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Abstract Introduction Despite the developing technology of cochlear implants (CIs), implanted prelingual hearing-impaired children exhibit variable speech processing outcomes. When these children match in personal and implant-related criteria, the CI outcome variability could be related to higher-order cognitive impairment. Objectives To evaluate different domains of cognitive function in good versus poor CI performers using a multidisciplinary approach and to find the relationship between these functions and different levels of speech processing. Methods This observational, cross-sectional study used the word recognition score (WRS) test to categorize 40 children with CIs into 20 good (WRS/65%) and 20 poor performers (WRS < 65%). All participants were examined for speech processing at different levels (auditory processing and spoken language) and cognitive functioning using (1) verbal tests (verbal component of Stanford-Binet intelligence [SBIS], auditory memory, auditory vigilance, and P300); and (2) performance tasks (performance components of SBIS, and trail making test). Results The outcomes of speech processing at different functional levels and both domains of cognitive function were analyzed and correlated. Speech processing was impaired significantly in poor CI performers. This group also showed a significant cognitive function deficit, in which the verbal abilities were more affected (in 93.5%) than in the good performers (in 69.5%). Moreover, cognitive function revealed a significant correlation and predictive effect on the CI speech outcomes. Conclusion Cognitive function impairment represented an important factor that underlies the variable speech proficiency in cochlear-implanted children. A multidisciplinary evaluation of cognitive function would provide a comprehensive overview to improve training strategies.
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Objective:To evaluate and compare the clinical efficacy and safety of three different medicated eye patches in the treatment of Demodex blepharitis. Methods:A multicenter, randomized, double-blind, parallel-controlled clinical trial was conducted.A total of 140 patients (280 eyes) with Demodex blepharitis were recruited in Shanghai Jing'an District Shibei Hospital, Xi'an Fourth Hospital and Kunming First People's Hospital from July 2021 to December 2022.The affected eyes were randomly divided into tea tree oil group, okra oil group, basal fluid control group and metronidazole group by the random number table method.Eye patches containing 20% tea tree oil, 1% okra oil, prepared base solution and 2% metronidazole were applied to the eyes for 28 days by the double-blind method.The count of Demodex was evaluated before treatment and on days 14 and 28 of treatment.Ocular surface symptoms were scored according to Ocular Surface Disease Index (OSDI). The degree of congestion at the eyelid margin and cylindrical dandruff at the root of eyelashes were scored under a slit lamp microscope.The effective rate was calculated according to the comprehensive scores above, and the adverse reactions of the subjects were observed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Shanghai Jing'an District Shibei Hospital (No.YL-20200320-05). All the subjects were informed of the significance, purpose and method of the study.Written informed consent was obtained from each subject before any medical examination. Results:All subjects completed the treatment and follow-up, and the loss to follow-up rate was 0%.After 14 and 28 days of treatment, the Demodex count was significantly decreased in all groups compared with before treatment (all at P<0.05). After 28 days of treatment, the number of Demodex in tea tree oil group, okra oil group and metronidazole group were significantly lower than that in basal fluid control group, with statistically significant differences (all at P<0.05). The OSDI score, palpebral margin congestion score and cylindrical dandruff score on 14 and 28 days after treatment in tea tree oil group, okra oil group and metronidazole group were significantly lower than before treatment, showing statistically significant differences (all at P<0.05). After 28 days of treatment, the effective rates of tea tree oil group, okra oil group and metronidazole group were 71.4%, 71.4% and 62.9%, respectively, which were significantly higher than 25.7% in basal solution control group.No serious local or systemic adverse reactions were found during the treatment and follow-up. Conclusions:Eye patches containing tea tree oil, okra oil and metronidazole have significant effects on the treatment of Demodex blepharitis, which can improve the biological environment of the palpebral margin and eliminate the inflammation related to blepharitis.
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@#Introduction: Alcohol, when used frequently, accelerates the ageing process, causes brain damage, and results in a reduced volume of grey and white matter, leading to frontal lobe abnormalities. The neurotoxicity resulting from alcohol overuse affects the higher functions of the brain. This study aimed to evaluate the effect of alcohol dependence on the executive functioning of the brain. Methods: This study was carried out as a case-control study among 60 patients with alcohol dependence and 60 controls. Assessment of executive function was carried out using the Comprehensive trail-making test (CTMT) and the Wisconsin card sorting test (WCST). Comparison between the alcohol dependence group and normal healthy controls were calculated using the Mann-Whitney U test as data followed a non-parametric distribution. Results: The mean age of the participants among the cases and controls was 38.3±5.5 years and 37.8±5.4 years, respectively. The results showed a significant difference in both WCST and CTMT between cases and controls (p<0.05). Conclusion: This study concludes that there was an impaired performance in executive functions in alcohol- dependence patients in early abstinence compared to normal controls showing frontal lobe impairment in alcohol-dependence patients.
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Extended circulation of anticancer nanodrugs in blood stream is essential for their clinical applications. However, administered nanoparticles are rapidly sequestered and cleared by cells of the mononuclear phagocyte system (MPS). In this study, we developed a biomimetic nanosystem that is able to efficiently escape MPS and target tumor tissues. The fabricated nanoparticles (TM-CQ/NPs) were coated with fibroblast cell membrane expressing tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL). Coating with this functionalized membrane reduced the endocytosis of nanoparticles by macrophages, but increased the nanoparticle uptake in tumor cells. Importantly, this membrane coating specifically induced tumor cell apoptosis via the interaction of TRAIL and its cognate death receptors. Meanwhile, the encapsulated chloroquine (CQ) further suppressed the uptake of nanoparticles by macrophages, and synergized with TRAIL to induce tumor cell apoptosis. The vigorous antitumor efficacy in two mice tumor models confirmed our nanosystem was an effective approach to address the MPS challenge for cancer therapy. Together, our TM-CQ/NPs nanosystem provides a feasible approach to precisely target tumor tissues and improve anticancer efficacy.
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Introduction: Depression in the elderly can have a different pathophysiology and clinical profile, and studies have shown pathological changes in the brain on radio imaging. The present study aimed to find out the association of white matter hyperintensities (WMH) on magnetic resonance imaging (MRI) with the severity of illness and cognition in elderly depressed patients. Methodology: This cross-sectional study included 68 elderly (>60 years of age) depressed patients who had undergone MRI at a tertiary care center, and based on the severity of WMH, they were divided into two groups: no or slight WMH group and moderate or severe WMH group. The severity of depression was assessed using the Hamilton Depression Rating Scale (HAM-D) scale, and neuropsychological assessments were made for testing attention, concentration and executive function. Results: HAM?D scores were found significantly higher in patients with moderate?to?severe WMH groups (22.6 ± 5.2) compared to those with no or slight WMH (16.3 ± 4.2). The cognitive performance evaluated by backward digit span test, Trail making Test A and B, and Color Stroop test was significantly poor in the moderate?to?severe WMH group. Conclusion: Elderly depressed patients having a greater WMH had more severe depression and poor cognitive performance, especially psychomotor and executive functioning. WMH could be a potential marker for the severity of illness and cognition in depression in elderly persons.
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The author has researched and reported on “Efforts to increase the demand for long-term stays in spa resorts” over three reports up until now. The target areas were spa health resorts and national park resort villages with spas. There, I pointed out the necessity to create programs for stays that combine the natural environments, historical and cultural environments, artificial environments and facilities, different environments by moving around and night-time hours that exist around each stay facility. In this repot, I investigated the creation of programs for public Kokumin Shukusha, which are dormitories for the people who can stay with peace of mind, even with their families, at a low cost. I investigated whether or not efforts are being made to create programs for staying, such as setting walking trails that make use of external environments around the public Kokumin Shukusha. As a result, although efforts were made, the number and diversity of course settings were insufficient. In order to increase the demand for long-term stays, it will be necessary to utilize the external environment that make the most of the nearness to existing villages. In addition, it became clear that the Onsen Stay policy promoted by the Ministry of the Environment has not been publicized, and it is necessary to promote the publicity of this policy in order to revitalize spa resorts nationwide.
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The author has researched and reported on “Efforts to increase the demand for long-term stays in spa resorts” over three reports up until now. The target areas were spa health resorts and national park resort villages with spas. There, I pointed out the necessity to create programs for stays that combine the natural environments, historical and cultural environments, artificial environments and facilities, different environments by moving around and night-time hours that exist around each stay facility. In this repot, I investigated the creation of programs for public Kokumin Shukusha, which are dormitories for the people who can stay with peace of mind, even with their families, at a low cost. I investigated whether or not efforts are being made to create programs for staying, such as setting walking trails that make use of external environments around the public Kokumin Shukusha. As a result, although efforts were made, the number and diversity of course settings were insufficient. In order to increase the demand for long-term stays, it will be necessary to utilize the external environment that make the most of the nearness to existing villages. In addition, it became clear that the Onsen Stay policy promoted by the Ministry of the Environment has not been publicized, and it is necessary to promote the publicity of this policy in order to revitalize spa resorts nationwide.
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@#AIM: To evaluate the clinical effects of using anti-VEGF drugs combined with Steroids to treat macular edema(ME)secondary to retinal vein occlusion. <p>METHODS: Chinese and English electronic databases(Pubmed, Embase, Cochrane, CNKI, Wanfang and Weipu)were searched to obtain qualified random controlled test(RCT)researches from their foundation to January 2020. According to inclusion and exclusion criteria, two researchers retrieved the literature independently, extracted data and evaluate methodological quality. Review Manager 5.3 was used for Meta-analysis.<p>RESULTS: A total of 5 RCTs were identified with 212 patients. There was no significant difference in patients' best correct visual acuity(BCVA)improvement in 1mo, 3mo and 6mo between anti-VEGF combined with steroids and anti-VEGF monopoly. Significant difference was found in the relieve of ME in 1mo and 3mo(1mo: <i>MD</i>=-20.89, 95% <i>CI</i>: -34.65 to -7.13, <i>P</i>=0.003; 3mo: <i>MD</i>=-22.83, 95% <i>CI</i>: -33.68 to -11.97, <i>P</i><0.0001), but not in 6mo between two groups. As for side effects and complications, the combination group occurs more often than the monopoly group(<i>P</i>=0.02). Meanwhile, significant difference was found in the number of injections between two groups(<i>P</i><0.001). <p>CONCLUSION: Compared with the single use of anti-VEGF drugs, anti-VEGF drugs combined with corticosteroids for the treatment of ME secondary to RVO have the characteristics of rapid onset, fewer injections, and more economical. The treatment process should closely follow the patient's intraocular pressure and lens status.
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Clinical trail report is a summary of the process and results of clinical trail, an important basis to support the effectiveness and safety evaluation of drug marketing and an important technical data required for drug registration. Safety analysis is the main part and the most common issue of clinical trial report. In this article, it is summarized and analyzed the common problems found in the safety analysis part of the clinical trial report of new drugs of traditional Chinese medicine(TCM) in combination with the clinical professional evaluation of the application for marketing license of innovative TCM. The common problems in writing the safety aspects of clinical trail reports were summarized and analyzed, including the omissions of adverse events and laboratory test results, the failure to provide a detailed list of laboratory test outliers, the lack of professional depth in the analysis of the causal relationship between adverse events and TCM. In view of the common problems, it is suggested that the drug use degree, adverse events and adverse reactions, as well as laboratory examination should be considered. Check the three dimensions for necessary medical analysis, collation and summary and continuously improve the quality of safety analysis in clinical trial reports.
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Clinical Trials as Topic , Drugs, Chinese Herbal/adverse effects , Medicine, Chinese TraditionalABSTRACT
Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) is an imaging method that uses magnetic resonance technology to perform objective, quantitative, and noninvasive assessment of fat in the whole liver. This article mainly analyzes the correlation between MRI-PDFF value and the “gold index” nonalcoholic steatohepatitis (NASH) liver histological evaluation and explores its advantages and disadvantages as a noninvasive evaluation index for NASH clinical trials. Current studies have shown that MRI-PDFF, as an emerging noninvasive technique, is suitable for quantifying liver fat content and evaluating the degree of hepatic steatosis, but it cannot replace liver biopsy as a tool for the diagnosis of NASH. Meanwhile, the relative reduction in MRI-PDFF after drug intervention is not only highly correlated with the improvement of fat deposition, but also correlated with the improvement of inflammation and ballooning degeneration, and MRI-PDFF can predict the overall improvement of liver histology to a certain extent. Therefore, MRI-PDFF is considered a potential surrogate endpoint for NASH clinical trials.
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The rapidly developing resistance of cancers to chemotherapy agents and the severe cytotoxicity of such agents to normal cells are major stumbling blocks in current cancer treatments. Most current chemotherapy agents have significant cytotoxicity, which leads to devastating adverse effects and results in a substandard quality of life, including increased daily morbidity and premature mortality. The death receptor of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can sidestep p53-dependent pathways to induce tumor cell apoptosis without damaging most normal cells. However, various cancer cells can develop resistance to TRAIL-induced apoptosis via different pathways. Therefore, it is critical to find an efficient TRAIL sensitizer to reverse the resistance of tumor cells to TRAIL, and to reinforce TRAIL's ability to induce tumor cell apoptosis. In recent years, traditional Chinese medicines and their active ingredients have shown great potential to trigger apoptotic cell death in TRAIL-resistant cancer cell lines. This review aims to collate information about Chinese medicines that can effectively reverse the resistance of tumor cells to TRAIL and enhance TRAIL's ability to induce apoptosis. We explore the therapeutic potential of TRAIL and provide new ideas for the development of TRAIL therapy and the generation of new anti-cancer drugs for human cancer treatment. This study involved an extensive review of studies obtained from literature searches of electronic databases such as Google Scholar and PubMed. "TRAIL sensitize" and "Chinese medicine" were the search keywords. We then isolated newly published studies on the mechanisms of TRAIL-induced apoptosis. The name of each plant was validated using certified databases such as The Plant List. This study indicates that TRAIL can be combined with different Chinese medicine components through intrinsic or extrinsic pathways to promote cancer cell apoptosis. It also demonstrates that the active ingredients of traditional Chinese medicines enhance the sensitivity of cancer cells to TRAIL-mediated apoptosis. This provides useful information regarding traditional Chinese medicine treatment, the development of TRAIL-based therapies, and the treatment of cancer.
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Objective@#This systematic review and meta-analysis was undertaken to evaluate the efficacy of antibacterial photodynamic therapy (aPDT) in the treatment of periodontitis in type-2 diabetes mellitus (T2DM) patients and to provide better treatment for patients with T2DM complicated with periodontitis.@*Methods@#The PubMed, Cochrane, Embase, Web of Science, CNKI, CBM, and Wanfang databases were searched for relevant randomized controlled trials (RCTs). RevMan 5.3 was applied for the meta-analysis, and a systematic evaluation was conducted.@*Results@#A total of 8 RCTs were included. The results showed that compared to simple subgingival scaling and root planing (SRP), aPDT assisted SRP had a better effect on improving the probing depth (PD) at 3 months after treatment, The difference was statistically significant [WMD=-0.32,95%CI（-0.45, -0.2）, P < 0.05], but 6 months after treatment, there was no significant difference in the two groups [ WMD=-0.15,95%CI（-0.40, 0.10）,P=0.23]. During the 6-month follow-up period, there were no significant differences in the clinical attachment level (CAL), bleeding on probing (BOP) or hemoglobin A1c (HbA1c) between the two groups (P> 0.05).@*Conclusion@#aPDT-assisted periodontal nonsurgical treatment in T2DM patients can improve PD in the short term but has no significant effect on the improvement of CAL, BOP and HbA1c.
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【Objective】 To explore the establishment methods of transgenic human umbilical cord mesenchymal stem cells (hUC-MSCs) overexpressing tumor necrosis factor(TNF)-related apoptosis-inducing ligand (TRAIL) based on the transposons, and attempt to apply it on the nude mice mode with glioma. 【Methods】 PiggyBac transposon system specially designed by us was used to prepare non-targeting and Her2-targeting hUC-MSCs that can stably express TRAIL through puromycin screening. The glioma cells expressing firefly luciferase (U87MG-LUC) were injected into the skull of the immunodeficient mice (BALB/c-nu/nu) with 1×106 cells per mouse. After 7 days of injection, the mice transplanted with U87MG were detected with a small animal living imager to determine the size and location of the tumors in skull. Then we injected the glioma-transplantation nude mouse with two kinds of transgenic hUC-MSCs expressing TRAIL (named as untarget-TRAIL and target-TRAIL, respectively), or the non-transgenic hUC-MSCs (all 1×106 cells per mouse) or PBS (named as WT-MSCs and PBS for negative control) respectively, and then monitored the changes of tumor signals by a small animal living imager every week for 3~4 weeks. 【Results】 After six passages to expand the cells, the both transgenic cell lines can stably express TRAIL gene. Their ratio of green fluorescent protein (GFP) positive cells can reach 93%-97%, and the positive ratio of their MSC-specific surface markers still maintained normal (CD34+, CD45+, and HLA-DR+ all <0.1%, CD90>99%, CD73>88%, and CD105 >60%). The median survival time (d) of U87MG-transplanted nude mice in the groups of untarget-TRAIL, target-TRAIL, WT-MSCs, and PBS was 41 vs 39 vs 24 vs 23(P<0.05). 【Conclusion】 The transgenic hUC-MSCs overexpressing TRAIL gene can significantly prolong the survival time of nude mice with brain glioma.
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Background: Cancer survivorship results in an increased number of physical and psychosocial health issues. Engaging in physical activity in natural environments is often thought of as restorative. Despite the potential benefits of engaging in physical activity in natural environments there are no sustainable community-based programs for cancer survivors that employ this form of physical activity. This study aims to evaluate the impact of an 8-week trail-walking (TW) program on anxiety in a population of adult cancer survivors. Methods: The TW program consisted of two trail walks per week for 8 weeks led by a hiking guide. Individuals were eligible to participate if they were 19 years or older, were a cancer survivor, were not on active immunotherapy, and had medical clearance from their physician for physical activity. While 12 participants signed up for the program, 9 participants (N = 9, 8 F, 1 M) completed the program. A mixed methodology included preand-post quantitative program surveys and post-program interviews. Questionnaires measured generalized anxiety, sleep disturbances, self-efficacy, self-esteem, psychological well-being and depression as well as pre-and-post hike state anxiety. Data was analysed using paired t-tests. Interviews were transcribed verbatim and an inductive thematic analysis was conducted to consolidate meaning and identify themes using NVivo 11 software. Results: Average attendance was 74% of the 16 hikes. There was no significant reduction in the primary outcome of generalized anxiety (p = .38). There was a significant reduction in perceived stress after 8-weeks (p = .03) and a significant reduction in state anxiety after TW (p < .001). None of the other secondary outcomes were statistically significant (p > .05). Four overarching themes, or benefits, emerged from qualitative data analysis: (a) benefits of program design (b) physical benefits, (c) psychological benefits, and (d) social benefits. Conclusions: These findings demonstrate the utility of a TW program for cancer survivors in order to promote physical, psychological and social health. Feasibility of a TW program would be contingent on access to natural areas for TW and an instructor-led program with other cancer survivors.
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Humans , Male , Female , Adult , Middle Aged , Aged , Anxiety , Walking , Exercise Therapy , Cancer Survivors/psychologyABSTRACT
Background: Preterm neonates post-natal growth should be similar to the intrauterine growth of the fetus of the same gestational age. This study aims to' evaluate the effects of full enteral feed (60 ml/kg/day of human milk on day one, 20ml/kg/day during feeding advancement) started from day one of life (intervention) in enhancing'' the regain of birth weight compared to that of standard feed (both human milk feeds and intravenous fluid) in a group.Methods: Babies were started on enteral feeds with human milk at the rate of 60ml/kg/day from day one and progressed by increments of 20 ml/kg/day up to maximum enteral feed of 180 ml/kg/day. The primary outcomes like Number of days taken to regain the birth weight, Duration of hospital stay, Incidence of Necrotising Enterocolitis (NEC), Incidence of sepsis, need for intravenous fluid therapy was assessed and statically analysed.Results: Full enteral feeding group infants had lesser days of intravenous fluids. Full enteral feeding group regained birth weight at a mean age of 17.37'4.9 days and in the standard feeding group, birth weight was regained at a mean age of 19.8'4.3. Full enteral feeding group regained birth weight at a mean age of 13.12'2.17 days and in standard feeding group at a mean age of 15.38'3.57and this was statistically significant (p - 0.009). Full enteral feeding group babies had lesser number of days of intravenous fluids compared to babies in standard feeding group. It was statistically significant (p - 0.003).Conclusions: Full enteral feeding practices from day one of life with human milk is feasible, cost effective and safe in hemodynamically stable VLBW infants and results in earlier regain of birth weight
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Abstract Aim: This study aimed to present the conceptual, procedural, and attitudinal knowledge of the trail guides (TG) in the Serra da Capivara National Park (SCNP) and Caparaó National Park (CNP). Results: Seventy-nine TGs participated in this descriptive-exploratory research, with a qualitative approach, representing 84% (n = 40) of CNP guides and 80% (n = 39) of SCNP guides. Conclusions: The evidence describes the conceptual, attitudinal, and procedural dimensions displayed before and during trail-walking, with differences in conceptual knowledge, discrepancies in procedural knowledge, and equality in attitudinal aspects. The importance of the participation of the area of physical education was highlighted in the training of TGs, alongside the need to include didactic-pedagogical content, environmental education, exercise physiology, movement biomechanics, flora, fauna, notions of minimal or desirable impact, and first aid.
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Humans , Physical Education and Training/methods , Exercise , Walking/physiology , Environmental Health Education , MovementABSTRACT
OBJECTIVES: The objectives of this study were to determine the sensitivity of ovarian cancer (OC) cell lines (TOV-21G and SKOV-3) to cisplatin and to the recombinant human TRAIL (rhTRAIL), and to evaluate the expression profile of TNFRSF10B, TNFRSF10C, TP53TG5, MDM2, BAX, BCL-2 and CASPASE-8 genes and their participation in the resistance/susceptibility mechanism of these tumor cell lines. METHODS: To determine the IC50 values associated with Cisplatin and rhTRAIL, inhibition of cell growth was observed using MTT assays in two human OC cell lines (SKOV-3 and TOV-21G). The analysis of gene expression was performed using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Both cell lines had different susceptibility profiles to the tested drugs. In the SKOV-3 cell line, the IC50 values for cisplatin and for rhTRAIL were 270.83 ug/mL and 196.5 ng/mL, respectively. The same concentrations were used for TOV-21G. Different gene expression profiles were observed in each tested cell line. CASPASE-8 and TNFRSF10B expression levels could predict the response of both the cell lines to rhTRAIL alone or the response to a combination of rhTRAIL and cisplatin. In addition, we observed a relationship between BCL-2 and BAX expression that may be helpful in estimating the proliferation rate of the OC cell lines. CONCLUSION: SKOV-3 and TOV-21G respond differently to cisplatin and rhTRAIL exposure, and expression of CASPASE-8 and TNFRSF10B are good predictors of responses to these treatments.
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Humans , Female , Ovarian Neoplasms , Cisplatin , Apoptosis , Cell Line, Tumor , Antineoplastic AgentsABSTRACT
Objective: To explore the possibility of promoting tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced apoptosis in prostate cancer PC-3 cell by inhibiting Krüppel-like factor 5 (KLF5). Methods: MTT assay, flow cytometry, Western blot assay and qRT-PCR assay were deployed to detect the cell viability, apoptosis and apoptotic markers in KLF5-inhibited and TRAIL-induced PC-3 cells. Results: After KLF5 was inhibited in TRAIL-induced PC-3 cells, cell viability reduced, apoptosis enhanced, the expressions of DR4 and DR5 increased while the expression of cellular fas-associated death domain-like interleukin-1β converting enzyme inhibitory protein (c-FLIP) decreased. Conclusion: Inhibiting KLF5 suppresses cell viability by promoting TRAIL-induced apoptosis in prostate cancer cell PC-3. It may be a potential means to treat hormone-insensitive prostate cancer.
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At present, SARS-CoV-2 is raging, and novel coronavirus pneumonia (COVID-19) has caused more than 35 million confirmed patients and more than 500 000 cases death, which seriously endanger human health, socioeconomic development, as well as global medical and public health systems. COVID-19 is highly contagious, has a long incubation period, and causes many death cases due to lack of effective specific treatment. Mesenchymal stem cells have powerful anti-inflammatory and immunoregulatory functions, and can effectively reduce the cytokine storm caused by coronavirus in patients, and improve the pulmonary fibrosis of patients, promote the repair of damaged lung tissue, and reduce the mortality. Currently, a number of related clinical trials of mesenchymal stem cell treatment of COVID-19 have been conducted, and have confirmed the safety and efficacy, suggesting a good clinical application prospect. While progress has been made in mesenchymal stem cell therapy for COVID-19, we should also catch sight of the problems and challenges faced by mesenchymal stem cell clinical trials under severe epidemic situation, including clinical trials design, stem cell quality management, and ethics in treatment. Only by paying attention to these can we guarantee the safe and effective development of mesenchymal stem cell clinical trials in the treatment of COVID-19.
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Humans , Betacoronavirus , COVID-19 , Clinical Trials as Topic , Coronavirus Infections/therapy , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/cytology , Pandemics , Pneumonia, Viral/therapy , SARS-CoV-2ABSTRACT
AIM: To estimate the treatment effect before and after patients stopped taking the drug, based on the combination of withdrawal randomized study and active extension trial design. METHODS: The short term treatment effect was estimated separately by the traditional method of using first stage data and the method of taking second or third stage data into consideration. And the treatment difference between long term and short term, also the treatment difference after patients discontinued from treatment were further assessed. The robustness of the result was tested by simulation assumed different scenario. RESULTS: The standard error (0.17) of the treatment effect estimation used more stage data was less than that of only used the first stage (Standard error: 0.19), besides much powerful for those treatment effect could be stabilized in the short period. CONCLUSION: Compared with the method only utilized the data of the first stage, the method developed here utilized second or third stage data. The utilization of more information leaded to decreasing of standard deviation and increasing of validity for the estimation of treatment effect. But the results will be influenced by the time required for the stabilization of the treatment effect, since the method was based on certain assumptions.