Coordination of LMO7 with FAK Signaling Sustains Epithelial Integrity in Renal Epithelia Exposed to Osmotic Pressure.

The kidney epithelial barrier has multifaceted functions in body fluids, electrolyte homeostasis, and urine production. The renal epithelial barrier (REB) frequently faces and challenges osmotic dynamics, which gives rise to osmotic pressure (a physical force). Osmotic pressure overloading can crack epithelial integrity and damage the REB. The endurance of REB to osmotic pressure forces remains obscure. LMO7 (LIM domain only 7) is a protein associated with the cell-cell junctional complex and cortical F-actin. Its upregulation was observed in cells cultured under hypertonic conditions. LMO7 is predominantly distributed in renal tubule epithelial cells. Hypertonic stimulation leads to LMO7 and F-actin assembly in the cortical stress fibers of renal epithelial cells. Hypertonic-isotonic alternation, as a pressure force pushing the plasma membrane inward/outward, was set as osmotic disturbance and was applied to test FAK signaling and LMO7 functioning in maintaining junctional integrity. LMO7 depletion in cells resulted in junctional integrity loss in the epithelial sheet-cultured hypertonic medium or hypertonic-isotonic alternation. Conversely, FAK inhibition by PF-573228 led to failure in robust cortical F-actin assembly and LMO7 association with cortical F-actin in epithelial cells responding to hypertonic stress. Epithelial integrity against osmotic stress and LMO7 and FAK signaling are involved in assembling robust cortical F-actin and maintaining junctional integrity. LMO7 elaborately manages FAK activation in renal epithelial cells, which was demonstrated excessive FAK activation present in LMO7 depleted NRK-52E cells and epithelial integrity loss when cells with LMO7 depletion were exposed to a hypertonic environment. Our data suggests that LMO7 regulates FAK activation and is responsible for maintaining REB under osmotic disturbance.

[Prognostic Value of Average Daily Platelet Increase in Childhood B-cell Acute Lymphoblastic Leukemia Patients].

OBJECTIVE: To evaluate the prognosis value of average daily platelet amount increase in children with B-cell acute lymphoblastic leukemia(B-ALL) treated by CCCG-ALL-2015 regimen. METHODS: 106 children with primary B-ALL were retrospective analyzed, standardized MRD test protocol was used to detect the MRD level (19 d and 46 d) after chemotherapy. The platelet count was measured by Sysmex XE-2100. Kaplan-Meier survival curve statistics was used to analyze the event free survival(EFS) rate of the children. RESULTS: The trend of negative correlation existed between PPC and TPR (rs=-0.519, P=0.021). The 3-year EFS rate of the patients in Ap>5.4×109/L group was 95.7%, which was significantly higher than those in Ap≤5.4×109/L group(79.5%) (χ2=5.236, P=0.035); multivariate analysis showed that Ap≤5.4×109/L was the independent prognostic factor affecting survival of the patients (RR=3.978; 95%CI: 1.336-11.523, P=0.041). With both MRD and Ap≤5.4×109/L as candidate variables, Ap≤5.4×109/L lost its independent prognostic value (RR=1.225; 95%CI: 0.892-13.696, P=0.089), the correlation between d 19/d 46 MRD levels and Ap>5.4×109/L (χ2=4.318, P=0.038) could explain the phenomenon. CONCLUSION: Ap can reflect the effect of B-ALL chemotherapy and can be used to monitor the curative effect and prognosis of B-ALL children.

[Prognostic Value of Average Daily Platelet Increase in Childhood B-cell Acute Lymphoblastic Leukemia Patients].

OBJECTIVE: To evaluate the prognosis value of average daily platelet amount increase in children with B-cell acute lymphoblastic leukemia(B-ALL) treated by CCCG-ALL-2015 regimen. METHODS: 106 children with primary B-ALL were retrospective analyzed, standardized MRD test protocol was used to detect the MRD level (19 d and 46 d) after chemotherapy. The platelet count was measured by Sysmex XE-2100. Kaplan-Meier survival curve statistics was used to analyze the event free survival(EFS) rate of the children. RESULTS: The trend of negative correlation existed between PPC and TPR (rs=-0.519, P=0.021). The 3-year EFS rate of the patients in Ap>5.4×109/L group was 95.7%, which was significantly higher than those in Ap≤5.4×109/L group(79.5%) (χ2=5.236, P=0.035); multivariate analysis showed that Ap≤5.4×109/L was the independent prognostic factor affecting survival of the patients (RR=3.978; 95%CI: 1.336-11.523, P=0.041). With both MRD and Ap≤5.4×109/L as candidate variables, Ap≤5.4×109/L lost its independent prognostic value (RR=1.225; 95%CI: 0.892-13.696, P=0.089), the correlation between d 19/d 46 MRD levels and Ap>5.4×109/L (χ2=4.318, P=0.038) could explain the phenomenon. CONCLUSION: Ap can reflect the effect of B-ALL chemotherapy and can be used to monitor the curative effect and prognosis of B-ALL children.

[Relationship between Immune Differentiation Antigen and Minimal Residual Disease in Childhood B-ALL].

OBJECTIVE: To determine whether immune differentiation antigen is related with clinical features and minimal residual disease (MRD) in childhood B-cell precursor acute lymphoblastic leukemia (B-ALL), who were treated with CCCG-ALL-2015 protocol. METHODS: A retrospective analysis was conducted in 132 B-ALL children, Multiparametric flow cytometry was used to analyze the immunophenotypes. The children were divided into 2 groups by MRD>0.1% on d 19 and / or d 46 after chemotherapy. The Wilcoxon rank-sum test and χ2 test were used for the comparison between groups, and P<0.05 was considered statistically significant. RESULTS: CD19 (100%), CD22 (99.3%) and cCD79a (97.9%) were specific markers for patients with B-ALL, the CD13 and CD33 were mainly cross myeloid antigen. The significant differences were found between CD45- and CD45+ in WBC counts when being firstly diagnosed (Z=6.845, P<0.01), risk stratification (χ2=8.260, P<0.05) and prednisone poor responder (χ2=18.420, P<0.01). Significant differences were found between CD10- and CD10+ in age (Z=6.253, P<0.05), risk stratification (χ2=6.699, P<0.05) and MRD (χ2=4.951, P<0.05). CONCLUSION: In CCCG-ALL-2015 protocol, the CD10 relates with the early MRD, suggesting a better prognosis, and reducing the adverse effects of CD20 and cross myeloid antigen on prognosis.

Prospective, sequential, longitudinal study of coagulation changes during pregnancy in Chinese women.

OBJECTIVE: To investigate changes and establish reference values for coagulation variables during normal pregnancy and after delivery in Chinese women. METHODS: A prospective, sequential, longitudinal study with strict inclusion and exclusion criteria was performed with 232 Chinese women. RESULTS: Prothrombin time, international normalized ratio, activated partial thromboplastin time, and activated partial thromboplastin time ratio were shorter, and platelet count decreased gradually during pregnancy, with no change in mean platelet volume; conversely, plasma concentration of both fibrinogen and fibrin/fibrinogen degradation product increased. All these variables were normalized during the postpartum. Reference values by gestational week were established for platelet count, fibrinogen concentration, and fibrin/fibrinogen degradation product concentration. CONCLUSIONS: These reference values may be used in the health assessment of pregnant women with a similar socioeconomic and ethnic background.