[Analysis of follow-up results of chrono-chemotherapy or conventional chemotherapy combined with intensity modulated radiotherapy in locally advanced nasopharyngeal carcinoma].

Objective: To evaluate the long-term effect and safety of chrono-chemotherapy combined with intensity modulated radiotherapy (IMRT) in locally advanced nasopharyngeal carcinoma (NPC). Methods: 160 patients with locally advanced NPC were randomly divided into a chrono group and conventional group according to random number table. In the first stage, all patients underwent two cycles of induced chemotherapy, consisting of docetaxel, cisplatin and 5-Fu every 21 days. Notably, patients received chrono-moduated chemotherapy according to circadian rhythm in the chrono group, and conventional chemotherapy in the conventional group. Then, 21 days after the completion of first stage, three cycles of concurrent cisplatin chemotherapy every 21 days were given to all patients during IMRT. The median follow-up after the completion of radiotherapy was 31 months. Long-term side effects and the survival of patients were observed. Results: Patients in the chrono group had significantly lower rates of hearing loss (22.72%), dysphagia (0) and neck fibrosis (4.54%) compared with those in the conventional group (39.13%、8.69%, 15.94%, respectively, all P<0.05). Meanwhile, the 1- year overall survival rates (97.0% vs 92.8%), 3-year overall survival rates (80.3% vs 81.2%), 1-year progression free survival rates (95.5% vs 87.0%), 3-year progression free survival rates (71.2% vs 73.9%), 1-year locoregional relapse-free survival rates (97.0% vs 95.7%), 1-year locoregional relapse-free survival rates (92.4% vs 92.8%), 1-year distant metastasis-free survival rates (97.0% vs 98.6%) and 3-year distant metastasis-free survival rates (90.9% vs 91.3%) between the chrono group and the conventional group were not statistically significant (all P>0.05). Conclusions: Compared with conventional chemotherapy, chrono-chemotherapy combined with IMRT didn't affect long-term survival, but reducing the incidence of adverse events in patients with locally advanced NPC.

[Esthetic proportions of maxillary anterior teeth of 120 Chinese adults].

OBJECTIVE: To analyze the esthetic proportions of maxillary anterior teeth in term of the apparent widths proportion of the adjacent teeth and width/height ratio of the clinical crown in 120 Chinese adults. METHODS: Maxillary gypsum casts were obtained from the dental laboratories of stomatological hospitals in North China, Southeast China, and Southwest China, according to the inclusion criteria and exclusion criteria. Standardized digital photographs of each cast were recorded. The apparent widths and actual widths and heights of the central incisors, lateral incisors and canines were determined by ImageJ software for the calculation of apparent widths proportion of the adjacent teeth and width/height ratio of the clinical crown. The ideal apparent widths proportion (Golden proportion and Preston proportion) and width/height ratio (0.80) were tested. The gender, arch side, and regional differences were investigated. RESULTS: The apparent widths proportion of the lateral/central incisor was 0.724±0.047, of the canine/lateral incisor was 0.814±0.092. The width/height ratio of the central incisor was 0.848±0.072, of the lateral incisor was 0.834±0.094, of the canine was 0.883±0.098. The esthetic proportions were different from the predicted ideal ratio (P < 0.001). The apparent widths proportion of lateral/central incisor was significantly larger in the right side than that in the left side (0.730± 0.044 vs. 0.718±0.050), and was significantly smaller in North China than that in Southwest China (0.711±0.051 vs. 0.731±0.044). The width/height ratio of the central incisor was significantly larger in the female than that in the male (0.855±0.074 vs. 0.835±0.068), and in the right side than that in the left side (0.855±0.073 vs. 0.842±0.072). The width/height ratio of the lateral incisor was significantly larger in the female than that in the male (0.843±0.097 vs. 0.817±0.084). CONCLUSION: The apparent widths proportion of adjacent teeth and the width/height ratio of the clinical crown in Chinese adults are different from the foreigner's. The esthetic proportion parameters have significant population specificity, and the measurements cannot be generalized as well as it should be applied with caution.

[Clinical features and prognosis of pediatric myelin oligodendrocyte glycoprotein antibody associated acute disseminated encephalomyelitis].

Objective: To analyze the clinical features, outcome and prognosis of pediatric myelin oligodendrocyte glycoprotein (MOG) antibody associated acute disseminated encephalomyelitis (ADEM), and provide evidence for improving the diagnosis and treatment of this disease. Methods: This study involved 30 MOG antibody-associated ADEM patients in the Department of Neurology, Guangzhou Women and Children's Medical Center. Patients' clinical information were analyzed. Results: The mean onset age was (5.2±3.3) years old, the ration of male to female was 16∶14. Fifty percent of these patients had a history of precede infection or vaccination before onset. Encephalopathy and seizures were the most common clinical manifestations, followed by movement disorder. In addition, some patients had other positive autoantibodies. Brain Magnetic resonance imaging (MRI) showed extensive, asymmetrical, indefinite large patchy lesions in bilateral cortical and subcortical areas and the spinal cord was characterized by long segmental myelitis. In acute attack, the patients had a good response to corticosteroid combined immunoglobulin therapy. Most of these patients had a good prognosis and recurrence rate was about 20%. Conclusions: The onset age of MOG antibody-associated ADEM is around 5 years old. Encephalopathy and seizures were the most common clinical manifestations. Most patients have a good response to corticosteroid combined immunoglobulin therapy. Some patients may have a recurrent disease course.

[Genotype distribution and molecular epidemiology of hepatitis E virus isolated in Shandong Province of China in 2017].

Objective: To understand the genotype distribution and molecular epidemiological characteristics of hepatitis E virus (HEV) isolated in Shandong Province, 2017. Methods: The cases of hepatitis E who were reported to the National Notifiable Disease Reporting System (NNDRS) from January to December 2017 in Shandong Province were chosen as the subjects in the study. Epidemiological information and blood samples were collected from 1 045 participants. Both anti-HEV IgM and anti-HEV IgG were detected using ELISA method. Viral nucleic acids were extracted only from those of anti-HEV IgM positive samples. Nested reverse transcription-polymerase chain reaction was carried out to amplify 644 bp nucleotide sequences within HEV open reading frame (ORF) 2 region. The sample sequences together with reference sequences from GenBank were subjected to phylogenetic analysis. Results: In total, 638 (61.1%) cases were detected positive for anti-HEV IgM. The average age of male was (57.9±12.2) years, and the anti-HEV IgM positive rate was 61.5% (496/807). The average age of female was (58.1±15.0) years, and the anti-HEV IgM positive rate was 59.7% (142/238). A total of 163 HEV strains were detected, and the positive rate was 25.6% (163/638). The positive rate of the eastern, central and western region was 23.0% (71/309), 33.6% (72/214) and 17.4% (20/115), respectively. Phylogenetic tree and homology analysis indicated that all isolates belonged to genotype Ⅳ, clustering into four different subgenotype (4a, 4b, 4d and 4h). Subgenotype 4d was predominant, accounting for 85.9% (140 strains), followed by 4b (7.4%, 12 strains), 4a (3.7%, 6 strains) and 4h (3.1%, 5 strains). The 4a, 4b, and 4h subgenotype were mainly detected in the eastern region, accounting for 3/5, 11/12, and 4/6, respectively. The 4d subgenotype was mainly in the middle region, accounting for 50.0% (70/140). The homology analysis showed that the 163 sequences shared 82.7% to 100.0% nucleotide sequence identity with each other. The 140 sequences of HEV 4d strains showed high similarity with swine-origin HEV（KF176351）, cattle-origin HEV（KU904278）and sheep-origin HEV（KU904267）isolated in Shandong Province, and the nucleotide homology was 93.1%-98.3%, 92.7%-97.9% and 92.7%-97.9%, respectively. Conclusion: HEV genotype Ⅳ(4d subgenotype) was dominant in Shandong province. A complicated interspecies transmission might be the main source of human HEV infection in Shandong Province, China.

Association of meteorological factors with seasonal activity of influenza A subtypes and B lineages in subtropical western China.

The seasonality of individual influenza subtypes/lineages and the association of influenza epidemics with meteorological factors in the tropics/subtropics have not been well understood. The impact of the 2009 H1N1 pandemic on the prevalence of seasonal influenza virus remains to be explored. Using wavelet analysis, the periodicities of A/H3N2, seasonal A/H1N1, A/H1N1pdm09, Victoria and Yamagata were identified, respectively, in Panzhihua during 2006-2015. As a subtropical city in southwestern China, Panzhihua is the first industrial city in the upper reaches of the Yangtze River. The relationship between influenza epidemics and local climatic variables was examined based on regression models. The temporal distribution of influenza subtypes/lineages during the pre-pandemic (2006-2009), pandemic (2009) and post-pandemic (2010-2015) years was described and compared. A total of 6892 respiratory specimens were collected and 737 influenza viruses were isolated. A/H3N2 showed an annual cycle with a peak in summer-autumn, while A/H1N1pdm09, Victoria and Yamagata exhibited an annual cycle with a peak in winter-spring. Regression analyses demonstrated that relative humidity was positively associated with A/H3N2 activity while negatively associated with Victoria activity. Higher prevalence of A/H1N1pdm09 and Yamagata was driven by lower absolute humidity. The role of weather conditions in regulating influenza epidemics could be complicated since the diverse viral transmission modes and mechanism. Differences in seasonality and different associations with meteorological factors by influenza subtypes/lineages should be considered in epidemiological studies in the tropics/subtropics. The development of subtype- and lineage-specific prevention and control measures is of significant importance.

[Persistence of immune memory and its related factors at 12 years after hepatitis B vaccination among adults].

Objective: To estimate the immune memory at 12 years after hepatitis B vaccination and its risk factors among adults. Methods: The study was conducted in 20 villages of Qudi town in Jiyang county, Shandong province, China in 2003. Hepatitis B surface antigen (HBsAg), antibody against HBsAg (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were tested for all healthy residents aged 15-40 years in these villages. Those who had no history of hepatitis B vaccination and were negative for all three indicators were divided into two groups randomly. Hepatitis B vaccine (HepB) was administrated to them on 0-6 month schedule or 0-1-6 month schedule respectively. Blood samples were obtained at one month after the last dose for each receipt and were quantitatively detected for anti-HBs. Finally a total of 629 participants completed HepB vaccination and anti-HBs testing, including 288 of two-dose group and 341 of three-dose group respectively. In 2015, an additional dose of HepB (challenge dose) was administrated to those who were negative for anti-HBs at follow-up (anti-HBs <10 mIU/ml) to evaluate the immune memory. A total of 93 blood samples, including 50 of two-dose group and 43 of three-dose group respectively, were drawn at 14 days after the challenge dose and anti-HBs was quantitatively detected. The anti-HBs geometric mean concentrations (GMCs) after the challenge dose were compared between the two groups. Multivariate linear regression model was built to find the independent risk factors associated with immune memory response (anti-HBs GMC after the challenge dose). Results: The challenge dose of HepB and post-challenge anti-HBs detection were completed among 93 participants. Totally 92 (98.92%, 92/93) participants were found holding immune memory (anti-HBs after the challenge dose was ≥10 mIU/ml). The immune memory positive rates were 100% (50/50) and 97.67% (42/43) in the two-dose group and three-dose group respectively and the corresponding anti-HBs GMC after challenge dose were 2 684.30 (95%CI: 1 721.71-4 185.08) mIU/ml and 3 527.48 (95%CI: 2 145.15-5 800.58) mIU/ml (P=0.410). The anti-HBs GMC after the challenge dose were 1 908.33 (95%CI: 1 190.01-3 060.27) mIU/ml, 4 004.20 (95%CI: 2 257.90-7 101.12) mIU/ml and 8 682.16 (95%CI: 5 813.94-12 965.36) mIU/ml among the participants whose anti-HBs titer was<4, 4-6 and 7-9 mIU/ml at follow-up, respectively (P=0.002). There was no correlation between immune schedule and anti-HBs GMC after the challenge dose; ß (95%CI) was -0.07 (-0.34-0.20), P=0.601. Conclusion: The immune memory after primary hepatitis B vaccination lasted for at least 12 years among adults. The immune memory response was independently associated with ant-HBs titer at follow-up, but might be similar between 0-6 month schedule and 0-1-6 month schedule.

[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.

[Anti-HBs persistence after revaccination with three doses of hepatitis B vaccine among low-responder infants following primary vaccination: 4-year of follow-up].

Objective: Assess the 4-year antibody against hepatitis B surface antigen (anti-HBs) persistence after revaccination with 3-dose of hepatitis B vaccine (HepB) among low-responder infants following primary vaccination. Methods: According to stratified cluster sampling, a total of 4 147 infants were enrolled and primarily vaccinated with 5 µg HepB derived in Saccharomyces Cerevisiae (HepB-SC) at 0-1-6 months schedule from 75 towns of Jinan, Weifang, Yantai, Weihai prefectures, Shandong Province, China in Aug and Sep 2009. Blood samples were collected one to six months after the third dose of primary immunization and tested for anti-HBs using chemiluminescence microparticle immunoassay (CMIA). 717 infants who appeared low response (10 mU/ml ≤ anti-HBs<100 mU/ml) were revaccinated with 3-dose of HepB. Blood samples were collected from a total of 315 infants one month (T(0)), four years (T(1)) after revaccination and anti-HBs, antibody against hepatitis B core antigen (anti-HBc) and hepatitis B surface antigen (HBsAg) were detected by CMIA. Information about their birth, primary vaccination were collected. The risk factors associated with positive rate of anti-HBs and GMC of anti-HBs were identified by multiple non-conditional logistic regression analysis and multifactor linear regression model analysis, respectively. Results: Among 315 children, 165 (52.38%) were male and 150 (47.62%) were female. The positive rate was 83.81% (264/315) at T(0) and it decreased to 16.51% (149/529) at T(1). The corresponding GMC decreased from 473.15 mU/ml to 17.37 mU/ml. The average annual decreasing rate of positive rate and GMC was 33.38% and 56.23% from T(0) to T(1). Multivariable analysis showed the positive rate and GMC among those whose anti-HBs titer higher at T(0) were significantly higher at T(1). The positive rate at T(1) among those whose anti-HBs titer 400-<600, 600-<800, 800-<1 000, ≥1 000 mU/ml at T(0) were significantly higher than those whose anti-HBs titer less than 200 mU/ml. The OR (95%CI) of the positive rate was 4.29 (1.03-17.84), 4.53 (1.25-16.47), 4.19 (1.10-15.97) and 9.13 (2.91-28.63), respectively. The GMC at T(1) among those whose anti-HBs titer 400-<600, 600-<800, 800-<1 000 mU/ml and those whose anti-HBs titer ≥1 000 mU/ml at T(0) were higher than those whose anti-HBs titer<200 mU/ml. The b value (95% CI) of GMC was 0.84 (0.06-1.62), 1.13 (0.46-1.79), 1.33 (0.65-2.01) and 1.88 (1.33-2.44), respectively. GMC among full-term infants were significantly higher than premature infants at T(1). The b value (95% CI) of GMC was 0.86 (0.04-1.68). Conclusion: Anti-HBs GMC decreased rapidly 4 years after revaccination among low-responder infants, but still kept good protection. The anti-HBs persistence after revaccination was associated with anti-HBs level of titer one month after revaccination.

[Antibody persistence following primary vaccination with hepatitis B vaccine among normal and high-responder adults: a 5-year follow-up study].

OBJECTIVE: To evaluate the 5-year antibody persistence and the risk factors associated with the persistence after primary vaccination of hepatitis B vaccine (HepB) among normal or high-response adults. METHODS: A total of 24 237 healthy adults who had no histories of hepatitis B infection and hepatitis B vaccination, resided in the local area for more than six months and were aged 18-49 years were selected from 79 villages in north 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 methods. 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). The normal and high-responder was followed up and their demographic characteristic (including age, gender), histories of hepatitis B infection, hepatitis B vaccination, smoking, drinking and chronic diseases were investigated. Blood samples were collected one month (T1) and five years (T2) and anti-HBs, anti-HBc and HBsAg (if anti-HBs<10 mU/ml) were detected by CMIA. A total of 1 902 participants were followed up and 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: Among 1 902 adults, 824 (43.32%) were male and 1 078 (56.68%) were female. The anti-HBs positive rate was 100% at T1 and it decreased to 73.29% (1 394 cases) at T2. The corresponding GMC was decreased from 1 527.15 (95%CI: 1 437.84-1 622.01) mU/ml at T1 to 35.07 (95%CI: 32.20-38.19) mU/ml at T2. When comparing with those vaccinated 20 µg HepB-SC, the significantly lower positive rate at T2 was observed in those vaccinated 10 µg HepB-SC group and 10 µg HepB-HP group. The OR (95% CI) was 0.41 (0.28-0.61) and 0.27 (0.18-0.39), respectively. The GMC of anti-HBs was also significantly lower among those vaccinated 10 µg HepB-SC and 10 µg HepB-HP. The b (95%CI) was -0.20 (-0.28- -0.12) and -0.36 (-0.44- -0.29) , respectively. When comparing with those occasionally drinking, the significantly lower positive rate at T2 was observed in those regular drinking. The OR(95%CI) was 0.51(0.30-0.87). The GMC of anti-HBs in age group of 18-29 was significantly higher than those in 40-49 age group; the b (95%CI) was -0.10(-0.18- -0.01). When comparing with those whose anti-HBs titer was less than 999 mU/ml at T1, the significantly higher positive rate of anti-HBs at T2 was observed in those whose anti-HBs titer was 1 000-1 999 mU/ml, those whose anti-HBs titer was 2 000-2 999 mU/ml and those whose anti-HBs titer was ≥10 000 mU/ml. The OR (95%CI) was 10.11 (6.90-14.82), 20.42 (13.98-29.82) and 54.58 (22.08-134.92), respectively. When comparing with those whose anti-HBs titer was ≤999 mU/ml at T1, the GMC of anti-HBs at T2 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 0.55 (0.47-0.62), 0.94 (0.88-1.00) and 1.63 (1.54-1.72), respectively. Nobody was found positive to HBsAg at T2 and the conversion rate of anti-HBc was 3.89% (74/1 902) at T2. CONCLUSION: Anti-HBs GMC decreased rapidly at T2 among normal and high-responder adults, while the positive rate of anti-HBs still kept at a high level. The antibody persistence among normal and high-responder adults at T2 was associated with HepB type, age, history of drinking and GMC of anti-HBs at T1.

[Anti-HBs persistence following revaccination with three doses of hepatitis B vaccine among low-responsive adults after primary vaccination: a 4-year follow-up study].

OBJECTIVE: To assess the 4-year anti-HBs persistence after revaccination with 3-dose of hepatitis B vaccine (HepB) among low-responsive adults. METHODS: A total of 24 237 healthy adults who had no history of hepatitis B infection and hepatitis B vaccination, resided in the local area 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). The 892 low-responders were revaccinated with three doses of HepB at 0-1-6 months schedule and the type of HepB was the same as which was used for primary immunization. During the follow-up to low-responders, the following informations were collected: the demographic characteristics (including age, gender), histories of hepatitis B infection, hepatitis B vaccination, smoking, drinking and chronic diseases. Blood samples were collected one month (T1) and four years after revaccination 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. Anti-HBs titer at T1 was grouped according to the level and was considered as the independent variable in the model analysis. RESULTS: A total of 529 participants were identified from 892 low-responders. Among 529 participants, 276 (52.2%) were males and 253 (47.8%) were females. The positive rate was 82.6% (437/529) at T1 and it decreased to 28.2% (149/529) four years after revaccination. The corresponding GMC decreased from 542.06 (95% CI: 466.72-629.56) mU/ml to 27.69 (95% CI: 23.08-33.23) mU/ml. Multivariable analysis showed the positive rate of anti-HBs 4 years after revaccination was independently associated with anti-HBs titer at T1. The positive rate among those whose anti-HBs titer more than 1 000 mU/ml at T1 was significantly higher than those whose anti-HBs titer less than 100 mU/ml. The OR (95%CI) was 39.67 (13.81-114.01). The GMC was associated with HepB type for revaccination and anti-HBs titer at T1. The GMC among those revaccinated 20 µg HepB was significantly higher than those revaccinated 20 µg HepB-CHO, 10 µg HepB-SC and 10 µg HepB-HP. The b (95% CI) was -0.40 (-0.78--0.02), -0.57 (-1.01- -0.15) and -0.63 (-1.03- -0.23), respectively. The GMC among those whose anti-HBs titer 100-999 mU/ml and those whose anti-HBs titer ≥1 000 mU/ml at T1 were higher than those whose anti-HBs titer <100 mU/ml. The b (95% CI) was 0.93 (0.53-1.33) and 3.31 (2.88-3.73) respectively. CONCLUSION: Anti-HBs GMC decreased rapidly 4 years after revaccination among low-responsive adults, but still kept good protecion. The anti-HBs persistence after revaccination was associated with HepB type for revaccination and anti-HBs level of titer one month after revaccination.

[Anti-HBs persistence after revaccination with three doses of hepatitis B vaccine among non-responsive adults: a 4-year of follow-up study].

OBJECTIVE: To explore anti-HBs persistence four years after revaccination with hepatitis B vaccine (HepB) among adults who were non-responsive to HepB primary immunization. METHODS: A total of 24 237 healthy adults who had no history of hepatitis B infection and hepatitis B vaccination, resided in the local area for more than six months and 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 methods. Each group was vaccinated with one of the following four types of HepB at 0-1-6months 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). The non-responders were followed up and their basic information and the histories of hepatitis B infection, HepB vaccination, smoking and drinking were investigated. Then they were revaccinated with three doses of HepB with the same schedule as the primary immunization. Blood samples were collected from all of them one month (T1), two years and four years after revaccination and anti-HBs, anti-HBc and HBsAg were detected by CMIA. A total of 356 participants were followed up from 645 low-responders four years after revaccination, and the ratio was 55.2%. The risk factors associated with the positive rate and geometric mean concentration (GMC) of anti-HBs after four years of revaccination were analyzed using multivariate unconditional logistic regression model and multivariate linear regression model, respectively. RESULTS: Among 356 participants, 172 (48.3%) were males and 184 (51.7%) were females. The anti-HBs positive rate was 90.4% (322 cases) at T1 and was 55.9% (199 cases) four years after revaccination. The GMC of anti-HBs was 240.5 (95% CI: 186.4-310.4)mU/ml at T1 and decreased to 15.0 (95%CI: 12.2-18.5) mU/ml four years after revaccination. The average annual decreasing rate of GMC was 50.63% from one month after revaccination to four years after revaccination. The corresponding rate was 64.89% in the first two years, which was 2.12 times the rate in the latter two years (30.57%). When compared with those whose anti-HBs titer was less than 99 mU/ml at T1, the significantly higher anti-HBs four years after revaccination was observed in those whose anti-HBs titer at T1 was 100-999 mU/ml and those whose anti-HBs titer at T1 was ≥1 000 mU/ml. The OR (95%CI) was 7.14 (3.90-13.05) and 28.40 (13.16-61.30) respectively. When compared with those whose anti-HBs titer was ≤99 mU/ml at T1, the GMC of anti-HBs four years after revaccination was also significantly higher among those whose anti-HBs titer at T1 was 100-999 mU/ml and those whose anti-HBs titer at T1 was ≥1 000 mU/ml. The b (95%CI) was 1.66 (1.26-2.05) and 3.16 (2.72-3.60), respectively. CONCLUSION: The positive rate and GMC of anti-HBs decreased four years after revaccination among non-responsive adults, but still kept anti-HBs above protective level. The immunity durability after revaccination is mainly associated with anti-HBs titer one month after revaccination.

[The influence of condensate in the piezometric tube on patient ventilator interaction during noninvasive positive pressure ventilation].

OBJECTIVE: To study the effects of condensate in the piezometric tube on patient ventilator interaction during noninvasive positive pressure ventilation. METHODS: Eleven healthy adults volunteered to receive noninvasive positive pressure ventilation. Different capacity of physiological saline was injected gradually into the piezometric tube until the volunteers could not trigger the ventilator or the total volume of the water reached 1.5 ml. The dynamic changes of the pressure of mask(Pmask), piezometric tube near mask (Ppro), piezometric tube near breathing machine(Pdis), and the flow were observed. RESULTS: With increasing volume of saline injected, the trigger time TItri(Pmask) increased from 0.09(0.07-0.11) to 0.31(0.22-0.39)s, the trigger pressure TPtri(Pmask) increased from 0.26(0.15-0.33) to 2.29(1.76-3.09)cmH2O, and the pressure-time product PTP (Pmask) increased from 0.02(0.01-0.03) to 0.55(0.41-0.68) cmH2O·s. Ineffective triggering rate increased from 0 up to 9 times/min, and spurious triggering rate increased from 0 up to 33 times/min. The plateau pressure of Pmask and Ppro exceeded the preset parameters, increased significantly as compared with 0 ml, from (9.74±0.34)to (15.79±3.10) cmH2O and from(9.80±0.31) to(15.44±3.47) cmH2O. The change of plateau pressure of Pdis was not significant [from (9.85±0.29)to (12.58±2.64)cmH2O]. The baseline pressure of Pmask, Ppro and Pdis changed from (3.67±0.36) to (8.40±3.22) cmH2O, from (3.71±0.32) to (8.13±3.55) cmH2O and from( 3.77±0.32) to (5.36±1.25) cmH2O, respectively. The pressure fluctuation of platform of Pmask increased significantly compare with 0 ml, from 0.60(0.48-0.71) to 7.94(7.11-8.63)cmH2O. The frequency of fluctuation of platform increased as many as 7 times during a single respiratory period. The time when the pressure of the Pdis began to change was delayed to Pmask and Ppro, 0.11(0.08-0.12)s compared with 0 ml. CONCLUSION: Condensate in the piezometric tube during noninvasive positive pressure ventilation could influence patient-ventilator synchrony. To improve patient ventilator interaction in noninvasive positive pressure ventilation, condensate in the piezometric tube should be avoided.

Correlation of spicule sign on computed tomography scans with peripheral lung cancers associated with interstitial lung disease and chronic obstructive pulmonary disease.

The objective of this study was to investigate the correlation between spicular signs on computed tomography (CT) scans and peripheral lung cancer (PLC) that is associated with interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD). We analyzed clinical data from 96 PLC cases and grouped patients based on whether they had interstitial pneumonia into either ILD/COPD group or non-ILD/COPD group. The occurrence rate of spicule sign was 90.3% in the ILD/COPD group and 61.8% in the non-ILD/COPD group, respectively. There was a significant difference between these groups (P < 0.05). There were no significant differences in the occurrence rate of spicular signs among patients with different pathological types of PLC. The severity of ILD affected the spicular morphology on CT scans directly. There was a significant correlation between the appearance of spicule sign on CT scans and PLC that was associated with ILD/COPD.

Analysis of the genetic diversity of beach plums by simple sequence repeat markers.

The purpose of this study was to measure the genetic diversity of wild beach plum and cultivated species, and to determine the species relationships using SSRs markers. An analysis of genetic diversity from ten beach plum germplasms was carried out using 11 simple sequence repeat (SSR) primers selected from 35 primers to generate distinct PCR products. From this plant material, 44 allele variations were detected, with 3-5 alleles identified from each primer. The analysis showed that the genetic similarity coefficient varied from 0.721 ± 0.155 to 0.848 ± 0.136 within each of the ten beach plum germplasms and changed within the range of 0.551 ± 0.084 to 0.695 ± 0.073 between any two pairs of germplasms. According to the genetic dissimilarity coefficient matrix, a cluster analysis of SSRs using the unweighted pair group mean average method in the NTSYSpc 2.10 software revealed that the ten germplasms could be divided into two groups at the dissimilarity coefficient of 0.606. Class I included 77.8, 12.5, 30, and 33.3% of MM, MI, NY, and CM, respectively. Class II contains the remaining 9 beach plum germplasms. The markers generated by 11 SSR primers proved very effective in distinguishing the beach plum germplasm resources. It was clear that the geographical distribution did not correspond with the genetic relationships among the different beach plum strains. This result will be of value to beach plum breeding programs.

A health risk assessment of reclaimed municipal wastewater for industrial and miscellaneous use.

The study evaluated the safety of reclaimed water using health risk assessment and biotoxicity tests. The reclaimed water was produced from reverse osmosis and used in industrial and miscellaneous purposes. The health risk assessment was conducted based on the concentrations of detectable pollutants in reclaimed water in a hypothetical scenario. The estimated carcinogenic and non-carcinogenic risks are lower than the generally accepted level. Biotoxicity evaluation included three genotoxicity tests, a chronic toxicity test using medaka fishes, and a subchronic toxicity test using mice. The reclaimed water is not genetically toxic, and does not cause significant chronic effects on these model organisms. These results confirm the safety of using reclaimed water from municipal wastewater treatment plants.

A novel intronic mutation and a missense mutation of MEN1 identified in two Chinese families with multiple endocrine neoplasia type 1.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) caused by MEN1 mutation is widely recognized. To date, 14 novel mutations were reported in Chinese and intronic mutations are getting more attention. AIM: To explore clinical features and MEN1 mutations in two Chinese families suffering from MEN1. METHODS: Nineteen individuals (10 males and 9 females) from two unrelated families with MEN1 were studied. Mutations of MEN1 were analyzed by direct sequencing of PCR products. In vitro splicing analysis was also performed with minigenes containing both wildtype and novel mutant fragments. Through the RNAstructure program, we analyzed the secondary structure of the wild type MEN1 pre-mRNA and then introduced T>G mutation at +2 donor splice site of intron 7. RESULTS: Clinical features of 3 patients in two families were described, and 5 individuals were proven to be carriers of MEN1 mutation without apparent symptoms. A novel splicing site mutation of the intron 7 (IVS7+2 T→G) was identified in the first family. In vitro analysis also verified this mutation caused the aberrant splicing of MEN1 mRNA. With the RNAstructure program, we could figure out that the global secondary structure as well as the number of stems and loops of pre-mRNA greatly changed after this mutation. The mutation c. 1227 C>A (C409X) was identified in another family, which also caused the truncation of menin. CONCLUSION: We reported a novel intronic mutation and a missense mutations in two Chinese families suffering from MEN1.

A risk model based on the tumor microenvironment to predict survival and immunotherapy efficacy for ovarian cancer.

OBJECTIVE: Based on the interactions between immune components in the tumor microenvironment and ovarian cancer (OC) cells, immunotherapies have been demonstrated to be effective in dramatically increasing survival rates. This study aimed to identify landmark genes, develop a prognostic risk model, and explore its relevance to the efficacy of immunotherapy. MATERIALS AND METHODS: A risk model was built based on the immune- and stromal-related genes, which were extracted from the OC gene expression data of "The Cancer Genome Atlas" (TCGA) database. Survival analysis and receiver operating characteristic (ROC) analysis were then conducted through the model's risk score pattern, which was established depending on the TCGA training cohort and verified based on the internal TCGA cohort and external "Gene Expression Omnibus" (GEO) datasets. Furthermore, the immune-related characteristics and prognostic values of the risk model were evaluated. RESULTS: The prognostic risk model for ovarian cancer demonstrated excellent performance in predicting survival rates, as validated in both the TCGA and GEO databases. The model showed significant associations with 17 functional immune cells, 17 immune checkpoints, PD-1, and several immune pathways, suggesting its potential to enhance the efficacy of immunotherapy in OC. CONCLUSIONS: The risk model developed in this study has the potential to serve as a prognostic marker for OC, enabling the development of personalized immunotherapy protocols and providing a theoretical basis for novel combinations of immunotherapeutic approaches.

[Measuring and analysis of the shoulder circumferences of 840 adults' permanent teeth crown preparations].

Objective: To measure and analyze the shoulder circumferences of adults' permanent teeth crown preparations based on data collected through the intraoral scanning, so as to provide dental anatomy data for clinical diagnosis and analysis. Methods: Intraoral scanning data of 840 complete crown preparations were collected, and were entrusted to the World Dental Laboratory Co., Ltd. in Fuzhou between March 2021 and June 2022. Except the data of the third molar, the rest data were categorized in terms of 14 tooth positions in the upper and lower jaw (each category involved 30 samples from male group and 30 samples from female group). Image measurement software was used to measure the shoulder circumferences of permanent teeth crown preparations. And analysis was conducted to reveal the difference of shoulder circumference diameters between male and female groups. And then they were grouped according to the mean value at each tooth position, on the premise that the difference between the maximum and minimum values and the mean value of the entire group was≤±1.00 mm. Analysis were further conducted to determine the differences of shoulder circumference diameters between each dental position and the differences between male and female in the same groups. Results: Bivariate analysis of variance showed that gender had no effect on the shoulder circumference of full crown preparations (F=0.55, P=1.457), while tooth position had a significant impact on the shoulder circumference of full crown preparations (F=273.15, P<0.001). The samples were classified into 5 groups according to the mean values of shoulder circumference diameters relating to each tooth position. Statistical analysis showed that Group 1, covering maxillary lateral incisor, mandibular central incisor and mandibular lateral incisor, had shoulder circumference with diameters of (16.62±2.21) mm; Group 2, consisting of maxillary central incisor, maxillary cusp, mandibular cusp, mandibular first premolar and mandibular second premolar, had diameters of (20.78±2.48) mm; Group 3, consisting of maxillary first premolar and maxillary second premolar, had diamerters of (22.09±2.72) mm; Group 4, covering maxillary first molar, maxillary second molar and mandibular first molar, had diamerters of (30.21±2.67) mm; while group 5, with mandibular second molar alone its member, had diamerters of (31.34±3.18) mm. The difference among the 5 groups was statistically significant (P<0.05). Conclusions: Significant differences of shoulder circumference diameters could be found between different tooth positions, while at the same tooth position, the differences between male and female are not significant. The 14 tooth positions could be grouped into 5 groups according to their shoulder circumference diameters. Future research could take the grouping as reference.

Over-expression of NYGGF4 (PID1) inhibits glucose transport in skeletal myotubes by blocking the IRS1/PI3K/AKT insulin pathway.

INTRODUCTION: Defects in insulin-stimulated glucose uptake in muscle are the important early events in the pathogenesis of insulin resistance. NYGGF4 (also named PID1) is a recently discovered gene which is suggested to be associated with obesity-associated insulin resistance. In this study, we aimed to investigate the effects of NYGGF4 on glucose uptake and insulin signaling in rat skeletal muscle cells. METHODS: Rat L6 myoblasts were transfected with either an empty vector or an NYGGF4-expressing vector and induced to differentiate into mature L6 skeletal myotubes. Glucose uptake was determined by measuring uptake of 2-deoxy-d-[(3)H] glucose. Immunoblotting was performed to detect the translocation of insulin-sensitive glucose transporter 4 (GLUT4). Immunoblotting was also used to measure phosphorylation and total protein levels of the insulin signaling proteins including insulin receptor (IR), insulin receptor substrate 1 (IRS1), Akt, extracellular signal-regulated kinase 1 and 2 (ERK1/2), p38, and c-Jun-N-terminal kinase (JNK). RESULTS: NYGGF4 over-expression in L6 skeletal myotubes reduced insulin-stimulated glucose uptake and impaired insulin-stimulated GLUT4 translocation. It also diminished insulin-stimulated tyrosine phosphorylation of IRS1 and serine phosphorylation of Akt without affecting the phosphorylation of IR, ERK1/2, p38, or JNK. CONCLUSIONS: Over-expression of NYGGF4 inhibits glucose transport in skeletal myotubes by blocking the IRS1/PI3K/AKT insulin pathway. These observations highlight the potential role of NYGGF4 in glucose homeostasis and the development of insulin resistance in obesity.