Structure of natural product-ursolic acid was modified for increasing its antitumor activity. Ursolic acid was acylated, esterified, hydrolized or oxidized to obtain target pentacyclic triterpenoid compounds with different substitutes. Sixteen derivatives of ursolic acid were designed and synthesized including eleven new compounds. Anti-tumor activities of ursolic acid and these derivatives against HeLa, SKOV3 and BGC-823 cells in vitro were investigated by MTT assay. The results indicated that compounds 7a and 8a were found to have stronger cell growth inhibitory than ursolic acid on HeLa cells and SKOV3 cells separately, and are worth to be intensively studied further.

AIM: To observe the effect of mouse Sim2 (mSim2) eukaryotic expression vector transfection on the cell cycle in PC12 cells in vitro and to explore the role of Sim2 in the pathogenesis of Down syndrome. METHODS: The full open reading frame of mSim2 was amplified by reverse transcription-polymerase chain reaction (RT-PCR) and cloned into the vector pcDNA3. Then the constructed pcDNA3-Sim2 vectors were transiently transfected into PC12 with Lipofectamine~ TM . The expression of mSim2 was detected by RT-PCR. The effect of mSim2 on the cell cycle was observed by flow cytometry. RESULTS: The eukaryotic expression vector mSim2 was successfully constructed. There was notable expression of mSim2 in the cells transfected with pcDNA3-Sim2. There were more cells in G_0/G_1 phase in the pcDNA3-Sim2 transfected cells than that in the control (P

Background and purpose: Solid papillary carcinoma (SPC) is an uncommon histological pattern accounting for <1% of breast carcinomas. It is a distinctive form of papillary carcinoma characterized by closely apposed expansile, cellar nodules. The present study aimed to investigate the clinicopathologic features, immunophenotype and prognosis of SPC of breast. Methods:We retrieved the data of 32 cases of SPC of the breast from pathology files, and determined the expressions of ER, PR, C-erbB-2, p63, Calponin, CK5/6, Ki-67, Syn and CgA by pathohistological observation and immunohistochemical examination. Results:All the patients were females with a mean age of 67.3 years. The clinical features were a palpable mass or bloody nipple discharge. The tumor was observed as a whitish-grey or yellowish-brown, lfeshy ifrm or soft, nodular circumscribed mass on gross examination. Microscopy showed solid and papillary area inside the capsule wall and that fine delicate fibrovascular septa were discovered amid the solid proliferation. The tumor cells were oval, polygonal, spindled or signet ring-like with abundant eosinophilic cytoplasm and contained mildly to moderately pleomorphic nuclei. Immunohistochemically, all tumor cells were strongly positive for ER and PR (++-+++), negative for C-erbB-2 and all cases were negative for CK5/6, p63 and Calponin in the cellular nodules. The positive expression rates of Syn and CgA were 68.8%and 78.2%, respectively. The average positive rate of Ki-67 in tumor cells was 7.5%(2%-20%). Twenty-seven patients were available for follow-up examination from 6 to 84 months and 25 patients were alive and disease free. One patient had tumor recurrence, and was alive after reoperation. Another patient died of the tumor metastasis. Conclusion:SPC is predominantly found in elderly females with distinctive pathological features and immunophenotype. SPC often carries an indolent clinical behavior, and even if accompanied by inifltration, very rare cases have recurrence and metastasis after resection, so its prognosis is better.

Objective To evaluate expression and significance of TLR4 and NF-κB on inflammatory injure after intracerebral hemorrhage in rats .Methods 60 Sprague Dawley maleness rats were randomly divided into Sham group ,12 h ,24 h ,72 h and 7 d af-ter ICH group(12 s) .The ICH was induced by injection of autologous blood in rats .The behavioral changes were detected by neu-rologic deficit score .The water content of the brain was used to evaluate brain edema changes .Number of TLR4 and NF-κB positive cells by Nissl staining and the expression of protein determined by immunohistochemistry and Western blot .Results After ICH 12 h ,expression of TLR4 and NF-κB positive cells around the hematoma were expressed ,with the extension of the time ,expression was gradually increasing ,and after ICH 72 h the expression of protein were the highest .Cerebral edema and severe neurological damage occurred .Western blot shows the amount of TLR4 expression and NF-κB were in line with the result .Conclusion After in-tracerebral hemorrhage in rat causing inflammatory injure of brain tissue around the hematoma .TLR4 may activate the expression of NF-κB involved in the secondary inflammatory injure after intracerebral hemorrhage in rats .

The effect of electroacupuncture (EA) on TRPM7 mRNA expression of focal cerebral ischemia in rats and further the role of EA in the relationship between TRPM7 and trkA pathway was investigated. Thirty SD rats were randomly divided into 5 groups : normal group, ischemia/reperfusion group, EA treated group (ischemic rats with EA treatment), TE infusion group (ischemic rats with EA treatment and TE buffer infusion), AS-ODN group (ischemic rats with EA treatment and antisense trkA oligonucleotide infusion). The stroke animal model was established by the modified method of middle cerebral artery occlusion. Antisense trkA oligonucleotide that blocked NGFs effects was injected into cerebroventricle before EA. The TRPM7 mRNA was detected by RT-PCR method. The results showed that there were low TRPM7 mRNA levels in cortex and hippocampus in normal group. Compared with normal group, TRPM7 mRNA expression was increased significantly in ischemia/reperfusion group (P<0.05). A significant reduction in the expression of TR-PM7 mRNA was found in EA treated group in contrast to ischemia/reperfusion group (P<0.05). The expression of TRPM7 mRNA in AS-ODN group was remarkably increased compared with EA treated group and TE infusion group (P<0.05). The results indicated that TRPM7 channels in the ischemic cortex and hippocampus in rats might play a key role in ischemic brain injury. EA could reverse the overexpression of TRPM7 in cerebral ischemia/reperfusion rats. And the inhibitory effect of EA on TRPM7 channels might be through trkA pathway.

Objective To evaluate Mycobacterium tuberculosis (M. tuberculosis)-specific cellular immunity in individuals with latent or active tuberculosis and human immunodeficiency virus (HIV) coinfection. Methods One hundred HIV-infected individuals in Yunnan Province were enrolled. The enzyme-linked immunospot (ELISPOT) assay using early secreted antigenic target (ESAT)-6 and culture filtrate protein (CFP)-10 was employed to detect M. tuberculosis-specific T cells in the peripheral blood. The absolute number of CD3+ CD4+and CD3+ CD8+ T cells in the peripheral blood from the enrolled subjects were determined by flow cytometry. Data were analyzed using nonparametric Mann-Whitney test. Results The prevalence of latent tuberculosis co-infection in HIV-infected individuals without any clinical evidence of active tuberculosis was 67.6%. The absolute numbers of CD3+ CD4+ (532 × 106/L) and CD3+ CD8+ (473 × 106×/L) T cell in HIV-infected individuals with latent tuberculosis co-infection were similar to those of only HIV-infeeted individuals (406 ×106×/L and 504 × 106/L). While those in HIV-infected individuals with active tuberculosis co-infection were 189 × 106/L and 293 × 106/L, respectively, which were both significantly lower than those in other two groups (U=168. 0,U=163. 0,U= 374. 0,U=147. 0, all P<0. 01). Furthermore, ESAT-6 (31/106 cells) and CFP-10 (82/106 cells) specific spot-forming cells in HIV-infected individuals with active tuberculosis co-infection were significantly less than those in HIV-infected individuals with latent tuberculosis co-infection (92 × 106 cells and 109 × 106 cells, U= 507. 0,U= 529. 5, both P<0. 01). Conclusions The prevalence of latent tuberculosis in HIV-positive individuals without any clinical evidence of active tuberculosis is high in China. Both overall cellular immunity and M. tuberculosis-specific immune response in HIV-positive individuals with active tuberculosis co-infection are severely impaired.

Objective: To investigate the antibiotic resistance status of Streptococcus pneumoniae isolates from hospitalized children in Shanxi Children′s Hospital. Method: E-test and Kirby-Bauer methods were applied to determine drug sensitivity of the isolates collected from the body fluid specimens of hospitalized children in Shanxi Children's Hospital from January 2012 to December 2014. The antimicrobial sensitivity and minimum inhibitory concentration (MIC) of Streptococcus pneumoniae to the conventional antibiotics were analyzed, in order to compare the annual trends of non-invasive isolates, while the differentiation of sensitivity from specimens. The comparison of rates was performed by Chi-squared test and Fisher's exact test. Result: A total of 671 isolates of streptococcus pneumoniae were obtained, which could be divided as non-invasive isolates(607), invasive isolates from non-cerebrospinal fluid(non-CSF)(40) and invasive isolates from cerebrospinal fluid(CSF)(24). The antimicrobial sensitivity(isolates(%)) of the 671 isolates were respectively vancomycin 671(100.0%), linezolid 671(100.0%), levofloxacin 665(99.1%), penicillin 595(88.7%), ceftriaxone 516(76.9%), cefotaxime 512(76.3%), sulfamethoxazole-trimethoprin(SMZ-TMP) 103(15.4%), clindamycin 28(4.2%), tetracycline 26(3.9%), erythromycin 12(1.8%). From 2012 to 2014, the susceptibility rates of non-invasive isolates to penicillin every year were 95.0%(96/101), 97.3%(110/113), 87.3%(343/393), respectively, and there was significant difference among the three years(χ²=13.266, P<0.05), and the values of MIC₅₀, MIC₉₀ and the maximum values of MIC(mg/L) of penicillin were 0.064, 2.000, 6.000 in 2012, which grew up to 1.000, 3.000, 16.000 in 2014. There was no significant difference in the susceptibility rate of non-invasive isolates to ceftriaxone and cefotaxime during these three years, (χ²=1.172, 1.198, both P>0.05). On the other hand, the values of MIC₅₀, MIC₉₀ and the maximum value of MIC(mg/L) of ceftriaxone and cefotaxime both increased from 0.500, 2.000, 8.000 in 2012 to 0.750, 4.000, 32.000 in 2014. There was no significant difference in the susceptibility rate of non-invasive isolates to the rest antibiotic. Based on the same examining standard of CSF, the antimicrobial sensitivity(isolates(%)) of the non-invasive isolates to ceftriaxone, cefotaxime, SMZ-TMP were respectively 281(46.3%), 278(45.8%), 78(12.9%), were significantly lower than the susceptibility rate of the invasive isolates from non-CSF (28(70%), 28(70%), 14(35%), χ²=8.453, 8.817, 15.094, all P<0.012 5), and lower than the invasive isolates from CSF (18(75%), 18(75%), χ²=7.631, 7.905, P<0.012 5; 11(45.8%), P=0.001). The sensitivity of the isolates to the rest antibiotics were similar(P>0.05). Conclusion More than 95.0% strains of the streptococcus pneumoniae isolates from the hospitalized children in Shanxi Children's Hospital were sensitive to vancomycin, linezolid, levofloxacin, and the susceptibility rate of penicillin, ceftriaxone, cefotaxime were 88.7%, 76.9%, 76.3%. However, less than 20.0% of streptococcus pneumoniae were sensitive to erythromycin, clindamycin, SMZ-TMP and tetracycline. The susceptibility rate of penicillin of non-invasive Streptococcus pneumoniae declined by these years, and the differences to ceftriaxone and cefotaxime can be neglected, but the values of MIC₅₀, MIC₉₀ and the maximum value of MIC of all were linearly rising. The susceptibility rate of antibiotics to ceftriaxone and cefotaxime of the non-invasive isolates was lower than the invasive isolates.

Summary: The effect of electroacupuncture (EA) on TRPM7 mRNA expression of focal cerebral ischemia in rats and further the role of EA in the relationship between TRPM7 and trkA pathway was investigated. Thirty SD rats were randomly divided into 5 groups : normal group, ischemia/reperfusion group, EA treated group (ischemic rats with EA treatment), TE infusion group (ischemic rats with EA treatment and TE buffer infusion),AS-ODN group (ischemic rats with EA treatment and antisense trkA oligonucleotide infusion). The stroke animal model was established by the modified method of middle cerebral artery occlusion. Antisense trkA oligonucleotide that blocked NGF's effects was injected into cerebroventricle before EA. The TRPM7 mRNA was detected by RT-PCR method. The results showed that there were low TRPM7 mRNA levels in cortex and hippocampus in normal group. Compared with normal group, TRPM7 mRNA expression was increased significantly in ischemia/reperfusion group (P<0.05). A significant reduction in the expression of TRPM7 mRNA was found in EA treated group in contrast to ischemia/reperfusion group (P<0.05). The expression of TRPM7 mRNA in AS-ODN group was remarkably increased compared with EA treated group and TE infusion group (P<0.05). The results indicated that TRPM7 channels in the ischemic cortex and hippocampus in rats might play a key role in ischemic brain injury. EA could reverse the overexpression of TRPM7 in cerebral ischemia/reperfusion rats. And the inhibitory effect of EA on TRPM7 channels might be through trkA pathway.

OBJECTIVE:To investigate the relationship of Cytochrome P450 (CYP)3A4* 18 gene polymorphism with therapeutic efficacy and ADR of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in non-small cell lung cancer (NSCLC) patients receiving primary treatment.METHODS:A total of 46 advanced NSCLC patients receiving primary EGFR-TKI (gefitinib or edotinib) treatment until disease progression or intolerance were selected from our hospital during Jan.2013-Mar.2016,and (gefitinib of erlotinib) treatment until disease progression or intolerance.CYP3A4*18 genotype was detected by PCR and direct sequencing.Clinical efficacies,progression-free survival (PFS) and the occurrence of ADR were compared among differ ent genotypes.RESULTS:Among 46 patients,there were 17 cases of CYP3A4*18 wild-type and 29 cases of CYP3A4*18 mutation-type,with mutation frequency of 63.0％.The objective response rate (ORR) of CYP3A4*18 wild-type patients was 23.5％,and disease control rate (DCR) of them was 70.6％.For CYP3A4*18 mutation-type patients,ORR and DCR were 27.6％ and 69.0％.There was no statistical significance in the proportion of patients with partial response,stable disease or progressive dis ease,ORR or DCR among different genotypes (P＞0.05).PFS of female patients were significantly longer than male patients;those of patients without smoking history were significantly longer than those with smoking history,with statistical significance (P＜0.05).There was no correlation between patients' age,therapy drugs,Eastern Oncology Collaboration scores,EGFR mutation types,CYP3A4*18 genotypes and PFS (P＞0.05).Patients'gender and smoking history were independent prognostic factors for PFS [odds ratios were 3.438,0.205,95％ CI were(1.393,8.488),(0.088,0.481)].Among CYP3A4* 18 wild-type patients,6 patients suffered from rash (35.3％) and 3 diarrhea (17.6％).Among mutation-type patients,26 patients suffered from rash (89.7％) and 15 diarrhea (51.7％),with statistical significance (P＜0.05).There was no statistical significance in the incidence of liver function injury and interstitial dermatitis among different genotypes (P＞0.05).CONCLUSIONS:CYP3A4*18 gene polymorphism may be not associated with therapeutic efficacy of EGFR-TKI in advanced NSCLC patients receiving primary treatment,but it is correlated with the occurrence of ADR.Mutation type patients are more likely to suffered from rash,diarrhea and other ADR.

OBJECTIVE:To observe therapeutic efficacy and safety of prucalopride in the treatment of chronic constipation (CC). METHODS:Totally of 100 CC patients were selected from anorectal department of our hospital during Jun. 2016-Jan. 2017, and then divided into control group and observation group according to random number table,with 50 cases in each group. Control group was given Mosapride citrate tablets 5 mg +Lactulose oral solution 10 mL orally,3 times a day. Observation group was given Prucalopride succinate tablets 2 mg orally,once a day. Both groups were treated for consecutive 4 weeks. Clinical efficacies of 2 groups were observed,and the levels of serum inflammatory factors(IL-6,TNF-α,IFN-γ)and colonic transit time(total colonic transit time,left colonic transit time,right colonic transit time,rectosigmoid colonic transit time)were observed before and after treatment. The occurrence of defecation disorders and ADR were recorded. RESULTS:None of patient in 2 groups was cured. Total response rate of observation group was 94.00%,which was significantly higher than 78.00% of control group,with statistical significance (P＜0.05). Before treatment,there was no statistical significance in the levels of serum inflammatory factors or colonic transit time (P＞0.05). After treatment,the levels of IL-6 and IFN-γ in control group,the levels of IL-6,TNF-α and IFN-γ in observation group were decreased significantly,and the levels of IL-6,TNF-α and IFN-γ in observation group were significantly lower than those of control group;the colonic transit time in 2 groups was shortened significantly,and observation group was significantly shorter than control group,with statistical significance (P＜0.05). After treatment,the incidence of defecation,incomplete emptying,sense of obstruction and sense of rectal tenesmus in observation group were significantly lower than control group,with statistical significance(P＜0.05). There was no statistical significance in the incidence of sense of rectal tenesmus after treatment or ADR between 2 groups (P＞0.05). CONCLUSIONS:Compared with traditional plan of mosapride combined with lactulose,prucalopride can more effectively reduce the levels of serum inflammatory factors,shorten colonic transit time,reduce the occurrence of defecation disorders as defecation and incomplete emptying,with equivalent safety.