Objective To investigate the therapeutic effect of hypericin on acute pancreatitis(AP)in mice and its effect on NLRP3 inflammasome signaling pathway.Methods The AP model in mice was established with caerulein(CER).The mice were divided into the normal control group,the model group(AP group),the low-dose HY group(CER+HY 5 mg/kg group),the medium-dose HY group(CER+HY 10 mg/kg group)and the high-dose HY group(CER+HY 20 mg/kg group),with 10 mice in each group.The 266-6 mouse pancreatic acinar cancer cells were treated with cholecystokinin(CCK)and divided into the control group,the AP group,the CCK+HY 1 μmol/L group,the CCK+HY 2 μmol/L group and the CCK+HY 4 μmol/L group.The activities of amylase(AMS),lipase,trypsin and myeloperoxidase(MPO)in the serum of each group of mice,and levels of inflammatory factors interleukin(IL)-1β and tumor necrosis factor(TNF)-α were detected by enzyme-linked immunosorbent assay(ELISA).The expression of NOD-like receptor family protein 3(NLRP3)was detected by Western blot assay.The mRNA levels of NLRP3,caspase(Caspase)-1,IL-1β,TNF-α and IL-18 in pancreatic tissue of mice were detected by real-time quantitative PCR(q-PCR).The cell survival rate of cells in each group was detected by CCK8 method.The mRNA expression levels of NLRP3,Caspase-1 and IL-18 in each group of cells were detected by q-PCR.Results Compared with the normal control group,the levels of AMS,lipase,MPO,trypsin,IL-1β and TNF-α in serum of the model group,and the mRNA and protein expression levels of NLRP3,IL-1β,TNF-α,IL-18 and Caspase-1 in pancreatic tissue were increased(P＜0.01).Compared with the model group,the levels of AMS,IL-1β and TNF-α,the enzymatic activity of trypsin in serum,and the mRNA levels of IL-1β,TNF-α,IL-18 and Caspase-1 in pancreatic tissue were decreased in the low-,medium-and high-dose HY groups.The serum levels of lipase and MPO and the mRNA expression levels of NLRP3 in pancreatic tissue were decreased in the medium-and high-dose HY groups(P＜0.05).Compared with the AP group,the cell survival rates were increased in the CCK+HY 1 μmol/L group,the CCK+HY 2 μmol/L group and the CCK+HY 4 μmol/L group,and the mRNA levels of NLRP3,IL-18 and Caspase-1 were decreased in a dose-dependent manner(P＜0.05).Conclusion Hypericin can effectively treat AP in vivo and in vitro,and its therapeutic effect may be related to the regulation of NLRP3 inflammasome signaling pathway.

Objective To investigate the therapeutic effect of hypericin on acute pancreatitis(AP)in mice and its effect on NLRP3 inflammasome signaling pathway.Methods The AP model in mice was established with caerulein(CER).The mice were divided into the normal control group,the model group(AP group),the low-dose HY group(CER+HY 5 mg/kg group),the medium-dose HY group(CER+HY 10 mg/kg group)and the high-dose HY group(CER+HY 20 mg/kg group),with 10 mice in each group.The 266-6 mouse pancreatic acinar cancer cells were treated with cholecystokinin(CCK)and divided into the control group,the AP group,the CCK+HY 1 μmol/L group,the CCK+HY 2 μmol/L group and the CCK+HY 4 μmol/L group.The activities of amylase(AMS),lipase,trypsin and myeloperoxidase(MPO)in the serum of each group of mice,and levels of inflammatory factors interleukin(IL)-1β and tumor necrosis factor(TNF)-α were detected by enzyme-linked immunosorbent assay(ELISA).The expression of NOD-like receptor family protein 3(NLRP3)was detected by Western blot assay.The mRNA levels of NLRP3,caspase(Caspase)-1,IL-1β,TNF-α and IL-18 in pancreatic tissue of mice were detected by real-time quantitative PCR(q-PCR).The cell survival rate of cells in each group was detected by CCK8 method.The mRNA expression levels of NLRP3,Caspase-1 and IL-18 in each group of cells were detected by q-PCR.Results Compared with the normal control group,the levels of AMS,lipase,MPO,trypsin,IL-1β and TNF-α in serum of the model group,and the mRNA and protein expression levels of NLRP3,IL-1β,TNF-α,IL-18 and Caspase-1 in pancreatic tissue were increased(P＜0.01).Compared with the model group,the levels of AMS,IL-1β and TNF-α,the enzymatic activity of trypsin in serum,and the mRNA levels of IL-1β,TNF-α,IL-18 and Caspase-1 in pancreatic tissue were decreased in the low-,medium-and high-dose HY groups.The serum levels of lipase and MPO and the mRNA expression levels of NLRP3 in pancreatic tissue were decreased in the medium-and high-dose HY groups(P＜0.05).Compared with the AP group,the cell survival rates were increased in the CCK+HY 1 μmol/L group,the CCK+HY 2 μmol/L group and the CCK+HY 4 μmol/L group,and the mRNA levels of NLRP3,IL-18 and Caspase-1 were decreased in a dose-dependent manner(P＜0.05).Conclusion Hypericin can effectively treat AP in vivo and in vitro,and its therapeutic effect may be related to the regulation of NLRP3 inflammasome signaling pathway.

Objective To study the clinical risk factors and the characteristics of cerebral magnetic resonance imaging (MRI) of hypoxic-ischemia encephalopathy (HIE) in full-term infants in high-altitude area.Method From January 2014 to December,2016 full-term Tibetan infants with HIE and healthy full-term Tibetan infants admitted to our hospital were enrolled in the study.General conditions and perinatal status were retrospectively analyzed.Univariate analysis and multivariate analysis were used to determine the risk factors of the HIE.MRI characteristics,location of the brain injuries and the correlation between HIE clinical grading and MRI grading were analyzed.Result During the study period,5 172 full-term Tibetan neonates were born in our hospital,198 of them were diagnosed of HIE and the incidence was 3.8％.According to HIE clinical grading,31 were mild,110 were moderate and 57 were severe.MRI grading included 34 mild,131 moderate and 33 severe.The main manifestations of MRI included white matter injury,especially subcortical white matter injury of frontal,parietal and occipital lobes,gray matter injury and diffuse cerebral edema.Mild HIE had a certain correlation with MRI grading,however,severe HIE had poor correlation with MRI grading.Multivariate Logistic regression analysis showed that abnormal birth weight (＜2 500 g or＞4 000 g) and intrauterine distress were independent risk factors of HIE in full-term Tibetan neonates[OR (95％ CI):3.663 (1.961～6.843) and 5.419 (2.487～11.807)].Conclusion Macrosomia at birth,low birth weight and intrauterine distress are independent risk factors of HIE in Tibetan full-term neonates in Lhasa.White matter injury is the main MRI manifestation of HIE.Clinical grading of Mild HIE has good consistency with the MRI grading,but MRI grading is milder than the clinical grading for those with moderate and severe HIE.

Objective To explore the effect of combination of telbivudine( LdT)and adefovir dipivoxil(ADV)on renal function in patients with chronic hepatitis B( CHB). Methods The CHB patients with renal injury due to lamivudine(LAM)resistance and combination with ADV,who visited in First Affiliated Hospital of Zhejiang Chinese Medical University were enrolled into this study. The randomized controlled trial was performed in this study. The patients were divided into two groups by table of random number:the LAM + ADV group( original treatment was continued)and the LdT + ADV group (LAM was replaced with LdT). The levels of HBV DNA,alanine aminotransferase( ALT),serum creatinine(Scr),estimated glomerular filtration rate(eGFR),urinary beta 2-microspheres(Uβ2-MG), and serum creatine kinase(sCK)were compared between the 2 groups at baseline,24 and 48 weeks of treatments. Results A total of 79 patients were enrolled into the study. There were 41 patients in the LAM + ADV group and 38 in the LdT + ADV group. The differences of sex distribution,age,body weight and the basal level between the 2 groups were not statistically significant(all P > 0. 05). There were no HBV DNA breakthrough in patients during 48 weeks of treatment in both groups. The differences of ALT levels at different time points in patients in the 2 groups were not statistically significant(all P > 0. 05). In the LAM + ADV group,the Scr levels at 24 and 48 weeks of treatment were higher than those at baseline [(117 ± 11),(122 ± 12)μmol/ L vs.(113 ± 12)μmol/ L]. The difference between the baseline and 48 weeks of treatment was statistically significant(P < 0. 05). The levels of Scr in the LdT + ADV group at 24 and 48 weeks of treatment were lower than those at baseline[(104 ± 10),(99 ± 9)μmol/ L vs. (109 ± 10)μmol/ L]( all P < 0. 05). The levels of eGFR in the LAM + ADV group at 24 and 48 weeks of treatment were lower than those at baseline[(68. 9 ±12. 2),(66. 1 ±7. 6)ml·min-1 ·1. 73 m-2 vs.(70. 9 ± 8. 1)ml · min-1 · 1. 73 m-2 ]. The difference between the baseline and 48 weeks of treatment was statistically significant(P < 0. 05). The levels of eGFR in the LdT + ADV group at 24 and 48 weeks of treatment were higher than those at baseline[(75. 1 ± 11. 4),(79. 6 ± 31. 1)ml·min-1 ·1. 73 m-2 vs. (71. 4 ± 10. 6)ml·min-1 ·1. 73 m-2 ](all P < 0. 05). The levels of Uβ2-MG in the group of LAM + ADV at 24 and 48 weeks of treatment were higher than those at baseline[4 611(23 920,740),4 719(24 109, 967)μg/ L vs. 4 601(23 807,611)μg/ L]. The difference between the baseline and 48 weeks of treatment was statistically significant(P < 0. 05). The levels of Uβ2- MG in the LdT + ADV group at 24 and 48 weeks of treatment were lower than those at baseline[3 251(12 890,220),1 950(10 119,73)μg/ L vs. 4 109 (24 703,633)μg/ L]. The difference between the baseline and 48 weeks of treatment was statistically significant(P < 0. 05). The difference of sCK levels between the baseline and 24 and 48 weeks of treatments [(99 ± 31),(99 ± 36),(96 ± 37)]were not statistically significant(all P > 0. 05). The sCK levels in the LdT + ADV group at 24 and 48 weeks of treatments were higher than those at baseline[(107 ± 38),(130 ± 56)U/ L vs. (97 ± 31)U/ L]. The difference between the baseline and 48 weeks of treatment was statistically significant(P < 0. 05). The differences of Scr,eGFR,Uβ2-MG,and sCK levels at baseline and 48 weeks of treatment in the 2 groups were statistically significant(all P < 0. 05). Conclusions The therapeutic regimen of telbivudine combination with adefovir dipivoxil can improve the renal function in patients with CHB. The change of sCK level should be monitor closely during the treatment.

Objective To explore the effect of combination of telbivudine( LdT)and adefovir dipivoxil(ADV)on renal function in patients with chronic hepatitis B( CHB). Methods The CHB patients with renal injury due to lamivudine(LAM)resistance and combination with ADV,who visited in First Affiliated Hospital of Zhejiang Chinese Medical University were enrolled into this study. The randomized controlled trial was performed in this study. The patients were divided into two groups by table of random number:the LAM + ADV group( original treatment was continued)and the LdT + ADV group (LAM was replaced with LdT). The levels of HBV DNA,alanine aminotransferase( ALT),serum creatinine(Scr),estimated glomerular filtration rate(eGFR),urinary beta 2-microspheres(Uβ2-MG), and serum creatine kinase(sCK)were compared between the 2 groups at baseline,24 and 48 weeks of treatments. Results A total of 79 patients were enrolled into the study. There were 41 patients in the LAM + ADV group and 38 in the LdT + ADV group. The differences of sex distribution,age,body weight and the basal level between the 2 groups were not statistically significant(all P > 0. 05). There were no HBV DNA breakthrough in patients during 48 weeks of treatment in both groups. The differences of ALT levels at different time points in patients in the 2 groups were not statistically significant(all P > 0. 05). In the LAM + ADV group,the Scr levels at 24 and 48 weeks of treatment were higher than those at baseline [(117 ± 11),(122 ± 12)μmol/ L vs.(113 ± 12)μmol/ L]. The difference between the baseline and 48 weeks of treatment was statistically significant(P < 0. 05). The levels of Scr in the LdT + ADV group at 24 and 48 weeks of treatment were lower than those at baseline[(104 ± 10),(99 ± 9)μmol/ L vs. (109 ± 10)μmol/ L]( all P < 0. 05). The levels of eGFR in the LAM + ADV group at 24 and 48 weeks of treatment were lower than those at baseline[(68. 9 ±12. 2),(66. 1 ±7. 6)ml·min-1 ·1. 73 m-2 vs.(70. 9 ± 8. 1)ml · min-1 · 1. 73 m-2 ]. The difference between the baseline and 48 weeks of treatment was statistically significant(P < 0. 05). The levels of eGFR in the LdT + ADV group at 24 and 48 weeks of treatment were higher than those at baseline[(75. 1 ± 11. 4),(79. 6 ± 31. 1)ml·min-1 ·1. 73 m-2 vs. (71. 4 ± 10. 6)ml·min-1 ·1. 73 m-2 ](all P < 0. 05). The levels of Uβ2-MG in the group of LAM + ADV at 24 and 48 weeks of treatment were higher than those at baseline[4 611(23 920,740),4 719(24 109, 967)μg/ L vs. 4 601(23 807,611)μg/ L]. The difference between the baseline and 48 weeks of treatment was statistically significant(P < 0. 05). The levels of Uβ2- MG in the LdT + ADV group at 24 and 48 weeks of treatment were lower than those at baseline[3 251(12 890,220),1 950(10 119,73)μg/ L vs. 4 109 (24 703,633)μg/ L]. The difference between the baseline and 48 weeks of treatment was statistically significant(P < 0. 05). The difference of sCK levels between the baseline and 24 and 48 weeks of treatments [(99 ± 31),(99 ± 36),(96 ± 37)]were not statistically significant(all P > 0. 05). The sCK levels in the LdT + ADV group at 24 and 48 weeks of treatments were higher than those at baseline[(107 ± 38),(130 ± 56)U/ L vs. (97 ± 31)U/ L]. The difference between the baseline and 48 weeks of treatment was statistically significant(P < 0. 05). The differences of Scr,eGFR,Uβ2-MG,and sCK levels at baseline and 48 weeks of treatment in the 2 groups were statistically significant(all P < 0. 05). Conclusions The therapeutic regimen of telbivudine combination with adefovir dipivoxil can improve the renal function in patients with CHB. The change of sCK level should be monitor closely during the treatment.