Costunolide covalently targets NACHT domain of NLRP3 to inhibit inflammasome activation and alleviate NLRP3-driven inflammatory diseases

The NLRP3 inflammasome's core and most specific protein, NLRP3, has a variety of functions in inflammation-driven diseases. Costunolide (COS) is the major active ingredient of the traditional Chinese medicinal herb Saussurea lappa and has anti-inflammatory activity, but the principal mechanism and molecular target of COS remain unclear. Here, we show that COS covalently binds to cysteine 598 in NACHT domain of NLRP3, altering the ATPase activity and assembly of NLRP3 inflammasome. We declare COS's great anti-inflammasome efficacy in macrophages and disease models of gouty arthritis and ulcerative colitis via inhibiting NLRP3 inflammasome activation. We also reveal that the α-methylene-γ-butyrolactone motif in sesquiterpene lactone is the certain active group in inhibiting NLRP3 activation. Taken together, NLRP3 is identified as a direct target of COS for its anti-inflammasome activity. COS, especially the α-methylene-γ-butyrolactone motif in COS structure, might be used to design and produce novel NLRP3 inhibitors as a lead compound.

Value of red blood cell distribution width in assessing the severity of acute pancreatitis / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the value of red blood cell distribution width (RDW) in assessment of the severity of acute pancreatitis (AP).</p><p><b>METHODS</b>This retrospective analysis was conducted among 527 patients with AP treated in our department from May, 2013 to May, 2016. According to the severity of the condition, the patients were classified into mild acute pancreatitis (MAP) group, moderately severe acute pancreatitis (MSAP) group and severe acute pancreatitis (SAP) group, with 105 subjects without AP as the control group. The demographic data and data of RDW were collected from all cases to evaluate the value of RDW in assessing the severity of AP in comparison with classic evaluation indicators glucose (Glu) and calcium (Ca).</p><p><b>RESULTS</b>The patients with AP and the control subjects showed significant differences in RDW, Glu and Ca (P<0.05). RDW and Glu was significantly higher but Ca was significantly lower in SAP patients than in MAP and MSAP patients (P<0.05). Binary classification logistic regression analysis showed that Glu (P<0.05, OR=2.343), Ca (P<0.05, OR=2.182) and RDW (P<0.05, OR=3.374) were all independent risk factors for AP. The area under the ROC curve for predicting SAP decreased in the order of RDW (0.801), Glu (0.658), and Ca (0.227).</p><p><b>CONCLUSION</b>RDW is a useful indicator for evaluation of the severity of AP.</p>

Study on effect of Fufang Xueshuantong capsule on serpine1,α-serpine1 protein and KLF2 in patients with lower extremity venous thrombosis / 中国生化药物杂志

Objective To explore the effect of serpine1, α-serpine1 protein and KLF2 in patients with lower extremity venous thrombosis by Fufang Xueshuantong capsule.Methods 44 patients were diagnosed with lower extremity venous thrombosis were collected, and randomly divided into experimental group and control group, 22 cases in each group, giving the conventional antiplatelet therapy, on the basis of this, the experimental group was given Fufang Xueshuantong capsule 1.5 g, three times a day orally, and the control group was given context Shutong granules 20 g, three times a day orally.2 weeks for a course of treatment, three courses of treatment.Before and after treatment in the detection of two groups of patients with serum serpine1, α-serpine1 KLF2 and protein contents, blood rheology, coagulation function, and carries on the analysis.ResuIts Compared with the control group, experimental group patients has better curative effect, the performance of: serum serpine1and α-serpine1 protein content were significantly decreased(P<0.05).KLF2 expression was significantly higher (P<0.05).Blood viscosity, erythrocyte aggregation index, erythrocyte sedimentation rate decreased significantly (P<0.05).Fib, D-D content significantly decreased (P<0.05).ConcIusions Fufang Xueshuantong capsule can reduce serum serpine1, α-serpine1 protein content and promote KLF2 expression, decrease the blood viscosity, erythrocyte sedimentation rate, improve patients with hypercoagulable state in patients with lower extremity venous thrombosis, so as to achieve good clinical efficacy.

The complications and prevention of percutaneous vertebral kyphoplasty for the treatment of the thoracic and lumbar osteoporotic compression fractures during the operation / 中华内分泌外科杂志

Objective To discuss the complications of percutaneous kyphoplasty (PKP) in treatment of osteoporotic compression fractures (OVCFs) of the thoracic and lumbar vertebrae,and to investigate their causes and prevention.Methods From Jan.2004 to Dec.2012,PKP or PKP combined with percutaneous vertebroplasty(PVP) was performed on 126 vertebrae in 112 thoracolumbar OVCFs patients.There were 21 males and 91 females.The average age was 69 years (ranging from 36 to 85).100 cases had single vertebra,10 cases had double vertebrae,and 2 cases had 3 vertebrae.The injured segments were identified by MRI before surgery,and the fractures of the vertebrae were observed clearly by X ray and CT scan.The causes of the complications were retrospective analyzed.Results Perioperative complication happened in 68 cases (54％).The leakage of the bone cement happened in 66 cases (52.4％):one of them had high fever after the leakage happened behind the post-wall of the vertebra body,and it disappeared after one week with the relevant treatment.There was no injury of the nerve.Most of the leakage happened in front of the vertebra body,few happened in the terminal plate,and few happened behind the vertebral plate.There was no pulmonary embolism.Toxic reaction of the bone cement wasn't found in this team.There was no artery or nerve injury.One temporary spinal cord injury happened,one case was punctured in a wrong vertebra,and balloon rupture happened in one case.One case didn't achieve pain release.No infection happened.Conclusion The bone cement leakage was the most common complication associated with PKP in treatment of OVCFs.The complication rate can be reduced if the operation indications are strict,the volume of the filling cementis is well controlled,and the operation is performed in experienced hands.

Epidemiological and clinical analysis of Mycoplasma pneumoniae infection in children with acute respiratory tract infection / 南方医科大学学报

<p><b>OBJECTIVE</b>To summarize the epidemiology and clinical characteristics of Mycoplasma pneumoniae (MP) infection in children with acute respiratory tract infection (ARI) in Guangzhou.</p><p><b>METHODS</b>MP was detected using an indirect immunofluorescent method in 2084 children with ARI. The relations between MP infection rate and the gender, age, season, site of infection and wheezing diseases were analyzed.</p><p><b>RESULTS</b>A total of 433 children (20.8%) were positive for MP, including 222 boys (19.8%) and 211 girls (21.9%) without significant difference in the infection rate between the genders (P>0.05). In 0- to 3-year-old group, 106 children were positive for MP (15.0%), while in 3- to 5-year-old group and 5- to 14-year-old group, 163 (25.2%) and 164 (22.5%) were positive, respectively, showing a significant difference in the infection rate between the 3 groups (P<0.05). The MP infection rate was 18.0% in January to March, 25.1% in April to June, 17.7% in July to September, and 20.5% in October to December, showing significant differences between the periods (P<0.05). No significant difference was found in the infection rate between children with acute upper respiratory tract infection (URI) and those with lower respiratory tract infection (LRI) (P>0.05). Among the children with LRI, those having wheezing disease had significantly higher MP positivity rate than those without wheezing.</p><p><b>CONCLUSION</b>MP is a common causative agent for ARI in children. MP infection is not related to gender and infection site, but to age and season. Children over 3 years old are vulnerable to MP infection. MP infection can be associated with wheezing in LRI.</p>

Clinical observation on effect of Jieyu Anshen Decoction combined with aripiprazole in treating chronic schizophrenia / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the efficacy and safety of Jieyu Anshen Decoction (JAD) combined with aripiprazole in treating chronic schizophrenia.</p><p><b>METHODS</b>All 100 patients with chronic schizophrenia diagnosed according to CCMD-3 criteria were equally randomly assigned to the study group (treated with JAD combined with aripiprazole) and the control group (treated with aripiprazole alone) for 12 weeks. The efficacy and safety were evaluated by Positive and Negative Syndrome Scale (PANSS) and Treatment Emergent Side Effect Scale (TESS).</p><p><b>RESULTS</b>After 12 weeks of treatment, the clinical efficacy in the study group was significantly higher than that in the control group, the PANSS score in the study group was significantly decreased with a higher speed and range of decreasing, becoming lower than that in the control group at the same period. But the difference between the two groups in scores of TESS at corresponding times showed no significance.</p><p><b>CONCLUSION</b>JAD combined with aripiprazole has definite effect in treating chronic schizophrenia, shows advantages of quickly initiating effect, high safety and with no harm for increasing adverse reactions, so it is better than using aripiprazole alone.</p>

Depressant Effect of siRNA on the Expression and Replication of Hepatitis B Virus in HepG2.2.15 Cell / 实用儿科临床杂志

Objective To explore the siRNA as a new antiviral therapy,evaluate the inhibition effect of siRNA based on vector on the HBV of HepG2.2.15 cell,and observe the side effect and toxicity of siRNA vector on cells and the off-target effect of siRNA.Methods Three pairs of siRNA duplexes targeting HBV C gene were designed as double strands,and the duplex were annealed and ligated into the p-Silencer-Cmv 4.1-hygro vector.The ligation products were used to transform JM109 cells.The clones with shRNA were obtained,and the vectors were purified.After the initial identification of the vector with agarose gel and the size of the inserted sequence got examined by native polyacrylamide gel electrophoresis,furthermore the sequencing was further carried out.The recombinant plasmids were purified with ultrapure Midipreps DNA Purification System.Then HepG2.2.15 cells were transfected with the plasmid mixed with siPort XP-1.The expression of HBsAg and HBeAg were detected by immunofluorescence and Western blot,and the HBV RNA was investigated by RT-PCR.Furthermore the real-time quantitive PCR was carried out to detect the changes of HBV DNA.In order to evaluate the toxicity of the shRNA,MTT was used to examine the growth rate and curve of cells.The ELISA was performed to detect the changes of interferon-? (IFN-?).Results The Western blot showed that the HBsAg and HBeAg protein were suppressed with (81.15?0.69)%,(88.12?0.92)% respectively by vector p-C2 on the third day of post-transfection.It had the similar result indicated by immunofluorescence.And the RT-PCR showed that the specific siRNA targeting HBV C gene could markedly suppress the expression of HBV mRNA and the HBV C gene mRNA was inhibited with 96.9%.The real-time quantitive PCR showed that the specific functional siRNA could markedly suppress HBV DNA copy with two orders of magnitude,while the siRNA vector had no effect on the growth of cell showed by MTT detection.Compared with the non-transfected group and p-NC group,the IFN-? level was almost the same with siRNA p-C1,p-C2,p-C3 groups.Conclusions The siRNA based on the expression vector can suppress the expression and replication of HBV in HepG2.2.15 cell.The inhibition effect was specific and had a certain dependency on siRNA concentration.No toxicity effect was found in the study.And the drug resistance wouldn′t happen because the silence was based on the split of gene.

Dynamic variation of endothelin in portal hypertensive patients with hemorrhage and its clinical significance / 中南大学学报(医学版)

OBJECTIVE@#To investigate variations of plasma endothelin (ET) and its clinical significance in portal hypertensive patients with esophageal variceal hemorrhage.@*METHODS@#Sixty-six patients with portal hypertension were randomly divided into 2 groups. Group I (32 patients) received general therapy and Group II (34 patients) received general therapy and UTI after hemorrhage. The plasma ET concentration and liver function were determined at 1, 2, 4, 7, 10, and 14 d after the hemorrhage. Another 20 patients without the hemorrhage were elected as the control group.@*RESULTS@#At 7 and 14 d after the hemorrhage, the levels of TBIL, ALT and AST were elevated at first and then decreased in Groups I and II. The decrease of TBIL, ALT and AST levels was significantly faster in Group II than in Group I (P < 0.05, P < 0.01, P < 0.05, respectively) on 14 d after the hemorrhage. At 1 d after the hemorrhage the ET concentration was markedly increased in Group I and II as compared with the control group (P < 0.01). Then it was gradually decreased on 10 d after the hemorrhage. The ET concentration in Group II was decreased more rapidly than that in Group I on 2, 4 and 7 d after the hemorrhage (P < 0.05; P < 0.01; P < 0.05, respectively). The ET concentration was positively correlated to TBIL levels in groups I and II (r = 0.734, P < 0.01). And the decreased index of ET concentration was negatively correlated to the increased index of TBIL (r = -0.486, P < 0.05).@*CONCLUSION@#The increased plasma ET in portal hypertensive patients with hemorrhage may contribute to liver injury. UTI can protect the liver function by inhibiting ALT, AST, TBIL and ET level.

The clinical significance of petrosal vein in operation of cerebellopontine angle tumor / 中华显微外科杂志

Objective To discuss the clinical significance of petrosal vein in operation of cerebel- lopontine angle(CPA)tumor.Methods From Dec.2004 to Mar.2006,33 patients with tumor in CPA were operated,the petrosal vein were protected well in 31 cases and failed to protect in 2 cases.Results No hemorrhagic infarction observed in 31 cases with well protection of petrosal vein.Two cases with petrosal vein damage occured with vein infarction and hemorrhagic edema.One was dead and the other was recovered well after decompression of posterior cranial fossa.Conclusion Petrosal vein should be well protected in the tumor operation of CPA area,the decompression of posterior cranial fossa should be considered if petrosal vein failed to protect.