[Dose-response relationship between age and Streptococcus pneumoniae vaccination coverage in kindergarten children]. / 幼儿园儿童年龄与肺炎链球菌疫苗覆盖率间的剂量-ååº”å ³ç³».

OBJECTIVES: To investigate the potential relationship between age and Streptococcus pneumoniae vaccination coverage in kindergarten children, and to provide a basis for guiding vaccination and developing new protein vaccines. METHODS: The stratified cluster random sampling method was used to select 1 830 healthy children from six kindergartens in Shunde District, Foshan City, China, and nasopharyngeal swabs were collected for the isolation and identification of Streptococcus pneumoniae. The logistic regression model based on restricted cubic spline was used to analyze the dose-response relationship between age and Streptococcus pneumoniae vaccination coverage. RESULTS: The rate of nasal Streptococcus pneumoniae carriage was 22.46% (411/1 830) among the kindergarten children, with the predominant serotypes of 6B, 19F, 15A, 23A, 34, and 23F. The coverage rates of 10-valent pneumococcal conjugate vaccine (PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13) were 53.0% and 57.9%, respectively, and there was a significant non-linear dose-response relationship between age and the coverage rates of PCV10 and PCV13 (P<0.05), with a higher coverage rate of PCV10 (88.0%) and PCV13 (91.1%) in the children aged 2 years. There was a significant non-linear dose-response relationship between age and the coverage rates of pilus islet 1 (PI-1) and pilus islet 2 (PI-2) (P<0.05), with a lower vaccination coverage rate for PI-1 (37.7%) and PI-2 (16.1%). The coverage rates of PI-1 (13.0%-58.5%) and PI-2 (6.0%-29.4%) were lower in all age groups. The virulence genes lytA (99.5%) and ply (99.0%) associated with candidate protein vaccines showed higher vaccination coverage rates. CONCLUSIONS: There is a significant non-linear dose-response relationship between the age of kindergarten children and the coverage rates of PCV10 and PCV13 serotypes, and kindergarten children aged 2 years have a relatively high coverage rate of PCV. The high prevalence of the virulence genes lytA and ply shows that they are expected to become candidate virulence factors for the development of a new generation of recombinant protein vaccines.

Comprehensive analysis of CXCR family members in lung adenocarcinoma with prognostic values.

BACKGROUND: The expression profiles and molecular mechanisms of CXC chemokine receptors (CXCRs) in Lung adenocarcinoma (LUAD) have been extensively explored. However, the comprehensive prognostic values of CXCR members in LUAD have not yet been clearly identified. METHODS: Multiple available datasets, including Oncomine datasets, the cancer genome atlas (TCGA), HPA platform, GeneMANIA platform, DAVID platform and the tumor immune estimation resource (TIMER) were used to detect the expression of CXCRs in LUAD, as well as elucidate the significance and value of novel CXCRs-associated genes and signaling pathways in LUAD. RESULTS: The mRNA and/or protein expression of CXCR1, CXCR2, CXCR3, CXCR4, CXCR5 and CXCR6 displayed predominantly decreased in LUAD tissues as compared to normal tissues. On the contrary, compared with the normal tissues, the expression of CXCR7 was significantly increased in LUAD tissues. Subsequently, we constructed a network including CXCR family members and their 20 related genes, and the related GO functions assay showed that CXCRs connected with these genes participated in the process of LUAD through several signal pathways including Chemokine signaling pathway, Cytokine-cytokine receptor interaction and Neuroactive ligand-receptor interaction. TCGA and Timer platform revealed that the mRNA expression of CXCR family members was significantly related to individual cancer stages, cancer subtypes, patient's gender and the immune infiltration level. Finally, survival analysis showed that low mRNA expression levels of CXCR2 (HR = 0.661, and Log-rank P = 1.90e-02), CXCR3 (HR = 0.674, and Log-rank P = 1.00e-02), CXCR4 (HR = 0.65, and Log-rank P = 5.01e-03), CXCR5 (HR = 0.608, and Log-rank P = 4.80e-03) and CXCR6 (HR = 0.622, and Log-rank P = 1.85e-03) were significantly associated with shorter overall survival (OS), whereas high CXCR7 mRNA expression (HR = 1.604, and Log-rank P = 4.27e-03) was extremely related with shorter OS in patients. CONCLUSION: Our findings from public databases provided a unique insight into expression characteristics and prognostic values of CXCR members in LUAD, which would be benefit for the understanding of pathogenesis, diagnosis, prognosis prediction and targeted treatment in LUAD.

[Application value of metagenomic next-generation sequencing for pathogen detection in childhood agranulocytosis with fever]. / ç— åŽŸä½“å®åŸºå› ç»„äºŒä»£æµ‹åºåœ¨å„¿ç«¥ç²’ç»†èƒžç¼ºä¹ä¼´å‘çƒ­ä¸­çš„åº”ç”¨ä»·å€¼.

OBJECTIVES: To study the application value of metagenomic next-generation sequencing (mNGS) for pathogen detection in childhood agranulocytosis with fever. METHODS: A retrospective analysis was performed on the mNGS results of pathogen detection of 116 children with agranulocytosis with fever who were treated from January 2020 to December 2021. Among these children, 38 children with negative mNGS results were enrolled as the negative group, and 78 children with positive results were divided into a bacteria group (n=22), a fungal group (n=23), and a viral group (n=31). Clinical data were compared between groups. RESULTS: For the 116 children with agranulocytosis and fever, the median age was 8 years at diagnosis, the median turnaround time of mNGS results was 2 days, and the positive rate of mNGS testing was 67.2% (78/116). Compared with the negative group, the bacterial group had a higher procalcitonin level (P<0.05), the fungal group had higher level of C-reactive protein and positive rate of (1,3)-ß-D glucan test/galactomannan test (P<0.05), and the fungal group had a longer duration of fever (P<0.05). Among the 22 positive microbial culture specimens, 9 (41%) were consistent with the mNGS results. Among the 17 positive blood culture specimens, 8 (47%) were consistent with the mNGS results. Treatment was adjusted for 28 children (36%) with the mNGS results, among whom 26 were cured and discharged. CONCLUSIONS: The mNGS technique has a shorter turnaround time and a higher sensitivity for pathogen detection and can provide evidence for the pathogenic diagnosis of children with agranulocytosis and fever.

Co-carriage of Streptococcus pneumoniae and Moraxella catarrhalis among preschool children and its influencing factors. / å­¦é¾„å‰å„¿ç«¥è‚ºç‚Žé“¾çƒèŒå’Œå¡ä»–èŽ«æ‹‰èŒæºå¸¦çŠ¶æ€åŠå½±å“å› ç´ åˆ†æž.

OBJECTIVES: To investigate the carriage status of Streptococcus pneumoniae (S.pneumoniae) and Moraxella catarrhalis (M. catarrhalis) in preschool children and the influencing factors for the carriage status. METHODS: The stratified cluster sampling method was used to select 2 031 healthy children from seven kindergartens in Shunde District of Foshan in Guangdong, China. Nasal swabs were collected from all children for the isolation and identification of S. pneumoniae and M. catarrhalis. The carriage status of S. pneumoniae and M. catarrhalis was analyzed in terms of its association with demographic features and hospital- and community-related factors. RESULTS: The carriage rates of S. pneumoniae and M. catarrhalis were 21.81% and 52.44%, respectively among the children. The co-carriage rate of S. pneumoniae and M. catarrhalis was 14.87%. The correspondence analysis showed that the factors such as lower grade, non-local registered residence, living in rural areas, small living area, history of respiratory tract infection but no history of antibiotic use, allergic skin diseases, and no hospital-related exposure history were significantly associated with the co-carriage of S. pneumoniae and M. catarrhalis among the children (P<0.05). CONCLUSIONS: Co-carriage of S. pneumoniae and M. catarrhalis can be observed in preschool children. Young age, poor living environment, a history of respiratory tract infection but no history of antibiotic use, allergic skin diseases, and no hospital-related exposure history are important risk factors for the co-carriage of S. pneumoniae and M. catarrhalis in preschool children.

[Clinical features and prognosis in 20 children with rhabdomyosarcoma]. / 20例横纹肌肉瘤患儿的临床特点及预后分析.

OBJECTIVES: To study the clinical features of children with rhabdomyosarcoma (RMS) and the influencing factors for prognosis. METHODS: A retrospective analysis was performed on the clinical and follow-up data of 20 children with RMS who were admitted to the Department of Pediatric Hematology, Xiangya Hospital of Central South University, from June 2014 to September 2020. RESULTS: The most common clinical symptoms of the 20 children with RMS at the first visit were painless mass (13/20, 65%), exophthalmos (4/20, 20%), and abdominal pain (3/20, 15%). According to the staging criteria of Intergroup Rhabdomyosarcoma Study Group (IRSG), there was 1 child (5%) with stage I RMS, 4 (20%) with stage II RMS, 9 (45%) with stage III RMS, and 6 (30%) with stage IV RMS. The median follow-up time was 19 months for the 20 children (range: 3-93 months), with a 2-year overall survival (OS) rate of 79.5% (95%CI: 20.1-24.3) and a 2-year event-free survival (EFS) rate of 72.0% (95%CI: 19.5-23.9). Pleomorphic RMS was associated with the reduced 2-year OS rate (P<0.05), and distant metastasis, IRSG stage IV RMS, and high-risk RMS were associated with the reduced 2-year EFS rate (P<0.05). CONCLUSIONS: RMS has no specific clinical symptoms at the first visit, with painless mass as the most common symptom. Distant metastasis, IRSG stage, and risk degree may be associated with the prognosis of children with RMS.

Endogenous HMGB1 regulates GSDME-mediated pyroptosis via ROS/ERK1/2/caspase-3/GSDME signaling in neuroblastoma.

Pyroptosis, a newly discovered mode of programmed cell death (PCD), is important in the regulation of cancer development. High mobility group box 1 (HMGB1) is a non-histone nuclear protein that is closely related to tumor development and chemotherapy resistance. However, whether endogenous HMGB1 regulates pyroptosis in neuroblastoma remains unknown. Here, we showed that HMGB1 showed ubiquitous higher expression in SH-SY5Y cells and clinical tumors, and was positively correlated with the risk factors of patients with neuroblastoma. Knockdown of GSDME or pharmacological inhibition of caspase-3 blocked pyroptosis and cytosolic translocation of HMGB1. Moreover, knockdown of HMGB1 inhibited cisplatin (DDP) or etoposide (VP16)-induced pyroptosis by decreasing GSDME-NT and cleaved caspase-3 expression, resulting in cell blebbing and LDH release. Knockdown of HMGB1 expression increased the sensitivity of SH-SY5Y cells to chemotherapy and switched pyroptosis to apoptosis. Furthermore, the ROS/ERK1/2/caspase-3/GSDME pathway was found to be functionally connected with DDP or VP16-induced pyroptosis. Hydrogen peroxide (H2O2, a ROS agonist) and EGF (an ERK agonist) promoted the cleavage of GSDME and caspase-3 in DDP or VP16 treatment cells, both of which were inhibited by HMGB1 knockdown. Importantly, these data were further supported by the in vivo experiment. Our study suggests that HMGB1 is a novel regulator of pyroptosis via the ROS/ERK1/2/caspase-3/GSDME pathway and a potential drug target for therapeutic interventions in neuroblastoma.

Proteome, phosphoproteome, and hydroxyproteome of liver mitochondria in diabetic rats at early pathogenic stages.

It has been proposed that mitochondrial dysfunction is involved in the pathogenesis of type 2 diabetes (T2D). To dissect the underlying mechanisms, we performed a multiplexed proteomics study on liver mitochondria isolated from a spontaneous diabetic rat model before/after they were rendered diabetic. Altogether, we identified 1091 mitochondrial proteins, 228 phosphoproteins, and 355 hydroxyproteins. Mitochondrial proteins were found to undergo expression changes in a highly correlated fashion during T2D development. For example, proteins involved in beta-oxidation, the tricarboxylic acid cycle, oxidative phosphorylation, and other bioenergetic processes were coordinately up-regulated, indicating that liver cells confronted T2D by increasing energy expenditure and activating pathways that rid themselves of the constitutively increased flux of glucose and lipid. Notably, activation of oxidative phosphorylation was immediately related to the overproduction of reactive oxygen species, which caused oxidative stress within the cells. Increased oxidative stress was also evidenced by our post-translational modification profiles such that mitochondrial proteins were more heavily hydroxylated during T2D development. Moreover, we observed a distinct depression of antiapoptosis and antioxidative stress proteins that might reflect a higher apoptotic index under the diabetic stage. We suggest that such changes in systematic metabolism were causally linked to the development of T2D. Comparing proteomics data against microarray data, we demonstrated that many T2D-related alterations were unidentifiable by either proteomics or genomics approaches alone, underscoring the importance of integrating different approaches. Our compendium could help to unveil pathogenic events in mitochondria leading to T2D and be useful for the discovery of diagnosis biomarker and therapeutic targets of T2D.

DNA Repair Gene Polymorphisms in the Nucleotide Excision Repair Pathway and Lung Cancer Risk: A Meta-analysis.

OBJECTIVE: A number of studies have reported the association of "XPA", "XPC", "XPD/ERCC2" gene polymorphisms with lung cancer risk. However, the results were conflict. To clarify the impact of polymorphisms of "XPA", "XPC", "XPD/ERCC2", on lung cancer risk, a meta-analysis was performed in this study. METHODS: The electronic databases PubMed and Embase were retrieved for studies included in this meta-analysis by "XPA", "XPC", "XPD/ERCC2", "lung", "cancer/neoplasm/tumor/carcinoma", "polymorphism" (An upper date limit of October, 31, 2009). A meta-analysis was performed to evaluate the relationship among XPA, XPC and XPD polymorphism and lung cancer risks. RESULTS: A total of 31 publications retrieved from Pubmed and Embase included in this study. XPC A939C CC genotype increased lung cancer risk in total population (recessive genetic model: OR=1.23, 95% CI:1.05-1.44; homozygote comparison: OR=1.21,95%CI:1.02-1.43and CC vs. CA contrast: OR=1.25,95%CI:1.06-1.48), except in Asians. XPD A751C, 751C allele and CC genotype also increased lung cancer risk in total population and in Caucasians (recessive genetic model: Total population: OR=1.20, 95%CI:1.07-1.35). No significant correlation was found between XPD A751C and lung cancer risk in Asians and African Americans. XPD G312A AA genotype increased lung cancer risk in total population, in Asians and Caucasians(recessive genetic model: Total population: OR=1.20, 95%CI: 1.06-1.36). No significant association was found between XPA G23A, XPC C499T, XPD C156A and lung cancer risk. CONCLUSION: Our results suggest that the polymorphisms in XPC and XPD involve in lung cancer risks. XPA polymorphisms is less related to lung cancer risk.

A diagnosis-based health economic analysis of postural orthostatic tachycardia syndrome in Chinese children.

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is a common clinical problem in children and adolescents. The previous diagnostic approach to POTS of children and adolescents is based on a series of tests to exclude all other causes, which is time and medical resource consuming. Recently, a new diagnostic approach has been developed. The present study was designed to statistically analyze the results of clinical investigation items and the cost for the diagnosis of POTS in children patients, and evaluate cost changes in the diagnosis of POTS. METHODS: A total of 315 children patients were divided into two groups according to diagnosis period, including group I diagnosed in 2002 - 2006 (100 cases) and group II in 2007 - 2010 (215 cases) and the diagnostic item-based distribution of the cost was analyzed. The diagnostic costs were compared between two groups using SPSS17.0. RESULTS: The per-capita cost of diagnosis in group I was (621.95 ± 21.10) Yuan, costs of diagnostic tests (head-up tilt test, standing test, etc) accounted for 8.68% and the exclusive tests for 91.32%. The per-capita cost of diagnosis in group II was (542.69 ± 23.14) Yuan, diagnostic tests accounted for 10.50% and exclusive tests for 89.50%. Comparison of the total cost of diagnostic tests between the two groups showed significant differences (P < 0.05). CONCLUSION: The cost of POTS diagnosis has been declined in recent years, but the cost of exclusive diagnosis is still its major part.

High-sensitivity analysis of human plasma proteome by immobilized isoelectric focusing fractionation coupled to mass spectrometry identification.

Immobilized pH gradients isoelectric focusing (IPG-IEF) is the first dimension typically used in two-dimensional gel electrophoresis (2-DE). It can also be used on its own in conjunction with tandem mass spectrometry (MS/MS) for the analysis of proteins. Here, we described a strategy combining isoelectric focusing in immobilized pH gradient strips, and mass spectrometry to create a new high-throughput and sensitive detection method. Protein mixture is separated by in-gel IEF, then the entire strip is cut into a set of gel sections. Proteins in each gel section are digested with trypsin, and the resulted peptides are subjected to reversed-phase high performance liquid chromatography followed by electrospray-linear ion-trap tandem mass analysis. Using this optimized strategy, we have identified 744 distinct human proteins from an IPG strip loaded only 300 microg of plasma proteins. When compared with other works in published literatures, this study offered a more convenient and sensitive method from gel to mass spectrometry for the separation and identification proteins of complex biological samples.