AIM:Xaf1-Saos inducible cell lines,which contain "gene switch" system were used to detect the effect of Xaf1 on tumor necrosis factor receptor(TNFR) signal pathway and to investigate the mechanism of cooperation between Xaf1 and TNF-? in inducing cell apoptosis.METHODS:Xaf1 on TNFR1 expression was measured by RT-PCR and Western blotting.The effect of NF-?B on Xaf1 induced apoptosis was detected by DNA content flow cytometry after co-transfection.DNA binding activity of NF-?B was identified by gel mobility shift assay and transcription activity of NF-?B was analyzed by luciferase assay and RT-PCR.SAPK/JNK activity was checked by SAPK/JNK assay.RESULTS:Xaf1 did not modulate TNFR1 at protein and mRNA levels.Increased NF-?B activity in cells inhibited Xaf1 induced apoptosis.Expression of Xaf1 impaired modestly TNF-? induced NF-?B DNA binding activation and transcription activation,also modestly reduced SAPK/JNK activity.CONCLUSION:Xaf1 inhibits TNFR signal pathway,partly contributing to cooperation with TNF-? to induce apoptosis.

Objective To investigate the effects of dapagliflozin on inflammatory cytokines,blood glucose control and cardiac function in elderly with preserved ejection fraction heart failure(HFpEF)combined with type 2 diabetes.Methods A total of 80 elderly HFpEF patients with type 2 diabetes mellitus were randomly divided into control group(40 cases)and study group(40 cases).The control group received hypoglycemic and anti-heart failure standard therapy,and the study group received hypoglycemic and anti-heart failure standard therapy and dapagliflozin therapy.Both groups were treated for 6 months.The levels of inflammatory factors,blood glucose control,myocardial markers,exercise endurance[6 min walking distance(6MWD)],cardiac ultrasound related indexes and adverse drug reactions were compared between the two groups.Results After 6 months of treat-ment,serum interleukin-6(IL-6),hypersensitive C-reactive protein(hs-CRP)and tumor necrosis fac-tor(TNF)-α in the study group were significantly lower than those in the control group(P＜0.05);the glycated hemoglobin(HbA1c),fasting blood glucose(FPG),amino terminal B-type brain natriuretic peptide precursor(NT-proBNP)and hypersensitive troponin(hs-TNT)of the study group were significantly lower than those of the control group(P＜0.05);the 6MWD and left ven-tricular ejection fraction(LVEF)of the study group were higher than those of the control group,and the left ventricular end-diastolic diameter(LVEDD),right atrial and right ventricular diameter,left atrial and left ventricular diameter,right ventricular wall thickness and pulmonary artery pressure of the study group were significantly lower than those of the control group(P＜0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion The use of dapagliflozin in the treatment of elderly HFpE patients complicated with type 2diabetes can effectively control their blood sugar level,reduce inflammation,improve exercise endurance,and improve patients'heart function without increasing adverse drug reactions.

Objective To investigate the effects of dapagliflozin on inflammatory cytokines,blood glucose control and cardiac function in elderly with preserved ejection fraction heart failure(HFpEF)combined with type 2 diabetes.Methods A total of 80 elderly HFpEF patients with type 2 diabetes mellitus were randomly divided into control group(40 cases)and study group(40 cases).The control group received hypoglycemic and anti-heart failure standard therapy,and the study group received hypoglycemic and anti-heart failure standard therapy and dapagliflozin therapy.Both groups were treated for 6 months.The levels of inflammatory factors,blood glucose control,myocardial markers,exercise endurance[6 min walking distance(6MWD)],cardiac ultrasound related indexes and adverse drug reactions were compared between the two groups.Results After 6 months of treat-ment,serum interleukin-6(IL-6),hypersensitive C-reactive protein(hs-CRP)and tumor necrosis fac-tor(TNF)-α in the study group were significantly lower than those in the control group(P＜0.05);the glycated hemoglobin(HbA1c),fasting blood glucose(FPG),amino terminal B-type brain natriuretic peptide precursor(NT-proBNP)and hypersensitive troponin(hs-TNT)of the study group were significantly lower than those of the control group(P＜0.05);the 6MWD and left ven-tricular ejection fraction(LVEF)of the study group were higher than those of the control group,and the left ventricular end-diastolic diameter(LVEDD),right atrial and right ventricular diameter,left atrial and left ventricular diameter,right ventricular wall thickness and pulmonary artery pressure of the study group were significantly lower than those of the control group(P＜0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion The use of dapagliflozin in the treatment of elderly HFpE patients complicated with type 2diabetes can effectively control their blood sugar level,reduce inflammation,improve exercise endurance,and improve patients'heart function without increasing adverse drug reactions.

Objective:To evaluate the efficacy and safety of eltrombopag for children with thrombocytopenia after hematopoietic stem cell transplantation (HSCT).Methods:Clinical data of 24 patients with thrombocytopenia after HSCT,who were treated with eltrombopag in the Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University from August 1, 2018 to April 1, 2019 were analyzed retrospectively. The response rate and adverse reactions of eltrombopag were evaluated. Patients were divided into groups by source of hematopoietic stem cells (umbilical cord blood group and peripheral stem cell group) and type of disease (malignant and non-malignant disease group) and the clinical outcomes between groups were compared. Rank Sum test was used for comparisons between groups.Results:Among 24 cases, 15 were males and 9 females, the age of starting eltrombopag was 7.7 (2.6-13.7) years, the time of eltrombopag treatment after HSCT was 27.5 (8.0-125.0) days, the time from treatment to complete response (CR) was 23.5 (6.0-83.0) days, with the treatment course 36.5 (8.0-90.0) days. The total dose of eltrombopag was 1 400(200-5 900) mg. Complete response rate was 92% (22/24),without eltrombopag related adverse reactions. Comparing with peripheral stem cell group ( n=8), the course and total dose of eltrombopag in umbilical cord blood group ( n=16) were significantly reduced(24.5 (8.0-81.0) vs. 65.5 (35.0-90.0) d, Z=-3.004, P=0.002; 900.0 (200.0-3 850.0) vs. 2 862.5 (1 175.0-5 900.0) mg, Z=-2.604, P=0.007), but no significant differences were found in the time from treatment to complete response, platelet count after 2 weeks of eltrombopag withdrawal or platelet count at the end point of follow-up (all P>0.05). Comparing malignant patients ( n=12) and non-malignant patients ( n=12), no significant differences were found in the time from treatment to complete response, course, total dose, platelet count after 2 weeks of eltrombopag withdrawal, and platelet count at the end point of follow-up in non-malignant patients (all P>0.05). Conclusion:Eltrombopag is safe and maybe effective for thrombocytopenia after HSCT, especially for umbilical cord blood transplantation.