Differentiation of the acute myeloid leukemia (AML) cell line HL-60 can be induced by all trans-retinoic acid (ATRA); however, the mechanism regulating this process has not been fully characterized.

Background: Treatment failure for esophageal carcinoma is frequently due to lymph node metastasis and invasion to neighboring organs. The aim of the present study was to investigate invasion- and metastasis-related genes in esophageal carcinoma cells in vitro and in vivo. Methods: A metastasis model using a Matrigel invasion clonal selection approach was employed to establish a highly invasive subline EC9706-P4 from the esophageal carcinoma cell (ESCC) line EC9706. The differentially expressed genes of the subline and the parental cells determined by gene microarrays were further analyzed by RT-PCR and Western blotting. Results: We identified sphingosine kinase 1 (SPHK1) as an invasion and metastasis-related gene of esophageal cancer. SPHK1 was overexpressed in the EC9706-P4 subline with high invasive capacity. Among six ESCC lines tested, KYSE2 and KYSE30 cells showed the highest SPHK1 mRNA and protein expressions as well as the most invasive phenotype. By Western blotting, in 7/12 cases (58%), SPHK1 expression was higher in esophageal carcinomas than in the companion normal tissue. In 23/30 cases (76%), SPHK1 protein expression was upregulated in the tumors compared to matched normal tissue by immunohistochemistry (IHC). Esophageal carcinoma tissue microarray analysis indicated that SPHK1 expression correlated with the depth of tumor invasion (P < 0.0001) and lymph node metastasis (P = 0.016). By Kaplan-Meier analysis, strong SPHK1 expression was significantly associated with clinical failure (P < 0.01), suggesting the involvement of SPHK1 in aggressiveness of human esophageal carcinoma. SPHK1 overexpression significantly increased the invasiveness of EC9706 cells in vitro and also increased EC9706 cell growth and spontaneous metastasis in vivo, promoting significant increases in tumor growth, tumor burden and spontaneous lung metastasis in nude mice. SPHK1 expression significantly correlated with the expression of many EGFR pathway genes associated with invasion of cancer cells. SPHK1 protein expression also significantly correlated with the phosphorylation of EGFR. Conclusion: In summary, our data implicate SPHK1 in the metastasis of esophageal cancer. Our study also identified downstream mediators of SPHK1 in esophageal cancer cells that may mediate enhanced malignant behavior, and several of these mediators may be useful as therapeutic targets.

Background: Nosocomial infections (NIs) are an important cause of mortality, and increasing evidence reveals that the prevalence of NIs can be reduced through effective prevention and control measures. The aim of this study was to investigate the impact of the prevention and control measures for the COVID-19 pandemic on NIs. Methods: A retrospective study was conducted to analyze the prevalence of NIs before and after COVID-19 pandemic for 6 months in the Children’s Hospital of Soochow University. Results: A total of 39,914 patients in 2019 and 34,645 patients in 2020 were admitted to the hospital during the study. There were 1.39% (481/34645) of patients with NIs in 2020, which was significantly lower than the 2.56% (1021/39914) of patients in 2019. The rate of critical and fatal cases was also decreased. In addition, the rate of appropriate handwashing, the number of protective gloves and aprons used per person and the number of healthcare staff per patients were significantly increased. Except for the ICU, the prevalence of nosocomial infection in most departments decreased from 2019 to 2020. Regarding the source of infections, a significant reduction was mainly observed in respiratory (0.99% vs 0.42%, p = 0.000) and digestive tract (0.63% vs 0.14%, p = 0.000). The microorganism analysis of respiratory infections indicated an obvious decline in acinetobacters and fungi. The most significant decline of pathogens in gastrointestinal infections was observed for rotavirus. The comparison of catheter-related nosocomial infections between 2019 and 2020 did not show significant differences. Conclusions: The prevention and control measures for the COVID-19 pandemic have reduced the nosocomial infection in almost all departments, except the ICU, mainly regarding respiratory, gastrointestinal, and oral infections, while catheter-related infections did not show any differences.

Background: Treatment failure for breast cancer is frequently due to lymph node metastasis and invasion to neighboring organs. The aim of the present study was to investigate invasion- and metastasis-related genes in breast cancer cells in vitro and in vivo. Identification of new targets will facilitate the developmental pace of new techniques in screening and early diagnosis. Improved abilities to predict progression and metastasis, therapeutic response and toxicity will help to increase survival of breast cancer patients. Methods: Differential protein expression in two breast cancer cell lines, one with high and the other with low metastatic potential, was analyzed using two-dimensional liquid phase chromatographic fractionation (Proteome Lab PF 2D system) followed by matrix-assisted laser desorption/time-of-flight mass spectrometry (MALDI-TOF/MS). Results: Up regulation of α-subunit of ATP synthase was identified in high metastatic cells compared with low metastatic cells. Immunohistochemical analysis of 168 human breast cancer specimens on tissue microarrays revealed a high frequency of ATP synthase α-subunit expression in breast cancer (94.6%) compared to normal (21.2%) and atypical hyperplasia (23%) breast tissues. Levels of ATP synthase expression levels strongly correlated with large tumor size, poor tumor differentiation and advanced tumor stages (P < 0.05). ATP synthase α-subunit over-expression was detected on the surface of a highly invasive breast cancer cell line. An antibody against the ATP synthase α-subunit inhibited proliferation, migration and invasion in these breast cancer cells but not that of a non-tumor derived breast cell line. Conclusions: Over-expression of ATP synthase α-subunit may be involved in the progression and metastasis of breast cancer, perhaps representing a potential biomarker for diagnosis, prognosis and a therapeutic target for breast cancer. This finding of this study will help us to better understand the molecular mechanism of tumor metastasis and to improve the screening, diagnosis, as well as prognosis and/or prediction of responses to therapy for breast cancer.

Background: Sodium bicarbonate (SB) infusion is commonly used to correct metabolic acidosis, but its clinical efficacy remains controversial. This study aims to investigate whether acid–base balance parameters should be a consideration for administering SB treatment. Methods: Children with metabolic acidosis (pH < 7.35 and bicarbonate < 22 mmol/L) who were treated with or without 50 mg/ml SB injection were grouped and extracted from a retrospective cohort database of the Pediatric Intensive Care Unit. The interaction between acid–base balance parameters and SB treatment on mortality was analyzed through mortality curves and cross-effect models. Logistic regression was conducted to estimate the risk of death following SB treatment in the overall children as well as in subgroups, and potential confounding factors were adjusted for. After employing propensity score matching to account for confounding factors, further analysis was performed to evaluate the effectiveness of SB treatment within each chloride subgroup. Results: A total of 5865 children with metabolic acidosis were enrolled, of which 2462 (42.0%) received SB treatment. In the overall population, it was found that SB treatment did not reduce hospital mortality or 28-day mortality. Interactions between acid–base balance parameters (chloride and anion gap) and SB treatment on mortality were observed. Subgroup analysis clarified that when chloride levels were below 107 mmol/L, children treated with SB had higher in-hospital mortality (29.8% vs 14.9%) and 28-day mortality (26.5% vs 13.4%), with adjusted ORs of 2.065 (95% CI, 1.435–2.97) and 1.947 (95% CI, 1.332–2.846), respectively. In contrast, when chloride levels were greater than or equal to 113 mmol/L, children treated with SB had a shorter stay in the PICU (median: 1.1 days vs 5.1 days, adjusted p = 0.004) and lower in-hospital mortality (4.3% vs 10.3%) and 28-day mortality (4.0% vs 8.4%), with adjusted ORs of 0.515 (95% CI, 0.337–0.788) and 0.614 (95% CI, 0.391–0.965), respectively. After controlling for confounding factors through matching, the impact of SB treatment on the risk of death in each chloride subgroup was consistent with the aforementioned results. However, treatment with SB did not significantly increase the risk of death in newborns or children with moderate to severe metabolic acidosis when chloride levels were below 107 mmol/L (p > 0.05). Conclusions: The use of sodium bicarbonate for treating metabolic acidosis has been found to increase mortality in children with low chloride levels but decrease mortality in those with high chloride levels in this study. Further prospective multi-center clinical studies and basic research are needed to validate these findings.

Chimeric antigen receptor T cell (CAR-T) therapy is effective in treating relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). However, the side effects of immune effector cell-associated neurotoxicity syndrome (ICANS) remain a problem. The current frontline therapies for ICANS include steroids and supportive care. For the steroid-refractory and severe ICANS, several studies have reported excellent efficacy of intrathecal (IT) corticosteroids alone or in combination with chemotherapy. However, whether patients can benefit from IT dexamethasone (dex) before grade 3 or refractory ICANS remains unclear. In this study, the patients with ICANS (≥1) after CAR-T cell therapy were assigned to the IT group and non-IT group. Clinical information, laboratory parameters, and serum cytokine levels were analyzed. A significant and rapid reduction in inflammatory cytokines and biomarkers was observed after 24 h of IT dex treatment. With IT dex, 83.3 % (15/18) of patients recovered from neurotoxicity. Moreover, this option significantly shortens the recovery time of ICANS without affecting the efficacy of CAR-T cell therapy. Earlier initiation of IT dex is the optimal management of ICANS resulting from CAR-T cell therapy, but larger sample studies are needed to determine its efficacy in these settings.