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Chenlu Wang,1,* Zhaojin Lu,1,* Guangpeng She,2 Kaining Chen,1 Huazhong Zhou,1 Xueli Zhan,3 Hongyan Yu,1 Lei Pi,1 Liandong Zuo,4 Di Che1 1Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, 510620, People’s Republic of China; 2Department of Laboratory Medicine, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510180, People’s Republic of China; 3Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, 510620, People’s Republic of China; 4Department of Andrology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, 510620, People’s Republic of China*These authors contributed equally to this workCorrespondence: Di Che, Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, No. 9 Jinsui Road, Guangzhou, Guangdong, 510620, People’s Republic of China, Email chedi@gwcmc.org Liandong Zuo, Department of Andrology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, Guangdong, 510620, People’s Republic of China, Email zuold@163.comPurpose: Recurrent abortion(RA) is a prevalent adverse pregnancy event. Exosomes, secreted by various body fluids, are known to play a role in disease diagnosis and serve as biomarkers through intercellular communication. This study aims to analyze single exosomes in patients with recurrent abortion to identify new biomarkers that may significantly contribute to recurrent abortion, providing new directions for its treatment.Patients and Methods: A total of 244 serum exosomes were collected, including 216 patients with recurrent abortion of varying outcomes and 28 normal pregnancies. We performed the proximity barcoding assay (PBA) to analyze single exosome surface proteins, which allowed us to identify individual exosomes related to the development of RA as well as the major subpopulations of exosomes. After PBA treatment, samples were analyzed for single exosomes, and exosomes from each group were compared using volcano plots, dot plots, and ROC curves.Results: By intersecting all significantly differentially expressed genes obtained from comparisons between the normal pregnancy control group and the recurrent abortion group, including the RA before abortion, RA after abortion, and RA non-pregnancy groups, we identified seven shared differential genes: FN1, APIPOQ, CDH13, DSG1, CLDN4, CD36, and ULBP3. Among these, FN1 was the most significantly differentially expressed gene in exosomes, with FN1 | log2 (fold change) |> 1.5 and an AUC of 0.7414. In addition, exosome subpopulation analyses showed that cluster 11 accounted for the largest proportion of the total 16 subpopulations, and FN1 was the marker with the highest concentration of cluster 11.Conclusion: Single-exosome profiling and exosome subpopulations of RA by PBA yielded significant differential gene FN1, which provides new possibilities for diagnostic screening of RA.Keywords: recurrent abortion, exosomes, FN1, PBA

Background: Digital stories have been shown to be effective in sharing information. The Partnerships for Inclusive Research and Learning (PIRL) was a 4-year international participatory research project focussed on the digital divide in inclusive research. Objectives: Members of PIRL share their experience of using digital storytelling to get key messages from the project to a wide range of people. Method: Members of PIRL were invited to develop digital stories and create project-specific guidelines for digital story development. Seven people participated in workshops given by experts, read literature, watched digital stories and discussed how to create digital stories. Results: The group created six digital stories, each one addressing a different aspect related to disability-inclusive research, with many having a focus on Africa and the creation of credible African evidence. The importance of assisting community members to think about and support research and evidence creation was one of the goals of the project. The videos provide an avenue to share insights about disability-inclusive development research. Group members stated that being part of the process significantly improved their understanding of translating evidence into formats that are more understandable. Conclusion: Creating digital stories requires commitment, a significant amount of time, access to digital tools, and financial resources. Working collaboratively on this project was not only meaningful but also encouraged positive working relationships and fostered critical thinking. Contribution: This article contributes to a better understanding of ways in which digital storytelling can be used in knowledge-sharing strategies to promote disability inclusion.

Zhaojin Lu,1,&ast; Zepeng Zheng,1,&ast; Yufen Xu,1,&ast; Chenlu Wang,1 Yueling Lin,1 Kun Lin,1 LanYan Fu,1 Huazhong Zhou,1 Lei Pi,1 Di Che,1 Xiaoqiong Gu1,2 1Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Department of Clinical Laboratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Di Che, Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, 510623, Guangdong, People’s Republic of China, Tel/Fax +86-20-38076562, Email chedi@gwcmc.org Xiaoqiong Gu, Department of Clinical Biological Resource Bank, Department of Clinical Laboratory, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, 510623, Guangdong, People’s Republic of China, Tel/Fax +86-20-38076561, Email guxiaoqiong@gwcmc.orgBackground: Kawasaki disease (KD) was one of the most common primary vasculitis. IVIG resistance was associated with an increased risk of coronary artery aneurysm. Accumulating evidences demonstrated that inflammatory gene polymorphisms might play important roles in IVIG resistance, and zinc finger proteins were closely related to immune inflammation regulation, but the effect of ZNF112/rs8113807 and ZNF180/rs2571051 on IVIG resistance in KD patients has not been reported.Methods: A total of 996 KD patients were recruited, and the assay of TaqMan-real-time polymerase chain reaction was used for ZNF112/rs8113807 and ZNF180/rs2571051 genotyping. Odds ratio (OR) and 95% confidence interval (CI) were calculated for estimating the relationship between the polymorphisms of the both SNPs (ZNF112/rs8113807 and ZNF180/rs2571051) and the risk of IVIG resistance.Results: Both of the ZNF112/rs8113807 CC/TC genotype and the ZNF180/rs2571051 TT/CT genotype increased the risk of IVIG resistance in KD (rs8113807: CC vs TT: adjusted OR = 1.83, 95% CI = 1.06– 3.16, p = 0.0293; CC/TC vs TT adjusted: OR = 1.49, 95% CI = 1.10– 2.02, p = 0.0094. rs2571051: TT vs CC adjusted: OR = 2.64, 95% CI = 1.62– 4.29, p < 0.0001; TT/CT vs CC adjusted: OR = 2.14, 95% CI = 1.37– 3.37, p = 0.0009; TT vs CC/CT adjusted: OR = 1.66, 95% CI = 1.22– 2.27, p = 0.0014). Furthermore, the combinative analysis of risk genotypes in ZNF112/rs8113807 and ZNF180/rs2571051 showed that patients with two unfavorable genotypes were more likely to increase risk of IVIG resistance than those who carried with zero or one unfavorable genotypes (adjusted: OR = 1.68, 95% CI = 1.24– 2.27, p = 0.0008).Conclusion: Our findings enriched the genetic background of IVIG resistance risk in the KD development and suggested that the ZNF112/rs8113807 C-carrier and the ZNF180/rs2571051 T-carrier were associated with increased risk of IVIG resistance in KD patients in Chinese southern population.Keywords: Kawasaki disease, ZNF112/rs8113807, ZNF180/rs2571051, IVIG resistance, inflammatory gene, polymorphism

Zhiyuan Wu,1,&ast; Yufeng Liang,1,&ast; Yunlong Zuo,1,&ast; Yufen Xu,2 Hanran Mai,2 Lei Pi,2 Di Che,2 Xiaoqiong Gu2 1Pediatric Intensive Care Unit. Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoqiong Gu; Di CheDepartment of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, 510623, People’s Republic of ChinaTel/Fax +86-20-38076561; +86-20-38076562Email guxiaoqiong@gwcmc.org; chedi@gwcmc.orgPurpose: Accumulating evidence demonstrates that genetic susceptibility genes can be used as biomarkers to assess sepsis susceptibility, and genetic variation is associated with susceptibility and clinical outcomes in patients with sepsis and inflammatory disease. Although studies have shown that the lncRNA CCAT2 is involved in inflammatory diseases, it remains unclear whether CCAT2 gene polymorphisms are associated with susceptibility to inflammatory diseases, such as sepsis, in children.Methods: We genotyped the rs6983267 CCAT2 polymorphism in 474 cases (pediatric sepsis) and 678 controls using TaqMan methods, and odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of associations.Results: Our results indicate that the rs6983267 T > G polymorphism is significantly associated with an increased risk of sepsis in children (TG and TT: adjusted OR = 1.311, 95% CI = 1.016– 1.743, GG and TT: adjusted OR = 1.444, 95% CI = 1.025– 2.034 dominant model: GG/TG vs TT adjusted OR = 1.362, 95% CI = 1.055– 1.756). Furthermore, the risk effect was more pronounced in children younger than 60 months who were male and who had sepsis.Conclusion: We found that the CCAT2 gene polymorphism rs6983267 T > G may be associated with an increased risk of pediatric sepsis in southern China. A larger multicenter study should be performed to confirm these results.Keywords: lncRNA CCAT2, sepsis, susceptibility, polymorphism

Di Che,1,&ast; Zhenzhen Fang,2,&ast; Hanran Mai,1,&ast; Yufen Xu,1 LanYan Fu,1 Huazhong Zhou,1 Linyuan Zhang,1 Lei Pi,1 Xiaoqiong Gu1 1Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Program of Molecular Medicine, Guangzhou Women and Children’s Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoqiong GuDepartment of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, 510623, Guangdong, People’s Republic of ChinaTel/Fax +86-20-38076561Email guxiaoqiong@gwcmc.orgBackground: Genetic factors may play an important role in susceptibility to recurrent miscarriage. Some cardiovascular disease-related candidate genes have been shown to be associated with recurrent miscarriage. Long noncoding RNA ANRIL has been confirmed to be associated with susceptibility to various diseases, such as cardiovascular disease. However, it remains unclear whether the ANRIL gene polymorphism is related to recurrent miscarriage susceptibility.Methods: Three ANRIL gene polymorphisms (rs2151280, rs1063192 and rs564398) were genotyped in 819 controls and 610 recurrent miscarriage patients through TaqMan real-time polymerase chain reaction. The odds ratios and 95% confidence intervals (CIs) were used to assess the strength of each association.Results: Our results showed that the ANRIL rs2151280 GG genotype was associated with increased susceptibility to recurrent miscarriage (GG vs AA: adjusted OR=1.527, 95% CI=1.051– 2.218, p=0.0262; GG vs AG/AA adjusted OR=1.460, 95% CI=1.021– 2.089, p=0.0381). By combining the analysis of the risk genotypes in the three SNPs, we found that individuals with 2– 3 risk genotypes had a significantly increased risk of recurrent miscarriage compared with those with a 0– 1 risk genotype (adjusted OR=1.728, 95% CI=1.112– 2.683, p=0.0149). This risk was more significant in subgroups of women less than 35– 40 years of age and women with 2– 3 miscarriages.Conclusion: These results suggested that a specific SNP in the ANRIL gene may be associated with increased susceptibility to recurrent miscarriage in a southern Chinese population.Keywords: recurrent miscarriage, lncRNA ANRIL, genetic susceptibility, polymorphism

Kun Lin,1,2,* Linyuan Zhang,1,2,* Yishuai Wang,1– 3,* Jinqing Li,1 Yufen Xu,1 Di Che,1 Hanran Mai,4 Hongyan Yu,1 Lanyan Fu,1 Bing Wei,2 Zhiyong Jiang,2 Lei Pi,1 Xiaoqiong Gu1,2 1Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, 510623, People’s Republic of China; 2Department of Blood Transfusion and Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, 510623, People’s Republic of China; 3School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510006, People’s Republic of China; 4Department of Andrology, Guangzhou Women and Children’s Medical Center. Guangzhou Medical University, Guangzhou, Guangdong, 510623, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoqiong Gu; Lei Pi Email guxiaoqiong@gwcmc.org; pilei@gwcmc.orgBackground: A large number of studies demonstrated that the key to the occurrence and development of Kawasaki disease (KD) is the over-activation of immune cells and the generation of various inflammatory factors, leading to the imbalance of the immune system. Recently, mutations in the FNDC1 gene have been shown to be associated with inflammatory responses. However, there have been no reports on the relationship between FNDC1 gene and KD so far.Methods: We enrolled 1611 controls and 1459 patients with KD, including 372 patients with coronary artery aneurysm (CAA) and 179 patients with coronary artery lesion (CAL). The relationship between FNDC1 rs3003174 polymorphism and KD with CAA or without CAA was investigated.Results: This study showed no evidence that the association between FNDC1 rs3003174 C>T polymorphism and KD susceptibility was statistically significant (CT versus CC: adjusted odds ratio (OR) =0.897, 95% confidence interval (CI) =0.769– 1.045, P=0.162; TT versus CC: adjusted OR=0.995, 95% CI=0.786– 1.260, P=0.968; dominant model: adjusted OR=0.916, 95% CI=0.792– 1.059, P=0.235; and recessive model: adjusted OR=1.055, 95% CI=0.845– 1.316, P=0.638). However, our further stratified analysis in the control and KD group bore out that the incidence of TT genotype of FNDC1 rs3003174 C > T polymorphism was higher than that of CC/CT genotype in KD patients stratified by CAA (adjusted OR=1.437, 95% CI=1.034– 1.996, P=0.031). Moreover, a stratified analysis of age and gender in KD patients indicated that the rs3003174 TT genotype increased the risk of CAA formation in aged ≦60 months (CC/CT vs TT: adjusted OR=1.580, 95% CI=1.106– 2.259, P=0.012) and male (CC/CT vs TT: adjusted OR=1.653, 95% CI=1.101– 2.481, P=0.015) KD patients.Conclusion: The results of this study demonstrated that the FNDC1 rs3003174 C>T polymorphism may be a hazard factor in the formation of CAA in KD patients that was not disclosed before.Keywords: coronary artery aneurysm, Kawasaki disease, fibronectin type III domain containing 1, polymorphisms

Di Che,1,* Zhenzhen Fang,2,* Lei Pi,1 Yufen Xu,1 LanYan Fu,1 Huazhong Zhou,1 Xiaoqiong Gu1,3,4 1Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Program of Molecular Medicine, Guangzhou Women and Children’s Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 3Department of Clinical Lab, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China; 4Department of Blood Transfusion, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoqiong GuDepartment of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, Guangdong 510623, People’s Republic of ChinaTel/Fax +86-20-38076561Email guxiaoqiong@gwcmc.orgBackground: Many inflammation-related gene polymorphisms are associated with susceptibility to recurrent miscarriage. SERPINA4 is involved in inflammation and is associated with susceptibility to a variety of diseases, but its relevance in recurrent miscarriage is unclear. Therefore, this study aimed to investigate the relationship between SERPINA4 gene polymorphisms and susceptibility to recurrent spontaneous abortion.Methods: Two SERPINA4 polymorphisms were genotyped in 631 patients with recurrent miscarriage and 771 controls by TaqMan real-time polymerase chain reaction, and the strength of each association was evaluated through 95% confidence intervals (CIs) and odds ratios (ORs).Results: The results showed that SERPINA4 rs2070777 AA genotypes were associated with an increased risk of recurrent miscarriage (AA vs AT/TT adjusted OR=1.409, 95% CI=1.032– 1.924, P=0.0309), and we also found a significant association between the rs910352 T allele in the SERPINA4 gene and susceptibility to recurrent miscarriage (CT vs CC adjusted OR=1.579, 95% CI=1.252– 1.992, P=0.0001; TT vs CC adjusted OR=1.524, 95% CI=1.134– 2.049, P=0.0052). The combined analysis of two SNPs of the SERPINA4 gene revealed that carriers with one to two unfavorable genotypes were associated with a higher risk for recurrent miscarriage compared with individuals with no unfavorable genotypes (adjusted OR=1.257, 95% CI=1.019-1.550). Moreover, our study indicates that having one to two unfavorable genotypes is associated with an increased risk of recurrent miscarriage in women 35– 40 years of age.Conclusion: Our study suggests that SERPINA4 rs2070777AA genotypes might contribute to an increased risk of recurrent miscarriage in a southern Chinese population.Keywords: recurrent miscarriage, SERPINA4, genetic susceptibility, polymorphism

Zhiyuan Wu,1,* Yongqin Yu,1,* Lanyan Fu,2 Hanran Mai,2 Li Huang,1 Di Che,2 Jianping Tao,1 Xiaoqiong Gu2– 4 1Department of Pediatric Intensive Care Unit, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, People’s Republic of China; 2Department of Clinical Biological Resource Bank, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, People’s Republic of China; 3Department of Blood Transfusion, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, People’s Republic of China; 4Department of Clinical Laboratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoqiong Gu; Jianping Tao Email guxiaoqiong@gwcmc.org; golou6354@163.comBackground: Sepsis in children is one of the main causes of death in pediatric intensive care units (PICUs); however, the pathogenesis of sepsis is not fully clear. Previous studies revealed that many genetic variations were related to sepsis susceptibility. A long non-coding RNA SOX2 overlapping transcript (SOX2OT) may play a role in mitochondrial homeostasis and antioxidative activity, but the relationship between the lncRNA SOX2OT polymorphism and sepsis susceptibility has not been reported.Methods: In this study, 474 pediatric sepsis patients and 678 healthy controls were recruited from southern China. After genotyping, the strength of the associations was evaluated through odds ratios (ORs) and 95% confidence intervals (CIs).Results: The SOX2OT rs9839776 T allele was associated with decreased susceptibility to sepsis in southern Chinese children (TT/CT vs CC adjusted OR = 0.778, 95% CI = 0.610– 0.992; P = 0.0431). Moreover, the difference in susceptibility was greater in children of age > 60 months (adjusted OR = 0.458, 95% CI = 0.234– 0.896; P = 0.0225), survivors (adjusted OR = 0.758, 95% CI = 0.585– 0.972; P = 0.0358), males (adjusted OR = 0.655, 95% CI = 0.479– 0.894; P = 0.0077) and the sepsis subgroup (adjusted OR = 0.548, 95% CI = 0.343– 0.876; P = 0.0120).Conclusion: The rs9839776 T allele may contribute to decreased sepsis risk in Chinese children. Future studies with a larger sample size are needed to verify these results.Keywords: sepsis, SOX2OT, rs9839776, susceptibility, polymorphism

Li Yu, Hai-Jin Ke, Di Che, Shao-Lan Luo, Yong Guo, Jie-Ling Wu Department of Children’s Health Care, Guangdong Women and Children Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Jie-Ling Wu; Yong GuoDepartment of Children’s Health Care, Guangdong Women and Children Hospital, Guangzhou Medical University, Guangzhou 511400, Guangdong, People’s Republic of ChinaTel +86 20 39151521Email jieling3861@163.com; geyong084@163.comPurpose: Pandemic-related confinement helps to contain the transmission of the novel coronavirus disease (COVID-19) but restricts children’s exposure to sunlight, thereby possibly affecting their 25-hydroxyvitamin D [25(OH)D] levels. This study aimed to examine the effect of COVID-19 measures on 25(OH)D levels in children.Patients and Methods: This study included children who underwent health checks between March 1 and June 30, 2020, and those over the equivalent period during 2017– 2019 (N = 3600). Children’s 25(OH)D levels and the proportion of children with vitamin D deficiency were compared between different observation periods.Results: The mean serum 25(OH)D level was 84 ± 25nmol/L. The overall proportion of children with vitamin D deficiency (25(OH)D level < 50 nmol/L) was 4.6%. Home confinement led to an increase in the proportion of children aged 3– 6 years with vitamin D deficiency during March 1–June 30, 2020 compared with the same months in previous years, and the most noticeable increase was found in March 2020. In children aged 3– 6 years, 25(OH)D levels were lower in 2020 (65 ± 17nmol/L) than during 2017– 2019, and the proportion of those with vitamin D deficiency was higher in 2020 (19.0%) than in previous years. Among children aged 0.5– 1 and 1– 3 years, 25(OH)D levels were higher (97 ± 25 nmol/L, 91 ± 27 nmol/L), while the proportion of children with vitamin D deficiency was lower in 2020 (2.3%, 3.0%) than during 2017– 2019.Conclusion: The 25(OH)D levels tended to decrease gradually with increasing age. Reduced sunlight exposure during confinement is associated with lower 25(OH)D levels among children aged 3– 6 years. Therefore, vitamin D supplementation for children aged > 3 years is recommended.Keywords: 25-hydroxyvitamin D, coronavirus disease, deficiency, sunlight exposure

Jing Shen,1,* Xin Sun,2,* Bo Pan,1 Shoubo Cao,1 Jingyan Cao,1 Dehai Che,1 Fang Liu,1 Shuai Zhang,1 Yan Yu1 1Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, People’s Republic of China; 2Department of Cardiology, The First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, People’s Republic of China *These authors contributed equally to this work Background: Tumor-associated macrophage (TAM) is emerging as one of the important complications in cancer promotion. Interleukin-17 (IL-17), a potent pro-inflammatory cytokine, plays an active role in promoting M2 macrophage differentiation (TAMs are M2-like phenotypes). In this study, we aimed to evaluate that IL-17 stimulates key phenotypic and functional signatures of M2 macrophages associated with cancer progression in non-small-cell lung cancer (NSCLC) patients.Patients and methods: The markers and cytokines of M2 macrophages were detected in THP-1-derived macrophages and mouse peritoneal macrophages treated with IL-17. The activation of nuclear factor kappa B (NF-κB) and nuclear localization of p65 in IL-17-treated cells were investigated. The BAY11-7082 inhibitor and the siRNA of p65 were used to block the NF-κB activation. A total of 85 patients who underwent surgery for histologically verified NSCLC were enrolled in this study. The expression of IL-17 and M2 macrophage markers were assessed by immunostaining. Survivals were estimated using the Kaplan–Meier method.Results: The CD163 and CD206 cell surface markers and transforming growth factor beta (TGF-β), vascular endothelial growth factor (VEGF) and IL-10 of M2 macrophages were significantly increased in IL-17-treated THP-1-derived macrophages in a dose-dependent manner. IL-17 increased the mRNA levels of Arginase I and Fizz1, the phosphorylation of IkBα and nuclear localization of p65 (a subunit of NF-κB). The BAY11-7082 abrogated IL-17-induced CD206 and CD163 expression, TGF-β, VEGF, IL-10, Arginase I and Fizz1 expression and p65 nuclear translocation. Further experiments showed that IL-17 induced the expression of CD206, CD163, Arginase I, Fizz1 and Ym1 in mouse peritoneal macrophages that were inhibited by siRNA of p65. The immunostaining experiments on human NSCLC tissues indicated that high IL-17 expression was significantly correlated with CD163 and c-Maf. The intratumoral IL-17+ CD163+ c-Maf+ cells were associated with NSCLC progression.Conclusion: IL-17 stimulated macrophages to M2-like phenotypes via NF-κB activation. IL-17 may be a potential therapeutic target for NSCLC. Keywords: IL-17, M2 macrophages, NF-κB, non-small-cell lung cancer, survival

Di Che,1,* Jiawen Li,2,* Lanyan Fu,1,* Lei Pi,1 Xing Rong,2 Yanfei Wang,3 Yufen Xu,1 Ping Huang,3 Maoping Chu,2 Xiaoqiong Gu1,4 1Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China; 2Children’s Heart Center, the Second Affiliated Hospital and Yuying Children’s Hospital, Institute of Cardiovascular Development and Translational Medicine, Wenzhou Medical University, Wenzhou, China; 3Department of Cardiology, Guangzhou Women and Children’s Hospital, Guangzhou Medical University, Guangzhou, China; 4Department of Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China *These authors contributed equally to this work Background: Kawasaki disease (KD) mainly manifests as excessive inflammation and vascular endothelial cell injury. This disease generally occurs in children younger than 5 years of age and is more severe in children younger than 12 months. KD affects males and females at a ratio of 1.5:1. Polymorphisms of the rs1625579 locus in the miR-137 gene are associated with schizophrenia susceptibility, and high glucose-induced upregulation of miR-137 in vascular endothelial cells promotes monocyte chemotaxis and inflammatory cytokine secretion in gestational diabetes mellitus. However, researchers have not reported whether rs1625579 is associated with KD susceptibility or onset. Therefore, we investigated the relationship between the miRNA-137 rs1625579 T>G polymorphism and KD susceptibility. Methods: TaqMan real-time polymerase chain reaction was applied to determine the genotypes of 532 patients with KD (365 males and 167 females) and 623 control subjects (402 males and 221 females). Results: Comparison of all cases with all controls revealed that the rs1625579 T>G polymorphism was not associated with KD susceptibility. However, a subgroup analysis revealed that subjects with the rs1625579 TG/GG genotypes exhibited a significantly higher onset risk for KD before 12 months of age than carriers of the TT genotype (adjusted age and gender odds ratio=1.99, 95% CI=1.04–3.83; P=0.039). Conclusion: Our results indicate that the rs1625579 T>G polymorphism confers a risk of early-onset KD in southern Chinese children. Keywords: Kawasaki disease, miRNA-137, rs1625579, susceptibility, early onset

Lei Pi,1,* Di Che,1,* Haifeng Long,2,3,* Zhenzhen Fang,4 Jiawen Li,1 Shuyi Lin,2 Yunfeng Liu,2 Meiai Li,2 Lijuan Bao,2 Wenli Li,2 Yuan Zhang,2 Qiulian Deng,2 Techang Liu,5 Li Zhang,5 Xiaoqiong Gu1,2 1Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China; 2Department of Clinical Laboratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China; 3Department of Clinical Laboratory, The First Clinical Medical College, Jinan University, Guangzhou, China; 4Program of Molecular Medicine, Guangzhou Women and Children’s Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China; 5Department of Cardiology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China *These authors contributed equally to this work Introduction: Kawasaki disease is a kind of systemic vasculitis that mainly damages moderate and small-sized blood vessels, and is a leading cause of coronary artery lesions (CAL). Antiplatelet therapy is a routine component of Kawasaki disease treatment strategies. So it is important to evaluate the antiplatelet effect of aspirin because of the individual biological variability of antiplatelet effect of aspirin. The immature platelet fraction (IPF) has attracted particular attention as it may influence the antiplatelet effect of aspirin. This study investigated the prognostic factors for evaluating the degree of vasculitis and the effect of antiplatelet therapy in children with Kawasaki disease. Materials and methods: Blood samples were collected from 44 patients with Kawasaki disease before aspirin treatment and 7 to 10 days after treatment. The IPF counts, percentage of the IPF, and highly fluorescent IPF were detected by a Sysmex XE-5000 instrument. The levels of 11-dehydrothromboxane B2 (11-DH-TXB2), soluble CD40 ligand (sCD40L), and soluble P-selectin (sP-selectin) were measured by ELISA. The correlation between the measured factors and the degree of coronary artery damage in Kawasaki disease was analyzed. Results: We found that 11-DH-TXB2, sP-selectin, and sCD40L levels were much more elevated in the CAL group than in the non-coronary artery lesions (NCAL) group before aspirin treatment. The concentrations of 11-DH-TXB2, sCD40L, sP-selectin, and IPF were reduced after aspirin treatment in the NCAL group but not the CAL group. This is related to the degree of coronary artery damage in Kawasaki disease patients. Additionally, 11-DH-TXB2, sCD40L, sP-selectin, and IPF were positively correlated with the degree of coronary artery damage in Kawasaki disease patients. Conclusion: The current study suggests that the presence of high plasma concentrations of 11-DH-TXB2, sCD40L, sP-selectin, and IPF can be considered a risk factor and experimental biomarker for CAL in Kawasaki disease patients. Keywords: Kawasaki disease, coronary artery lesions, aspirin, immature platelet fraction

Youwen Zhang, Deyin Tong, Daobiao Che, Bing Pei, Xiaodong Xia, Gaofeng Yuan, Xin Jin Department of Hospital Pharmacy, The First Hospital of Suqian, Suqian, People’s Republic of China Abstract: The roles of ginsenoside compound K (CK) in inhibiting tumor have been widely recognized in recent years. However, low water solubility and significant P-gp efflux have restricted its application. In this study, CK ascorbyl palmitate (AP)/d-α-tocopheryl polyethylene glycol 1000 succinate monoester (TPGS) mixed micelles were prepared as a delivery system to increase the absorption and targeted antitumor effect of CK. Consequently, the solubility of CK increased from 35.2±4.3 to 1,463.2±153.3 µg/mL. Furthermore, in an in vitro A549 cell model, CK AP/TPGS mixed micelles significantly inhibited cell growth, induced G0/G1 phase cell cycle arrest, induced cell apoptosis, and inhibited cell migration compared to free CK, all indicating that the developed micellar delivery system could increase the antitumor effect of CK in vitro. Both in vitro cellular fluorescence uptake and in vivo near-infrared imaging studies indicated that AP/TPGS mixed micelles can promote cellular uptake and enhance tumor targeting. Moreover, studies in the A549 lung cancer xenograft mouse model showed that CK AP/TPGS mixed micelles are an efficient tumor-targeted drug delivery system with an effective antitumor effect. Western blot analysis further confirmed that the marked antitumor effect in vivo could likely be due to apoptosis promotion and P-gp efflux inhibition. Therefore, these findings suggest that the AP/TPGS mixed micellar delivery system could be an efficient delivery strategy for enhanced tumor targeting and antitumor effects. Keywords: ginsenoside CK, ascorbyl palmitate, TPGS, mixed micelles, anti-tumor therapy

Background: Digital stories have been shown to be effective in sharing information. The Partnerships for Inclusive Research and Learning (PIRL) was a 4-year international participatory research project focussed on the digital divide in inclusive research. Objectives: Members of PIRL share their experience of using digital storytelling to get key messages from the project to a wide range of people. Method: Members of PIRL were invited to develop digital stories and create project-specific guidelines for digital story development. Seven people participated in workshops given by experts, read literature, watched digital stories and discussed how to create digital stories. Results: The group created six digital stories, each one addressing a different aspect related to disability-inclusive research, with many having a focus on Africa and the creation of credible African evidence. The importance of assisting community members to think about and support research and evidence creation was one of the goals of the project. The videos provide an avenue to share insights about disability-inclusive development research. Group members stated that being part of the process significantly improved their understanding of translating evidence into formats that are more understandable. Conclusion: Creating digital stories requires commitment, a significant amount of time, access to digital tools, and financial resources. Working collaboratively on this project was not only meaningful but also encouraged positive working relationships and fostered critical thinking. Contribution: This article contributes to a better understanding of ways in which digital storytelling can be used in knowledge-sharing strategies to promote disability inclusion. [ABSTRACT FROM AUTHOR]

This work took the kitchen wastes from Liuta Mining Area of Shendong Coal as example, to investigate the effects of hydrogen peroxide(H2O2) pretreatment on the performance of kitchen waste and the production efficiency of volatile fatty acid(VFAs) from anaerobic fermentation. Then the nitrogen and phosphorus removal effect of wastewater treatment with anaerobic fermentation slurry from kitchen waste as carbon source were investigated. Results indicated that the H2O2 pretreatment could promote the release of dissolved organic matters in kitchen wastes and enhance the fluidity of kitchen waste slurry. As a result, the VFAs production after H2O2 pretreatment increased from 10 810-18 131 mg/L to 21 000-28 000 mg/L, while the dominant fermentation products were converted from butyric acid to acetic acid. These suggested that the H2O2 pretreatment achieved a significant improvement in the production efficiency of VFAs. Furthermore, when the anaerobic fermentation slurry from pre-treated kitchen waste as carbon source of wastewater treatment plants, the concentration of NH4+-N and TP in the effluent was less than 1 mg/L and 0.5 mg/L, which was equivalent to the treatment effect when glucose was used as the carbon source. All these demonstrated that the kitchen waste in the mining area had good usability.