The nucleotide-binding domain,leucine-rich repeat,and pyrin domain-containing protein 3(NLRP3)inflammasome is a critical modulator in inflammatory disease.Activation and mutation of NLRP3 can cause severe inflammation...The nucleotide-binding domain,leucine-rich repeat,and pyrin domain-containing protein 3(NLRP3)inflammasome is a critical modulator in inflammatory disease.Activation and mutation of NLRP3 can cause severe inflammation in diseases such as chronic infantile neurologic cutaneous and articular syndrome,Muckle-Wells syndrome,and familial cold autoinflammatory syndrome 1.To date,a great effort has been made to decode the underlying mechanisms of NLRP3 activation.The priming and activation of NLRP3 drive the maturation and release of active interleukin(IL)-18 and IL-1βto cause inflammation and pyroptosis,which can significantly trigger many diseases including inflammatory diseases,immune disorders,metabolic diseases,and neurodegenerative diseases.The investigation of NLRP3 as a therapeutic target for disease treatment is a hot topic in both preclinical studies and clinical trials.Developing potent NLRP3 inhibitors and downstream IL-1 inhibitors attracts wide-spectrum attention in both research and pharmaceutical fields.In this minireview,we first updated the molecular mechanisms involved in NLRP3 inflammasome activation and the associated downstream signaling pathways.We then reviewed the molecular and cellular pathways of NLRP3 in many diseases,including obesity,diabetes,and other metabolic diseases.In addition,we briefly reviewed the roles of NLRP3 in cancer growth and relative immune checkpoint therapy.Finally,clinical trials with treatments targeting NLRP3 and its downstream signaling pathways were summarized.展开更多
Objective To observe the therapeutic effect of electro acupuncture at QIǖXǖ（丘墟GB40） for treating migraine and provide clinical study for Acupoints Dictionary of People＇s Republic of China. Methods Multi-center ...Objective To observe the therapeutic effect of electro acupuncture at QIǖXǖ（丘墟GB40） for treating migraine and provide clinical study for Acupoints Dictionary of People＇s Republic of China. Methods Multi-center （3 First-Class hospitals） study was adopted, and the involved 3 hospitals did clinical observation according to the requirements of the project. The methods are as follows. All cases were randomized into treatment group and control group according to their sequence. QIǖXǖ（丘墟GB40） was selected in treatment group, while Tiānshū （天枢 ST25） was selected in control group. Both groups were performed electro acupuncture, and syndromes indexes of migraine and 5-HT were observed before and after treatment. All data were analyzed by statistic software SPSS11.5. Results There was significant difference of VAS margin between two groups in each center and the combined center （u= -3. 362, P=0. 001 ）. There was significant difference of therapeutic effect of 4-week treatment between two groups in each clinical center and the combined center. The therapeutic effect of 3-month treatment between two groups in No. 1 and No. 3 hospitals, showed significant difference, the treatment group was better; while that of No. 2 hospital had no obvious difference. The therapeutic effect of 6-month treatment between two groups in each center and the combined center had significant difference, the treatment group was better. Conclusion The therapy of electro acupuncture at QIǖXǖ（丘墟GB40） is effective for migraine.展开更多
Colorectal cancer(CRC)is a complex disease with diverse etiologies and clinical outcomes.Despite considerable progress in development of CRC therapeutics,challenges remain regarding the diagnosis and management of adv...Colorectal cancer(CRC)is a complex disease with diverse etiologies and clinical outcomes.Despite considerable progress in development of CRC therapeutics,challenges remain regarding the diagnosis and management of advanced stage metastatic CRC(mCRC).In particular,the five-year survival rate is very low since mCRC is currently rarely curable.Over the past decade,cancer treatment has significantly improved with the introduction of cancer immunotherapies,specifically immune checkpoint inhibitors.Therapies aimed at blocking immune checkpoints such as PD-1,PD-L1,and CTLA-4 target inhibitory pathways of the immune system,and thereby enhance anti-tumor immunity.These therapies thus have shown promising results in many clinical trials alone or in combination.The efficacy and safety of immunotherapy,either alone or in combination with CRC,have been investigated in several clinical trials.Clinical trials,including KEYNOTE-164 and CheckMate 142,have led to Food and Drug Administration approval of the PD-1 inhibitors pembrolizumab and nivolumab,respectively,for the treatment of patients with unresectable or metastatic microsatellite instability-high or deficient mismatch repair CRC.Unfortunately,these drugs benefit only a small percentage of patients,with the benefits of immunotherapy remaining elusive for the vast majority of CRC patients.To this end,primary and secondary resistance to immunotherapy remains a significant issue,and further research is necessary to optimize the use of immunotherapy in CRC and identify biomarkers to predict the response.This review provides a comprehensive overview of the clinical trials involving immune checkpoint inhibitors in CRC.The underlying rationale,challenges faced,and potential future steps to improve the prognosis and enhance the likelihood of successful trials in this field are discussed.展开更多
BACKGROUND Biliary tract cancers(BTCs)are a heterogeneous group of tumors with high malignancy,poor prognosis,and limited treatment options.AIM To explore the efficacy and safety of nab-paclitaxel plus capecitabine as...BACKGROUND Biliary tract cancers(BTCs)are a heterogeneous group of tumors with high malignancy,poor prognosis,and limited treatment options.AIM To explore the efficacy and safety of nab-paclitaxel plus capecitabine as first-line treatment for advanced and metastatic BTCs.METHODS This open-label,non-randomized,double-center,phase II clinical trial recruited systemic therapy-naive patients with unresectable or metastatic BTCs between April 2019 and June 2022 at Beijing Cancer Hospital and the First Hospital of China Medical University.Eligible patients were administered nab-paclitaxel(150 mg/m^(2),day 1)and capecitabine(2000 mg/m^(2),twice daily,days 1-7)in 14-day cycles until experiencing intolerable toxicity or disease progression.The primary outcome was the objective response rate(ORR).The secondary outcomes included the disease control rate(DCR),overall survival(OS),progression-free survival(PFS),and safety.RESULTS A total of 44 patients successfully completed the trial,with a median age of 64.00 years(interquartile range,35.00-76.00),and 26(59.09%)were females.Tumor response assessment was impeded for one patient due to premature demise from tumor hemorrhage.Among the remaining 43 patients undergoing at least one imaging assessment,the ORR was 23.26%[95%confidence interval(CI):11.80%-38.60%],and the DCR was 69.77%(95%CI:53.90%-82.80%).The median OS was 14.1 months(95%CI:8.3-19.9),and the median PFS was 4.4 months(95%CI:2.5-6.3).A total of 41 patients(93.18%)experienced at least one adverse event(AE),with 10 patients(22.73%)encountering grade≥3 AEs,and the most frequent AEs of any grade were alopecia(79.50%),leukopenia(54.55%),neutropenia(52.27%),and liver dysfunction(40.91%),and no treatment-related deaths were documented.CONCLUSION Nab-paclitaxel plus capecitabine may be an effective and safe first-line treatment strategy for patients with advanced or metastatic BTCs.展开更多
Any new report on the anticancer properties of natural products always awakens new satisfaction and hope about the role of the international scientific community in its continuous contributions to human health,particu...Any new report on the anticancer properties of natural products always awakens new satisfaction and hope about the role of the international scientific community in its continuous contributions to human health,particularly when those reports contribute to both the understanding and therapeutics of cancer.For many de-cades,natural products have been pivotal in drug discovery programs because they offer a diverse array of anticancer therapeutic possibilities.Recently,two manuscripts published in the World Journal of Gastrointestinal Oncology added new data to the already extensive body of anticancer preclinical evidence for resvera-trol and senegenin,two compounds widely present in herbal preparations used in traditional Chinese medicine.The first one,with comprehensive and recognized anticancer properties,and the second one,shows a compelling body of evidence supporting its neuroprotective effects,but with emerging anticancer activities.Natural products have become key elements in the expanding and dynamic field of anticancer drug discovery.However,urgent and collective efforts are still needed to bridge the gap between preclinical and clinical research and thus bring new anticancer therapeutic breakthroughs.展开更多
1|OVERVIEW.Machine learning(ML)has been increasingly used for tackling various diagnostic,therapeutic,and prognostic tasks owing to its capability to learn and reason without explicit programming[1].Most developed ML ...1|OVERVIEW.Machine learning(ML)has been increasingly used for tackling various diagnostic,therapeutic,and prognostic tasks owing to its capability to learn and reason without explicit programming[1].Most developed ML models have had their accuracy proven through internal validation using retrospective data.However,external validation using retrospective data,continual monitoring using prospective data,and randomized controlled trials(RCTs)using prospective data are important for the translation of ML models into real-world clinical practice[2].展开更多
Objectives:Rural patients have poor cancer outcomes and clinical trial(CT)enrollment compared to urban patients due to attitudinal,awareness,and healthcare access differential.Knowledge of cancer survival disparities ...Objectives:Rural patients have poor cancer outcomes and clinical trial(CT)enrollment compared to urban patients due to attitudinal,awareness,and healthcare access differential.Knowledge of cancer survival disparities and CT enrollment is important for designing interventions and innovative approaches to address the stated barriers.The study explores the potential disparities in cancer survival rates and clinical trial enrollments in rural and urban breast and lung cancer patients.Our hypotheses are that for both cancer types,urban cancer patients will have longer 5-year survival rates and higher enrollment rates in clinical trials than those in rural counties.Methods:We compared breast and lung cancer patients’survival rates and enrollment ratios in clinical trials between rural(RUCC 4-9)and urban counties in Georgia at a Comprehensive Cancer Center(CCC).To assess these differences,we carried out a series of independent samples t-tests and Chi-Square tests.Results:The outcomes indicate comparable 5-year survival rates across rural and urban counties for breast and lung cancer patients,failing to substantiate our hypothesis.While clinical trial enrollment rates demonstrated a significant difference between breast and lung cancer patients at CCC,no significant variation was observed based on rural or urban classification.Conclusion:These findings underscore the need for further research into the representation of rural patients with diverse cancer types at CCC and other cancer centers.Further,the findings have considerable implications for the initiation of positive social change to improve CT participation and reduce cancer survival disparities.展开更多
AIM:To explore the factors influencing individuals’willingness to participate in ophthalmic clinical trials.METHODS:A questionnaire survey was conducted from January to April 2021 among patients and their family memb...AIM:To explore the factors influencing individuals’willingness to participate in ophthalmic clinical trials.METHODS:A questionnaire survey was conducted from January to April 2021 among patients and their family members at Zhongshan Ophthalmic Center,Sun Yat-sen University,in Guangzhou,China.The survey gathered data on respondents’willingness,demographic and socioeconomic profiles,as well as their reasons and concerns regarding engagement in clinical trials.RESULTS:Of the 1078 residents surveyed(mean age 31.2±13.1y;65.8%females)in Guangzhou,749(69.5%)expressed a willingness to participate in future ophthalmic clinical trials.Specific characteristics associated with greater willingness included a younger age,lower annual income,higher education,prior participation experience,previous ophthalmic treatment,and a better understanding of clinical trials.With the exception of age,these characteristics were significantly linked to a higher willingness.The primary barrier to participation,expressed by 64.8%of those willing and 54.4%of those unwilling,was“Uncertain efficacy”.In terms of motivations,the willing group ranked“Better therapeutic benefits”(35.0%),“Professional monitoring”(34.3%),and“Trust in healthcare professionals”(33.1%)as their top three reasons,whereas the unwilling participants indicated“Full comprehension of the protocol”(46.2%)as the key facilitator.CONCLUSION:This study reveals a substantial willingness to participate in ophthalmic clinical trials and demonstrates the predictive role of demographic and socioeconomic factors.Variations in motivators and concerns between willing and unwilling participants highlight the significance of tailored recruitment strategies.Importantly,the need for and trust in healthcare professionals stand out as powerful motivations,underscoring the importance of enhancing physician-patient relationships,adopting patient-centered communication approaches,and addressing individualized needs to improve accrual rates.展开更多
Objective:To investigate the efficacy and safety of Liqingtong(LQT)granules in patients with dampness-heat hyperuricemia.Methods:A randomized,double-blind,placebo-controlled pilot trial was conducted at the 983rd Hos-...Objective:To investigate the efficacy and safety of Liqingtong(LQT)granules in patients with dampness-heat hyperuricemia.Methods:A randomized,double-blind,placebo-controlled pilot trial was conducted at the 983rd Hos-pital of the Joint Logistic Support Force of the People's Liberation Army from March 15,2023,to August 10,2023.In total,119 participants were enrolled in this trial,and participants were given either LQT granules or placebo for 60 days based on a health education.The primary outcome was serum uric acid(SUA)level,and the secondary outcome was the traditional Chinese medicine(TCM)symptom score,measured on days 0,30,and 60.Safety indicators,including liver function,kidney function,blood routine,glucose,blood lipid,blood pressure,and heart rate were tested on days 0 and 60 of the trial.The data were analyzed using Prism 9 software,and the significance level was set at P<0.05.Results:Among 119 participants,six in the LQT granule group and seven in the placebo group dropped out,and 106 participants completed clinical observation.Baseline information,including SUA levels,TCM symptom scores,and other clinical characteristics,did not differ between the groups.At the end of the trial,compared with baseline values,the SUA levels in the LQT granule group decreased(P<0.001),and no significant change was observed in the placebo group(P=0.422);compared with the placebo group,the SUA levels decreased in the LQT granule group(P=0.001).Compared with baseline values,the total TCM symptom scores in the LQT granule group decreased(P<0.001),with no change in the placebo group(P=0.136).Safety indicators did not differ significantly between the two groups.Conclusion:The pilot trial demonstrated the potential of LQT granules to lower SUA levels and improve symptoms of dampness and heat.展开更多
Gastric cancer(GC)is the leading diagnosed malignancy worldwide,especially in China.Radical surgery is the cornerstone of GC treatment.We reviewed previous clinical trials and aimed to provide an update on the factors...Gastric cancer(GC)is the leading diagnosed malignancy worldwide,especially in China.Radical surgery is the cornerstone of GC treatment.We reviewed previous clinical trials and aimed to provide an update on the factors related to the surgical treatment of GC.The number of registered clinical trials in the field of GC surgery is rapidly increasing.With the development and popularization of endoscopic,laparoscopic,and robotic techniques,GC surgery has gradually entered a new era of precise minimally invasive surgery.Postoperative quality of life has become a major issue in addition to surgical oncological safety.Although great progress has been made in clinical research on GC in China,there are still deficiencies.Many studies enrolled large numbers of patients,but the research data were not of high quality.The characteristics of GC in China include a high incidence,large population,and large proportion of patients with advanced GC,which provides sufficient reason for studying this disease.There is still a need for well-designed,large,randomized clinical trials to improve our knowledge of the surgical treatment of GC.展开更多
This study examined the application of the Rumsfeld Matrix to acupuncture clinical trials,particularly those published in leading medical journals such as The Journal of the American Medical Association(JAMA),British ...This study examined the application of the Rumsfeld Matrix to acupuncture clinical trials,particularly those published in leading medical journals such as The Journal of the American Medical Association(JAMA),British Medical Journal(BMJ),The Lancet,and The New Eng-land Journal of Medicine(NEJM).The integration of randomized clinical trials(RCTs)has in-troduced a level of academic rigor to acupuncture research,challenging the classical deter-ministic model and revealing a complex landscape of known knowns,known unknowns,un-known knowns,and unknown unknowns.While RCTs have validated acupuncture’s efficacy in certain conditions,they have also highlighted considerable challenges,including the limi-tations of control group designs and the potential influence of placebo effects.The recurring issue of no significant differences between real and sham acupuncture in many studies un-derscores the need for refined control strategies and a more nuanced understanding of acupuncture’s mechanisms.This investigation calls for continued rigorous research to fully explore acupuncture’s therapeutic potential and its integration into evidence-based medicine,ultimately contributing to improved patient care and broader acceptance within the medical community.展开更多
BACKGROUND To date,no specific treatment has been established to reverse progressive chronic kidney disease(CKD).AIM To evaluate the safety and efficacy of autologous CD34^(+)cell transplantation in CKD patients who e...BACKGROUND To date,no specific treatment has been established to reverse progressive chronic kidney disease(CKD).AIM To evaluate the safety and efficacy of autologous CD34^(+)cell transplantation in CKD patients who exhibited a progressive decline in renal function.METHODS The estimated glomerular filtration rate(eGFR)at the beginning of the study was 15.0-28.0 mL/minute/1.73 m^(2).After five days of treatment with the granulocyte colony-stimulating factor,mononuclear cells were harvested and CD34^(+)cells were magnetically collected.CD34^(+)cells were directly injected into the bilateral renal arteries twice(at 0 and 3 months),and their safety and efficacy were evaluated for 6 months.RESULTS Four patients were enrolled and completed the study.Three of four patients showed improvement in eGFR slope(eGFR slope>0 mL/minute/1.73 m^(2)),with the monthly slope of eGFR(delta eGFR)changing from-1.36±1.1(pretreatment)to^(+)0.22±0.71(at 6 months)mL/minute/1.73 m^(2)/month(P=0.135)after cell therapy.Additionally,intrarenal resistive index(P=0.004)and shear wave velocity(P=0.04)were significantly improved after cell therapy.One patient experienced transient fever after cell therapy,and experienced bone pain during granulocyte colony-stimulating factor administration.However,no severe adverse events were reported.CONCLUSION In conclusion,our findings suggest that repetitive peripheral blood-derived autologous CD34^(+)cell transplantation into the renal arteries is safe,feasible,and may be effective for patients with progressive CKD.However,a large-scale clinical trial is warranted to validate the efficacy of repetitive regenerative cell therapy using autologous CD34^(+)cells in patients with progressive CKD.展开更多
1) Background: Osteoarthritis (OA) is defined as a degenerative joint disease that mainly affects the bone. This study aims to evaluate the effect of low-intensity continuous ultrasound (LICUS) treatment on the knee o...1) Background: Osteoarthritis (OA) is defined as a degenerative joint disease that mainly affects the bone. This study aims to evaluate the effect of low-intensity continuous ultrasound (LICUS) treatment on the knee of osteoarthritis patients through home-based intervention using the LICUS medical device. 2) Methods: The clinical trials were designed in a single-arm, open-label, and intervention study. Thirty-five participants, including those who dropped out (12%), were screened and enrolled. The patients received LICUS (1.1 MHz, 1.5 W/cm2, collimated beams) on the knee by the instructions of the investigator at home (5 min/session, 3 times/day, for four-weeks). Outcome measures were assessed using the Visual Analog Scale (VAS) as a primary endpoint and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) as a secondary endpoint to evaluate pain relief and functional recovery of the knee between pre-treatment (baseline) and post-treatment (four-weeks). 3) Results: Knee pain scores measured using the VAS and WOMAC indices were significantly reduced after a four-week treatment with LICUS compared to baseline. Knee stiffness and functional capacity were significantly reduced after the LICUS application. In addition, there were no reports of adverse effects during the study period. 4) Conclusion: Long-term and home-based application of LICUS can be recommended as an alternative option for the treatment of OA patients, as evidenced by the effect of pain relief and knee function recovery.展开更多
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
Purpose:The purpose of this study was to identify the knowledge and attitudes of oncology nurses toward clinical trials and to provide evidence for the development of clinical trial education programs for oncology nur...Purpose:The purpose of this study was to identify the knowledge and attitudes of oncology nurses toward clinical trials and to provide evidence for the development of clinical trial education programs for oncology nurses.Methods:The study was conducted on 142 nurses who had more than six months of nursing experience working with cancer patients at a tertiary hospital in Seoul,Korea.A structured questionnaire was used to measure the knowledge and attitudes of oncology nurses toward clinical trials.Results:The participants scored an average of 15.03±3.52 out of 19 in terms of knowledge about clinical trials.In terms of attitudes toward clinical trials,the participants scored an average of 5.91±1.37 out of 8.There was a significant positive correlation between the knowledge and attitudes of the participants toward clinical trials(r=0.23,P=0.007).Conclusion:This study found that there was a relationship between the knowledge and attitudes of oncology nurses toward clinical trials.To improve the competency of oncology nurses and provide high-quality care to patients participating in clinical trials,more systematic and sustainable education is required.展开更多
Objective To provide suggestions and a reference for improving the quality management system of clinical trials of therapeutic vaccines and promoting the development of therapeutic vaccines in China.Methods Literature...Objective To provide suggestions and a reference for improving the quality management system of clinical trials of therapeutic vaccines and promoting the development of therapeutic vaccines in China.Methods Literature research,case study and comparative study were used to analyze the quality management system of clinical trials of therapeutic vaccines.Results and Conclusion From the perspective of the sponsor,investigators and the thirdparty technical service company,the problems such as the low efficiency of clinical trial sample preparation and the lax implementation of the protocol by hospital departments in the quality management of clinical trials of therapeutic vaccines in China were found.Then,the optimization plan for the quality management of clinical trials of therapeutic vaccines is proposed,including optimizing the preparation process of therapeutic vaccines and strengthening the training of hospital department personnel.展开更多
文摘The nucleotide-binding domain,leucine-rich repeat,and pyrin domain-containing protein 3(NLRP3)inflammasome is a critical modulator in inflammatory disease.Activation and mutation of NLRP3 can cause severe inflammation in diseases such as chronic infantile neurologic cutaneous and articular syndrome,Muckle-Wells syndrome,and familial cold autoinflammatory syndrome 1.To date,a great effort has been made to decode the underlying mechanisms of NLRP3 activation.The priming and activation of NLRP3 drive the maturation and release of active interleukin(IL)-18 and IL-1βto cause inflammation and pyroptosis,which can significantly trigger many diseases including inflammatory diseases,immune disorders,metabolic diseases,and neurodegenerative diseases.The investigation of NLRP3 as a therapeutic target for disease treatment is a hot topic in both preclinical studies and clinical trials.Developing potent NLRP3 inhibitors and downstream IL-1 inhibitors attracts wide-spectrum attention in both research and pharmaceutical fields.In this minireview,we first updated the molecular mechanisms involved in NLRP3 inflammasome activation and the associated downstream signaling pathways.We then reviewed the molecular and cellular pathways of NLRP3 in many diseases,including obesity,diabetes,and other metabolic diseases.In addition,we briefly reviewed the roles of NLRP3 in cancer growth and relative immune checkpoint therapy.Finally,clinical trials with treatments targeting NLRP3 and its downstream signaling pathways were summarized.
文摘Objective To observe the therapeutic effect of electro acupuncture at QIǖXǖ（丘墟GB40） for treating migraine and provide clinical study for Acupoints Dictionary of People＇s Republic of China. Methods Multi-center （3 First-Class hospitals） study was adopted, and the involved 3 hospitals did clinical observation according to the requirements of the project. The methods are as follows. All cases were randomized into treatment group and control group according to their sequence. QIǖXǖ（丘墟GB40） was selected in treatment group, while Tiānshū （天枢 ST25） was selected in control group. Both groups were performed electro acupuncture, and syndromes indexes of migraine and 5-HT were observed before and after treatment. All data were analyzed by statistic software SPSS11.5. Results There was significant difference of VAS margin between two groups in each center and the combined center （u= -3. 362, P=0. 001 ）. There was significant difference of therapeutic effect of 4-week treatment between two groups in each clinical center and the combined center. The therapeutic effect of 3-month treatment between two groups in No. 1 and No. 3 hospitals, showed significant difference, the treatment group was better; while that of No. 2 hospital had no obvious difference. The therapeutic effect of 6-month treatment between two groups in each center and the combined center had significant difference, the treatment group was better. Conclusion The therapy of electro acupuncture at QIǖXǖ（丘墟GB40） is effective for migraine.
基金Supported by IU Simon Comprehensive Cancer Center grant,No.5P30CA082709-24.
文摘Colorectal cancer(CRC)is a complex disease with diverse etiologies and clinical outcomes.Despite considerable progress in development of CRC therapeutics,challenges remain regarding the diagnosis and management of advanced stage metastatic CRC(mCRC).In particular,the five-year survival rate is very low since mCRC is currently rarely curable.Over the past decade,cancer treatment has significantly improved with the introduction of cancer immunotherapies,specifically immune checkpoint inhibitors.Therapies aimed at blocking immune checkpoints such as PD-1,PD-L1,and CTLA-4 target inhibitory pathways of the immune system,and thereby enhance anti-tumor immunity.These therapies thus have shown promising results in many clinical trials alone or in combination.The efficacy and safety of immunotherapy,either alone or in combination with CRC,have been investigated in several clinical trials.Clinical trials,including KEYNOTE-164 and CheckMate 142,have led to Food and Drug Administration approval of the PD-1 inhibitors pembrolizumab and nivolumab,respectively,for the treatment of patients with unresectable or metastatic microsatellite instability-high or deficient mismatch repair CRC.Unfortunately,these drugs benefit only a small percentage of patients,with the benefits of immunotherapy remaining elusive for the vast majority of CRC patients.To this end,primary and secondary resistance to immunotherapy remains a significant issue,and further research is necessary to optimize the use of immunotherapy in CRC and identify biomarkers to predict the response.This review provides a comprehensive overview of the clinical trials involving immune checkpoint inhibitors in CRC.The underlying rationale,challenges faced,and potential future steps to improve the prognosis and enhance the likelihood of successful trials in this field are discussed.
文摘BACKGROUND Biliary tract cancers(BTCs)are a heterogeneous group of tumors with high malignancy,poor prognosis,and limited treatment options.AIM To explore the efficacy and safety of nab-paclitaxel plus capecitabine as first-line treatment for advanced and metastatic BTCs.METHODS This open-label,non-randomized,double-center,phase II clinical trial recruited systemic therapy-naive patients with unresectable or metastatic BTCs between April 2019 and June 2022 at Beijing Cancer Hospital and the First Hospital of China Medical University.Eligible patients were administered nab-paclitaxel(150 mg/m^(2),day 1)and capecitabine(2000 mg/m^(2),twice daily,days 1-7)in 14-day cycles until experiencing intolerable toxicity or disease progression.The primary outcome was the objective response rate(ORR).The secondary outcomes included the disease control rate(DCR),overall survival(OS),progression-free survival(PFS),and safety.RESULTS A total of 44 patients successfully completed the trial,with a median age of 64.00 years(interquartile range,35.00-76.00),and 26(59.09%)were females.Tumor response assessment was impeded for one patient due to premature demise from tumor hemorrhage.Among the remaining 43 patients undergoing at least one imaging assessment,the ORR was 23.26%[95%confidence interval(CI):11.80%-38.60%],and the DCR was 69.77%(95%CI:53.90%-82.80%).The median OS was 14.1 months(95%CI:8.3-19.9),and the median PFS was 4.4 months(95%CI:2.5-6.3).A total of 41 patients(93.18%)experienced at least one adverse event(AE),with 10 patients(22.73%)encountering grade≥3 AEs,and the most frequent AEs of any grade were alopecia(79.50%),leukopenia(54.55%),neutropenia(52.27%),and liver dysfunction(40.91%),and no treatment-related deaths were documented.CONCLUSION Nab-paclitaxel plus capecitabine may be an effective and safe first-line treatment strategy for patients with advanced or metastatic BTCs.
文摘Any new report on the anticancer properties of natural products always awakens new satisfaction and hope about the role of the international scientific community in its continuous contributions to human health,particularly when those reports contribute to both the understanding and therapeutics of cancer.For many de-cades,natural products have been pivotal in drug discovery programs because they offer a diverse array of anticancer therapeutic possibilities.Recently,two manuscripts published in the World Journal of Gastrointestinal Oncology added new data to the already extensive body of anticancer preclinical evidence for resvera-trol and senegenin,two compounds widely present in herbal preparations used in traditional Chinese medicine.The first one,with comprehensive and recognized anticancer properties,and the second one,shows a compelling body of evidence supporting its neuroprotective effects,but with emerging anticancer activities.Natural products have become key elements in the expanding and dynamic field of anticancer drug discovery.However,urgent and collective efforts are still needed to bridge the gap between preclinical and clinical research and thus bring new anticancer therapeutic breakthroughs.
文摘1|OVERVIEW.Machine learning(ML)has been increasingly used for tackling various diagnostic,therapeutic,and prognostic tasks owing to its capability to learn and reason without explicit programming[1].Most developed ML models have had their accuracy proven through internal validation using retrospective data.However,external validation using retrospective data,continual monitoring using prospective data,and randomized controlled trials(RCTs)using prospective data are important for the translation of ML models into real-world clinical practice[2].
文摘Objectives:Rural patients have poor cancer outcomes and clinical trial(CT)enrollment compared to urban patients due to attitudinal,awareness,and healthcare access differential.Knowledge of cancer survival disparities and CT enrollment is important for designing interventions and innovative approaches to address the stated barriers.The study explores the potential disparities in cancer survival rates and clinical trial enrollments in rural and urban breast and lung cancer patients.Our hypotheses are that for both cancer types,urban cancer patients will have longer 5-year survival rates and higher enrollment rates in clinical trials than those in rural counties.Methods:We compared breast and lung cancer patients’survival rates and enrollment ratios in clinical trials between rural(RUCC 4-9)and urban counties in Georgia at a Comprehensive Cancer Center(CCC).To assess these differences,we carried out a series of independent samples t-tests and Chi-Square tests.Results:The outcomes indicate comparable 5-year survival rates across rural and urban counties for breast and lung cancer patients,failing to substantiate our hypothesis.While clinical trial enrollment rates demonstrated a significant difference between breast and lung cancer patients at CCC,no significant variation was observed based on rural or urban classification.Conclusion:These findings underscore the need for further research into the representation of rural patients with diverse cancer types at CCC and other cancer centers.Further,the findings have considerable implications for the initiation of positive social change to improve CT participation and reduce cancer survival disparities.
基金Supported by the Science and Technology Program of Guangzhou(No.201803010066)the High-level Hospital Construction Project,Zhongshan Ophthalmic Center,Sun Yat-sen University(No.303010202).
文摘AIM:To explore the factors influencing individuals’willingness to participate in ophthalmic clinical trials.METHODS:A questionnaire survey was conducted from January to April 2021 among patients and their family members at Zhongshan Ophthalmic Center,Sun Yat-sen University,in Guangzhou,China.The survey gathered data on respondents’willingness,demographic and socioeconomic profiles,as well as their reasons and concerns regarding engagement in clinical trials.RESULTS:Of the 1078 residents surveyed(mean age 31.2±13.1y;65.8%females)in Guangzhou,749(69.5%)expressed a willingness to participate in future ophthalmic clinical trials.Specific characteristics associated with greater willingness included a younger age,lower annual income,higher education,prior participation experience,previous ophthalmic treatment,and a better understanding of clinical trials.With the exception of age,these characteristics were significantly linked to a higher willingness.The primary barrier to participation,expressed by 64.8%of those willing and 54.4%of those unwilling,was“Uncertain efficacy”.In terms of motivations,the willing group ranked“Better therapeutic benefits”(35.0%),“Professional monitoring”(34.3%),and“Trust in healthcare professionals”(33.1%)as their top three reasons,whereas the unwilling participants indicated“Full comprehension of the protocol”(46.2%)as the key facilitator.CONCLUSION:This study reveals a substantial willingness to participate in ophthalmic clinical trials and demonstrates the predictive role of demographic and socioeconomic factors.Variations in motivators and concerns between willing and unwilling participants highlight the significance of tailored recruitment strategies.Importantly,the need for and trust in healthcare professionals stand out as powerful motivations,underscoring the importance of enhancing physician-patient relationships,adopting patient-centered communication approaches,and addressing individualized needs to improve accrual rates.
基金funded by the National Key Research and Development Plan of the Traditional Chinese Medicine Modernization Research Key Project(2018YFC1706800).
文摘Objective:To investigate the efficacy and safety of Liqingtong(LQT)granules in patients with dampness-heat hyperuricemia.Methods:A randomized,double-blind,placebo-controlled pilot trial was conducted at the 983rd Hos-pital of the Joint Logistic Support Force of the People's Liberation Army from March 15,2023,to August 10,2023.In total,119 participants were enrolled in this trial,and participants were given either LQT granules or placebo for 60 days based on a health education.The primary outcome was serum uric acid(SUA)level,and the secondary outcome was the traditional Chinese medicine(TCM)symptom score,measured on days 0,30,and 60.Safety indicators,including liver function,kidney function,blood routine,glucose,blood lipid,blood pressure,and heart rate were tested on days 0 and 60 of the trial.The data were analyzed using Prism 9 software,and the significance level was set at P<0.05.Results:Among 119 participants,six in the LQT granule group and seven in the placebo group dropped out,and 106 participants completed clinical observation.Baseline information,including SUA levels,TCM symptom scores,and other clinical characteristics,did not differ between the groups.At the end of the trial,compared with baseline values,the SUA levels in the LQT granule group decreased(P<0.001),and no significant change was observed in the placebo group(P=0.422);compared with the placebo group,the SUA levels decreased in the LQT granule group(P=0.001).Compared with baseline values,the total TCM symptom scores in the LQT granule group decreased(P<0.001),with no change in the placebo group(P=0.136).Safety indicators did not differ significantly between the two groups.Conclusion:The pilot trial demonstrated the potential of LQT granules to lower SUA levels and improve symptoms of dampness and heat.
基金Shanghai Pudong New Area Science and Technology Development Fund Special Project for People's Livelihood Scientific Research,No.PKJ2023-Y38.
文摘Gastric cancer(GC)is the leading diagnosed malignancy worldwide,especially in China.Radical surgery is the cornerstone of GC treatment.We reviewed previous clinical trials and aimed to provide an update on the factors related to the surgical treatment of GC.The number of registered clinical trials in the field of GC surgery is rapidly increasing.With the development and popularization of endoscopic,laparoscopic,and robotic techniques,GC surgery has gradually entered a new era of precise minimally invasive surgery.Postoperative quality of life has become a major issue in addition to surgical oncological safety.Although great progress has been made in clinical research on GC in China,there are still deficiencies.Many studies enrolled large numbers of patients,but the research data were not of high quality.The characteristics of GC in China include a high incidence,large population,and large proportion of patients with advanced GC,which provides sufficient reason for studying this disease.There is still a need for well-designed,large,randomized clinical trials to improve our knowledge of the surgical treatment of GC.
文摘This study examined the application of the Rumsfeld Matrix to acupuncture clinical trials,particularly those published in leading medical journals such as The Journal of the American Medical Association(JAMA),British Medical Journal(BMJ),The Lancet,and The New Eng-land Journal of Medicine(NEJM).The integration of randomized clinical trials(RCTs)has in-troduced a level of academic rigor to acupuncture research,challenging the classical deter-ministic model and revealing a complex landscape of known knowns,known unknowns,un-known knowns,and unknown unknowns.While RCTs have validated acupuncture’s efficacy in certain conditions,they have also highlighted considerable challenges,including the limi-tations of control group designs and the potential influence of placebo effects.The recurring issue of no significant differences between real and sham acupuncture in many studies un-derscores the need for refined control strategies and a more nuanced understanding of acupuncture’s mechanisms.This investigation calls for continued rigorous research to fully explore acupuncture’s therapeutic potential and its integration into evidence-based medicine,ultimately contributing to improved patient care and broader acceptance within the medical community.
文摘BACKGROUND To date,no specific treatment has been established to reverse progressive chronic kidney disease(CKD).AIM To evaluate the safety and efficacy of autologous CD34^(+)cell transplantation in CKD patients who exhibited a progressive decline in renal function.METHODS The estimated glomerular filtration rate(eGFR)at the beginning of the study was 15.0-28.0 mL/minute/1.73 m^(2).After five days of treatment with the granulocyte colony-stimulating factor,mononuclear cells were harvested and CD34^(+)cells were magnetically collected.CD34^(+)cells were directly injected into the bilateral renal arteries twice(at 0 and 3 months),and their safety and efficacy were evaluated for 6 months.RESULTS Four patients were enrolled and completed the study.Three of four patients showed improvement in eGFR slope(eGFR slope>0 mL/minute/1.73 m^(2)),with the monthly slope of eGFR(delta eGFR)changing from-1.36±1.1(pretreatment)to^(+)0.22±0.71(at 6 months)mL/minute/1.73 m^(2)/month(P=0.135)after cell therapy.Additionally,intrarenal resistive index(P=0.004)and shear wave velocity(P=0.04)were significantly improved after cell therapy.One patient experienced transient fever after cell therapy,and experienced bone pain during granulocyte colony-stimulating factor administration.However,no severe adverse events were reported.CONCLUSION In conclusion,our findings suggest that repetitive peripheral blood-derived autologous CD34^(+)cell transplantation into the renal arteries is safe,feasible,and may be effective for patients with progressive CKD.However,a large-scale clinical trial is warranted to validate the efficacy of repetitive regenerative cell therapy using autologous CD34^(+)cells in patients with progressive CKD.
文摘1) Background: Osteoarthritis (OA) is defined as a degenerative joint disease that mainly affects the bone. This study aims to evaluate the effect of low-intensity continuous ultrasound (LICUS) treatment on the knee of osteoarthritis patients through home-based intervention using the LICUS medical device. 2) Methods: The clinical trials were designed in a single-arm, open-label, and intervention study. Thirty-five participants, including those who dropped out (12%), were screened and enrolled. The patients received LICUS (1.1 MHz, 1.5 W/cm2, collimated beams) on the knee by the instructions of the investigator at home (5 min/session, 3 times/day, for four-weeks). Outcome measures were assessed using the Visual Analog Scale (VAS) as a primary endpoint and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) as a secondary endpoint to evaluate pain relief and functional recovery of the knee between pre-treatment (baseline) and post-treatment (four-weeks). 3) Results: Knee pain scores measured using the VAS and WOMAC indices were significantly reduced after a four-week treatment with LICUS compared to baseline. Knee stiffness and functional capacity were significantly reduced after the LICUS application. In addition, there were no reports of adverse effects during the study period. 4) Conclusion: Long-term and home-based application of LICUS can be recommended as an alternative option for the treatment of OA patients, as evidenced by the effect of pain relief and knee function recovery.
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.
文摘Purpose:The purpose of this study was to identify the knowledge and attitudes of oncology nurses toward clinical trials and to provide evidence for the development of clinical trial education programs for oncology nurses.Methods:The study was conducted on 142 nurses who had more than six months of nursing experience working with cancer patients at a tertiary hospital in Seoul,Korea.A structured questionnaire was used to measure the knowledge and attitudes of oncology nurses toward clinical trials.Results:The participants scored an average of 15.03±3.52 out of 19 in terms of knowledge about clinical trials.In terms of attitudes toward clinical trials,the participants scored an average of 5.91±1.37 out of 8.There was a significant positive correlation between the knowledge and attitudes of the participants toward clinical trials(r=0.23,P=0.007).Conclusion:This study found that there was a relationship between the knowledge and attitudes of oncology nurses toward clinical trials.To improve the competency of oncology nurses and provide high-quality care to patients participating in clinical trials,more systematic and sustainable education is required.
文摘Objective To provide suggestions and a reference for improving the quality management system of clinical trials of therapeutic vaccines and promoting the development of therapeutic vaccines in China.Methods Literature research,case study and comparative study were used to analyze the quality management system of clinical trials of therapeutic vaccines.Results and Conclusion From the perspective of the sponsor,investigators and the thirdparty technical service company,the problems such as the low efficiency of clinical trial sample preparation and the lax implementation of the protocol by hospital departments in the quality management of clinical trials of therapeutic vaccines in China were found.Then,the optimization plan for the quality management of clinical trials of therapeutic vaccines is proposed,including optimizing the preparation process of therapeutic vaccines and strengthening the training of hospital department personnel.
