Genotype-degree of hemolysis correlation in hereditary spherocytosis.

BACKGROUND: Hereditary spherocytosis (HS) is a common inherited hemolytic anemia, caused by mutations in five genes that encode erythrocyte membrane skeleton proteins. The red blood cell (RBC) lifespan could directly reflect the degree of hemolysis. In the present cohort of 23 patients with HS, we performed next-generation sequencing (NGS) and Levitt's carbon monoxide (CO) breath test to investigate the potential genotype-degree of hemolysis correlation. RESULTS: In the present cohort, we identified 8 ANK1,9 SPTB,5 SLC4A1 and 1 SPTA1 mutations in 23 patients with HS, and the median RBC lifespan was 14(8-48) days. The median RBC lifespan of patients with ANK1, SPTB and SLC4A1 mutations was 13 (8-23), 13 (8-48) and 14 (12-39) days, respectively, with no statistically significant difference (P = 0.618). The median RBC lifespan of patients with missense, splice and nonsense/insertion/deletion mutations was 16.5 (8-48), 14 (11-40) and 13 (8-20) days, respectively, with no significant difference (P = 0.514). Similarly, we found no significant difference in the RBC lifespan of patients with mutations located in the spectrin-binding domain and the nonspectrin-binding domain [14 (8-18) vs. 12.5 (8-48) days, P = 0.959]. In terms of the composition of mutated genes, 25% of patients with mild hemolysis carried ANK1 or SPTA1 mutations, while 75% of patients with mild hemolysis carried SPTB or SLC4A1 mutations. In contrast, 46.7% of patients with severe hemolysis had ANK1 or SPTA1 mutations and 53.3% of patients with severe hemolysis had SPTB or SLC4A1 mutations. However, there was no statistically significant difference in the distribution of mutated genes between the two groups (P = 0.400). CONCLUSION: The present study is the first to investigate the potential association between genotype and degree of hemolysis in HS. The present findings indicated that there is no significant correlation between genotype and degree of hemolysis in HS.

Venetoclax plus cyclophosphamide and cytarabine as induction regimen for adult acute myeloid leukemia.

Background: The efficacy of induction chemotherapy (IC) for acute myeloid leukemia (AML) has improved significantly with the application of targeting drugs. Our previous study showed that a 4-day IC regimen of cyclophosphamide (CTX) and Ara-C [CA (4 + 3)] achieved similar complete remission (CR) rate (80%) compared with the traditional 7-day regimen, and the survival rate appeared to be better. Methods: In this pilot study, we further shortened the CA regimen to 3 days, added low-dose venetoclax (VEN, 200 mg/day) (VCA), and reported the efficacy and safety here. Results: Twenty-five newly diagnosed adult AML patients were enrolled in this study and evaluated for the remission rate after one cycle of the VCA regimen. The CR/Cri was 92%, and all these patients had undetectable minimal residual disease (MRD-). The estimated overall survival at 12 months was 79.3%. The median time for both platelet recovery and absolute neutrophil count recovery was 16 days, faster than that of traditional IC. Compared with the previous CA (4 + 3) regimen, a higher CR rate (92% vs. 80%, P < 0.01) and a deeper degree of remission (CRMRD- rate, 92% vs. 45%, P < 0.01) were found in the VCA group. Conclusions: This study showed that the 3-day CTX and Ara-C regimen is highly effective in newly diagnosed AML patients, and the addition of VEN to the CA regimen achieves higher and deeper one-course remission.

Efficacy of eltrombopag with immunosuppressive therapy for children with acquired aplastic anemia.

Background: Eltrombopag (EPAG), an oral thrombopoietin receptor agonist (TPO-RA), has been proven to improve the hematologic response without increasing toxic effects as a first-line therapy combined with standard immunosuppressive treatment (IST) in adults with severe aplastic anemia (SAA). Nevertheless, the clinical evidence on the efficacy of EPAG in children with acquired aplastic anemia is limited and controversial. Methods: We performed a single-center, retrospective study to analyze the clinical outcomes of fifteen patients aged ≤18 years with newly diagnosed acquired SAA who received first-line IST and EPAG (EPAG group) compared with those of forty-five patients who received IST alone (IST group) by propensity score matching (PSM). Results: There was no difference in the overall response (OR) rate between the EPAG group and IST group (53.3% vs. 46.7% at 3 months, P = 0.655; 66.7% vs. 57.8% at 6 months, P = 0.543), but the complete response (CR) rate was statistically significant (20.0% vs. 4.4% at 3 months, P = 0.094; 46.7% vs. 13.3% at 6 months, P = 0.012). The median time to achieve a hematological response in the EPAG and IST groups was 105 days and 184 days, respectively. No difference was observed in the event-free survival (EFS) or overall survival (OS) rates. Conclusion: Adding EPAG to standard IST as the first-line treatment for children with acquired SAA improved the rapidity of hematological response and the CR rate but did not improve the OR or EFS rates.

Capsaicin attenuates liver fibrosis by targeting Notch signaling to inhibit TNF-α secretion from M1 macrophages.

BACKGROUND: Capsaicin is a chili pepper extract with multiple therapeutic properties including anti-liver fibrosis. However, the paucity of its underlying mechanisms limited its widely clinical application. METHODS: In the present study, carbon tetrachloride (CCl4) was used to induce liver fibrosis in mice, and transforming growth factorß1 (TGFß1) was used to mimic liver fibrosis in vitro. Flow cytometry was conducted to determine the expression of CD80. The inflammatory factors level was examined by ELISA, and gene expression was detected by real-time PCR and western blot. RESULTS: Here, we show that capsaicin attenuates liver fibrosis progression by mediating macrophage inflammatory response. Capsaicin inhibited M1 polarization of macrophage by regulating Notch signaling leading to the reduced secretion of inflammatory cytokine TNF-α that correspondingly attenuates myofibroblasts regeneration and fibrosis formation of hepatocyte stellate cells (HSCs). CONCLUSION: Taken together, capsaicin alleviates liver fibrosis by inactivation of Notch signaling and further inhibiting TNF-α secretion from M1 macrophage. Targeting TNF-α or Notch signaling in macrophage represents a promising strategy to combat liver fibrosis.

[Diagnosis and treatment of urachal remnants with heterotopia sinus: a report of 2 cases].

OBJECTIVE: To probe into the diagnosis and treatment of urachal remnants with heterotopic sinus. METHODS: Two cases with penis dorsal drainage for 5 approximately 6 years were diagnosed as urachal anomaly by sinus probing, methylene blue injection test, cystoscope examination, and type B ultrasonic examination, and both received surgical removal of the urachus and all the abnormal tissues associated with it. RESULTS: Surgery and pathology proved urachal cyst with communication drainage in both of the patients. Follow-up survey showed no recurrence and malignancy. CONCLUSION: Sinus probing, mythylene blue injection test and type B ultrasonic examination are effective methods for the diagnosis of urachal remnants with heterotopic sinus. Surgical treatment should include radical removal of the urachus and the abnormal tissues associated with it.