Objective:To investigate the clinical characteristics and prognostic factors of TCF3-PBX1 fusion gene-positive childhood B-cell precursor acute lymphoblastic leukemia (B-ALL).Methods:The clinical data of 1 287 newly diagnosed children with B-ALL who were admitted to five hospital in Fujian province (Fujian Medical University Union Hospital, the First Affiliated Hospital of Xiamen University, Zhangzhou Affiliated Hospital of Fujian Medical University, Quanzhou First Hospital Affiliated to Fujian Medical University, Nanping First Hospital of Fujian Province) from April 2011 to December 2020 were retrospectively analyzed. According to the results of TCF3-PBX1 fusion gene testing, all the patients were divided into TCF3-PBX1-positive group and TCF3-PBX1-negative group. The clinical characteristics, early treatment response [minimal residual disease (MRD) at middle stage and end of induction chemotherapy] and long-term efficacy [overall survival (OS) and event-free survival (EFS)] of the patients in both groups were compared. Kaplan-Meier method was used for survival analysis. The prognostic factors of TCF3-PBX1-positive B-ALL were analyzed by using Cox proportional hazards model. Among 83 children with TCF3-PBX1-positive B-ALL, the treatment regimens, risk stratification and efficacy evaluation of 62 cases were performed by using Chinese Children's Leukemia Group (CCLG)-ALL 2008 regimen and 21 cases were performed by using Chinese Children's Cancer Group (CCCG)-ALL 2015 regimen, and the efficacy and incidence of serious adverse events (SAE) between the two groups compared.Results:Among 1 287 B-ALL patients, 83 patients (6.4%) were TCF3-PBX1-positive. The proportion of patients with initial white blood cell count (WBC)≥50×10 9/L in the TCF3-PBX1-positive group was higher than that in the TCF3-PBX1-negative group, while the proportions of patients with MRD ≥1% on induction chemotherapy day 15 or day 19, and MRD ≥0.01% on induction chemotherapy day 33 or day 46 in the TCF3-PBX1-positive group were lower than those in the TCF3-PBX1-negative group (all P < 0.05). Univariate Cox regression analysis showed that MRD ≥1% on induction chemotherapy day 15 or day 19 and TCF3-PBX1 ≥0.01% on induction chemotherapy day 33 or day 46 were risk factors for OS and EFS (all P < 0.05). Multivariate analysis showed that MRD ≥1% on induction chemotherapy day 15 or day 19 was an independent risk factor for OS ( HR = 10.589, 95% CI 1.903-58.933, P = 0.007) and EFS ( HR = 10.218, 95% CI 2.429-42.980, P = 0.002). TCF3-PBX1≥0.01% on induction chemotherapy day 33 or day 46 was an independent risk factor for EFS ( HR = 6.058, 95% CI 1.463-25.087, P = 0.013) but not for OS ( HR = 3.550, 95% CI 0.736-17.121, P = 0.115). The 10-year EFS and OS rates of the TCF3-PBX1-positive group were 84.6% (95% CI 76.9%-93.1%) and 89.1% (95% CI 82.1%-96.6%), and the differences between the two groups were not statistically significant (both P > 0.05). Among 80 children who received standardized treatment, compared with children who were treated with CCLG-ALL 2008 regimen, the incidence of infection-related SAE was lower in children who were treated with CCCG-ALL 2015 regimen [0 (0/21) vs. 20.3% (12/59), χ2 = 5.22, P = 0.022], but there were no statistical differences in treatment-related mortality, relapse rate, EFS and OS between the two groups (all P > 0.05). Conclusions:Children with TCF3-PBX1-positive B-ALL have a good prognosis, and MRD≥1% at middle stage of induction chemotherapy and TCF3-PBX1≥0.01% at the end of induction chemotherapy may be influencing factors for poor prognosis. CCCG-ALL 2015 regimen can reduce infection-related SAE while achieving good efficacy.

Hypoxia conditioning could increase the survival of transplanted neuronal progenitor cells (NPCs) in rats with cerebral ischemia but could also hinder neuronal differentiation partly by suppressing mitochondrial metabolism. In this work, the mitochondrial metabolism of hypoxia-conditioned NPCs (hcNPCs) was upregulated via the additional administration of resveratrol, an herbal compound, to resolve the limitation of hypoxia conditioning on neuronal differentiation. Resveratrol was first applied during the in vitro neuronal differentiation of hcNPCs and concurrently promoted the differentiation, synaptogenesis, and functional development of neurons derived from hcNPCs and restored the mitochondrial metabolism. Furthermore, this herbal compound was used as an adjuvant during hcNPC transplantation in a photothrombotic stroke rat model. Resveratrol promoted neuronal differentiation and increased the long-term survival of transplanted hcNPCs. 18-fluorine fluorodeoxyglucose positron emission tomography and rotarod test showed that resveratrol and hcNPC transplantation synergistically improved the neurological and metabolic recovery of stroke rats. In conclusion, resveratrol promoted the neuronal differentiation and therapeutic efficiency of hcNPCs in stroke rats via restoring mitochondrial metabolism. This work suggested a novel approach to promote the clinical translation of NPC transplantation therapy.
Animals ; Brain Ischemia/drug therapy* ; Cell Differentiation ; Hypoxia ; Neurons ; Rats ; Resveratrol/pharmacology*

OBJECTIVE: To establish a clinically applicable model of rapid identification of adverse drug reaction program (RiADP) for risk management and decision-making of clinical drug use. METHODS: Based on the theory of disproportion analysis, frequency method and Bayes method, a clinically applicable RiADP model in R language background was established, and the parameters of the model were interpreted by MedDRA coding. Based on the actual monitoring data of FDA, the model was validated by the assessing hepatotoxicity of lopinavir/ritonavir (LPV/r). RESULTS: The established RiADP model included four parameters: standard value of adverse drug reaction signal information, empirical Bayesian geometric mean value, ratio of reporting ratio and number of adverse drug reaction cases. Through the application of R language parameter package "phViD", the model parameters could be output quickly. After being encoded by MedDRA, it was converted into clinical terms to form a clinical interpretation report of adverse drug reactions. In addition, the evaluation results of LPV/r hepatotoxicity by the model were matched with the results reported in latest literature, which also proved the reliability of the model results. CONCLUSIONS In this study, a rapid identification method of adverse reactions based on post marketing drug monitoring data was established in R language environment, which is capable of sending rapid warning of adverse reactions of target drugs in public health emergencies, and providing intuitive evidence for risk management and decision-making of clinical drugs.
Databases, Pharmaceutical ; Decision Making, Computer-Assisted ; Drug Monitoring ; Drug-Related Side Effects and Adverse Reactions ; HIV Protease Inhibitors ; adverse effects ; pharmacology ; Humans ; Liver ; drug effects ; Lopinavir ; adverse effects ; toxicity ; Models, Statistical ; Reproducibility of Results ; Software ; standards

Objective To explore the related factors which affect the prognosis of traumatic brain injury (TBI) patients and provide the basis for clinical diagnosis and treatment.Methods One hundred and thirty-four TBI patients were selected from May 2017 to April 2018 in the Department of Neurosurgery of Wuwei Liangzhou Hospital.Death and discharge were used as endpoint events.The patients were divided into survival group (n =103) and death group (n =31) according to their prognosis.The abbreviated injury scale (AIS),glasgow coma scale (GCS),vital signs,thrombelastography,coagulation function and Chinese DIC scoring system (CDSS) of the patients at the time of admission was completed.The measurement data were compared with the t test,the count data were compared with chi-square test and logistic regression was used for multivariate regression analysis.Results The AIS was (4.7 ± 0.9) scores,CDSS was (7.8 ± 1.1) scores,GCS was (5.8 ± 1.4) scores,the R time of thrombelastography was (15.1 ± 5.6) min in death group.The AIS was (4.3 ± 0.8) scores,CDSS was (6.6 ± 0.6) scores,GCS was (8.6 ± 1.7) scores,the R time of thrombelastography was (8.6 ± 3.4) min in survival group.Single factor analysis showed that the AIS and CDSS were higher,GCS was lower and the R time of thrombelastography was longer in death group than in survival group,and there were statistical differences between the two groups (P ＜ 0.05).The multivariate logistic regression analysis showed that GCS,CDSS and R time were the independent risk factors of the prognosis of TBI patients.The area under the receiver operating characteristic curves of GCS,CDSS and R time were 0.731,0.648 and 0.635,respectively.Conclusion GCS,CDSS and R time can be used as predictive risk factors for prognosis of TBI patients.

OBJECTIVE:To explore an effective method to formulate management-related strategies for off-lable use of drugs by the evidence-based medicine. METHODS:The process of guideline formulation included seven procedures,i.g. establishment ofguideliesformulation workgroup;investigation and selection of the status quo on off-label drug use;identification of the clinical problems;retrieval and evaluation and comprehensing of evidence;applification of GRADE in evidence quality grading;formation of the recommendations consensus;peer review and result publication. And eventually guidelines were formed based on the steps. This study took off-label use of rheumatoid immunoprotective subjects as a case to explore. RESULTS & CONCLUSIONS:Based on the evidence evaluation system and above 7 steps,the methods and process of guideline formulation on off-label use of rheuma-toid immunoprotective subjects that integrated administration,law,clinical medicine,pharmacy subjects were made .The process of guideline formulation fully reflects multidisciplinary characteristics of the workgroup,the advanced nature of the process,the comprehensiveness of evidence ,the rigor of evidence quality grading,and the normalization of consensus. It provides reference in methodology for establishing a comprehensive evidence-based evaluation and management system of off-label use of drugs for all clinical specialist disease. Therefore,this scientific research results may promote the standardization and legalization of the off-label use of drugs management in China.

Objective To observe the clinical efficacy and safety of direct-acting antiviral agents(DAAs)in the treatment of hepatitis C after renal transplantation. Methods Six patients were complicated with hepatitis C virus(HCV) at 8 to 43 months after renal transplantation with a median time of 19 months. Prior to treatment, the virus load was detected from 4.03×103 to 8.18×107 IU/mL. Four cases were administered with tacrolimus(FK506)+mycophenolate mofetil(MMF)+prednisone(Pred), and the remaining 2 received cyclosporin(CsA)+MMF+Pred. The serum creatinine level was lower than 200μmol/L. The amount of urine and body weight remained stable. No severe mental irritation or trauma history wasreportedwithin6monthsbeforeantiviraltherapy.SixpatientsdidnotreceivegenotypetestofHCVbeforeDAAstherapy. Fourpatientswereadministeredwithsofosbuvir,1withsofosbuvir+ledipavirand1withsofosbuvir+daclatasvirfor12weeks. The complete blood cel count, serum transaminase level, creatinine level and blood concentration of immunosuppressive agents were measured each week and serum HCV RNA level was quantitatively detected every 4 weeks. Results Among 6 patients, 5 were negative for HCV at 4 weeks after DAAs therapy and obtained sustained virological response(SVR)after DAAs treatment. One case administered with sofosbuvir alone was positive for HCV after DAAs therapy. The patient was infected with genotype 5 HCV. After 12-week administration of sofosbuvir+daclatasvir, the patient was negative for HCV and obtained SVR. No significant changes were observed in complete blood cel count, serum transaminase level, creatinine level and blood concentration of immunosuppressive agents. Adverse reactions included evanescent eruption in 1 case and mild dizziness in 1 case. Conclusions DAAs treatment is an effective and safe approach for patients with stable renal function after renal transplantation. Combined use of sofosbuvir+daclatasvir is recommended as the optimal therapy.

Objective To investigate the correlation between red cell volume distribution width (RDW) and the mortality rate of acute respiratory distress syndrome (ARDS) patients after renal transplantation. Methods Clinical data of 106 ARDS patients undergoing renal transplantation were retrospectively analyzed. According to RDW, all patients were assigned into the normal (≤15.0%, n=68) and increasing RDW groups (>15.0%, n=38). Baseline data and the incidence of adverse events were statistically compared between two groups. Kaplan-Meier survival curve was adopted to compare the 50 d-mortality rate between two groups. Cox's proportional hazards regression model was utilized to identify the risk factors of the mortality of ARDS patients. Results Among 106 patients, the 50 d-mortality rate was calculated as 43.4% (46/106). The sequential organ failure assessment (SOFA) score, serum creatinine, hemoglobin and platelet count significantly differed between two groups (all P<0.05). In the increasing RDW group, the 50 d-mortality rate and the incidence of infectious shock were significantly higher than those in the normal RDW group (both P<0.05). Kaplan-Meier survival curve demonstrated that the 50 d-mortality rate significantly differed between two groups (P<0.01). Cox's proportional hazards regression model univariate analysis revealed that hemoglobin level<100 g/L, serum creatinine>133 μmol/L, platelet count<100×109/L, severe ARDS and RDW>15.0% were the potential risk factors of the 50 d-mortality rate in ARDS patients (all P<0.05). Multivariate analysis demonstrated that severe ARDS [odd ratio (OR)=12.77, 95%confidence interval (CI) 11.63-15.39, P<0.001] and RDW>15.0% (OR=2.01, 95%CI 1.02-3.94, P<0.043) were the independent risk factors of the 50 d-mortality rate in ARDS patients. Conclusions RDW elevation is correlated with the severity of disease and 50 d-mortality rate in ARDS patients following renal transplantation. RDW can serve as a clinical parameter to predict the prognosis of ARDS patients after renal transplantation.

BACKGROUNDOur goal was to evaluate the outcomes of kidney transplants from controlled cardiac death donors compared with brain death donors by conducting a meta-analysis of cohort studies.

METHODSThe PubMed database and EMBASE were searched from January 1980 to July 2013 to identify studies that met pre-stated inclusion criteria. Reference lists of retrieved articles were also reviewed. Two authors independently extracted information on the designs of the studies, the characteristics of the study participants, and outcome assessments.

RESULTSNine cohort studies involving 84 398 participants were included in this meta-analysis; 3 014 received kidneys from controlled cardiac death donors and 80 684 from brain death donors. Warm ischemia time was significantly longer for the controlled cardiac death donor group. The incidence of delayed graft function was 2.74 times (P < 0.001) greater in the controlled cardiac death donor group. The results are in favor of the brain death donor group on short-term patient and graft survival while this difference became nonsignificant at mid-term and long term. Sensitivity analysis yielded similar results. No evidence of publication bias was observed.

CONCLUSIONThis meta-analysis of retrospective cohort studies suggests that the outcome after controlled cardiac death donors is comparable with that obtained using kidneys from brain death donors.

Objective To investigate modified technique of renal transplantation model in rats.Methods Sprague-Dawley rats were selected as donors ( n=21 ) and Wistar rats as recipients ( n=42 ) .Renal allografts of both sides were harvested from the donors for renal transplantation.After resection of left kidney , end-to-end anastomosis of renal arteries between donor and recipient was performed by the assistance of home-made catheter.And end-to-end anastomosis between recipient's renal vein and donor's inferior vena cava was also performed.The donor's ureter with bladder patch was anastomosed to the recipient's bladder.Finally the right kidney was removed , cefminox (10 mg) was injected intraperitoneally , and then the abdominal cavity was closed.The operation data were recorded , including the operation time , artery and vein anastomosis time , cold and warm ischemia time and so on.Living for 3 days after operation was regarded as a success model.The success rate of modeling was calculated and the cause of death was analyzed.Results The operation time of donor was (32.7 ±5.6) min, and repair time for kidney was (4.2 ±1.1) min.The operation time of recipient was (42.3 ±42.3) min, including (10.1 ±3.2) min of the artery anastomosis time , (13.9 ±2.5) min of vein anastomosis time, (6.3 ±1.4) min of urinary tract reconstruction time.Warm ischemia time was (5.4 ± 1.8) s, and cold ischemia time was (56.2 ±7.3) min.In 42 recipient rats, 40 rats were successful modeling and the success rate was 95.2%.Two rats died.One died of artery anastomosis hemorrhage , and the other died of diffuse peritonitis caused by urine leakage.Conclusions Renal transplantation model in rats with modified vascular end-to-end anastomosis has the characters of simple handling , short operation time and high success rate.

Objective:To identify the polymorphisms of cytochrome P450 3A5 gene (CYP3A5) and multidrug resistance gene 1 (MDR-1) and their distributions in Hans renal transplant recipients in Hunan province, we analyzed the difference of the gene polymorphisms and distributions between Hunan province and 11 other provinces of China.
Methods:We collected 598 Hans renal transplant recipients who had operation or follow-up examination in 3rd Xiangya Hospital from Hunan province. We examined the gene polymorphisms of CYP3A5 and MDR-1 and compared their distributions with the data from 11 other provinces of China by chi-square test.
Results:hTere were CYP3A5*1/*1 genotype in 58 cases (9.7%), CYP3A5*1/*3 genotype in 251 cases (42.0%), CYP3A5*3/*3 genotype in 289 cases (48.3%);MDR-1 3435CC genotype in 238 cases (39.8%), MDR-1 3435CT genotype in 263 cases (44.0%), MDR-1 3435TT genotype in 97 cases (16.2%). Frequency of CYP3A5*1/*1 and*1/*3 genotypes of Hunan province was higher than the that from the 11 other provinces of China and the frequency of mutator*3 was lower. Frequency of MDR-1 3435CC and 3435CT genotypes of Hunan province was higher and the frequency of mutator T was lower than that from the 11 other provinces of China.
Conclusions:There were significant difference in gene polymorphisms and distributions of CYP3A5 and MDR-1 between Hunan province and the 11 other provinces of China. It may be a guideline for us to use calcineurin inhibitor drugs in the early stage atfer renal transplantation.