Objective To study the effect of pentoxifylline (PTX) on acute lung injury (ALI) in murine sepsis induced by intra abdominal infection. Methods Wistar rats were subjected to sepsis caused by cecal ligation and puncture (CLP), and animals were randomly divided into normal controls ( n =6), sepsis group ( n =18), and PTX treated group ( n =18). Pulmonary biopterin, nitric oxide (NO) levels, and pulmonary myeloperoxidase (MPO) activities were measured, guanosine triphosphate cyclohydrolase Ⅰ (GTP CHI), inducible nitric oxide synthase (iNOS), and tumor necrosis factor ? (TNF ?) mRNA expression were determined.Results Early treatment with PTX significantly decreased pulmonary MPO activities and TNF ?mRNA expression at 2 hours after CLP. Meanwhile, pulmonary biopterin, NO, GTP CHI, and iNOS mRNA expression levels were much lower in the treatment group than those in the non treatment group ( P

Prader-Willi syndrome (PWS) is a multisystemic complex genetic disorder caused by the lack of expression of genes associated with the 15q11.2-q13 region of the paternal chromosome.There are three main types of genetic mechanisms, deletion of the paternal critical region, maternal uniparental disomy and imprinting center defect.Genetic counseling can be carried out based on different genetic mechanisms of PWS, both re-fertility assessments and prenatal diagnoses were performed on couples whose children have already had the disease.The pathogeny and mechanism of PWS are complex.The rapid development of molecular genetics and related research have provided a basis for further understanding of this disease.In this paper, the advances in the genetics of PWS were reviewed.

Objective:To explore the association between the CYP21A2 genotype and the virilization severity in girls with classic 21-hydroxylase deficiency (21-OHD), so as to further the understanding of virilization in females and provide guidance for prenatal diagnosis and genetic counseling. Methods:A total of 23 patients with two X chromosomes (46, XX) who were newly diagnosed with classic 21-OHD in Wuhan Children′s Hospital from August 2010 to March 2019 were included.These patients were divided into 3 groups according to the Prader grades of the degree of external genitalia masculinization.The 17-hydroxyprogesterone (17-OHP) level, androstenedione (AND) level, testosterone (T) level, dehydroepiandrosterone sulphate (DHEAS) level and genotypes were recorded.The gene mutations were divided into the Null group(the enzyme activity was completely impaired), group A(1% of the normal enzyme activity was retained), group B(2% of the normal enzyme activity was retained) and group C(20%-60% of the normal enzyme activity was retained). The correlation between the gene variation of different Prader grades and the corresponding gene groups were analyzed.Results:All 23 girls showed different degrees of external genitalia masculi-nization.There was a significant positive correlation between the Prader grades and the type of gene variation ( rs=0.696, P<0.001). The gene group A and Null group were highly matched with the Prader Ⅳ(the matching rate: 77.8%). Eighty percent of girls with Prader Ⅱ and Prader Ⅲ were classified as the gene group B. The testosterone le-vel of girls with Prader Ⅳ at first diagnosis was significantly higher than that of girls with Prader Ⅱ [4.6(4.0, 15.0)μg/L vs.0.63(0.40, 1.39)μg/L]( χ2=15.117, P<0.05). Conclusions:There is a significantly positive and strong correlation between the degree of external genitalia masculinization and the degree of deficiency of enzyme activity caused by gene variation in girls with typical 21-OHD.It can provide reference for both parents carrying CYP21A2 gene in prenatal diagnosis, genetic counseling and individualized diagnosis and treatment.

Objective To investigate the response of multiple myeloma (MM) cells to 8-chloroadenosine 3',5'-monophosphate (8-Cl-cAMP) and the impact of arsenic trioxide (As2O3) on the above reaction.Methods MM-derived cell lines RPMI8226 and U266 were used as in vitro models.Cell apoptosis was evaluated according to cellular morphology and DNA content measured by flow cytometry.Meanwhile,rhodamine 123 (Rh123) staining and flow cytometry assay were used to detect the changes of mitochondrial transmembrane potentials (△ψm) in MM cells before and after the treatment.The synergic effects of 8-Cl-cAMP and As2O3 were evaluated by King' s formula.Results The 8-Cl-cAMP could induce growth inhibition of RPMI8226 and U266 cells in dose and time-related manners.The 8-Cl-cAMP could trigger apoptosis and △ψm collapse in MM cells through cellular morphology and flow cytometry analysis.As2O3 accelerated 8-Cl-cAMP-mediated apoptosis of RPMI8226 cells,but there were few synergic effects observed.Conclusion 8-Cl-cAMP could induce cell proliferation inhibition and apoptosis in MM cells.Mitochondria may be one of targets in 8-Cl-cAMP-mediated apoptosis.Furthermore,As2O3 catalyzes 8-Cl-cAMP-induced apoptosis.

Aim To observe the improved effects of Shuangshen Ningxin capsule on ventricular remodeling and wall motion in myocardial ischemic miniature swine induced by thrombus.Methods Myocardial ischemic model miniature swine induced by self-thrombus via cardiac catheter in left anterior descending coronary artery(LAD)were administrated Shuangshen Ningxin capsule for 6 days.The changes of cardiac form,left heart systolic and diastolic function,left ventricular wall motion were observed by the technology of conventional ultrasound and Doppler tissue imaging.Results 6 days after myocardial ischemia and administration,miniature swine of model group showed ventricular wall thinning,chambers heart dilating,ventricle remodeling and wall motion weak,but Shuangshen Ningxin capsule obviously lowered left ventricular internal diameter at end-diastole(LVIDd),left ventricular internal diameter at end-systole(LVIDs),end-systolic volume(ESV),end-diastolic volume(EDV)and isovolumic relaxation time(IVRT),and increased ejection fraction(EF),tissue velocity and tissue trace of left ventricle anterior wall cardiac apex segment.Conclusion Shuangshen Ningxin capsule has anti-myocardial ischemia effect by improving left ventricular remodeling,increasing left cardiac work,improving left heart systolic and diastolic function and increasing left ventricular wall motion.

Objective To evaluate the efficacy of pegaspargase (PEG-ASP) combined with GEMOX regimen for the treatment of extranodal natural killer (NK) / T-cell lymphoma (ENKL),and to observe the changes of coagulation function.Methods 35 patients with histologically confirmed ENKL were enrolled from January 2010 to December 2014.All patients received 180 cycles of PEG-ASP combined with GEMOX chemotherapy and the efficacies were observed.The coagulation items such as prothrombin time (PT),activated partial thromboplastin time (APTT),fibrinogen (Fbg) and international normalized ratio (INR) were tested respectively on day 1st,day 8th and day 14th of every treatment cycle.Results Among 35 patients,11 patients (31.43 ％) were in stage Ⅰ-Ⅱ,and 24 patients (68.57 ％) were in stage Ⅲ-Ⅳ.All patients were subjected to 180 cycles of PEG-ASP combined with GEMOX chemotherapy,and each case was estimated to receive 6 cycles.The overall response (CR+PR) rate (ORR) was 71.43 ％ (25/35),the ORR was 81.82 ％ (9/11) in stage Ⅰ-Ⅱ group,and 66.67 ％ (16/24) in stage Ⅲ-Ⅳ group.The increased PT and APTT and decreased Fbg were observed on day 8th of the chemotherapy.The increased APTT and decreased Fbg were still observed on day 14th of the chemotherapy.Compared the data of patients one day before chemotherapy with healthy persons,the changes had statistical significance (P ＜ 0.05).Conclusions PEG-ASP combined with GEMOX regimen in the treatment of ENKL is safer and more effective compared with traditional chemotherapy,but the abnormal alternations of coagulation might be common during therapy.Dealing with the bleeding risk and supplement with plasma,PPSB or Fbg in time should be necessary.

OBJECTIVE:To investigate the efficacy and safety of carvedilol in patients with chronic heart failure(CHF). METHODS:46patients with CHF were randomly divided into carvedilol group(n=26)and control group(n=20),thareinto,standard therapeutic scheme is used in control group,standard therapeutic scheme+carvedilol is used in carve diol greup.The treatment courses were6months in both groups.RESULTS:Left ventricular end-diastolic diameter(LVEDD)reduced and left ventricular ejection fraction(LVEF)increased in carvedilol group with significant difference comparing with control group(P

Objective To investigate the effects of arsenic trioxide (AS2O3)on SOCS-1 gene methylation and expression of P-STAT3 in multiple myeloma (MM) cells.Methods MM cell lines U266 and CZ-1 were used as in vitro models.Methylation status of SOCS-1 gene was detected by the methylation specific PCR (MSP)while P-STAT3 protein expression was determined by Western blotting assay before and after AS2O3 treatment.Meanwhile growth inhibition and apoptosis of MM cells were determined by flow cytometry.Results Hypermethylation of SOCS-1 gene was observed in each MM cell line compared with wide type.After exposure to AS2O3,it was shown that SOCS-1 gene was demethylated obviously,meanwhile the expression level of P-STAT3 protein and cell proliferation was inhibited significantly in each cell line.The apoptosis rate was increased.When U266 and CZ-1 were treated with AS2O3 of 0,0.5,1.0,2.0 μmol/L respectively,the total cell apoptosisis ratio of U266 was 0.06％,0.56％,48.96％,61.07％ (X2 =9.19,P ＜ 0.05); and the total cell apoptosisis ratio of CZ-1 was 4.2％,,40.3％,,47.72％,,68.49％ (X2 =8.96,P ＜0.05 ).Conclusion AS2O3 could inhibit JAK/STAT signal transduction pathway by inducing SOCS-1 gene demethylation in MM cells which might be related to cell apoptosis.

10.3969/j.issn.1007-3969.2013.04.010

OBJECTIVE: To explore the antitumor activities of kushen (Sophora flavescens) flavonoids (KS-Fs) in vivo and in vitro. METHODS: Cell proliferation was assayed by using methyl thiazolyl tetrazolium (MTT) method. H22 hepatocellular carcinoma and S180 sarcoma were induced in ICR mice. Lewis lung carcinoma was induced in C57BL/6 mice. H460 and Eca-109 tumor were induced in Balb/c nude mice by injecting 5x10(5) or 5x10(6) tumor cells in the right flank, respectively. RESULTS: KS-Fs could inhibit the growth of a variety of human tumor cell lines (A549, SPC-A-1, NCI-H460, etc.) in vitro. The antitumor efficacies were confirmed in the mice models of H22, S180 and Lewis lung tumors and the nude mice models of human H460 and Eca-109 xenografted tumors. The oral or intravenous maximum tolerated dose of KS-Fs was more than 2.8 g/kg or 750 mg/kg respectively, far more than the oral medial lethal dose of kushen alkaloids (< or = 1.18 g/kg). No adverse reactions were observed. CONCLUSION: These results suggest that KS-Fs or kurarinone may be developed as a novel antitumor agent.