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Comparison of high-dose IVIG and rituximab versus rituximab as a preemptive therapy for de novo donor-specific antibodies in kidney transplant patients
Kim HW, Lee J, Heo SJ, Kim BS, Huh KH, Yang J
Scientific reports. 2023;13(1):7682
Abstract
De novo donor-specific antibody (dnDSA) is associated with a higher risk of kidney graft failure. However, it is unknown whether preemptive treatment of subclinical dnDSA is beneficial. Here, we assessed the efficacy of high-dose intravenous immunoglobulin (IVIG) and rituximab combination therapy for subclinical dnDSA. An open-label randomized controlled clinical trial was conducted at two Korean institutions. Adult (aged ≥ 19 years) kidney transplant patients with subclinical class II dnDSA (mean fluorescence intensity ≥ 1000) were enrolled. Eligible participants were randomly assigned to receive rituximab or rituximab with IVIG at a 1:1 ratio. The primary endpoint was the change in dnDSA titer at 3 and 12 months after treatment. A total of 46 patients (24 for rituximab and 22 for rituximab with IVIG) were included in the analysis. The mean baseline estimated glomerular filtration rate was 66.7 ± 16.3 mL/min/1.73 m(2). The titer decline of immune-dominant dnDSA at 12 months in both the preemptive groups was significant. However, there was no difference between the two groups at 12 months. Either kidney allograft function or proteinuria did not differ between the two groups. No antibody-mediated rejection occurred in either group. Preemptive treatment with high-dose IVIG combined with rituximab did not show a better dnDSA reduction compared with rituximab alone.Trial registration: IVIG/Rituximab versus Rituximab in Kidney Transplant With de Novo Donor-specific Antibodies (ClinicalTrials.gov Identifier: NCT04033276, first trial registration (26/07/2019).
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Effect Evaluation of Platelet-Rich Plasma Combined with Vacuum Sealing Drainage on Serum Inflammatory Factors in Patients with Pressure Ulcer by Intelligent Algorithm-Based CT Image
Yang J, Xiao C, Wen H, Sun K, Wu X, Feng X
Computational and mathematical methods in medicine. 2022;2022:8916076
Abstract
This work was to explore the efficacy of intelligent algorithm-based computed tomography (CT) to evaluate platelet-rich plasma (PRP) combined with vacuum sealing drainage (VSD) in the treatment of patients with pressure ulcers. Based on the u-net network structure, an image denoising algorithm based on double residual convolution neural network (Dr-CNN) was proposed to denoise the CT images. A total of 84 patients who were hospitalized in hospital were randomly divided into group A (without any intervention), group B (PRP treatment), group C (VSD treatment), and group D (PRP+VSD treatment). Procalcitonin (PCT) was detected by enzyme-linked immunosorbent assay (ELISA) combined with immunofluorescence method, C-reactive protein (CRP) was detected by rate reflectance turbidimetry (RRT), and interleukin-6 (IL-6) was detected by electrochemiluminescence method. The results showed that after treatment, 44 cases (52.38%) of pressure ulcers patients recovered, 24 cases (28.57%) had no change in stage, and 16 cases (19.04%) developed pressure ulcers. The pain scores of group D at 1 week (3.35 ± 0.56 points) and 2 weeks (2.76 ± 0.55 points) after treatment were significantly lower than those in group C (7.77 ± 0.58 points and 6.34 ± 0.44 points, respectively). The time of complete wound healing in group D (24.5 ± 2.32) was obviously lower in contrast to that in groups A, B, and C (35.54 ± 3.22 days, 30.23 ± 2 days, and 29.34 ± 2.15 days, respectively). In addition, the medical satisfaction of group D (8.74 ± 0.69) was significantly higher than that of groups A, B, and C (4.69 ± 0.85, 5.22 ± 0.31, and 5.18 ± 0.59, respectively). The levels of IL-6 and PCT in group D were lower than those in groups A, B, and C, and the differences were statistically significant (P < 0.01). The average values of peak signal to noise ratio (PSNR) and structural similarity index measure (SSIM) of the Dr-CNN network model were 37.21 ± 1.09 dB and 0.925 ± 0.01, respectively, which were higher than other algorithms. The mean values of root mean square error (MSE) and normalized mean absolute distance (NMAD) of the Dr-CNN network model were 0.022 ± 0.002 and 0.126 ± 0.012, respectively, which were significantly lower than other algorithms (P < 0.05). The experimental results showed that PrP combined with VSD could significantly reduce the inflammatory response of patients with pressure ulcers. PRP combined with VSD could significantly reduce the pain of dressing change for patients. Moreover, the performance model of image denoising algorithm based on double residual convolutional neural network was better than other algorithms.
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Comparative Efficacy and Safety of Thrombopoietin Receptor Agonists in Adults With Thrombocytopenia: A Systematic Review and Network Meta-analysis of Randomized Controlled Trial
Deng J, Hu H, Huang F, Huang C, Huang Q, Wang L, Wu A, Yang J, Qin D, Zou W, et al
Frontiers in pharmacology. 2021;12:704093
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Editor's Choice
Abstract
Thrombopoietin receptor agonists (TPO-RAs) play a crucial role in stimulating thrombopoiesis. However, conventional meta-analyses have shown inconsistent results regarding the efficacy of thrombopoietin receptor agonists versus placebo. Therefore, we performed a network meta-analysis to assess the effects of five TPO-RAs via indirect comparison. For this network meta-analysis, we considered randomized trials that included any of the following interventions: avatrombopag, lusutrombopag, eltrombopag, romiplostim, recombinant human thrombopoietin (rhTPO). We searched the Medline, PubMed, Embase, the Cochrane Library, and Web of Science databases for randomized controlled clinical trials from inception to January 31, 2021. We use randomized controlled clinical trials of TPO-RAs for treatment of immune thrombocytopenia in adults. The primary outcome was the number of patients achieving platelet response which was defined as the achievement of a platelet count of more than 30 or 50 cells × 10(9)/L in the absence of rescue therapy, and the secondary outcome was the therapy-related serious adverse events and incidence of bleeding episodes. To obtain the estimates of efficacy and safety outcomes, we performed a random-effects network meta-analysis. These estimates were presented as odds ratios with 95% confidence intervals. We use surface under the cumulative ranking probabilities to rank the comparative effects and safety of all drugs against the placebo. In total, 2,207 patients were analyzed in 20 clinical trials. All preparations improved the point estimates of platelet response when compared with the placebo. Avatrombopag and lusutrombopag had the best platelet response compared to the placebo, the former had a non-significant advantage compared to the latter [odds ratio (OR) = 1.91 (95% confidence interval: 0.52, 7.05)]. The treatments were better than eltrombopag, romiplostim, rituximab, and rhTPO + rituximab, with corresponding ORs of 3.10 (1.01, 9.51), 9.96 (2.29, 43.29), 33.09 (8.76, 125.02), and 21.31 (3.78, 119.98) for avatrombopag and 1.62 (0.63, 4.17), 5.21 (1.54, 17.62), 17.34 (5.15, 58.36), and 11.16 (2.16, 57.62) for lusutrombopag. Regarding bleeding, the placebo group had the highest probability of bleeding, whereas lusutrombopag had the lowest risk of bleeding when compared to the placebo. Adverse events were slightly higher in patients receiving rituximab than in those receiving placebo or other treatments. Overall, this meta-analysis showed that avatrombopag may yield the highest efficacy because it has the most favorable balance of benefits and acceptability.
PICO Summary
Population
Adults with thrombocytopenia (20 studies, n= 2,207).
Intervention
Thrombopoietin receptor agonists: avatrombopag, lusutrombopag, eltrombopag, romiplostim, recombinant human thrombopoietin.
Comparison
Placebo.
Outcome
All preparations improved the point estimates of platelet response when compared with the placebo. Avatrombopag and lusutrombopag had the best platelet response compared to the placebo, the former had a non-significant advantage compared to the latter [odds ratio (OR)= 1.91 (95% confidence interval: 0.52, 7.05)]. The treatments were better than eltrombopag, romiplostim, rituximab, and rhTPO + rituximab, with corresponding ORs of 3.10 (1.01, 9.51), 9.96 (2.29, 43.29), 33.09 (8.76, 125.02), and 21.31 (3.78, 119.98) for avatrombopag and 1.62 (0.63, 4.17), 5.21 (1.54, 17.62), 17.34 (5.15, 58.36), and 11.16 (2.16, 57.62) for lusutrombopag. Regarding bleeding, the placebo group had the highest probability of bleeding, whereas lusutrombopag had the lowest risk of bleeding when compared to the placebo. Adverse events were slightly higher in patients receiving rituximab than in those receiving placebo or other treatments.
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Recombinant human thrombopoietin prior to mobilization chemotherapy facilitates platelet recovery in autologous transplantation in patients with lymphoma: Results of a prospective randomized study
Mo H, Liu P, Qin Y, He X, Han X, Yao J, Su W, Zhang S, Tang L, Zhao F, et al
Chronic diseases and translational medicine. 2021;7(3):190-198
Abstract
BACKGROUND Chemotherapy plus granulocyte colony-stimulating factor (GCSF) regimen is one of the available approaches to mobilize peripheral blood progenitor cells (PBPCs). It causes thrombocytopenia and delays leukapheresis. This study aimed to evaluate the role of recombinant human thrombopoietin (rhTPO) before mobilization chemotherapy in facilitating leukapheresis in patients with lymphoma. METHODS In this randomized open-label phase 2 trial, patients were randomly assigned in a 1:2 ratio to receive mobilization with rhTPO plus GCSF in combination with chemotherapy (the rhTPO plus GCSF arm) or GCSF alone in combination with chemotherapy (the GCSF alone arm). The recovery of neutrophils and platelets and the amount of platelet transfusion were monitored. RESULTS Thirty patients were enrolled in this study between March 2016 and August 2018. Patients in the rhTPO plus GCSF arm (n = 10) had similar platelet nadir after mobilization chemotherapy (P=0.878) and similar amount of platelet transfusion (median 0 vs. 1 unit, P=0.735) when compared with the GCSF alone arm (n = 20). On the day of leukapheresis, the median platelet count was 86 × 10(9)/L (range 18-219) among patients who received rhTPO and 73 × 10(9)/L (range 42-197) among those who received GCSF alone (P=0.982). After the use of rhTPO, the incidence of platelet count <75 × 10(9)/L on the day of leukapheresis did not decrease significantly (30.0% vs. 50.0%, P=0.297). Platelet recovery after PBPC transfusion was more rapid in the rhTPO plus GCSF arm (median 8.0 days [95% confidence interval 2.9-13.1] to platelets ≥50 × 10(9)/L vs. 11.0 days [95% confidence interval 8.6-13.4], P=0.011). The estimated total cost of the mobilization and reconstitution phases per patient was similar between the two treatmtent groups (P=0.362 and P=0.067, respectively). CONCLUSIONS Our findings indicate that there was no significant clinical benefit of rhTPO use in facilitating mobilization of progenitor cells, but it may promote platelet recovery in the reconstitution phase after high-dose therapy. TRIAL REGISTRATION This trial has been registered in Clinicaltrials.gov as NCT03014102.
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Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19: A Randomized Clinical Trial
Li L, Zhang W, Hu Y, Tong X, Zheng S, Yang J, Kong Y, Ren L, Wei Q, Mei H, et al
Jama. 2020
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Abstract
Importance: Convalescent plasma is a potential therapeutic option for patients with coronavirus disease 2019 (COVID-19), but further data from randomized clinical trials are needed. Objective: To evaluate the efficacy and adverse effects of convalescent plasma therapy for patients with COVID-19. Design, Setting, and Participants: Open-label, multicenter, randomized clinical trial performed in 7 medical centers in Wuhan, China, from February 14, 2020, to April 1, 2020, with final follow-up April 28, 2020. The trial included 103 participants with laboratory-confirmed COVID-19 that was severe (respiratory distress and/or hypoxemia) or life-threatening (shock, organ failure, or requiring mechanical ventilation). The trial was terminated early after 103 of a planned 200 patients were enrolled. Intervention: Convalescent plasma in addition to standard treatment (n = 52) vs standard treatment alone (control) (n = 51), stratified by disease severity. Main Outcomes and Measures: Primary outcome was time to clinical improvement within 28 days, defined as patient discharged alive or reduction of 2 points on a 6-point disease severity scale (ranging from 1 [discharge] to 6 [death]). Secondary outcomes included 28-day mortality, time to discharge, and the rate of viral polymerase chain reaction (PCR) results turned from positive at baseline to negative at up to 72 hours. Results: Of 103 patients who were randomized (median age, 70 years; 60 [58.3%] male), 101 (98.1%) completed the trial. Clinical improvement occurred within 28 days in 51.9% (27/52) of the convalescent plasma group vs 43.1% (22/51) in the control group (difference, 8.8% [95% CI, -10.4% to 28.0%]; hazard ratio [HR], 1.40 [95% CI, 0.79-2.49]; P = .26). Among those with severe disease, the primary outcome occurred in 91.3% (21/23) of the convalescent plasma group vs 68.2% (15/22) of the control group (HR, 2.15 [95% CI, 1.07-4.32]; P = .03); among those with life-threatening disease the primary outcome occurred in 20.7% (6/29) of the convalescent plasma group vs 24.1% (7/29) of the control group (HR, 0.88 [95% CI, 0.30-2.63]; P = .83) (P for interaction = .17). There was no significant difference in 28-day mortality (15.7% vs 24.0%; OR, 0.65 [95% CI, 0.29-1.46]; P = .30) or time from randomization to discharge (51.0% vs 36.0% discharged by day 28; HR, 1.61 [95% CI, 0.88-2.93]; P = .12). Convalescent plasma treatment was associated with a negative conversion rate of viral PCR at 72 hours in 87.2% of the convalescent plasma group vs 37.5% of the control group (OR, 11.39 [95% CI, 3.91-33.18]; P < .001). Two patients in the convalescent plasma group experienced adverse events within hours after transfusion that improved with supportive care. Conclusion and Relevance: Among patients with severe or life-threatening COVID-19, convalescent plasma therapy added to standard treatment, compared with standard treatment alone, did not result in a statistically significant improvement in time to clinical improvement within 28 days. Interpretation is limited by early termination of the trial, which may have been underpowered to detect a clinically important difference. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2000029757.
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Association between ABO blood groups and COVID-19 infection, severity and demise: A systematic review and meta-analysis
Wu BB, Gu DZ, Yu JN, Yang J, Chen HL
Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases. 2020;:104485
Abstract
BACKGROUND AND AIMS The COVID-19 spreads rapidly around the world which has brought a global health crisis. The pathogen of COVID-19 is SARS-COV-2, and previous studies have proposed the relationship between ABO blood group and coronavirus. Here, we aim to delve into the association between ABO blood group and COVID-19 infection, severity and demise. METHODS The relevant studies were retrieved from five databases: PubMed, MedRxiv, BioRxiv,Web of Science and CNKI. Members of cases(symptomatic cases, severe cases, died cases) and controls(asymptomatic controls, non-severe controls, alive controls) were extracted from collected studies. Odds ratios (OR) and 95% confidence intervals (CI) were calculated and interpreted from extracted data. Publication bias and sensitivity analysis were also applied to confirm our discovery. RESULTS Overall 31,100 samples were included in the analysis. Compared to other ABO blood type, an increased odds of infecting COVID-19 among individuals with A blood group (OR: 1.249, 95%CI: 1.114-1.440, P < 0.001) and a decreased odds of infecting COVID-19 among individuals with blood group O (OR: 0.699, 95%CI: 0.635-0.770, P < 0.001) were found. Besides, individuals with blood group AB seems to link a higher risk to COVID-19 severity (OR: 2.424, 95%CI: 0.934-6.294) and demise (OR: 1.348, 95%CI: 0.507-3.583). Meantime, individuals with O blood group might had lower risk to COVID-19 severity (OR: 0.748, 95%CI: 0.556-1.007), and individuals with B blood group were likely to relate a lower risk to COVID-19 demise. CONCLUSIONS The current meta-analysis suggest that blood type A might be more susceptible to infect COVID-19 while blood type O might be less susceptible to infect COVID-19; there were no correlation between ABO blood group and severity or demise of COVID-19. However, more investigation and research are warranted to clarify the relationship between COVID-19 and ABO blood type.
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[Micro-fracture therapy combined with intra-articular injection of platelet-rich plasma for small sized osteochondral lesion of the talus]
Yang J
Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery. 2020;34(1):53-56
Abstract
Objective: To investigate the effectiveness of micro-fracture therapy combined with intra-articular injection of platelet-rich plasma (PRP) in the treatment of small sized osteochondral lesion of the talus (OLT). Methods: Between September 2014 and October 2017, 43 patients with small sized OLT met the inclusive criteria were admitted and randomly divided into micro-fracture group (21 cases) and combined group (22 cases). Patients in the micro-fracture group were treated with micro-fracture therapy, and patients in the combined group were treated with micro-fracture therapy combined with intra-articular injection of PRP. There was no significant difference in gender, age, disease duration, side of OLT, injured position, lesion area, Mintz classification, and preoperative American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hind foot score and visual analogue scale (VAS) score between the two groups ( P>0.05). After treatment, MRI, VAS score, and AOFAS ankle-hind foot score were used to evaluate the recovery of OLT and the ankle function. Results: All incisions healed by first intention, and no complications such as venous thrombosis and ankle joint infection occurred. All patients were followed up 12-18 months after operation, with an average of 15.6 months. The VAS scores and the AOFAS ankle-hind foot scores were significantly improved at 6 and 12 months after operation in the two groups ( P<0.05), and the scores at 12 months were significantly improved when compared with postoperative scores at 6 months ( P<0.05). Compared with the micro-fracture group, the VAS score and the AOFAS ankle-hind foot score were significantly improved in the combined group at 6 and 12 months after operation ( P<0.05). MRI showed that OLT was well filled in both groups at 12 months after operation. Conclusion: Compared with micro- fracture therapy, micro-fracture therapy combined with intra-articular injection of PRP can effectively reduce pain, improve ankle function, and has a good effectiveness in the treatment of small sized OLT.
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Platelet-rich plasma versus autologous blood versus corticosteroid injections in the treatment of lateral epicondylitis: a systematic review, pairwise and network meta-analysis of randomized controlled trials
Tang S, Wang X, Wu P, Wu P, Yang J, Du Z, Liu S, Wei F
PM & R : the journal of injury, function, and rehabilitation. 2019
Abstract
OBJECTIVE To compare the effectiveness of platelet-rich plasma (PRP), autologous blood (AB), and corticosteroid injections in patients with lateral epicondylitis. TYPE OF STUDY Network meta-analysis. LITERATURE SURVEY Randomized controlled trials (RCTs) that compared any two forms of injections among PRP, AB, and corticosteroid for the treatment of lateral epicondylitis were searched from inception to November 30, 2018, on PubMed, Embase, and Cochrane library. METHODOLOGY Two researchers independently selected and assessed the quality of RCTs with the Cochrane Risk of Bias Tool. All relevant data from the included studies were extracted and heterogeneity was checked by Cochran's Q test and inconsistency statistic (I(2) ). Publication bias was evaluated by constructing contour-enhanced funnel plots. Stata 15 software was applied for pairwise meta-analysis and network meta-analysis. To explore the efficacy between different follow-up periods, we considered the duration within two months to be short-term, whereas two months or more was considered long-term. SYNTHESIS Twenty RCTs (n = 1,271) were included in this network meta-analysis. According to ranking probabilities, corticosteroid ranked first for visual analog score (VAS) (Surface Under the Cumulative Ranking [SUCRA] = 90.7), modified Nirschl score (MNS) (82.9), maximum grip strength (MGS) (69.5), modified Mayo score (MMS) (77.9), and Patient-Related Tennis Elbow Evaluation (PRTEE) score (93.3) for the short-term period. For the long-term period, PRP ranked first for VAS (94.3), pressure pain threshold (PPT) (99.8), Disabilities of Arm Shoulder and Hand (DASH) score (75.2), MMS (88.2), and the PRTEE score (81.8). CONCLUSION PRP was associated with more improvement in pain intensity and 29 function in the long-term than the comparators. However, in the short-term, corticosteroids were associated with the most improvement. This article is protected by copyright. All rights reserved.
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Efficacy and Safety of Avatrombopag in Patients With Thrombocytopenia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Li C, Li X, Huang F, Yang J, Wu A, Wang L, Qin D, Zou W, Wu J
Frontiers in pharmacology. 2019;10:829
Abstract
Background: Avatrombopag is a novel oral, nonpeptide thrombopoietin receptor agonist (TPO-RA). A few studies have shown that avatrombopag is effective against thrombocytopenia. However, no systematic review has been conducted on the efficacy and safety of avatrombopag. Therefore, the aim of this study was to comprehensively assess the efficacy and safety of avatrombopag patients with thrombocytopenia. Methods: Databases including Medline, PubMed, Embase, the Cochrane Library and ClinicalTrials.gov were searched for randomized controlled trials that compared avatrombopag with placebo in patients with thrombocytopenia. The deadline was March 2019. Results: In total, 743 patients were analyzed in five clinical trials. Patients treated with avatrombopag achieved higher platelet response (OR: 17.71, 95% CI [11.01 to 28.48], p < 0.00001) than with placebo. Avatrombopag produced an absolute increment in platelet count (WMD: 31.13%, 95% CI [22.27 to 39.99], p < 0.00001) unlike the placebo. In addition, the incidence of serious adverse events (RR: 1.18, 95% CI [0.72 to 1.93], p = 0.51) and deaths (RR: 0.93, 95% CI [0.19 to 4.45], p = 0.93) in patients treated with avatrombopag was not significantly different from that in patients treated with placebo. The incidence of adverse events in patients treated with avatrombopag was slightly higher than that in patients treated with placebo (RR: 1.25, 95% CI [1.05 to 1.49], p = 0. 01) after one trial with high heterogeneity was removed. Conclusions: This meta-analysis showed that avatrombopag was an effective treatment for thrombocytopenia, but there is sufficient evidence to indicate that adverse events may occur.
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Influence of tourniquet use in primary total knee arthroplasty with drainage: a prospective randomised controlled trial
Zhou K, Ling T, Wang H, Zhou Z, Shen B, Yang J, Kang P, Pei F
Journal of Orthopaedic Surgery and Research. 2017;12((1)):172.
Abstract
BACKGROUND We aimed to compare the effect of tourniquet use or lack of it on recovery following uncomplicated primary total knee arthroplasty (TKA). METHODS In a prospective randomised double-blinded study, 150 patients undergoing primary TKA were assigned to either a tourniquet or non-tourniquet group. At the early phase, 3 and 6 months after surgery, an independent observer assessed the primary outcome measure (i.e. total blood loss) and secondary outcome measures (i.e. wound complications, visual analogue scale pain score and knee range of motion). RESULTS The tourniquet group exhibited reduced intraoperative blood loss (215.7 +/- 113.7 ml vs. 138.6 +/- 93.9 ml, P < 0.001) and shorter operating time (77.2 +/- 14.5 min vs. 82.0 +/- 12.7 min, P = 0.038). However, the non-tourniquet group showed less postoperative blood loss (180.2 +/- 117.0 ml vs. 253.7 +/- 144.2 ml, P = 0.001) and drainage volume (89.2 +/- 66.3 ml vs. 164.5 +/- 97.8 ml, P = 0.004), less thigh pain (all P < 0.001) in the initial 3 weeks, better knee range of motion (ROM) in the initial 3 days (day 1 81.6 +/- 17.1 vs. 75.95 +/- 14.55, P = 0.036; day 3 99.8 +/- 13.7 vs. 93.95 +/- 11.15, P = 0.005) and fewer wound tension vesicles (10.3 vs. 29.2%, P = 0.005). Earlier straight-leg raising (4.6 +/- 3.8 h vs. 6.4 +/- 4.3 h, P = 0.01) and shorter length of stay (6.3 +/- 1.7 days vs. 7.1 +/- 1.9 days, P = 0.001) were found in the non-tourniquet group. Similar total blood loss and blood transfusion rate were observed for both groups. All other parameters revealed no significant differences. CONCLUSIONS Our study suggests that a non-tourniquet TKA would lead to early rehabilitation without increasing side effects. TRIAL REGISTRATION Chinese Clinical Trials Registry, ChiCTR-IOR-16007851 , 1/29/2016.