[Analysis of current epidemiological and clinical characteristics for laboratory confirmed epidemic cerebrospinal meningitis cases in Shandong Province, 2007-2016].

Objective: To analyze epidemiological and clinical characteristics of laboratory confirmed epidemic cerebrospinal meningitis cases. Methods: Epidemiological and clinical informations and cerebrospinal fluid (CSF) and blood specimens of AMES (acute meningitis/encephalitis syndrome) cases were collected in the six sentinel hospitals from 2007 to 2016. neisseria meningitides (Nm) species and serogroup identification were detected by the methods of real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) and bacterial culture, and epidemiological and clinical characteristics of laboratory confirmed epidemic cerebrospinal meningitis cases were analyzed. Results: 6 809 AMES cases were reported from 2007 to 2016. Total 4 422 cases were detected, and 90 cases were Nm positive. Through the methods of Real-time PCR, bacterial blood culture and CSF culture, the numbers of Nm positive cases were 90, 2 and 1 respectively. Twenty-two Nm cases were identified from 2007 to 2011 (4 cases were ungrouped), which with the highest incidence in serogroup C cases (17/18), and one cases was ungroupable Nm. Nm laboratory confirmed cases (68 cases) were increased dramatically and mainly occurred in serogroup B cases (43/67, 64.2%) from 2012 to 2016, with serogroup C cases highly decreased (5/67, 7.5%) and ungroupable Nm cases increased (13/67, 19.4%) meanwhile. Serogroup W135 and X cases were first detected at 2012 and 2014, and serogroup A remaining a low level which only detected one case at 2013. The morbidity of epidemic cerebrospinal meningitis was occured in the whole year, and mainly in winter and spring. The ratio of Nm laboratory confirmed cases to AMES cases during November to May (3.5%, 67/1 920) was higher than that during June to October (0.9%, 23/2 502) (χ(2)=34.45, P<0.001). Most Nm cases were children, students and farmers, and account for 30.0% (27/90), 31.1% (28/90), 18.9% (17/90), respectively. The majority of Nm cases were under 20 years old (60/90, 66.67%), and serogroup C cases (17/22, 77.3%) mainly occurred in over 12 years old population, while serogroup B (24/43, 55.8%) and ungroupable (6/14) cases mainly occurred in under 12 years old population. The main clinical symptoms of epidemic cerebrospinal meningitis cases were fever (78/90, 86.7%), headache (59/90, 65.6%) and vomiting (51/90, 56.7%). Misdiagnosis rate of admitting diagnosis was up to 87.8% (79/90) for the reason of atypical features in specific symptoms and blood or CSF positive index. The well-healed ratio in correct diagnosed group (7/11) was higher than that in misdiagnosed group (2.5%, 2/79) (χ(2)=40.61, P<0.001). Conclusion: The clinical symptoms of epidemic cerebrospinal meningitis cases were atypical, and the diagnosed sensitivity and accuracy would be improved by enhanced molecular biology detection. The predominant epidemic serogroup of Nm switched from serogroup C to B, and the key work was surveaylance of serogroup transition.

[Etiologic surveillance and analysis of acute meningitis and encephalitis syndrome in Jinan city in 2013-2016].

Objective: To characterize the etiology and epidemiological characteristics of the acute meningitis and encephalitis syndrome (AMES) in Jinan city in 2013-2016. Methods: The epidemiological data, clinical diagnosis, serum and cerebrospinal fluid (CSF) specimens were collected from 3 577 AMES cases in 6 sentinel hospitals in Jinan city in 2013-2016. Samples of all cases were made sero-diagnosis for Immunoglobulin (Ig) M antibody to Japanese encephalitis virus (JEV) and negative cases of JEV for enterovirus (EV), mumps virus (MuV) and herpes simplex virus (HSV) by enzyme-linked immunosorbent assay (ELISA). Virus isolation and molecular identification were performed. Positive rates were analyzed by Chi-square test. Results: In 2013-2016, the positive rates of JEV, EV, MuV and HSV were 9.0% (322/3 577 cases), 22.1% (643/2 916 cases), 9.9% (289/2 916 cases), 26.9% (783/2 916), respectively. Of these, the positive rates of JEV were 32.9% (261/794), 1.2% (14/1 175), 1.0% (8/807) and 4.9% (39/801 cases); EV: 19.5% (91/466), 35.1% (342/974 cases), 15.5% (115/743) and 13.0% (95/733); MuV: 9.2% (43/466), 14.4% (140/974), 9.0% (67/743) and 5.3% (39/733). HSV: 35.4% (165/466), 38.5% (375/974), 25.7% (191/743) and 7.1% (52/733). There were significant differences in positive rates of 4 kinds of viruses in 2013-2016 (P<0.001). A total of 81 EV strains belonging to 8 serotypes were isolated from 1 020 CSF specimens. The positive rates were 4.8% (6 cases), 13.1% (55 cases), 4.1% (7 cases) and 4.2% (13 cases) from 2013 to 2016. Coxsackievirus (CV) B5, echovirus (E) 6 and E30 accounted for 46% (37 isolates), 22% (18 isolates) and 21% (17 isolates) of all strains. Conclusion: The AMES cases in Jinan city in 2013-2016 were mainly caused by HSV, EV, MuV, JEV. CVB5, E6 and E30 were the dominant serotypes of EV associated with AMES cases in Jinan city.

[Analysis of common pathogens and epidemiological characteristics of acute bacterial meningitis cases in Shandong Province].

Objective: To analyze epidemiological characteristics of acute bacterial meningitis (ABM) cases and the common pathogens infected in Jinan, Shandong Province. Methods: Epidemiological and clinical informations and cerebrospinal fluid (CSF) and blood specimens of acute meningitis/encephalitis syndrome (AMES) cases (total 3 918 cases) were collected in the six sentinel hospitals from 2013 to 2016. neisseria meningitidis (Nm), streptococcus pneumoniae (Sp) and haemophilus influenza (Hi) were detected by the methods of real-time fluorescent quantitative polymerase chain reaction (Real-time PCR), bacterial culture and latex agglutination. χ(2) test was used to compare ABM cases with different feasures, and compare the difference of Nm, Sp and Hi cases in clinical and epidemiological characteristics. Results: A total of 479 cases were diagnosed as ABM from 2013 to 2016, 82 cases of which were laboratory confirmed, including 54 cases infected with Nm, 25 cases infected with Sp, and 3 cases infected with Hi. The disease course in different age groups of ABM cases has statistically difference (χ(2)=40.95, P<0.001). The disease course of under 6 (63.6%, 161/253) and 7 to 17 (55.9%, 33/59) years old ABM cases mainly required 14-28 days, and over 18 years old cases mainly required less than 14 days (59.9%, 100/167). For Nm cases, there was a main onset period from October to March (75.9%, 41/54); on the disease course, under 6 (81.0%, 17/21) and 7 to 17 (16/18) years old cases mainly required less than 14 days, while over 18 years old cases mainly required 14-28 days (8/15), and there was a statistically difference in different age groups (χ(2)=8.44, P=0.015). For Sp cases, the major onset period was from December to May (84.0%, 21/25); on the disease course, all of under 6 and 7 to 17 years old cases were required 14-28 days, while over 18 years old cases mainly required less than 14 days (9/17), and there was a statistically difference in different age groups (χ(2)=6.62, P=0.037). 91.0% of the ABM cases (436/479) were healed or improvement, with the relatively higher ratio in under 6 (94.9%, 240/253) and 7 to 17 (98.3%, 58/59) years old groups, and poorer ratio in over 18 years old group (82.6%, 138/167), and the difference was significant in different age groups (χ(2)=22.77, P<0.001). For Nm, Sp and Hi cases, the ratio of cases that were healed or improvement were 87.0% (47/54), 92.0% (23/25) and 3/3, respectively, and there were no death cases. Conclusion: ABM cases were found mostly in under 18 years old group in Jinan, Shandong Province, and the bigger age group had poor prognosis. Nm was the major pathogen causing ABM, followed by Sp and Hi. Distinguished differences of epidemiological characteristics were found on ABM cases suffered with different pathogens infected.

[Evaluation on the short term effectiveness of two doses mumps-containing vaccine policy in Shandong, China].

Objective: To evaluate the effectiveness of mumps prevention and control after implementation of two doses mumps-containing combined vaccine (MuCV) policy by analyzing epidemiological characteristics of mumps and mumps antibody levels in general population. Methods: We obtained data on cases of mumps reported during 2004-2015 from National Notifiable Diseases Reporting System (NNDRS). Descriptive analysis methods were used to describe the epidemiological characteristics of mumps during 2004-2015. MuCV immunization information from 2005 to 2015 was obtained from the immunization information management system in Shandong Province. Antibody data of mumps in healthy people were from a cross-sectional survey according to the principle of stratified random sampling from 0 to 60 years old healthy people in 2015. Commercial ELISA kits were used to detect and quantify human IgG antibodies against mumps virus in sera, and the results were analyzed statistically. Results: The average incidence of mumps from 2004 to 2015 was 11.43/100 000 in Shandong. The incidence of mumps in the central region (14.64/100 000) was higher than that in the eastern and western regions (11.14/100 000, 11.33/100 000). The incidence of mumps was still high in 2009-2013 (stage of one-dose MuCV free, 16.07/100 000) with the highest incidence of 25.33/100 000 and 24.45/100 000 occurred in 2012 and 2013 and the cases were mainly 6 to 9 years old group (172.67/100 000). Since the second dose MuCV was introduced into NIP for 6 years old children in May 2013 in Shandong, the incidence of mump decreased significantly in 2014-2015 (7.81/100 000), especially in children of 6-8 years old who were vaccinated with two doses of MuCV (2009-2013 was 114.02/100 000; 2014-2015 was 45.66/100 000) and lower than 3-5 years old vaccinated one doses of MuCV. A total of 1 785 serum samples were collected from the healthy population, the average seroprevalence was 80.62% and Geometric Mean Concentration (GMC) was 38.11 IU/ml (95%CI: 37.03-39.19 IU/ml) . There was no significant difference about seroprevalence in different regions, while the GMC in middle region was significantly higher compared to east and west region. The prevalence and GMC in children aged 19 months-2 years and 3-5 years old who received one dose of MuCV were significantly higher than those of <19 months old children. The GMC (46.88 IU/ml, 95%CI: 39.43-55.74 IU/ml) in children aged 6-9 years old who received the two doses MuCV was significantly higher than that of aged 3-5 years old children (31.71 IU/ml, 95%CI: 27.23-36.93 IU/ml). Conclusion: The incidence of mumps in Shandong was still at a high level in spite of coverage one doses MuCV to children. Compared with the period of the 1 dose MuCV immunization strategy, the incidence the groups coverage two doses MuCV was significantly reduced and lower the groups coverage one dose MuCV, but the prevalence and GMC were higher than that of the groups coverage one dose MuCV.

[A sero-epidemiological study of hepatitis E among general population in Shandong Province of China in 2014].

Objective: To analyze the sero-epidemiological characteristics of hepatitis E virus (HEV) in Shandong province, and thereby to provide evidence for the policy-making of hepatitis E prevention and control. Methods: The inhabitants aged between 1-59 years old were randomly selected to participate in the study by two-stage stratified random sampling method from 12 counties in Shandong province in October, 2014. Firstly two townships were selected from each county by probability proportional to size sampling (PPS) method. A total of 5 229 participants aged 1-59 years old were selected by stratified random sampling method. All the participants finished a questionnaire survey and a venous blood sample (3-5 ml) was collected from each to test anti-HEV IgG by enzyme-linked assay (ELISA). The weighted prevalence of anti-HEV IgG with different demographic characteristics was estimated. The variance of the positive rate of anti-HEV IgG was calculated by Taylor series linearization method, as well as its 95%CI. A statistical test was conducted to compare the rate of its 95%CI, and the results in the present study were compared with those in sero-survey in 2006. Results: A total of 5 229 subjects entered the final analysis in 2014. The overall weighed prevalence of anti-HEV IgG was 9.19% (95%CI: 6.18%-12.20%) among natural population in Shandong province, decreased by 19.88% in comparison with that in 2006 sero-survey (11.47%, 95%CI: 8.92%-14.02%). The prevalence increased with age increasing (χ(2trend)=288.11, P<0.001) in 2014, which was similar to the result in 2006 sero-survey. Except for 1-4 years old group, the prevalence of anti-HEV IgG in the other age groups were lower than it in the corresponding groups in 2006. The prevalence of anti-HEV IgG in urban (8.19%, 95%CI: 0.00-22.23%), rural areas (9.69%, 95%CI: 4.99%-14.38%), eastern areas (12.70%, 95%CI: 0.00-27.72%), central areas (4.74%, 95%CI: 0.00-9.91%) and western areas (9.32%, 95%CI: 0.69%-17.94%) in 2014 were all lower than the corresponding prevalences (11.39%, 95%CI: 8.17%-14.62%; 11.92%, 95%CI: 8.75%-15.08%; 22.77%, 95%CI: 14.99%-30.55%; 7.97%, 95%CI: 4.75%-11.20%; 10.59%, 95%CI: 6.37%-14.82%) in 2006 survey. The prevalence of anti-HEV IgG in coastal areas (16.56%, 95%CI: 12.94%-20.18%) and inland areas (7.63%, 95%CI: 5.16%-10.10%) in 2014 were lower than it in the corresponding areas (28.04%, 95%CI: 20.45%-35.64%; 9.50%, 95%CI: 7.31%-11.70%) in 2006 survey. The prevalence among peasant (11.98%, 95%CI: 8.20%-15.76%), worker (9.68%, 95%CI: 4.48%-14.88%), cadre (13.90%, 95%CI: 7.47%-20.33%), service provider (12.26%, 95%CI: 1.80%-22.73%) in 2014 survey were lower than it among the corresponding populations (13.76%, 95%CI: 10.15%-17.38%; 21.11%, 95%CI: 12.67%-29.55%; 17.81%, 95%CI: 7.63%-28.00%; 21.08%, 95%CI: 0.03%-42.12%) in 2006 survey. Conclusion: The prevalence of anti-HEV IgG has decreased in Shandong province in the recent years, but the epidemiological characteristics found no obvious changes. HEV susceptibility in natural population was generally high. Hepatitis E vaccines were recommended to be used in HEV high-risk population in the province.

[Hepatitis B prevalence among women in child-bearing age in Shandong Province, China, 2014].

Objective: To know the prevalence of hepatitis B virus (HBV) among women in child-bearing age in Shandong Province, China, providing references to the improvement of HBV control strategy. Methods: The participants were randomly selected by two-stage sampling method from 12 counties which were representative for the whole province. Firstly two townships were selected from each county by probability proportional to size sampling (PPS) method. Then participants aged 1-4 years, 5-14 years, 15-29 years and 30-59 years were selected by stratified random sampling method. The women in child-bearing age (20-49 years) were involved in this study. Questionnaire survey and 5 ml blood collection were conducted among all participants. Blood samples were detected for hepatitis B surface antigen (HBsAg), antibody against HBsAg (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc). Those who were positive for HBsAg were further detected for hepatitis e antigen (HBeAg), antibody against HBeAg (anti-HBe) and the load of HBV DNA. The basic information of the participants including age, gender, occupation, nationality and residence place were collected. The prevalence of HBV infection indicators after weight adjustment were calculated and compared between participants with different demographic characteristics. Results: A total of 1 151 women in child-bearing age were involved in this study. Twenty-seven participants were positive for HBsAg and the prevalence rate was 2.10% (95% CI: 0.97%-3.23%). Five participants were positive for both HBsAg and HBeAg and the prevalence rate was 0.36% (95% CI: 0-0.84%). There were 567 and 291 participants who were positive for anti-HBs and anti-HBc respectively and the corresponding prevalence rates were 47.72% (95%CI: 41.68%-53.75%) and 24.40% (95% CI: 18.50%-30.30%). The number of participants susceptible for HBV was 527 and the percentage of HBV susceptible women was 47.55% (95% CI: 41.63%-53.47%). Conclusion: HBV infection among women in child-bearing age has attained very low level in Shandong Province, China. However, the high proportion of women in child-bearing age were still susceptible for HBV and hepatitis B immunization should be improved among them.

[Prevalence of hepatitis A antibody among population covered by different hepatitis A immunization strategies in Shandong Province, 2015, China].

Objective: To evaluate prevalence of hepatitis A antibody (anti-HAV IgG) among population covered by different hepatitis A vaccine immunization strategies in Shandong Province in 2015. Methods: In October 2015, according to the geographical location of Shandong Province, the stratified random sampling method was used to stratify the 17 municipal distrcts, and the random number table method was used for sampling, First, two eastern cites (Qingdao, Rizhao), two western cities (Liaocheng, Zaozhuang) and three central cities (Jinan, Zibo and Laiwu) were selected; secondly, one county was drawn from each city. Finally, the participants were divided into five age groups including ≤7 years (age group covered by free hepatitis A vaccination strategy), 8-11 years (age group who receive hepatitis A vaccination at their own charge), 12-24 years (age group covered by catch-up vaccination of hepatitis A), 25-34 years (age group born before hepatitis A vaccine was used) and ≥35 years (age group born before hepatitis A vaccine was used). After all the paticipants or their guardians asked and registered basic information such as age, gender, home address, blood samples were collected from them and anti-HAV IgG was detected by ELISA method. The positive rate of anti-HAV IgG and 95%CI were calculated. Results: A total of 1 654 participants were involved in the final analysis, including 856 males (51.75%) and 798 females (48.25%) whose mean age was (13.44±13.06) years. The crude positive rate of anti-HAV IgG was 91.41% (1 512/1 654, 95%CI: 89.96%-92.72%) and the age-adjusted rate was 90.93% (95%CI: 90.92%-90.94%). The positive rates of anti-HAV IgG was at the highest level in the age group of ≤7 years (95.90%, 95%CI: 95.88%-95.91%) and was at the lowest level in the age group of 25-34 years (83.23%, 95%CI: 83.21%-83.25%). The age-specific positive rates of anti-HAV IgG in eastern areas (96.79%, 95%CI: 96.78%-96.80%) were higher than those in both middle areas (86.66%, 95%CI: 86.65%-86.67%) and western areas (91.96%, 95%CI: 91.95%-91.97%). Conclusion: The positive rate of anti-HAV IgG was high among the general population in Shandong Province, but relatively low among young and middle-aged adults. Besides the routine immunization of hepatitis A among the children, more efforts should be taken for the prevention and control of hepatitis A among young and middle-aged adults in Shandong Province, especially in central and western areas.

[Anti-HBs persistence following primary vaccination with three doses of hepatitis B vaccine among normal and high-responder adults: a 3-year follow-up study].

OBJECTIVE: To assess the 3-year anti-HBs persistence after primary vaccination with three-dose of hepatitis B vaccine (HepB) among normal and high-responder adults. METHODS: A total of 24 237 healthy adults who had no histories of hepatitis B infection and hepatitis B vaccination, resided in local areas for more than six months and were aged 18-49 years were selected from 79 villages of Zhangqiu county, Shandong province, China in 2009. Blood samples were obtained and hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were detected using ELISA method. A total of 11 590 persons who were negative for all of these indicators were divided into four groups by cluster sampling method. Each group was vaccinated with one of the following four types of HepB at 0-1-6 months schedule: 20 µg HepB derived in Saccharomyces cerevisiae (HepB-SC), 20 µg HepB derived in Chinese hamster ovary cell (HepB-CHO), 10 µg HepB-SC and 10 µg HepB derived in Hansenula polymorpha (HepB-HP). Blood samples were collected one month after the third dose of primary immunization and tested for anti-HBs using chemiluminescence microparticle immunoassay (CMIA). During the follow-up to normal and high-responders, the following information was collected: the demographic characteristic (including age and gender), histories of hepatitis B infection, hepatitis B vaccination, smoking, drinking and chronic diseases. Blood samples were collected one month (T1) and three years after primary vaccination (T2) and anti-HBs, anti-HBc and HBsAg (if anti-HBs<10 mU/ml) were detected by CMIA. The risk factors associated with positive rate of anti-HBs and GMC of anti-HBs were identified by multiple logistic regression analysis and multifactor linear regression model analysis, respectively. RESULTS: A total of 4 677 normal and high-responders were identified. Among 4 677 participants, 2 014 (43.06%) were males and 2 663 (56.94%) were females. The positive rate was 100% at T1 and it decreased to 80.99% (3 788/4 677) three years after vaccination. The corresponding GMC was decreased from 1 413.48 (95%CI: 1 358.86-1 470.30) mU/ml to 60.33 (95%CI: 56.97-63.90) mU/ml. When comparing with those vaccinated 20 µg HepB-CHO, the significantly lower positive rate of anti-HBs three years after vaccination was observed in those vaccinated 20 µg HepB-SC, 10 µg HepB-SC and 10 µg HepB-HP. The OR (95%CI) was 0.65 (0.50-0.84), 0.52 (0.41-0.67) and 0.31 (0.28-0.45), respectively. The GMC of anti-HBs was also significantly lower among those vaccinated 20 µg HepB-SC, 10 µg HepB-SC and 10 µg HepB-HP. The b (95%CI) was -0.33 (-0.47- -0.20), -0.41 (-0.55- -0.28) and -0.78 (-0.92- -0.65), respectively. The GMC of anti-HBs in those aged 30-39 years old and 40-49 years old were lower than that in 18-29 years. The b (95%CI) was -0.31 (-0.47- -0.15) and -0.24 (-0.39- -0.09), respectively. When comparing with those whose anti-HBs titer was less than 999 mU/ml at T1, the significantly higher positive rate of anti-HBs three years after vaccination was observed in those whose anti-HBs titer was 1 000-1 999 mU/ml, those whose anti-HBs titer was 2 000-9 999 mU/ml and those whose anti-HBs titer was ≥10 000 mU/ml. The OR (95%CI) was 4.97 (3.80-6.49), 7.87 (16.19-10.01) and 9.67 (6.47-14.44), respectively. When comparing with those whose anti-HBs titer was ≤999 mU/ml at T1, the GMC of anti-HBs three years after vaccination was also significantly higher among those whose anti-HBs titer at T1 was 1 000-1 999 mU/ml, those whose anti-HBs titer at T1 was 2 000-2 999 mU/ml and those whose anti-HBs titer at T1 was ≥10 000 mU/ml. The b (95%CI) was 1.00 (0.87-1.14), 1.85 (1.74-1.97) and 3.28 (3.12-3.44), respectively. Four subjects showed HBsAg seroconversion and anti-HBc conversion rate was 4.68% at T2. CONCLUSIONS: Anti-HBs GMC decreased rapidly three years after primary vaccination among normal and high-responder adults, while the positive rate of anti-HBs still kept at a high level. The anti-HBs persistence after primary vaccination was associated with HepB type, age and GMC of anti-HBs one month after vaccination.

Src controls neuronal migration by regulating the activity of FAK and cofilin.

Migration of postmitotic neurons in the developing cortex along radial glial fiber is essential for the formation of cortical layers. Several neurological diseases are caused by defects in neuronal migration, underlining the importance of this process for brain function. Multiple molecules are involved in this process. However, the precise mechanisms are largely unknown. In the present study, we examined the expression of Src in the developing cortex and investigated the role of Src in neuronal migration and its cellular and molecular mechanisms. Our results showed that Src was strongly expressed in the cerebral cortex during corticogenesis and mainly targeted to the leading processes of migrating neurons. Overexpression of wildtype Src (Src-WT) and its mutants, constitutively active Src (Src-CA) and dominant negative Src (Src-DN) in the mouse brain by in utero electroporation perturbed neuronal migration through affecting the adhesion properties and cytoskeletal dynamics of migrating neurons. Overexpression of Src-WT and Src-CA induced aggregation and branching of migrating neurons, whereas overexpression of Src-DN led to abnormal elongation of the leading processes of migrating neurons. Furthermore, we showed that Src activates the focal adhesion kinase (FAK) and cofilin by regulating their phosphorylation levels. We conclude that Src controls neuronal migration by regulating adhesion properties and F-actin dynamics of migrating neurons.

Activation of C3a receptor is required in cigarette smoke-mediated emphysema.

Exposure to cigarette smoke can initiate sterile inflammatory responses in the lung and activate myeloid dendritic cells (mDCs) that induce differentiation of T helper type 1 (Th1) and Th17 cells in the emphysematous lungs. Consumption of complement proteins increases in acute inflammation, but the contribution of complement protein 3 (C3) to chronic cigarette smoke-induced immune responses in the lung is not clear. Here, we show that following chronic exposure to cigarette smoke, C3-deficient (C3(-/-)) mice develop less emphysema and have fewer CD11b(+)CD11c(+) mDCs infiltrating the lungs as compared with wild-type mice. Proteolytic cleavage of C3 by neutrophil elastase releases C3a, which in turn increases the expression of its receptor (C3aR) on lung mDCs. Mice deficient in the C3aR (C3ar(-/-)) partially phenocopy the attenuated responses to chronic smoke observed in C3(-/-) mice. Consistent with a role for C3 in emphysema, C3 and its active fragments are deposited on the lung tissue of smokers with emphysema, and smoke-exposed mice. Together, these findings suggest a critical role for C3a through autocrine/paracrine induction of C3aR in the pathogenesis of cigarette smoke-induced sterile inflammation and provide new therapeutic targets for the treatment of emphysema.

Heart-focused attention and heart-brain synchronization: energetic and physiological mechanisms.

CONTEXT: Many relaxation, meditation, and imagery techniques that implicitly or explicitly involve focused attention on the body, including qigong, massage, and noncontact therapeutic touch, purportedly employ energetic and physiological mechanisms. OBJECTIVE: To show that, from a perspective of dynamical energy systems, relaxed self-attention enhances connectivity between the brain and body. This enhanced connectivity may be achieved by at least 2 mechanisms: (1) physiological mechanisms employing peripheral negative feedback loops, and (2) bioelectromagnetic mechanisms involving direct energetic resonance between the peripheral organ and the brain. DESIGN: 19 channels of electroencephalogram, 1 electrocardiogram, and 2 channels of electro-oculogram were recorded from 22 subjects who focused their attention on their heartbeats or eye movements, with and without kinesthetic (touch) biofeedback to increase somatic awareness. RESULTS: Analyses of the electroencephalogram synchronized with the electrocardiogram revealed significant effects for heart-focused attention, primarily with touch biofeedback, following the contraction of the ventricles (possibly reflecting increased baroreceptor and somatosensory feedback); and significant effects for heart-focused attention, with and without touch biofeedback, preceding the contraction of the ventricles (possibly reflecting direct electromagnetic interactions between the heart and the brain). CONCLUSIONS: These findings suggest that energetic and physiological mechanisms may be involved in techniques in which the goal is to promote mind-body integration and health.

[A serological study on the immunization schedule at first dose of domestic BRD II strain rubella vaccine].

In order to develop a valid immunization schedule on the initial vaccination at different age of domestic BRD II strain rubella vaccine, a total number of 268 children at the age of 6 to 18 months from Yantai city of Shandong Province, China were selected for the serological study on hemagglutination inhibition (HI) antibody level against rubella from August to October, 1995. The results showed that the negative rates of HI antibody among children of 6, 7, 8, 9, 12 and 18 month olds before inoculation with rubella vaccine were 100.00%, 95.56%, 93.02%, 96.36%, 97.96% and 93.94% with geometric mean titers (GMTs) 0.00, 1.17, 1.21, 1.12, 1.07 and 1.13, respectively. After one month of immunization with rubella vaccine, the positive rates and GMTs of HI antibody were 97.67%, 95.56% 97.67%, 98.18%, 97.96%, 96.67% and 110.17, 197.02, 155.32, 177.63, 192.92, 142.17, respectively. There was no significant difference on immuno-response to rubella vaccine in children regardless the previous titers. Taking these results together with the current vaccine immunization schedule for expanded programme on immunization (EPI) in China into consideration, the author recommended that the immunization schedule at first vaccination for BRD II strain rubella vaccine should be started at 8 month olds.

Effective lowering of plasma, LDL, and esterified cholesterol in LDL receptor-knockout mice by adenovirus-mediated gene delivery of ApoB mRNA editing enzyme (Apobec1).

Adenovirus-mediated gene delivery of apolipoprotein (apo)B mRNA editing enzyme (AvApobec1) was used to study the effect of apoB mRNA editing on apoB production in homozygous LDL receptor-deficient (LDLR-/-) mice. Intravenous injection of AvApobec1 into these mice resulted in a >80% decrease in plasma apoB-100 with a concomitant increase in plasma apoB-48 level. The plasma apoE level also increased. In all cases, total plasma apoB (apoB-100 + apoB-48) decreased by 60% at day 5 and remained approximately 40% lower in AvApobec1-treated compared with control vector Av1LacZ4-treated animals at day 12. On day 12, total plasma cholesterol decreased by 29% in male mice and 18% in female mice that were transduced with AvApobec1. This was reflected in a reduction in apoB-containing lipoprotein cholesterol, which decreased by 34% and 27% in male and female mice, respectively. Apobec1 gene transfer also decreased the cholesteryl ester contents in the LDL fraction, which were 16%, 22%, and 22% in female and 20%, 20%, and 15% in male animals on days 5, 7, and 12, respectively, compared with Av1LacZ controls with 29%, 32%, and 33%, respectively, in female and 29%, 38%, and 36%, respectively, in male animals. Nondenaturing gradient gel electrophoresis indicated almost complete elimination of LDL particles of 29, 27, and 25 nm at days 7 and 12. We conclude that in the absence of a functioning LDL receptor, hepatic overexpression of Apobec1 is highly efficient in lowering plasma apoB-100 levels, leading to the almost complete elimination of LDL particles and a reduction in LDL cholesterol and cholesteryl ester content.

Cloning of the bacteriophage T7 lysozyme gene.

Plasmid pBR322 and its derivative containing strong promoter phi 10 of bacteriophage T7 RNA polymerase were used as vectors. A fragment of bacteriophage T7 DNA which was digested with two restriction endonucleases (AvaII and HaeIII) was cloned in the BamHI site of plasmid pBR322 and its derivative pAR951, respectively. The inserted DNA is a segment of 632 base pairs containing the complete coding sequence of both T7 gene 3.5 and weak promoter phi 3.8 for bacteriophage T7 RNA polymerase. The function of T7 gene 3.5 is known to code for bacteriophage T7 lysozyme. Transformants that carry the recombinant plasmid were tested for intracellular lysozyme by adding CHCl3. Both cloned strains produce active T7 lysozyme. The gene product, T7 3.5 protein, was analyzed by 10 -20% gradient polyacrylamide- SDS electrophoresis. The result showed that the expression of inserted T7 gene 3.5 in pBR322 derivative is stronger than that in pBR322.