatory ethical bases. Analyze the methodological characteristics and good practices of the interventional study protocols. Methods We reviewed databases of Brazilian National Research Ethics Committee, databases of Brazilian National Health Surveillance Agency (Agência Nacional de Vigilância Sanitária - ANVISA), Brazilian Clinical Trials Registry (Registro Brasileiro de Ensaios Clínicos - ReBEC), ClinicalTrials.gov, International Clinical Trials Registry Platform (ICTRP), US Food and Drug Administration (FDA) and Brazilian National Institute of Industrial Property (Instituto Nacional de Propriedade Industrial-INPI). Results 53 clinical studies on Covid-19 were found with the participation of Fiocruz in 39 of them as a proponent institution. Among the 53 studies, 19 are on registration platforms. Of the registered interventional studies, 5 are for prevention and 9 for treatment. The intervention most frequently evaluated in these studies was chloroquine / hydroxychloroquine. There was also a greater concentration of clinical studies in the southeastern region, with a total of 37 studies. Conclusion Some limitations in the methodological design were analyzed, which may affect the scope of the studies. It is expected that the data obtained will be used to guide future clinical studies on Covid-19 with Fiocruz participation.
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Osteonecrosis of the femoral head （ONFH） is a painful and debilitating disease caused by impaired blood supply to the femoral head and cellular and tissue degeneration， leading to gradual destruction of the bone structure and progressive collapse of the femoral head. The main pathological mechanism of ONFH is the disruption of the balance between bone absorption and the reconstruction of new bone， resulting from microcirculation damage and decreased cellular tissue ability. This imbalance leads to biomechanical changes and accelerates the pathological progression of ONFH. In the early stages， clinical manifestations may not be obvious， mainly presenting as pain or discomfort in the hip or groin area， which can be relieved after rest. In the later stage of the disease， pain intensifies， and limb shortening， lower limb weakness， difficulty walking， or limping may occur. Currently， western medicine commonly uses osteogenic agents， anticoagulants， and artificial joint replacement for treatment， but there are also many issues such as prosthesis loosening and infection. Research has shown that traditional Chinese medicine （TCM） treatment of ONFH takes a holistic approach and employs multi-functional， multi-target， and multi-system Chinese medicine therapies， ensuring the safety and effectiveness of the treatment. The osteoprotegerin （OPG）/receptor activator of nuclear factor-κB （RANK）/RANK ligand （RANKL） signaling pathway plays a crucial role in maintaining the dynamic balance of bone remodeling. TCM treatments utilize this pathway to promote apoptosis of osteoclasts， reduce bone resorption， and accelerate bone formation， thereby playing an important role in the prevention and treatment of ONFH. This paper reviewed the role of OPG/RANK/RANKL signaling pathway and related cytokine expression in ONFH by reviewing relevant literature in China and abroad and research status of Chinese medicinal monomers， Chinese medicinal formulations， and combinations with physical therapy in increasing osteoblast secretion， promoting OPG expression， enhancing cytokine expression levels， and inhibiting osteoclast activity for the prevention and treatment of ONFH. This paper is expected to provide new ideas and directions for TCM in the prevention and treatment of ONFH.
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Cerebral hemorrhage accounts for about 10%-15% of all strokes， and its pathogenesis is complex. Currently， the main clinical treatment is mainly medical symptomatic treatment， including the use of antihypertensive drugs， hypoglycemic drugs， and hemostatic drugs， and surgical treatment is required in some cases， but there is still a lack of effective treatment. In recent years， traditional Chinese medicine and proprietary Chinese medicine have been widely accepted for their stable efficacy， high safety， and low cost. Rhei Radix et Rhizoma is one of the most commonly used herbal medicines for the treatment of cerebral hemorrhage. This paper summarizes the relevant literature on the treatment of cerebral hemorrhage with Rhei Radix et Rhizoma and finds that its active ingredients are mainly anthraquinones， such as emodin， Rhei Radix et Rhizoma acid， and Rhei Radix et Rhizoma phenol. The herbal formulas are Da Chengqitang， Shengdi Dahuangtang， Liangxue Tongyufang， and Naoxueshu oral liquid. The effects involve protecting the blood-brain barrier， promoting hematoma absorption， reducing inflammation levels， decreasing lactic acid accumulation at the bleeding site， and increasing the expression of brain-derived neurotrophic factors. The pathways involved include aquaporin 4 （AQP4）， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， extracellular signal-regulated kinase 1/2 （ERK1/2）， Toll-like receptor 4 （TLR4）， nuclear transcription factor-κB （NF-κB）， nuclear factor E2-related factor 2 （Nrf2）， and Wnt3a/β-linked protein pathway. This paper summarizes the progress of clinical studies and animal experiments on the treatment of cerebral hemorrhage with active ingredients of Rhei Radix et Rhizoma and herbal compounds containing Rhei Radix et Rhizoma， so as to provide a reference for the treatment protocol of cerebral hemorrhage.
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With the upsurge of artificial intelligence(AI)technology in the medical field, its application in ophthalmology has become a cutting-edge research field. Notably, machine learning techniques have shown remarkable achievements in diagnosing, intervening, and predicting ophthalmic diseases. To meet the requirements of clinical research and fit the actual progress of clinical diagnosis and treatment of ophthalmic AI, the Ophthalmic Imaging and Intelligent Medicine Branch and the Intelligent Medicine Special Committee of Chinese Medicine Education Association organized experts to integrate recent evaluation reports of clinical AI research at home and abroad and formed a guideline on clinical research evaluation of AI in ophthalmology after several rounds of discussion and modification. The main content includes the background and method of developing this guideline, introduction to international guidelines on the clinical research evaluation of AI, and the evaluation methods of ophthalmic AI models. This guideline introduces general evaluation methods of clinical ophthalmic AI research, evaluation methods of clinical AI models, and common indices and formulae for clinical AI model evaluation in detail, and amply elaborates the evaluation method of clinical ophthalmic AI trials. This guideline aims to provide guidance and norms for clinical researchers of ophthalmic AI, promote the development of regularization and standardization, and further improve the overall level of clinical ophthalmic AI research evaluations.
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ObjectiveTo reveal the clinical efficacy of Yunpi Huatan Tongqiao prescription in relieving inflammation， hypoxia， and adenoidal hypertrophy （AH）， and improving the quality of sleep-disordered breathing in children with AH by promoting M2-type polarization of macrophages through a randomized double-blind clinical trial. MethodSeventy-one AH children who met the research criteria and were treated in the Department of Pediatrics of Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from March 2022 to February 2023 were divided into an observation group （36 cases） and a control group （35 cases）. A randomized double-blind method was adopted. The patients in the observation group were given Yunpi Huatan Tongqiao prescription combined with placebo of montelukast sodium chewable tablets， while those in the control group were given montelukast sodium chewable tablets combined with placebo of Yunpi Huatan Tongqiao prescription. The treatment course was 84 days. After treatment， the therapeutic effect and sleep monitoring indicators were compared. Before and after treatment， venous blood was collected to compare the levels of macrophage polarization-related inflammatory factors between the two groups. ResultThe adenoidal/nasopharyngeal space （A/N） integral in the nasal and pharyngeal lateral radiographs， After treatment， the AH therapeutic effect score， and the traditional Chinese medicine （TCM） syndrome therapeutic effect score in both groups were lower than those before treatment （P<0.01）. Compared with the control group after treatment， the observation group showed a more significant reduction in various integral levels （P<0.05， P<0.01）. The improvement degree of A/N in the nasal and pharyngeal lateral radiographs in the observation group was better than that in the control group （Z=-2.970， P<0.01）， and the total effective rate of the therapeutic effect of AH （χ2=7.715， P<0.01） and the TCM syndrome therapeutic effect （χ2=13.239， P<0.01） were superior to those in the control group. The levels of interleukin-6 （IL-6） and tumor necrosis factor-alpha （TNF-α） in both groups after treatment were lower， and the level of interleukin-10 （IL-10） was higher than those before treatment （P<0.01）. The level of transforming growth factor-beta （TGF-β） showed an increasing trend， but the difference was not statistically significant. Compared with the control group after treatment， the observation group showed more significant improvement in IL-10 and TNF-α levels （P<0.01）， a decreasing trend in IL-6， and an increasing trend in TGF-β， but the difference was not statistically significant. Compared with the results before treatment， the apnea-hypopnea index （AHI） and oxygen desaturation index （ODI） in both groups decreased significantly （P<0.01）. The observation group showed a significant reduction in the duration of the longest apnea and the longest hypopnea， as well as a significant increase in the mean and lowest oxygen saturation （P<0.01）. The control group also showed improvements in the above indicators， but the difference was not statistically significant. Compared with the control group after treatment， the observation group showed a more significant improvement in AHI， ODI， the duration of the longest hypopnea， and mean and lowest oxygen saturation （P<0.05， P<0.01）. There was a decreasing trend in the longest duration of apnea， but the difference was not statistically significant. ConclusionYunpi Huatan Tongqiao prescription can reduce the size of adenoids， alleviate clinical symptoms and signs in AH children， improve the constitution characterized by "spleen deficiency and phlegm obstruction"， reduce the occurrence of sleep-disordered breathing events， alleviate the degree of hypoxia in the child's body during sleep at night， and has satisfactory clinical efficacy. The improvement of clinical symptoms and sleep quality in AH children by Yunpi Huatan Tongqiao prescription may be achieved by promoting macrophage polarization from M1 to M2.
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ObjectiveTo explore the effects of Bushen Jianpi prescription on the autophagy and phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway in the patients with aplastic anemia （AA）. MethodA total of 30 AA patients admitted to Xiyuan Hospital and 6 healthy donors who were prepared to undergo peripheral blood hematopoietic stem cell transplantation in 304 Hospital from September 2020 to August 2021 were enrolled and assigned into an AA group and a control group. The AA group was treated with Bushen Jianpi prescription combined with cyclosporin A （CsA） and androgen for 3 months. The mononuclear cells from bone marrow in the AA group before and after treatment and the peripheral blood of the control group were collected. Transmission electron microscopy was then employed to detect autophagosomes. Western blotting was employed to determine the protein levels of microtuble-associated protein 1 light chain 3 （LC3）Ⅰ， LC3Ⅱ， mTOR， phosphorylated （p）-mTOR， Akt， p-Akt， PI3K， and p-PI3K， and real-time polymerase chain reaction （PCR） to determine the mRNA levels of LC3， mTOR， Akt， and PI3K. ResultIn the AA group， the treatment was completed in 29 patients， and the total response rate was 51.72% （15/29）. ① The AA group showed lower levels of white blood cell （WBC）， hemoglobin （HGB）， platelet （PLT）， and absolute neutrophil count （ANC） in the peripheral blood （P<0.01） and lower number of intracellular autophagosomes than the control group before treatment. Moreover， the AA group showed lower mRNA level of LC3 （P<0.01） and protein levels of LC3Ⅰ and LC3Ⅱ （P<0.01） and higher mRNA levels of mTOR， Akt， and PI3Kα （P<0.01） and protein levels of Akt， p-Akt， PI3K， p-PI3K， mTOR， and p-mTOR （P<0.01） than the control group. ② In AA group， the levels of HGB and PLT elevated （P<0.05） and the number of intracellular autophagosomes increased after treatment compared with those before treatment. Moreover， the mRNA level of LC3 and the protein levels of LC3Ⅰ and LC3Ⅱ were up-regulated （P<0.01）， the mRNA levels of mTOR， Akt， and PI3Kα （P<0.01） and the protein levels of Akt， p-PI3K （P<0.01）， p-Akt， PI3K， mTOR， p-mTOR （P<0.05） were down-regulated after treatment. ConclusionAA patients show lower autophagy levels， while Bushen Jianpi prescription can effectively improve the autophagy level and down-regulated the expression of PI3K/Akt/mTOR signaling pathway in AA patients.