Aim To investigate the effects of leptin on ?1(Ⅰ) collagen mRNA expression and protein production, and the roles of Janus kinase/signal transducers and activators transcription(JAK/STAT) signaling transduction pathway in increased ?1(Ⅰ) collagen mRNA expression stimulated by leptin in activated hepatic stellate cells(HSCs).Methods Firstly, ?1(Ⅰ) collagen mRNA expression and protein production as well as JAK1 and STAT3 phosphorylation induced by leptin at different doses in a human HSC cell line, LX-2 were determined by RT-PCR, ELISA, and Western-blot.Secondly, the effects of JAK1 inhibitor AG490 on JAK1 phosphorylation and ?1(Ⅰ) collagen mRNA expression stimulated by leptin were detected by Western blot and RT-PCR. Thirdly, the roles of AG490 and transfection with STAT3 antisense oligonucleotide(STAT3-ASON) in STAT3 phosphorylation after leptin were detected by Western blot. Finally, the effect of transfection with STAT3-ASON on ?1(Ⅰ) collagen mRNA expression after leptin was measured by RT-PCR.Results Leptin increased ?1(Ⅰ) collagen mRNA expression and protein production in a dose-dependent manner in LX-2, reaching a maximal level at 80 ?g?L-1 leptin. In addition, phosphorylation of JAK1 and STAT3 after leptin exhibited a time-dependent effect. Besides, JAK1 inhibitor AG490 completely blocked JAK1 and STAT3 phosphorylation and increased in ?1(Ⅰ) collagen gene expression after leptin in LX-2. Transfection with STAT3-ASON blocked STAT3 phosphorylation and increased ?1(Ⅰ) collagen mRNA by leptin in LX-2.Conclusion Leptin had a direct action on liver fibrogenesis by stimulating ?1(Ⅰ) collagen mRNA expression and protein production in activated HSC, and JAK/STAT signaling transduction pathway was involved in the process. JAK1 inhibitor AG490 and transfection with STAT3-ASON blocked the transduction pathway effectively in LX-2. Leptin may be an important factor in the development of hepatic fibrosis. Activated JAK1 and STAT3 signaling in human HSC line provided a novel molecular target for therapeutic intervention of liver fibrosis.

BACKGROUND: Peri-intraventricular hemorrhage (PIVH) in preterm infants is one of the most important reasons for mortality and disability. Moreover, investigative exponents may bring supported data for incidence rate of PIVH and high-risk factors of preterm infants with PIVH.OBJECTIVE: To explore the incidence rate and analyze the high-risk factors of PIVH in preterm infants.DESIGN: Survey and analysis.SETTING: Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology; Beijing Obstetrics & Gynecology Hospital, Capital Medical Universit; Qinhuangdao Maternity and Infants' Hospital of Hebei Province.PARTICIPANTS: A total of 1 122 preterm infants of 26.3-36.8 gestational age were selected from Beijing Obstetrics & Gynecology Hospital, Qinhuangdao Maternity and Infants' Hospital from January 2002 to August 2005. All infants received ultrasonic examination on skull within 1 week. There were 594 boys and 528 girls, and the birth weight was 850-4 500 g.METHODS: All infants received ultrasonic examination on skull within 1 week. New Philips 5500 and GE Healthcare Logiq 400 ultrasonic diagnosis devices were provided by Philip Company, Dutch and GE Company, respectively.MAIN OUTCOME MEASURES: The incidence rate and related high-risk factors of PIVH.RESULTS: All 1 122 preterm infants were involved in the final analysis. Among 1 122 preterm infants, 619 cases (55.2%) had PIVH; especially, 110 had severe PIVH with the degree more than Ⅲ, which was accounted for 17.8%.High-risk factors were mainly low gestational age, low birth weight, mechanical ventilation, hypoglycemia, hypercapnia,hyperlactic acidemia, acidosis, hypoxia, abnormal blood coagulation, and so on. Antenatal corticosteroid could reduce the incidence rate of PIVH. However, there was no obvious effect on preterm infants of old gestational age.CONCLUSION: Routine intracranial ultrasonic examination is useful for the diagnosis of PIVH in preterm infants.

Objective To investigate the clinical,electroencephalogram (EEG) and genetic features of nocturnal frontal lobe epilepsy (NFLE) in the Chinese population.Methods Clinical examination,EEG recording,mutation screenings in transmembrane domains 1-3 of neuronal nicotinic acetylcholine receptor (nAChR) α4 (CHRNA4),β2 (CHRNB2) and α2 (CHRNA2) using PCR amplification and sequencing were carried out on 6 patients and some members in 3 families with NFLE.Results Among 6 patients (5 male) with NFLE,the mean age was (20.5±11.5) years and the mean age at onset was (7.3±5.5) years.Clinical features included seizures of dystonic posturing in 2 patients and seizures of hyperkinetic movements in 4 patients with the maximum frequency of 6 seizures within one night.The ictal and interictal video-EEG (VEEG) of frontal lobes showed epileptic discharges,slow wave activity,normal activity or electrode artifacts.There weren' t abnormity in other clinical examination and neuroimagings.No mutations were identified in the genes screened.Conclusion NFLE is a heterogenetic epilepsy syndrome.

Objective To investigate whether paclitaxel can efficiently induce the apoptosis of ovarian cell HO-8910,and to study the relationship between the apoptosis of cells and the cell cycle.Methods With the treatment of paclitaxel with different concentrations and different time,the morphologic change of HO-8910 ovarian cells was observed using fluorescence microscopy and transmission electron microscopy(TEM),and the apoptosis of cells and the changes of cell cycle were determined by flow cytometry(FCM). Results The typical changes of HO-8910 cell apoptosis were observed by TEM and Fluorescence microscopy.With the treatment of paclitaxel,the HO-8910 ovarian cells were firstly arrested in G_2/M phase,and the typical ultrastructural changes of apoptosis were appeared only after the cells were apparently arrested in G_2/M phase.Conclusion Paclitaxel can induce the apoptosis of HO-8910 cells and the apoptosis is associated with the blockage of G_2/M phase in cell cycle.

Objective: To investigate the preparation procedure of Zhenjing Xiehuo granules. Methods: Using the dry extract yielding rate and the contents of liquiritin and salvianolic acid B as the indices, an orthogonal test was adopted to choose the best ex-traction and purification technology. Using the qualified ratio of granules as the index, an orthogonal test was adopted to choose the best preparation process of the granules. Results:The optimized preparation conditions were as follows:Pulvis ferri was decocted first for 60 min. The other medicines were dipped in 8-fold amount of water for 90 min, and then added into pulvis ferri extracts and decocted for 3 times with 90 min for each time. The extracts were collected and concentrated till the relative density was 1. 3 (measured at 60℃), water was added with the dilution ratio of 1:2, ethanol was added till the percentage of ethanol was 50%, and then the mixed liquid was filtered after 24 hours. After ethanol was recycled from the filtrate, the filtrate was concentrated till the relative density was 1. 3 (measured at 60℃), and then dried at 60℃. Starch as the diluent, the ratio of extract to excipient was 1:0. 8, and the wet granules were prepared with 90% ethanol as the wetting agent, dried 3 hours at 60℃ followed by size stabilization to obtain the products. Con-clusion:The optimized preparation procedure of Zhenjing Xiehuo granules is stable and feasible.

Objective To evaluate the value and feasibility of tissue mitral annular displacement (TMAD) in the assessment of left ventricular global and segmental longitudinal systolic function and synchronization in patients with hypertrophic cardiomyopathy.Methods The study population consisted of 39 on-obstructive hypertrophic cardiomyopathy (nHCM) patients and 39 healthy volunteers matched by gender and age.Left ventricular global and segmental longitudinal were measured by speckle tracking imaging(STI).The mitral annular displacement (MAD) (anterioseptal,posterioseptal,anterior,lateral,posterior and inferior sites,respectively),peak of time (PT) and left ventricular systolic dyssynchrony index (SDI) were measured by TMAD.The correlation between LSR and MAD was analyzed,and the parameters of MAD and SDI for tow groups were compared.Results The rate of effectively track segments of TMAD was significantly higher than that of STI(98.7％ vs 77.9％,P ＜0.001).There were high correlationship between segmental LSR and MAD(r =-0.784,P ＜0.001),and global and MADglobal (r =-0.897,P ＜0.001).Compared with the control group,MAD of six spots and MADglobal were significantly decreased (P ＜ 0.001,respectively),SDI was significantly increased(P ＜0.001).Conclusions TMAD is a sensitive and reproducible method for the assessment of LV longitudinal functionin patients with nHCM.

Pain is one of the common clinical symptom, previous studies have implicated sodium channels as a key constituent in pain signaling. Sodium channel blockers with efficient sodium channel blockade effect play an important role in analgesic treatment. However, most drugs used in clinic have many drawbacks and can not meet the demand of the clinical use. Therefore, for the development of new generation of sodium channel blockers, it is of great significance to find small molecule sodium channel blocking lead compounds with novel chemical scaffolds and new structures, sodium channel blocking activity and structure-activity relationship are discussed in detail, and current problems and trends in future research are also emphasized.
Analgesics ; chemistry ; pharmacology ; therapeutic use ; Animals ; Drug Design ; Humans ; Molecular Structure ; Neuralgia ; drug therapy ; Pain ; drug therapy ; Pain Measurement ; Sodium Channel Blockers ; chemistry ; pharmacology ; therapeutic use ; Sodium Channels ; drug effects ; Structure-Activity Relationship

Objective To obtain monoclonal antibodies ( mAbs ) against neutrophil gelatinase-associated lipocalin ( NGAL ) and a chemiluminescense immune quantification assay based one paired mAbs.Methods Six-to-eight weeks old female BALB/c mice were immunized with the purified recombinant human NGAL antigen( rhNGAL) that was produced by the Escherichia coil expression system.The spleen was fused with hybridoma for screening anti-NGAL monoclonal antibodies by indirect ELISA.Western blot was implemented to identify the reactivity with native NGAL. Results The rhNGAL antigen was found to form disulfide cross-linked dimers and present excellent immunogenicity.The reaction titer of the immune serum of NGAL immunized mice was about 106.Thirty mAbs were screened by indirect ELISA, hereinto;the EC50 values of mAb23C12 and 38D10 were 0.034 g/mL, 0.022 g/mL respectively.The antibodies pair, 38D10/23C12-SAE labeled with AcridiniumEster(AE), were shown to work well in chemiluminescense immune response quantitative detection which was screened by NGAL standardand clinical urine samples.This detection can resolve positive and negative samples with a statistically significant difference (P<0.0001).And the correlation coefficient R2between NGAL quantitative results and that of the Abbott's NGAL chemiluminescence immune assay kit was greater than 0.97.The detection linear range was 10-1500 ng/mL, analytical sensitivity of the method was 0.63 ng/mL.Conclusion Highly purified rhNGAL antigen and specific anti-NGAL monoclonal antibodies are generated in this study.The detection capability of method is comparable with that of the international commercial kit.

0bjective To investigate the characteristics of myocardial acceleration (ACC) in normal left ventricle(LV)by velocity vector imaging (ⅤⅥ). Methods The myocardial velocities of sixteen LV wall segments in fifty normal volunteers were detected by ⅤⅥ.Segmental myocardial ACC was calculated by using special software and the distribution of ACC in LV wall was analyzed.Results There were significant differences among the levels of LV in the early systolic peak ACC (ACCs) and early diastolic peak ACC (ACCd),and both of ACCS and ACCd increased from apex to base in the same LV wall (allP＜0.05). However,there were no significant differences among six LV walls at the same level in ACCs and ACCd(allP＞0.05).In the same segment,ACCd was significantly higher than ACCs (all P＜0.05).Conclusions Myocardial ACC can be detected by ⅤⅥ.which is the basis for further investigation of ACC in the diseased myocardium.

Background and Purpose:Lung cancer is the most malignant tumour in the world.Its incidence is growing and NSCLC is predominent(80%) in lung cancer.Most patients with lung cancer were diagnosed in late stages.The tumour could be shrunk by neoadjuvant chemotherapy when the case with stage Ⅲ NSCLC was considered not possible for radical operated neoadjuvant chemotherapy may lead to the following,operation could be improved,micrometastasis could be annihilated and survival could be extended.Objective of this paper was to analyse the prognostic factors for survival in patients treated by surgery and chemotherapy for NSCLC.Methods:98 cases of neoadjuvant chemotherapy combined with surgery for NSCLC,stageⅠ~Ⅲ,were collected retrospectively in our hospital from 1995 to 1997.35 cases were stageⅠ.21 cases were stage Ⅱ.42 cases were stage Ⅲ.83 cases had 1 cycle of chemotherapy pre-operatively.15 cases had 2 cycles chemotherapy pre-operatively.Regimes of chemotherapy were MVP,MOP and MAP et al.Response rate(RR) of chemotherapy was:45 cases had partial response(PR) and 53 cases were stable disease(SD).Operative mode was lobectomy and pneumectomy with lymph nodes dissection.Pathologic type was squamous,adeno,adeno-squamous and others.All the patients were treated by chemotherapy for two or three cycles after surgery except for the patients in stageⅠin 1996~1997.After being followed-up for more than 5 years,data were examined using life table,KaplanMeier method,Log Rank statistic and Cox-mantel test.The possible factors affecting survival were tested with univariate and multivariate analysis.Results:The median followed-up time of 98 cases for NSCLC was 41.2 months.36 cases were alive.62 cases were dead.The 1-,3-,5-year survival rate of 98 cases for NSCLC was 88.78%、49.63% and 18.46%.The 5-year survival rates of stageⅠ、ⅡandⅢ were 33.23%、20.26% and 5.52% respectively(P=0.0002).The 5-year survival rates of N_(0)、N_(1)、N_(2) were 35.49%、19.08% and 4.90% respectively(P=0.0004).In the 98 cases of NSCLC,better prognosis was correlated with earlier stage.The prognosis was better if the period from last chemotherapy before operation to operation was no more than 1 month. The prognosis of lobectomy,lung hila activity,thorax lymph nodes negativity and squamous cancer was better.The prognosis was poorer if the tumor had invaded big vessels,viscera,chest wall,pericardium and quantity bleeding during≥400ml.The prognosis was better if the tumor was fibrotic.The prognosis of 2 cycles of chemotherapy pre-operatively might be better than 1 cycle.The prognosis of tumor necrosis was poorer and the prognosis of chemotherapy post-operatively was better.Conclusions:The main prognostic factors affecting survival in patients treated by surgery and chemotherapy for NSCLC was stage,the period from last chemotherapy before operation to operation,operation mode,lung hila activity,thorax lymph nodes,site of tumor invasion,bleeding quantity,pathologic type,tumor fibrosis and necrotis,cycles chemotherapy pro-operation and chemotherapy post-operation.