In the past two decades,with the increase of smoking population,more and more people are suffering from small cell lung cancer(SCLC).Besides,it is difficult to find an effective way to cure SCLC,since patience can easily develop drug resistance.On the other hand,with the development of science and technology,people began to study the anti-cancer strategy to increase apoptosis,such as inhibiting the overexpression of survival factors.In these survival factors,BCL-2 family has attracted a lot of attention.BH3-only protein is a member of BCL-2 family and it can directly inhibit the expression of BCL-2 protein,thereby prompting apoptosis.Since the BH3-only protein itself is difficult to become a clinical drug, to find alternatives BH3-only protein-BH3 mimetics is particularly important. Plus, more and more researchers have paid attention on the natural BH3 mimetic since it has less side-effect than artificial BH3 mimetics.To find possible BH3 mimetics,we made a primary screening with this pharma-cophore on a small molecular compounds library via Discovery Studio software. And then MTS assay were introduced to verify the activity of compounds. After that, we use Western Blot and Co-IP meth-ods to test the effect of BH3 mimetics.And finally use CDOCKER to predict the further mechanism on autophagy and apoptosis.In our studies, we found 3 possible BH3 mimetics compounds from 170,000 natural small molecular compounds via pharmacophore-based virtual screening.Furthermore,we dem-onstrated AD23,one of the 3 possible natural BH3 mimetics,induced autophagy and apoptosis simulta-neously in dose-time dependence in SCLC cell line. Finally, we use Molecular Docking to predict the further mechanism on autophagy and apoptosis. We believe our works would provide evidences and clues for the structural optimizing and further study of new drugs in the future.

OBJECTIVETo evaluate incidence of postoperative delirium after hip surgery in elderly patients by meta-analysis.

METHODSFrom January 1, 2014 to December 31, 2013, clinical literatures about postoperative delirium after hip surgery in elderly patients,were searched from the Pubmed. Literature extract table were formed according to inclusion and exclusion criteria. Stata-12.0 was applied for Meta-analysis. P was used to test heterogeneity of study, random-effect model was performed when I2 > 50%. Subgroup analysis was used according to stage of age, assessment scale of delirium and statistical area of literature. Begg test was used to test publication bias.

RESULTSTwenty-one literatures were included. Incidence of postoperative delirium after hip surgery in elderly patients by weighted and combination was 17% [95% CI (16%, 18%)]. Incidence of postoperative delirium after optional hip surgery was decreased more than emergency operation in included 5 literatures [OR = 0.32, 95% CI (0.22, 0.45)]. Incidence of postoperative delirium in patients less than 80 years old was 21% [95% CI (19%, 23%)], while 21% [95% CI (19%, 24%)] in patients more than 80 years old. Incidence of postoperative delirium in CAM evaluation scale was 23% [95% CI (21%, 26%)], while 19% [95% CI (17%, 21%)] in other evaluation scales. Incidence of postoperative delirium in Asian area was 17% [95% CI (15%, 20%)], while 23% [95% CI (21%, 25%)] in European and American area. There was no publication bias tested by Begg test (P < 0.05).

CONCLUSIONIncidence of postoperative delirium after hip surgery in elderly patients increases higher, especially in emergency operation. A standardizing research method is benefit for evaluate incidence of postoperative delirium after hip surgery in elderly patients, decreasing heterogeneity and publication bias.

Aged ; Delirium ; epidemiology ; Hip Fractures ; surgery ; Humans ; Incidence ; Postoperative Complications ; epidemiology ; Publication Bias

OBJECTIVETo develop and evaluate the efficiency of air purification and sterilization instrument based on nano-sized TiO(2) photocatalytic technique.

METHODSThe nano-sized TiO(2) photocatalytic air purification and sterilization instrument was designed and a sample had been prepared. The sterilization efficiencies for E.coli and Klebsiella by the nano-sized TiO(2) photocatalytic instrument and ultraviolet (UV) were measured in closed labs. The on-site efficiency of the instrument was evaluated, too.

RESULTSThe nano-sized TiO(2) photocatalytic air purification and sterilization instrument was composed of five units: rough filter, nano-sized TiO(2) photocatalytic unit, activated carbon fiber filter, negative ion generator, and programmed control unit. The E.coli killing rates by the nano-sized TiO(2) photocatalytic instrument were 76.0%, 81.8%, 77.5%, and 80.7% at 30, 60, 90, and 120 minutes, respectively. There was no significant difference between the E.coli killing rates of the instrument and UV (P > 0.05), except the 120 minutes timepoint. The Klebsiella killing rates by the instrument were 78.4%, 79.5%, 67.3%, and 58.5% at 30, 60, 90, and 120 minutes, respectively. The Klebsiella killing efficiencies of the instrument at 30 and 60 minutes were better than that of UV (P < 0.01). There was no significant difference between the Klebsiella killing efficiencies of the instrument and UV (P > 0.05).

CONCLUSIONThe air sterilization efficiency of the nano-sized TiO(2) photocatalytic instrument should be equivalent or better as compared with the UV. This instrument might be used for the air purification and sterilization of the public locations.

Air Pollution ; prevention & control ; Decontamination ; methods ; Disinfection ; methods ; Nanostructures ; Photochemistry ; Titanium

OBJECTIVETo determine the correlation of the CYP1A1 (rs4646422) gene polymorphisms with male infertility in the Chinese Han population.

METHODSUsing the Mass ARRAY iPLEX GOLD technique, we conducted a case-control study on theCYPlA1 (rs4646422) gene polymorphisms in 636 infertile males aged 21-49 years (case group) and 442 normal healthy men aged 23-47 years (control group) of the Chinese Han population. We analyzed the genotypes and allele frequencies in the two groups ofsubjects with the SPSS 20.0 software.

RESULTSCompared with the wild homozygous genotype GG, the heterozygous genotype AG (OR = 1.06, 95% CI 0.81-1.38) and homozygous genotype AA (OR = 1.11, 95% CI 0.56-2.21) showed no correlation with male infertility, nor did the mutant allele A (OR = 1.06, 95% CI 0.85-1.32) in comparison with the wild allele G.

CONCLUSIONThe CYP1A1 (rs4646422) gene polymorphisms might not be correlated with male infertility in the Chinese Han population.

Adult ; Alleles ; Case-Control Studies ; China ; Cytochrome P-450 CYP1A1 ; genetics ; Gene Frequency ; Genotype ; Homozygote ; Humans ; Infertility, Male ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic ; Young Adult

Objective: To evaluate the immunogenicity of high-dose inactivated quadrivalent influenza serial vaccines (split virion) for elderly people. Methods: Immunogenicity assays on mouse as research animal model with inactivated quadrivalent influenza serial vaccines (split virion) were carried out. Then rates of seroconversion and geometric mean hemagglutination inhibition titers (GMTs) at day 21 after the last vaccination among those who received high-dose (HD) A+ B influenza vaccine, were compared with those who received other vaccines by hemagglutination inhibition (HAI) test. Results: The result of HAI test showed in HD serial vaccine groups, GMTs for all kinds of HA in the two HD serial vaccine groups were significantly different from that of the two SD serial vaccine groups, respectively (P<0.0001), but not the titers for A3 in one B dose first group. Further- more, GMTs for strain A in one B dose first groups were significantly higher than that of one B dose first groups in both HD and SD groups, and vice versa in the GMTs for strain B. The result of the assay of the impact of different immunization intervals of HD serial influenza vaccine on immunogenicity indicated that the immunity responses in 7 or 10 d groups were higher than that in 3 d group. Conclusions It is a new method to prevent the flu for elderly by HD A+ B serial influenza vaccine, whose HA dose per immunization was reduced into two injections, worked best when the immunization interval was 7-10 d. The protective immunity can be improved by selecting immune procedure of the serial vaccine according to the epidemic type surveillance of influenza virus A and B strains.

Objective: Quadrivalent influenza vaccines contain two lineages of type B virus, this study aimed to assess whether the result of single radial immunodiffusion (SRID) are accurate. The cross-interference of two type B hemagglutinins remains unknown. Methods: We detected the vaccine samples developed by Jiangsu GDK Biological Technology Co., ltd by SRID. Results: There was no significant difference between the HA content of antigen reagent, bulk sample and mixed sample of two B bulk within 10 to 40 μg/ml (P>0.05). Then each hemagglutinin B was diluted respectively by other three HA, 30 μg/ml, the other hemagglutinin B or phosphate buffer solution were measured within 10-160 μg/ml. Within 10-40 μg/ml, the HA content was proportional to the diameters of immunodiffusion (R²=0.998), while within the higher content range, a ternary linear regression equation fitted best (R²=0.999). Conclusions No cross-interference between B/Brisbane and B/Phuket was found in SRID within both detection ranges.

Objective To investigate the status of self‐management of blood pressure (BP) among elderly hypertensive patients living in new rural communities of Shanghai. Methods We enrolled a total of 2 241 hypertensive patients over 60 years old who participated in the National Key Research and Development Project "Cohort study on hypertension" of the 13th Five‐Year Plan in Langxia, Shanghai from May to July 2018. Questionnaires, physical examinations, and laboratory tests were conducted. We collected participants' demographic information, cardiovascular history, and self‐management behaviors related to hypertension. The status of self‐management of BP among participants with hypertension was analyzed. Pearson's chi‐squared test was used to explore the differences between males and females. Results Participants'mean age was (70.0±6.8) years, and males accounted for 38.8% of all participants. The systolic and diastolic BP levels of participants were (147.8±15.4) mmHg (1 mmHg=0.133 kPa) and (82.8±9.8) mmHg, respectively. The systolic blood pressure level of women was higher than that of men, and the diastolic blood pressure level of men was higher; the difference was statistically significant (all P<0.05). The awareness, treatment, and control rate of hypertension were 79.0%, 78.0%, and 25.6%, respectively. Males had a significantly higher control rate than females (P<0.05). The status of self‐management of blood pressure was as follows: (1) As to lifestyle, 84.4% of participants lacked exercise, and 69.2% were overweight or obese. The prevalence of smoking and drinking was higher in males (40.7% and 46.2%, respectively), and the proportion of females (12.4%) with anxiety and/or depression was higher than that of males (P all<0.001). (2) Concerning BP‐monitoring, only 10.1% of participants measured BP every week, 22.9% had BP measurement instruments at home, and 4.6% recorded their BP levels. There was no significant difference in self‐blood pressure monitoring behavior between men and women. (3) Regarding adherence to medication treatment, 97.6% took antihypertensive drugs regularly, and 21.6% were on combination therapy. The proportion of men taking combined drugs was higher than that of women, but there was no significant difference. Conclusions The rates of awareness, treatment, and control of hypertension in elderly hypertensive patients in new rural communities of Shanghai were above the national average. However, the status of self‐management of BP was still not satisfactory. More attention should be paid to healthy lifestyle, home BP monitoring, and effective pharmaceutical treatment strategies for hypertension.

OBJECTIVETo detect the expression of PTPN11 gene in acute myeloid leukemia (AML) cell line and to explore the effects of PTPN11 over expressing on proliferation and apotosis of AML cell lines.

METHODSThe expression of PTPN11 in AML cell lines（HEL,U937, K562, KG-1, HL -60） was detected by RT-PCR, Q-PCR and Western blot. The PTPN11 gene was amplified by RT-PCR. PTPN11 DNA fragement and the lentiviral vector PCDH-CD513B were digested by BamHI and EcoRI, and then ligated by T4 DNA ligase. Recombinant lentivirus was generated by co-transfection of three-plasmids into 293FT cells using lipofectamine 2000. Then Q-PCR and Western blot were used to detect the expression of PTPN11 in the lentivirus infected HEL and U937 cells. The CCK-8 and Annexin V/7-AAD assays were performed to evaluate effects of PTPN11 on proliferation, apoptosis of HEL and U937 cells.

RESULTSAll 5 AML cell lines expressed the PTPN11 gene, restriction analysis and gene sequencing confirmed that recombinant lentiviral vector was successfully constructed. After transfection of cells with the lentivirus, the recombinant plasmid could stably up-regulate the expression of PTPN11. Analysis of the proliferation and apoptosis of transfected AML cells indicated that as compared with the control group, the OD values of over-expression group were significantly higher and the apoptotic rates were significantly lower (P<0.05).

CONCLUSIONPTPN11 is expressed in all the 5 AML cell lines. The lentiviral expression vector carrying human PTPN11 and the engineered HEL and U937 cell lines stably up-regulating PTPN11 gene expression are successfully obtained. Over-expression of PTPN11 promotes the proliferation of AML cell lines and inhibit then apoptosis.

Apoptosis ; Cell Line, Tumor ; Gene Expression ; Genetic Vectors ; Humans ; Lentivirus ; Leukemia, Myeloid, Acute ; Plasmids ; Protein Tyrosine Phosphatase, Non-Receptor Type 11 ; Transfection

BACKGROUND: Cumulative blood pressure (BP), a measure incorporating the level and duration of BP exposure, is associated with the risk of cardiovascular disease (CVD). However, the level at which cumulative BP could significantly increase the risk remains unclear. This study aimed to investigate the association of 15-year cumulative BP levels with the long-term risk of CVD, and to examine whether the association is independent of BP levels at one examination. METHODS: Data from a 26-year follow-up of the Chinese Multi-provincial Cohort Study-Beijing Project were analyzed. Cumulative BP levels between 1992 and 2007 were calculated among 2429 participants free of CVD in 2007. Cardiovascular events (including coronary heart disease and stroke) occurring from 2007 to 2018 were registered. Adjusted hazard ratios (HRs) for CVD incidence associated with quartiles of cumulative systolic blood pressure (SBP) and diastolic blood pressure (DBP) were calculated. RESULTS: Of the 2429 participants, 42.9% (1042) were men, and the mean age in 2007 was 62.1 ± 7.9 years. Totally, 207 CVD events occurred during the follow-up from 2007 to 2018. Participants with higher levels of cumulative SBP or DBP exhibited a higher incidence rate of CVD (P < 0.001). Compared with the lowest quartile of cumulative SBP, the HR for CVD was 1.03 (95% confidence interval [CI]: 0.59-1.81), 1.69 (95% CI: 0.99-2.87), and 2.20 (95% CI: 1.21-3.98) for the second to the fourth quartile of cumulative SBP, and 1.46 (95% CI: 0.86-2.48), 1.99 (95% CI: 1.18-3.35), and 2.08 (95% CI: 1.17-3.71) for the second to the fourth quartile of cumulative DBP, respectively. In further cross-combined group analyses with BP measurements in 2007, 15-year cumulative BP levels higher than the median, that is, 1970.8/1239.9 mmHg·year for cumulative SBP/DBP, which were equivalent to maintaining SBP/DBP levels of 131/83 mmHg or above on average in 15 years, were associated with higher risk of CVD in subsequent years independent of BP measurements at one-time point. CONCLUSION Cumulative exposure to moderate elevation of BP is independently associated with increased future cardiovascular risk.
Aged ; Asian Continental Ancestry Group ; Blood Pressure/physiology* ; Cardiovascular Diseases/etiology* ; China/epidemiology* ; Cohort Studies ; Humans ; Hypertension/epidemiology* ; Incidence ; Male ; Middle Aged ; Risk Factors

By studying the relationship between syndromes, physique and MMP-9, IL-6 and MTHFR gene polymorphisms in patients with ischemic stroke,The relationship between MMP-9, IL-6 and MTHFR gene polymorphism was analyzed in patients with ischemic stroke.The data were collected by collecting the data of patients with ischemic stroke, and the statistical analysis was carried out. Syndrome：61 cases of ischemic stroke patients with stroke phlegm stasis syndrome in patients with the highest frequency, a total of 30 cases; Physical constitution： phlegm is ischemic stroke patients prone to physical, a total of 20 cases; The analysis of the relationship between constitution and syndrome shows that the patients with qi deficiency constitution tend to show qi deficiency and blood stasis syndrome after onset, The analysis of the relationship between constitution and syndrome shows that the patients with qi deficiency constitution tend to show qi deficiency and blood stasis syndrome after onset, Phlegm constitution and physical condition after the onset of symptoms tend to wind phlegm stasis syndrome; Syndrome and MMP-9, IL-6 relationship：The distribution of MMP-9 and IL-6 in patients with qi and phlegm stasis syndrome and qi deficiency and blood stasis syndrome was significantly different from that in Z test (P<0.05). The level of MMP-9 in patients with qi deficiency and blood stasis syndrome was significantly higher than that in patients with wind phlegm and blood stasis syndrome;The level of IL-6 in patients with phlegm and blood stasis syndrome was significantly higher than that in patients with qi deficiency and blood stasis syndrome. Syndrome, constitution and MTHFR gene polymorphism： among the 61 samples, 34 were heterozygous mutations, 15 were pure and mutated, 12 had no mutation, The mutation rate of this locus was 4.08 times that of patients without mutations.The genotype of MTHFR C677T in patients with phlegm dampness tends to be CT genotype. Wind phlegm stasis syndrome in patients with easy to appear after the TT genotype; Yin deficiency syndrome in patients prone to miscellaneous and mutations, the performance of CT genotype; Analysis of the relationship between syndromes and physique in patients with ischemic stroke,Phlegm and dampness, flat quality patients after the onset of easy to show the wind phlegm stasis syndrome; Qi deficiency after the onset of symptoms in patients with Qi and blood stasis. Suggesting that before the onset of such as for the partial physical conditioning, may be on the prevention of ischemic stroke have a certain effect; Analysis of the relationship between syndromes and MMP-9 and IL-6 in patients with ischemic stroke, Wind phlegm stasis syndrome and IL-6 levels are related, Qi deficiency and blood stasis syndrome and MMP-9 levels are related. Analysis of the relationship between syndromes and MTHFR gene polymorphism in patients with ischemic stroke, TT genotype after the onset of symptoms prone to wind phlegm stasis syndrome, CT genotype patients after the onset of easy manifestations of Yin deficiency wind syndrome; Analysis of the relationship between physique and MTHFR gene polymorphism in patients with ischemic stroke, CT genotype is easy to show phlegm.For more in-depth understanding of pathogenesis of ischemic stroke to provide the basis, For the clinical treatment and prevention to provide intervention strategies.