Cancer survival analysis and spatial distribution during 2014-2016 in Shandong Province, China.

We aimed to analyse cancer survival and its spatial distribution in Shandong Province. A total of 609,861 cancer cases from 2014 to 2016 were included in the analysis. Survival analysis was performed using strs in Stata. Spatial analysis was performed with GeoDa to determine measures of global and local spatial autocorrelation. Hotspot analysis was used to identify spatial clusters of high values (hotspots) and low values (cold spots) through ArcGIS. The 5-year relative survival rates were 37.85% for all cancers combined, 29.29% for males and 48.88% for females. After age standardisation, the survival rates were 34.47% for all cancers, 28.43% for males and 41.56% for females. Cancers with higher survival rates included thyroid (78.80%), breast (69.52%), uterus (64.51%) and bladder (62.54%) cancers. However, cancers with lower survival rates included pancreatic (11.34%), liver (13.19%), lung (18.39%), bone (19.71%), gallbladder (19.78%), oesophagus (24.52%), and stomach (28.85%) cancers and leukaemia (26.30%). Cancer survival rates in urban areas (37.53%) were higher than those in rural areas (32.83%). From the geographic distribution of cancer survival, we observed that the survival rate displayed a downward trend from east to west and from north to south. The hotspot analysis revealed that some counties of Qingdao, Jinan, Zibo, Dongying and Yantai cities were hotspots, whereas almost all counties of Linyi city and some counties of Weifang, Heze, Rizhao, and Dezhou cities were cold spots. In conclusion, the cancer survival rate in Shandong is still lower than that in China overall. The early diagnosis and treatment of lung and digestive tract cancers need to be further strengthened. Nevertheless, our results reflect a critical first step in obtaining and reporting accurate and reliable estimates of survival in Shandong.

Epidemiology of human papillomavirus on condyloma acuminatum in Shandong Province，China.

Condyloma acuminatum (CA) is a sexually transmitted disease (STD) caused by human papillomavirus (HPV) infection. It is important to study the prevalence and distribution of HPV genotypes before implementing the HPV vaccination program. Therefore, the aim of this study was to evaluate the epidemiological characteristics of CA cases and the distribution of HPV genotypes in Shandong Province, China. One-to-one questionnaire surveys were conducted on all patients diagnosed with CA in sentinel hospitals from Shandong Province, China. HPV genotypes were determined using the polymerase chain reaction (PCR)-reverse dot blot hybridization method. The study enrolled 1185 patients (870 males and 315 females) and found that CA patients are mainly males and sexually active people between the ages of 20 and 40. Recurrence occurred in 34.7% patients. Among the 880 CA patients who underwent HPV typing, the HPV test positivity rate was 91.4%. In these cases, low-risk (LR) HPV infection was predominant, with an infection rate of 91.3%, while high-risk (HR) HPV genotypes were found in 53.5% patients. The most frequent HPV genotypes encountered were HPV6 (57.8%), HPV11 (37.2%), HPV16 (13.7%), and HPV42 (10.3%). HPV6 and/or HPV11 are the main infections in all patients, and more than half of the patients are coinfected with HR-HPV. However, unlike other regions, HPV42 has a higher prevalence rate among CA patients in Shandong Province and is a nonvaccine HPV genotype. Therefore, regular HPV typing helps to understand the characteristics of specific genotypes and the choice of the best type for vaccine coverage.

Impaired long-term anti-HBs responses in choronic hepatitis C patients: Results from a five-year follow-up study with healthy control.

Although hepatitis B virus (HBV) vaccination is recommended for hepatitis C virus (HCV)-infected individuals to avoid HBV superinfection, the persistence of their humoral and cell-mediated immunity responses to HBV vaccination is still under investigation. Patients with chronic hepatitis C (CHC) and matched healthy controls, who completed three doses of hepatitis B vaccine (HepB) in 2014, were followed up five years later. One booster dose of HepB was given to those with antibody against hepatitis B surface antigen (anti-HBs) lower than 10mIU/mL. Anti-HBs was tested at follow-up and on the 14th day after the booster dose, as well as HBsAg specific spot-forming cells of interferon γ and interleukin (IL) 2, 4, 5, and 6. At five years, only 56.58% of the CHC patients had sero-protective titers (≥10mIU/mL) of anti-HBs, compared to 70.83% in the controls (P < .05). Similarly, the geometric mean concentration (GMC) of anti-HBs in CHC patients was significantly lower than that in controls (16.95 vs 37.34 mIU/mL, P < .05). After the booster, both GMC and the rate of anamnestic response increased to a very high level in the two groups and the difference between them disappeared (P > .05). Multivariable analysis showed that HCV infection was an independent predictor factor to anti-HBs level at follow-up. HBsAg specific IL-6 was stronger in the CHC patients compared to the controls (P < .05). The data indicate that the durability of protective anti-HBs is poorer in CHC patients compared to healthy individuals, and impaired long-term anti-HBs responses might be associated with the increased HBsAg specific IL-6 responses.

[Cancer survival during 2012-2018 in cancer registries of Shandong Province].

Objective: To analyze the 5-year cancer relative survival rate in cancer registries of Shandong Province during 2012-2018. Methods: 399 072 new cancer cases were collected in 23 cancer registries in Shandong Province during 2012-2018. All malignant tumors (C00-C97, D45-D47), benign central nervous system tumors (D32-D33), and central nervous system tumors (D42-D43) were registered according to the 10th revision of international classification of diseases (ICD). The survival of cancer patients was obtained by passive and active follow-up. The follow-up date was December 31, 2020. The diagnostic years were divided into three periods: 2012-2014, 2015-2017 and 2018-2020. The 5-year cancer survival rates were calculated by cohort approach, period analysis and hybrid approach, and the survival status of different sex, urban and rural areas, cancer species and age groups were analyzed. Results: The age of 399 072 new cancer cases was (63.5±13.7) years old, with 57.77% (230 538 cases) about male and 32.89% (131 247 cases) from urban. During 2012-2014, 2015-2017 and 2018-2020, the 5-year cancer survival rates in Shandong Province were 32.3%, 34.7% and 40.2%, respectively. In 2018-2020, the first five cancers with survival rates were thyroid cancer (86.0%), breast cancer (78.2%), testicular cancer (75.7%), bladder cancer (70.3%) and uterine cancer (69.2%), and the last five cancers with survival rates were pancreatic cancer (15.5%), liver cancer (16.8%), gallbladder cancer (19.6%), bone cancer (22.7%) and lung cancer (24.4%). The 5-year survival rate for cancer of women (47.8%) was higher than that of men (33.8%), and the rate of urban areas (45.7%) was higher than that of rural areas (37.3%) during 2018-2020. The first five cancers in men were thyroid (87.1%), testicular (75.7%), bladder (70.9%), kidney (65.6%) and prostate (62.8%) cancers, and the last five cancers were pancreatic (14.3%), liver (16.8%), gallbladder (18.2%), bone (19.9%) and lung (21.7%) cancers. The first five cancers in women were thyroid (85.5%), breast (78.0%), uterine (69.2%), bladder (68.8%) and kidney (66.8%) cancers, and the last five cancers were liver (17.2%), pancreatic (17.2%), gallbladder (22.0%), bone (27.2%) and lung (29.1%) cancers. Conclusion: The 5-year cancer survival rate in Shandong Province was on the rise from 2012 to 2018, and the survival rates of different cancers were different.

[Spatio-temporal trend of female breast cancer mortality in Shandong Province from 1970 to 2013].

The mortality of female breast cancer in Shandong Province has increased since the 1970. The differential decomposition analysis found that the slight decline in the crude mortality of breast cancer among women was entirely due to non-demographic factors during the 1970-1990, and the significant increase in the crude mortality was due to a combination of demographic and non-demographic factors since the 1990. The contribution rate of demographic factor has gradually increased from 53.5% in 2004-2005 to 59.5% in 2011-2013, while that of non-demographic factor has decreased from 46.5% to 40.5%. The women aged 45-64 years old were the major population of female breast cancer deaths, accounting for 40%-60% of total breast cancer deaths in different times, and then the mortality in female aged 55-64 years old increased rapidly, with increases of 52.12%, 115.19% and 29.01% in 2011-2013 over the 1970-1974, 1990-1992 and 2004-2005, respectively (Z=-7.342,P<0.001). Compared with 1970-1974, the age-standardized mortality rate of rural women increased by 41.86% in 2011-2013 (Z=-17.933, P<0.001), and that of urban women increased by 18.62% in 2011-2013 (Z=-25.642, P<0.001). The age-standardized mortality rate of breast cancer in urban women was higher than that in rural women in different times (all P<0.05). The spatial scan analysis found that eastern Shandong Province was found to be a sustained high-risk area for death, and other high-risk areas were transferred from north to southwest of Shandong between 1970 and 2013.

[Deaths and life expectancy losses attributed to high-salt diet in Shandong province].

Objective: To estimate the deaths and life expectancy losses attributed to diet with high salt in Shandong province. Methods: Based on 24 h urinary sodium and blood pressure levels from the final evaluation survey of Shandong-Ministry of Health Action on Salt and Hypertension Project (SMASH) in 2016 and death cause data from Shandong Mortality Surveillance System, the population attributable fractions (PAF) and the deaths due to high-salt diet were calculated based on the framework of comparative risk assessment and the life expectancy loss was calculated by life table method. Results: A total of 32 987 deaths caused by high-salt diets were reported in 2016, accounting for 11.74% of related disease deaths and 4.95% of all deaths. The proportion of deaths due to high-salt diet in men (13.51%) was higher than that in women (9.17%). Cardiovascular diseases were the major causes of deaths due to high salt diet, accounting for 90.82% of all disease deaths caused by high-salt diets. The other causes were gastric cancer (8.10%) and chronic kidney disease (1.08%). The PAF in urban residents (13.87%) was higher than that in rural residents (10.87%). A loss of 0.58 years of the life expectancy were attributed to the high-salt diet. The different diseases caused by high-salt diet had different effects on life expectancy loss, ischemic heart disease ranked first, followed by cerebral hemorrhage and cerebral infarction. Conclusions: The proportion of deaths attributed to high-salt diets was high in Shandong. Cardiovascular diseases were the most important causes of deaths caused by high-salt diets. High-salt diet is still seriously affecting the health of residents in Shandong, indicating that salt reduction interventions need to be strengthened.

Genomic diversity of human papillomavirus type 6 from patients with condyloma acuminatum in Eastern China.

OBJECTIVE: Human papillomavirus type 6 (HPV6) is the major etiological agent of anogenital warts both men and women. However, there is limited data on its genomic characterization in mainland China. The aim of this study was to understand the complete genomic diversity of HPV6 from patients with condyloma acuminatum (CA) and to explore the prevalence of different variant lineages/sublineages in eastern China. METHODS: CA samples were collected in 3 hospitals in Shandong Province, China from January 2020 to March 2021. DNA extraction, PCR amplification, Sanger sequencing and sequence assembly were performed on HPV6-positive samples. The complete genomes obtained in this study were analyzed phylogenetically with global HPV6 sequences in GenBank database using MEGA 11. RESULTS: A total of 55 complete genomic sequences of HPV6 were obtained in this study. They were classified as HPV6 variant lineage A (n = 20), sublineage B1 (n = 34) and sublineage B3 (n = 1) by phylogenetic analysis. Sequence alignment showed E1, E5A, E5B, L1, L2, LCR were relatively highly variable regions for sublineage B1 whereas E1, E5A, L2 for lineage A. Both phylogenetic trees of lineage A and sublineage B1 composed of two main branches. Chinese sequences of lineage A segregated into the major branch while those in sublineage B1 belonged to both branches. Genomic divergence between sequences from China and other countries was 0.00% - 0.33% in lineage A and 0.00% - 0.40% in sublineage B1. CONCLUSIONS: This is the first study on HPV variant lineages circulating in mainland China. The results revealed that lineage A and sublineage B1 were prevalent and they had different highly variable regions. Further surveillance is needed to understand the dynamic change of different variants in the population.

Spatial distribution and clusters of pancreatic cancer mortality in Shandong Province, China.

This study aimed to explore the geographic distribution and risk clusters of pancreatic cancer mortality from 2011 to 2013 in Shandong, China, and to detect the differences between urban and rural areas. Our data were obtained from the Shandong Death Registration System (SDRS) and were adjusted according to the underreporting level. The distribution of mortality was displayed with GIS-based maps at the county level. The results showed an increasing trend in pancreatic cancer mortality from the western region to the eastern region of Shandong. Additionally, four significant risk clusters were detected, and the most likely cluster was focused in the northeastern and northern regions. Urban-rural differences in the mortality distribution and risk clusters were also detected. In conclusion, our study identified pancreatic cancer mortality clusters in Shandong in urban and rural areas; these results can contribute to the development of effective and targeted strategies to control pancreatic cancer in different areas.

Individual- and Area-Level Socioeconomic Inequalities in Esophageal Cancer Survival in Shandong Province, China: A Multilevel Analysis.

BACKGROUND: China contributes to almost half of the esophageal cancer cases diagnosed globally each year. However, the prognosis information of this disease in this large population is scarce. METHODS: Data on a population-based cohort consisting of residents of Shandong Province, China who were diagnosed with esophageal cancer during the period from 2005 to 2014 were analyzed. The cancer-specific survival rates were estimated using Kaplan-Meier analysis. Discrete-time multilevel mixed-effects survival models were used to investigate socioeconomic status (SES) disparities on esophageal cancer survival. RESULTS: The unadjusted 1-, 3-, and 5-year cause-specific survival rates were 59.6% [95% confidence interval (CI), 59.2%-59.9%], 31.9% (95% CI, 31.5%-32.3%), and 23.6% (95% CI, 23.1%-24.0%), respectively. Patients of blue-collar occupations had higher risk of esophageal cancer-related death than those of white-collar occupations in the first 2 years after diagnosis. Rural patients had higher risk of death than urban patients in the first 3 years after diagnosis. The risks of esophageal cancer-related death among patients living in low/middle/high SES index counties were not different in the first 2 years after diagnosis. However, patients living in high SES index counties had better long-term survival (3-5 years postdiagnosis) than those living in middle or low SES index counties. CONCLUSIONS: Socioeconomic inequalities in esophageal cancer survival exist in this Chinese population. Higher individual- or area-level SES is associated with better short-term or long-term cancer survival. IMPACT: Elucidation of the relative roles of the SES factors on survival could guide interventions to reduce disparities in the prognosis of esophageal cancer.

Area socioeconomic status is independently associated with esophageal cancer mortality in Shandong, China.

Esophageal cancer (EC) is a leading cause of cancer death in China. Within Shandong Province, a geographic cluster with high EC mortality has been identified, however little is known about how area-level socioeconomic status (SES) is associated with EC mortality in this province. Multilevel models were applied to EC mortality data in 2011-13 among Shandong residents aged 40+ years. Area-level SES factors consisted of residential type (urban/rural) of the sub-county-level units (n = 262) and SES index (range: 0-10) of the county-level units (n = 142). After adjustment for age and sex, residents living in rural areas had a 22% (95% CI: 13-32%) higher risk of dying from EC than those in urban areas. With each unit increase in the SES index, the average risk of dying from EC reduced by 10% (95% CI: 3-18%). The adjustment of area-level SES variables had little impact on the risk ratio of EC mortality between the high-mortality cluster and the rest of Shandong. In conclusion, rural residence and lower SES index are strongly associated with elevated risks of EC death. However, these factors are independent of the high mortality in the cluster area of Shandong. The underlying causes for this geographic disparity need to be further investigated.

Spatial Analysis of Esophageal Cancer Mortality in a High-risk Population in China: Consistent Clustering Pattern in 1970-74 and 2011-13

Purpose: Almost half of the global esophageal cancer (EC) deaths occurred in China. This study aims to examine the geographic spread of EC mortality in two periods in a large Chinese population. Methods: Age-standardized mortality rates (ASMRs) for 140 county-level units in Shandong Province during the periods 1970-74 and 2011-13 were derived using data from the First National Cause-of-Death Survey and the Shandong Death Registration System, respectively. ASMRs were smoothed using Area-to-Area Poisson kriging technique. Spatial scan statistics were used to detect spatial clusters with higher EC mortality and clusters with greater temporal changes in EC mortality. Results: The provincial average ASMR decreased from 13.0 per 100,000 in 1970-74 to 5.8 in 2010-13. Almost all counties or districts have experienced a decrease in EC mortality, while the reduction was particularly pronounced in the mid-west region. This study has identified a geographical cluster with much higher EC mortality rates and the clustering pattern has largely unchanged over the past 40 years. Residents living in the cluster during 1970-74 were 2.7 (95% CI: 2.2-3.4) times more likely to die from EC than the rest of the province. The corresponding risk ratio for the 2011-13 cluster was 3.7 (95% CI: 2.8-5.0). Conclusions: This study detected a geographically defined subpopulation in Shandong, China with much higher risk of dying from EC. This spatial pattern has been consistent over the past few decades. The results suggest the key drives for geographic variations in esophageal cancer may not have changed.

Lung cancer mortality clusters in Shandong Province, China: how do they change over 40 years?

Lung cancer has long been a major health problem in China. This study aimed to examine the temporal trend and spatial pattern of lung cancer mortality in Shandong Province from 1970 to 2013. Lung cancer mortality data were obtained from Shandong Death Registration System and three nationwide retrospective cause-of-death surveys. A Purely Spatial Scan Statistics method with Discrete Poisson models was used to detect possible high-risk spatial clusters. The results show that lung cancer mortality rate in Shandong Province increased markedly from 1970-1974 (7.22 per 100,000 person-years) to 2011-2013 (56.37/100, 000). This increase was associated with both demographic and non-demographic factors. Several significant spatial clusters with high lung cancer mortality were identified. The most likely cluster was located in the northern region of Shandong Province during both 1970-1974 and 2011-2013. It appears the spatial pattern remained largely consistent over the last 40 years despite the absolute increase in the mortality rates. These findings will help develop intervention strategies to reduce lung cancer mortality in this large Chinese population.

Female Breast Cancer Mortality Clusters in Shandong Province, China: A Spatial Analysis.

This study aimed to detect the spatial distribution and high-risk clusters of female breast cancer mortality for the years 2011 to 2013 in Shandong Province, China. The urban-rural difference in the spatial distribution and clusters of disease mortality were also examined. Breast cancer mortality data were obtained from the Shandong Death Registration System (SDRS) during 2011 to 2013 and were adjusted for the underreporting rate. The purely spatial scan Statistics method was performed using Discrete Poisson model. Seven significant spatial clusters for high mortality of female breast cancer were detected in Shandong Province at the county level; these clusters were mainly located in the eastern, southern, southwestern, central and northern regions. The spatial distributions differed significantly between urban and rural populations. Population ageing influenced the distribution of breast cancer clusters for the urban eastern residents. This study provided evidence for the presence of clusters of breast cancer mortality in Shandong, China and found urban-rural difference in the clusters, which is helpful for developing effective strategies to control breast cancer in different areas.

Polymorphisms in IRG1 gene associated with immune responses to hepatitis B vaccination in a Chinese Han population and function to restrain the HBV life cycle.

Vaccination against the hepatitis B virus (HBV) is extensively used as an effective method to prevent HBV infection. However, nearly 10% of healthy adults fail to produce a protective level of antibodies against the hepatitis B vaccine, and multiple genetic variants are known to affect the immune response to the hepatitis B vaccine. The aim of the present study was to investigate the association between polymorphisms in immunoresponsive gene 1 (IRG1) gene and the immune response to hepatitis B vaccination in a Chinese Han population. Four single nucleotide polymorphisms (SNPs) located in the IRG1 gene were genotyped in 1230 high-responders and 451 non-responders to hepatitis B vaccination. The SNPs rs17470171 and rs17385627 were associated with the immune response to hepatitis B vaccination (P = 0.014 and 0.029, respectively). In addition, the haplotypes G-A-A-A (rs614171-rs17470171-rs9530614-rs17385627, P = 0.0042, OR = 0.68) and A-A (rs17470171-rs17385627, P = 0.0065, OR = 0.72) exerted a protective role in the immune response to hepatitis B vaccination. Allele 'A' of rs17470171 and allele 'A' of rs17385627 show higher levels of expression for the IRG1 gene compared with allele 'C' of rs17470171 and allele 'T' of rs17385627 as demonstrated by luciferase reporter and overexpression assays. In addition, we observed that IRG1 inhibited the HBV life cycle and that IRG1 rs17385627 allele 'A' was more effective than rs17385627 allele 'T' at eliminating HBV in HepG2.2.15 cells. These findings suggest that polymorphisms in the IRG1 gene are associated with the immune response to hepatitis B vaccination. The antiviral effect of IRG1 was confirmed using HBV infection cell models.

One-year Survey of human enteroviruses from sewage and the factors affecting virus adsorption to the suspended solids.

This study described the results of environmental enterovirus surveillance conducted in Shandong Province of China in 2013. Altogether 39 sewage samples were collected and 873 enterovirus isolates (including 334 polioviruses) belonging to 22 serotypes were obtained. Echovirus (E) -7, coxsackievirus (CV) -B5, E-11, E-6, and E-3 were the most commonly detected non-polio enterovirus serotypes, and phylogeny of E-7 and CV-B5 was described. The numbers of isolates of different serotypes from sewage supernatant were compared with those from the solids. Interestingly, dramatic divergence was observed between the supernatant and solids origin for the serotypes of E-3 and E-6, which were prone to the solids and supernatant, respectively. A following adsorption test with E-3 and E-6 added sewage specimens confirmed the different preference. Furthermore, the adsorption of Sabin poliovirus type 1 to the solids under different conditions was investigated, and the results showed that acid medium, cold temperature, and high solids concentration facilitated the viral adsorption to the solids, whereas change of virus titer did not influence the proportion of adsorption. These results highlighted the importance of combining the enterovirus isolates from the supernatant and solids together in environmental surveillance so as to better understand the local circulation of different serotypes.

Human Papillomavirus Infection and Vaccination: Awareness and Knowledge of HPV and Acceptability of HPV Vaccine among Mothers of Teenage Daughters in Weihai, Shandong, China.

In preparation for the introduction of human papillomavirus (HPV) vaccine, we investigated awareness and knowledge of HPV/HPV vaccine and potential acceptability to HPV vaccine among mothers with a teenage daughter in Weihai, Shandong, China. A cross-sectional survey was conducted in 2013 with a sample of 1850 mothers who had a daughter (aged 9-17 years) attending primary, junior and senior high schools. In the final sample (N = 1578, response rate 85.30%), awareness of HPV was reported by 305 (19.32%) mothers. Awareness varied significantly by daughter's age (P<0.01), mother's education level (P<0.01), mother's occupation (P<0.01), household income (P<0.01) and residence type (P<0.01). Knowledge about HPV/HPV vaccine was poor with a mean total score of 3.56 (SD = 2.40) out of a possible score of 13. Mothers with a higher education level reported higher levels of knowledge (P = 0.02). Slightly more than one-fourth (26.49%) of mothers expressed their potential acceptability of HPV vaccine for their daughters. Acceptability increased along with increased daughters' age (P<0.01), household income (P<0.01) and knowledge level (P<0.01). House wives and unemployed mothers had the highest acceptability (P<0.01). The most common reasons for not accepting HPV vaccination were "My daughter is too young to have risk of cervical cancer (30.95%)", "The vaccine has not been widely used, and the decision will be made after it is widely used (24.91%)", "Worry about the safety of the vaccine (22.85%)". Awareness and knowledge of HPV/HPV vaccines are poor and HPV vaccine acceptability is low among these Chinese mothers. These results may help inform appropriate health education programs in this population.

Molecular characterization of coxsackievirus A21 in Shandong, China.

Coxsackievirus A21 (CV-A21) is a rarely detected serotype belonging to the species Enterovirus C (EV-C). In this study, we report the isolation and genetic characterization of CV-A21 in Shandong Province, China, during 1997 to 2013. A total of 13 strains were obtained from surveillance of cases of acute flaccid paralysis (AFP) (n = 9) and from environmental sewage (n = 4). Sequence comparison of the VP1 genes revealed high nucleotide sequence similarity (94.1 % to 99.8 % identity) among these Shandong strains during the period of 17 years and 75.8 % to 98.5 % sequence identity to foreign strains. Bayesian phylodynamic evolutionary analysis of Shandong and global CV-A21 VP1 sequences revealed that the inferred CV-A21 ancestral sequence dated back to 1750 (1643-1841) and evolved with 2.943 × 10(-3) substitutions per site per year. Alignment of the deduced VP1 amino acid sequences revealed changes that might alter the hydropathicity of the encoded protein. The complete genome of one strain from 2013 was sequenced and evidence of recombination was detected by similarity plot and bootscanning analyses. This study describes the complete genome characterization and molecular epidemiology of CV-A21 in China and gives further insight into CV-A21 evolution.

[DIFFERENTIATION AND PROLIFERATION POTENTIAL OF NEURAL STEM CELLS IN SUBVENTRICULAR ZONE OF MICE IN VITRO].

OBJECTIVE: To establish the system of isolation, cultivation, and identification of the neural stem cells (NSCs) from subventricular zone (SVZ) of neonatal mice so as to seek for the appropriate seed cells for potential therapeutic interventions of neurological disorders. METHODS: NSCs were isolated enzymatically and mechanically from SVZ of neonatal mice and cultured. The cellular morphology was observed by inverted microscopy. Immunocytochemical stainings of anti-Nestin and anti-SOX-2 were used to identify NSCs of passage 3. To study the differentiation of NSCs, NSCs were plated into 24-wells in the medium supplemented without epidermal growth factor (EGF) and basic fibroblastic growth factor (bFGF) for 3 or 7 days. To compare the differentiation and proliferation potential of NSCs with different cultivation time, the BrdU pulse-labeling method and MTT test were used. To identify neurons and astrocytes, the anti-ß-tubulin III (Tuj-1) and anti-glial fibrillary acidic protein (GFAP) staining were used. RESULTS: The cells of the SVZ can be isolated and cultured in vitro, and these cells began to form neurospheres after cultured for 3 days at primary passage. While cultured for 7 days, these cells formed more neurospheres, and the volume of the neurospheres became bigger than neurospheres cultured for 3 days. In addition, after cultured for 7 days, the phenomena of fusion of neurospheres and adherent differentiation of neurospheres were observed under inverted microscope. These cells were provided with the typical phenotype of NSCs. The immunofluorescence staining results revealed that these cells showed positive immunoreactivity to Nestin and SOX-2. During the 4 hours BrdU pulse, the number of proliferated NSCs cultured for 3 days (75.817 ± 2.961) was significantly higher than that of NSCs cultured for 7 days (56.600 ± 4.881) (t = 3.366, P = 0.028). The results of MTT assay revealed that the absorbance (A) value of NSCs cultured for 3 days (0.478 ± 0.025) was significantly higher than that of NSCs which were cultured for 7 days (0.366 ± 0.032)(t = 2.752, P = 0.011). After cultivated without EGF and bFGF, the percentage of Tuj-1 and GFAP positive cells in NSCs was 23.1% ± 3.7% and 23.7% ± 3.8% for 3 days and was 40.1% ± 3.6% and 37.1% ± 4.5% for 7 days, respectively, all showing significant differences (t = 3.285, P = 0.030; t = 3.930, P = 0.017). CONCLUSION: The NSCs from SVZ of neonatal mice have potentials of self-renewal and multipotential differentiation in vitro. With different cultivation time, the potentials of proliferation and differentiation of NSCs are different.

Viral Etiology of acute respiratory tract infections in hospitalized children and adults in Shandong Province, China.

BACKGROUND: The dominant viral etiologies responsible for acute respiratory infections (ARIs) are poorly understood, particularly among hospitalized patients. Improved etiological insight is needed to improve clinical management and prevention of ARIs. METHODS: Clinical and demographic information and throat swabs were collected from 607 patients from 2011 to 2013 in Shandong Province, China. Multiplex RT-PCR (SeeplexTM RV detection, Seegene) was performed to detected 12 respiratory viral pathogens. RESULTS: A total of 607 hospitalized patients were enrolled from 2011 to 2013. Viruses were identified in 35.75 % (217/607) of cases, including 78 influenza virus A and B (IVA and IVB), 47 para-influenza viruses (PIVs), 41 respiratory syncytial virus (RSV) and 38 adenovirus (ADV). For the children under 15 year old, the common detected viruses were influenza viruses, RSV, PIVS and ADV, while the principal respiratory viruses were human coronaviruses (HCoV), PIVs, influenza viruses for the old adults. Co-infections with multiple viruses were detected in 15.67 % of patients. Children under 5 years were more likely to have one or more detectable virus associated with their ARI. The peak of ARI caused by the respiratory viruses occurred in winter. CONCLUSION: This study demonstrated respiratory viruses were the major cause of hospitalized ARI patients in Shandong Province, influenza virus was the most common detected, RSV was the highest incidence among the young children (≤5 years). These findings also gave a better understand of virus distribution among different age and seasons, which help to consider potential therapeutic approaches and develop effective prevention strategies for respiratory virus infection.

Perinatal hepatitis B prevention program in Shandong Province, China. Evaluation and progress.

Post-exposure prophylaxis with hepatitis B vaccine (HepB) alone is highly effective in preventing perinatal hepatitis B virus (HBV) transmission and the World Health Organization recommends administering HepB to all infants within 24 h after delivery. Maternal screening for HBsAg and administration of hepatitis B immune globulin (HBIG) in addition to HepB for infants born to HBsAg-positive pregnant women can increase the effectiveness of post-exposure prophylaxis for perinatal HBV transmission. In Shangdong Province, China which has a high prevalence of chronic HBV infection, HepB birth dose and HBIG were integrated into the routine childhood immunization program in 2002 and July 2011 respectively. We assessed progress toward implementation of these measures. Hospital-based reporting demonstrated an increase in maternal screening from 70.7% to 96.9% from 2004-2012; HepB birth dose coverage (within 24 h) remained high (96.3-97.1%) during this period. For infants with known HBsAg-positive mothers, the coverage of HBIG increased from 85.0% (before July 2011) to 92.1% (after July 2011). However, HBIG coverage in western areas of Shandong Province remained at 81.1% among infants with known HBsAg-positive mothers. Preterm/low-birth-weight and illness after birth were the most commonly reported reasons for delay in the first dose of HepB to >24 h of birth. Additional education on the safety and immune protection from HepB and HBIG might help to correct delays in administering the HepB birth dose and low HBIG coverage in the western areas of the Shandong Province.