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Hypertriglyceridemia （HTG） is the second leading cause of acute pancreatitis in China and can be caused by primary factors， namely gene mutations， which may lead to recurrent hypertriglyceridemic acute pancreatitis （HTG-AP） and difficulties in effective control of triglyceride. This article reports an adult Chinese male patient who experienced eight attacks of HTG-AP and was found to carry a de novo heterozygous mutation， p.K327N， of the GPD1 gene， which may cause the persistent high level of triglyceride and recurrent attacks of HTG-AP.
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Objective:To analyze the change rules of quantitative parameters of magnetic resonance-perfusion weighted imaging (MR-PWI) in cynomolgus monkeys with different degrees of liver fibrosis, and to explore the best parameter of MR-PWI in evaluating the severity of liver fibrosis.Methods:Liver fibrosis models of twenty-two cynomolgus monkeys were successfully established by subcutaneous injection of carbon tetrachloride and feeding with high-fat food. Among them, 15 cynomolgus monkeys developed into early liver cirrhosis (stage S4 of liver fibrosis). Compatibility group design was adopted, the comparative study on MR-PWI of exchange double blood supply model of liver was carried out in these 15 cynomolgus monkeys with a complete development process of liver fibrosis. The quantitative parameters of MR-PWI included endothelial transfer constant ( ktrans), reflux rate constant ( kep), extravascular extracellular space fractional volume ( ve), fractional plasma volume ( vp) and hepatic artery perfusion index (HPI). The change rules of the above parameters and their correlation with the severity of hepatic fibrosis were analyzed. The best parameter of MR-PWI was explored. Compatibility group design (randomized block design), analysis of variance, SNK- q test, Spearman rank correlation analysis and receiver operating characteristic (ROC) curve analysis were used for statistical analysis. Results:ktrans and kep of MR-PWI of cynomolgus monkeys decreased along with the progress of hepatic fibrosis, and the differences were statistically significant ( F=685.228, 99.718, both P<0.01). There were statistically significant differences between each stage of hepatic fibrosis (S1 to S4) and normal liver tissue (S0) ((0.527±0.038), (0.479±0.035), (0.432±0.032) and (0.387±0.031) mL/min vs.(0.584±0.044) mL/min, all P<0.01; (2.193±0.307), (1.997±0.301), (1.624±0.174) and (1.532±0.130) mL/min vs. (2.565±0.482) mL/min, all P<0.01). There were statistically significant in ktrans and kep between stage S3, S4 severe liver fibrosis and stage S1 mild liver fibrosis, stage S2 moderate liver fibrosis (all P<0.01), however there were no statistically significant differences between stage S3 and stage S4 liver fibrosis, between stage S1 and stage S2 liver fibrosis (all P>0.05). Along with the development of the severity of liver fibrosis, HPIs increased gradually, and the differences were statistically significant ( F=839.883, P<0.01). The HPIs of stage S0 to S4 were 0.244±0.022, 0.317±0.035, 0.421±0.046, 0.546±0.043 and 0.651±0.058, respectively, and there were statistically significant differences between groups (all P<0.01). Along with the progression of the severity of liver fibrosis, vp decreased while ve increased gradually, but there were no statistically significant differences among groups (all P>0.05). The results of Spearman rank correlation analysis indicated that ktrans and kep were negatively correlated with the severity of liver fibrosis ( rs=-0.875 and -0.797, both P<0.01), however HPI was positively correlated with the severity of liver fibrosis ( rs=0.959, P<0.01). The results of ROC curve analysis showed that area under curves (AUCs) of ktrans, kep and HPI in the diagnosis of early cirrhosis were 0.852 (95% CI 0.767 to 0.937), 0.799 (95% CI 0.700 to 0.897) and 0.967 (95% CI 0.932 to 1.002), respectively. The best cut-off values were 0.395 mL/min, 1.561 mL/min and 0.590, respectively. The sensitivity was 86.7%, 79.6% and 97.4%, respectively and the specificity was 77.4%, 71.9% and 93.1%, respectively. The thresholds of HPI in the diagnosis of liver fibrosis at stage S1, stage S2, stage S3 and stage S4 were 0.291, 0.376, 0.503 and 0.590, respectively; the sensitivity was 95.7%, 93.8% and 94.4% and 97.4%, respectively and the specificity was 89.5%, 84.7%, 91.3% and 92.7%, respectively. Conclusions:The parameters of MR-PWI change regularly with the development of liver fibrosis in the cynomolgus monkey model, among which HPI is the best parameter for quantitative evaluation of the severity of liver fibrosis.
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Objective To study the clinical efficacy and safety of clopidogrel combined with aspirin in doub-le loading dosage and ordinary dosage in the treatment of acute non -cardiac cerebral infarction.Methods A total of 110 patients with acute non -cardiac infarction were equally assigned into two groups,each group had 55 patients.The patients in group A were treated with clopidogrel 300mg and aspirin 300mg on the 1st day,and followed by clopidogrel 75mg and aspirin 100mg every day.Patients in group B were treated with clopdogrel 75mg and aspirin 100mg every day.Clinical efficacy and safety were evaluated in one week,NIHSS scores were evaluated,and adverse effects were recorded during treatment.Results After one week treatment,the deteriorate rates of group A and B were 12.7%, 18.2%.Compared with group B,group A had lower cerebral infarction deteriorate rate,but there was no statistically significant difference(P =0.429).After seven days treatment,the NIHSS score of A group had improved[(4.42 ± 3.34)points vs.(3.15 ±2.58)points],the difference was statistically significant(t =3.713,P <0.01 ),which in group B had no significant improvement[(4.16 ±2.76)points vs.(3.80 ±3.15)points,t =1.209,P =0.232].After seven days treatment,the NIHSS score improvement of group A was (1.27 ±2.54)points,which of group B was (0.36 ±2.23)points,the difference was statistically significant(t =1.994,P =0.049).No severe adverse effects occurred in both two groups.Conclusion Using clopidogrel combined with aspirin in double loading dosage may effectively attenuate stroke process and improve prognosis than ordinary dosage.Using clopidogrel combined with aspirin had no severe adverse effects in short -term treatment of acute non -cardiac cerebral infarction.
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Non-proline cis peptide bond is rarely found in proteins. The recent surveys revealed that this unusual peptide configuration is by no means a curiosity, but overwhelmingly occurs at functionally important sites. However one still doubts whether it is related to crystal packing interactions, since all non-proline cis peptide bonds identified so far are from crystal structures. A toxin BmK M1 from the scorpion Buthus martensii Karsch have been crystallized as a dimer in space group P212121 with unit-cell dimensions a = 76.39 (A),b=52.77 (A), c=27.12 (A). This dimeric structure was solved by molecular replacement and refined to R=0.109 for all reflections at a resolution of 1.4 (A). The extensively refined structure definitely shows that the cis peptide bond Pro9-His10 equally occurs in both molecule A and molecule B in the dimer. The observation manifested that this striking non-proline cis peptide is not related to crystal packing, but caused by certain intrinsic factors. The detailed analyses and comparison with the structure of BmK M8, which is homologous to M1 but has trans peptide bond 9-10, showed that the five-residue reverse (8 ～12) with a consensus sequence (-KPXNC-) may be the intrinsic structural element for the cis form of this peptide bond. A pair of well organized main-chain hydrogen bond between residues 10 in cis unit and 64 at C-terminus forms main tertiary interactions to stabilize this energetically unfavorable peptide bond.