Decitabine as epigenetic priming with CLAG induce improved outcome of relapsed or refractory acute myeloid leukemia in children.

BACKGROUND: Decitabine (DAC), a DNA methyltransferase inhibitor, has shown efficacy combined with chemotherapy for relapsed or refractory (R/R) acute myeloid leukemia (AML) in adults, but less is known about its efficacy in children. Accordingly, we conducted a study which involved a priming regimen consisting of DAC with cladribine, cytarabine, and granulocyte-stimulating factor (DAC-CLAG) and compared the efficacy and safety of this regimen with CLAG alone. METHODS: A total of 39 R/R AML children who received the CLAG or DAC-CLAG regimen in Shanghai Children's Hospital were retrospectively enrolled in this non-randomized study. These regimens were studied sequentially over time. Twenty-two patients received CLAG from 2015, while 17 patients were administered epigenetic priming with DAC before CLAG from 2020. Patients were subsequently bridged to stem cell transplantation (SCT) or consolidation chemotherapy. Complete remission (CR) and adverse effects were analyzed by Fisher's exact test, and survival was analyzed by the Kaplan-Meier method. RESULTS: DAC-CLAG conferred a numerically higher CR compared to CLAG (70.59% vs 63.64%; P = 0.740). High CR rates occurred in patients with good cytogenetics (P = 0.029) and prior induction without cladribine (P = 0.099). The 1-year event-free survival (EFS) was 64.71% ± 11.59% and 63.31% ± 10.35% in the DAC-CLAG and CLAG group (P = 0.595), and 1-year overall survival (OS) was 81.45% ± 9.72% and 77.01% ± 9.04%, respectively (P = 0.265). The 1-year OS and EFS after SCT were higher in the DAC-CLAG than in the CLAG cohort (100% vs 92.31% ± 7.39%, P = 0.072; 92.31% ± 7.39% vs 85.71% ± 9.35%, P = 0.158). Univariate analysis revealed that a good prognosis included good cytogenetics (P = 0.002), non-complex karyotype (P = 0.056), CR on reinduction (P < 0.0001), and bridging to SCT (P = 0.0007). Use of a hypomethylating agent (P = 0.049) and bridging to SCT (P = 0.011) were independent prognostic factors. Grade 3/4 hematologic toxicity and infection were the main adverse events. CONCLUSIONS: DAC prior to the CLAG regimen improved remission in pediatric R/R AML, and was feasible and well tolerated. CLAG ± DAC as a salvage therapy prior to SCT induced improved survival.

[Prognostic analysis of childhood T-lymphoblastic lymphoma treated with leukemia regimen]. / 儿童Tæ·‹å·´æ¯ç»†èƒžæ·‹å·´ç˜¤é‡‡ç”¨ç™½è¡€ç— æ–¹æ¡ˆæ²»ç–—çš„é¢„åŽåˆ†æž.

OBJECTIVES: To investigate the prognosis of childhood T-lymphoblastic lymphoma (T-LBL) treated with acute lymphoblastic leukemia (ALL) regimen and related influencing factors. METHODS: A retrospective analysis was performed for the prognostic characteristics of 29 children with T-LBL who were treated with ALL regimen (ALL-2009 or CCCG-ALL-2015 regimen) from May 2010 to May 2022. RESULTS: The 29 children with T-LBL had a 5-year overall survival (OS) rate of 84%±7% and an event-free survival (EFS) rate of 81%±8%. The children with B systemic symptoms (unexplained fever >38°C for more than 3 days; night sweats; weight loss >10% within 6 months) at initial diagnosis had a lower 5-year EFS rate compared to the children without B symptoms (P<0.05). The children with platelet count >400×109/L and involvement of both mediastinum and lymph nodes at initial diagnosis had lower 5-year OS rates (P<0.05). There were no significant differences in 5-year OS and EFS rates between the children treated with CCCG-ALL-2015 regimen and those treated with ALL-2009 regimen (P>0.05). Compared with the ALL-2009 regimen, the CCCG-ALL-2015 regimen reduced the frequency of high-dose methotrexate chemotherapy and the incidence rate of severe infections (P<0.05). CONCLUSIONS: The ALL regimen is safe and effective in children with T-LBL. Children with B systemic symptoms, platelet count >400×109/L, and involvement of both mediastinum and lymph nodes at initial diagnosis tend to have a poor prognosis. Reduction in the frequency of high-dose methotrexate chemotherapy can reduce the incidence rate of severe infections, but it does not affect prognosis.

Immunophenotype of lymphocytes and real-world outcome of COVID-19 infection in children with hematology and oncology.

BACKGROUND: Patients with immunocompromise were suspected to encounter a high risk for severe coronavirus disease 2019 (COVID-19) infection on early period; however, data is lacking nowadays and immune response remain unclear. METHODS: In this retrospective study, internet questionnaire survey and medical records were acquired in pediatric hematology oncology patients. Clinical severity, immunological characteristics, and outcomes were analyzed from December 1, 2022 to January 31, 2023 at the 3rd year of pandemic in China. RESULTS: A total of 306 patients were included, with 21 patients (6.9%) asymptomatic, 262 (85.6%) mild severity, 17 (5.6%) moderate severity, 5 (1.6%) severe severity, and 1 (0.3%) critical severity. Seventy-eight (25.5%) patients were on intensive chemotherapy, and 32.0% children were on maintenance chemotherapy. Delays in cancer therapy occurred in 86.7% patients. Univariable analysis revealed active chemotherapy (P < 0.0001), long duration of symptom (P < 0.0001), low lymphocytes count (P = 0.095), low CD3 + and CD8 + T cell count (P = 0.013, P = 0.022), high percentage of CD4 + TCM (P = 0.016), and low percentage of transitional B cells (P = 0.045) were high risk factors for severe COVID-19 infection. Cox regression model showed that the absolute lymphocytes count (P = 0.027) and long duration of symptom (P = 0.002) were the independent factors for severity. Patients with CD8 + dominant and B cell depletion subtype wasn't related with severity, but had higher percentage of CD8 + effector memory T cells (TEM) and terminally differentiated effector memory T cells (TEMRA) (P < 0.001, P < 0.001), and a longer COVID-19 duration (P = 0.045). CONCLUSION: The severity was relatively mild in children with immunodeficiencies in the third year of COVID-19 pandemic. Low lymphocyte count and long duration of symptom were the independent risk factors with COVID-19 severity. Delays in cancer care remain a major concern and the long outcome is pending.

Cytopenia: a report of haplo-cord transplantation in twin brothers caused by a novel germline GATA1 mutation and family survey.

Cytopenia due to the abnormal regulation of GATA1 could manifest as varying degrees of thrombocytopenia and/or anemia and more severely in male children than in female children. Here, we describe the case of pancytopenic and transfusion-dependent twin brothers at our center whose bone marrow puncture revealed low bone marrow hyperplasia. Whole-exome sequencing revealed that the twins had a new germline GATA1 mutation (nm_002049: exon 3:c.515 T >C:p.F172S), which confirmed the diagnosis of GATA1 mutation-related pancytopenia. The mutation was inherited from their mother, who was heterozygous for the mutation. Sanger sequencing verified the pathogenicity of the mutation. Further family morbidity survey confirmed that GATA1 mutation-related pancytopenia is an X-linked recessive genetic disorder. We developed haploid hematopoietic stem cell transplantation programs for twins, with the father as the only donor, and finally, the hematopoietic reconstruction was successful. Although they experienced acute graft-versus-host disease, hemorrhagic cystitis, and a viral infection in the early stage, no abnormal manifestations or transplant-related complications were observed 3 months after transplantation. Through hematopoietic stem cell transplantation technology for one donor and two receptors, we eventually cured the twins. The p.F172S variant in the new germline GATA1 mutation may play an essential role in the pathogenesis of GATA1 mutation-related cytopenia.

[Effectiveness of autologous hematopoietic stem cell transplantation in the treatment of high-risk neuroblastoma in children: a single-center clinical study]. / å•ä¸­å¿ƒå„¿ç«¥é«˜å±ç¥žç»æ¯ç»†èƒžç˜¤è‡ªä½“é€ è¡€å¹²ç»†èƒžç§»æ¤çš„ç–—æ•ˆåˆ†æž.

OBJECTIVES: To investigate the effectiveness of high-dose chemotherapy combined with autologous hematopoietic stem cell transplantation (ASCT) in the treatment of children with high-risk neuroblastoma (NB). METHODS: A retrospective analysis was performed on 29 children with high-risk NB who were admitted to Shanghai Children's Hospital and were treated with high-dose chemotherapy combined with ASCT from January 2013 to December 2021, and their clinical features and prognosis were analyzed. RESULTS: Among the 29 children treated by high-dose chemotherapy combined with ASCT, there were 18 boys (62%) and 11 girls (38%), with a median age of onset of 36 (27, 59) months. According to the International Neuroblastoma Staging System, 6 children (21%) had stage III NB and 23 children (79%) had stage IV NB, and the common metastatic sites at initial diagnosis were bone in 22 children (76%), bone marrow in 21 children (72%), and intracalvarium in 4 children (14%). All 29 children achieved reconstruction of hematopoietic function after ASCT. After being followed up for a median time of 25 (17, 45) months, 21 children (72%) had continuous complete remission and 8 (28%) experienced recurrence. The 3-year overall survival rate and event-free survival rate were 68.9%±16.1% and 61.4%±14.4%, respectively. Presence of bone marrow metastasis, neuron-specific enolase ≥370 ng/mL and positive bone marrow immunophenotyping might reduce the 3-year event-free survival rate (P<0.05). CONCLUSIONS: Children with high-risk NB who have bone marrow metastasis at initial diagnosis tend to have a poor prognosis. ASCT combined with high-dose chemotherapy can effectively improve the prognosis of children with NB with a favorable safety profile.

Mucin 1 expression correlation with lymph node metastasis and micrometastasis and poor prognosis in patients with esophageal squamous cell carcinomas.

Introduction: Lymph node metastasis (LNM) and lymph node micrometastasis (LNMM) are prognostic factors in esophageal squamous cell carcinoma (ESCC) patients. The purpose of this research is to investigate whether mucin 1 expression detected by immunohistochemistry in lymph nodes correlates with LNM, LNMM and prognosis in ESCC patients. Material and methods: There were 92 ESCC patients enrolled in the research, and 1382 lymph nodes were obtained from these 92 patients. All lymph nodes were immunohistochemically analyzed using an anticytokeratin and mucin 1 antibody cocktail. Results: In the pN1-2 patients' group, 68 lymph nodes from 15 patients had tumor metastasis. All these 68 tumor metastatic lymph nodes were positive for mucin 1. Mucin 1 was detected in another 231 lymph nodes and among them, 3 (3/231 1.3%) lymph nodes from 2 (2/15 13.3%) patients were positive for mucin 1. In 77 pN0 patients, mucin 1 was detected in 1083 lymph nodes from the 77 patients; 17 (17/1083 1.6%) lymph nodes from 15 (15/77 19.5%) patients were positive for mucin 1. The 5-year survival rate was 39.1%, and it was significantly related to tumor invasion (pT, p < 0.05), lymph node metastasis (pN, p < 0.01), pTNM stage (p < 0.01) and mucin 1 expression (p < 0.01). Cox regression of multivariate analysis demonstrated that mucin 1 expression and pT were independent prognostic factors. Conclusions: Mucin 1 expression was related to LNM and LNMM and poor prognosis in ESCC patients. Immunohistochemistry for mucin 1 can be applied for the detection of LNM and LNMM.

Targeted next-generation sequencing identifies a novel nonsense mutation in ANK1 for hereditary spherocytosis: A case report.

BACKGROUND: Hereditary spherocytosis (HS) is characterized by anemia, jaundice, splenomegaly, and cholelithiasis, and is caused by abnormal genes encoding red blood cell membrane components. The most common mutations found in HS are in the ANK1 gene. CASE SUMMARY: A 4-mo-old girl was admitted to our hospital with pallor that had lasted for more than 2 mo. She presented with jaundice, anemia and splenomegaly. A heterozygous mutation of ANK1 (exon23: c.G2467T:p.E823X) was identified, and the mutation was determined to be autosomal dominant. This mutation is linked to the relatively serious anemia she had after birth; this anemia improved with age. CONCLUSION: The utilization of next-generation sequencing may assist with the accurate diagnosis of HS, especially in atypical cases.

Allogeneic Hematopoietic Stem Cell Transplantation for PEX1-Related Zellweger Spectrum Disorder: A Case Report and Literature Review.

Zellweger spectrum disorder (ZSD) is a heterogeneous group of autosomal recessive disorders characterized by a defect in peroxisome formation and attributable to mutations in the PEX gene family. Patients with ZSD have profound neurologic impairments, including seizures, severe retardation, and dysmorphic features, and poor prognosis. Currently, there is no specific, effective treatment. Here, we investigated the effects of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on PEX1-related ZSD. The suspected clinical proband was first diagnosed at the Department of Neurology of our hospital. The proband died soon after diagnosis, and his family was studied. We found that a brother had the same genetic alterations, and he was diagnosed with Infantile Refsum disease (IRD) as the mildest form of ZSD. We implemented treatment with allo-HSCT, at the request of the child's parents. After transplantation, we observed significant improvements in the clinical manifestations, very-long-chain fatty acids, and brain MRI. The patient has recovered well and not showed any abnormal clinical manifestations after 2 years of follow-up. We have achieved satisfactory short-term results in the treatment of ZSD-IRD with allo-HSCT. Long-term follow-up and observation will be performed to determine the long-term prognosis.

Is Creative Description Always Effective in Purchase Intention? The Construal Level Theory as a Moderating Effect.

Recent years has witnessed a rapid growth in online shopping. This paper draws from the construal level theory to examine the divergent effects of the creative text descriptions of products on consumers' purchase intention in an online context. It also investigates consumers' construal level and the moderating role of construal level in this relationship. An assumption has been made that the creative description embraces more rhetorical devices with analogies. In doing so, such texts are in need of consumers who are having a more abstract, top-down, flexible mindset, which makes it more persuasive to some consumers with high-level construal. Three experiments add evidence to this study. These results suggest that the creative text descriptions are generally more persuasive than the non-creative ones in an online context, and that the persuasiveness of the creative descriptions can be accentuated (vs. attenuated) especially for high- (vs. low-) level construal individuals. The findings hold various theoretical implications for the creative marketing messages and construal level theory. First, in the current research, broadening, and integrating relevant research were possible by exploring the creative language in an online context. Also, it demonstrates that construal level-that is, consumers' internal thoughts, rather than external factors-influences their preference for a creative description style, thus helping extend the applications of the construal level theory to the field of creative marketing communications and integrate the research discoveries in metaphor communication.

Sequential infection of Epstein-Barr virus and cryptococcal encephalitis after umbilical cord blood transplantation in a child with X-linked adrenoleukodystrophy.

Dual infection with two pathogens can be found in few cases of encephalitis. Cases of sequential infection with EBV and cryptococcal encephalitis in post-transplant patients are rare. We describe a 5-year-old boy with X-linked adrenoleukodystrophy who presented sequential infection with EBV and cryptococcal encephalitis after umbilical cord blood transplant. The patient showed fever, vomiting and emotional agitation with EBV DNA detected in CSF on day 100. The child underwent 3 doses of intravenous rituximab with a good response. However, the child presented with right facial paralysis, headache, and fever on day 130 after 2 weeks of clinical stability. Brain MRI demonstrated chronic granuloma formed with ring enhancement. FilmArray ME PCR confirmed the existence of Cryptococcus neoformans/gattii in the CSF. The child underwent sequential treatment with amphotericin liposome B and flucytosine. Maintenance treatment with fluconazole was administered for 1 year. Facial paralysis was on longer present on day 260. Cryptococcus neoformans/gattii was not detected on day 310. The biochemistry and cell count of the CSF were completely normal on day 520. Follow-up 2.5 years after presentation, brain MRI changes showed near complete resolution of the lesions. The child survived for 3 years to the last following-up. Invasive cryptococcal encephalitis is rare and life-threatening complication of transplantation. It is important to recognize dual infections, and perform treatment quickly to improve the prognosis of encephalitis after transplantation.

Kinesin superfamily protein 21B acts as an oncogene in non-small cell lung cancer.

BACKGROUND: Kinesin superfamily proteins (KIFs) serve as microtubule-dependent molecular motors, and are involved in the progression of many malignant tumors. In this study, we aimed to investigate the expression pattern and precise role of kinesin family member 21B (KIF21B) in non-small cell lung cancer (NSCLC). METHODS: KIF21B expression in 72 cases of NSCLC tissues was measured by immunohistochemical staining (IHC). We used shRNA-KIF21B interference to silence KIF21B in NSCLC H1299 and A549 cells and normal lung epithelial bronchus BEAS-2B cells. The biological roles of KIF21B in the growth and metastasis abilities of NSCLC cells were measured by Cell Counting Kit-8 (CCK8), colony formation and Hoechst 33342/PI, wound-healing, and Transwell assays, respectively. Expression of apoptosis-related proteins was determined using western blot. The effect of KIF21B on tumor growth in vivo was examined using nude mice model. RESULTS: KIF21B was up-regulated in NSCLC tissues, and correlated with pathological lymph node and pTNM stage, its high expression was predicted a poor prognosis of patients with NSCLC. Silencing of KIF21B mediated by lentivirus-delivered shRNA significantly inhibited the proliferation ability of H1299 and A549 cells. KIF21B knockdown increased apoptosis in H1299 and A549 cells, down-regulated the expression of Bcl-2 and up-regulated the expression of Bax and active Caspase 3. Moreover, KIF21B knockdown decreased the level of phosphorylated form of Akt (p-Akt) and Cyclin D1 expression in H1299 and A549 cells. In addition, silencing of KIF21B impeded the migration and invasion of H1299 and A549 cells. Further, silencing of KIF 21B dramatically inhibited xenograft growth in BALB/c nude mice. However, silencing of KIF21B did not affect the proliferation, migration and invasion of BEAS-2B cells. CONCLUSIONS: These results reveal that KIF21B is up-regulated in NSCLC and acts as an oncogene in the growth and metastasis of NSCLC, which may function as a potential therapeutic target and a prognostic biomarker for NSCLC.

Re-induction with modified CLAG regimen in relapsed or refractory acute myeloid leukemia in children bridging to allogeneic hematopoietic stem cell transplantation.

BACKGROUND: The prognosis for relapsed or refractory acute myeloid leukemia (RR-AML) in children is poor, and the preferred salvage chemotherapy is unclear. One regimen is cladribine, cytarabine, and granulocyte-colony stimulating factor (CLAG), but little is known about its efficacy and safety in children with RR-AML. METHODS: We enrolled RR-AML patients aged 0-18 years who received modified CLAG regimen for re-induction between July 1, 2015 and April 1, 2018, or conventional induction between August 1, 2011 and April 1, 2018. Patients were followed up to March 31, 2019. Patients underwent allogeneic stem cell transplantation (allo-SCT) or chemotherapy after the induction of complete remission (CR). The CR rate, survival, and side effects were analyzed. RESULTS: The CR rate for induction was 66.7% after one cycle and 75.0% after two cycles of the CLAG regimen in 12 children. The nine children who received conventional chemotherapy had a CR rate of 22.2% after one cycle and 33.3% after two cycles (P = 0.087 vs. CLAG). The 3-year event-free survival (EFS) of the CLAG group and the conventional treatment group were 44.4 ± 15.7% and 22.2 ± 13.8% (P = 0.112). The 3-year overall survival of the two groups were 59.5 ± 16.2% and 22.2% ± 13.8% (P = 0.057). The 3-year EFS for allo-SCT and chemotherapy after CLAG regimen was 66.7 ± 19.2% and 25.0 ± 21.7% (P = 0.015). A single case of chemotherapy-related death was recorded. CONCLUSION: Our data suggest a promising CR rate using CLAG salvage treatment in childhood RR-AML. Allo-SCT after CR may improve the long-term outcome in these patients.

The KLF6 splice variant KLF6-SV1 promotes proliferation and invasion of non-small cell lung cancer by up-regultating PI3K-AKT signaling pathway.

Non-small cell lung cancer (NSCLC) is an aggressive type of lung malignancy. Most of the patients have poor prognosis. Increasing evidence has revealed an association between KLF6-SV1, known as an oncogenic splice variant of KLF6, and metastatic potential or poor prognosis in many cancers. We previously demonstrated the increased KLF6-SV1 expression in NSCLC samples. There was a significant association between increased expression of KLF6-SV1 with the pN and pTNM stages and poor survival in NSCLC patients. In the present study, we aimed to further investigate the functional role of KLF6-SV1 in the progression of NSCLC. SK-MES-1 cells were infected with Lenti-virus containing KLF6-SV1 to up-regulate its expression, and the small interfering RNA (siRNA) was designed to knock down KLF6-SV1 transcript level in A549 cells. CCK8, colony formation, wound-healing, and transwell assays were performed to examine cell proliferation, migration, and invasion respectively. Western blot assay was used to detect the expression or phosphorylation of related proteins. We found that in vitro silencing of KLF6-SV1 by siRNA inhibited A549 cell proliferation, migration, and invasion through changes in E-cadherin, N-cadherin, Vimentin, Snail1 and Snail2 expression. Furthermore, KLF6-SV1 isoform knockdown triggered caspase-dependent apoptosis of A549 cells through downregulation of the phosphatidylinositol 3-OH kinase (PI3K)/Akt signaling pathway and apoptosis-related protein expression. Overexpression of KLF6-SV1 transcript induced significant increase in proliferation, migration, invasion and changes in expression of related proteins. Our study support KLF6-SV1 might be an important player in modulating the growth, migration, invasion, and survival of NSCLC cells, and that silencing KLF6-SV1 siRNA has the potential to be a powerful gene therapy strategy for NSCLC.

Hypoxia-inducible factor 1α in combination with vascular endothelial growth factor could predict the prognosis of postoperative patients with oesophageal squamous cell cancer.

The purpose of the study is to investigate the clinicopathological and prognostic features of dual hypoxia-inducible factor 1a (HIF-1a) and vascular endothelial growth factor (VEGF) expression in oesophageal squamous cell carcinoma (OSCC) patients. A total of 73 patients were enrolled in this study. The positive expression of HIF-1a was identified in 69.9% of the cases. Hypoxia-inducible factor 1a expression was correlative with pT (p = 0.008) and pTNM stage (p = 0.002). The positive expression of VEGF was identified in 63.0% of the cases. Vascular endothelial growth factor expression was correlative with pT (p = 0.005), pN (p = 0.045), and pTNM stage (p < 0.05). HIF-1a and VEGF expressions had a significantly positive correlation (p = 0.010). Dual positive expression of HIF-1a and VEGF was identified in 50.7% (37/73) of the cases, and it was significantly correlative with pT (p = 0.025), pN (p = 0.008), and pTNM stage (p = 0.014). The OSCC patients' 5-year survival rate was correlative with pT (p < 0.05), pN (p < 0.01), pTNM stage (p < 0.01), VEGF expression (p < 0.01), and dual expressions of HIF-1a and VEGF (p < 0.01). Cox regression analysis showed that pN and dual HIF-1a and VEGF expression were independent prognostic factors for the 5-year survival rate of the patients. In conclusion, HIF-1a combined with VEGF could enable us to more accurately predict the prognosis of OSCC patients.

Microwave ablation combined with chemotherapy improved progression free survival of IV stage lung adenocarcinoma patients compared with chemotherapy alone.

BACKGROUND: Microwave ablation (MWA) has recently become an established treatment option for topical therapy of lung cancer patients. In this study, we evaluated whether MWA combined with chemotherapy could improve progression-free survival (PFS) of patients with stage IV lung adenocarcinoma compared with chemotherapy alone. METHODS: A total of 49 patients were enrolled into the study; 21 patients accepted MWA therapy combined with chemotherapy, 28 patients accepted only chemotherapy. Enumeration data were analyzed using χ2 test or Fisher's exact probability test and univariate analysis was analyzed using Kaplan-Meier survival curves. Multivariate analysis was carried out with the Cox proportional hazard model. RESULTS: The treatment regimen was not correlated with clinical features of the patients, which included gender, age, smoking history, tumor site, tumor size and Eastern Cooperative Oncology Group (ECOG). The patients' 3-year overall survival (OS) was 12.5%, and median survival time was 19.3 months. The median PFS was 6.1 months and the 1-year PFS was 0.0%. The PFS was significantly associated with tumor size (P < 0.05), ECOG (P < 0.01) and treatment regimen (P < 0.01). The median time to local progression (TTLP) was 8.4 months and the 3-year TTLP was 2.0%. The TTLP was significantly associated with tumor size (P < 0.05) and treatment regimen (P < 0.01). Cox multivariate regression demonstrated that MWA combined with chemotherapy was the independent factor for both the PFS and TTLP. CONCLUSION: MWA, as a topical treatment method, when combined with chemotherapy improved the PFS and TTLP of patients with stage IV lung adenocarcinoma.

Preventive Effects of Different Drugs on Asymptomatic Lower Extremities Deep Venous Thrombosis After Artificial Joint Replacement: A Mixed Treatment Comparison.

This network meta-analysis aims to compare the preventive effects of 8 drugs (edoxaban, dabigatran, apixaban, rivaroxaban, warfarin, bemiparin, ximelagatran, and enoxaparin) on asymptomatic deep venous thrombosis (DVT) of lower extremities after artificial joint replacement. PubMed, Cochrane Library, and Embase were searched from their inception through October 2015 for randomized controlled trials comparing 8 drugs for the prevention of asymptomatic DVT of lower extremities after artificial joint replacement. Network meta-analysis combined the direct and indirect evidence to evaluate odd ratios (ORs) and surface under the cumulative ranking curves values. A total of 15 randomized controlled trials satisfying the inclusion criteria were enrolled. Edoxaban, apixaban, and rivaroxaban had poorer preventive effects on asymptomatic DVT of lower extremities after undergoing artificial joint replacement when compared with warfarin [OR = 0.16, 95% confidence interval (CI), 0.04-0.60; OR = 0.22, 95% CI, 0.07-0.64; OR = 0.16, 95% CI, 0.05-0.49, respectively]. When compared with enoxaparin, the preventive effects of edoxaban and rivaroxaban were poorer (OR = 0.37, 95% CI, 0.15-0.85; OR = 0.37, 95% CI, 0.21-0.59, respectively). The preventive effects of edoxaban and rivaroxaban were poorer than dabigatran (OR = 0.38, 95% CI, 0.14-0.99; OR = 0.38, 95% CI, 0.18-0.73, respectively). The surface under the cumulative ranking curves values showed that warfarin had better preventive effects on asymptomatic DVT of lower extremities after undergoing artificial joint replacement. Among the 8 drugs (edoxaban, dabigatran, apixaban, rivaroxaban, warfarin, bemiparin, ximelagatran, and enoxaparin), warfarin had better preventive effects on asymptomatic DVT of lower extremities after undergoing artificial joint replacement.

The mechanism of epithelial-mesenchymal transition induced by TGF-ß1 in neuroblastoma cells.

Neuroblastoma is the second most common extracranial malignant solid tumor that occurs in childhood, and metastasis is one of the major causes of death in neuroblastoma patients. The epithelial-mesenchymal transition (EMT) is an important mechanism for both the initiation of tumor invasion and subsequent metastasis. Therefore, this study investigated the mechanism by which transforming growth factor (TGF)-ß1 induces EMT in human neuroblastoma cells. Using quantitative RT-qPCR and western blot analyses, we found that the mRNA and protein expression levels of E-cadherin were significantly decreased, whereas that of α-SMA was significantly increased after neuroblastoma cells were treated with different concentrations of TGF-ß1. A scratch test and Transwell migration assay revealed that cell migration significantly and directly correlated with the concentration of TGF-ß1 indicating that TGF-ß1 induced EMT in neuroblastoma cells and led to their migration. Inhibiting Smad2/3 expression did not affect the expression of the key molecules involved in EMT. Further investigation found that the expression of the glioblastoma transcription factor (Gli) significantly increased in TGF-ß1-stimulated neuroblastoma cells undergoing EMT, accordingly, interfering with Gli1/2 expression inhibited TGF-ß1-induced EMT in neuroblastoma cells. GANT61, which is a targeted inhibitor of Gli1 and Gli2, decreased cell viability and promoted cell apoptosis. Thus, TGF-ß1 induced EMT in neuroblastoma cells to increase their migration. Specifically, EMT induced by TGF-ß1 in neuroblastoma cells did not depend on the Smad signaling pathway, and the transcription factor Gli participated in TGF-ß1-induced EMT independent of Smad signaling.

Plumbagin Mediates Cardioprotection Against Myocardial Ischemia/Reperfusion Injury Through Nrf-2 Signaling.

BACKGROUND Plumbagin is a potent antioxidant with anti-inflammatory and anti-carcinogenic action. Myocardial ischemia/reperfusion injury results in organ damage through oxidative stress and inflammatory mechanisms. In this study, we analyzed the potential role of plumbagin against myocardial I/R injury in Wistar rats. MATERIAL AND METHODS Oxidative stress was measured through ROS, lipid peroxide content, and antioxidant enzyme activities. The expression of redox signaling and inflammatory proteins was analyzed through Western blotting. Inflammatory cytokine expressions were determined through ELISA. RESULTS Oxidative stress status was reduced by plumbagin by decreasing ROS and lipid peroxide levels in rats with myocardial I/R (MI/R) injury. Plumbagin regulated redox imbalance induced by I/R injury by modulating the transcription factors NF-κB and Nrf-2. Further, downstream targets of NF-κB (COX-2, iNOS) and Nrf-2 (HO-1, NQO1 and GST) expression were significantly downregulated by plumbagin treatment. Pro-inflammatory cytokine expressions were significantly abrogated by plumbagin treatment. CONCLUSIONS This study shows the protective role of plumbagin against myocardial I/R injury by regulating antioxidant and inflammatory mechanisms.

Real-time polymerase chain reaction for diagnosing infectious mononucleosis in pediatric patients: A systematic review and meta-analysis.

In this meta-analysis, we evaluated the diagnostic role of Epstein-Barr virus deoxyribonucleic acid detection and quantitation in the serum of pediatric and young adult patients with infectious mononucleosis. The primary outcome of this meta-analysis was the sensitivity and specificity of Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA) detection and quantitation using polymerase chain reaction (PCR). A systematic review and meta-analysis was performed by searching for articles that were published through September 24, 2014 in the following databases: Medline, Cochrane, EMBASE, and Google Scholar. The following keywords were used for the search: "Epstein-Barr virus," "infectious mononucleosis," "children/young adults/infant/pediatric," and "polymerase chain reaction or PCR." Three were included in this analysis. We found that for detection by PCR, the pooled sensitivity for detecting EBV DNA was 77% (95%CI, 66-86%) and the pooled specificity for was 98% (95%CI, 93-100%). Our findings indicate that this PCR-based assay has high specificity and good sensitivity for detecting of EBV DNA, indicating it may useful for identifying patients with infectious mononucleosis. This assay may also be helpful to identify young athletic patients or highly physically active pediatric patients who are at risk for a splenic rupture due to acute infectious mononucleosis.

A single center clinical analysis of children with neuroblastoma.

In the present study, the cases of 59 children diagnosed with neuroblastoma (NB) were retrospectively analyzed to assess the association between the short-term efficacy of treatment and prognostic factors. In total, 59 patients with NB that were diagnosed between July 1, 2008 and June 30, 2013 at Shanghai Children's Hospital were enrolled in the present study. The follow-up was performed until December 31, 2013, and the data revealed that 43 patients (72.9%) achieved complete remission (CR) or partial remission (PR). The 3-year overall survival (OS) rate of patients with stage I, II, III, IV and IVs disease was 100, 100, 65.6, 34.8 and 85.7%, respectively (P=0.02). The 3-year OS and event-free survival rates were evidently increased in patients with favorable histology compared with the rates in the patients with unfavorable histology (P=0.046 and 0.030, respectively). Univariate statistical analysis revealed that the factors significantly associated with prognosis were patient age, tumor stage and risk group (P=0.004, 0.02 and 0.001, respectively). The present study identified that tumor stage, risk group and patient age are important prognostic factors for NB. An age of 18 months was also hypothesized to be the cut-off for the prognosis of patients.