Granzyme B: A novel therapeutic target for treatment of atopic dermatitis

Granzyme B is a serine protease that can play multiple roles in intracellular and extracellular perforin-dependent or non-perforin-dependent mechanisms. Granzyme B has been found to be an important factor involved in the pathogenesis of atopic dermatitis and is increased in both skin lesions and peripheral blood of atopic dermatitis patients. In this article, we review the correlation between granzyme B and atopic dermatitis to provide a novel therapeutic targeting option for clinical treatment of the latter.

Curative effect of capreomycin in adjuvant treatment of multidrug-resistant pulmonary tuberculosis and its effect on quality of life and immune function / 中国热带医学

@#Abstract: Objective To investigate the efficacy of capreomycin adjuvant therapy for multidrug-resistant pulmonary tuberculosis (MDR-TB) and its effect on quality of life and immune function. Methods Eighty-eight elderly pulmonary tuberculosis patients admitted to Affiliated Hospital of Hebei University from October 2019 to October 2020 were selected and divided into two groups according to the random number table method. The control group (n=44) used 4-6Am-Mfx（Lfx）-Pto-Cfz-Z-Hhigh-dose-E/5 Mfx（Lfx）-Cfz-Z-E, the research group (n=44) used capreomycin on the basis of the control group. The 6-Minute Walk Test (6MWT) measured value/predicted value and quality of life [36-Item Short Form Health Survey Questionnaire (SF-36)] scores, safety evaluation results, chest CT cavity and lesion absorption rate and sputum culture turned negative were compared between the two groups, and the serum procalcitonin (PCT) expression levels and immune function were detected before and after treatment. Results The 6MWT measured value/predicted value of the research group and control group before the treatment were (0.48±0.11) and (0.64±0.13), which were significantly higher than corresponding (0.51±0.12) and (0.58±0.14) after treatment (t=6.23, 2.520, P<0.05), the measured/expected value of 6MWT increased in both groups after treatment. Compared with the same group before treatment, the SF-36 scores for each dimension increased in both groups after treatment (P<0.01). The expression levels of serum PCT in the research group and control group before the treatment were (0.37±0.09) ng/mL and (0.12±0.03) ng/mL versus (0.36±0.11) ng/mL and (0.21±0.06) ng/mL after treatment (t=17.480, 7.940, P<0.01). Compared with the same group before treatment, serum PCT expression levels decreased in both groups after treatment. Compared with the same group before treatment, CD3+, CD4+ and CD4+/CD8+ were elevated in both groups after treatment (P<0.05 or P<0.01); after treatment, CD3+, CD4+, and CD4+/CD8+ were significantly higher in research group compared to the control group (t=4.21, 8.02, 2.04, P<0.05). The absorption rate of chest CT cavity and lesions and negative rate of sputum culture in the research group were 88.64% (39/44) and 81.82% (36/44), which were significantly higher than corresponding 63.64% (28/44) and 61.36% (27/44) in the control group (P<0.05). Conclusions　Capreomycin can improve the quality of life of MDR-TB patients, extend the 6-minute walking distance, and regulate serum PCT expression levels and immune function, to promote the absorption of chest CT cavity and lesions, and sputum culture to turn negative, and the security is acceptable.

Analysis of AI image recognition approach for monitoring primary school students outdoor activity time in school / 中国学校卫生

Objective@#To develop a method that can continuously monitor duration of students outdoor activities for a long time, so as to provide data support for the relationship between outdoor activity duration and students health.@*Methods@#From April 28 to July 6, 2022, 1 168 students from a primary school in Shenzhen were selected. Fixed cameras were placed on the top of school classrooms, corridors and critical paths were used to identify student data and duration in the picture. And AI, cloud computing and other methods were used to measure students-non-classroom time instead of outdoor activity time in school.@*Results@#The average length of time spend on outdoor activities in school of the 24 pilot classes were 67.6-113.0 min, and showed a downward trend by grade ( F =42.74, P <0.05). The duration of outdoor activities among students was negatively correlated with the detection rate of myopia and overweight( r =-0.74, -0.45, P <0.05).@*Conclusion@#The data on outdoor activity time calculated by AI image recognition is basically in line with the reality. Monitoring students outdoor activity time at school through AI image recognition is feasible and popularized.

Clinical significance of ferroptosis-related lncRNAs in prognosis and immune infiltration in clear cell renal cell carcinoma based on bioinformatics analysis / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：采用生物信息学方法探索与肾透明细胞癌(ccRCC)组织中铁死亡相关的lncRNA，并探讨其与免疫细胞浸润及患者预后的相关性，为ccRCC患者提供新的分子靶点。方法：从癌症基因组图谱(TCGA)数据库下载ccRCC的转录本数据和临床数据，利用单样本基因集富集分析(ssGSEA)及相关性分析获得与铁死亡相关的lncRNA；通过单因素和多因素回归分析构建与铁死亡相关的lncRNA特征图，分析其与预后的关系；利用R软件分析铁死亡相关lncRNA与肿瘤免疫细胞浸润和药物敏感性之间的关系。构建铁死亡相关RNA网络，并通过qPCR验证中国人ccRCC组织和癌旁组织（取自2019年12月至2021年03月间在西南医科大学附属医院手术切除8例标本）中关键lncRNA的表达。结果：Kaplan-Meier分析表明，铁死亡评分高的患者总OS率低于铁死亡评分低的患者。单因素和多因素回归分析确定11个ccRCC铁死亡相关lncRNA可评估患者预后，并构建ccRCC患者1、3、5年预后预测列线图。免疫细胞浸润分析表明，铁死亡相关lncRNA与ccRCC免疫细胞浸润密切相关，其中LINC01871、PRKAR1B-AS1和CYTOR是调节肿瘤免疫细胞浸润的关键lncRNA。化疗药物敏感性分析表明，高风险患者对甲氨蝶呤、紫杉醇、顺铂和多柔比星更为敏感。构建的包含3个lncRNA、15个miRNA和15个mRNA的RNA网络中，验证实验显示LINC01871、LINC00472和CYTOR在ccRCC组织中显著上调。结论：通过生物信息学方法获得11个与铁死亡相关的lncRNA，证明其与ccRCC组织免疫细胞浸润、化疗药物敏感性和患者预后相关，为探索ccRCC铁死亡相关lncRNA标志物提供重要参考。

Renewed understanding of nicotinic acid and its derivatives: from traditional nutrients to cancer prevention and treatment / 中国肿瘤生物治疗杂志

@#[摘 要] 烟酸属于B族维生素，是人体必需的维生素之一。过去对烟酸功能的认知主要停留在营养素层面，如参与维持神经功能、促进代谢和发育、保护心脑血管等。随着研究的不断深入，近年来已有多项研究表明，烟酸及其衍生物能起到预防和辅助治疗癌症的作用。烟酸及其衍生物不仅影响肿瘤细胞的生物学功能、参与免疫调节，还能对烟酰胺磷酸核糖转移酶（NAMPT）抑制剂的抗肿瘤疗效起到辅助作用，并以多聚ADP-核糖聚合酶（PARP）依赖方式通过多种分子途径维持基因组的稳定性。本文总结了烟酸及其衍生物在肿瘤中作用的研究脉络和最新进展，并展望其进一步研究和应用方向，对烟酸及其衍生物在肿瘤综合防治中的应用有一定的指导作用。

Acupuncture regulates the apoptosis of ovarian granulosa cells in polycystic ovarian syndrome-related abnormal follicular development through LncMEG3-mediated inhibition of miR-21-3p

Background The main features of polycystic ovary syndrome (PCOS) are abnormal follicular development and ovulatory dysfunction, which are caused by excessive apoptosis of ovarian granulosa cells. Acupuncture has been shown to improve follicular development abnormalities in patients with PCOS, but its mechanism is unknown. This study hypothesized that the mechanism of acupuncture on follicular development abnormalities in PCOS patients is the inhibition of granulosa cell apoptosis through LncMEG3-mediated regulation of miR-21-3p. Methods A PCOS-like rat model was established using subcutaneous injection of dehydroepiandrosterone (DHEA). Acupuncture was performed on rats for 15 d (CV-4, RN-3, CV-6, SP-6 and EX-CA 1). Ovarian morphology was observed by HE staining, and sex hormone and AMH levels were detected by ELISA. Primary granulosa cells were isolated from each group of rats to assess the association of acupuncture treatment, LncMEG3, miR-21-3p, and granulosa cell apoptosis in rats with PCOS. Results LncMEG3 and miR-21-3p were highly expressed in the ovarian granulosa cells of rats with PCOS, and LncMEG3-mediated regulation of miR-21-3p was involved in the development of PCOS in rats. Silencing of MEG3 attenuated sex hormone dysregulation and ovarian histopathological changes in PCOS rats and promoted follicle cell development and maturation. In addition, silencing MEG3 increased the viability and number of granulosa cells. In addition, silencing MEG3 further inhibited early and late apoptosis of ovarian granulosa cells in PCOS rats. Acupuncture improved polycystic ovarian morphology and sex hormone levels in PCOS rats. Acupuncture intervention increased the viability and number of granulosa cells. Acupuncture intervention inhibited early and late apoptosis of ovarian granulosa cells in PCOS rats by targeting miR-21-3p via LncMEG3. Conclusion These results suggest that acupuncture can downregulate LncMEG3, thereby targeting and regulating miR-21-3p to suppress early and late granulosa cell apoptosis and normalize their proliferation. These factors ultimately compensate for abnormal follicular development. These findings shed light on the clinical potential of acupuncture as a safe treatment for follicular developmental abnormalities in PCOS. Highlights LncMEG3-mediated inhibition of miR-21-3p regulates ovarian granulosa cell apoptosis. LncMEG3 and miR-21-3p are involved in the occurrence and development of PCOS-related abnormal follicular development. CuONPs induce co-occurrence of autophagy activation and autophagic flux blockade. Acupuncture can improve the sex hormone levels and follicular development in the context of PCOS. The underlying mechanism of acupuncture in the treatment of PCOS abnormal follicular development was revealed.

Abnormal expression of miRNA-122 in cerebral infarction and related mechanism of regulating vascular endothelial cell proliferation and apoptosis by targeting CCNG1

Abstract Objective: To analyze the value of serum miRNA-122 expression in the diagnosis, severity, and prognosis of Acute Cerebral Infarction (ACI) and the correlation mechanism of serum miRNA-122 on the proliferation and apoptosis of vascular endothelial cells in ACI. Method: A total of 60 patients with ACI who were admitted to the emergency department of the Taizhou People's Hospital from January 1, 2019, to December 30, 2019, and 30 healthy controls during the same period were selected. General clinical data of all patients at admission were collected. Including age, sex, medical history, and inflammatory factors (C-Reactive Protein [CRP], Interleukin-6 [IL-6], Procalcitonin [PCT], Neutrophil Gelatinase-Associated Lipid carrier protein [NGAL]). The National Institutes of Health Stroke Scale (NIHSS) score at admission and short-term prognosis (the Modified Rankin Score [mRS]) score at 3 months after onset were recorded. The expression level of miRNA-122 in the serum of patients with ACI and normal controls was detected by reverse-transcription quantitative Real-Time Polymerase Chain Reaction (RT-QPCR), and the correlation between the expression level of miRNA-122 in the serum of patients with ACI and the level of inflammatory factors, NIHSS and mRS scores were analyzed. The expression levels of miRNA-122 in the serum of patients with ACI, normal people, and Human Umbilical cord Endothelial Cells (HUVECs) cultured in a blank control group were detected by RT-QPCR and statistically analyzed. MTT and flow cytometry was used to compare the proliferation and apoptosis of vascular endothelial cells in the miRNA-122 mimics and inhibitors transfection groups and the corresponding negative control group. The mRNA and protein levels of apoptosis-related factors Bax, Bcl-2, Caspase-3, and angiogenesis-related proteins Hes1, Notch1, Vascular Endothelial Growth Factors (VEGF), and CCNG1 were detected by RT-QPCR and Western blot. Bioinformatics methods predicted CCNG1 to be the target of miRNA-122, and the direct targeting relationship between CCNG1 and miRNA-122 was verified by a dual-luciferase reporting assay. Result: Serum miRNA-122 expression in patients with ACI was significantly higher than that in healthy controls, with an area under the receiver operating characteristic curve of 0.929, 95% Confidence Interval of 0.875‒0.983, and an optimal cut-off value of 1.397. The expression levels of CRP, IL-6, and NGAL in patients with ACI were higher than those in healthy control groups, p < 0.05; miRNA-122 was positively correlated with CPR, IL-6, NIHSS score, and mRS score. At 48h and 72h, the proliferation rate of HUVECs cells in the miRNA-122 mimics group decreased and the apoptosis rate increased. Cell proliferation rate increased, and apoptosis rate decreased significantly in the groups transfected with miRNA-122 inhibitors. The mRNA and protein levels of pro-apoptotic factors Bax and caspase-3 were significantly increased in the miRNA-122 mimics transfection group, while those of anti-apoptotic factor Bcl-2 were significantly decreased compared to those of the control group. The expression of Bax and Caspase-3 decreased, and the expression of anti-apoptotic factor Bcl-2 increased in the transfected miRNA-122 inhibitors group. mRNA expression levels of Hes1, Notch1, VEGF, and CCNG1 in the miRNA-122 mimic transfected group were significantly decreased, while mRNA expression levels in the miRNA-122 inhibitors transfected group were significantly increased. Bioinformatics showed that there was a miRNA-122 binding site in the 3′UTR region of CCNG1, and dual luciferase assay confirmed that CCNG1 was the target of miRNA-122.

A consensus on the management of allergy in kindergartens and primary schools / 中国学校卫生

Abstract@#Allergic diseases can occur in all systems of the body, covering the whole life cycle, from children to adults and to old age, can be lifelong onset and even fatal in severe cases. Children account for the largest proportion of the victims of allergic disease, Children s allergies start from scratch, ranging from mild to severe, from less to more, from single to multiple systems and systemic performance, so the prevention and treatment of allergic diseases in children is of great importance, which can not only prevent high risk allergic conditions from developing into allergic diseases, but also further block the process of allergy. At present, there is no consensus on the management system of allergic children in kindergartens and primary schools. The "Consensus on Allergy Management and Prevention in Kindergartens and Primary Schools", which includes the organizational structure, system construction and management of allergic children, provides evidence informed recommendations for the long term comprehensive management of allergic children in kindergartens and primary schools, and provides a basis for the establishment of the prevention system for allergic children.

Relationship between polycyclic aromatic hydrocarbons internal exposure and lung function change among healthy college students / 中国学校卫生

Objective@#To investigate the relationship between urinary monohydroxylated metabolites of hydroxyl polycyclic aromatic hydrocarbons (OH-PAHs) and lung function, as well as the role of oxidative stress in these associations, so as to provide a scientific basis for air pollution control and policy formulation.@*Methods@#A panel study was carried out among 45 young healthy adults. Four follow up surveys and health examinations were conducted from November 2017 to October 2018 to measure lung function parameters [forced vital capacity (FVC), second forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), FEV1/FVC, and forced expiratory flow between 25% and 75% vital capacity (FEF 25%~75% )], markers of exposure to 7OHPAHs [∑ 7OH PAHs], and markers of oxidative stress[8 hydroxy 2 deoxyguanosine (8 OHdG) and 8 isoprostaglandin F 2α (8 iso PGF 2α )]. The relationship between urinary PAH metabolites and lung function was quantified by linear mixed effects models. Mediation analysis was performed to assess the role of oxidative stress in the relationship between OH PAHs and lung function.@*Results@#The median values of FVC, FEV1, FEVI/FVC, PEF, and FEF 25%-75% were 4.37 L, 3.58 L, 83.00%, 4.38 L/s, and 3.32 L/s, respectively. The results showed that each 1 unit increase in log transformed value of 2 Hydroxyfluorene (2 OHFlu) was associated with a 5.05% decrease ( β %=-5.05%，95% CI =-8.85%--1.09%) in FVC, 4.15% decrease ( β %=-4.15%，95% CI =-7.94%- -0.22% ) in FEV1 and 5.87% decrease ( β %=-5.87%，95% CI =-11.35%--0.05%) in FEF 25%-75% , respectively. Each 1 unit increase in log transformed values of 2 OHFlu and 9 Phenanthrol (9 OHPhe) was associated with a 7.03% decrease ( β %=-7.03%，95% CI =-12.60%--1.11%) and a 7.08% decrease ( β%=-7.08%，95% CI =-13.50%--0.17%) in PEF, respectively. Additionally, urinary ∑ 7OH PAHs had a positive correlation with the levels of urinary 8 OHdG and 8 iso PGF 2α ( r =0.64, 0.69, P <0.01). Meanwhile, the levels of 8 OHdG mediated 17.06% and 15.71% of the association between 2 OHFlu with FVC and FEV1.@*Conclusion@#The finding reveales a negative relationship between urinary OH PAHs and lung function among young healthy adults. The 8 OHdG plays a mediated role in the correlation of 2 OHFlu with FVC and FEV1. Active relevant policies are needed to control air pollution and maintain the healthy living conditions of young people.

Relationship between urinary metals and lung function in college students / 中国学校卫生

Objective@#To explore the association between urinary metals and lung function among college students, and to provide a theoretical basis for related research on metal exposure and lung function injury.@*Methods@#A total of 45 healthy college students were recruited from North China University of Science and Technology in Caofeidian between 2017-2018. During the four seasons, information was obtained from questionnaires and physical examinations, lung function parameters were assessed, including FVC, FEV1, PEF, FEV1/FVC and FEF 25-75 , and morning urine samples were collected simultaneously. The urinary levels of 15 metals were measured by inductively coupled plasma mass spectrometry (ICP/MS); a Kruskal Wallis H test was used to compare differences in urinary metals during the four seasons; and a mixed effect model was used to assess correlations between urinary metals and lung function.@*Results@#There were significant differences in the levels of urinary chromium, iron, nickel, copper, zinc, arsenic, selenium, selenium, molybdenum, cadmium, antimony and lead from 15 metals over the four seasons ( H =9.79- 20.61 , P <0.05). The differences observed in five lung function parameters over the four seasons were statistically significant ( F =61.72, 45.30, 47.61, 25.47, 35.13, P <0.05). The linear mixed effect model analysis showed that urinary concentrations of vanadium, manganese, iron, cobalt, nickel and antimony were negatively correlated with FEV1( B =0.202, 0.192, 0.181, 0.154, 0.131 , 0.283); urinary concentrations of aluminum, vanadium, manganese, iron, cobalt, nickel, zinc, cadmium, and antimony were negatively correlated with FVC ( B =0.252, 0.290, 0.292, 0.271, 0.201, 0.180, 0.171, 0.163, 0.381); urinary concentrations of manganese and antimony were negatively correlated with PEF ( B =0.291, 0.354)( P <0.05).@*Conclusion@#The increase of multiple metal concentrations among college students was related to lung function decline, the long term metal exposure might lead to lung function damage. So environmental metal pollution should be controlled.

The risk of nonsyndromic cleft lip with or without cleft palate and Vax1 rs7078160 polymorphisms in southern Han Chinese / Risco de fenda labial não sindrômica com ou sem fenda palatina e polimorfismo Vax1 rs7078160 em indivíduos da etnia Han do sul da China

Abstract Introduction: Non-syndromic cleft lip with or without cleft palate is a common worldwide birth defect due to a combination of environmental and genetic factors. Genome-wide association studies reported the rs7078160 of Vax1 is closely related to non-syndromic cleft lip with or without cleft palate in European populations. The following studies showed the same results in Mongolian, Japanese, Filipino, Vietnamese populations etc. However, conflicting research had been reported in Chinese population, Objective: The aim of this study was to investigate the association between the rs7078160 polymorphism and non-syndromic cleft lip with or without cleft palate in Southern Chinese patients. Methods: In this study, we investigated the polymorphism distribution of rs7078160 in 100 complete patient trios (39 patients with non-syndromic cleft lip and palate; 36 patients with non-syndromic cleft lip only; 25 had non-syndromic cleft palate only; and their parents) from Southern ethnic Han Chinese. 60 healthy trios were selected as control. Polymerase chain reaction and Sanger sequencing were used to genotype rs7078160 in Vax1; both case-control and family-based associations were analyzed. Results: The case-control analyses revealed the rs7078160 polymorphism was significant, associated with non-syndromic cleft lip with or without cleft palate (p = 0.04) and non-syndromic cleft lip and palate (p = 0.01), but not associated with non-syndromic cleft lip only and nonsyndromic cleft palate only patients. The genotype composition of rs7078160 comprises mutated homozygous AA, heterozygous AG and wild homozygous GG. Cases with AG + AA genotypes compared with GG homozygotes showed an increased risk of non-syndromic cleft lip with or without cleft palate (p = 0.04, OR = 2.05, 95% CI: 1.01-4.16) and non-syndromic cleft lip and palate (p = 0.01, OR = 3.94, 95% CI: 1.34-11.54). In addition, we did not detect any transmissiondisequilibrium in rs7078160 (p = 0.68). Conclusion: This study suggests that rs7078160 polymorphism is a risk factor of non-syndromic cleft lip with or without cleft palate, and Vax1 is strongly associated with non-syndromic cleft lip with or without cleft palate in Southern Chinese Han populations.

Resumo Introdução: A fenda labial não sindrômica, com ou sem fenda palatina, é um defeito congênito comum em todo o mundo, devido a uma combinação de fatores ambientais e genéticos. O genome-wide association studies relatou que o polimorfismo rs7078160 do Vax1 está intimamente relacionado à fenda labial não sindrômica, com ou sem fenda palatina em populações europeias. Estudos subsequentes mostraram os mesmos resultados nas populações mongol, japonesa, filipina e vietnamita etc. No entanto, pesquisas conflitantes foram relatadas na população chinesa. Objetivo: Investigar a associação entre o polimorfismo rs7078160 e fenda labial não sindrômica, com ou sem fenda palatina, em pacientes do sul da China. Método: Tentamos investigar a distribuição do polimorfismo rs7078160 em 100 trios completos de pacientes (39 pacientes com fenda labial e palatina não sindrômica; 36 pacientes com fenda labial somente, não sindrômica; 25 com fenda palatina somente, não sindrômica e seus pais), da etnia Han do sul da China, e em 60 trios saudáveis selecionados como controle. Reação de polimerase em cadeia e o sequenciamento de Sanger foram uszados para genotipar o polimorfismo rs7078160 do Vax1 e tanto os casos-controle quanto as associações baseadas na família foram analisadas. Resultados: As análises de caso-controle revelaram que o polimorfismo rs7078160 estava significativamente associado a fenda labial não sindrômica, com ou sem fenda palatina (p = 0,04) e fenda labial e palatina não sindrômica (p = 0,01), mas não estava associado a pacientes com fenda labial somente não sindrômica e fenda palatina somente não sindrômica. A composição do genótipo de rs7078160 compreende AA homozigoto mutado, AG heterozigoto e GG homozigoto selvagem. Casos com genótipos AG + AA comparados com GG homozigotos mostraram um risco aumentado de fenda labial não sindrômica, com ou sem fenda palatina (p = 0,04, OR = 2,05, IC de 95%: 1,01 ± 4,16) e fenda labial e palatina não sindrômica (p = 0,01, OR = 3,94, IC 95%: 1,34-11,54). Além disso, não detectamos desequilíbrio de transmissão em rs7078160 (p = 0,68). Conclusão: Este estudo sugere que o polimorfismo rs7078160 foi um fator de risco para fenda labial não sindrômica, com ou sem fenda palatina, e o gene Vax1 está fortemente associado com fenda labial não sindrômica, com ou sem fenda palatina em populações da etnia Han do sul da China.

Biomimetic restoration and regeneration of dentin and cementum / 口腔疾病防治

@#Dental hard tissues lack the ability to self-heal. In dentin and cementum, hydroxyapatite (HA) can exist outside and/or inside collagen fibers. It is difficult to repair or regenerate HA with a highly ordered orientation in the presence of collagen fibers. At present, the biomimetic mineralization of dentin and cementum, mainly carried out by imitating its biological formation process and its physiological structure, can be divided into those originating from the fiber mineralization mechanism and those with HA as the main component. The materials used include natural materials such as demineralized dentin matrix (DDM) and calcined bovine hydroxyapatite (BHA), and synthetic materials such as polymer-induced liquid precursor (PILP) and synthetic HA. In the future, natural materials and synthetic materials should be combined for the restoration and regeneration of dentin and cementum by means of biomimetic mineralization of calcium phosphate released by remineralization solution-HA.

Transcriptomic markers in pediatric septic shock prognosis: an integrative analysis of gene expression profiles

The goal of this study was to identify potential transcriptomic markers in pediatric septic shock prognosis by an integrative analysis of multiple public microarray datasets. Using the R software and bioconductor packages, we performed a statistical analysis to identify differentially expressed (DE) genes in pediatric septic shock non-survivors, and further performed functional interpretation (enrichment analysis and co-expression network construction) and classification quality evaluation of the DE genes identified. Four microarray datasets (3 training datasets and 1 testing dataset, 252 pediatric patients with septic shock in total) were collected for the integrative analysis. A total of 32 DE genes (18 upregulated genes; 14 downregulated genes) were identified in pediatric septic shock non-survivors. Enrichment analysis revealed that those DE genes were strongly associated with acute inflammatory response to antigenic stimulus, response to yeast, and defense response to bacterium. A support vector machine classifier (non-survivors vs survivors) was also trained based on DE genes. In conclusion, the DE genes identified in this study are suggested as candidate transcriptomic markers for pediatric septic shock prognosis and provide novel insights into the progression of pediatric septic shock.

Micro-morphology and phase of zirconia-based nano-hydroxyapatite functional gradient biomaterials / 中国组织工程研究

BACKGROUND: The successfully prepared zirconia-based nano-hydroxyapatite functional gradient bioceramics has mechanical properties of strong interlayer bonding, high compressive and shear strength, but its biological properties are yet to be studied. OBJECTIVE: To detect the micro-morphology and phase of the zirconia-based nano-hydroxyapatite functional gradient bioceramics using scanning electron microscope and X-ray diffractometer. METHODS: Cylindrical zirconia-based nano-hydroxyapatite functional gradient bioceramics were longitudinally sectioned into thin-shaped specimens with turbine handpieces. The profile (intersections of layers) was polished with sandpaper. Its surface micro-morphology and layered structure were observed with a scanning electron microscope after spraying gold. The test piece was ground into a powder in an agate mortar and filtered with gauze. Ceramic powder was sieved with smaller particle size for phase analysis with X-ray diffractometer. RESULTS AND CONCLUSION: (1) Scanning electron microscopy showed that the gradient layers were tightly bound. The grain volume was basically uniform. There was a small amount of ZrO2 agglomeration. The closer to the surface layer, the higher the nHA content and the uniform small pores. (2) The X-ray diffractometer detected mainly the tetragonal phase ZrO2 and nHA diffraction peaks, and a small amount of β-TCP, α-TCP, CaZrO3 and a small amount of monoclinic phase ZrO2 crystal. (3) The research results indirectly indicate that the surface layer nHA is firmly bonded to the ZrO2 matrix layer under the transition of the gradient layer. ZrO2 based nHA functional gradient biomaterial is a ceramic material with excellent mechanical and biological properties.

Anti-inflammation and anti-apoptosis effects of growth arrest-specific protein 6 in acute liver injury induced by LPS/D-GalN in mice

Abstract Purpose To investigate the effect of growth arrest-specific protein 6 (Gas6) on acute liver injury in mice and related mechanisms. Methods Thirty C57BL/6 (6-8 weeks old) mice were randomly divided into control, LPS/D-GalN, and LPS/D-GalN+Gas6 groups (10 mice in each group). The LPS/D-GalN group was intraperitoneally administered with LPS (0.25 mg/Kg) and D-GalN (400 mg/Kg) for 5h. The LPS/D-GalN+Gas6 group was intraperitoneally administered with rmGas6 one hour before intraperitoneal application of LPS/D-GalN. All subjects were sacrificed at 5 h for blood and tissue analysis. The expression of protein and mRNA was assessed by western blotting and RT-PCR, respectively. Results Compared with the control group, AST, ALT, IL-1β, TNF-α, IL-6 IL-10, MPO activity were increased in the LPS/D-GalN group. However, they were significantly inhibited by Gas6. Gas6 markedly suppressed the expression of apoptosis-related protein induced by LPS/D-GalN. Moreover, Gas6 attenuated the activation of the NF-κB signaling pathway in acute liver injury induced by LPS/D-GalN. Conclusions Gas6 alleviates acute liver injury in mice through regulating NF-κB signaling pathways. Gas6 can be a potential therapeutic agent in treating LPS/D-GalN-induced acute liver injury in the future.

Safety and tolerability of a single dose T0001 in Chinese healthy adult volunteers: a first-in-human ascending dose study

T0001 is the first mutant of etanercept with a higher affinity to tumor necrosis factor α (TNF-α) than etanercept. In order to investigate the safety and tolerability of T0001, a study was carried out in healthy Chinese subjects. A first-in-human, dose escalation study was conducted in healthy Chinese subjects. Fifty-six subjects were divided into six dose cohorts (10 mg, 20 mg, 35 mg, 50 mg, 65 mg and 75 mg) to receive a single subcutaneous injection of T0001. Safety and tolerability assessment were based on the records of vital signs, physical examinations, clinical laboratory tests, 12-lead electrocardiograms and adverse events (AEs). All subjects were in good compliance and none withdraw due to AEs. No serious AEs occurred. A total of twenty-three AEs in sixteen subjects were recorded, and eighteen of these AEs were believed to be related to T0001. The most frequently reported AEs were injection site reactions and white blood cell count increase. All these AEs were of mild to moderate intensity and most of them recovered spontaneously within 14 days. In this study, no dose-limiting toxicity was observed, and the maximum tolerated dose was identified as 75 mg. T0001 was considered safe and generally well tolerated at doses up to 75 mg in healthy Chinese volunteers

Association between BDNF G196A (Val66Met) polymorphism and cognitive impairment in patients with Parkinson's disease: a meta-analysis

Brain-derived neurotrophic factor (BDNF) is widely expressed in the central nervous system and prolongs the survival of dopaminergic neurons in the substantia nigra. Several studies have recently investigated the association between BDNF G196A (Val66Met), a single nucleotide polymorphism influencing cognitive processes, and cognitive impairment in Parkinson's disease (PD), but with contradictory findings. Thus, this meta-analysis was performed to clarify the possible association. Relevant studies were identified by a systematic search of PubMed, Embase, and China National Knowledge Infrastructure (CNKI) databases. The strength of the association was evaluated using crude odds ratios and 95% confidence interval. Finally, six studies involving 532 cases and 802 controls were included. Our analyses suggested the G196A (Val66Met) polymorphism was significantly associated with cognitive impairment in PD, especially in Caucasian populations. In conclusion, BDNF G196A (Val66Met) is confirmed to be a risk factor for cognitive impairment in PD.

Milk fat globule-epidermal growth factor 8 (MFG-E8) attenuates sepsis-induced acute kidney injury by inhibiting NF-κB signaling pathway1

Abstract Purpose: To explore the effect of milk fat globule-epidermal growth factor 8 (MFG-E8) on sepsis-induced acute kidney injury (SAKI). Methods: Male C57BL/6 mice were randomized to control, sham, CLP, CLP+PBS, and CLP+rmMFG-E8 groups. SAKI was induced by cecal ligation and puncture (CLP). Recombinant mouse MFG-E8 (rmMFG-E8) (20 μg/kg) or PBS (vehicle) was administered intraperitoneally. Blood, urine and renal tissue were collected at 24 h after CLP. Blood samples were tested for serum kidney injury biomarker and cytokines. Urine samples were collected to detect KIM-1, and NGAL. Real-time PCR was tested for Bax and Bcl-2. TUNEL staining was used to determine renal apoptosis. Western blot was used to detect the expression of Bax, Bcl-2, and proteins in the NF-κB pathway. Results: MFG-E8 alleviated SAKI by decreasing serum Cre, BUN, urine KIM-1 and NGAL and by mitigating renal pathological changes significant (p < 0.05). IL-1β, IL-6, TNF-α were significantly inhibited by MFG-E8 (p < 0.05). Apoptosis induced by SAKI was markedly suppressed by MFG-E8. Finally, MFG-E8 attenuated the activation of the NF-��B signaling pathway in SAKI. Conclusion: MFG-E8 has beneficial effects on SAKI, which may be achieved by inhibiting the NF-κB pathway.

Analysis of the current situation and related factors of beverage consumption in college sports specialty / 中国学校卫生

Objective@#To study the consumption status of sports drinks in colleges and universitiesand its influencing factors,so as to provide the scientific basis for conducting nutrition education and making interventional measures.@*Methods@#2 610 college students from arts school, PE school and Chemistry and Environmental Science Institute of a university in Shangrao city, Jiangxi Province were randomly selected by random cluster sampling method to investigate the frequency and types of drinking beverages.@*Results@#In terms of gender, apart from lactic acid drinks, there was significant statistical significance in whether men and women regularly consumed beverages (fruit and vegetable juice drinks, χ2=24.20;Tea beverage, χ2=45.58;Carbonated beverage, χ2=57.27;Energy drink χ2=86.68, P<0.01).In addition to lactic acid drinks, there was statistically significant difference in whether the college regularly consumed beverages (fruit and vegetable juice drinks, χ2=54.72;Tea beverage, χ2=25.97;Carbonated beverages, χ2=46.64;Energy drinks χ2=74.81, P<0.01).In terms of family residence, only tea beverage (χ2=25.97) and carbonated beverage (χ2=46.64) had statistical significance（P<0.01）. In terms of monthly living expenses, all beverage types had statistical significance (milk beverage, χ2=11.69;Fruit and vegetable juice beverage, χ2=18.92;Tea beverage, χ2=20.09;Carbonated beverages,χ2=29.98;Energy drink χ2=17.71, P<0.01). Logistic regression analysis showed that apart from lactic beverages, male students were more likely to consume fruit and vegetable juice, tea beverage, carbonated drinks and functional drinks than female students(OR=1.60, 2.38, 2.50, 4.95, P<0.01); The students in PE school were more likely to consume lactic beverages and functional drinks than those in Arts school, while the students in Chemistry and environmental science institute were less likely to consume fruit and vegetable juice, tea beverage, carbonated drinks and functional drinks than those in Art school (OR=1.29, 2.19, 0.43, 0.50, 0.42, 0.42, P<0.05); The students who spent >1 500 yuan monthly were more likely to consume lactic beverages, fruit and vegetable juice, tea beverage, carbonated drinks than those spent <1000 yuan monthly, and they consumed more functional than those spent<1 000 yuan monthly(OR=1.68, 1.75, 1.73, 2.15, 1.69, P<0.05).@*Conclusion@#The students of different characters have different kinds of beverages. Therefore, health education should focus on male students who spend <1 500 monthly, and targeted measures should be taken to help college students build up a reasonable concept of beverage consumption so as to promote the formation of a scientific behavior of beverage consumption.

The improvement of bioactive secondary metabolites accumulation in Rumex gmelini Turcz through co-culture with endophytic fungi

Abstract Aspergillus sp., Fusarium sp., and Ramularia sp. were endophytic fungi isolated from Rumex gmelini Turcz (RGT), all of these three strains could produce some similar bioactive secondary metabolites of their host. However the ability to produce active components degraded significantly after cultured these fungi alone for a long time, and were difficult to recover. In order to obtain more bioactive secondary metabolites, the co-culture of tissue culture seedlings of RGT and its endophytic fungi were established respectively, and RGT seedling was selected as producer. Among these fungi, Aspergillus sp. showed the most significant enhancement on bioactive components accumulation in RGT seedlings. When inoculated Aspergillus sp. spores into media of RGT seedlings that had taken root for 20 d, and made spore concentration in co-culture medium was 1 × 104 mL-1, after co-cultured for 12 d, the yield of chrysophaein, resveratrol, chrysophanol, emodin and physcion were 3.52-, 3.70-, 3.60-, 4.25-, 3.85-fold of the control group. The extreme value of musizin yield was 0.289 mg, which was not detected in the control groups. The results indicated that co-culture with endophytic fungi could significantly enhance bioactive secondary metabolites production of RGT seedlings.