Design, synthesis and antitumor activities of novel E-substituted 2,3-diaryl propenoic acyloxy phosphonate derivatives / 药学学报

According to the super-position principle of the reinforcement of biological activities, a series of novel E-substituted 2, 3-diaryl propenoic acyloxy phosphonate derivatives were designed and synthesized. And the structures of the target compounds were confirmed by IR, 1H NMR, 13C NMR and elemental analysis. Furthermore, the cytotoxicities of all compounds on A-549, SGC-7901 and EC-109 in vitro were evaluated by MTT assay, and some of them showed good antitumor activity. Among the active compounds, especially, the IC50 value of compound 3e was (12.7 ± 1.9) μmol x L(-1) against A-549 cells, similar to cisplatin [IC50 = (8.0 ± 1.5) μmol x L(-1)], compounds 3g and 3k had better inhibition effect on EC-109 cells growth, with the IC50 values of (9.5 ± 1.8) μmol x L(-1) and (11.5 ± 0.9) μmol x L(-1) respectively, and compounds 3i and 3k exhibited good cytotoxic property on A-549, SGC-7901 and EC-109, which were worth further investigation.

Roles of PKCβ/P66Shc oxidative stress signal pathway in mediating hyperoxia-induced ROS production in alveolar epithelial cells / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To explore the roles of PKCβ/P66Shc oxidative stress signal pathway in mediating hyperoxia-induced reactive oxgen species (ROS) production in alveolar epithelial cells (A549) and the protective effects of PKCβ inhibitor on hyperoxia-induced injuries of alveolar epithelial cells.</p><p><b>METHODS</b>A549 cells were cultured in vitro and randomly divided into three groups: control, hyperoxia and PKCβ inhibitor LY333531 treatment. The hyperoxia group was exposed to a mixture of O2 (950 mL/L) and CO2 (50 mL/L) for 10 minutes and then cultured in a closed environment. The LY333531 group was treated with PKCβ inhibitor LY333531 of 10 µmol/L for 24 hours before hyperoxia induction. Cells were collected 24 hours after culture and the levels of PKCβ, Pin1, P66Shc and P66Shc-Ser36 were detected by Western blot. The intracellular translocation of P66Shc, the production of ROS and cellular mitochondria membrane potential were measured using the confocal microscopy.</p><p><b>RESULTS</b>Compared with the control group, the levels of PKCβ, Pin1, P66Shc and P-P66Shc-Ser36 in A549 cells 24 hours after culture increased significantly in the hyperoxia group. These changes in the hyperoxia group were accompanied with an increased translocation rate of P66Shc from cytoplasm into mitochondria, an increased production of mitochondrial ROS, and a reduced mitochondrial membrane potential. Compared with the hyperoxia group, the levels of Pin1, P66Shc and P66Shc-Ser36 in A549 cells, the translocation rate of P66Shc from cytoplasm into mitochondria and the production of mitochondrial ROS decreased significantly, while the mitochondrial membrane potential increased significantly in the LY333531 treatment group. However, there were significant differences in the above mentioned measurements between the LY333531 treatment and control groups.</p><p><b>CONCLUSIONS</b>Hyperoxia can increase the expression of PKCβ in alveolar epithelial cells and production of mitochondrial ROS and decrease mitochondrial membrane potential. PKCβ inhibitor LY333531 can partially disrupt these changes and thus alleviate the hyperoxia-induced alveolar epithelial cell injury.</p>

Chest radiographic findings in children with 2009 influenza A (H1N1) virus infection / 中华儿科杂志

<p><b>OBJECTIVE</b>To evaluate chest radiographic findings of children with 2009 influenza (H1N1) virus infection.</p><p><b>METHOD</b>Data of 235 patients who had microbiologically confirmed H1N1 infection and available chest radiograph obtained between May 1(st) 2009 and Jan. 31(st) 2010 were retrospectively analyzed. The final study group was divided on the basis of clinical course [group 1 mild, outpatients without hospitalization (n = 172); group 2 moderate, inpatients with brief hospitalization (n = 49); group 3 severe, ICU admission (n = 14)]. Four pediatric radiologists reviewed all the chest radiographs of lung parenchyma, airway, pleural abnormalities and also anatomic distribution of the disease.</p><p><b>RESULT</b>No significant sex or age differences were found among the study groups (P > 0.05). The mean interval between the onset of clinical symptom and the initial chest radiography was (5.91 ± 1.64) days (group 1), (3.60 ± 1.43) days (group 2) and (1.21 ± 0.41) days (group 3), respectively. The differences among the three groups were significant statistically (χ(2) = 13.368, P < 0.01). The ratio of abnormality presented at initial chest X-ray was 79.7% in group 1, 91.8% in group 2 and 100% in group 3. Radiographically, there were prominent peribronchial markings (group 1, 55.2%; group 2, 83.7%; and group 3, 78.6%), consolidation (group 1, 34.3%; group 2, 69.4%; and group 3, 100.0%), hyperinflation (group 1, 22.1%; group 2, 44.9%; and group 3, 50.0%) and ground glass opacity (group 1, 0.6%; group 2, 2.0%; and group 3, 14.3%) in the chest radiographs. The differences of presenting were statistically significant (P < 0.01). In the severe group, the lesions distributed diffusely and asymmetrically with multi-lobe involvements.</p><p><b>CONCLUSION</b>In children with 2009 influenza A H1N1 viral infection, the interval between the onset of clinical symptom and initial chest radiography, the ratio of abnormality presented at initial chest X-ray film and the severity of chest film are parallel to their clinical situation.</p>

Effect of electro-acupuncture on tumor necrosis factor-α and vascular endothelial growth factor in peripheral blood and joint synovia of patients with rheumatoid arthritis / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the effect of electro-acupuncture (EA) on tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) in peripheral blood and joint synovia in patients with rheumatoid arthritis (RA) to verify the clinical efficacy of EA.</p><p><b>METHODS</b>Adopting randomized controlled principle, the 63 RA patients enrolled were assigned to two groups, the 32 patients in the EA group were treated with EA, and the 31 patients in the simple needling (SN) group treated with simple needling. According to the integral-local combining method, the acupoints were selected mainly from yang-meridian and local Ashi points (pain-point). EA or SN was applied every other day, 10 times as a course, and each patient received a total of 3 courses of treatment.</p><p><b>RESULTS</b>Blood and synovial levels of TNF-α and VEGF were reduced significantly after treatment in both groups. The lowering (absolute value and difference value) of TNF-α as well as the absolute value of VEGF, either in blood or in synovia, were similar in the two groups (P>0.05); but the lowering of VEGF after treatment was more significant in the EA group than that in the SN group (P<0.05).</p><p><b>CONCLUSION</b>EA could effectively lower the contents of TNF-α and VEGF in peripheral blood and joint synovia to improve the internal environment for genesis and development of RA, so as to enhance the clinical therapeutic effectiveness.</p>

Concurrent versus sequential systemic chemotherapy and whole brain radiation therapy for brain matastases in non-small-cell lung cancer patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy, survival and toxicity in patients with brain metastases from non-small cell lung cancer (NSCLC), treated with concurrent systemic chemotherapy and whole brain radiation therapy (WBRT) or sequential systemic chemotherapy/WBRT.</p><p><b>METHODS</b>A total of 60 NSCLC patients with brain metastases were divided into two groups in this prospective clinical study: concurrent systemic chemotherapy and WBRT group (concurrent group) and sequential systemic chemotherapy/WBRT group (sequential group).</p><p><b>RESULTS</b>Of 59 assessable patients, the overall response rate was 22.0%, and the brain response rate was 35.6%; the median progression-free survival time was 3.0 months, and the overall 1- and 2-year survival rates were 55% and 24.4%, respectively, with a median survival time of 16.0 months. The overall response rate was 20.0% in the concurrent group and 24.1% in sequential group (P > 0.05). The brain response rates of 43.3% in concurrent group and 27.6% in sequential group were also not significantly different (P > 0.05). The median progression-free survival time for the patients in the concurrent group was 3.0 months versus 4.0 months in the sequential group, and the median survival time was 16.0 months versus 13.0 months (all P > 0.05). The 1- and 2-year survival rates were 58.5% and 37.2% versus 52.9% and 18.9%, respectively, with a significant difference in the 2-year survival rate between the two groups (P = 0.011). In the sequential group, leukopenia was more frequent during chemotherapy than that in the concurrent group (P = 0.029).</p><p><b>CONCLUSION</b>Concurrent systemic chemotherapy and WBRT is effective with tolerable adverse events in treating brain metastasis from NSCLC with an encouraging survival, and deserves further large sample and randomized multicenter clinical trials.</p>

Effects of electroacupuncture and simple acupuncture on changes of IL-1, IL-4, IL-6 and IL-10 in peripheral blood and joint fluid in patients with rheumatoid arthritis / 中国针灸

<p><b>OBJECTIVE</b>To explore the mechanism of electroacupuncture on rheumatoid arthritis (RA).</p><p><b>METHODS</b>In a randomized and controlled trial, sixty-three cases with RA were randomly divided into an electroacupuncture group (n = 32) and a simple acupuncture group (n = 31). Baihui (GV 20), Fengchi (GB 20), Quchi (LI 11), Waiguan (TE 5), Guanyuan (CV 4) and Zusanli (ST 36) were selected by coordination method combined whole and local acupoints. The electroacupuncture group was treated with electroacupuncture at the local acupoints near painful joints, continuous wave, retaining needle for 30 minutes, and then electroacupuncture at Back-shu acupoints, retaining needle for 15 minutes, and the simple acupuncture group was treated with the same acupoints selection and acupuncture manipulation without electroacupuncture apparatus. They were all treated once every other day for 20 days as one course. After 3 courses, changes of interleukins in peripheral blood and joint fluid of patients were observed.</p><p><b>RESULTS</b>Both of electroacupuncture and simple acupuncture had significant effect on IL-1, IL-4, IL-6 and IL-10 in peripheral blood and joint fluid of patients with RA ( P < 0.01, P < 0.05). But after electroacupuncture, the absolute value and improvement value of decreasing IL-1 in peripheral blood and joint fluid were super than those of simple acupuncture (all P < 0.05), and of IL-4 in joint fluid was super than that after simple acupuncture (P < 0.05), and of IL-6 and the absolute value of decreasing IL-10 were almost the same after both treatment (all P > 0.05), and after electroacupuncture, the improvement value of IL-10 in peripheral blood and joint fluid were super than those after simple acupuncture (both P < 0.05).</p><p><b>CONCLUSION</b>Electroacupuncture can effectively decrease the proinflammatory cytokine of IL-1 and IL-6 and increase the inhibition cytokine of IL-4 and IL-10 and improve the internal environment of occurrence and progression of RA.</p>

Surveillance for influenza B virus infections in infants and young children in Beijing, China / 中华儿科杂志

<p><b>OBJECTIVE</b>To characterize the prevalence of influenza B virus infection in infants and young children in Beijing.</p><p><b>METHODS</b>MDCK cell culture, indirect fluorescence assay (IFA) and hemagglutination inhibition (HI) assay were used to isolate and identify type B influenza viruses from clinical samples collected from outpatients and inpatients who visited the Affiliated Children's Hospital because of acute respiratory infections from Nov. 2000 to Jun. 2006.</p><p><b>RESULTS</b>Out of 10,770 clinical samples collected during this surveillance period, 384 (3.57%, 384/10,770) were positive for influenza B viruses. Circulation of influenza B viruses was revealed in the later epidemic season of influenza viruses each year. The detection rate for influenza B virus was higher than 10% each year during the survey, except in the period from 2003--2004 which was 2.91%. The highest detecting rate was 23.69% of the specimens collected in Mar. 2006. During the period of this study, most of the influenza B virus were identified from children who visited the outpatient department of the Affiliated Children's Hospital. Among those outpatients who were positive for influenza B, 77.6% (264/340) were older than 3 years of age, whereas the inpatients positive for influenza B, 66.0% (29/44) were under 3 years of age. Coinfection of influenza B virus with other respiratory viruses was not common, only one of the influenza B virus positive specimen was found also positive for influenza A3. There was no significant difference in positive rate between influenza virus B and A3. A significantly higher positive rate of influenza B virus than that of influenza A3 virus was seen from Sep. 2005 to May 2006 (23.9% vs 1.1%). B/Yamagata/16/168 lineage viruses were dominant during 2000--2002, and B/Victoria/2/87 lineage viruses became dominant during 2002--2003. After 2003, co-circulation of Victoria and Yamagata lineages of influenza B viruses was identified with predominance of Yamagata lineage viruses, while Victoria lineage viruses predominated during the 2005--2006 epidemic season.</p><p><b>CONCLUSION</b>Influenza B viruses were identified from February to May in every influenza season during this surveillance period of 2000--2006. Most of the positive specimens were those collected from outpatient department. Victoria and Yamagata lineages of influenza B viruses co-circulated in Beijing, China in recent years.</p>

Surveillance for influenza A virus infections in infants and young children in Beijing, China, 2001-2005 / 中华儿科杂志

<p><b>OBJECTIVE</b>To characterize the prevalence and antigenic drift of influenza A viruses isolated during the period from 2001 to 2005 in infants and young children in Beijing.</p><p><b>METHODS</b>MDCK cell culture, indirect immunofluorescence assay (IFA) and hemagglutination inhibition (HI) assay were used to isolate and identify type A influenza viruses (H1N1 and H3N2) from clinical samples collected from outpatients and inpatients who visited the Affiliated Children's Hospital because of acute respiratory infections from Oct. 2001 to Aug. 2005. The HA1 regions of hemagglutinin gene of H3N2 isolates were amplified by using RT-PCR followed by sequencing.</p><p><b>RESULTS</b>Out of 7338 clinical samples collected during this surveillance period, 347 (4.7%) were positive for influenza A viruses, including 48 (13.8%) of H1N1, 273 (78.7%) of H3N2 and 26 (7.5%) of subtype-unidentified influenza A viruses. Although there was a prevalence season of influenza A from October each year to April of next year during the 2001-2004 period, it was worth noting that a consecutive influenza A activity was detected from Aug. 2004 to Aug. 2005, when some influenza A viruses were detected even in summer. The positive rate of H3N2 was 14.2% in August, 2005, which was equal to that of the peak season of 2003-2004. H3N2 were predominant in most of the influenza seasons during the surveillance period, and H1N1 was detected only in the influenza seasons of the 2001-2002 and 2004-2005 along with H3N2. The positive rates for both H3N2 and H1N1 were higher in specimens from outpatients than those from inpatients. A total of 46.6% (110/236) of the H3N2 were detected from children younger than 2 years of age, and 14.0% (33/236) were from children older than 5 years, whereas, more H1N1 was found in children older than 5 years (48.0%, 12/31) than in those younger than 2 years (6.5%, 2/31) during a period from Nov. 2003 to Aug. 2005. Sequence analysis of the HA1 regions of hemagglutinin of H3N2 isolated in a series of years revealed amino acid changes in the HA1 domain of H3N2 isolates in the antigenic sites (A-E) each year.</p><p><b>CONCLUSION</b>H3N2 and H1N1 prevailed in each influenza season during the surveillance period in Beijing, and H3N2 strains were predominant. The data from all-year around surveillance of influenza in Beijing indicate that continuous surveillance throughout a year and use of both antigenic and molecular analysis will be more helpful for early identification of any antigenic variants as well as prevention and control of influenza by promoting development of vaccines.</p>

Study and clinical application of the theory "moxibustion can be used for heat syndrome" / 中国针灸

In order to study on the clinically difficult problem, "is moxibustion suitable for heat syndrome?" cite and analyze relative papers in classical treaties about acupuncture and moxibustion, in combination with the many years' practical experiences of the author and experimental studies of modern medicine. And Textually research the treatment principle of "positive and negative go against" and the treatment method of "using heat to induce heat", which is a theoretical basis of "moxibustion being suitable for heat syndrome". Experimental studies have proved that moxibustion has bacteriostatic effect, and functions abatement of fever and improving microcirculation. It is indicated that moxibustion is suitable to treatment of all heat syndromes including excess-heat and deficiency-heat syndromes.

Observation on therapeutic effect of plum-blossom needle therapy on peripheral facial neuritis at acute stage / 中国针灸

<p><b>OBJECTIVE</b>To compare difference between plum-blossom needle therapy and hormonotherapy in the The treatment group of 32 cases with periphtherapeutic effect on peripheral facial neuritis at acute stage.</p><p><b>METHODS</b>eral facial neuritis at acute stage were treated with plum-blossom needle therapy and the control group of 32 cases with oral administration or intravenous drip of dexamethasone. Their therapeutic effects were compared.</p><p><b>RESULTS</b>The total effective rate was 100.0% in the treatment group and 93.4% in the control group, with a significant difference between the two groups (P < 0.05).</p><p><b>CONCLUSION</b>The therapeutic effect of plum-blossom needle therapy on peripheral facial neuritis at acute stage is better than that of the hormonotherapy.</p>

Expression of genes related to Sonic Hedgehog signaling in human hepatocellular carcinomas / 北京大学学报(医学版)

Objective:To investigate the expression status of Sonic Hedgehog signaling genes and molecules in human hepatocellular carcinomas(HCC),and to explore the relationship between these genes and clinical prognosis.Methods:HCC tissue and adjacent normal tissue from 29 HCC patients were assayed for the expression of hedgehog signaling genes by reverse transcription-polymerase chain reaction chain reaction(RT-PCR) techniques and for the expression of hedgehog signaling molecules by immunohistochemistry.The expressions of Shh,Ptch,Smoh,Gli-1 mRNA were assayed as well as Shh,Ptch proteins in 29 cases of HCC and in 29 liver tissues adjacent to the tumor.Results:Expression of Shh mRNA was detectable in about 51% of HCCs examined.Consistent with this,hedgehog target genes Ptch,Smoh and Gli-1 mRNA were expressed in over 68%,48% and 62% of the tumors,respectively,and the expressions of Shh and Ptch proteins in HCC tumor tissues correlated with those of Shh and Ptch mRNA in tumor tissues(P=0.041 and P=0.035).This suggested that the hedgehog pathway was frequently activated in HCCs.The simultaneous expression of Gli-1 in HCC and liver tissues adjacent to the tumor had significantly relationship with poor prognosis.Conclusion:Hedgehog signaling activation is an important event for development of human HCCs.It also suggests that markers for hedgehog signaling activation may be useful for the determination of prognosis.

Ancient Chinese Model of Doctor-patient Relationship / 中国医学伦理学

Doctor-patient relationship has attracted increasing attention.In the light of modern model to study the related theory,a preliminary study of the ancient Chinese doctor-patient relationship model has been done.The doctor-patient relationship in ancient society is the same complex and multi-level.Therefore,doctor-patient model could not be lumped together.According to the social status of patients and the extent of their demand for medical services,and the social status of doctors and their medical technique,the doctor-patient relationship could be divided into three typies-equality type,authority type,and principal and subordinate type.With a view of doctor-patient relationship of traditional Chinese medicine,there draws an acquisition value of the current complex patient relationship.