BACKGROUND: Treatment with chimeric antigen receptor-T (CAR-T) cells has shown promising effectiveness in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), although the process of preparing for this therapy usually takes a long time. We have recently created CD19 Fast-CAR-T (F-CAR-T) cells, which can be produced within a single day. The objective of this study was to evaluate and contrast the effectiveness and safety of CD19 F-CAR-T cells with those of CD19 conventional CAR-T cells in the management of R/R B-ALL. METHODS: A multicenter, retrospective analysis of the clinical data of 44 patients with R/R B-ALL was conducted. Overall, 23 patients were administered with innovative CD19 F-CAR-T cells (F-CAR-T group), whereas 21 patients were given CD19 conventional CAR-T cells (C-CAR-T group). We compared the rates of complete remission (CR), minimal residual disease (MRD)-negative CR, leukemia-free survival (LFS), overall survival (OS), and the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) between the two groups. RESULTS: Compared with the C-CAR-T group, the F-CAR-T group had significantly higher CR and MRD-negative rates (95.7% and 91.3%, respectively; 71.4% and 66.7%, respectively; P = 0.036 and P = 0.044). No significant differences were observed in the 1-year or 2-year LFS or OS rates between the two groups: the 1-year and 2-year LFS for the F-CAR-T group vs.C-CAR-T group were 47.8% and 43.5% vs. 38.1% and 23.8% (P = 0.384 and P = 0.216), while the 1-year and 2-year OS rates were 65.2% and 56.5% vs. 52.4% and 47.6% (P = 0.395 and P = 0.540). Additionally, among CR patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CAR-T-cell therapy, there were no significant differences in the 1-year or 2-year LFS or OS rates: 57.1% and 50.0% vs. 47.8% and 34.8% (P = 0.506 and P = 0.356), 64.3% and 57.1% vs. 65.2% and 56.5% (P = 0.985 and P = 0.883), respectively. The incidence of CRS was greater in the F-CAR-T group (91.3%) than in the C-CAR-T group (66.7%) (P = 0.044). The incidence of ICANS was also greater in the F-CAR-T group (30.4%) than in the C-CAR-T group (9.5%) (P = 0.085), but no treatment-related deaths occurred in the two groups. CONCLUSION Compared with C-CAR-T-cell therapy, F-CAR-T-cell therapy has a superior remission rate but also leads to a tolerably increased incidence of CRS/ICANS. Further research is needed to explore the function of allo-HSCT as an intermediary therapy after CAR-T-cell therapy.

Objective : To explore the role and mechanism of 25-hydroxycholesterol (25-HC) in inflammatory bow- el disease (IBD) in mice． Methods : All mice were divided into three groups : the control group was fed normally ; the DSS model group was fed with 2. 5% dextran sulfate sodium (DSS) solution ; the DSS + 25-HC experimental group was fed with 2. 5% DSS solution and he mice in the experimental group were intraperitoneally injected with 25-HC．The symptom changes of the mice were evaluated by assessing the disease activity index(DAI) ，and the tis- sue changes were judged by histological scoring．The expression of interleukin-17 and its signaling pathways in the mice were detected by Western blot，qRT-PCR, immunohistochemistry /fluorescence，and flow cytometry．Combined with the detection of tight junction proteins in the intestinal epithelium of the mice，the mechanism by which 25-HC affects IBD in mice was explored． Results : In comparison to the DSS control group，The DSS + 25-HC experimen- tal group mice exhibited a reduction in body weight ( F = 30. 1，P ＜0. 000 1) ，a shortened colon ( F = 63. 8，P < 0. 05) ，and elevated DAI(F = 774. 5，P＜0. 000 1) and histopathological scores(F = 141. 5，P＜0. 05) ．Addition- ally，the expression of tight junction-associated proteins(ZO-2，Occludin，JAM and Claudin-4) was found to be sig- nificantly reduced．The level of IL-17 significantly decreased，and its expression level was positively correlated with tight junction proteins． Conclusion 25-HC inhibited IL-17 production by colonic γδ T cells through the RORγt pathway，aggravated mucosal injury，and promoted the development of DSS-induced acute colitis in mice．

BACKGROUND: Intensive systolic blood pressure (SBP) control improved outcomes in the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial. Whether baseline serum lipid parameters influence the benefits of intensive SBP control is unclear. METHODS: The STEP trial was a randomized controlled trial that compared the effects of intensive (SBP target of 110 to <130 mmHg) and standard (SBP target of 130 to <150 mmHg) SBP control in Chinese patients aged 60 to 80 years with hypertension. The primary outcome was a composite of cardiovascular disease events. A total of 8283 participants from the STEP study were included in this post hoc analysis to examine whether the effects of the SBP intervention differed by baseline low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) concentrations. RESULTS: Regardless of the randomized SBP intervention, baseline LDL-C and non-HDL-C concentrations had a J-shaped association with the hazard of the primary outcome. However, the effects of the intensive SBP intervention on the primary outcome were not influenced by baseline LDL-C level ( P for interaction = 0.80) and non-HDL-C level ( P for interaction = 0.95). Adjusted subgroup analysis using tertiles in LDL-C1 (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.52-1.13; P = 0.18), LDL-C2 (HR, 0.81; 95% CI, 0.55-1.20; P = 0.29), and LDL-C3 (HR, 0.68; 95% CI, 0.47-0.98; P = 0.04) was provided, with an interaction P value of 0.49. Similar results were showed in non-HDL-C1 (HR, 0.87; 95% CI, 0.59-1.29; P = 0.49), non-HDL-C2 (HR, 0.70; 95% CI, 0.48-1.04; P = 0.08), and non-HDL-C3 (HR, 0.67; 95% CI, 0.47-0.95; P = 0.03), with an interaction P -value of 0.47. CONCLUSION: High baseline serum LDL-C and non-HDL-C concentrations were associated with increased risk of primary cardiovascular disease outcome, but there was no evidence that the benefit of the intensive SBP control differed by baseline LDL-C and non-HDL-C concentrations. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, NCT03015311.
Aged ; Humans ; Cardiovascular Diseases ; Blood Pressure/physiology* ; Cholesterol, LDL ; Hypertension ; Cholesterol ; Risk Factors

Objective To develop a simple,multi-dimensional self-screening questionnaire for som-atoform symptoms(SQSS). Methods Based on theoretical framework,the study developed the items of the questionnaire. The first draft of the questionnaire was screened through the expert evaluation method. Four groups of 359 subjects were selected to test the reliability and validity of questionnaire. Results The explor-atory factor analysis showed that the four factors(somatic symptoms,negative perception,illness behavior and social function) were extracted and the interpretable percentage of variance was 61. 165%. The correlation between the subscales and the total scales was 0. 740-0. 887,and the correlation coefficient between the sub-scales was 0. 503-0. 625. The Crobanch's α coefficient of the questionnaire was 0. 926,and the Spearman-Brown score of the questionnaire was 0. 868. The retest correlation coefficient of the total scale was 0. 876. A cutoff of 23 points in the SQSS was identified for screening somatoform disorders, and the sensitivity was 0. 880 and the specificity was 0. 606. Conclusion SQSS has good reliability and validity,and can be prelim-inarily used as a self-screening tool for patients with somatoform symptoms or disorders in clinical settings.

Objective To explore the detection rate and clinical characteristics of multiple somatic symptoms among adult outpatients in cardiology,neurology and GI clinics.Methods The general demographic data and disease-related information of 1 497 patients in Beijing Chaoyang Hospital,Beijing Anzhen Hospital and Beijing Tongren Hospital were collected through continuous inquiry and screening.Physical symptoms and depressive symptoms were assessed by Patient Health Questionnaire-15 (PHQ-15) and Patient Health Questionnaire-9 (PHQ-9).The patients were divided into multiple somatic symptoms group (SOM+group,PHQ-15≥10) and non-multiple somatic symptoms group (SOM-group,PHQ-15＜10).The detection rate of multiple somatic symptoms was calculated.Partial correlation analysis was used to analyze the correlation of PHQ-15 with the demographic,course of disease,cumulative number of visits,and the total score of PHQ-9.Results The overall detection rate of multiple somatic symptoms was 32.67％ (489/1 497)in the three hospitals,and the highest was found in the department of digestive medicine (37.74％,191/506).There were significant differences in gender (x2=36.85,P＜0.01),working status (x2=19.78,P＜0.01),visiting department (x2=9.64,P＜0.01),first visiting/repeated visiting (x2=6.67,P＜0.01),and the total score of PHQ-9 (x2=231.52,P＜0.01).The detection rate of female patients was higher than that of male patients.The detection rates of retired patients and patients who had no daily stable work were higher than patients who had daily stable work.The detection rate of re-visited patients was higher than that of first-visited patients.The illness duration (r=0.07,P＜0.05,Bonferroni correction) and the total score of PHQ-9 (r=0.66,P＜0.05,Bonferroni correction) were positively correlated with the severity of somatic symptoms measured by PHQ-15.Conclusions The detection rate of multiple somatic symptoms was high in general hospitals,especially highest in digestive outpatient clinics,and significantly higher in female,retired,unemployed,re-visited and patients who have depressive symptoms.Depressive symptoms and the illness duration were positively correlated with the severity of somatic symptoms.

Objective To explore the detection rate and clinical characteristics of multiple somatic symptoms among adult outpatients in cardiology,neurology and GI clinics.Methods The general demographic data and disease-related information of 1 497 patients in Beijing Chaoyang Hospital,Beijing Anzhen Hospital and Beijing Tongren Hospital were collected through continuous inquiry and screening.Physical symptoms and depressive symptoms were assessed by Patient Health Questionnaire-15 (PHQ-15) and Patient Health Questionnaire-9 (PHQ-9).The patients were divided into multiple somatic symptoms group (SOM+group,PHQ-15≥10) and non-multiple somatic symptoms group (SOM-group,PHQ-15＜10).The detection rate of multiple somatic symptoms was calculated.Partial correlation analysis was used to analyze the correlation of PHQ-15 with the demographic,course of disease,cumulative number of visits,and the total score of PHQ-9.Results The overall detection rate of multiple somatic symptoms was 32.67％ (489/1 497)in the three hospitals,and the highest was found in the department of digestive medicine (37.74％,191/506).There were significant differences in gender (x2=36.85,P＜0.01),working status (x2=19.78,P＜0.01),visiting department (x2=9.64,P＜0.01),first visiting/repeated visiting (x2=6.67,P＜0.01),and the total score of PHQ-9 (x2=231.52,P＜0.01).The detection rate of female patients was higher than that of male patients.The detection rates of retired patients and patients who had no daily stable work were higher than patients who had daily stable work.The detection rate of re-visited patients was higher than that of first-visited patients.The illness duration (r=0.07,P＜0.05,Bonferroni correction) and the total score of PHQ-9 (r=0.66,P＜0.05,Bonferroni correction) were positively correlated with the severity of somatic symptoms measured by PHQ-15.Conclusions The detection rate of multiple somatic symptoms was high in general hospitals,especially highest in digestive outpatient clinics,and significantly higher in female,retired,unemployed,re-visited and patients who have depressive symptoms.Depressive symptoms and the illness duration were positively correlated with the severity of somatic symptoms.

Objective To observe the clinical efficacy of dye laser combined with Xin'an repair solution in the treating superficial infantile hemangioma(IH). Methods 100 patients with superficial IH were randomly divided into observation group and control group.The observation group received dye laser combined with Xin'an re-pair solution,while the control group was treated only with dye laser.The clinical efficacy and the rate of complica-tions after treatment were compared between the two groups,and the different efficacy between the head neck group and the non head neck group in the observation group was further analyzed. Results The total effective rate of the observation group(90%)was significantly higher than the control group(70%),and the difference was sta-tistically significant(P<0.05).The rate of complications in the observation group was significantly lower than that in the control group(6%vs.32%,P<0.05).In the observation group,the total effective rate of head neck group was better than that the non head neck group(P<0.05). Conclusion Dye laser combined with Xin'an repair so-lution is effective in the treatment of superficial IH,and it can significantly reduce complications.It is evidently ef-fective for head and neck superficial IH.

BACKGROUND:Acellular nerve scaffolds have the three-dimensional structure of natural nerves and low immunogenicity,but their effect on long nerve defects is still not ideal.Therefore,it is necessary to construct tissueengineered nerve using acellular nerve and seed cells in order to improve the therapeutic effect.OBJECTIVE:To systemically review the efficacy of combination of acellular nerve grafts (ANGs) and mesenchymal stem cells (MSCs) or Schwann cells (SCs) transplantation in the treatment of sciatic nerve defects in a rat model.METHODS:Randomized controlled trials (RCTs) about the effects of combination of ANGs and MSCs or SCs transplantation for sciatic nerve defects in rats were searched in PubMed,The Cochrane Library,EMbase,CNKI,WanFang and VIP from inception to July 2016.Three reviewers independently screened literature according to the inclusion and exclusion criteria,extracted data,and assessed the risk of bias of included studies.Then,a Meta-analysis was performed using Review Manger5.3 software.RESULTS AND CONCLUSION:A total of 10 RCTs involving 252 rats were included.The results of meta-analysis showed that:compared with the control group (simple acellular nerve scaffold group),the sciatic functional index (SFI) of the combined group (combination of ANGs and MSCs or SCs transplantation) were superior at 2 weeks [SMD=2.73,95％ CI (1.92,3.45),P ＜ 0.000 01],4 weeks [SMD=4.57,95％ CI (3.43,5.70),P ＜ 0.000 01],6 weeks [SMD=1.62,95％CI (0.18,3.06),P=-0.03],8 weeks [SMD=4.90,95％ CI (2.96,6.84),P ＜ 0.000 01] after surgery.The nerve conduction velocity [SMD=1.39,95％ CI (0.99,1.78),P ＜ 0.000 01),latency period (MD=-0.98,95％ CI (-1.19,-0.76),P ＜ 0.000 01],and amplitude [SMD=1.23,95％ CI (0.62,1.85),P ＜ 0.000 1] were superior at 12 weeks after surgery.The myelin sheath thickness was superior at 8 weeks [MD=0.14,95％ CI (0.07,0.21),P ＜ 0.000 1],12 weeks [SMD=1.85,95％ CI (1.63,2.08),P ＜ 0.000 01] and the number of myelinated nerve fibers were superior at 12 weeks [SMD=3.59,95％CI (2.63,4.55),P ＜ 0.000 01] after surgery.The gastrocnemius wet weight was superior at 8 weeks after surgery [SMD=4.22,95％ CI (2.40,6.03),P ＜ 0.000 01].Current evidence indicates that the combination of ANGs and MSCs or SCs can promote the regeneration and functional recovery of the peripheral nerve.Due to the limited quality of the included studies,the above conclusion should be verified by conducting high-quality and large-scale RCTs.

Objective To investigate the risk factors of delayed gastric emptying (DGE) after pancreaticoduodenectomy,in order to provide a theoretical basis for prevention and treatment of this complication.Methods The term DGE was searched in Pubmed,Medline,EMBASE,Cochrane Library,CNKI,Wanfang,and published literatures were collected to determine the risk factors of DGE after pancreaticoduodenectomy.The Review Manager 5.3 software was used in the analysis.Results A total of 52 articles were included.The results of Meta-analysis showed that age and preoperative bilirubin levels did not significantly influence the incidence of DGE.Preoperative cholangitis (OR =3.39,95％ CI 1.97 ～ 5.82),hypoalbuminemia (OR =2.53,95％ CI 1.59 ～4.02),and intraoperative blood loss of more than 1 L (OR =1.98,95％ CI 1.18 ～ 3.33) significantly increased the incidence of DGE.Pyloric resection (RR =2.06,95％ CI 1.05 ～4.05),antecolic reconstruction (RR =0.74,95％ CI 0.56 ～ 0.99) and Braun enteroenterostomy (OR =0.36,95％ CI 0.17 ～0.77) significantly decreased the risk of DGE.When compared with Roux-enY enteroenterostomy,Billroth Ⅱ enteroenterostomy reduced the incidence of clinically relevant DGE (RR =0.30,95 ％ CI 0.11 ～ 0.79).Postoperative pancreatic fistula (OR =3.84,95 ％ CI 2.71 ～ 5.44) and intraabdominal infection/abscess (OR =3.95,95％ CI 2.87 ～ 5.43) were significantly associated with a high incidence of DGE.Conclusions Hypoalbuminemia,cholangitis,large blood loss,and postoperative abdominal complications were the risk factors of DGE.Pyloric resection,antecolic reconstruction,Billroth Ⅱ enteroenterostomy,and Braun enteroenterostomy significantly reduced the incidence of DGE.Subgroup analysis showed that differences on DGE definition in studies might be an important cause for the heterogeneity in the results of the different studies.

OBJECTIVETo investigate the effect of pretreatment with ulinastatin on liver regeneration and TNF-α/IL-6/STAT-3 signal pathway in rats after 70% hepatectomy combined with ischemia-reperfusion injury.

METHODSA total of 120 normal male SD rats weighing 230-280 g were randomized into 3 groups (n=40), namely simple partial hepatectomy (PH) group, partial hepatectomy with ischemia-reperfusion (PHIR) group, and ulinastatin group. All the rats received resection of the left and middle liver lobes. In PHIR group, the remnant right lobes were subjected to blood flow occlusion for 30 min; in UTI group, the rats were given 50 000 U/kg UTI intravenously prior to the occlusion, and in PH group, the blood flow was not occluded. At 1, 6, 12, 24, and 48 after the reperfusion, the remnant liver tissues were examined for regenerated liver weight, PCNA staining, TNF-α and IL-6, STAT-3, cyclin D1, and Cdk4 expressions.

RESULTSThe regenerated liver weight and PCNA positivity rates were significantly higher in ulinastatin group than in PHIR group at 24 h and 48 h after the reperfusion (P<0.05). In ulinastatin group, the levels of TNF-α and IL-6 were significantly lower, and IL-6 level and the expressions of STAT-3, cyclin D1, and Cdk4 mRNA and cyclin D1 and Cdk4 proteins were significantly higher in ulinastatin group than in PHIR group at 24 h and 48 h (P<0.05).

CONCLUSIONUlinastatin can promote liver regeneration after major hepatectomy and ischemia-reperfusion injury, and the effect is possibly related with activation of IL-6/STAT-3 signal pathway, which promotes the synthesis of cyclin Dl-Cdk4 complex and hepatocyte proliferation.

Animals ; Cell Proliferation ; Cyclin D1 ; metabolism ; Cyclin-Dependent Kinase 4 ; metabolism ; Glycoproteins ; pharmacology ; Hepatectomy ; adverse effects ; Hepatocytes ; cytology ; drug effects ; Interleukin-6 ; metabolism ; Liver ; blood supply ; Liver Regeneration ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; etiology ; metabolism ; STAT3 Transcription Factor ; metabolism ; Signal Transduction ; drug effects ; Tumor Necrosis Factor-alpha ; metabolism