Oxidative stress disturbs the balance between the production of reactive oxygen species(ROS)and the detoxification biological process.It plays an important role in the development and progression of many chronic disea...Oxidative stress disturbs the balance between the production of reactive oxygen species(ROS)and the detoxification biological process.It plays an important role in the development and progression of many chronic diseases.Upon exposure to oxidative stress or the inducers of ROS,the cellular nucleus undergoes some biological processes via different signaling pathways,such as stress adaption through the forkhead box O signaling pathway,inflammatory response through the IκB kinase/nuclear factor-κB signaling pathway,hypoxic response via the hypoxia-inducible factor/prolyl hydroxylase domain proteins pathway,DNA repair or apoptosis through the p53 signaling pathway,and antioxidant response through the Kelch-like ECH-associated protein 1/nuclear factor E2-related factor 2 signaling pathway.These processes are involved in many diseases.Therefore,oxidative stress has gained more attraction as a targeting process for disease treatment.Meanwhile,anti-oxidative stress agents have been widely explored in pre-clinical trials.However,only limited clinical trials are performed to evaluate the efficacy of anti-oxidative stress agents or antioxidants in diseases.In this letter,we further discuss the current clinical trials related to anti-oxidative stress treatment in different diseases.More pre-clinical studies and clinical trials are expected to use anti-oxidative stress strategies as disease treatment or dietary supplementation to improve disease treatment outcomes.展开更多
Retinal and optic nerve diseases are degenerative ocular pathologies which lead to irreversible visual loss. Since the advanced therapies availability, cell-based therapies offer a new all-encompassing approach. Advan...Retinal and optic nerve diseases are degenerative ocular pathologies which lead to irreversible visual loss. Since the advanced therapies availability, cell-based therapies offer a new all-encompassing approach. Advances in the knowledge of neuroprotection, immunomodulation and regenerative properties of mesenchymal stem cells(MSCs) have been obtained by several preclinical studies of various neurodegenerative diseases. It has provided the opportunity to perform the translation of this knowledge to prospective treatment approaches for clinical practice. Since 2008, several first steps projecting new treatment approaches, have been taken regarding the use of cell therapy in patients with neurodegenerative pathologies of optic nerve and retina. Most of the clinical trials using MSCs are in Ⅰ/Ⅱ phase, recruiting patients or ongoing, and they have as main objective the safety assessment of MSCs using various routes of administration. However, it is important to recognize that, there is still a long way to go to reach clinical trials phase Ⅲ-Ⅳ. Hence, it is necessary to continue preclinical and clinical studies to improve this new therapeutic tool. This paper reviews the latest progress of MSCs in human clinical trials for retinal and optic nerve diseases.展开更多
Objective: Psychedelic drug therapy is banned in all countries of the world except Australia, where the government regulatory watchdog, the Therapeutic Goods Administration, is planning to allow approved psychiatrists...Objective: Psychedelic drug therapy is banned in all countries of the world except Australia, where the government regulatory watchdog, the Therapeutic Goods Administration, is planning to allow approved psychiatrists, as of July 1, 2023, to prescribe psilocybin to treat depression and MDMA to treat post-traumatic stress disorder, a move precipitated by the U.S. Food and Drug Administration’s designation of these two drugs as “breakthrough therapy”. The objective of the present article is to demonstrate that the evidence on which the FDA and then the TGA relied is irretrievably flawed and should be dismissed. Method: Expert review of psychedelic therapy clinical trials and specifically of the methodology and measures used. Results: The present review demonstrates that the studies the U.S. FDA and the Australian TGA relied on to approve these two psychedelic drugs for therapy are irretrievably flawed. All future trials will follow the same procedure and are therefore bound to be flawed as well. Conclusions: Psychedelic drug studies have so far provided no trustworthy evidence of their effectiveness for treating mental disorders and are not likely to produce this evidence in the future. Psychedelic drug therapy is in any event impractical because of its specialized training requirements and very high treatment costs. It is also dangerous because false publicity about its effectiveness will almost certainly lead to unsupervised self-dosing with drugs that not only are illegal but have an unacceptably high addiction rate.展开更多
Respiratory diseases,including coronavirus disease 2019 and chronic obstructive pulmonary disease(COPD),are leading causes of global fatality.There are no effective and curative treatments,but supportive care only.Cel...Respiratory diseases,including coronavirus disease 2019 and chronic obstructive pulmonary disease(COPD),are leading causes of global fatality.There are no effective and curative treatments,but supportive care only.Cell therapy is a promising therapeutic strategy for refractory and unmanageable pulmonary illnesses,as proved by accumulating preclinical studies.Stem cells consist of totipotent,pluripotent,multipotent,and unipotent cells with the potential to differentiate into cell types requested for repair.Mesenchymal stromal cells,endothelial progenitor cells,peripheral blood stem cells,and lung progenitor cells have been applied to clinical trials.To date,the safety and feasibility of stem cell and extracellular vesicles administration have been confirmed by numerous phase I/II trials in patients with COPD,acute respiratory distress syndrome,bronchial dysplasia,idiopathic pulmonary fibrosis,pulmonary artery hypertension,and silicosis.Five routes and a series of doses have been tested for tolerance and advantages of different regimes.In this review,we systematically summarize the global trends for the cell therapy of common airway and lung diseases registered for clinical trials.The future directions for both new clinical trials and preclinical studies are discussed.展开更多
<strong>Objective</strong><span style="font-family:;" "=""><span style="font-family:Verdana;"><strong>:</strong> To explore the establishment and ...<strong>Objective</strong><span style="font-family:;" "=""><span style="font-family:Verdana;"><strong>:</strong> To explore the establishment and roles of study nurses in IBD drug clinical trials. </span><b><span style="font-family:Verdana;">Methods</span></b><span style="font-family:Verdana;">: The management experience of this department’s study nurses in IBD drug clinical trials was retrospectively analyzed. </span><b><span style="font-family:Verdana;">Results</span></b><span style="font-family:Verdana;">: The study nurses played very important roles at all links during the preliminary preparation of IBD drug clinical trials, the whole-process management after project initiation, and the later work of project conclusion. </span><b><span style="font-family:Verdana;">Conclusions</span></b><span style="font-family:Verdana;">: As direct participants in drug clinical trials, study nurses play a very important role in ensuring standardization of the trial process, safeguarding patient’s rights and safety, and assisting investigators in carrying out study works smoothly.</span></span>展开更多
Objective To provide a basis for future regulation reform of drug clinical trials in China in the context of the continuous deepening of drug regulation reform. Methods Literature review and regulation study were cond...Objective To provide a basis for future regulation reform of drug clinical trials in China in the context of the continuous deepening of drug regulation reform. Methods Literature review and regulation study were conducted to analyze the course and development trend of drug clinical trial regulation in China. Results and Conclusion It is found that the regulation system and the standardization for clinical trials in China are gradually improving, but there is still a gap compared with developed countries. In the future, the regulation authorities still need to further improve relevant regulations, clarify regulation responsibilities, and to improve the drug clinical trial review system to ensure the quality of clinical trials and the safety and effectiveness of listed drugs.展开更多
Mesenchymal stem cell(MSC)therapy has attracted the attention of scientists and clinicians around the world.Basic and pre-clinical experimental studies have highlighted the positive effects of MSC treatment after spin...Mesenchymal stem cell(MSC)therapy has attracted the attention of scientists and clinicians around the world.Basic and pre-clinical experimental studies have highlighted the positive effects of MSC treatment after spinal cord and peripheral nerve injury.These effects are believed to be due to their ability to differentiate into other cell lineages,modulate inflammatory and immunomodulatory responses,reduce cell apoptosis,secrete several neurotrophic factors and respond to tissue injury,among others.There are many pre-clinical studies on MSC treatment for spinal cord injury(SCI)and peripheral nerve injuries.However,the same is not true for clinical trials,particularly those concerned with nerve trauma,indicating the necessity of more well-constructed studies showing the benefits that cell therapy can provide for individuals suffering the consequences of nerve lesions.As for clinical trials for SCI treatment the results obtained so far are not as beneficial as those described in experimental studies.For these reasons basic and pre-clinical studies dealing with MSC therapy should emphasize the standardization of protocols that could be translated to the clinical set with consistent and positive outcomes.This review is based on pre-clinical studies and clinical trials available in the literature from 2010 until now.At the time of writing this article there were 43 and 36 pre-clinical and 19 and 1 clinical trials on injured spinal cord and peripheral nerves,respectively.展开更多
INTRODUCTION E radication of Helicobacter pylori(Hp)infection isgenerally not easy.Various clinical regimens havebeen recommended in the literature.With theexperience from the other countries and the practicein China,...INTRODUCTION E radication of Helicobacter pylori(Hp)infection isgenerally not easy.Various clinical regimens havebeen recommended in the literature.With theexperience from the other countries and the practicein China,Chinese doctors have tried manyregimens.In this study,we collected and pooled thedata from Chinese literature to evaluate the effectof different regimens in Chinese patients infectedwith Hp.展开更多
Recurrence is a major concern for adult patients with glioblastomas(GBMs), and the prognosis remains poor.Although several therapies have been assessed, most of them have not achieved satisfactory results. Therefore, ...Recurrence is a major concern for adult patients with glioblastomas(GBMs), and the prognosis remains poor.Although several therapies have been assessed, most of them have not achieved satisfactory results. Therefore, there is currently no standard treatment for adult recurrent GBM(r GBM). Here, we review the results of clinical trials for the systematic therapy of r GBM. Regorafenib, rindopepimut and neoadjuvant programmed death 1(PD-1)inhibitors are promising agents for r GBM, while regorafenib is effective in both O6-methylguanine DNA methyltransferase(MGMT) promoter methylated and unmethylated patients. Temozolomide rechallenge and alkylating agents combined with bevacizumab can be useful for patients with MGMT methylation, and patients with isocitrate dehydrogenase(IDH) mutations or second recurrence can benefit from vocimagene amiretrorepvec(Toca511). Some phase I trials on targeted therapy and immunotherapy have shown positive results, and results from further studies are expected. In addition to the analysis of existing clinical trial results, forthcoming trials should be well designed, and patients are encouraged to participate in appropriate clinical trials.展开更多
AIM:To present statistical tools to model and optimize the cost of a randomized clinical trial as a function of the stringency of patient inclusion criteria.METHODS: We consider a two treatment, dichotomous outcome tr...AIM:To present statistical tools to model and optimize the cost of a randomized clinical trial as a function of the stringency of patient inclusion criteria.METHODS: We consider a two treatment, dichotomous outcome trial that includes a proportion of patients who are strong responders to the tested intervention. Patients are screened for inclusion using an arbitrary number of test results that are combined into an aggregate suitability score. The screening score is regarded as a diagnostic test for the responsive phenotype, having a specific cutoff value for inclusion and a particular sensitivity and specificity. The cutoff is a measure of stringency of inclusion criteria. Total cost is modeled as a function of the cutoff value, number of patients screened, the number of patients included, the case occurrence rate, response probabilities for control and experimental treatments, and the trial duration required to produce a statistically significant result with a specified power. Regression methods are developed to estimate relevant model parameters from pilot data in an adaptive trial design. RESULTS: The patient numbers and total cost are strongly related to the choice of the cutoff for inclusion. Clear cost minimums exist between 5.6 and 6.1 on arepresentative 10-point scale of exclusiveness. Potential cost savings for typical trial scenarios range in millions of dollars. As the response rate for controls approaches 50%, the proper choice of inclusion criteria can mean the difference between a successful trial and a failed trial. CONCLUSION: Early formal estimation of optimal inclusion criteria allows planning of clinical trials to avoid high costs, excessive delays, and moral hazards of Type II errors.展开更多
The hypothesis in drug clinical trials is that the drug is better than a placebo in patients suffering from a disease. The unstated assumption is that the drug cures the disease or is a powerful treatment for the dise...The hypothesis in drug clinical trials is that the drug is better than a placebo in patients suffering from a disease. The unstated assumption is that the drug cures the disease or is a powerful treatment for the disease. This is an incorrect assumption. Drugs do not cure or treat diseases. The body heals itself; drugs promote this ability of the body to heal itself. Placebos are assumed to be inactive; however, placebos can also promote the ability of the body to heal itself. Placebos are actually treatments that can stimulate endogenous healing mechanisms. The possible place of placebos in health management is controversial. Clinical trial design should be altered. The hypothesis of clinical trials should be that the drug speeds up or improves the healing of the patient, putting patient healing as the first objective. Placebos should not be used as controls but could be tested as drugs in their own right. The control in clinical trials should be no treatment. Alternatively, new drugs could be compared to existing drugs in clinical trials.展开更多
Background:The wide use of antibody‐drug conjugates(ADCs)is transforming the cancer‐treatment landscape.Understanding the treatment‐related adverse events(AEs)of ADCs is crucial for their clinical application.We co...Background:The wide use of antibody‐drug conjugates(ADCs)is transforming the cancer‐treatment landscape.Understanding the treatment‐related adverse events(AEs)of ADCs is crucial for their clinical application.We conducted a meta‐analysis to analyze the profile and incidence of AEs related to ADC use in the treatment of solid tumors and hematological malignancies.Methods:We searched the PubMed,Embase,and Cochrane Library databases for articles published from January 2001 to October 2022.The overall profile and incidence of all‐grade and grade≥3 treatment‐related AEs were the primary outcomes of the analysis.Results:A total of 138 trials involving 15,473 patients were included in this study.The overall incidence of any‐grade treatment‐related AEs was 100.0%(95%confidence interval[CI]:99.9%–100.0%;I2=89%)and the incidence of grade≥3 treatment‐related AEs was 6.2%(95%CI:3.0%–12.4%;I2=99%).Conclusions:This study provides a comprehensive overview of AEs related to ADCs used for cancer treatment.ADC use resulted in a high incidence of any‐grade AEs but a low incidence of grade≥3 AEs.The AE profiles and incidence differed according to cancer type,ADC type,and ADC components.展开更多
To understand the current situation of institutional registration in Shaanxi Province after the implementation ofregistration system management in drug clinical trial institutions.Relevant information was collected on...To understand the current situation of institutional registration in Shaanxi Province after the implementation ofregistration system management in drug clinical trial institutions.Relevant information was collected on the“Announcement on the Accreditation of Drug Clinical Trial Institutions”issued by the National Medical Products Administration from 2005 to August 2022,the record management information system of drug and medical device clinical trial institutions,and the drug clinical trial registration and information publicity platform.A retrospective analysis was carried out in terms of institutional development,regional distribution,registered majors,principal investigators,and the number of drug clinical trials.After the implementation of institution registration,the number of drug clinical trial institutions in Shaanxi Province increased by 47.4%,884 principal investigators were registered,the number of registered majors expanded from 58 qualified to 117,and the professional scope increased by 50.4%.The policy of institution registration is conducive to promoting the rational use of medical resources and the development of drug clinical trial institutions and improving the healthy development of the pharmaceutical industry in Shaanxi Province.展开更多
Glioblastoma(GBM)is the most common primary central nervous system tumor,whose prognosis remains poor under the sequential standard of care,such as neurosurgery followed by concurrent temozolomide radiochemotherapy an...Glioblastoma(GBM)is the most common primary central nervous system tumor,whose prognosis remains poor under the sequential standard of care,such as neurosurgery followed by concurrent temozolomide radiochemotherapy and adjuvant temozolomide chemotherapy in the presence or absence of tumor treating fields.Accordingly,the advent of molecular targeted therapy and immunotherapy has opened a new era of tumor management.A diverse range of targeted drugs have been tested in patients with GBM in phase III clinical trials.However,these drugs are ineffective for all patients,as evidenced by the fact that only a minority of patients in these trials showed prolonged survival.Furthermore,there are several published phase III clinical trials that involve immune checkpoint inhibitors,peptide vaccines,dendritic cell vaccines,and virotherapy.Accordingly,this review comprehensively overviews existing studies of targeted drugs and immunotherapy for glioma and discusses the challenge and perspective of targeted drugs and immunotherapy for glioma to clarify future directions.展开更多
Children recurrent respiratory infection (CRRI) indicates that children suffer from frequent infections along the upper or lower respiratory tract for a certain number of times. It is not an independent disease but ...Children recurrent respiratory infection (CRRI) indicates that children suffer from frequent infections along the upper or lower respiratory tract for a certain number of times. It is not an independent disease but a clinical syndrome mostly brought about by some basic diseases such as nonspecific immunity, specific immune suppression or deficiency disease, congenital bronchopulmonary dysplasia, vitamin or microelement deficiency, or is induced by some factors such as smoking, cross infection, and nursing errors.(2) Clinically, CRRI is commonly treated by anti-infective agents, symptomatic and supportive treatment, and immune-regulatory therapy. However, the therapeutic effectiveness is always imperfect, which could even lead to a premium on asthma, or nephritis, etc.展开更多
New targeted therapies have been developed to overcome resistance to endocrine therapy(ET)and improve the outcome of HR^(+)/HER2^(-)advanced breast cancer(ABC).We conducted a meta-analysis and systemic review on rando...New targeted therapies have been developed to overcome resistance to endocrine therapy(ET)and improve the outcome of HR^(+)/HER2^(-)advanced breast cancer(ABC).We conducted a meta-analysis and systemic review on randomized controlled trials evaluating various targeted therapies in combination with ET in HR^(+)/HER2^(-)ABC.PUBMED and EMBASE databases were searched for eligible trials.Hazard ratios(HRs)for progression-free survival(PFS),odds ratios(ORs)for objective response rate(ORR),clinical benefit rate(CBR),and toxicity were meta-analyzed.Twenty-six studies with data on 10347 patients were included and pooled.The addition of cyclin-dependent kinase 4/6 inhibitors to ET significantly improved median PFS(pooled HR=0.547,P<0.001),overall survival(pooled HR=0.755,P<0.001),and tumor response rates(ORR,pooled OR=1.478,P<0.001;CBR,pooled OR=1.201,P<0.001)with manageable toxicities(pooled OR=3.280,P<0.001).The mammalian targets of rapamycin inhibitors and exemestane were not clinically beneficial for this pooled population including ET-naïve and ET-resistant patients.Moderate improvement in PFS(pooled HR=0.686,P<0.001)yet pronounced toxicities(pooled OR=2.154,P<0.001)were noted in the combination of phosphatidylinositol-4,5-bisphosphate 3-kinase inhibitors with fulvestrant.Future studies are warranted to optimize the population and the dosing sequence of these available options.展开更多
Molecular target inhibitors have been regularly approved by Food and Drug Administration(FDA)for tumor treatment,and most of them intervene in tumor cell proliferation and metabolism.The RAS-RAF-MEK-ERK pathway is a c...Molecular target inhibitors have been regularly approved by Food and Drug Administration(FDA)for tumor treatment,and most of them intervene in tumor cell proliferation and metabolism.The RAS-RAF-MEK-ERK pathway is a conserved signaling pathway that plays vital roles in cell proliferation,survival,and differentiation.The aberrant activation of the RAS-RAF-MEK-ERK signaling pathway induces tumors.About 33%of tumors harbor RAS mutations,while 8%of tumors are driven by RAF mutations.Great efforts have been dedicated to targeting the signaling pathway for cancer treatment in the past decades.In this review,we summarized the development of inhibitors targeting the RAS-RAF-MEK-ERK pathway with an emphasis on those used in clinical treatment.Moreover,we discussed the potential combinations of inhibitors that target the RAS-RAF-MEK-ERK signaling pathway and other signaling pathways.The inhibitors targeting the RAS-RAF-MEK-ERK pathway have essentially modified the therapeutic strategy against various cancers and deserve more attention in the current cancerresearchandtreatment.展开更多
This study aimed to construct a quality management model for phase I clinical drug trials.A cross-sectional survey was conducted and data were collected from 604 respondents at 69 institutions in China engaged in phas...This study aimed to construct a quality management model for phase I clinical drug trials.A cross-sectional survey was conducted and data were collected from 604 respondents at 69 institutions in China engaged in phase I clinical drug trials.Exploratory and confirmatory factor analyses were used to develop the survey tool.Structural equation modeling was used to construct a quality management model for phase I clinical drug trials.The results showed that the final survey tool had good reliability and validity(Cronbach’sα=0.938,root mean square error of approximation=0.074,comparative fit index=0.962,and Tucker—Lewis index=0.955).The model included five dimensions:government regulation,industry management,medical institution management,research team management,and contract research organization(CRO)management.In total,22 measurement items were obtained.The structural equation model indicated government regulation,industry management,medical institution management,and CRO management significantly affected the quality of phase I clinical drug trials(β=0.195,β=0.331,β=0.279,andβ=−0.267,respectively;P<0.05).Research team management had no effect on the quality of trials(β=0.041,P=0.610).In conclusion,the model is valuable for identifying factors influencing phase I clinical drug trials and guiding quality management practices.展开更多
Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monocl...Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monoclonal antibodies that selectively inhibit programmed cell death-1(PD-1)activity has now become standard of care in the treatment of ESCC in metastatic settings,and has a high expectation to provide clinical benefit during perioperative period.Further,anti-cytotoxic T-lymphocyte–associated protein 4(CTLA-4)monoclonal antibody has also been approved in the treatment of recurrent/metastatic ESCC in combination with anti-PD-1 antibody.Well understanding of the existing evidence of immune-based treatments for ESCC,as well as recent clinical trials on various combinations with chemotherapy for different clinical settings including neoadjuvant,adjuvant,and metastatic diseases,may provide future prospects of ESCC treatment for better patient outcomes.展开更多
文摘Oxidative stress disturbs the balance between the production of reactive oxygen species(ROS)and the detoxification biological process.It plays an important role in the development and progression of many chronic diseases.Upon exposure to oxidative stress or the inducers of ROS,the cellular nucleus undergoes some biological processes via different signaling pathways,such as stress adaption through the forkhead box O signaling pathway,inflammatory response through the IκB kinase/nuclear factor-κB signaling pathway,hypoxic response via the hypoxia-inducible factor/prolyl hydroxylase domain proteins pathway,DNA repair or apoptosis through the p53 signaling pathway,and antioxidant response through the Kelch-like ECH-associated protein 1/nuclear factor E2-related factor 2 signaling pathway.These processes are involved in many diseases.Therefore,oxidative stress has gained more attraction as a targeting process for disease treatment.Meanwhile,anti-oxidative stress agents have been widely explored in pre-clinical trials.However,only limited clinical trials are performed to evaluate the efficacy of anti-oxidative stress agents or antioxidants in diseases.In this letter,we further discuss the current clinical trials related to anti-oxidative stress treatment in different diseases.More pre-clinical studies and clinical trials are expected to use anti-oxidative stress strategies as disease treatment or dietary supplementation to improve disease treatment outcomes.
基金Supported by A grants from the Consejería de Educación de la Junta de Castilla y León,No.VA118U14the Centro en Red de Medicina Regenerativa y Terapia Celular de la Junta de Castilla y León,47011 Valladolid
文摘Retinal and optic nerve diseases are degenerative ocular pathologies which lead to irreversible visual loss. Since the advanced therapies availability, cell-based therapies offer a new all-encompassing approach. Advances in the knowledge of neuroprotection, immunomodulation and regenerative properties of mesenchymal stem cells(MSCs) have been obtained by several preclinical studies of various neurodegenerative diseases. It has provided the opportunity to perform the translation of this knowledge to prospective treatment approaches for clinical practice. Since 2008, several first steps projecting new treatment approaches, have been taken regarding the use of cell therapy in patients with neurodegenerative pathologies of optic nerve and retina. Most of the clinical trials using MSCs are in Ⅰ/Ⅱ phase, recruiting patients or ongoing, and they have as main objective the safety assessment of MSCs using various routes of administration. However, it is important to recognize that, there is still a long way to go to reach clinical trials phase Ⅲ-Ⅳ. Hence, it is necessary to continue preclinical and clinical studies to improve this new therapeutic tool. This paper reviews the latest progress of MSCs in human clinical trials for retinal and optic nerve diseases.
文摘Objective: Psychedelic drug therapy is banned in all countries of the world except Australia, where the government regulatory watchdog, the Therapeutic Goods Administration, is planning to allow approved psychiatrists, as of July 1, 2023, to prescribe psilocybin to treat depression and MDMA to treat post-traumatic stress disorder, a move precipitated by the U.S. Food and Drug Administration’s designation of these two drugs as “breakthrough therapy”. The objective of the present article is to demonstrate that the evidence on which the FDA and then the TGA relied is irretrievably flawed and should be dismissed. Method: Expert review of psychedelic therapy clinical trials and specifically of the methodology and measures used. Results: The present review demonstrates that the studies the U.S. FDA and the Australian TGA relied on to approve these two psychedelic drugs for therapy are irretrievably flawed. All future trials will follow the same procedure and are therefore bound to be flawed as well. Conclusions: Psychedelic drug studies have so far provided no trustworthy evidence of their effectiveness for treating mental disorders and are not likely to produce this evidence in the future. Psychedelic drug therapy is in any event impractical because of its specialized training requirements and very high treatment costs. It is also dangerous because false publicity about its effectiveness will almost certainly lead to unsupervised self-dosing with drugs that not only are illegal but have an unacceptably high addiction rate.
文摘Respiratory diseases,including coronavirus disease 2019 and chronic obstructive pulmonary disease(COPD),are leading causes of global fatality.There are no effective and curative treatments,but supportive care only.Cell therapy is a promising therapeutic strategy for refractory and unmanageable pulmonary illnesses,as proved by accumulating preclinical studies.Stem cells consist of totipotent,pluripotent,multipotent,and unipotent cells with the potential to differentiate into cell types requested for repair.Mesenchymal stromal cells,endothelial progenitor cells,peripheral blood stem cells,and lung progenitor cells have been applied to clinical trials.To date,the safety and feasibility of stem cell and extracellular vesicles administration have been confirmed by numerous phase I/II trials in patients with COPD,acute respiratory distress syndrome,bronchial dysplasia,idiopathic pulmonary fibrosis,pulmonary artery hypertension,and silicosis.Five routes and a series of doses have been tested for tolerance and advantages of different regimes.In this review,we systematically summarize the global trends for the cell therapy of common airway and lung diseases registered for clinical trials.The future directions for both new clinical trials and preclinical studies are discussed.
文摘<strong>Objective</strong><span style="font-family:;" "=""><span style="font-family:Verdana;"><strong>:</strong> To explore the establishment and roles of study nurses in IBD drug clinical trials. </span><b><span style="font-family:Verdana;">Methods</span></b><span style="font-family:Verdana;">: The management experience of this department’s study nurses in IBD drug clinical trials was retrospectively analyzed. </span><b><span style="font-family:Verdana;">Results</span></b><span style="font-family:Verdana;">: The study nurses played very important roles at all links during the preliminary preparation of IBD drug clinical trials, the whole-process management after project initiation, and the later work of project conclusion. </span><b><span style="font-family:Verdana;">Conclusions</span></b><span style="font-family:Verdana;">: As direct participants in drug clinical trials, study nurses play a very important role in ensuring standardization of the trial process, safeguarding patient’s rights and safety, and assisting investigators in carrying out study works smoothly.</span></span>
文摘Objective To provide a basis for future regulation reform of drug clinical trials in China in the context of the continuous deepening of drug regulation reform. Methods Literature review and regulation study were conducted to analyze the course and development trend of drug clinical trial regulation in China. Results and Conclusion It is found that the regulation system and the standardization for clinical trials in China are gradually improving, but there is still a gap compared with developed countries. In the future, the regulation authorities still need to further improve relevant regulations, clarify regulation responsibilities, and to improve the drug clinical trial review system to ensure the quality of clinical trials and the safety and effectiveness of listed drugs.
文摘Mesenchymal stem cell(MSC)therapy has attracted the attention of scientists and clinicians around the world.Basic and pre-clinical experimental studies have highlighted the positive effects of MSC treatment after spinal cord and peripheral nerve injury.These effects are believed to be due to their ability to differentiate into other cell lineages,modulate inflammatory and immunomodulatory responses,reduce cell apoptosis,secrete several neurotrophic factors and respond to tissue injury,among others.There are many pre-clinical studies on MSC treatment for spinal cord injury(SCI)and peripheral nerve injuries.However,the same is not true for clinical trials,particularly those concerned with nerve trauma,indicating the necessity of more well-constructed studies showing the benefits that cell therapy can provide for individuals suffering the consequences of nerve lesions.As for clinical trials for SCI treatment the results obtained so far are not as beneficial as those described in experimental studies.For these reasons basic and pre-clinical studies dealing with MSC therapy should emphasize the standardization of protocols that could be translated to the clinical set with consistent and positive outcomes.This review is based on pre-clinical studies and clinical trials available in the literature from 2010 until now.At the time of writing this article there were 43 and 36 pre-clinical and 19 and 1 clinical trials on injured spinal cord and peripheral nerves,respectively.
文摘INTRODUCTION E radication of Helicobacter pylori(Hp)infection isgenerally not easy.Various clinical regimens havebeen recommended in the literature.With theexperience from the other countries and the practicein China,Chinese doctors have tried manyregimens.In this study,we collected and pooled thedata from Chinese literature to evaluate the effectof different regimens in Chinese patients infectedwith Hp.
基金supported by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (No. 2016-I2M2-001)the Beijing Municipal Natural Science Foundation [No. 7202150 and 19JCZDJC 64200(Z)]the Tsinghua University-Peking Union Medical College Hospital Initiative Scientific Research Program (No. 2019ZLH101)。
文摘Recurrence is a major concern for adult patients with glioblastomas(GBMs), and the prognosis remains poor.Although several therapies have been assessed, most of them have not achieved satisfactory results. Therefore, there is currently no standard treatment for adult recurrent GBM(r GBM). Here, we review the results of clinical trials for the systematic therapy of r GBM. Regorafenib, rindopepimut and neoadjuvant programmed death 1(PD-1)inhibitors are promising agents for r GBM, while regorafenib is effective in both O6-methylguanine DNA methyltransferase(MGMT) promoter methylated and unmethylated patients. Temozolomide rechallenge and alkylating agents combined with bevacizumab can be useful for patients with MGMT methylation, and patients with isocitrate dehydrogenase(IDH) mutations or second recurrence can benefit from vocimagene amiretrorepvec(Toca511). Some phase I trials on targeted therapy and immunotherapy have shown positive results, and results from further studies are expected. In addition to the analysis of existing clinical trial results, forthcoming trials should be well designed, and patients are encouraged to participate in appropriate clinical trials.
文摘AIM:To present statistical tools to model and optimize the cost of a randomized clinical trial as a function of the stringency of patient inclusion criteria.METHODS: We consider a two treatment, dichotomous outcome trial that includes a proportion of patients who are strong responders to the tested intervention. Patients are screened for inclusion using an arbitrary number of test results that are combined into an aggregate suitability score. The screening score is regarded as a diagnostic test for the responsive phenotype, having a specific cutoff value for inclusion and a particular sensitivity and specificity. The cutoff is a measure of stringency of inclusion criteria. Total cost is modeled as a function of the cutoff value, number of patients screened, the number of patients included, the case occurrence rate, response probabilities for control and experimental treatments, and the trial duration required to produce a statistically significant result with a specified power. Regression methods are developed to estimate relevant model parameters from pilot data in an adaptive trial design. RESULTS: The patient numbers and total cost are strongly related to the choice of the cutoff for inclusion. Clear cost minimums exist between 5.6 and 6.1 on arepresentative 10-point scale of exclusiveness. Potential cost savings for typical trial scenarios range in millions of dollars. As the response rate for controls approaches 50%, the proper choice of inclusion criteria can mean the difference between a successful trial and a failed trial. CONCLUSION: Early formal estimation of optimal inclusion criteria allows planning of clinical trials to avoid high costs, excessive delays, and moral hazards of Type II errors.
文摘The hypothesis in drug clinical trials is that the drug is better than a placebo in patients suffering from a disease. The unstated assumption is that the drug cures the disease or is a powerful treatment for the disease. This is an incorrect assumption. Drugs do not cure or treat diseases. The body heals itself; drugs promote this ability of the body to heal itself. Placebos are assumed to be inactive; however, placebos can also promote the ability of the body to heal itself. Placebos are actually treatments that can stimulate endogenous healing mechanisms. The possible place of placebos in health management is controversial. Clinical trial design should be altered. The hypothesis of clinical trials should be that the drug speeds up or improves the healing of the patient, putting patient healing as the first objective. Placebos should not be used as controls but could be tested as drugs in their own right. The control in clinical trials should be no treatment. Alternatively, new drugs could be compared to existing drugs in clinical trials.
基金the Thousand Talents of Program of High-end Innovation of Qinghai Province in China(for Dr.Jiuda Zhao).
文摘Background:The wide use of antibody‐drug conjugates(ADCs)is transforming the cancer‐treatment landscape.Understanding the treatment‐related adverse events(AEs)of ADCs is crucial for their clinical application.We conducted a meta‐analysis to analyze the profile and incidence of AEs related to ADC use in the treatment of solid tumors and hematological malignancies.Methods:We searched the PubMed,Embase,and Cochrane Library databases for articles published from January 2001 to October 2022.The overall profile and incidence of all‐grade and grade≥3 treatment‐related AEs were the primary outcomes of the analysis.Results:A total of 138 trials involving 15,473 patients were included in this study.The overall incidence of any‐grade treatment‐related AEs was 100.0%(95%confidence interval[CI]:99.9%–100.0%;I2=89%)and the incidence of grade≥3 treatment‐related AEs was 6.2%(95%CI:3.0%–12.4%;I2=99%).Conclusions:This study provides a comprehensive overview of AEs related to ADCs used for cancer treatment.ADC use resulted in a high incidence of any‐grade AEs but a low incidence of grade≥3 AEs.The AE profiles and incidence differed according to cancer type,ADC type,and ADC components.
基金Project of Xi’an Science and Technology Plan(23YXYJ0163)Education and Teaching Reform Research Project of Xi’an Medical University in 2023(S202311840061)+1 种基金First Affiliated Hospital of Xi’an Medical University of China(XYYFY-2023-01)2021 Xi’an Medical University University-Level Science and Technology Innovation Team(2021TD14)。
文摘To understand the current situation of institutional registration in Shaanxi Province after the implementation ofregistration system management in drug clinical trial institutions.Relevant information was collected on the“Announcement on the Accreditation of Drug Clinical Trial Institutions”issued by the National Medical Products Administration from 2005 to August 2022,the record management information system of drug and medical device clinical trial institutions,and the drug clinical trial registration and information publicity platform.A retrospective analysis was carried out in terms of institutional development,regional distribution,registered majors,principal investigators,and the number of drug clinical trials.After the implementation of institution registration,the number of drug clinical trial institutions in Shaanxi Province increased by 47.4%,884 principal investigators were registered,the number of registered majors expanded from 58 qualified to 117,and the professional scope increased by 50.4%.The policy of institution registration is conducive to promoting the rational use of medical resources and the development of drug clinical trial institutions and improving the healthy development of the pharmaceutical industry in Shaanxi Province.
基金Clinical Major Specialty Projects of BeijingNational High Level Hospital Clinical Research Funding,Grant/Award Number:2022-PUMCH-A-019。
文摘Glioblastoma(GBM)is the most common primary central nervous system tumor,whose prognosis remains poor under the sequential standard of care,such as neurosurgery followed by concurrent temozolomide radiochemotherapy and adjuvant temozolomide chemotherapy in the presence or absence of tumor treating fields.Accordingly,the advent of molecular targeted therapy and immunotherapy has opened a new era of tumor management.A diverse range of targeted drugs have been tested in patients with GBM in phase III clinical trials.However,these drugs are ineffective for all patients,as evidenced by the fact that only a minority of patients in these trials showed prolonged survival.Furthermore,there are several published phase III clinical trials that involve immune checkpoint inhibitors,peptide vaccines,dendritic cell vaccines,and virotherapy.Accordingly,this review comprehensively overviews existing studies of targeted drugs and immunotherapy for glioma and discusses the challenge and perspective of targeted drugs and immunotherapy for glioma to clarify future directions.
基金Supported by the National Natural Science Foundation of China (No.80172842)Shanghai Municipal Fund of Natural Sciences (No.11ZR1423500)the Shanghai Municipal Health Bureau Fund for Traditional Chinese Medicine Research(No.2010L70A)
文摘Children recurrent respiratory infection (CRRI) indicates that children suffer from frequent infections along the upper or lower respiratory tract for a certain number of times. It is not an independent disease but a clinical syndrome mostly brought about by some basic diseases such as nonspecific immunity, specific immune suppression or deficiency disease, congenital bronchopulmonary dysplasia, vitamin or microelement deficiency, or is induced by some factors such as smoking, cross infection, and nursing errors.(2) Clinically, CRRI is commonly treated by anti-infective agents, symptomatic and supportive treatment, and immune-regulatory therapy. However, the therapeutic effectiveness is always imperfect, which could even lead to a premium on asthma, or nephritis, etc.
文摘New targeted therapies have been developed to overcome resistance to endocrine therapy(ET)and improve the outcome of HR^(+)/HER2^(-)advanced breast cancer(ABC).We conducted a meta-analysis and systemic review on randomized controlled trials evaluating various targeted therapies in combination with ET in HR^(+)/HER2^(-)ABC.PUBMED and EMBASE databases were searched for eligible trials.Hazard ratios(HRs)for progression-free survival(PFS),odds ratios(ORs)for objective response rate(ORR),clinical benefit rate(CBR),and toxicity were meta-analyzed.Twenty-six studies with data on 10347 patients were included and pooled.The addition of cyclin-dependent kinase 4/6 inhibitors to ET significantly improved median PFS(pooled HR=0.547,P<0.001),overall survival(pooled HR=0.755,P<0.001),and tumor response rates(ORR,pooled OR=1.478,P<0.001;CBR,pooled OR=1.201,P<0.001)with manageable toxicities(pooled OR=3.280,P<0.001).The mammalian targets of rapamycin inhibitors and exemestane were not clinically beneficial for this pooled population including ET-naïve and ET-resistant patients.Moderate improvement in PFS(pooled HR=0.686,P<0.001)yet pronounced toxicities(pooled OR=2.154,P<0.001)were noted in the combination of phosphatidylinositol-4,5-bisphosphate 3-kinase inhibitors with fulvestrant.Future studies are warranted to optimize the population and the dosing sequence of these available options.
基金This work is supported by the Key R&D Project of Sichuan Province,China(No.2020YFS0553)the National Science Fund for Excellent Young Scholars,China(No.32122052)the National Natural Science Foundation Regional Innovation and Development,China(No.U19A2003).
文摘Molecular target inhibitors have been regularly approved by Food and Drug Administration(FDA)for tumor treatment,and most of them intervene in tumor cell proliferation and metabolism.The RAS-RAF-MEK-ERK pathway is a conserved signaling pathway that plays vital roles in cell proliferation,survival,and differentiation.The aberrant activation of the RAS-RAF-MEK-ERK signaling pathway induces tumors.About 33%of tumors harbor RAS mutations,while 8%of tumors are driven by RAF mutations.Great efforts have been dedicated to targeting the signaling pathway for cancer treatment in the past decades.In this review,we summarized the development of inhibitors targeting the RAS-RAF-MEK-ERK pathway with an emphasis on those used in clinical treatment.Moreover,we discussed the potential combinations of inhibitors that target the RAS-RAF-MEK-ERK signaling pathway and other signaling pathways.The inhibitors targeting the RAS-RAF-MEK-ERK pathway have essentially modified the therapeutic strategy against various cancers and deserve more attention in the current cancerresearchandtreatment.
基金This study was supported by the Fundamental Research Funds for the Central Universities(No.5003516009).
文摘This study aimed to construct a quality management model for phase I clinical drug trials.A cross-sectional survey was conducted and data were collected from 604 respondents at 69 institutions in China engaged in phase I clinical drug trials.Exploratory and confirmatory factor analyses were used to develop the survey tool.Structural equation modeling was used to construct a quality management model for phase I clinical drug trials.The results showed that the final survey tool had good reliability and validity(Cronbach’sα=0.938,root mean square error of approximation=0.074,comparative fit index=0.962,and Tucker—Lewis index=0.955).The model included five dimensions:government regulation,industry management,medical institution management,research team management,and contract research organization(CRO)management.In total,22 measurement items were obtained.The structural equation model indicated government regulation,industry management,medical institution management,and CRO management significantly affected the quality of phase I clinical drug trials(β=0.195,β=0.331,β=0.279,andβ=−0.267,respectively;P<0.05).Research team management had no effect on the quality of trials(β=0.041,P=0.610).In conclusion,the model is valuable for identifying factors influencing phase I clinical drug trials and guiding quality management practices.
文摘Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monoclonal antibodies that selectively inhibit programmed cell death-1(PD-1)activity has now become standard of care in the treatment of ESCC in metastatic settings,and has a high expectation to provide clinical benefit during perioperative period.Further,anti-cytotoxic T-lymphocyte–associated protein 4(CTLA-4)monoclonal antibody has also been approved in the treatment of recurrent/metastatic ESCC in combination with anti-PD-1 antibody.Well understanding of the existing evidence of immune-based treatments for ESCC,as well as recent clinical trials on various combinations with chemotherapy for different clinical settings including neoadjuvant,adjuvant,and metastatic diseases,may provide future prospects of ESCC treatment for better patient outcomes.