Analysis of actionable gene fusions in a large cohort of Chinese patients with colorectal cancer.

Background: The prevalence of gene fusion is extremely low in unselected patients with colorectal cancer (CRC). Published data on gene fusions are limited by relatively small sample sizes, with a primary focus on Western populations. This study aimed to analyse actionable gene fusions in a large consecutive Chinese CRC population. Methods: This study included 5,534 consecutive CRC patients from the Genecast database. Genomic profiling was performed using a panel of 769 cancer-related genes. Data for 34 CRC patients with actionable gene fusions were also collected from cBioPortal and ChimerSeq. Results: Among 5,534 CRC patients, 54 (0.98%) had actionable gene fusions, with NTRK1/2/3 being the most common fusion (0.38%), accounting for 38.9% (21/54) of those with fusions. Actionable gene fusion enrichment was higher in patients with microsatellite instability-high (MSI-H) (6.7% vs. 0.5%, P < 0.001), RAS/BRAF wildtype (2.0% vs. 0.2%, P < 0.001) and RNF43 mutation (7.7% vs. 0.4%, P < 0.001) than in patients with microsatellite stability/MSI-low, RAS/BRAF mutation and RNF43 wildtype, respectively. When these markers were combined, the fusion detection rate increased. Among patients with RAS/BRAF wildtype and MSI-H, fusions were detected in 20.3% of patients. The fusion detection rate further increased to 37.5% when RNF43 mutation was added. The fusion detection rate was also higher in colon cancer than in rectal cancer. No significant differences in clinical or molecular features were found in patients with actionable gene fusions between the Genecast, cBioPortal, and ChimerSeq databases. Conclusions: Approximately 1% of the unselected Chinese CRC population carries actionable gene fusions, mostly involving NTRK. Actionable gene fusions are more prevalent in MSI-H, RAS/BRAF wildtype, or RNF43-mutated CRC, as well as in colon cancer. Mapping of these molecular markers can markedly increase the fusion detection rate, which can help clinicians select candidates for fusion testing and targeted therapy.

Current status and trend of mitochondrial research in lung cancer: A bibliometric and visualization analysis.

This study summarizes and analyzes the relationship between mitochondria and the pathogenesis of lung cancer. The related articles in the Web of Science core literature database are searched and collected, and the data are processed by R software, Citespace, VOSviewer, and Excel. A total of 4476 related papers were retrieved, 4476 articles from 20162 co-authors of 3968 institutions in 84 countries and published in 951 journals. Through various bibliometric analysis tools, the relationship between mitochondria and the pathogenesis of lung cancer was analyzed, the previous research results were summarized, and the potential research direction was found.

Construction and validation of chronic pain prediction model after total knee arthroplasty.

Objective: To explore the risk factors of chronic pain after total knee arthroplasty (TKA) and to establish and verify a prediction model. Methods: As a retrospective observational study, medical records of 239 patients who underwent TKA in Affiliated Hospital of Jiangnan University from January 2020 to December 2022 were reviewed. Fifty four patients suffered from chronic pain after TKA surgery. Univariate and multivariate logistic regression were used to analyze factors associated with the occurrence of chronic pain after TKA. A nomogram prediction model was established based on the identified independent risk factors, and its predictive effectiveness was evaluated. Results: Gender, postoperative 24-hourss numerical rating scale (NRS) and postoperative three months Hospital for Special Surgery Knee-Rating (HSS) scores were independent risk factors for chronic pain after TKA (p<0.05). The area of the receiver operating characteristic (ROC) of the nomogram model based on these factors was 0.904 (95% confidence interval [CI): 0.861-0.947), which indicates a good predictive value for the postoperative chronic pain. When the optimal cut off value was selected, the sensitivity and specificity of the model were 92.6% and 74.1%, respectively, indicating that the predictive model is effective. Conclusions: Gender, postoperative 24-hours NRS and postoperative three months HSS score are independent risk factors for chronic pain after TKA. The nomogram prediction model based on these factors is effective and can provide auxiliary reference for patients with chronic pain after TKA.

Composite diffuse large B-cell lymphoma and peripheral T-cell lymphoma: a case report with two-year follow-up and literature review.

Composite lymphoma is an uncommon type of lymphoid malignancy, and those consisting of concurrent diffuse large B-cell lymphoma (DLBCL) and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) in the same organ are rare. Here, we report a case of a 75-year-old male patient admitted to our emergency department with intestinal obstruction presenting with abdominal pain and vomiting. He underwent partial resection of the small intestine under general anesthesia, and subsequent histopathology confirmed the mass to be composite DLBCL and PTCL-NOS. The patient received chemotherapy with a rituximab-based regimen and achieved complete remission (CR). However, the recurrent disease presented with obstruction again ten months after treatment. He refused a second surgery, but salvage treatment was not effective. The patient survived for 20 months after diagnosis. In addition, we did a literature review to understand the clinical features, pathology, treatment, and prognosis of this type of composite lymphoma.

Histiocytic sarcoma following CAR T-cell therapy: a case report.

BACKGROUND: Development of secondary tumor after CART treatment is not well investigated. We report a pediatric B-cell acute lymphoblastic leukemia (B-ALL) patient who developed histiocytic sarcoma shortly after CART therapy. CASE REPORT: A 9-year-old boy diagnosed with relapsed B-ALL presenting the KRAS A146T mutation received autologous mouse-derived CD19 and CD22 chimeric antigen receptor T-cell therapy at our center (Chinese Clinical Trial Registry: ChiCTR2000032211). Thirty days post-CART therapy, the bone marrow showed complete remission. At 85 days post-CART therapy, the boy presented with fever and chills. An abdominal CT scan showed massive hepatomegaly with multiple low-density lesions in the liver. At 130 days post-CART therapy, a bone marrow smear showed abnormal proliferation of macrophages, some of which exhibited phagocytosis. On day 136 post-CART therapy, laparoscopic liver biopsy was performed, revealing multiple yellow-white lesions on the surface of the liver. Microscopically, multifocal lesions were observed, predominantly composed of cells with abundant cytoplasm. Immunohistochemical staining indicated histiocytic origin. Based on the immunohistochemical results, histiocytic sarcoma was diagnosed. The same cytogenetic markers were identified in histiocytic sarcoma. CONCLUSION: Our case illustrates a rare complication after CART therapy. The diagnosis and treatment of histiocytic sarcoma pose many challenges.

Case Report: Unedited allogeneic chimeric antigen receptor T cell bridging to conditioning-free hematopoietic stem cell transplantation for a child with refractory Burkitt lymphoma.

Purpose: Burkitt lymphoma (BL) is the most common tumor of non-Hodgkin's lymphoma (NHL) in children, accounting for about 40% of cases. Although different combined short-course chemotherapies have achieved a good effect, refractory/relapsed BL has a poor prognosis with cure rates less than 30%. Chimeric antigen receptor T cell (CAR-T) therapy has developed rapidly in recent years and achieved excellent results in acute lymphoblastic leukemia (ALL). However, in some cases, there is a failure to produce autologous CAR-T cells because of T-cell dysfunction. In such cases, allogeneic CAR-T therapy has to be considered. Methods: A 17-year-old boy with stage II BL did not respond to extensive chemotherapy and sequential autologous CAR-T therapy. Lentiviral vectors containing anti-CD20-BB-ζ (20CAR) and anti-CD22-BB-ζ (22CAR) transgenes were used to modify the T cells from an HLA-identical matched unrelated donor. Flow cytometry was used to assess the cytokine analyses and CAR-T cell persistence in peripheral blood, enumerated by qPCR as copies per ug DNA. Informed consent for autologous/allogeneic CAR-T therapy was obtained from the patient and his legal guardian. Results: Unedited HLA-matched allogeneic CD20 and CD22 CAR-T cells were infused after lymphodepletion chemotherapy with cyclophosphamide and fludarabine. The patient experienced Grade IV cytokine release syndrome (CRS) and went into complete remission (CR) after anti-inflammatory treatment including tocilizumab. Because of persistent pancytopenia and full donor chimerism, the same donor's conditioning-free peripheral blood stem cells were successfully transplanted 55 days post CAR-T. Neutrophils were engrafted at day +11 and platelets were rebuilt at day +47 without obvious acute graft-versus-host disease (GVHD), but there was mild chronic GVHD in the skin and eyes. Currently, active anti-rejection therapy is still underway. Conclusion: Unedited HLA-matched allogeneic CAR-T cell therapy could be an innovative, effective, and safe treatment for children with refractory/relapse BL without obvious acute GVHD. Conditioning-free allogeneic hematopoietic stem cell transplantation (HSCT) from the same donor is feasible for a patient with full donor T-cell chimerism after allogeneic CAR-T. It cannot be ignored that close GVHD monitoring is needed post HSCT.

Coadministration of CD19- and CD22-Directed Chimeric Antigen Receptor T-Cell Therapy in Childhood B-Cell Acute Lymphoblastic Leukemia: A Single-Arm, Multicenter, Phase II Trial.

PURPOSE: We determined the safety and efficacy of coadministration of CD19- and CD22-chimeric antigen receptor (CAR) T cells in patients with refractory disease or high-risk hematologic or isolated extramedullary relapse of B-acute lymphoblastic leukemia. PATIENTS AND METHODS: This phase II trial enrolled 225 evaluable patients age ≤ 20 years between September 17, 2019, and December 31, 2021. We first conducted a safety run-in stage to determine the recommended dose. After interim analysis of the first 30 patients treated (27 at the recommended dose) showing that the treatment was safe and effective, the study enrolled additional patients according to the study design. RESULTS: Complete remission was achieved in 99.0% of the 194 patients with refractory leukemia or hematologic relapse, all negative for minimal residual disease. Their overall 12-month event-free survival (EFS) was 73.5% (95% CI, 67.3 to 80.3). Relapse occurred in 43 patients (24 with CD19+/CD22+ relapse, 16 CD19-/CD22+, one CD19-/CD22-, and two unknown). Consolidative transplantation and persistent B-cell aplasia at 6 months were associated with favorable outcomes. The 12-month EFS was 85.0% (95% CI, 77.2 to 93.6) for the 78 patients treated with transplantation and 69.2% (95% CI, 60.8 to 78.8) for the 116 nontransplanted patients (P = .03, time-dependent covariate Cox model). All 25 patients with persistent B-cell aplasia at 6 months remained in remission at 12 months. The 12-month EFS for the 20 patients with isolated testicular relapse was 95.0% (95% CI, 85.9 to 100), and for the 10 patients with isolated CNS relapse, it was 68.6% (95% CI, 44.5 to 100). Cytokine release syndrome developed in 198 (88.0%) patients, and CAR T-cell neurotoxicity in 47 (20.9%), resulting in three deaths. CONCLUSION: CD19-/CD22-CAR T-cell therapy achieved relatively durable remission in children with relapsed or refractory B-acute lymphoblastic leukemia, including those with isolated or combined extramedullary relapse.[Media: see text].

CMaf-Inducing Protein Promotes LUAD Proliferation and Metastasis by Activating the MAPK/ERK Pathway.

Objective: Previous studies have shown that cMaf-inducing protein (CMIP) promotes tumorigenesis and progression, however, the role of CMIP in lung adenocarcinoma (LUAD) and its molecular mechanism remain unclear. Methods: In this study, the Human Protein Atlas and Kaplan-Meier Plotter database were used to analyze the expression and prognostic value of CMIP in LUAD. Then, the expression levels of CMIP in LUAD tissues and cells were detected by qRT-PCR and western blot. The lentiviral vector was used to establish a stable transfected cell line, and the transfection efficiency was detected by qRT-PCR. MTT assay, colony formation assay, transwell assay, and wound healing assay were used to evaluate the function of CMIP in LUAD. In addition, the effect of CMIP on the MAPK/ERK pathway in LUAD cells was analyzed by western blot. Results: The expression level of CMIP was significantly increased in LUAD cell and tissue samples, and the high expression of CMIP was associated with overall survival (OS) and progression-free survival (PFS) in LUAD patients. In vitro experiments showed that CMIP overexpression significantly promoted the proliferation, migration, and invasion of A549 cells. CMIP knockout significantly inhibited the proliferation, migration, and invasion of H1299 cells. In addition, it was observed that the expression levels of the MAPK/ERK pathway-related proteins were significantly increased in CMIP-overexpressed A549 cells, and promoted cell proliferation, migration, and invasion, while U0126 could significantly reverse the activation of the MAPK/ERK pathway by CMIP overexpression, and inhibit the proliferation, migration, and invasion of A549 cells. Conclusion: Our study shows that CMIP, as an oncogene, is associated with poor patient prognosis, and may promote the proliferation and metastasis of LUAD by activating the MAPK/ERK pathway. Therefore, CMIP may be a new potential therapeutic target for LUAD.

Comparison of Global and Regional Compliance-Guided Positive End-Expiratory Pressure Titration on Regional Lung Ventilation in Moderate-to-Severe Pediatric Acute Respiratory Distress Syndrome.

Purpose: To investigate the difference in the positive end-expiratory pressure (PEEP) selected with chest electrical impedance tomography (EIT) and with global dynamic respiratory system compliance (Crs) in moderate-to-severe pediatric acute respiratory distress syndrome (pARDS). Methods: Patients with moderate-to-severe pARDS (PaO2/FiO2 < 200 mmHg) were retrospectively included. On the day of pARDS diagnosis, two PEEP levels were determined during the decremental PEEP titration for each individual using the best compliance (PEEPC) and EIT-based regional compliance (PEEPEIT) methods. The differences of global and regional compliance (for both gravity-dependent and non-dependent regions) under the two PEEP conditions were compared. In addition, the EIT-based global inhomogeneity index (GI), the center of ventilation (CoV), and standard deviation of regional delayed ventilation (RVDSD) were also calculated and compared. Results: A total of 12 children with pARDS (5 with severe and 7 with moderate pARDS) were included. PEEPC and PEEPEIT were identical in 6 patients. In others, the differences were only ± 2 cm H2O (one PEEP step). There were no statistical differences in global compliance at PEEPC and PEEPEIT [28.7 (2.84-33.15) vs. 29.74 (2.84-33.47) ml/cm H2O median (IQR), p = 0.028 (the significant level after adjusted for multiple comparison was 0.017)]. Furthermore, no differences were found in regional compliances and other EIT-based parameters measuring spatial and temporal ventilation distributions. Conclusion: Although EIT provided information on ventilation distribution, PEEP selected with the best Crs might be non-inferior to EIT-guided regional ventilation in moderate-to-severe pARDS. Further study with a large sample size is required to confirm the finding.

Knockdown of lncRNA AL928768.3 inhibits multiple myeloma cell proliferation by inducing cell cycle arrest in G0/G1 phase.

Background: Multiple myeloma (MM) is a B-lymphocyte-derived malignancy. It ranks as the second most common hematological malignancy, with relatively high morbidity and mortality. However, the molecular mechanisms of MM occurrence and development remain elusive. This study found that long non-coding RNA AL928768.3 (lncRNA AL) was abnormally expressed in MM samples. However, the effect and molecular mechanism of lncRNA AL on the occurrence and development of MM remains unclear. Methods: Bone marrow fluids of MM patients (n=54) and volunteers (n=13) were collected and CD138+ cells were isolated. The expression level of lncRNA AL in MM cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR), and the correlation between the expression level of lncRNA AL and the clinicopathological features of patients was analyzed. Lentiviral vectors targeting lncRNA AL knockdown were constructed and transfected into cells. After transfection, the effects of lncRNA AL knockdown on MM cell proliferation and the cell cycle were detected by the CCK-8 assay, clone formation assay, and flow cytometry. The effect of lncRNA AL knockdown on MM cell cycle-related proteins was detected by Western blot. In addition, tumorigenicity experiments were performed in nude mice to detect the effect of lncRNA AL knockdown on MM cell proliferation in vivo. Results: LncRNA AL was highly expressed in MM patient samples and cell lines, and was significantly correlated with the disease stage of patients. Knockdown of lncRNA AL significantly inhibited the proliferation and colony formation of MM cells and induced cell cycle arrest in G0/G1 phase. Western blot analysis showed that knockdown of lncRNA AL significantly inhibited the expression of CDK2 and cyclin D1 and promoted the expression of cyclin suppressor p21. Knockdown of lncRNA AL significantly inhibited the proliferation of MM cells in nude mice. Conclusions: LncRNA AL was highly expressed in MM patients. Knockdown of this gene significantly inhibited the proliferative ability of MM cells and induced cell cycle arrest in G0/G1 phase. Therefore, lncRNA AL may be a novel biological target molecule for the early diagnosis, treatment, and prognostic evaluation of MM patients.

Clinical value of pediatric sepsis-induced coagulopathy score in diagnosis of sepsis-induced coagulopathy and prognosis in children.

BACKGROUND: In adults, sepsis-induced coagulopathy (SIC) is diagnosed by the SIC score, known as sepsis-3. There is no pediatric SIC (pSIC) score at present. OBJECTIVES: We proposed a pSIC scoring method and evaluated the diagnostic efficacy of the score in the diagnosis of SIC in children. PATIENTS/METHODS: Patient data were retrospectively analyzed from Shanghai Children's Medical Center between February 2014 and January 2015. The pSIC score was modified from the SIC score. The area under ROC curve (AU-ROC) was used to compare the prognostic values of pSIC with other scores for pediatric sepsis-induced disseminated intravascular coagulation (DIC) to arrive at a 28-day outcome. RESULTS AND CONCLUSIONS: There were 54 patients in the pSIC group and 37 in the non-pSIC group. The Kaplan-Meier survival curve analysis showed that the 28-day prognosis was better in the non-pSIC than in the pSIC group (p < .001). The AU-ROC of the pSIC score in predicting 28-day mortality in sepsis was 0.716, with the optimal cutoff value of >3 inferior to that of pediatric sequential organ failure (0.716 vs. 0.921, p < .001). The AU-ROC of pSIC in predicting nonovert DIC was 0.845 and the optimal cutoff value was >3. The AU-ROC of pSIC in predicting overt DIC was 0.901, with the best optimal cutoff value of >4. The pSIC score can be used to diagnose SIC in children, screen potential nonovert DIC, and assess the severity of sepsis, organ dysfunction, and 28-day outcome in children.

Atorvastatin improves bone marrow endothelial progenitor cell function from patients with immune-related hemocytopenia.

BACKGROUND: Immune-related hemocytopenia (IRH) is a type of autoimmune disease that targets bone marrow hematopoietic cells. This study investigated the influence of atorvastatin on the functional aspects of bone marrow endothelial progenitor cells (BM EPCs) in IRH patients. METHODS: BM EPCs were isolated from 15 patients with IRH and 20 normal controls. The isolated BM EPCs were characterized by flow cytometry. Cell counting kit-8, flow cytometry, and Transwell migration assays were used to determine the proliferation, apoptosis, and migration of BM EPCs, respectively. Protein levels were determined by western blot assay. RESULTS: The BM EPCs isolated from IRH patients showed reduced proliferation, increased apoptosis, and attenuated migratory ability compared to those from normal controls. Western blot analysis showed that the protein level of p-p38 was significantly increased, while that of Phosphorylated protein kinase B (p-AKT) was significantly decreased in the BM EPCs from IRH patients, compared to BM EPCs from healthy subjects. Cell proliferation and migration were significantly enhanced by atorvastatin, recombinant human thrombopoietin, and SB20358 compared to the untreated BM EPCs from IRH patients. Atorvastatin, Recombinant human thrombopoietin (TPO), and SB20358 treatment significantly suppressed the protein levels of p-p38 protein, but increased those of p-AKT in BM EPCS from IRH patients. CONCLUSIONS: In summary, atorvastatin increases the number and function of BM EPCs in IRH patients by regulating the p38 and AKT signaling pathways.

The Clinical Characteristics of ARDS in Children With Hematological Neoplasms.

In order to explore the clinical characteristics of pediatric patients admitted to the pediatric intensive care unit (PICU) who suffered from hematological neoplasms complicated with acute respiratory distress syndrome (ARDS), we retrospectively analyzed 45 ARDS children with hematological neoplasms who were admitted to the PICU of Shanghai Children's Medical Center from January 1, 2014, to December 31, 2020. The 45 children were divided into a survival group and a non-survival group, a pulmonary ARDS group and an exogenous pulmonary ARDS group, and an agranulocytosis group and a non-agranulocytosis group, for statistical analysis. The main clinical manifestations were fever, cough, progressive dyspnea, and hypoxemia; 55.6% (25/45) of the children had multiple organ dysfunction syndrome (MODS). The overall mortality rate was 55.6% (25/45). The vasoactive inotropic score (VIS), pediatric critical illness scoring (PCIS), average fluid volume in the first 3 days and the first 7 days, and the incidence of MODS in the non-survival group were all significantly higher than those in the survival group (P < 0.05). However, total length of mechanical ventilation and length of hospital stay and PICU days in the non-survival group were significantly lower than those in the survival group (P < 0.05). The PCIS (OR = 0.832, P = 0.004) and the average fluid volume in the first 3 days (OR = 1.092, P = 0.025) were independent risk factors for predicting death. Children with exogenous pulmonary ARDS were more likely to have MODS than pulmonary ARDS (P < 0.05). The mean values of VIS, C-reactive protein (CRP), and procalcitonin (PCT) in children with exogenous pulmonary ARDS were also higher (P < 0.05). After multivariate analysis, PCT was independently related to exogenous pulmonary ARDS. The total length of hospital stay, peak inspiratory pressure (PIP), VIS, CRP, and PCT in the agranulocytosis group were significantly higher than those in the non-agranulocytosis group (P < 0.05). Last, CRP and PIP were independently related to agranulocytosis. In conclusion, children with hematological neoplasms complicated with ARDS had a high overall mortality and poor prognosis. Children complicated with MODS, positive fluid balance, and high VIS and PCIS scores were positively correlated with mortality. In particular, PCIS score and average fluid volume in the first 3 days were independent risk factors for predicting death. Children with exogenous pulmonary ARDS and children with agranulocytosis were in a severely infected status and more critically ill.

Class IIa HDAC Downregulation Contributes to Surgery-Induced Cognitive Impairment Through HMGB1-Mediated Inflammatory Response in the Hippocampi of Aged Mice.

OBJECTIVE: Perioperative neurocognitive disorders (PND) are a common complication in the elderly. Histone deacetylases (HDACs) are a class of enzymes that control the acetylation status of intracellular proteins. Thus, we explored whether HDACs trigger the release of high mobility group box 1 (HMGB1) through altering the acetylation status in the hippocampi of aged mice. MATERIALS AND METHODS: The effect of the Class IIa HDAC in PND was explored using an in vivo form of splenectomy. Sixteen-month-old healthy male C57BL/6J mice were randomly divided into five groups: control, anesthesia plus sham surgery, anesthesia plus splenectomy, LMK235 treatment, and PBS treatment. The hippocampi were harvested on either first, third, or seventh postoperative day. Cognitive function was assessed via a Morris water maze (MWM) test. Quantitative RT-PCR, Western blots and ELISAs were carried out to assess the targeted gene expression at transcriptional and translational levels. RESULTS: Splenectomy led to a significant deficiency in spatial memory acquisition, marked decreases in mRNA and protein levels of HDAC4 and HDAC5 in the hippocampus, and increases in the levels of total HMGB1 and acetylated HMGB1. In a similar fashion to splenectomy, treatment with the HDAC4/5 inhibitor LMK235 produced impaired spatial memory and an increase in the expression of HMGB1 and its acetylated counterpart in the hippocampus. CONCLUSION: These results suggest that surgery leads to PND through class IIa HDAC downregulation-triggered HMGB1 release in hippocampus of aged mice. HDACs may be a potential therapeutic target for postoperative cognitive dysfunction.

The clinical outcomes and biomarker features of severe sepsis/septic shock with severe neutropenia: a retrospective cohort study.

BACKGROUND: Severe sepsis/septic shock with severe neutropenia often leads to poor prognosis. However, it is unknown if severe neutropenia is associated with different clinical outcomes and biomarker features in severe sepsis/septic patients. METHODS: This retrospective cohort study enrolled 141 severe sepsis/septic shock patients admitted to intensive care unit of Shanghai Children's Medical Center between January 2015 and November 2019. Patients were followed up for the development of ventilation support, the use of vasoactive drugs, continuous renal replacement therapy (CRRT) procedure, and mortality. Biomarkers that reflect the level of inflammation in severe sepsis/septic shock patients with neutropenia were compared to that in patients without neutropenia. RESULTS: Of 141 patients enrolled, 54 patients suffered from severe sepsis/septic shock with severe neutropenia. In patients with severe sepsis/septic shock, severe neutropenia as a complication was an independent risk factor for the use of vasoactive drugs (RR 9.796; 95% CI: 3.774, 25.429; P<0.001), but not for ventilation support (RR 0.157; 95% CI: 0.06, 0.414; P<0.001), CRRT procedure (RR 1.032; 95% CI: 0.359, 2.969; P=0.953) or 28-day mortality (RR 1.405; 95% CI: 0.533, 3.708; P=0.492). Severe sepsis/septic patients with severe neutropenia had a higher plasma level of the following biomarkers: c-reaction protein (CRP) (180.5 vs. 121 mg/mL, P<0.001), procalcitonin (PCT) (12.15 vs. 2.7 ng/mL; P=0.005), interleukin (IL)-6 (316.83 vs. 55.77 pg/mL, P<0.001), IL-10 (39.165 vs. 10.09 pg/mL, P<0.001), interferon (IFN)-γ (6.155 vs. 3.71 pg/mL, P=0.016), and the percentage of regulatory T cells (Tregs) (2.7% vs. 2.09%, P=0.003). Based on the receiver operating characteristic curves, IL-10 exhibited high specificity (79.4%) in evaluating the prognosis of septic patients with neutropenia. CONCLUSIONS: In patients with severe sepsis/septic shock, being complicated with severe neutropenia is associated with higher proportion of using vasoactive drugs, and those patients tend to have higher plasma levels of IL-6, IL-10, IFN-γ and percentage of Treg.

An email-based survey of practice regarding hemodynamic monitoring and management in children with septic shock in China.

BACKGROUND: Understanding current hemodynamic monitoring (HM) practice patterns is essential to determine education and training strategies in China. The survey was to describe the practice of HM and management in children with septic shock in China. METHODS: We conducted an Email-based survey of members of sub-association of pediatric intensive care physicians. The questionnaire consisted of 22 questions and gathered the following information: (I) general information on the hospitals, respective ICUs and participants, (II) the availability of technical equipment and parameters of HM and (III) management simulation of septic shock in three clinical case vignettes. RESULTS: Surveys were received from 68 institutions (87.2%) and 368 questionnaires (response-rate 45.1%) were included. Basic HM (93-100%) were reported as the most utilized parameters, followed by advanced HM which included central venous pressure (CVP) (56.0%), cardiac output (53.5%), and central venous oxygen saturation (36.7%), 61.1% (225/368) of respondents stated the utilization of non-invasive HM equipment. The factors such as ICU specialist training center (P=0.003) and more than 30 cases of septic shock per year (P=0.002) were related to the utilization of non-invasive monitoring equipment. In the simulated case vignette, 49.7% (183/368) of respondents reported performing fluid responsiveness and volume status (FR-VS) assessment. Despite differences in training centers (P=0.005) and educational backgrounds (P=0.030), FR-VS assessment was not related to the volume expansion decision. CONCLUSIONS: There is a large variability in use advanced HM parameters, an increasing awareness and acceptance of non-invasive HM devices and a potential need for hemodynamic education and training in pediatric intensive care medicine in China.

Thrombopoietin Promotes Cell Proliferation and Attenuates Apoptosis of Aplastic Anemia Serum-Treated 32D Cells via Activating STAT3/STAT5 Signaling Pathway and Modulating Apoptosis-Related Mediators.

The present study aimed to investigate the effect and possible mechanism of recombinant human thrombopoietin (rhTPO) on mouse 32D cells (a mouse myeloid progenitor cell line) treated with serum from patients with aplastic anemia and to elucidate the potential mechanism of rhTPO in the treatment of aplastic anemia. After treatment with aplastic anemia serum, the apoptotic rate of 32D cells was increased and the proliferation of 32D cells was significantly inhibited. rhTPO reduced the apoptotic rate and promoted the proliferation of 32D cells, while rhTPO failed to restore the cell proliferation of 32D cells from aplastic anemia serum group to the normal level as compared to that from the normal serum group. The phosphorylation level of STAT3 protein was higher, and the phosphorylation level of STAT5 protein was lower in 32D cells from aplastic anemia serum group than that in normal serum group. After rhTPO treatment, the phosphorylation level of STAT3 protein in aplastic anemia serum group was decreased and the phosphorylation level of STAT5 protein was increased. The expression levels of Survivin and Bcl-2 were significantly decreased in 32D cells from aplastic anemia serum group, which were significantly increased after rhTPO treatment. The expression level of Bax protein in 32D cells from the normal serum group after rhTPO treatment was significantly decreased; while the mRNA expression level of Bax was not affected by rhTPO. The expression levels of Bax mRNA and protein were significantly up-regulated in 32D cells from aplastic anemia serum group, which was significantly decreased by rhTPO treatment. In conclusion, our results indicated that aplastic anemia serum impaired proliferative potential and enhanced apoptosis of 32D cells. Further mechanistic studies revealed that rhTPO promoted cell proliferation and attenuated apoptosis of aplastic anemia serum-treated 32D cells via activating STAT3/STAT5 signaling pathway and modulating apoptosis-related mediators.

Inhibition of YBX1 by miR-216a Suppresses Proliferation and Invasion of Diffuse Large B-Cell Lymphoma.

BACKGROUND: MicroRNAs (miRNAs) could be implicated in tumorigenesis of diffuse large B-cell lymphoma (DLBCL). AIMS: To determine the role of MiR-216a in DLBCL. STUDY DESIGN: Cell culture study. METHODS: Expression of miR-216a in DLBCL cells was examined by qRT-PCR. Cell counting kit-8, bromodeoxyuridine staining and transwell assays were performed to evaluate role of miR-216a on DLBCL cell growth. Target gene of miR-216a was verified by luciferase reporter assay. RESULTS: MiR-216a was dramatically reduced in DLBCL cells compared to the normal B-cell line (P < .01). MiR-216a reduced the viability and retarded DLBCL cell proliferation. The invasion of DLBCL was suppressed by miR-216a. Y box binding protein 1 (YBX1) was validated as a target of miR-216a. Its expression was reduced by miR-216a mimic and enhanced by miR-216a inhibitor in DB and SU-DHL-10 cells. Knockdown of YBX1 reduced cell viability, proliferation, and invasion of DB and SU-DHL-10 cells. CONCLUSION: MiR-216a exerted tumor-suppressive effects on DLBCL cells through inhibition of YBX1, providing a new strategy for DLBCL.