Objective To explore the effects of the heterocyclic oleanolic acid derivatives-aspirin conjugates on inhibition of serotonin biosynthesis and increase of bone formation.Methods The inhibition rate,content and mRNA expression of heterocyclic oleanolic acid derivatives-aspirin conjugates on tryptophan hydroxylase 1 (TPH-1),which was the principal enzyme in the biosynthesis of serotonin,were tested by HPLC,ELISA kit and real-time PCR,respectively.Osteoporosis model was established by ovariectomy (OVX).The rats were randomly divided into conjugate groups,parathyroid hormone group,model control group and sham operation group.Serum and gut serotonin levels were tested by HPLC after 35 days of administration,and the antiosteoporosis activity of the heterocyclic oleanolic acid derivatives-aspirin conjugates was evaluated by using osteoblast-like cells isolated from murine calvaria by MTT assay.Results The preliminary biological results showed that heterocyclic oleanolic acid derivatives-aspirin conjugates displayed a dose-dependent suppression on TPH-1 in RBL-2H3,and the inhibition rate was 20.4%-92.5%.Specifically,conjugate 7 at 10 μmol·L-1 concentration showed the greatest inhibition rate on TPH-1 (92.5%).Content of TPH-1 was 51 ng mL-1,significantly lower than that in the control group (216 ng·mL-1),as well as the TPH-1 mRNA.Compared with the sham operation group,levels of serum and gut serotonin were increased in OVX group,while they were significanlty decreased in conjugate groups,and reduced significantly in conjugate 7 group (232 and 155 ng·mL-1) as compared with OVX group (1 050 and 783 ng·mL-1);Moreover,heterocyclic oleanolic acid derivatives-aspirin conjugates could increase the bone formation.Conclusion This study provides information and basis for development of novel,efficient and harmfulless oleanolic acid derivatives with anti-osteoporosis.

Aim To observe the effects of simvastatin on PPARγ and p65 subunit of NF-κB and to invest the mechanism of simvastatin preventing hypertrophy and keeping cardiac function.Methods 24 rabbits were divided into 4 groups.Rabbits received sham operation as health control in group I. In other groups, aortic regurgitation and coarctation of ascending aorta were operated in rabbits.Rabbits received no drugs in Group Ⅱ. In group Ⅲ, rabbits were given simvastatin 5 mg·kg~(-1)·d~(-1) after the operation for 8 weeks. In group Ⅳ, rabbits were given simvastatin 5 mg·kg~(-1)·d~(-1) after 4 weeks of operation for 4 weeks. At the beginning and the end of the experiment, left ventricular end diastolic pressure (LVEDP) was measured with catheter. At the end of the experiment, heart weight (HW), left ventricular weight (LVW), body weight (BW), heart weight/body weight radio (HW/BW radio), left ventricular weight/body weight radio (LVW/BW radio) were measured.The PPARγ mRNA expression was analyzed by RT-PCR. PPARγ and p65 protein expression in cardiomyocyte nuclear were analyzed through Western blot. The activity of p65 was analyzed with EMSA.Results The HW, LVW, HW/BW were significantly decreased in the early and late treatment group than in CHF group(P<0.05,P<0.01). The LVW/BW was significantly decreased inearly treatment group than in CHF group, too (P<0.01). The LVEDP was significantly decreased in the early and late treatment group than in CHF group (P<0.01). The mRNA and protein of PPARγ significantly fell in CHF heart (P<0.01). The activity and protein expression of p65 were significantly increased in CHF heart (P<0.01). Simvastatin increased the mRNA and protein expression of PPARγ and decreased the activity and protein expression of p65 (P<0.01).Conclusions Simvastatin inhibits the cardiac hypertrophy and improves cardiac function. The mechanism of simvastatin on cardiac remodeling and function relates to the increase of PPARγ expression and preventing the NF-κB activation.

Objective:To analyze the diagnostic and prognostic value of routine bone marrow examination in patients with extranodal NK/T-cell lymphoma (ENKTCL) based on PET-CT staging.Methods:Clinical data of 186 patients who received bone marrow biopsy and bone marrow aspiration in Fujian Medical University Union Hospital from 2013 to 2021 were retrospectively analyzed. All patients were divided into bone marrow biopsy + bone marrow aspiration group ( n=186) and PET-CT + bone marrow biopsy group ( n=139). The sensitivity, specificity, positive and negative predictive values were compared between two groups. The data were analyzed and plotted. Survival analysis was performed using Kaplan-Meier method and log-rank test. Results:In the whole cohort, 45 patients were positive for bone marrow biopsy, and 30 of them were positive for bone marrow aspiration. A total of 141 patients who were negative for bone marrow biopsy also achieved negative results for bone marrow aspiration. A total of 139 patients completed PET-CT staging and bone marrow biopsy. And 30 patients were diagnosed with positive bone marrow by PET-CT, in which 22 of them were confirmed positive by bone marrow biopsy. Among 109 patients diagnosed with negative bone marrow by PET-CT, 5 of them were confirmed positive by bone marrow biopsy. All these cases were classified as stage Ⅳ due to distant metastases. PET-CT had a diagnostic sensitivity of 81.5%, a specificity of 92.9%, a positive predictive value of 73.3%, and a negative predictive value of 95.4%. Among early stage (Ⅰ-Ⅱ stage) patients diagnosed with PET-CT, all of them were negative for bone marrow biopsy (the negative predictive value was 100%). In stage Ⅳ patients ( n=55), the 1-year overall survival of patients with bone marrow involvement by bone marrow biopsy or PET-CT ( n=35) compared with their counterparts with the involvement of other organs ( n=20) was 28.7% vs.42.0% ( P=0.13), and 1-year progression free survival rates was 23.2% vs. 23.3% in ( P=0.94). Conclusions:Routine bone marrow biopsy does not change the original staging of patients with early stage ENKTCL based on PET-CT staging. Advanced stage patients with positive bone marrow biopsy tend to obtain worse prognosis, indicating that bone marrow biopsy still has certain value.