Development of a novel multi-functional integrated bioconjugate effectively targeting K-Ras mutant pancreatic cancer / 药物分析学报

Folate receptor(FR)overexpression occurs in a variety of cancers,including pancreatic cancer.In addi-tion,enhanced macropinocytosis exists in K-Ras mutant pancreatic cancer.Furthermore,the occurrence of intensive desmoplasia causes a hypoxic microenvironment in pancreatic cancer.In this study,a novel FR-directed,macropinocytosis-enhanced,and highly cytotoxic bioconjugate folate(F)-human serum albumin(HSA)-apoprotein of lidamycin(LDP)-active enediyne(AE)derived from lidamycin was designed and prepared.F-HSA-LDP-AE consisted of four moieties:F,HSA,LDP,and AE.F-HSA-LDP presented high binding efficiency with the FR and pancreatic cancer cells.Its uptake in wild-type cells was more extensive than in K-Ras mutant-type cells.By in vivo optical imaging,F-HSA-LDP displayed prominent tumor-specific biodistribution in pancreatic cancer xenograft-bearing mice,showing clear and lasting tumor localization for 360 h.In the MTT assay,F-HSA-LDP-AE demonstrated potent cytotoxicity in three types of pancreatic cancer cell lines.It also induced apoptosis and caused G2/M cell cycle arrest.F-HSA-LDP-AE markedly suppressed the tumor growth of AsPc-1 pancreatic cancer xenografts in athymic mice.At well-tolerated doses of 0.5 and 1 mg/kg,(i.v.,twice),the inhibition rates were 91.2％and 94.8％,respectively(P＜0.01).The results of this study indicate that the F-HSA-LDP multi-functional bioconjugate might be effective for treating K-Ras mutant pancreatic cancer.

A survey of major depression among elderly population in Wuhan / 中国心理卫生杂志

Objective:To know about the prevalence and related factors of major depressive disorder (MDD) in older adults of Wuhar.Methods:A total of 1572 older adults from 30 communities were selected through multistage random cluster sampling and interviewed with the Chinese version of the Mini International Neuropsychiatric Interview.The older adults diagnosed with MDD were further interviewed for their mental health services use.Results:The overall adjusted prevalence of current MDD was 5.9％.In multiple logistic regression,female,being 80 years or older,being rural residence,feeling lonely,having chronic illnesses,and having difficulties in mobility,self-care and getting along were risk factors for MDD of older adults (OR =1.60-3.90,P≤0.047).Only 3.9％ of the depressed older adults had received professional help for their emotional problem.Conclusion:It suggests that the prevalence of MDD among older adults in Wuhan is higher,but the rate of mental health services use is extremely lower.Psychosocial supports such as reducing loneliness,treating physical illnesses,and reducing difficulties in activities and participation may be effective for MDD prevention.

Sexual satisfaction and its associated factors among individuals with hearing disability / 中华男科学杂志

<p><b>Objective</b>To investigate sexual satisfaction (SS) and the factors associated with decreased SS among individuals with hearing disability.</p><p><b>METHODS</b>We conducted an investigation on SS among 439 individuals (268 males and 171 females, aged ≥18 yr) with hearing disability using a general information questionnaire, Center for Epidemiologic Studies Depression Scale, Social Support Rating Scale, and a self-report on SS. We identified the factors of decreased SS by multivariate ordinal logistic regression analysis.</p><p><b>RESULTS</b>Totally 76 (17.3%) of the hearing-disability individuals investigated were dissatisfied with their sexual life. SS reduction was significantly correlated with the status of being single (OR=1.72), grade-1 or -2 disability (OR=1.78), physical diseases (OR=2.46), depression (OR=6.61), or inadequate subjective social support (OR=3.28).</p><p><b>CONCLUSIONS</b>SS of hearing-disability persons is relatively low, which can be improved by treating physical diseases, promoting mental health, and providing psycho-social support.</p>

Exposure to avian influenza virus and the infection status of virus among people breeding or butchering ducks in the suburb of Beijing / 中华流行病学杂志

Objective To understand the exposure and the infection status of virus among people engaging in breeding or butchering ducks in the suburb of Beijing.Methods People from six districts (Daxing,Fangshan,Huairou,Miyun,Shunyi,Tongzhou) who engaged in breeding or butchering ducks were studied and the status of infecting avian influenza virus was obtained by testing antibody level in serum.Information on demographic characteristics,status of regular exposure and exposure to sick or dead poultry were collected through a self-designed questionnaire.Results 1741people were involved in this study in which 313 (18.0％ ) were workers in duck-breeding enterprise,562 (32.3％) were workers in duck slaughterhouse,261 (15.0％) farmers were in individualsmall-scale duck farms,605 (34.7％) were farmers raising duck in backyard.Among farmers raising duck in backyard,the percentage of people whose ducks ever contacted with wild birds was higher than the other three groups (66.8％)(P＜0.05).Among farmers who bred their ducks in the backyard (35.2％) and those abattoir workers (31.3％ ),the percentage of people who had contacted ducks but not been vaccinated with avian influenza vaccine was higher than the other two groups (P＜0.05).Regarding the status on cleaning and disinfection among the studied farmers who had bred their ducks in the backyard,the percentage of people who had closer contact with ducks would clean the settings more than 4 times per month (8.8％) and disinfected those places more than 12 times per year (27.3％) but still lower than the other three groups (P＜0.05).Among those farmers who bred ducks in the backyard,the percentage of people who had ever touched duck with their hands was high (34.4％) (P＜ 0.05).Regarding exposure to sick or dead poultry,higher proportion was found among those who had ever closely contacted sick or dead poultry commercial duck raisers (36.1％) and individuals who raise large amount of ducks (36.0％).70.8％ of the individual duck raisers had never taken any protective measures when closely contacting the sick or dead poultry.Among 1741 samples,0 were positive to avian influenza virus H5 and H7 subtypes.12 were positive to H9 subtype (positive rate was 0.7％ ),in which 10 were farmers raising ducks in backyard (the positive rate of 1.7％ ).Differences between H9 subtype antibody positive rates difference in 4 population groups were statistically significant (x2=13.699,P＜0.05).Conclusion Farmers who bred their ducks in the backyard had greater risk of contracting the avian influenza.Individual duckers who raise ducks in large scale and the farmers who bred their ducks in the backyard were in lack of protective measures when contacting the sick or dead poultry.Our findings suggested that some intervention measures should be taken to reduce the risk of avian influenza infection.

Investigation on Ehrlichia chaffeensis and Anaplasma phagocytophilum infection among farmers and domestic animals in rural areas of Beijing, China / 中华流行病学杂志

Objective To investigate the status of Ehrlichia (E.)chaffeensis and A naplasma (A.) phagocytophilum infection among farming populations and domestic animals in the rural area of Beijing,China.Methods Blood samples from 562 farmers and 163 blood samples including 90 goats,71 ox and 2 dogs,were collected.Specificity of IgG antibodies against E.chaffeensis and A.phagocytophilum were tested by micro-indirect immunofluorescent assay (mIFA).16S rRNA genes of A.phagocytophilum were amplified from the domestic animal blood samples and products were sequenced and analyzed by nested PCR.Results The positive rates of E.chaffeensis and A.phagocytophilum antibody were 16.5％ and 14.0％ respectively for farmers.The total positive rates of A.phagocytophilum were 2.3％ and 0 for both goats and oxen respectively.No antibody was found for the 2 tested dogs.The PCR positive rates were 48.9％ and 23.9％ for goats and oxen respectively.Three dominant varieties of A.phagocytophilum were demonstrated in goats and oxen.Conclusion The prevalence rates of E.chaffeensis and A.phagocytophilum were identified in the rural areas of Beijing.

Investigation on the source of the first human of avian influenza A (H5N1) case in Beijing / 中华流行病学杂志

Objective To investigate the source of the first human case of avian influenza A (H5N1) infection in Beijing. Methods Interviewing the relatives of the case and other key persons, collecting and detecting samples of related biological, epidemiological and environmental data of the case were conducted. Later, the infection source was thoroughly investigated. Results The case ever contacted a slaughtered duck 5 days prior to the onset of illness, and the duck was bought from a stall of a wet market in Yanjiao area of Hebei province. Ten environmental samples were collected in this stall and the neighboring stall of the market. Another 6 samples were tested positive for H5N1 virus by PCR method, with 5 virus strains isolated. The whole-genome sequencing indicated that the amino acid homology between the H5N1 virus strains from the environment and the virus isolated from the case reached 99.8%-100%. Conclusion From both epidemiological and virological evidence, it was proved that the first human case of avian influenza A (H5N1) infection in Beijing was infected by a duck that carrying H5N1 virus the case contacted 5 days proceeding the onset of illness.

Rhein lysinate induces apoptosis in breast cancer SK-Br-3 cells by inhibiting HER-2 signal pathway / 药学学报

This study is to investigate the effect of rhein lysinate on inducing human breast cancer cell line SK-Br-3 apoptosis and the role of HER-2 signal pathway in the apoptosis. MTT assay was used to detect SK-Br-3 cell proliferation. Cell cycle and apoptosis were analyzed by flow cytometry. The protein expression and the protein phosphorylation of HER-2 signal pathway were detected by Western blotting. The level of HER-2 mRNA was detected by RT-PCR and the level of HER-2 expression was also detected by immunofluorescence cytochemical methods. The results showed that rhein lysinate remarkably inhibited breast cancer SK-Br-3 cell proliferation. The IC50 value for 48 h treatment was 85 micromol x L(-1). Apoptosis in SK-Br-3 cells was induced by rhein lysinate in a dose dependent manner. The protein expressions of HER-2, NF-KB, and the protein phosphorylation of HER-2 were downregulated, however the protein expression of p53 and p21 was upregulated after rhein lysinate treatment. The level of HER-2 mRNA decreased by using RT-PCR assay and the level of HER-2 expression was also decreased by using immunofluorescence cytochemical assay after rhein lysinate treatment. It can be concluded that rhein lysinate could inhibit SK-Br-3 cell proliferation and induce apoptosis. HER-2/NF-kappaB/p53/p21 signal pathway might be involved in this process. Rhein lysinate has a good prospect to be an adjuvant chemotherapeutic drug.

A sero-epidemiologiecal study on hepatitis B among general population in Beijing / 中华流行病学杂志

<p><b>OBJECTIVE</b>To explore the serological infection rate of hepatitis B virus (HBV) in general population aged over one year old in Beijing and to provide information for control and prevention of the disease.</p><p><b>METHODS</b>A multistage randomized cluster sampling was carried out in general population of Beijing, aged over one year old. Every study subject's hepatitis B immunization history and main risk factors were investigated through questionnaire. Venous blood samples were collected and then tested for five hepatitis B serological antigens and antibodies by means of Abbott Microparticle Enzyme Immunoassy method.</p><p><b>RESULTS</b>The prevalence rates of HBsAg, anti-HBs, anti-HBc and total HBV infection rate were 3.49% (95% CI:2.99-3.99), 37.79% (95% CI: 36.46-39.12), 35.04% (95% CI: 33.72-36.35) and 35.09% (33.78-36.40) respectively. The age standardized rates were 3.02% ,42.47% ,26.86% and 26.90% respectively.</p><p><b>CONCLUSION</b>Achievement in hepatitis B control and prevention was made in Beijing since the prevalence rate of hepatitis B surface antigen had been below 1% for children aged less than 5 years old. As for the general population, the prevalence rate of hepatitis B surface antigen had reduced to</p>

Antitumor effect of the novel immunoconjugate composed of pingyangmycin and anti-type IV collagenase monoclonal antibody / 药学学报

<p><b>AIM</b>To study the antitumor effect of an immunoconjugate composed of pingyangmycin (PYM) and anti-type IV collagenase monoclonal antibody (mAb) 3G11.</p><p><b>METHODS</b>3G11-PLG-PYM immunoconjugate was prepared by linking 2-iminothiolane (2-IT) modified mAb to PYM via N-succinimidyl-3-(2-pyridyldithiol) -propionate (SPDP) derived poly-alpha-L-glutamic acid (PLG) backbone as the intermediate drug carrier. Characterization of the conjugate was performed by SDS-PAGE and spectrophotometry. Immunoreactivity of the conjugate against type IV collagenase was determined by ELISA. The cytotoxicity of the conjugate to hepatoma 22 (H22) and KB cells was examined by MTT assay. Antitumor effect of the conjugate in vivo was evaluated in mice bearing subcutaneously implanted H22 tumor, the candidate drugs were administered intravenously by "q2d x 6" regimen.</p><p><b>RESULTS</b>The molecular weight of the conjugate was approximately 170 kD. The molecular ratio of 3G11-PLG-PYM was 1 : 2. 4 : 10. The conjugate retained part of the immunoreactivity of mAb 3G11 against the antigen. The cytotoxicity of the conjugate to H22 and KB cells was moderate comparing with free PYM. In vivo however, free PYM inhibited the growth of H22 by 60.6% on day 22 at the dose of 10 mg x kg(-1), while the equivalent dose of 3G11-PLG-PYM conjugate reached 90.8%. The median survival time of the mice treated with the conjugate was prolonged by 71.7% as compared with that of the untreated group, whereas that of free PYM prolonged only 10.9%. 3G11-PLG-PYM conjugate was notably more effective than free PYM in tumor suppression and life span prolongation.</p><p><b>CONCLUSION</b>3G11-PLG-PYM displayed more marked antitumor efficacy than free PYM in vivo and might be a novel candidate for cancer treatment.</p>