Hedgehog (Hh) pathway plays a critical role in embryonic development period,which regulates cell proliferation and differentiation,and coordinates the key step of organs' development process such as skin,brain,neural tube,bowels,appendage and lung.In the adult stage,Hh signaling regulates proliferation of stem cells.At this time,Hh signaling is strictly controlled by time and space.In recent years,studies have shown aberrant activation of the Hh pathway is closely related to various types of malignancies,and would be a new therapeutic target of tumor treatment.This paper will review the characteristic of Hh signaling pathway and its research status in lung cancer.

Objective:To explore the inhibitory effects of gefitinib (epidermal growth factor receptor inhibitor) com-bined with celecoxib (cyclooxygenase-2 inhibitor) against human lung cancer A549 cells and the possible mechanism. Methods: A549 cells were cultured in RPMI 1640 medium and were divided into 4 groups: normal control group, 5 μmoL/L gefitinib group, 25 μmol/L celecoxib group, and 5 μ mol/L gefitinib + 25 μmol/L celecoxib group. The morpho-logical changes of A549 cells were observed under inverted microscope 48 h after treatment ; the effects of drugs on growth of A549 Cells were detected by MTT assay; the apoptosis and cell cycles of A549 cells were measured by Annexin V/PI and Hoechst 33258 staining, respectively; and the expression of EGFR protein, COX-2 protein, and EGFR mRNA were determined by immunofluorescenee and real-time PCR. Results: Compared with gefitinib and celecoxib groups, many granules and vacuoles were observed in the gefitinib and celecoxib combination group, and cells became round and there was defluxion. Both gefitinib and celecoxib inhibited the growth of A549 cells in a time- and dose-dependent manner. Af-ter treatment for 48 h, the inhibitory rate was (58.2±4.6) % in the combination group, which was significantly higher than those of the other two groups. Apoptosis rate in the combination group was also significantly higher than those in the other two groups (33.9% vs 6.0%, 8.8%), and the cell proportion in S phase significantly decreased and in G_0/G_1 phases significantly increased(P <0.01). EGFR protein, COX-2 protein, and EGFR mRNA expression in A549 cells was significantly decreased in the combination treatment group compared with those in the other two groups (P < 0.05). Conclusion : Gefitinib and celecoxib can synergistically inhibit the growth of A549 cells, possibly through promoting apop-tosis, G_0/G_1 arrest, and down-regulating activated EGFR and COX-2 expression.

Objective:To explore the inhibitory effects of gefitinib(epidermal growth factor receptor inhibitor) combined with celecoxib(cyclooxygenase-2 inhibitor) against human lung cancer A549 cells and the possible mechanism.Methods: A549 cells were cultured in RPMI 1640 medium and were divided into 4 groups: normal control group,5 ?mol/L gefitinib group,25 ?mol/L celecoxib group,and 5 ?mol/L gefitinib+25 ?mol/L celecoxib group.The morphological changes of A549 cells were observed under inverted microscope 48 h after treatment;the effects of drugs on growth of A549 Cells were detected by MTT assay;the apoptosis and cell cycles of A549 cells were measured by Annexin V/PI and Hoechst 33258 staining,respectively;and the expression of EGFR protein,COX-2 protein,and EGFR mRNA were determined by immunofluorescence and real-time PCR.Results: Compared with gefitinib and celecoxib groups,many granules and vacuoles were observed in the gefitinib and celecoxib combination group,and cells became round and there was defluxion.Both gefitinib and celecoxib inhibited the growth of A549 cells in a time-and dose-dependent manner.After treatment for 48 h,the inhibitory rate was(58.2?4.6)% in the combination group,which was significantly higher than those of the other two groups.Apoptosis rate in the combination group was also significantly higher than those in the other two groups(33.9% vs 6.0%,8.8%),and the cell proportion in S phase significantly decreased and in G0/G1 phases significantly increased(P

Objective To investigate the association of α-synaptophysin A53T gene polymorphism with parkinson's disease(PD) in Chinese people.Methods The conventional polymerase chain reaction was used to detect the α-synaptophysin A53T gene polymorphism in 224 sporadic PD patients(PD group)and 154 healthy individuals(control group).According to the Hoehn-Yahr(H-Y) classification standard, PD patients were divided into H-Y ≥ 3 group(n=172) and H-Y ≤ 2.5 group(n=52).Each genotype and alleles frequencies as well as the A53T gene expression and their relation to the severity of parkinson's disease were analyzed with Chi-square test of SPSS19.0.Results The frequency of the A53T genotype of A/A were 40(17.9％) and 10(6.5％) (x2 =10.267, P=0.001, OR=3.13,95％ CI =1.514-6.473) in the PD group and control group, respectively.The frequency of the allele A was 160(35.7％) and 70(22.7％) (x2 =14.543, P=0.000, OR=1.889,95％ CI =1.359-2.625) in the PD group and control group,respectively.The frequency of the A53T genotype of A/A was 30(17.4％) and l0 (19.2％) in the H-Y ≥ 3 group and H-Y ≤ 2.5 group, respectively, with significant difference (P=0.003,0.007) as compared to the control group.The frequency of the allele A was 122(35.5％) and 38(36.5％) in the the H-Y ≥ 3 group and H-Y ≤ 2.5 group,respectively, with significant difference (P=0.000,0.006) as compared to the control group.There was no statistically significant difference of the A53T genotype of A/A and the allele A between the H-Y≥3 group and H-Y≤2.5 group (P=0.768,0.841).Conclusion The A53T gene polymorphism is the risk factor of Parkinson's disease in Chinese people, but it isn't correlated to stage of sporadic parkinson' s disease.

Objective To analyze the expression stability of the three widely used reference genes β-glueuronidase (GUSB), glycera]dehydes-3-phosphate dehydrogenase (GAPDH), β2-microglobulin (β2-M) in Chinese lung cancer tissue specimens and normal lung tissue specimens. Methods Gene expression wasmeasured by quantitative real time PCR and expression stability was analyzed with two widely used softwares genorm and normfinder. Results The intra-and inter-group difference of GAPDH is maximum (The intra and inter-group s is 1.07 and 0.93 respectively, |△ Ct|=2.01±1.06; P =0.000). The mean of these three genes' Ct value is the most stable one analyzed by the two softwares. But the t test showed that the mean of Ct value of GUSB and β2-M is the unique combination that had the minimum intra-and inter-group difference, with no statistically significant differences between normal and malignant samples (The intra-and inter-group s is 0.53 and 0.79 respective]y, |△Ct|= 0.73±0.53; P =0.053). Conclusion It is inappropriate to normalize data derived from lung tissue specimens using one of these three housekeeping genes alone. Among the different combinations of these three genes, the mean of the Ct values of GUSB and β2-M is the best choice as the internal control of lung tissue specimens.

Objective To investigate the effect of stellate ganglion block on the pain and quality of life in patients with lung cancer.Methods 90 patients with lung cancer were divided into observation group and control group according to random number table method.The control group was treated with morphine 10mg,orally,1 time/ 12h.The observation group was treated with stellate ganglion block and morphine.For the patients with poor analgesic effect,50％ doses were added gradually.The analgesic effect,quality of life and changes of immune function were compared between the two groups.Results After treatment,the VAS scores of the two groups were significantly decreased.And the VAS score reduction in the observation group was significantly better than that in the control group [(2.5 ± 0.7) points vs.(3.7 ± 0.9) points],the difference was statistically significant (t =7.060,P ＜ 0.05).The analgesic efficacy of the observation group was significantly higher than that of the control group(91.1％ vs.75.6％,x2 =3.920,P ＜ 0.05),the duration of analgesia of the observation group was longer than that of the control group (t =20.681,P ＜ 0.05).For the total morphine dosage method,the observation group was significantly lower than the control group[(143.5 ± 21.3) mg vs.(238.7 ± 38.3) mg] (t =14.572,P ＜ 0.05).After treatment,the scores of quality of life of the two groups were significantly improved,and the improvement degree of the observation group was significantly better than that of the control group [(86.5 ± 14.3) vs.(79.6 ± 15.7),t =2.179,P ＜ 0.05].After treatment,the TGF-beta level of the observation group was significantly reduced,which was significantly lower than that of the control group[(215.4 ± 38.7)pg/mL vs.(240.5 ± 41.2)pg/mL],the difference was statistically signifi cant (t =2.979,P ＜ 0.05).Conclusion Stellate ganglion block has good therapeutic effect in the treatment of lung cancer patients with pain.

Objective To investigate the prevention and nursing measures of chemotherapeutic phlebitis in hematonosis children.Methods 233 children with first-attack of hematonosis were admitted to our department from January 2010 to January 2012,among whom 80 cases appeared different degrees of chemotherapeutic phlebitis.The related factors of chemotherapeutic phlebitis were explained and the nursing measures were established.Results After effective nursing measures,the chemotherapeutic phlebitis were properly handled.Conclusions Correct selection of vascular puncture site,strict aseptic operation and implementation of relevant nursing measures can prevent the incidence of chemotherapeutic phlebitis,and local closure,using of patches and external application of scald ointment can be adopted to treat chemotherapeutic phlebitis.

Objective To explore the role of human urinary trypsin inhibitor(UTI) in severe acute pancreatitis (SAP). Methods UTI was highly purified from the urine of patients with acute pancreatitis by column chromatography. SAP models were established by injection of 5% sodium taurocholate(NaTc) at dose of 0.1 ml/100 g weight under pancreatic capsule. The interleukin 6(IL 6) level in each group was measured by ELISA. Results ① The highly purified UTI with high yield was harvested. ② SAP models were established successfully. ③ The level of IL 6 in SAP group was significantly higher than that in NC, but in UTI group, the increase was not obvious. Conclusion The alleviating effect of UTI on the pathological damage degree in rats with SAP is related to the inhibitive effect of UTI on the expression of IL 6.

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Objective To explore the role of phospholipase A2 receptor 1 (PLA2R1) in the diagnosis,differential diagnosis and evaluation of idiopathic membranous nephropathy (IMN) in adult patients.Methods A total of 242 renal disease patients diagnosed by renal biopsy from March 2015 to January 2016 were enrolled,consisting of 90 IMN,20 secondary membranous nephropathy (SMN),82 IgA nephropathy (IgAN),30 minimal changed disease (MCD),16 focal segmental glomerulosclerosis (FSGS) and 4 membranoproliferative glomerulonephritis (MPGN).Their clinical data including age,sex,serum creatinine (Scr),serum albumin and 24 h urinary protein were collected.Serum PLA2R1 was measured by enzyme linked immunosorbent assay.PLA2R and IgG subclasses in glomeruli were detected by indirect immunofluorescence assay.The positive rate of serum PLA2R1 among those groups and its correlation with clinical-pathological parameters were analyzed.Results Compared with IMN patients,SMN,MCD and FSGS patients were younger (all P ＜ 0.01); IgAN patients were younger and had higher serum albumin and lower 24 h proteinuria (all P ＜ 0.001); MPGN patients had higher Scr (all P ＜ 0.01).The positive rate of serum PLA2R1 was 75.6％ in IMN patients,while it was 0.0％ in non-IMN patients.The distribution between serum PLA2R1 and pathological diagnosis had difference (P ＜ 0.001),their positive coincidence rate was 100％,negative coincidence rate was 87.4％,total coincidence rate was 90.9％ and their consistency was well (Kappa=0.795,P ＜ 0.001).Among IgG subtype comparisons between IMN patients and SMN patients in the glomeruli,only moderate or more positive IgG4 had statistical differences (82.2％ vs 5.0％,P ＜ 0.001); the positive rate of glomerular PLA2R1 was 41.1％ in IMN patients,higher than 10.0％ in SMN patients (P=0.009); positive PLA2R1 with moderate or more positive IgG4 in glomeruli in IMN patients was more than that in SMN patients (40.0％ vs 0.0％,P ＜ 0.001),which could improve the diagnostic specificity of IMN.In IMN patients serum PLA2R1 and glomerular PLA2R1 had statistical differences (P＜0.001).Spearman rank correlation analysis showed that serum PLA2R1 of IMN patients positively correlated with 24 h proteinuria (r=0.315,P=0.002),negatively correlated with serum albumin (r=-0.228,P=0.030) and didn't correlate with Scr (r=0.199,P=0.059).Conclusions Serum PLA2R can be used as the specific indicator for diagnosis,differential diagnosis of IMN and to reflect the severity of IMN in patients.