Objective To observe the relationship between Toll-like receptor 4 (TLR4) and the sensitivity of PANC1 cells to gemcitabine (GEM),and to analyze the potential mechanism.Methods PANC1 cells were divided into GEM group,lipopolysaccharide (LPS) + GEM group and TLR4-siRNA + GEM group.GEM group was treated by GEM alone.LPS + GEM group was pretreated with 1 mg/L LPS for 4 h and then treated by GEM.TLR4-siRNA + GEM group was transfected with 100 pmol/mL TLR4-siRNA for 4 h and then treated by GEM.The untreated cells were used as the control group.MTT method was used to detect the cell proliferation.Morphological changes and apoptosis rate of the cells were examined by Hoechst33258 staining and flow cytometry,respectively.The protein expression of TLR4,phosphorylated AKT (p-AKT) and activated Caspase-3 were detected by Western blot.Results The median inhibition concentration (ICs0) of GEM in the GEM group,LPS + GEM group and TLR4-siRNA + GEM group was (8.9 ± 0.32),(14.21 ±0.95),(3.96 ± 0.27) mg/L,respectively.The IC50 in LPS + GEM group was significantly higher than that in GEM group (P ＜ 0.01),and the IC50 of GEM in TLR4-siRNA + GEM group was significantly lower than that in GEM group (P ＜0.01).Compared with that in GEM group,the cells with typical apoptotic morphological changes were decreased in LPS + GEM group,which was increased in TLR4-siRNA + GEM group.The apoptotic rate in control group,GEM group,LPS + GEM group,TLR4-siRNA + GEM group was (2.1 ± 0.3) ％,(15.1 ± 2.3) ％,(9.8 ± 1.5) ％,(22.9 ± 3.1) ％,respectively.Compared with that in GEM group,the cells apoptotic rate was significantly reduced in LPS + GEM group (P ＜0.01),which was significantly increased in TLR4-siRNA + GEM group (P ＜0.01).TLR4 protein level in the 4 groups was 0.83 ±0.08,0.81 ±0.07,0.85 ±0.07 and 0.16 ±0.03;p-AKT protein level 0.61 ±0.05,0.36 ±0.03,0.73 ± 0.07 and 0.21 ± 0.02;activated Caspase-3 protein level was 0.66 ± 0.05,0.73 ± 0.07,0.45 ± 0.04 and 0.91 ± 0.07,respectively.The expression of TLR4 and p-AKT in TLR4-siRNA + GEM group was significantly lower than that in GEM group (P ＜0.01),while the expression of activated Caspase-3 protein was increased significantly (P ＜ 0.05).Compared with the GEM group,the expression of p-AKT protein in LPS + GEM group was significantly increased (P＜0.01),and the expression of activated Caspase-3 protein was significantly decreased (P＜0.01).Conclusions TLR4 can inhibit the sensitivity of pancreatic cancer PNAC1 cells to GEM,and the mechanism is related to the activation of PI3K/AKT pathway and downregulation of activated Caspase-3.

Objective To investigate the role of TLR4/NF-kB signaling pathway in inhibited invasion ability of pancreatic cancer cells caused by triptolide (TP).Methods PANC1 cells were divided into parental cells group,TP group,lipopolysaccharide (LPS) group and TP + LPS group.50 ng/ml of TP was added in culture medium in TP group,and 1 μg/ml of LPS was added in culture medium in LPS group,while 50 ng/ml of TP was pretreated for 2 h and 1 μg/ml of LPS was added in culture medium in TP + LPS group.All the ceils were cultured for 24 h.The TLR4 and matrix metalloproteinase-9 (MMP-9) mRNA and protein expression were evaluated by real-time PCR and Western blot.The NF-kB activity was determined by dual-luciferase reporter assay system.The invasion ability of pancreatic cancer cells was evaluated by transwell invasion chamberassay.Results The TLR4 mRNA expressions in parental cells group,TP group,LPS group and TP + LPS group were 0.41 ± 0.06,0.46 ± 0.10,0.20 ± 0.04,0.25 ± 0.06 ; the TLR4 protein expressions were 0.55 ±0.06,0.55 ±0.06,0.18 ±0.04,0.13 ±0.00; the activities of NF-kB were 13.0 ±3.0,31.6 ±4.3,7.3 ±1.5 and 10.8 ± 2.1,and the numbers of invasion cell were (56.8 ± 8.6),(104.5 ± 12.8),(32.0 ± 5.7) and (46.8 ± 7.0) ; the MMP-9 mRNA expressions were 0.36 ± 0.05,0.58 ± 0.07,0.18 ± 0.03,0.30 ± 0.004 ;the MMP-9 protein expressions were 0.31 ± 0.04,0.53 ± 0.08,0.11 ± 0.02,0.15 ± 0.00.In LPS group,TLR4 mRNA and protein expressions were not statistic significant when compared with those in parental cells group,but the activities of NF-kB,the numbers of invasion cell,MMP 9 mRNA and protein expressions were statistically increased when compared with those in parental cells group (t =8.654,7.593,6.655,4.982,P ＜0.01).TLR4 mRNA and protein expressions,activities of NF-kB,the numbers of invasion cell,MMP 9 mRNA and protein expressions in TP group were significantly lower than those in parental cells group (t =-7.609,-9.948,-4.176,-5.915,-8.179,-9.948,P＜ 0.01).TLR4 mRNA and protein expressions,activities of NF-kB,the numbers of invasion cell,MMP 9 mRNA and protein expressions in TP +LPS group were significantly lower than those in LPS group (t =-4.437,-14.805,-10.506,-9.700,-9.055,-8.932,P＜ 0.01).Conclusions TP can inhibit pancreatic cancer cell invasion,and the mechanism is related to the inhibition of TLR4/NF-kB signaling pathway and down-regulation of MMP-9 expression.

AIM: To investigate the influences of native and oxidized lipoprotein(a) on human arterial smooth muscle cell (SMC) proliferation, change of intracellular free calcium concentration ([Ca 2+ ] i) and the protective effect of sodium ferulate(SF). METHODS: Lp(a) was oxidized by Cu 2+ and the extent of oxidation was assessed by the MDA content.Human SMC were incubated in culture media with SF for 12 h, then exposed to Lp(a) and oxidized-Lp(a), respectively. MTT colorimetry and flow cytometry were used to evaluated the proliferation of SMC and flurorescent indicator Fura-2/AM was used to determined [Ca 2+ ] i. RESULTS: ox-Lp(a) significantly promoted proliferation of SMC and increased[Ca 2+ ] i compared with Lp(a). SF(40,80 mg/L) remarkedly inhibited SMC proliferation and decreased the rising of [Ca 2+ ] i induced by ox-Lp(a) in a dose-dependent manner, but no effect on SMC proliferation and the increase in [Ca 2+ ] i induced by Lp(a).CONCLUSION: ox-Lp(a) induces the strong growth-promoting effect in SMC through increasing in [Ca 2+ ] i, which might be one of the cellular mechanisms responsible for the higher atherogenic potential of ox-Lp(a) compared with Lp(a), and this process can be prevented by inhibiting of oxidation by SF.

Adult ; Female ; Granuloma, Plasma Cell ; pathology ; Humans ; Maxillary Sinus ; pathology ; Paranasal Sinus Diseases ; pathology

Objective To investigate whether non-critical coronary stenosis can be detected by coherent contrast imaging(CCI) at rest without stress.Methods Three degrees of stenosis were made in left anterior descending of 12 dogs.Myocardial contrast echocardiography(MCE) was performed with CCI and the correlation among the variables of MCE curve and the degrees of stenosis were analyzed by cubic regression.Results The time to peak was significantly prolonged with progressive coronary stenosis (P＜0.01) and related to the degree of stenosis (R~2=0.991,P＜0.001).Conclusions CCI could be used to detected non-critical coronary stenosis at rest without stress.

might be related to the growth and metastasis of HCC.

Objective To investigate the risk factors for childhood acute leukemia complicated with streptococcus mitis bacteriaemia and to explore a better therapeutic regimen of antibiotics.Methods Seventy-eight cases of childhood acute leukemia complicated with bacteriaemia hospitalized in Zhujiang Hospital of Southern Medical University from January 2012 to December 2016 were collected,among them there were 8 cases (10.26％) caused by streptococcus mitis.The susceptible factors,clinical manifestations,drug susceptibility,treatments and outcomes of 8 cases of streptococcus mitis bacteriaemia were summarized and analyzed.Results All of 8 cases were attacked during the agranulocytosis phase lasting for more than 1 week after chemotherapy for acute leukemia.Four cases of them had been exposed to the third-generation cephalosporins for more than 7 days,and 5 cases exposed to proton pump inhibitor (PPI) for more than 10 days.The incidence of remittent fever,shiver,stomatitis and pneumonia was 100.0％ (8/8 cases),62.5％ (5/8 cases),62.5％ (5/8 cases) and 62.5％ (5/8 cases),respectively.And severe pneumonia occurred at a rate of 37.5％ (3/8 cases).The sensitivity to Linezolid,Vancomycin,Penicillin and Cefotaxime was 100.0％,100.0％,37.5％ and 25.0％,respectively.Five of the 7 cases treated with Meropenem had a fever 3 days later and then they took Linezolid as a replacement according to the drug sensitivity.One case was treated with Cefoperazone-Sulbactam.The duration time of fever,positive blood culture,agranulocytosis and course of antibiotics therapy was 1-19 d(10.4 d on average),4-22 d(13.4 d on average),10-30 d (21.6 d on average),9-26 d (18.3 d on average),respectively.Among 3 patients with severe pneumonia,1 patient received the respirator assisted ventilation for 1 week.Conclusions Streptococcus mitis is one of the major causes of severe infection among children with acute leukemia.Agranulocytosis after chemotherapy,stomatitis,exposure to PPI and antibiotics may be the risk factors for streptococcus mitis infection.Fever,stomatitis,respiratory and digestive symptoms are the common clinical manifestations.Streptococcus mitis is resistant to Penicillin and Cefotaxime,but sensitive to Linezolid,which can shorten the course of infection and improve the outcomes.Thus,Linezolid may serve as an optional therapy for streptococcemia mitis bacteriaemia.

Objective To observe the efficacy and side effects of combined therapy with victoria A acid,arsenic trioxide and chemotherapeutics for newly diagnosed acute promyelocytic leukemia (APL). Methods 40 cases of patients were treated with combined therapy of ATRA, As2O3 and chemotherapy. The efficacy and side effects were analysed. Results 92.5 % (37/40) achieved complete remission(CR). The CR time was 27(22-61) d by average; leukocytes≥ 10×109/L group complete remission was 72.7 % (8/11), leukocytes < 10×l09/L group complete remission was 100 % (29/29). There was a significant different (x2 =8.550, P =0.004). No severe side effects was observed except one who developed retinoic acid syndrom. Conclusion The combined regimen of ATRA and As2O3 with chemotherapy for acute promyelocytic leukemia should be the first choice management.

Abstract: Objective To study the effect and mechanism of Huaxian Sanjie compound granule on silicosis fibrosis in rats. Methods The specific pathogen free male SD rats were randomly divided into control group, silicosis model group and - interventiongroup,withsixratsineachgroup.Disposableventilatorcombinedwithnon exposedintratrachealdripwasused,the ratsinthesilicosismodelgroupandinterventiongroupweretreatedwith 1.0mLsilica suspensionwithamassconcentrationof 50.0 g/L to establish silicon dust rat model, while the rats in the control group were treated with equal volume of 0.9% sodium chloride solution. After 24 hours of dust exposure, the rats in the intervention group were given 10 mL/kg body weight of Huaxian Sanjie compound granule suspension with a mass concentration of 212.5 g/L by gavage, while the rats in the control group and silicosis model group were given the same amount of 0.9% sodium chloride solution, once a day. Three rats in each groupweresacrificedonthe14thand28thday,respectively,andtheirlungtissueswereseparatedforpathologicalexamination.----Thelevelsofinterleukin6(IL6)andtransforminggrowthfactorβ