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Objective: The occurrence of chickenpox in rapidly developing areas poses substantial seasonal risk to children. However, certain factors influencing local chickenpox outbreaks have not been studied. Here, we examined the relationship between spatial clustering, heterogeneity of chickenpox outbreaks, and socioeconomic factors in Southern China., Methods: We assessed chickenpox outbreak data from Southern China between 2006 and 2021, comprising both relatively fast-growing parts and slower sub-regions, and provides a representative sample of many developing regions. We analyzed the spatial clustering attributes associated with chickenpox outbreaks using Moran's I and local indicators of spatial association and quantified their socioeconomic determinants using Geodetector q statistics., Results: There were significant spatial heterogeneity in the risk of chickenpox outbreaks, with strong correlations between chickenpox risk and various factors, particularly demographics and living environment. Furthermore, interactive effects among specific are factors, such as population density and per capita residential building area, percentage of households with toilets, percentage of rental housing, exhibited q statistics of 0.28, 0.25, and 0.24, respectively., Conclusion: This study provides valuable insights into the spatial dynamics of chickenpox outbreaks in rapidly developing regions, revealing the socioeconomic factors affecting disease transmission. These implications extend the formulation of effective public health strategies and interventions to prevent and control chickenpox outbreaks in similar global contexts., (Copyright © 2024 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Objective: To understand the epidemiological characteristics of public health emergency events (PHEE) of varicella in China from 2006 to 2021 and related response performances. Methods: The data of varicella PHEE in 31 provinces of China from 2006 to 2021 were collected through the Public Health Emergency Management Information System, Microsoft Excel 2019 software and SPSS 26.0 statistical software were used to conduct descriptive epidemiological, statistical analysis on the time, area, location distribution, scale and epidemic management. Results: A total of 11 443 PHEE involving 341 048 related cases were reported from 2006 to 2021, with an annual attack rate of 1.78%-3.80% and a total attack rate of 2.33% (341 048/14 624 042). The number of PHEE and related cases of varicella decreased from 1 107 (35 349) in 2007 to 262 (6 884) in 2012 ( Z =-2.40, P <0.001), then increased year by year to 1 318 (42 649) in 2019 ( Z =2.58, P <0.001), with a significant decline since 2020. The varicella PHEE in China presents the seasonal characteristics,the peak is from April to June and from October to December, respectively. The sub-peak of varicella PHEE in eastern China generally appears 1-2 months earlier than in central and western China. Varicella PHEE reports are mainly distributed in eastern China, the attack rate is relatively high in western China, school-reported varicella PHEE was 88.26% of the total reports (10 099/11 443). The epidemic scale of varrcella PHEE typically range from 10 to 29 cases per year among the given outbreaks. The M ( Q 1 , Q 3 ) of average number of cases, average duration, and average reporting interval of PHEE were 23 (16,35), 20 (14, 26) days, and 9 (5,19) days, respectively, and the reporting interval was positively correlated with the duration ( r =0.854, P <0.001). Conclusions: The varicella PHEE in China from 2006 to 2021 has not been effectively controlled. Schools are the key places to prevent and control varicella PHEE. Improving the sensitivity of varicella PHEE monitoring, strengthening the timely disposal of varicella epidemic, and promoting varicella vaccination are effective measures to prevent and control varicella PHEE.

The current study tested the expression and potential functions of Gαi1 in nasopharyngeal carcinoma (NPC). The Cancer Genome Atlas (TCGA) database results demonstrate that Gαi1 transcripts' number in NPC tissues is significantly higher than that in the normal nasal epithelial tissues. Its overexpression correlates with poor survival in certain NPC patients. Moreover, Gαi1 is significantly upregulated in NPC tissues of local primary patients and in different primary human NPC cells. Whereas its expression is relatively low in cancer-surrounding normal tissues and in primary nasal epithelial cells. Genetic silencing (via shRNA strategy) or knockout (via CRISPR-sgRNA method) of Gαi1 substantially suppressed viability, proliferation, cell cycle progression, and migration in primary NPC cells, causing significant caspase-apoptosis activation. Contrarily, ectopic Gαi1 expression exerted pro-tumorigenic activity and strengthened cell proliferation and migration in primary NPC cells. Gαi1 is important for Akt-mTOR activation in NPC cells. Akt-S6K phosphorylation was downregulated after Gαi1 shRNA or KO in primary NPC cells, but strengthened following Gαi1 overexpression. In Gαi1-silenced primary NPC cells, a S473D constitutively-active mutant Akt1 (caAkt1) restored Akt-S6K phosphorylation and ameliorated Gαi1 shRNA-induced proliferation inhibition, migration reduction and apoptosis. Bioinformatics analyses proposed zinc finger protein 384 (ZNF384) as a potential transcription factor of Gαi1. In primary NPC cells, ZNF384 shRNA or knockout (via CRISPR-sgRNA method) decreased Gαi1 mRNA and protein expression, whereas ZNF384 overexpression upregulated it. Importantly, there was an increased binding between ZNF384 protein and the Gαi1 promoter in human NPC tissues and different NPC cells. In vivo studies showed that intratumoral injection of Gαi1-shRNA-expressing adeno-associated virus (AAV) impeded subcutaneous NPC xenograft growth in nude mice. Gαi1 downregulation, Akt-mTOR inactivation, and apoptosis induction were detected in Gαi1-silenced NPC xenograft tissues. Gαi1 KO also effectively inhibited the growth of NPC xenografts in nude mice. Together, overexpressed Gαi1 exerts pro-tumorigenic activity in NPC possibly by promoting Akt-mTOR activation., (© 2023. The Author(s).)

To explore the characteristics of big data of patients with allergic rhinitis, including the time, population and spatial distribution of allergic rhinitis in Beijing from 2016 to 2021, so as to provide reference for the prevention and treatment of this disease. Descriptive epidemiological methods were used to analyze the distribution (including gender, age and location)and trend of allergic rhinitis patients in 30 pilot hospitals from January 2016 to December 2021, T test and Kruskal-Wallis rank sum test were used to test the statistical differences. The results showed that the number of patients with allergic rhinitis in 30 hospitals increased year by year from 2016 to 2019, with an increase of 97.9%. In 2020, the number of patients decreased. In 2021, the number of visits returned to the pre-epidemic level (461 332); The number of patients with allergic rhinitis was the highest in September, with a seasonal index of 177.6%, while the lowest number was in February, accounting for only 47.2%; a significant difference was observed in the number of patients in different age groups( H =45 319.48, P <0.05), and patients under 15 years old accounted for the highest proportion(819 284 visits); There were significant differences between patients of different genders in the 45-59 year old group ( t =-4.26, P <0.05).There were relatively more patients with allergic rhinitis in Dongcheng District(31.1%) than in Huairou District and Miyun District (0.4%). In conclusion, since 2016, the number of patients increased significantly, with a varied trend in different seasons. Most patients were children. There were more patients in the central urban area than in the outer suburbs.

To discuss the effect of varicella vaccination on the clinical characteristics of herpes zoster (shingles) cases aged 20 years and under, and analyze its clinical features. Based on the Yichang Health Big Data Platform, a descriptive study was conducted to collect the information of cases aged 20 years and under in three medical institutions of Yichang Central People's Hospital, Yichang First People's Hospital and Yichang Second People's Hospital from March 2019 to September 2020. According to the history of varicella vaccine, cases were divided into vaccination group and non-vaccination group, and their clinical features and outcomes were compared. The results showed that 46 shingles cases, aged from 7 to 20 years old, were included in this study. 26 males (56.5%), 20 females (43.5%), 15 cases in vaccination group (32.6%) and 31 cases in non-vaccination group (67.4%). 28 cases had thoracic involvement, followed by lumbar ( n =8), cranial ( n =7) involvements and extremities ( n =7). The spread of herpes skin area: 2 cases involved too large area, 21 cases of 10 cm×10 cm, 14 cases of 5 cm×5 cm, 9 cases of 1 cm×1 cm. Herpes number: 26 cases had 10-49 herpes, followed by <10 herpes ( n =9), uncountable herpes ( n =7) and 50-99 herpes ( n =4). The clinical course[ M ( Q 1 , Q 3 )] lasted 20.5 (13.5,24.8) d averagely, 5 cases had postherpetic neuralgia (PHN) and 1 case had respiratory complications. Shingles decrustation time was significantly shorter in vaccination group ( Z =-2.01, P< 0.05), and there was no significant difference in other characteristics by vaccination. In conclusion, the number and spread of shingles in most children and adolescents are less, and the complications such as PHN are less. Varicella vaccination can reduce the decrustation time and relieve shingles cases with some clinical symptoms.

Objective: To analyze the genetic characteristics of varicella-zoster virus (VZV) in people aged 20 years and under in Yichang City of Hubei Province from 2019 to 2020. Methods: Based on the Yichang Health Big Data Platform, we investigated cases 20 and under clinically diagnosed as herpes zoster in three hospitals from March 2019 to September 2020. Collecting vesicle fluid and throat swab samples of the cases and completing questionnaires to obtain basic information. Real-time fluorescent quantitative PCR was used for positive identification of the virus. PCR amplification of VZV's open reading frame (ORF) and sequencing of the products to determine the VZV genotype. Analyze mutations at some specific single nucleotide polymorphism (SNP) sites. Results: Among 46 cases of herpes zoster, the male to female ratio was 1.3∶1 (26∶20) and the age ranged from 7 to 20 years old. Fifteen cases had been vaccinated against varicella, including 13 and 2 cases of 1 and 2 doses, respectively. VZV strains were detected in 34 samples (73.91%), all belonging to Clade 2. Phylogenetic tree analysis of the nucleotide of ORF22 showed, compared with Clade 2 referenced strains, the sequence matching degree of nucleotide for all 34 samples was 99.0% to 100.0%. Conclusion: The main VZV strain causing herpes zoster in people aged 20 years and under in Yichang from 2019 to 2020 was Clade 2.

Here we studied expression and potential functions of Gαi3 in cervical cancer. The bioinformatics analysis together with the results from local patients' tissues revealed that Gαi3 expression was remarkably elevated in human cervical cancer tissues and different cervical cancer cells, and was associated with poor overall survival and poor disease-specific survival of patients. Gαi3 depletion resulted in profound anti-cervical cancer activity. In primary or immortalized cervical cancer cells, Gαi3 shRNA or CRISPR/Cas9-caused Gαi3 knockout/KO largely hindered cell proliferation and migration, and provoked apoptosis. On the contrast, ectopic Gαi3 overexpression further enhanced cervical cancer proliferation and migration. Akt-mTOR activation in primary cervical cancer cells was significantly reduced after Gαi3 silencing or KO, but was augmented following Gαi3 overexpression. Further studies revealed that the transcription factor GATA4 binding to Gαi3 promoter region was significantly enhanced in cervical cancer tissues and cells. Gαi3 expression was decreased by GATA4 shRNA, but upregulated following GATA4 overexpression. In vivo , the growth of cervical cancer xenografts was robustly suppressed after Gαi3 silencing or KO. Gαi3 depletion and Akt-mTOR inactivation were detected in Gαi3-silenced/-KO cervical cancer xenograft tissues. Together, upregulated Gαi3 is a valuable oncotarget of cervical cancer., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Introduction: Obesity and diabetes are characterized by chronic inflammatory responses. Roux-en-Y gastric bypass (RYGB) is increasingly regarded as an effective approach for the improvement of glucose homeostasis. In this study, we examined the effects of RYGB on the regulation of early inflammatory responses in the liver and adipose tissue in high-fat diet (HFD)-induced obese (DIO) mice., Materials and Methods: RYGB was performed in DIO mice followed by analyses of adiposity, insulin sensitivity, plasma and tissue cytokines and adipokines, tissue NF-κB and JNK/c-Jun activation, and tissue macrophage and T-cell subsets., Results: We found that RYGB resulted in sustained improvement of adiposity and insulin sensitivity. Plasma insulin and leptin levels were increased in untreated DIO mice and reduced in RYGB mice. RYGB maintained plasma adiponectin levels and inhibited monocyte chemoattractant protein-1 and interleukin 6 in white adipose tissue (WAT) and liver. RYGB inhibited NF-κB activation in WAT and muscle, but not in the liver. However, RYGB attenuated the JNK/c-Jun signaling pathway in the liver and WAT at 1 wk after surgery, suggesting that RYGB regulates the tissue-specific inflammatory pathway. RYGB reduced M1-like (F4/80 + /CD11c + ) differentiation and enhanced M2-like population (F4/80 + /CD206c + ). RYGB also regulated CD4 + and CD8 + T-cell infiltration and increased T reg cells in the liver and WAT at the same time point., Conclusions: Our findings demonstrate that RYGB improves obesity and insulin resistance, which are associated with the regulation of early inflammatory reactions in the liver and WAT., (Copyright © 2022 Elsevier Inc. All rights reserved.)

It is urgent to identify and validate biomarkers for early diagnosis and efficient treatment of nasopharyngeal carcinoma (NPC). Recent studies have proposed p38 gamma (p38γ) as a cyclin-dependent kinase (CDK)-like kinase that phosphorylates retinoblastoma (Rb) to promote cyclins expression and tumorigenesis. Here the Gene Expression Profiling Interactive Analysis (GEPIA) database and results from the local NPC tissues demonstrate that p38γ is significantly upregulated in NPC tissues, correlating with poor overall survival. Furthermore, p38γ mRNA and protein expression is elevated in established NPC cell lines (CNE-1 HONE-1 and CNE-2) and primary human NPC cells, but low expression detected in human nasal epithelial cells. In established and primary NPC cells, p38γ depletion, using the shRNA strategy or the CRISPR/Cas9 gene-editing method, largely inhibited cell growth, proliferation and migration, and induced significant apoptosis activation. Contrarily, ectopic p38γ overexpression exerted opposite activity and promoted NPC cell proliferation and migration. Retinoblastoma (Rb) phosphorylation and cyclin E1/A expression were decreased in NPC cells with p38γ silencing or knockout, but increased after p38γ overexpression. Moreover, mitochondrial subcellular p38γ localization was detected in NPC cells. Significantly, p38γ depletion disrupted mitochondrial functions, causing mitochondrial depolarization, reactive oxygen species production, oxidative injury and ATP depletion in NPC cells. In vivo, intratumoral injection of adeno-associated virus-packed p38γ shRNA potently inhibited primary human NPC xenograft growth in nude mice. In p38γ shRNA virus-injected NPC xenograft tissues, p38γ expression, Rb phosphorylation, cyclin E1/A expression and ATP levels were dramatically decreased. Taken together, we conclude that p38γ overexpression is required for NPC cell growth, acting as a promising therapeutic target of NPC., (© 2022. The Author(s).)

Based on Yichang health big data platform, 850 608 patients from September 2018 to September 2019 were included in this study. According to the date of birth, the participants were divided into early childhood famine exposure group, fetal famine exposure group and non-famine exposure group. The incidence of adult herpes zoster (HZ) in Yichang city was analyzed, and the correlation between early life famine exposure and adult HZ was analyzed. In 2019, the crude incidence rate of adult HZ in Yichang was 6.83‰. The crude incidence rate of adult HZ in females (7.26‰) was higher than that in males (6.40‰). Compared with the non-famine exposure group, fetal famine exposure was associated with the incidence of adult HZ ( OR =1.21; 95% CI : 1.01-1.45, P =0.041). After stratification by sex, fetal famine exposure was only found to be associated with the onset of adult HZ in females ( OR =1.28, 95% CI :1.02-1.61, P =0.034).

Obese subjects have increase probabilities of developing type 2 diabetes (T2D). In this study, we sought to determine whether gastric bypass prevents the progression of prediabetes to overt diabetes in genetically modified mice and chemically induced diabetic mice. Roux-en-Y gastric bypass (RYGB) was performed in C57BL/KsJ-db/db null (BKS-db/db,) mice, high-fat diet (HFD)-fed NONcNZO10/LtJ (NZO) mice, C57BL/6 db/db null (B6-db/db) mice and streptozotocin (STZ)-induced diabetic mice. Food consumption, body weight, fat mass, fast blood glucose level, circulating insulin and adiponectin and glucose tolerance test were analyzed. The liver and pancreatic tissues were subjected to H&E and immunohistochemistry staining and islet cells to flow cytometry for apoptotic analysis. RYGB resulted in sustained normoglycemia and improved glucose tolerance in young prediabetic BKS-db/db mice (at the age of 6 weeks with hyperglycemia and normal insulinemia) and HFD-fed NZO and B6-db/db mice. Remarkably, RYGB improved liver steatosis, preserved the pancreatic β-cells and reduced β-cell apoptosis with increases in circulating insulin and adiponectin in young prediabetic BKS-db/db mice. However, RYGB neither reversed hyperglycemia in adult diabetic BKS-db/db mice (12 weeks old) nor attenuated hyperglycemia in STZ-induced diabetic mice. These results demonstrate that gastric bypass improves hyperglycemia in genetically modified prediabetic mice; however, it should be performed prior to β-cells exhaustion., Competing Interests: The authors have declared that no competing interests exist.

Objective: To systematically analyze and evaluate the IgG antibody levels of varicella-zoster virus (VZV) in healthy population in China. Methods: CNKI, Wanfang, CBM and PubMed databases were used for the retrieval of literatures about VZV IgG antibody levels in healthy people in China from January 1, 2000 to November 3, 2020. The quality of the included papers was evaluated by the critical appraisal tools for cross sectional study from Joanna Briggs Institute (JBL). The stratified analysis on the IgG antibody levels in populations in different age groups, provinces, regions, gender groups, and years was performed by using software Stata 14.0. Results: A total of 59 papers were included that met the inclusion criteria, including 51 papers in Chinese and 8 papers in English. There were 22 papers with quality score of 8, 16 papers with quality score of 7, 15 papers with quality score of 6, and 6 papers with quality score of 5. Meta-analysis showed that the positive rate of VZV IgG antibody in healthy population in China was 64% (95% CI :60%-67%, I 2 =98.7%), and the IgG antibody levels were reported in the papers for 22 provinces of China. The positive rate of VZV IgG antibody was highest in Yunnan (79%, 95% CI : 64%-93%, I 2 =94.7%) and lowest in Inner Mongolia (50%, 95% CI : 46%-54%); the positive rate of VZV IgG antibody was highest in Northeastern China (71%, 95% CI : 69%-73%) and lowest in Eastern China (62%, 95% CI : 57%-67%); the positive rate of VZV IgG antibody in urban population was higher than that in rural population ( RR =1.08, 95% CI : 1.04-1.11). The positive rate of VZV IgG antibody in women was higher than that in men ( RR =1.10, 95% CI : 1.08-1.11); the positive rate of VZV IgG antibody in the population increased with age; and the positive rate of VZV IgG antibody increased with the change of sampling time. Conclusion: The positive rate of VZV IgG antibody in healthy population in China was relatively low; the coverage of varicella vaccine should be improved for the outbreak control and incidence reduction of varicella in China.

Objective: To explore the relationship between exposure to famine in early life and the risk of hypertension in adulthood. Methods: The medical data of Yichang Health Management Big Data Center from 2018 to 2019 were analyzed. A retrospective cohort study design was adopted, with hypertension as the study outcome, and different life periods exposed to the Great Famine in China were divided into groups. Multivariate logistic regression model was used to analyze the relationship between famine exposure in early life and hypertension in adulthood. At the same time, the interaction between gender and famine exposure was analyzed. Results: The age of 142 016 subjects was (60. 56±4.43). Among them, men accounted for 46.36% (65 845/142 016) and women accounted for 53.64% (76 171/142 016). There are 42 575(29.98%), 19 644(13.83%), 28 405(20.00%), 28 305(19.93%), 23 087 (19.93%) in non-famine exposure group, fetal famine exposure group, early childhood famine exposure group and late childhood famine exposure group, respectively. The prevalence of hypertension was 17.57% (24 947 cases). Multivariate logistic regression model analysis showed that after adjusting for related confounding factors, compared with non-famine exposure group, the risk of hypertension in fetal, early childhood, middle childhood and late childhood famine exposure group was higher and the OR (95% CI ) values were 1.16 (1.11-1.22), 1.27 (1.21-1.33), 1.54 (1.47-1.60) and 1.84 (1.76-1.92), respectively. There was an interaction between sex and famine exposure group ( P <0.001). The above association is stronger among women than among men. Conclusion: Famine exposure in early life may increase the risk of hypertension in adulthood, and the risk of women is greater than that of men.

Objective: To examine increases in average height among Chinese children and adolescents., Methods: The data were obtained from the China Health and Nutrition Survey conducted during the period 1989-2015. A stratified multistage cluster sampling method was utilized to select participants aged 2-22 years in each province. Linear regression was used to examine the effects of age, birth cohort, and survey period on height., Results: A total of 15,227 males and 13,737 females were included in the final analysis. Age (A) showed a continuous effect on height. The average heights of the investigated groups increased continuously during the investigation period. By 2015, the average height of the overall group increased by 7.87 cm compared to the average height during the 1989 survey. Moreover, birth year (cohort, C) also had a stable effect on height. Using the height of individuals born in or before 1975 as a reference, the average height of each birth cohort increased in comparison to the previous birth cohort., Conclusions: The height of Chinese children and adolescents was affected by age, period, and cohort effects, and this effect is governed by certain rules. The age-period-cohort model can be used to analyze the trends of children's and adolescent's heights. The findings provide a scientific basis for the formulation of children's and adolescents' growth and development policies in China., (Copyright © 2021 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

As the progress of population aging in China, the proportion of elderly population is increasing. Both chronic diseases and infectious diseases can threaten the health of the elderly. There are many kinds of infectious diseases, including vaccine preventable infectious diseases affecting the health of adults, such as influenza, pneumococcal diseases and herpes zoster. In addition, the newly emerged COVID-19 has caused a pandemic in the world, resulting the highest proportion of deaths occurred in the elderly and posing a serious threat to the health of the elderly. This paper mainly summarizes the prevention and control of vaccine preventable diseases and COVID-19 to which the elderly are susceptible, analyzes the infectious disease problems affecting the health of elderly population, and recommends countermeasures for the prevention and control of these diseases in elderly population.

Three novel Zr-substituted polyoxotungstate aggregates [H 2 N(CH 3 ) 2 ] 7 NaH 2 [Zr 2 Sb 2 O 3 ( A -α-PW 9 O 34 ) 2 ]·16H 2 O ( 1 ), [H 2 N(CH 3 ) 2 ] 6 H 12 [ZrSb 4 (OH)O 2 ( A -α-PW 8 O 32 )( A -α-PW 9 O 34 )] 2 ·33H 2 O ( 2 ), and [H 2 N(CH 3 ) 2 ] 4 Na 11.5 H 4.5 [Zr 4 W 8 Sb 4 P 5 O 49 (OH) 5 ( B -α-SbW 9 O 33 ) 2 ]·53H 2 O ( 3 ) have been made in hydrothermal reactions of the [ B -α-SbW 9 O 33 ] 9- precursor with Zr 4+ cations and PO 4 3- anions in the presence of dimethylamine hydrochloride and sodium acetate buffer (pH = 4.8) and structurally characterized. Different pH values induce structural transformation from tungstoantimonate (TA) to tungstophosphate (TP). 1 is a di-Zr-substituted sandwich-type TP, the tetranuclear heterometallic [Zr 2 Sb 2 O 3 ] 8+ entity sandwiched by two [ A -α-PW 9 O 34 ] 9- moieties. 2 is a double sandwich-type structure, which can be perceived as two equivalent sandwiched [Sb 3 (PW 8 O 32 )(PW 9 O 34 )] 11- further sandwiching one [Sb 2 Zr 2 (OH) 2 O 4 ] 4+ core to form a novel large-size sandwich-type architecture. Different from 1 and 2 , 3 is a tetra-Zr-substituted sandwiched configuration, in which two [ B -α-SbW 9 O 33 ] 9- fragments sandwich a unique 21-core Sb-P-W-Zr oxo cluster ({Zr 4 W 8 Sb 4 P 5 }). Furthermore, the catalytic oxidation of aromatic thioethers by 3 as the heterogeneous catalyst has been investigated, showing high conversion and remarkable selectivity as well as excellent recyclability.

A new nonanuclear heterometal five-layer sandwich silicotungstate [H 2 N(CH 3 ) 2 ] 6 H 5 NaK{[NaMn 8 O 6 (OAc) 6 ][ A-α- SiW 9 O 34 ] 2 }·34H 2 O ( 1 ) has been made under hydrothermal reactions of MnCl 2 ·4H 2 O, KMnO 4 , trivacant [ A -α-SiW 9 O 34 ] 10- {SiW 9 } fragment, and [H 2 N(CH 3 ) 2 ]·Cl in NaOAc-HOAc buffer (pH = 4.8). The polyoxoanion of 1 is a sandwich architecture, in which the nonanuclear heterometal cluster [NaMn 8 O 6 (OAc) 6 ] 7+ made of two triangular pyramid clusters [Mn 4 O 3 (OAc) 3 ] 3+ {Mn 4 } via a hexacoordinate antitrigonal prism Na + linkage is encapsulated by two trivacant fragments of {SiW 9 }. Furthermore, magnetic measurements of compound 1 reveal the existence of antiferromagnetic exchange interactions between the metal centers.

Purpose: We investigated whether metabolic phenotype improvements following gastric bypass are associated with gastric resection strategy in high-fat diet-induced obese (DIO) mice., Materials and Methods: We developed the mouse Roux-en-Y gastric bypass (RYGB) model with different gastric pouch sizes: (i) RYGB with a large gastric pouch (RYGB-LP), where the stomach was transected, and the jejunum was anastomosed to the residual forestomach, in which 30% of the stomach is retained. (ii) RYGB with a small remnant gastric pouch (RYGB-SP), where the stomach was transected 0.8 cm distal to the esophagogastric junction, and the jejunum is attached to a small remnant of the forestomach (~ 10% of the stomach). (iii) RYGB without gastric pouch (RYGB-NP), where the jejunum is anastomosed to the lower portion of the esophagus., Results: Surgical success rate (or 4-week mouse survival rate) of the RYGB-LP, RYGB-SP, and RYGB-NP procedures was 50, 75, and 85%, respectively. Our data demonstrate that all RYGB procedures improved body weight, glucose tolerance, and liver steatosis, compared with untreated DIO mice at 8-week post-surgery. Major surgical complication, such as obstruction at the forestomach, occurred predominantly in RYGB-LP mice, resulting in a higher mortality. Pre- and post-prandial plasma ghrelin levels did not correlate with improved metabolic phenotype after gastric bypass., Conclusions: We conclude that RYGB with different gastric pouch equally improves obesity and glucose tolerance independent of gastric pouch size and total plasma ghrelin levels in the mouse model of RYGB surgery.

A novel octa-Mn-substituted silicotungstate (ST) [H 2 N(CH 3 ) 2 ] 8 H 19 Na 4 {[K(H 2 O) 4 WO 4 ][SiMnW 10 O 38 ] 3 }[SiMnW 10 O 38 ]·27H 2 O (1) has been made by the hydrothermal reaction of the trivacant [A-α-SiW 9 O 34 ] 10- ({SiW 9 }) building block with Mn 2+ and Mn 7+ cations in the presence of dimethylamine hydrochloride and systematically characterized by IR spectroscopy, elemental analysis, thermogravimetric analysis (TGA), powder X-ray diffraction (PXRD) and single crystal X-ray diffraction. 1 is a tetrameric cluster formed by a hexa-Mn II substituted cyclic trimeric {[K(H 2 O) 4 WO 4 ][SiMnW 10 O 38 ] 3 } unit and a {SiMnW 10 O 38 } fragment via two W-O-Mn III linkers. Furthermore, its electrochemistry, thermal stability and magnetic properties have been studied.

Objective: The current study investigated whether bile diversion (BD) improves metabolic phenotype under farnesoid X receptor (FXR) deficiency., Methods: BD was performed in high-fat diet (HFD)-fed FXR knockout (FXRko) and wild-type (WT) animals. Metabolic phenotypes, circulating enteroendocrine hormones, total bile acids (BAs) and BA composition, and cecal gut microbiota were analyzed., Results: FXR-deficient mice were resistant to HFD-induced obesity; however, FXR-deficient mice also developed hyperglycemia and exhibited increased liver weight, liver steatosis, and circulating triglycerides. BD increased circulating total BAs and taurine-b-muricholic acid, which were in line with normalized hyperglycemia and improved glucose tolerance in HFD-fed WT mice. FXR deficiency also increased total BAs and taurine-b-muricholic acid, but these animals remained hyperglycemic. While BD improved metabolic phenotype in HFD-fed FXRko mice, these improvements were not as effective as in WT mice. BD increased liver expression of fibroblast growth factor 21 and peroxisome proliferator-activated receptor γ coactivator-1β and elevated circulating glucagon-like peptide-1 levels in WT mice but not in FXRko mice. FXR deficiency altered gut microbiota composition with a specific increase in phylum Proteobacteria that may act as a possible microbial signature of some diseases. These cellular and molecular changes in FXRko mice may contribute to resistance toward improved metabolism., Conclusions: FXR signaling plays a pivotal role in improved metabolic phenotype following BD surgery., (© 2019 The Obesity Society.)

Traumatic brain injury (TBI) can result in poor functional outcomes and death, and overall outcomes are varied. Growth factors, such as angiopoietin-1 (Ang-1), vascular endothelial growth factor (VEGF), and granulocyte-colony stimulating factor (G-CSF), play important roles in the neurological functions. This study investigated the relationship between serum growth factor levels and long-term outcomes after TBI. Blood samples from 55 patients were collected at 1, 3 and 7 days after TBI. Blood samples from 39 healthy controls were collected as a control group. Serum Ang-1, G-CSF, and VEGF levels were measured using ELISA. Patients were monitored for 3 months using the Glasgow Outcome Scale-Extended (GOSE). Patients having a GOSE score of > 5 at 3 months were categorized as a good outcome, and patients with a GOSE score of 1-5 were categorized as a bad outcome. Our data demonstrated that TBI patients showed significantly increased growth factor levels within 7 days compared with healthy controls. Serum levels of Ang-1 at 1 and 7 days and G-CSF levels at 7 days were significantly higher in patients with good outcomes than in patients with poor outcomes. VEGF levels at 7 days were remarkably higher in patients with poor outcomes than in patients with good outcomes. Receiver operating characteristic analysis showed that the best cut-off points of serum growth factor levels at 7 days to predict functional outcome were 1,333 pg/mL for VEGF, 447.2 pg/mL for G-CSF, and 90.6 ng/mL for Ang-1. These data suggest that patients with elevated levels of serum Ang-1, G-CSF, and decreased VEGF levels had a better prognosis in the acute phase of TBI (within 7 days). This study was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR1800018251) on September 7, 2018., Competing Interests: None

Objective: To analyze the clinical characteristics of pediatric external auditory canalkeratosis obturans(KO). Method: Retrospective analyze the clinical data of twenty-three patients were diagnosed with external auditory canal cholesteatoma(EACC). Their chief complaint, the course of the disease, clinical characteristics,CT manifestations,surgical procedure and prognosis were retrospectively analyzed. The clinical characteristics between EACC and KO were compared. Result: Twenty cases(22 ears) were eventually diagnosed as KO. Among them, 2 cases were bilaterally involved. In the remaining unilateral cases, right ear was involved in 11 cases and left ear in 7 cases. All patients complained otalgia(100%). Purulent otorrhea was found in 17 ears(77.3%), and hearing loss withpurulent otorrhea in 3 ears(13.6%). Otoscopic examination found 17 ear with granulation(77.3%).CT scan found deformation of the osseous ear canal and displacement of the tympanic membrane because of compression in 18 ears(81.8%), and the bony canal was absorpt because of pression in 7 cases(38.9%).All patients underwent otoendoscopic operation,and tympanic membrane perforation was found in 4 cases.Postoperative pathologic examination results were keratin epithelial. Conclusion: EACC is easily confused with KO. KO should be considered in the following circumstances: patient who complained of ear pain, ear granulation with purulent discharge, or circinate deformation of the osseous ear canal and displacement of the tympanic membrane in CT scan., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Primary pancreatic α, β, δ, and pancreatic polypeptide (PP) cells are reliable cell models for diabetes research. However, the separation and purification of these cells in living conditions remains an obstacle for researchers. The interaction of visible light with cellular molecules can produce Raman scattering, which can be analyzed to obtain cellular intrinsic molecular fingerprints. It has been speculated that primary pancreatic α, β, δ, and PP cells can be identified and separated from each other according to their spectral differences. To test this hypothesis, Raman spectra detection was performed on rat islet cells. Single islet cells identified by Raman scattering under living conditions were verified using immunohistochemistry. Thus, Raman data were acquired from a pure line of islet cells as a training sample and then used to establish the discriminant function. Then, using the principal component analysis-linear discriminate analysis (PCA-LDA) method, the four types of islet cells could be identified and discriminated by Raman spectroscopy. This study provides a label-free and noninvasive method for discriminating islet cell types in a randomly distributed mixed islet cell population via their physical properties rather than by using antibodies or fluorescence labeling.

Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose.

Background: Rotavirus is the leading cause of severe diarrhea among young children worldwide. Rotavirus vaccines have demonstrated substantial benefits in many countries that have introduced vaccine nationally. In China, where rotavirus vaccines are not available through the national immunization program, it will be important to review relevant local and global information to determine the potential value of national introduction. Therefore, we reviewed evidence of rotavirus disease burden among Chinese children younger than 5 years to help inform rotavirus vaccine introduction decisions., Methods: We reviewed scientific literature on rotavirus disease burden in China from 1994 through 2014 in China National Knowledge Infrastructure, Wanfang and PubMed. Studies were selected if they were conducted for periods of 12 month increments, had more than 100 patients enrolled and used an accepted diagnostic test., Results: Overall, 45 reports were included and indicate that rotavirus causes ~40% and ~30% of diarrhea-related hospitalizations and outpatient visits, respectively, among children younger than 5 years in China. Over 50% of rotavirus-related hospitalizations occur by age 1 year; ~90% occur by age 2 years. Regarding circulating rotavirus strains in China, there has been natural, temporal variation, but the predominant local strains are the same as those that are globally dominant., Conclusions: These findings affirm that rotavirus is a major cause of childhood diarrheal disease in China and suggest that a vaccination program with doses given early in infancy has the potential to prevent the majority of the burden of severe rotavirus disease.

The metabolic benefits induced by gastric bypass, currently the most effective treatment for morbid obesity, are associated with bile acid (BA) delivery to the distal intestine. However, mechanistic insights into BA signaling in the mediation of metabolic benefits remain an area of study. The bile diversion () mouse model, in which the gallbladder is anastomosed to the distal jejunum, was used to test the specific role of BA in the regulation of glucose and lipid homeostasis. Metabolic phenotype, including body weight and composition, glucose tolerance, energy expenditure, thermogenesis genes, total BA and BA composition in the circulation and portal vein, and gut microbiota were examined. BD improves the metabolic phenotype, which is in accord with increased circulating primary BAs and regulation of enterohormones. BD-induced hypertrophy of the proximal intestine in the absence of BA was reversed by BA oral gavage, but without influencing BD metabolic benefits. BD-enhanced energy expenditure was associated with elevated TGR5, D2, and thermogenic genes, including UCP1, PRDM16, PGC-1α, PGC-1β, and PDGFRα in epididymal white adipose tissue (WAT) and inguinal WAT, but not in brown adipose tissue. BD resulted in an altered gut microbiota profile (i.e., Firmicutes bacteria were decreased, Bacteroidetes were increased, and Akkermansia was positively correlated with higher levels of circulating primary BAs). Our study demonstrates that enhancement of BA signaling regulates glucose and lipid homeostasis, promotes thermogenesis, and modulates the gut microbiota, which collectively resulted in an improved metabolic phenotype., (Copyright © 2016 the American Physiological Society.)

Objective: To analyze the diagnosis and treatment of acute sinusitis or nasal furuncle derived periorbital cellulitis in children. Method: The clinical data of 18 children with acute sinusitis or nasal furuncle derived orbital cellulitis was analyzed retrospectively. Result: Sixteen cases(88.89%) had acute sinusitis and 2(11.11%) had furuncle of nose.All cases were treated with antibiotics and steroids.And 16 cases were cured and the other two received surgery.The median length of hospitalization was 7.33 days(5-13 days). Conclusion: Sufficient antibiotics combined with steroids and local treatment is critical in treating pediatric orbital cellulitis.Timely and decisive surgical intervention can effectively control the progression of disease., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

At present, there is no effective treatment for the repair of the optic nerve after injury, or improvement of its microenvironment for regeneration. Intravitreally injected ciliary neurotrophic factor (CNTF) and olfactory ensheathing cells (OECs) promote the long-distance regrowth of severed optic nerve fibers after intracranial injury. Here, we examined the efficacy of these techniques alone and in combination, in a rat model of optic nerve injury. We injected condensed OEC suspension at the site of injury, or CNTF into the vitreous body, or both simultaneously. Retrograde tracing techniques showed that 4 weeks postoperatively, the number of surviving retinal ganglion cells and their axonal density in the optic nerve were greater in rats subjected to OEC injection only than in those receiving CNTF injection only. Furthermore, combined OEC + CNTF injection achieved better results than either monotherapy. These findings confirm that OECs are better than CNTF at protecting injured neurons in the eye, but that combined OEC and CNTF therapy is notably more effective than either treatment alone.

Background: The last case of infection with wild-type poliovirus indigenous to China was reported in 1994, and China was certified as a poliomyelitis-free region in 2000. In 2011, an outbreak of infection with imported wild-type poliovirus occurred in the province of Xinjiang., Methods: We conducted an investigation to guide the response to the outbreak, performed sequence analysis of the poliovirus type 1 capsid protein VP1 to determine the source, and carried out serologic and coverage surveys to assess the risk of viral propagation. Surveillance for acute flaccid paralysis was intensified to enhance case ascertainment., Results: Between July 3 and October 9, 2011, investigators identified 21 cases of infection with wild-type poliovirus and 23 clinically compatible cases in southern Xinjiang. Wild-type poliovirus type 1 was isolated from 14 of 673 contacts of patients with acute flaccid paralysis (2.1%) and from 13 of 491 healthy persons who were not in contact with affected persons (2.6%). Sequence analysis implicated an imported wild-type poliovirus that originated in Pakistan as the cause of the outbreak. A public health emergency was declared in Xinjiang after the outbreak was confirmed. Surveillance for acute flaccid paralysis was enhanced, with daily reporting from all public and private hospitals. Five rounds of vaccination with live, attenuated oral poliovirus vaccine (OPV) were conducted among children and adults, and 43 million doses of OPV were administered. Trivalent OPV was used in three rounds, and monovalent OPV type 1 was used in two rounds. The outbreak was stopped 1.5 months after laboratory confirmation of the index case., Conclusions: The 2011 outbreak in China showed that poliomyelitis-free countries remain at risk for outbreaks while the poliovirus circulates anywhere in the world. Global eradication of poliomyelitis will benefit all countries, even those that are currently free of poliomyelitis.

Objective: This study is to investigate the effect of the combination of the olfactory ensheathing cells (OEC) transplantation and intravitreous injection of ciliary neurotrophic factor (CNTF) on the retinal ganglia cells' (RGC) apoptosis and axonals' reparation and regeneration., Methods: In this study, the supraorbital margin exposure of the optic nerves was used to establish adult SD rats' optic nerve inhausted injury model as control group. Then the purified OECs were injected into the optic nerve sheaths, and CNTF was injected into the vitreous body simultaneously. The rats were divided into control group, CNTF group, OECs group, and OEC+CNTF combined group. At 4 weeks postoperatively, a cholera toxin B subunit (CTB) anterograde tracing technique and fluorescence (FG) biotinylated dextran amine (BDA) retrograde tracing technique were adopted to evaluate the survival of RGC and the regeneration of optic nerve axons. The number of survival neurons of the same vision field and the density of neurons were evaluated by analysis of variance., Results: At the one and three quadrant distance between optic disc 2 mm spot, the number of the RGC in the control group was significantly (F = 633.38, P < 0.01) decreased compared with the normal group (46.00 ± 1.42, 34.80 ± 1.34, 25.00 ± 1.61, 15.40 ± 2.30). The survived RGC in OEC group was significantly more than that in CNTF group, while the combined treatment with CNTF and OEC had strongest repair effect. The neuron axon density showed a statistically significant difference in the average optical density value at distance between foramen opticum 2 mm spot (OEC+CNTF: 3.18 ± 0.26, OEC: 2.96 ± 0.28, CNTF: 2.83 ± 0.37, and control: 2.75 ± 0.12, respectively, F = 17.66, P < 0.01) ., Conclusions: Optic nerves damage can be repaired and regenerated by the combined treatment with OEC and CNTF suggesting that CNTF and OEC have synergistic effect on the treatment of optic nerve injury and repair. Transplantation of OECs may genetically modify the secretion of human CNTF and promote optic nerve injury repair.

We have previously shown that mice deficient in protein kinase C theta (PKCθ) have the ability to reject cardiac allografts, but are susceptible to tolerance induction. Here we tested role of B cells in assisting alloimmune responses in the absence of PKCθ. Mouse cardiac allograft transplantations were performed from Balb/c (H-2d) to PKCθ knockout (PKCθ(-/-)), PKCθ and B cell double-knockout (PBDK, H-2b) mice and wild-type (WT) C57BL/6 (H-2b) mice. PBDK mice spontaneously accepted the allografts with the inhibition of NF-κB activation in the donor cardiac allograft. Anti-B cell antibody (rituximab) significantly delayed allograft rejection in PKCθ(-/-), but not in WT mice. Co-transfer of PKCθ(-/-) T plus PKCθ(-/-) B cells or primed sera triggered allograft rejection in Rag1(-/-) mice, and only major histocompatibility complex class II-enriched B cells, but not class I-enriched B cells, were able to promote rejection. This, together with the inability of PKCθ(-/-) and CD28(-/-) double-deficient (PCDK) mice to acutely reject allografts, suggested that an effective cognate interaction between PKCθ(-/-) T and B cells for acute rejection is CD28 molecule dependent. We conclude that T-B cell interactions synergize with PKCθ(-/-) T cells to mediate acute allograft rejection., (© 2013 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Morbid obesity is linked to increased incidences of glucose intolerance, Type 2 diabetes mellitus, cardiovascular diseases, various forms of liver disease, and specific forms of cancer. Treatment of obesity by lifestyle modifications (i.e. changes in diet and exercise) and drug therapy is generally ineffective. Bariatric surgery is currently the most effective means of treating obesity and related disorders. We as well as others have developed surgical procedures for application to genetic mouse models that mimic an array of human bariatric surgical procedures used in the treatment of obesity. The application of bariatric surgery to genetic mouse models will broaden our understanding of the role of the gut in metabolic disease. Models that have been developed include gastric banding, sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB) with a complete exclusion of the stomach, duodenal-jejunal bypass (DJB) and biliopancreatic diversion (BPD). The detailed methods of these procedures are provided.

Morbid obesity is linked to increased incidence of glucose intolerance, Type 2 diabetes mellitus, cardiovascular diseases, various forms of liver disease, and specific forms of cancer. Treatment of obesity by lifestyle modifications (i.e., changes in diet and exercise) and drug therapy is generally ineffective. Bariatric surgery is currently the most effective means of treating obesity and related disorders. We as well as others have developed surgical procedures for application to genetic mouse models that mimic an array of human bariatric surgical procedures used in the treatment of obesity. The application of bariatric surgery to genetic mouse models will broaden our understanding of the role of the gut in metabolic disease. Models that have been developed include gastric banding, sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB) with a complete exclusion of the stomach, duodenal-jejunal bypass (DJB), and biliopancreatic diversion (BPD). The detailed methods of these procedures are provided. Curr. Protoc. Mouse Biol. 2:295-306 © 2012 by John Wiley & Sons, Inc., (Copyright © 2012 John Wiley & Sons, Inc.)

Context: Roux-en-Y gastric bypass (RYGB) is one of the most effective long-term therapies for the treatment of severe obesity. Recent evidence indicates that RYGB effects weight loss through multiple physiological mechanisms, including changes in energy expenditure, food intake, food preference, and reward pathways., Objective: Because central melanocortin signaling plays an important role in the regulation of energy homeostasis, we investigated whether genetic disruption of the melanocortin-4 receptor (MC4R) in rodents and humans affects weight loss after RYGB., Methods and Results: Here we report that MC4R(-/-) mice lost substantially less weight after surgery than wild-type animals, indicating that MC4R signaling is necessary for the weight loss effects of RYGB in this model. Mice heterozygous for MC4R remain fully responsive to gastric bypass. To determine whether mutations affect surgically induced weight loss in humans, we sequenced the MC4R gene in 972 patients undergoing RYGB. Patients heterozygous for MC4R mutations exhibited the same magnitude and distribution of postoperative weight loss as patients without such mutations, suggesting that although two normal copies of the MC4R gene are necessary for normal weight regulation, a single normal copy of the MC4R gene is sufficient to mediate the weight loss effects of RYGB., Conclusions: MC4R is the first gene identified that is required for the sustained effects of bariatric surgery. The need for MC4R signaling for the weight loss effects of RYGB in mice underscores the physiological mechanisms of action of this procedure and demonstrates that RYGB both influences and is dependent on the normal pathways that regulate energy balance.

Objective: To evaluate the effect of the aluminum hydroxide (Al-OH) adjuvant on the 2009 pandemic influenza A/H1N1 (pH1N1) vaccine., Methods: In a multicenter, double-blind, randomized, placebo-controlled trial, participants received two doses of split-virion formulation containing 15 μg hemagglutinin antigen, with or without aluminum hydroxide (Al-OH). We classified the participants into six age categories (>61 years, 41-60 years, 19-40 years, 13-18 years, 8-12 years, and 3-7 years) and obtained four blood samples from each participant on days 0, 21, 35, and 42 following the first dose of immunization. We assessed vaccine immunogenicity by measuring the geometric mean titer (GMT) of hemagglutination inhibiting antibody. We used a two-level model to evaluate the fixed effect of aluminum Al-OH and other factors, accounting for repeated measures., Results: The predictions of repeated measurement on GMTs of formulations with or without Al-OH, were 80.35 and 112.72, respectively. Al-OH significantly reduced immunogenicity after controlling for time post immunization, age-group and gender., Conclusion: The Al-OH adjuvant does not increase but actually reduces the immunogenicity of the split-virion pH1N1 vaccine., (Copyright © 2011 The Editorial Board of Biomedical and Environmental Sciences. Published by Elsevier B.V. All rights reserved.)

Objective: To assess the effects of different bariatric surgical procedures on the treatment of obesity and insulin resistance in high fat diet-induced obese (DIO) mice., Background: Bariatric surgery is currently considered the most effective treatment for morbid obesity and its comorbidities; however, a systematic study of their mechanisms is still lacking., Methods: We developed bariatric surgery models, including gastric banding, sleeve gastrectomy, Roux-en-Y gastric bypass (RYGB), modified RYGB (mRYGB) and biliopancreatic diversion (BPD), in DIO mice. Body weight, body fat and lean mass, liver steatosis, glucose tolerance and pancreatic beta cell function were examined., Results: All bariatric surgeries resulted in significant weight loss, reduced body fat and improved glucose tolerance in the short term (4 weeks), compared with mice with sham surgery. Of the bariatric surgery models, sleeve gastrectomy and mRYGB had higher success rates and lower mortalities and represent reliable restrictive and gastrointestinal (GI) bypass mouse bariatric surgery models, respectively. In the long term, the GI bypass procedure produced more profound weight loss, significant improvement of glucose tolerance and liver steatosis than the restrictive procedure. DIO mice had increased insulin promoter activity, suggesting overactivation of pancreatic beta cells, which was regulated by the mRYGB procedure. Compared with the restrictive procedure, the GI bypass procedure showed more severe symptoms of malnutrition following bariatric surgery., Discussions: Both restrictive and GI bypass procedures provide positive effects on weight loss, fat composition, liver steatosis and glucose tolerance; however, in the long term, the GI bypass shows better results than restrictive procedures.

Background: On September 21, 2009, China began administering vaccines, obtained from 10 different manufacturers, against 2009 pandemic influenza A (H1N1) virus infection in priority populations. We aimed to assess the safety of this vaccination program., Methods: We designed a plan for passive surveillance for adverse events after immunization with the influenza A (H1N1) vaccine. Physicians or vaccination providers were required to report the numbers of vaccinees and all adverse events to their local Center for Disease Control and Prevention (CDC), which then reported the data to the Chinese CDC through the online National Immunization Information System's National Adverse Event Following Immunization Surveillance System. Data were collected through March 21, 2010, and were verified and analyzed by the Chinese CDC., Results: A total of 89.6 million doses of vaccine were administered from September 21, 2009, through March 21, 2010, and 8067 vaccinees reported having an adverse event, for a rate of 90.0 per 1 million doses. The age-specific rates of adverse events ranged from 31.4 per 1 million doses among persons 60 years of age or older to 130.6 per 1 million doses among persons 9 years of age or younger, and the manufacturer-specific rates ranged from 4.6 to 185.4 per 1 million doses. A total of 6552 of the 8067 adverse events (81.2%; rate, 73.1 per 1 million doses) were verified as vaccine reactions; 1083 of the 8067 (13.4%; rate, 12.1 per 1 million doses) were rare and more serious (vs. common, minor events), most of which (1050) were allergic reactions. Eleven cases of the Guillain-Barré syndrome were reported, for a rate of 0.1 per 1 million doses, which is lower than the background rate in China., Conclusions: No pattern of adverse events that would be of concern was observed after the administration of influenza A (H1N1) vaccine, nor was there evidence of an increased risk of the Guillain-Barré syndrome.

From March 2009 to October 2009, three pediatric patients with parotid tumor were cured. Preoperative physical examination showed regional swelling in parotid area, the surface skin was in moderate reddish purple, the border was vague, and the swelling was inactive. The patients' IgE were significantly increased. B ultrasound examination demonstrated the focus was an isoecho with ringlike dark band around, which was concluded as bull's-eye sign. Magnetic resonance imaging (MRI) examination indicated a cystic mass between the skin and parotid. Preoperative diagnosis was eosinophilichyperplastic lymphogranuloma (Kimura's disease) and the granuloma was excised by operation. Pathological examination revealed the capillary vessel hyperplasia in local tissue with a plenty of eosinophils and lymphocytes infiltrating. The disease was confirmed. Although the disease is rare, the diagnosis still could be made by preoperative physical examination, laboratory and imaging examinations.

We have previously shown that islet emboli in the portal vein block blood flow and induce local inflammatory reaction, resulting in functional loss of islet grafts following intraportal transplantation. This study was designed to test whether Toll-like receptor (TLR) activation mediates early islet graft failure. Syngeneic islet grafts were transplanted into chemically induced diabetic mice, and TLR deficient mice were used as donors and/or recipients of islet grafts. Islet viability, proinflammatory cytokines, high-mobility group box-1 (HMGB1) and NF-kappaB activation were analyzed by bioluminesce imaging (BLI), quantitative RT-PCR (qRT-PCR) and histology. Early islet graft failure was observed in mice with intraportal islet engrafts with increased proinflammatory cytokines, HMGB1 expression, NF-kappaB activation, caspase-3 and TUNEL positive cells. Deficiency of TLR4 in donor, but not in recipient, inhibited NF-kappaB activation, reduced proinflammatory cytokines and improved viability of islet grafts. Blockade of HMGB1 with anti-HMGB1 monoclonal antibody (mAb, 2g7) inhibited inflammatory reactions, as evidenced by reduced TNFalpha and IL-1ss production, and improved islet viability. We conclude that TLR4 activation mediates early graft failure following intraportal islet transplantation. Inhibition of TLR4 activation represents a novel strategy to attenuate early graft failure following intraportal islet transplantation.

Liver allografts are spontaneously accepted in the liver transplantation mouse model; however, the basis for this tolerance and the conditions that abrogate spontaneous tolerance to liver allografts are incompletely understood. We examined the role of CpG oligodeoxynucleotide (ODN) in triggering the liver inflammatory reaction and allograft rejection. Bioluminescence imaging quantified the activation of nuclear transcriptional factor kappaB (NF-kappaB) at different time points post-transplantation. Intrahepatic lymphocyte subsets were analyzed by immunofluorescence assay and flow cytometry. The results showed that liver allografts survived for more than 100 days without a requirement for any immunosuppressive therapy. Donor-matched cardiac allografts were permanently accepted, whereas third-party cardiac grafts were rejected with delayed kinetics; this confirmed donor-specific tolerance. NF-kappaB activation in the liver allografts was transiently increased on day 1 and diminished by day 4; in comparison, it was elevated up to 10 days post-transplantation in the cardiac allografts. When CpG ODN was administered at a high dose (50 microg per mouse x 1) to the recipients on day 7 post-transplantation, it induced an acute liver inflammatory reaction with elevated NF-kappaB activation in both allogeneic and syngeneic liver grafts. Multiple doses of CpG ODN (10 microg per mouse x 3) elicited acute rejection of the liver allografts with significant T cell infiltration in the liver allografts, reduced T regulatory cells, and enhanced interferon gamma-producing cells in the intrahepatic infiltrating lymphocytes. These data demonstrate that CpG ODN initiates an inflammatory reaction and abrogates spontaneous tolerance in the liver transplantation mouse model. Liver Transpl 15:915-923, 2009. (c) 2009 AASLD.

Objective: To analyse the economic burden of outpatient with varicella in China in 2007., Methods: In three provinces, the sample were places are stratified by economic condition in district, county and township level. 811 outpatient cases were sampled and analysized., Results: The cost of outpatient was 493.66 RMB per case, including direct expenses 219.52 RMB and indirect expenses 274.14 RMB per case. The total cost of outpatient varicella in China was 2.3 billion RMB in 2007., Conclusions: The disease burden was heavy in China.

Objective: To analyse the incidence character of varicella in Shandong, Gansu and Hunan provinces in 2007., Method: One township of rural area and one community of urban area were selected from Shandong, Gansu and Hunan each province for sampling. 34578 children were sampled and 1213 clinical diagnostic cases were confirmed., Result: The incidence of 0-14 ys was 1836.72/100,000 and the estimated incidence of entire population was 357.95/100,000. The peak age of incidence was 5-9 age group children., Conclusion: The incidence of varicella in China was high and the incidence was different between areas or ages.

Background: Protein kinase C-theta (PKCtheta) mediates critical T-cell receptor signals required for T-cell activation. We have recently shown that PKCtheta knockout (PKCtheta, H-2b) T cells, when transferred into T/B cell-deficient mice, failed to reject fully allogeneic (H-2d) cardiac grafts and that transgenic expression of antiapoptotic Bcl-xL gene in PKCtheta T cells restored allograft rejection., Methods: We used PKCtheta mice as recipients of cardiac allografts, compared with wild-type (WT) cardiac allograft transplantation. Anti-CD154 monoclonal antibody (MR1) and human CTLA4Ig were sued to induce donor-specific tolerance. T-cell proliferation, T-cell subsests, nuclear factor kappa B (NF-kappaB) activation, and Bax and Bcl-xL were analyzed., Results: Although suboptimal anti-CD154 monoclonal antibody or human CTLA4Ig failed to delay cardiac allograft rejection in WT mice, the same therapy induced long-term survival of cardiac allografts in PKCtheta mice. Donor-type second cardiac allografts (H-2d) were accepted, and third-party heart allografts (H-2k) were rejected by tolerant PKCtheta mice. However, tolerance state could not be effectively transferred with T cells from tolerance PKCtheta mice. Compared with WT mice, reduced NF-kappaB activation, T-cell proliferation, and T-cell infiltration in PKCtheta spleens were observed. PKCtheta mice reveal reduced CD4/CD25/FoxP3, Th1/Th17 subsets, and mouse MHC class II (IE)-reactive CD4Vbeta11 T cells. Apoptotic molecule, Bax, was increased and antiapoptotic molecule, Bcl-xL, was reduced in PKCtheta spleen cells., Conclusion: We concluded that PKCtheta mice have a defected alloimmune response and are susceptible to tolerance induction, which is associated with a clonal deletion of T-cell subsets.

Background: We characterized the role of T cell subsets and major histocompatibility complex molecules in allograft rejection and recurrence of autoimmune diabetes., Methods: Adoptive cell transfer and vascularized segmental pancreas transplantation were performed in mice., Results: In an alloimmune response model, transfer of nondiabetic CD4, but not CD8 T cells, elicited pancreas allograft rejection in streptozotocin (STZ)-induced diabetic NOD/scid mice. Pancreas allografts were acutely rejected in STZ-induced diabetic NOD/beta2m mice (confirmed the absence of major histocompatibility complex [MHC] class I and CD8 T cells) and permanently accepted in NOD/CIIT mice (confirmed the absence of MHC class II and CD4 T cells). The results suggest that rejection of pancreas allograft is CD4-dependent and MHC class I-independent. In the autoimmune diabetes model, whole spleen cells obtained from diabetic NOD mice induced autoimmune diabetes in NOD/scid and NOD/CIIT mice, but the onset of diabetes was delayed in NOD/beta2m mice. However, the purified diabetic T cells failed to elicit autoimmune diabetes in NOD/beta2m mice. NOD/scid and NOD/CIIT pancreas grafts were acutely destroyed whereas four of six NOD/beta2m pancreas grafts were permanently accepted in autoimmune diabetic NOD mice., Conclusion: CD4 T cells are sufficient for the induction of allograft rejection, and MHC class I molecule is required to induce recurrent autoimmune diabetes after pancreas transplantation in mice.

Background: The purpose of the current study was to evaluate the role of bioluminescence imaging (BLI) in the determination of nuclear factor (NF)-kappaB activation in cardiac allograft rejection and ischemia-reperfusion injury., Methods: To visualize NF-kappaB activation, luciferase transgenic mice under the control of a mouse NF-kappaB promoter (NF-kappaB-Luc) were used as donors or recipients of cardiac grafts. Alternatively, NF-kappaB-Luc spleen cells were adoptively transferred into Rag2 -/- mice with or without cardiac allografts. BLI was performed posttransplantation to detect luciferase activity that represents NF-kappaB activation., Results: The results show that luciferase activity was significantly increased in the cardiac allografts when NF-kappaB-Luc mice were used as recipients as well as donors. Luciferase activity was also elevated in the wild-type cardiac allografts in Rag2 -/- mice that were transferred with NF-kappaB-Luc spleen cells. CD154 monoclonal antibody (mAb) therapy inhibited luciferase activity and induced long-term survival of cardiac allografts. toll-like receptor-9 ligand, CpG DNA, enhanced luciferase activity and abrogated tolerance induction by CD154 mAb. Luciferase activity was also increased in ischemia-reperfusion injury of the cardiac grafts., Conclusion: BLI using Luc-NF-kappaB mice is a noninvasive approach to visualize the activation of NF-kappaB signaling in mouse cardiac allograft rejection and ischemia-reperfusion injury. CD154 mAb can inhibit NF-kappaB activation, which is reversed by toll-like receptor engagement.

E2F-1 mediates apoptosis through transcriptional regulation of its targets. We report here that E2F-1 acts as a direct transcriptional regulator of dual specificity phosphatase 1 (DUSP1; CL100), a threonine and tyrosine phosphatase that inhibits mitogen-activated protein (MAP) kinases. We found that DUSP1 is transcriptionally induced by ectopic E2F-1 expression and that extracellular signal-regulated kinase 1/2 are dephosphorylated in the presence of E2F-1 and DUSP1. E2F-1 mediates apoptosis in the cellular response to oxidative stress. DUSP1 levels are significantly increased in an E2F-1-dependent manner following oxidative stress but not other stresses examined. DUSP1 mediates the cellular response to oxidative stress. We found that E2F-1 binds to chromatin encompassing the DUSP1 promoter and greatly stimulates the promoter activity of the DUSP1 gene. In particular, E2F-1 physically binds to an E2F-1 consensus sequence and a palindromic motif in the DUSP1 promoter. Interestingly, E2F-1 is acetylated following oxidative stress. Our findings show that E2F-1 is a transcriptional activator of DUSP1 and that DUSP1 is a link between E2F-1 and MAP kinases.

Objective: To investigate the immunity level of diphtheria antibody among children living in the areas where different coverage rates of 4-vaccines stratified by results of national immunization program (NIP) reviewed in 2004., Methods: According to data from 4-vaccine coverage rates of NIP reviewed in 2004, 3 levels could be set. We randomly selected 2 counties at each level and then 10 villages from each county with 42 children involved who were born between 1992 and 2003. ELISA quantitative method was used to test IgG of diphtheria antitoxin., Results: (1) The positive rate of diphtheria antitoxin was only 49.6% with the highest as 78.1% and lowest as 33.0%. There was a significant decreasing trend of this positive rate with the increase of age. The highest (61.2%) fell in the group that were born in 2003 and the lowest (37.6%) was seen among children born in 1992 to 1995. (2) Geometric mean concentrations (GMCs) was only 0.48 IU/ml with a trend of decrease when age was increasing. There was no GMCs peak seen in children who were at the age of boosting, as expected. (3) Positive rates of children born between 2001 and 2003 were lower than 62% while the diphtheria-pertussis-tetanus (DPT) vaccine coverage rates were all higher than 90%. (4) There was no significant difference of diphtheria antitoxin positive rates between children with eligible routine immunization (58.1%) and those were ineligible (59.6%)., Conclusion: Other than some specific ones, children from most of the investigated counties had a low level of antibody against diphtheria. The coverage rate of DPT vaccine did not necessarily reflect the immunity against diphtheria, suggesting the increase of immunity against diphtheria an urgent task to be taken care of.

Background: FK778 is a malononitrilamide, a class of immune suppressive compounds with antiviral features and experimental activity in chronic rejection, a potentially interesting combination for organ transplantation. The goal of this project was to study the tolerability, immune suppressive efficacy, and anti-cytomegalovirus (CMV) activity of FK778 and to assess the in vivo relevance of its previously described inhibition of de novo pyrimidine synthesis., Methods: Heart transplants were performed in rats (Brown Norway [BN] to Lewis) and treated with varying doses of FK778 or leflunomide for 28 days. At 28 days, at the time of rejection or at the death of the animal, the allograft and other vital organs were obtained for study by light microscopy and immunohistochemistry. In separate experiments, Lewis rats were given sublethal irradiation, inoculated with rat CMV (Maastricht strain), and treated with varying doses of FK778 and leflunomide. In both the transplant and CMV studies, IP uridine was given at 250 mg/kg to cohorts or animals receiving FK778 and leflunomide., Results: FK778 controls acute rejection and inhibits CMV replication at 20 mg/kg but is toxic at 25 mg/kg. Toxicity is manifested as anemia, changes in hepatic and intestinal histology, and mortality. The toxicity but not the immune suppressive or antiviral efficacy, is reduced significantly by exogenous uridine administration., Conclusion: FK778 has both immune suppressive and antiviral activities, neither of which is entirely dependent on inhibition of pyrimidine synthesis. These, and other published observations, suggest that the antiviral activity and a considerable part of the efficacy of the malononitrilamide family of drugs is attributable to activities other than drug induced pyrimidine deficiency.

Background: Immune response to incompatible ABO antigens on allografts may result in rejection, accommodation, or immune tolerance. Our objective has been to develop a model for studying these three types of immune response to incompatible carbohydrate antigen in alpha1,3-galactosyltransferase knockout (KO) mice. KO mice lack the alpha-gal epitope and can produce the anti-Gal antibody against it after immunization with pig kidney membranes (PKM) that express this epitope., Methods: KO mice were transplanted with syngeneic wild-type (WT) heart expressing alpha-gal epitopes. Subsequently, the mice were lethally irradiated and received lymphocytes including memory anti-Gal B cells from PKM immunized KO mice. Immune response to incompatible alpha-gal epitopes on the graft was determined by transplanted-heart function and by production of anti-Gal after PKM immunizations., Results: Anti-Gal B cells exposed for 1 to 2 weeks to alpha-gal epitopes of WT hearts differentiate into cells producing noncytolytic accommodating antibodies. Exposure for longer periods (2-4 weeks) induces a transition from accommodation into tolerance, indicated by the inability of mice to produce anti-Gal antibodies despite repeated PKM immunizations. WT hearts in accommodating and in tolerized mice continue to function for months., Conclusions: In the absence of T-cell help, anticarbohydrate B cells exposed to incompatible carbohydrate antigens of transplanted organs differentiate first into cells capable of producing accommodating antibodies, but, after prolonged exposure, these B cells gradually become tolerized. These findings suggest that prolonged T-cell suppression in recipients of ABO-incompatible allografts may result in a similar induction of tolerance to incompatible blood-group antigens.