The evaluation of different types fecal bacteria products for the treatment of recurrent Clostridium difficile associated diarrhea: A systematic review and network meta-analysis.

Purpose: To determine the efficacy of different types of fecal microbiota transplantation for the treatment of recurrent clostridium difficile associated diarrhea (RCDAD). Methods: We searched PubMed, Embase, The Cochrane Library, Web of Science, China Biomedical Medicine (CBM), China National Knowledge Infrastructure (CNKI) and WanFang database. We also tracked the references found in systematic reviews of RCDAD treated with fecal microbiota transplantation. We included randomized controlled trials (RCTs) comparing different types of fecal microbiota transplantation with other methods for the treatment of RCDAD. The search period was from the date of inception of this treatment method to January 16, 2022. Two reviewers independently screened the published literature, extracted the data and assessed the risk of bias. Systematic review and network meta-analysis were conducted using RevMan 5.4, Stata 16.0 and R 4.1.2 software. Results: Ten RCTs involving 765 patients were included in this network meta-analysis. The results showed that treatment with fresh fecal bacteria and frozen fecal bacteria were better than vancomycin, fresh vs. vancomycin [odds ratio, (OR) = 8.98, 95% confidence interval (95% CI) (1.84, 43.92)], frozen vs. vancomycin [OR = 7.44, 95% CI (1.39, 39.75)]. However, there were no statistically significant differences in cure rate [fresh vs. frozen: OR = 1.21, 95% CI (0.22, 6.77); fresh vs. lyophilized, OR = 1.95, 95% CI (0.20, 19.44); frozen vs. lyophilized, OR = 1.62, 95% CI (0.30, 8.85)]. The Surface Under the Cumulative Ranking (SUCRA) indicated that fresh fecal bacteria were the best treatment for RCDAD. Conclusions: Fresh fecal bacteria are the best treatment of RCDAD, frozen fecal bacteria and lyophilized fecal bacteria can achieve the same effect. Fecal microbiota transplantation is worthy of clinical and commercial application.

Enhanced recovery after surgery management of perioperative period in surgical lung cancer patients: protocol for a systematic review and meta-analysis of randomised controlled trials.

INTRODUCTION: Enhanced recovery after surgery (ERAS) has been widely used in the perioperative period of lung cancer surgery. However, there remains a lack of comprehensive and systematic evidence on the effectiveness and safety of ERAS. This study aims to evaluate the efficacy and safety of ERAS in patients with lung cancer. METHODS AND ANALYSIS: Eight databases (PubMed, Web of Science, Embase, Cochrane Library, CNKI, CBM, VIP and WANFANG) will be searched from inception to November 2021. Two reviewers will independently screen studies, extract data of interest and assess the risk of bias. The revised risk of bias tool 2 will be used to assess the risk of bias in randomised controlled trials. We will use the Grading of Recommendations, Assessment, Development and Evaluations to assess the certainty of evidence. We will carry out a random-effect meta-analysis focusing on the efficacy and safety variables. All analyses will be conducted using RevMan V.5.3. ETHICS AND DISSEMINATION: Since the study will be a systematic review and will not involve direct contact with patients or make alterations to patient care, ethical approval and informed consent are not required for this study. The results of this review will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42021250761.

Cultural Adaptation and Validation of Questionnaires for Evaluation of Health-Related Quality of Life with Dysphagia in Different Countries: A Systematic Review.

Dysphagia can have devastating and long-lasting effects on the patient's health-related quality of life (HRQoL). In recent years, a number of questionnaires for the evaluation of the HRQoL of patients with dysphagia have been developed and have been adapted for use in different countries and cultures. However, problems may arise in the process of cultural adaptation and validation, which can affect the quality of the questionnaires and their measurements. This study was conducted to systematically summarize the cultural adaptation and validation of questionnaires for the evaluation of dysphagia-related HRQoL in different countries, assessing the varieties, measurement properties, and qualities of these questionnaires, with the aim of identifying the status of their adaptation and validation and ways in which they might be improved. Four databases were searched, and relevant articles were screened, with data from eligible reports extracted and reviewed. The methodological quality of the included articles was evaluated using the QualSyst critical appraisal tool. The HRQoL questionnaires for patients with dysphagia were assessed using the quality criteria for the measurement properties of health status questionnaires proposed by Terwee et al. and Timmerman et al. 29 studies published between 2008 and 2020 were included. The questionnaires described in these 29 studies were translated into 19 languages and culturally adapted to 21 countries. The adapted questionnaires were based on the Swallowing quality of life questionnaire (SWAL-QOL) by Mchorney et al., the Dysphagia Handicap Index (DHI) by Silbergleit et al., the M.D. Anderson Dysphagia Inventory (MDADI) by Chen et al., and the Eating Assessment Tool-10 (EAT-10) by Belafsky et al. It was found that the questionnaires were reliable and valid instruments for the assessment of dysphagia-related HRQoL, but the quality criteria for cultural adaptation and validation were not strictly followed, especially in the categories of criterion validity, agreement, responsiveness, and interpretability. In conclusion, although the questionnaires were found to be both reliable and valid, the quality criteria should be considered and strictly followed in the cultural adaptation and validation process in the future.

Current practice and barriers to ICU-acquired weakness assessment: a cross-sectional survey.

BACKGROUND: Intensive-care-unit-acquired weakness (ICU-AW) not only leads to difficulty weaning off mechanical ventilation, prolonged hospital stay and increased medical costs, but also reduces the patient's quality of life after discharge and increases the 1-year mortality rate. Early identification and intervention can improve the prognosis of critically ill patients. However, much remains unknown about current clinical practice for ICU-AW assessment by ICU staff in China. OBJECTIVES: To investigate current practices and barriers to ICU-AW assessment among ICU staff, and provide insights to improve ICU-AW assessment in ICUs in China. METHODS: Qualitative interviews were used to construct a survey questionnaire (test-retest reliability 0.92, validity 0.96). This survey was subsequently completed by 3206 ICU staff from 31 provinces, municipalities and autonomous regions in China. RESULTS: In total, 3206 ICU staff responded to the survey (response rate 90%): 616 doctors (19%), 2371 nurses (74%), 129 respiratory therapists (4%), 51 physiotherapists (2%) and 39 dieticians (1%). Only 27% of the respondents had treated/cared for patients with ICU-AW. Reported methods for ICU-AW assessment were clinical experience (53%), ICU-AW assessment tools (12%), and physiotherapy consultation (35%). Forty-three percent of respondents felt that their ICU-AW-related knowledge did not meet clinical needs, only 10% had received ICU-AW-related training, and 19% proactively assessed whether their patients had ICU-AW. In terms of frequency of assessment, 42%, 16% and 11% of respondents considered that ICU-AW should be assessed daily, every 3 days, and on ICU admission and discharge, respectively. The Medical Research Council scale, electrophysiological assessment and the Manual Muscle Testing scale were considered to be optimal tools for ICU-AW diagnosis by 79%, 70%, and 73% of respondents, respectively. The main reported barriers to ICU-AW assessment were lack of knowledge, cognitive impairment among patients, and lack of ICU-AW assessment guidelines and procedures. CONCLUSION: Current practices for ICU-AW assessment are non-specific, and the main barriers include lack of skills and knowledge.

Chinesisation, adaptation and validation of the Chelsea Critical Care Physical Assessment Tool in critically ill patients: a cross-sectional observational study.

PURPOSE: To translate and adapt the Chelsea Critical Care Physical Assessment Tool (CPAx) into Chinese version ('CPAx-Chi'), test the reliability and validity of CPAx-Chi, and verify the cut-off point for the diagnosis of intensive care unit-acquired weakness (ICU-AW). STUDY DESIGN: Cross-sectional observational study. METHODS: Forward and back translation, cross-cultural adaptation and pretesting of CPAx into CPAx-Chi were based on the Brislin model. Participants were recruited from the general ICU of five third-grade class-A hospitals in western China. Two hundred critically ill adult patients (median age: 53 years; 64% men) with duration of ICU stay ≥48 hours and Glasgow Coma Scale ≥11 were included in this study. Two researchers simultaneously and independently assessed eligible patients using the Medical Research Council Muscle Score (MRC-Score) and CPAx-Chi. RESULTS: The content validity index of items was 0.889. The content validity index of scale was 0.955. Taking the MRC-Score scale as standard, the criterion validity of CPAx-Chi was r=0.758 (p<0.001) for researcher A, and r=0.65 (p<0.001) for researcher B. Cronbach's α was 0.939. The inter-rater reliability was 0.902 (p<0.001). The area under the receiver operating characteristic curves of CPAx-Chi for diagnosing ICU-AW based on MRC-Score ≤48 were 0.899 (95% CI 0.862 to 1.025) and 0.874 (95% CI 0.824 to 0.925) for researcher B. The best cut-off point for CPAx-Chi for the diagnosis of ICU-AW was 31.5. The sensitivity was 87% and specificity was 77% for researcher A, whereas it was 0.621, 31.5, 75% and 87% for researcher B, respectively. The consistency was high when taking CPAx-Chi ≤31 and MRC-Score ≤48 as the cut-off points for the diagnosis of ICU-AW. Cohen's kappa=0.845 (p=0.02) in researcher A and 0.839 (p=0.04) for researcher B. CONCLUSIONS: CPAx-Chi demonstrated content validity, criterion-related validity and reliability. CPAx-Chi showed the best accuracy in assessment of patients at risk of ICU-AW with good sensitivity and specificity at a recommended cut-off of 31.

[Early mobilization on mortality of patients with mechanical ventilation in intensive care unit after discharge: a Meta-analysis].

OBJECTIVE: To evaluate the effect of early mobilization on mortality in intensive care unit (ICU) patients with mechanical ventilation after discharge by Meta-analysis. METHODS: Databases including SinoMed, China National Knowledge Infrastructure (CNKI), Wanfang data, PubMed, the Cochrane Library, Web of Science, and Embase were searched from inception to September 17th, 2020, to collect randomized controlled trials (RCT) about early mobilization on mortality of patients with mechanical ventilation in ICU after discharge, the references included in the literature were traced. The control group was given routine care, the experimental group was given early mobilization on the basis of the control group, including passive or active mobilization on the bed, sitting on the bed, standing by the bed, transferring to the bedside chair and assisting walking. The literature screening, data extracting, and the bias risk assessment of included studies were conducted independently by two reviewers. Stata 12.0 software was then used to perform Meta-analysis. Funnel plot was used to test publication bias. RESULTS: A total of 10 RCT studies involving 1 323 patients were included, with 660 patients in the control group and 663 patients in the experimental group. The results of literature quality evaluation showed that 7 studies were grade A and 3 studies were grade B, indicating that the overall quality of included literatures was high. The Meta-analysis results showed that early mobilization did not increase the mortality of patients with mechanical ventilation in ICU after discharge [odds ratio (OR) = 0.92, 95% confidence interval (95%CI) was 0.75-1.13, P = 0.449]. Subgroup analysis results showed that early mobilization had a tendency to reduce the mortality of ICU patients with mechanical ventilation at 3, 6 and 12 months after discharge, but the difference was not statistically significant (3-month mortality: OR = 1.02, 95%CI was 0.74-1.40, P = 0.927; 6-month mortality: OR = 0.95, 95%CI was 0.70-1.27, P = 0.712; 12-month mortality: OR = 0.60, 95%CI was 0.33-1.10, P = 0.101). Funnel plot showed that the distribution of included literatures was not completely symmetrical, suggesting that publication bias might exist. CONCLUSIONS: Early mobilization does not increase the mortality of ICU patients with mechanical ventilation after discharge. Although it tends to have a favorable outcome in reducing mortality, and has a trend to reduce the mortality. However, due to the small number of included literatures, small sample size and differences in the specific implementation of early mobilization among various studies, a large number of high-quality RCT studies are still needed for further verification.

[Current practice and obstacle factors of intensive care unit-acquired weakness assessment].

OBJECTIVE: To investigate the current status of intensive care unit-acquired weakness (ICU-AW) assessment, analyze the assessment barriers, and to provide reference to improve ICU-AW assessment. METHODS: A convenient sampling cross-sectional survey was conducted. First, an interview outline which based on related domestic and international literatures and combining with the research purpose of this study were designed. Thirteen medical personnel (8 ICU nurses, 3 ICU doctors, 1 respiratory therapist and 1 physiotherapist) who worked in the intensive care unit (ICU) of the First Hospital of Lanzhou University were enrolled with convenience sampling method to interview. Second, the topics were comprehensively analyzed and extracted, and then a questionnaire was constructed, and the reliability and validity was assessed. Finally, the questionnaire survey including the general situation of ICU medical staffs, the current practices of ICU-AW and influencing factors was implemented in China. RESULTS: The retest reliability was 0.92 and expert validity was 0.96 of the questionnaire. There were 3 563 respondents in 31 provinces, municipalities and autonomous regions which eliminated 357 unqualified questionnaires, including 173 respondents from neonatal or pediatric ICU, 89 respondents whose working time was less than 6 months, and 95 invalid respondents, and then there were finally 3 206 valid questionnaires and the response rate were 90.0%. Those 3 206 respondents included 616 doctors (19.2%), 2 371 nurses (74.0%), 129 respiratory therapists (4.0%), 51 physiotherapist (1.6%) and 39 dietitians (1.2%). The mean age was (30.7±6.3) years old. Most of them had bachelor's degree (65.9%), master and above was 14.1%. Associate senior physician and above was 8.0%; ICU working time was (5.94±4.50) years. In clinical practice, only 26.5% of the ICU medical staffs confirmed that they had treated or taken care for ICU-AW patients; 52.9% of medical staffs evaluated ICU-AW only based on clinical experience, and only 12.3% used ICU-AW assessment tools. The majority of respondents believed that ICU-AW knowledge training should be performed (81.8%), ICU-AW assessment should be as important as other complications (pressure sore, infected ventilator associated pneumonia, etc., 75.1%), and ICU-AW assessment should be part of daily treatment and care activities (61.2%). However, only 10.2% of respondents had received ICU-AW related knowledge training, and 42.7% respondents believed that their ICU-AW related knowledge could not meet clinical needs. Only 18.7% respondents would actively assess whether patients suffered from ICU-AW or not, and 42.3% respondents thought that ICU-AW should be assessed every day, and the assessment tools were also inconsistent. There were 44.0% respondents considered the Medical Research Council Muscle score (MRC-score) scale was the optimal tool for diagnosing ICU-AW, the following were neuro-electrophysiological examination (17.2%) and manual muscle strength (MMT, 11.1%). The main cause of the ICU-AW assessment barriers was the lack of ICU-AW related knowledge (88.1%), and the following were lack of ICU-AW assessment guidelines (76.5%), patients' cognitive impairment or limited understanding ability (84.6%), unable to cooperate with the assessment due to critical illness (83.0%), and inadequate attention to ICU-AW assessment by the department (77.5%). CONCLUSIONS: The current status of ICU-AW assessment were unsatisfying in China, and the main barriers were lack of skills and knowledge.

[Evaluation of pharmaceutical prevention and treatment of intensive care unit-acquired weakness: a Meta-analysis].

OBJECTIVE: To evaluate the effect of preventing and treatment of pharmaceuticals on intensive care unit-acquired weakness (ICU-AW) by systematic review. METHODS: The randomized controlled trials (RCTs) concerning pharmaceutical prevention and treatment about ICU-AW in SinoMed, CNKI, Wanfang data, PubMed, Cochrane Library, Web of Science, EMbase, and other sources were searched from their foundation to May 30th, 2019. The patients in the intervention group were treated with drugs to prevent or treat ICU-AW; and those in control group were treated with other rehabilitation methods. Data searching, extracting and quality evaluation were assessed by two reviewers independently. Stata 12.0 software was then used for Meta-analysis. Only descriptive analysis was conducted when only one study was enrolled. RESULTS: A total of 11 RCTs were enrolled with 1 865 patients in the intervention group and 1 894 in the control group. The results of quality evaluation showed that 4 studies were A-level and 7 studies were B-level, indicating that the overall quality of the enrolled literature was high. Meta-analysis showed that intensive insulin therapy could prevent ICU-AW [relative risk (RR) = 0.761, 95% confidence interval (95%CI) was 0.662-0.876, P = 0.000], but reduced phenylalanine loss (nmol×100 mL-1×min-1: -3±3 vs. -11±3, P < 0.05) and glutamine intake (nmol×100 mL-1×min-1: -97±22 vs. -51±13, P < 0.05). There was no significant difference in the prevention and treatment of ICU-AW between other drugs (including growth hormone, glutamine, dexmedetomidine, neostigmine, oxandrolone, and intravenous immunoglobulin) and control group. CONCLUSIONS: Intensive insulin therapy can prevent ICU-AW, but the risk of hypoglycemia will increase. Other drugs including growth hormone, glutamine, dexmedetomidine, neostigmine, oxandrolone, and intravenous immunoglobulin have no obvious advantages in the prevention and treatment of ICU-AW, so no drug has been recommended to prevent and treat ICU-AW.

Effects of different oral care scrubs on ventilator-associated pneumonia prevention for machinery ventilates patient: A protocol for systematic review, evidence mapping, and network meta-analysis.

BACKGROUND: Ventilator-associated pneumonia (VAP) is defined as pneumonia develops in intensive care unit (ICU) patients who have been mechanically ventilated for at least 48 hours. Implementing effective oral car could reduce the incidence of VAP. However, previous studies on scrubs in oral care have failed to suggest which the best choice. Therefore, this protocol proposes to perform a network meta-analysis to evaluate the effectiveness of different oral care scrubs in preventing VAP. METHODS: We are going to search the electronic databases: Cochrane Oral Health's Trials Register, CENTRAL, MEDLINE, EMBASE, CINAHL, and Chinese Biomedical Literature Database. Study selection and data collection will be performed independently by 2 reviewers. Cochrane Risk of Bias tool will be used to assess the risk of bias of included studies. Odds ratio (OR) and 95% confidence intervals (CIs) will be used to assess the incidence rate of VAP in critical patients. The evidence mapping (EM) method will be introduce as a tool intended to complement the conventional systematic review (SR) and is suitable for this issue, at the same time, R software will be used for representing the outcome of EM-SR. We shall assess the heterogeneity on the bias of the magnitude of heterogeneity variance parameter (I or Cochrane Q). We are also going to conduct subgroup analysis and sensitivity analysis if needed. The application of Stata and R software will be performed the calculations. RESULTS: The results of this study will be submitted to a peer-reviewed journal for publication. CONCLUSION: This network meta-analysis will provide comprehensive evidence of different scrubs in oral care for preventing VAP. PROSPERO REGISTRATION NUMBER: CRD42018117019.

Single- Versus Double-Unit Umbilical Cord Blood Transplantation for Hematologic Diseases: A Systematic Review.

Controversial results exist regarding the clinical benefits of single- vs double-unit umbilical cord blood transplantation (UCBT) in patients with hematologic diseases. A systematic review was conducted to evaluate this issue. The PubMed, Embase, and Cochrane Library databases were searched up to May 2018. A total of 25 studies including 6571 recipients were identified. Although double-unit UCB contained higher doses of total nucleated cells and CD34+ cells, it offered no advantages over single-unit UCB in terms of hematologic recovery, including the rate and speed of neutrophil and platelet engraftment. Double-unit UCBT was associated with higher incidences of grades II-IV acute and extensive chronic graft-vs-host disease, accompanied by a lower relapse incidence, which may be attributed to a graft-vs-graft effect induced by double-unit UCB. However, transplant-related mortality, disease-free survival, and overall survival were comparable between single- and double-unit UCBT. Although double-unit UCBT confers no clinical advantages over single-unit UCBT, certain patients, such as those at high risk of relapse, might benefit from double-unit UCBT, a possibility that needs to be clarified in future randomized trials.

[Application of Chimeric Antigen Receptor-Modified NK Cells in Multiple Myeloma].

OBJECTIVE: To explore the killing effect of CAR (CD138-CD28-CD3ζ)-NK cells on myeloma cells through construction of CAR(CD138-CD28-CD3)-NK cells. METHODS: The antiCD138scFv-CD28-CD3 zeta plasmid pcDNA3.1 was constructed, which then together with 3 plasmid lentiviral packaging system were transfected into 293T cells, the virus was collected. Furthermore, in order to get the stably transfected cell line, the NK92MI cell line was infected by the virus, then the positive cells were screened by puromycin. The expression of the CARNK cells were verified by RT-PCR and Western blot. At last the ability of secreting cytokine CD107a was detected by flow cytometry, and the statistical analysis was carried out to verify the anti-myeloma effect of CAR-NK cells. RESULTS: Gene fragment of the CAR(antiCD138scFv-CD28-CD3ζ) was constructed successfully by gene engineering technique in vitro, and the gene sequence was verified to be correct by sequencing. By virus packaging technology, the virus expressing the protein of the CAR was obtained. PCR and Western blot verified the expression of CAR fusion protein on the sufurce of NK cells. The cell killing experiment confirmed that the CAR-NK cells possessed the ability to secrete cytokine CD107a superior to control cells and showed the obvious killing effect on multiple myeloma cells. CONCLUSION: The CAR can be constructed in vitro, and express on NK92 cells. The CAR-NK cells can kill the multiple myeloma cells expressing CD138 antigen, thereby plays an antimyeloma effect.

T Cell-Replete Haploidentical Peripheral Blood Hematopoietic Cell Transplantation for Treatment of T-Lymphoblastic Lymphoma.

BACKGROUND There is currently little information on haploidentical hematopoietic cell transplantation (haplo-HCT) for T-lymphoblastic lymphoma (T-LBL). Data about peripheral blood stem cells (PBSC) as a reliable graft source for T-LBL treatment are lacking. MATERIAL AND METHODS T-LBL patients who underwent T cell-replete haploidentical peripheral blood hematopoietic cell transplantation (haplo-PBHCT) from July 2007 to January 2017 were retrospectively evaluated. RESULTS A total of 25 patients (age ≥15 years) with median age of 24 (range 15-51) years were enrolled. The median number of CD34+ cells infused was 5.0 (1.6-14.4) 106/kg. Sustained myeloid engraftment with full donor chimerism was achieved in all patients. The cumulative incidence of grades 2 to 4 acute graft-versus-host disease (GVHD) at day 100 was 24%. Two-year extensive chronic GVHD cumulative incidence was 20%. The 3-year overall survival rate for all patients was 70%. The median survival time of the complete remission (CR) group was better than that of the non-CR group (not reached vs. 9 m) (P<0.01). The relapse rate was 17% for patients who obtained CR and were given haplo-HCT as consolidation treatment. CONCLUSIONS This study indicates that haplo-PBHCT is a safe and effective method for the treatment of T-LBL.

Risk Factors for Acute Graft-Versus-Host Disease After Allogeneic Haematopoietic Stem Cell Transplantation: A Single-Center Experience.

BACKGROUND Acute graft-versus-host disease (aGVHD) remains the most common and challenging complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). An important obstacle to the therapeutic effect of aGVHD is the inability to identify risk factors for an individual patient at the onset of symptoms. We performed a retrospective study with the aim of defining clinically meaningful pre-transplantation risk factors for grades II-IV aGVHD patients. MATERIAL AND METHODS To identify pre-transplantation risk factors for grades II-IV aGVHD after allo-HSCT, we performed a retrospective study in 292 patients who underwent allo-HSCT at our center from January 2010 to July 2015. RESULTS The cumulative incidence of grades II-IV aGVHD was 36.6±2.8%. The most common target organ of aGVHD was the skin (46.7%), followed by the gastrointestinal tract (29.9%). The risk factors we identified included HLA-mismatched related donors (odds ratio [OR], 3.21; 95% confidence interval [CI], 1.82-5.67) and conditioning regimens containing TBI but no ATG (OR, 2.66; 95% CI, 1.40-5.06). Simultaneously, transplantation with an identical sibling donor (OR, 0.31; 95% CI, 0.18-0.55) and the use of ATG in the conditioning regimen containing TBI (OR 0.37; 95% CI, 0.15-0.93) were two factors found to be associated with a decreased risk of grades II-IV aGVHD. CONCLUSIONS Our study suggests that pre-transplantation characteristics of donor and recipient play an important role in identifying patients at high risk for grades II-IV aGVHD, which provide a direction for the prevention and treatment of aGVHD in the future.

Efficacy and safety of thrombopoietin receptor agonists in patients with primary immune thrombocytopenia: A systematic review and meta-analysis.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by increased platelet destruction and impaired platelet production. In this study, we conducted a systematic review and meta-analysis to determine the efficacy and safety of thrombopoietin receptor agonists (TPO-RAs) in primary ITP patients. Thirteen randomized controlled trials were included in this study, the pooled results of which demonstrated that TPO-RAs significantly increased platelet response (R) and durable response (DR) rates [risk ratio (RR): 2.77, 95% confidence interval (CI): 2.01-3.82, P = 5.9 × 10-10; RR: 7.52, 95% CI: 3.94-14.35, P = 9.2 × 10-10; respectively] and that TPO-RAs significantly reduced the incidences of any or severe bleeding events (RR: 0.80, 95% CI: 0.67-0.95, P = 0.013; RR: 0.52, 95% CI: 0.27-0.99, P = 0.048; respectively). Moreover, our results indicated that there was a significant reduction in the proportion of patients needing rescue medications in the TPO-RA groups compared with the control groups (RR: 0.50, 95% CI: 0.42-0.59, P = 2.0 × 10-15) and that the rates of any or severe adverse events were similar between the TPO-RA and control regimens (RR: 1.01, 95% CI: 0.92-1.10; RR: 0.74, 95% CI: 0.54-1.01; respectively). These findings demonstrate that TPO-RAs are an effective and safe second-line treatment option for primary ITP patients.

Extracellular Vesicles Released from Human Umbilical Cord-Derived Mesenchymal Stromal Cells Prevent Life-Threatening Acute Graft-Versus-Host Disease in a Mouse Model of Allogeneic Hematopoietic Stem Cell Transplantation.

Mesenchymal stromal cells (MSCs) are attractive agents for the prophylaxis of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, safety concerns remain about their clinical application. In this study, we explored whether extracellular vesicles released from human umbilical cord-derived MSCs (hUC-MSC-EVs) could prevent aGVHD in a mouse model of allo-HSCT. hUC-MSC-EVs were intravenously administered to recipient mice on days 0 and 7 after allo-HSCT, and the prophylactic effects of hUC-MSC-EVs were assessed by observing the in vivo manifestations of aGVHD, histologic changes in target organs, and recipient mouse survival. We evaluated the effects of hUC-MSC-EVs on immune cells and inflammatory cytokines by flow cytometry and ProcartaPlex™ Multiplex Immunoassays, respectively. The in vitro effects of hUC-MSC-EVs were determined by mitogen-induced proliferation assays. hUC-MSC-EVs alleviated the in vivo manifestations of aGVHD and the associated histologic changes and significantly reduced the mortality of the recipient mice. Recipients treated with hUC-MSC-EVs had significantly lower frequencies and absolute numbers of CD3+CD8+ T cells; reduced serum levels of IL-2, TNF-α, and IFN-γ; a higher ratio of CD3+CD4+ and CD3+CD8+ T cells; and higher serum levels of IL-10. An in vitro experiment demonstrated that hUC-MSC-EVs inhibited the mitogen-induced proliferation of splenocytes in a dose-dependent manner, and the cytokine changes were similar to those observed in vivo. This study indicated that hUC-MSC-EVs can prevent life-threatening aGVHD by modulating immune responses. These data provide the first evidence that hUC-MSC-EVs represent an ideal alternative in the prophylaxis of aGVHD after allo-HSCT.

[Effect of rhG-CSF Mobilization on S1P5 Expression in T Lymphocyte Subsets of Allo-HSCT Donors].

OBJECTIVE: To explore the effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) mobilization on S1P5 expression in T lymphocyte subsets of allo-HSCT donors. METHODS: The peripheral blood was collected from 10 allo-hematopoietic stem cell transplantation (allo-HSCT) donors before and after mobilization with rhG-CSF for 4 days. The flow cytometry was used to detect S1P5 expression in T lymphocyte subsets. RESULTS: There was no S1P5 expression on the surface of T-lymphocytes both before and after rhG-CSF mobilization. After fixation with permeabilization agent, S1P5 expression could be detected in lymphocytes after rhG-CSF mobilization, which indicates S1P5 may be located in cells. Compared with level before rhG-CSF mobilization, S1P5 expression was significantly increased in T lymphocyte subsets after rhG-CSF mobilization, CD3(+)T cells (57.92±2.32)% vs (7.94±1.47)%(P<0.05）, CD4(+)T cells (72.58±1.73)% vs （5.48±0.82）%(P<0.05）, CD8(+)T cells（51.79±3.57）% vs （6.46±1.01）%（P<0.05）,CD3-/CD56(+)NK cells（40.00±1.47）% vs（4.97±0.74）%（P<0.05）. The up-regulated level of S1P5 expression in CD4(+)T cells was most high(P<0.05). CONCLUSION: S1P5 expression significantly increases in T lymphocyte subsets after rhG-CSF mobilization, and the up-regulated level of S1P5 expression in CD4(+)T cells is the most high.

[Expression Profile of lncRNA NONHSAT040475 in Peripheral Blood Leukocytes of Healthy Persons].

OBJECTIVE: To investigate the expression profile of lncRNA NONHSAT040475 in peripheral blood leukocytes of healthy persons. METHODS: The peripheral blood mononuclear cells were collected from 10 healthy volunteers, the CD3(+) T cells,CD19(+) B cells,CD56(+) NK cells and granulocytes were purified and sorted by flow cytometry. Then, the expression of lncRNA NONHSAT040475 in peripheral blood leukocyte subsets was detected by real-time quantitative PCR. RESULTS: the expression levels of lncRNA NONHSAT040475 were various in lymphocyte subsets, its expression in B lymphocytes was significantly higher, as compared with T lymphocytes, while the expressions of lncRNA NONHSAT040475 in NK cells and granulocytes were relative low（P<0.01）. CONCLUSION: lncRNA NONHSAT040475 is widely expressed in human peripheral blood leukocytes, and mainly expressed in B lymphocytes, therefore, laying the foundation for further study of B lymphocyte-related diseases. This study has brought a new opportunity for diagnosing and illustrating the molecular mechanism of hematologic disorder or autoimmune disease.

Mesenchymal stem cells provide prophylaxis against acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation: A meta-analysis of animal models.

A meta-analysis of animal models was conducted to evaluate the prophylactic effects of mesenchymal stem cells (MSCs) on acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation. A total of 50 studies involving 1848 animals were included. The pooled results showed that MSCs significantly reduced aGVHD-associated mortality (risk ratio = 0.70, 95% confidence interval 0.62 to 0.79, P = 2.73×10-9) and clinical scores (standardized mean difference = -3.60, 95% confidence interval -4.43 to -2.76, P = 3.61×10-17). In addition, MSCs conferred robust favorable prophylactic effects on aGVHD across recipient species, MSC doses, and administration times, but not MSC sources. Our meta-analysis showed that MSCs significantly prevented mortality and alleviated the clinical manifestations of aGVHD in animal models. These data support further clinical trials aimed at evaluating the efficacy of using MSCs to prevent aGVHD.

[Therapeutic Efficacy Analysis of Allogeneic Peripheral Blood Hematopoietic Stem Cell Transplantation for 14 Adult Patients with T Lymphoblastic Lymphoma].

OBJECTIVE: To investigate the therapeutic efficacy of allogeneic peripheral blood hematopoietic stem cell transpdantation (allo-HSCT) for T lymphoblastic lymphoma (T-LBL). METHODS: The clinical data of 14 adult patients with T-LBL treated with allo-HSCT were collected, the hematopoietic reconstruction, survival and relapse, as well as overall survival (OS) rate, event-free survival (EFS) rate of 1, 3 and 5 years were analysed retrospectively. RESULTS: All the patients were engrafted with neutrophil successfully, the median time of absolute neutrophil count >0.5 × 10(9)/L was 13 (10-19) d; 13 patients were engrafted with platelets successfully, the median time of Plt count >20 × 10(9)/L was 17 (12-62) days. The acute GVHD occurred in 6 patients, but among them only 1 case with 3 grade of aGVHD; out of 14 patients, 5 developed chronic GVHD. The transplant-related mortality at 100 days was 7.1% (1/14), mainly from coronary heart disease and pulmonary infection. The median follow-up time was 26.5 months, the estimated 1, 3 and 5 year OS rate was 85.7%, 47.6% and 38.1%, respectively, and estimated 1, 3 year EFS rate was 85.7%, 34.4% and 34.1%, respectively. The relapse rate was 42.8% (6/14) and the median relapse time was 22.5% months after transplantation. Up to now, 7 patients still survive, 1 patient out of them have survived for 103 months. CONCLUSION: The allo-HSCT is a safe and effective method for treatment of T-LBL.

[Expression and Prognostic Value of BCL-2 Protein in Diffuse Large B-cell Lymphoma].

OBJECTIVE: To explore the value of BCL-2 protein for evaluating the prognosis of patients with diffuse large B cell lymphama (DLBCL). METHODS: The clinical data of 128 patients with DLBCL including clinical features, BCL-2 protein expression, therapeutic outcome and so on were analyzed retrospectively in departenent of hematology, Chinese PLA general hospital from January 2008 to December 2010, and the prognosis of DLBCL patients with different expression levels of BCL-2 protein was compared, including overall survival (OS) and progression-free survival (PFS) rates. RESULTS: The BCL-2 expression postive was found in 83 cases (64.8%), while BCL-2 expression negative was observed in 45 cases (35.2%). The OS rates in BCL-2 expression positive and negative groups were 76.6% vs 76.8% in 3 years (P >0.05), and the PFS rates in BCL-2 expression positive and negative groups were 57.1% vs 70.5% (P >0.05) in 3 years, suggesting that BCL-2 expression level had no significant impact on OS and PFS rates in all DLBCL patients. However, among the older patients aged ≥ 60 years, there was singnificant different of 3 year OS rates in BCL-2 expression positive and negative groups (66.7% vs 76.4%, P >0.05), while 3-year PFS rate in BCL-2 expression positive group was obviosusly lower than that in BCL-2 expression negative group (35.8% vs 83.3%, P < 0.05). CONCLUSION: The positive expression of BCL-2 protein is a poor prognostic factor for older patients aged ≥ 60 years, thus this indicator possesses the prognostic value for these patients with DLBCL.