BACKGROUND:Primary spontaneous pneumothorax is a rare disease commonly found in young adults, with unknown aetiology. We aimed to investigate the susceptibility genes and the downstream signalling involved in the development of primary spontaneous pneumothorax. METHODS:We conducted the first large-scale genome-wide association study (GWAS) composed of 2223 patients and 3838 controls. The functional role of the novel susceptibility loci was investigated by both in vivo and in vitro assays. Gene expression profiling in lung epithelial cell lines was performed, and conditional gene knockout mice were generated. RESULTS:We identified four novel susceptibility loci at 14q32.2 near C14orf177, at 15q26.3 near CHSY1, at 16q23.1 near CFDP1 and at 22q13.1 near CBX7. The fine-mapping of 22q13.1 revealed a functional variant which regulated CBX7 expression by disrupting the binding activity of transcription factor CREB1. Conditional knockout of Cbx7 in mouse lung epithelial cells resulted in lung cyst formation. Meanwhile, downregulation of the CBX7 elevated the expression of MMP9 and MMP16, which are part of extracellular matrix regulators and may lead to lung injury. CONCLUSIONS:Our GWAS discovered four novel susceptibility loci of primary spontaneous pneumothorax and presented a mechanistic basis for the genetic association with primary spontaneous pneumothorax. The novel susceptibility gene CBX7 and downstream MMP signalling give a new clue to the pathogenesis of primary spontaneous pneumothorax.

Hereditary antithrombin deficiency (HATD) is a rare disease caused by mutations in the SERPINC1 gene characterized with venous thromboembolism and/or arterial thrombotic events. We identified a proband with recurrent arterial and venous thrombosis at multiple anatomical sites and subsequently performed comprehensive thrombophilia screening and genetic analysis within the kindred. Mutation screening of the SERPINC1 gene in the proband and family members was conducted using Sanger sequencing. Wild-type and mutant (c.473T > A; p.Leu158Gln) SERPINC1 expression plasmids were constructed and transiently transfected into HEK293T cells. Functional consequences of the variant were assessed through immunoblotting, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and computational structural analysis. Thrombophilia evaluation revealed significantly reduced antithrombin activity (46.2

Primary spontaneous pneumothorax (PSP) or pulmonary cyst is one of the manifestations of Birt-Hogg-Dubé syndrome, which is caused by pathogenic variants in FLCN gene. Genetic testing in patients with PSP identifies a certain number of missense or intronic variants. These variants are usually considered as variants of uncertain significance, whose functional interpretations pose a challenge in clinical genetics. To improve recognition of pathogenic splice-altering variants in FLCN gene, computational tools are used to prioritize potential splice-altering variants and then a hybrid minigene assay is performed to verify the RNA splicing pattern. Herein, variants in FLCN exon 11 and its flanking sequence are focused. Eight variants detected in 11 patients with PSP are evaluated, and six variants are prioritized by in silico tools as potential splice-altering variants of uncertain significance. Four variants (c.1177-5_1177-3delCTC, c.1292_1300+4del, c.1300+4C>T, and c.1300+5G>A) are demonstrated by minigene assay to alter RNA splicing of FLCN, and the last three of them are novel. RT-PCR of patient-derived RNA gives consistent results. Genotype-phenotype correlation analysis in patients with PSP with these variants demonstrates good concordance. Our results underline the importance of RNA analysis, which could provide molecular evidence for pathogenicity of a variant, and provide essential information for the clinical interpretation of variants. Combining the clinical information, a definitive diagnosis could be made.

Background X-linked early-onset osteoporosis, caused by mutations in plastin3 (PLS3), is an extremely rare disease characterized by low bone mineral density (BMD) and recurrent osteoporotic fractures. There is limited information on genetic and phenotypic spectrum, as well as genotype-phenotype correlations of the disease. Moreover, whether decreased PLS3 levels were also involved in osteoporosis among subjects without PLS3 pathogenic mutations remains unknown. Methods Whole-exome sequencing and bidirectional Sanger sequencing were performed for screening and validation of pathogenic mutations. Serum biochemical parameters and clinical information of the subjects were retrospectively collected. ELISA and online datasets were utilized to investigate the association between PLS3 expression and BMD. Results We identified a novel splicing mutation (c.892-2A > G) which led to the skipping of exon 9 in a family with X-linked early-onset osteoporosis. Scoliosis represents a potential new phenotype in the patients harboring PLS3 mutations, which may be corrected by brace treatment. Genotype-phenotype analysis reveals that there was no significant difference in BMD z-scores between different types of reported mutations including this study (p = 0.5). There is a marginally significant negative correlation between age and BMD z-score (p = 0.059, r = - 0.30). The conditions of osteoporosis in all patients were improved after bisphosphonates therapy, with mean BMD z-score increased from - 2.9 to - 0.57 (p < 0.0001). Serum PLS3 levels in adolescents and adults without PLS3 pathogenic mutations but representing osteoporosis were also evaluated, while no association was found between bone mineral density and PLS3 levels (p > 0.05). Conclusions Our findings expanded the mutation and phenotype spectrum of the rare disease and highlights the importance of early diagnosis and early treatment with bisphosphonates. More reports of cases with PLS3 mutation and function studies of the gene are warranted to understand genotype-phenotype correlations.

Abstract Background Diagnosis of rare diseases remains a challenge in China. We describe our experience with Birt-Hogg-Dubé syndrome (BHDS) encountered at a Rare Lung Disease Clinic recently established in China. Methods After the first patient with BHDS was recognized in 2017, a Rare Lung Disease Clinic with a multidisciplinary team of specialists was established. We retrospectively analyzed the data of consecutive patients with BHDS encountered from inception to December 2021. Results There were 1, 1, 15, 12 and 21 cases with BHDS diagnosed from year 2017 to 2021, respectively. All 50 patients (34 women) were of Han race with a mean age of 47.4 years. The common manifestations were pulmonary cysts (98%), pneumothorax (54%) and skin lesions (68%). Renal cancer was detected in two patients and renal angiomyolipoma in four other patients. The main presentations leading to diagnosis were pneumothorax (42%), family screening (36%), and lung cysts identified on radiologic imaging (20%). The average delay in diagnosis was 8.3 years, and 4.7 years in patients with only pulmonary cysts. The most frequent pathogenic variant was c.1285del/dup on exon 11 (23%) among 44 patients confirmed by genetic testing. Renal cancer has not been found on follow-up surveillance thus far. Conclusions Increasing number of patients with BHDS are being recognized in China, facilitated by establishment of a Rare Lung Disease Clinic. Pulmonary cysts and pneumothorax were commonly encountered features, but skin lesions appeared to be more prevalent in Chinese subjects than previously reported in other Asian countries.

Duchenne muscular dystrophy (DMD, MIM #310200) and Becker muscular dystrophy (BMD, MIM #300376) are X-linked recessive hereditary diseases caused by pathogenic variants in the DMD gene. Genetic testing of DMD identifies a certain number of variants of uncertain clinical significance (VUS) whose functional interpretations pose a challenge for gene-based diagnosis. To improve the accuracy of variant interpretation in public mutation repositories, we used computational tools to prioritize VUS and developed a cell-based minigene assay to confirm aberrant splicing. Using this procedure, we evaluated rare variants in exon and intron 10 of the DMD gene. We demonstrated that 16 variants, including both canonical and non-canonical splice sites, altered RNA splicing in variable patterns. Using the example of exon and intron 10 of the DMD gene, we demonstrated the utility of the in vitro minigene assay in the effective assessment of the spliceogenic effect for VUS identified in clinical practice and underlined the necessity of precise variant classification. This is the first systematic characterization of DMD splicing variants, besides, through our study, some undetermined variants are demonstrated to be pathogenic by altering RNA splicing of DMD.

Birt–Hogg–Dubé syndrome (BHDS, MIM #135150), caused by germline mutations of FLCN gene, is a rare autosomal dominant inherited disorder characterized by skin fibrofolliculomas, renal cancer, pulmonary cysts and spontaneous pneumothorax. The syndrome is considered to be under-diagnosed due to variable and atypical manifestations. Herein we present a BHDS family. Targeted next generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA) revealed a novel FLCN intragenic deletion spanning exons 10-14 in four members including the proband with pulmonary cysts and spontaneous pneumothorax, one member with suspicious skin lesions and a few pulmonary cysts, as well as two asymptomatic family members. In addition, a linkage analysis further demonstrated one member with pulmonary bullae to be a BHDS-ruled-out case, whose bullae presented more likely as an aspect of paraseptal emphysema. Furthermore, the targeted NGS and MLPA data including our previous and present findings were reviewed and analyzed to compare the advantages and disadvantages of the two methods, and a brief review of the relevant literature is included. Considering the capability of the targeted NGS method to detect large intragenic deletions as well as determining deletion junctions, and the occasional false positives of MLPA, we highly recommend targeted NGS to be used for clinical molecular diagnosis in suspected BHDS patients.

Objectives: The aim of our study was to elucidate the association between severity of postoperative hypocalcemia and the prognosis of the patients with 22q11DS. Methods: Data retrospectively were collected from 23 children with 22q11DS who underwent cardiac correction surgery. Area under the receiver operating characteristic curve (AUC) and diagnostic odds ratio were calculated to determine the tendency of perioperative mortality rate, according to the minimum levels of serum calcium and the duration of hypocalcemia. A novel risk assessment system for perioperative mortality was established according to these valid parameters. Results: The death group had lower minimum levels of serum calcium and longer duration of hypocalcemia. The AUC of minimum levels of serum calcium was 0.912 (95% CI: 0.753-1; P = .003) and qualified its high accuracy for perioperative mortality. The AUC of duration of hypocalcemia was 0.804 (95% CI: 0.561-1; P = .03) and qualified its moderate accuracy. The tendency analyses also indicated the correlation between these two parameters and perioperative mortality. Based on the cut-off values from ROC analysis, a novel risk assessment system for perioperative mortality was established according to these two parameters. The patients with the lowest serum calcium level <0.885 mmol/L or duration of the hypocalcemia > 90.33 hours would be sorted into a high-risk group; others were divided into a low-risk group. The diagnostic odds ratio for this assessment system was 143(95% CI: 5.13-3982.52). No significant difference was found with regard to patient age, weight, preoperative serum total calcium, cardiopulmonary bypass (CPB) time, and aortic cross-clamp time between the high- and low-risk groups. Conclusions: The minimum levels of serum calcium and duration of hypocalcemia were valid predictors for preoperative mortality of 22q11DS patients.

The DENND1A gene is one of the most important sites associated with polycystic ovary syndrome (PCOS). We attempted to analyze the correlation between five single nucleotide polymorphisms (SNPs) in the DENND1A gene and the development of PCOS. A total of 346 PCOS patients and 225 normal ovulatory women were involved in the case-control study. Clinical variables and hormones were recorded. According to the Hap Map database, five tagging SNPs (rs2479106, rs2768819, rs2670139, rs2536951 and rs2479102) in the DENND1A gene were identified. The TaqMan probe and the PCR–RFLP (restriction fragment length polymorphism) methods were used for revealing these genotypes. TaqMan Genotype Software was used to analyze the alleles of the five SNPs. Linkage disequilibrium and the gene frequency analysis demonstrated that the CCGGG haplotype might increase the risk of PCOS (P = 0.038, OR = 1.89, 95% CI = 1.027–3.481). Significant differences were found in genotypic and allelic distributions at the rs2536951 and rs2479102 loci between PCOS women and controls (P <  0.001). The LH levels and LH/FSH ratios were higher in PCOS patients than in the control group. A detailed analysis revealed that for the rs2479106 locus, these two values were significantly different in the control subjects who had AA, AG and GG genotypes (P = 0.013 and P = 0.007, respectively), and for the rs2468819 locus, these two values were significantly different among the PCOS patients with AA, AG and GG genotypes (P = 0.013 and 0.002, respectively). The tagging SNPs rs2479106 and rs2468819 in the DENND1A gene are associated with PCOS in the Chinese population, whereas rs2670139, rs2536951 and rs2479102 are not correlated with PCOS in the same population.

目的 为家族性肥厚型心肌病的遗传病因学提供一个新的、需进一步研究的候选致病基因.方法 收集2018年8月就诊于本院的1例肥厚型心肌病患者及其家族成员的临床资料,然后对确诊为肥厚型心肌病的先证者的外周血样本进行基因二代测序及分析,筛选出三个候选致病基因:LAMA2、TTN和OBSCN,最后对家系中12例成员进行候选致病基因的Sanger测序验证及遗传传递分析.结果 OBSCN基因编码的第6721位苯丙氨酸突变为亮氨酸的杂合突变可能是该家族潜在致病病因,该突变位点可能损害该基因的功能.结论 OBSCN基因可能是这个家系的家族性肥厚型心肌病的致病基因.

Background Birt-Hogg-Dubé Syndrome (BHDS) characterised by skin fibrofolliculomas, kidney tumour and pulmonary cysts/pneumothorax is caused by folliculin (FLCN) germline mutations. The pathology of both neoplasia and focused tissue loss of BHDS strongly features tissue-specific behaviour of the gene. Isolated cysts/pneumothorax is the most frequent atypical presentation of BHDS and often misdiagnosed as primary spontaneous pneumothorax (PSP). Deferential diagnosis of BHDS with isolated pulmonary presentation (PSP-BHD) from PSP is essential in lifelong surveillance for developing renal cell carcinoma. Methods The expression profiles of microRNAs (miRNAs) in cystic lesions of PSP-BHD and PSP were determined via microarray. The selected upregulated miRNAs were further confirmed in the plasma of an expanded cohort of PSP-BHD patients by reverse transcription quantitative PCR (RT-qPCR). Their diagnostic accuracy was evaluated. Moreover, the cellular functions and targeted signalling pathways of FLCN-regulated miRNAs were assessed in various cell lines and in the lesion tissue contexts. Results Cystic lesions of PSP-BHD and PSP showed different miRNAs profiles with a significant upregulation of miR-424–5p and let-7d-5p in PSP-BHD. The combination of the two effectively predicted BHDS patients. In vitro studies revealed a suppressive effect of FLCN on miR-424–5p and let-7d-5p expressions specifically in lung epithelial cells. The ectopic miRNAs triggered epithelial apoptosis and epithelial transition of mesenchymal cells and suppressed the reparative responses in cells and tissues with FLCN deficiency. Conclusion The upregulation of miR-424–5p and let-7d-5p by FLCN deficiency occurred in epithelial cells and marked the PSP-BHD condition, which contributed to a focused degenerative pathology in the lung of PSP-BHD patients.

Aim: Brain injury after sepsis leads to high mortality and long-term brain dysfunction in patients. Previous studies revealed that borneol has a protective effect on the brain, but its function on sepsis associated encephalopathy (SAE) remains unknown. Herein, we investigated the protective effect of borneol against sepsis-related brain injury. Main methods: Lipopolysaccharide (LPS)-induced sepsis mice and cells were treated with borneol at the dose of 100 mu g/kg by gavage or 10 mu g/ml in culture, respectively. The protective effect of borneol on neurons and the microglia were assessed in vivo and in vitro. Key findings: We observed that borneol attenuated brain neuronal and microglial inflammation in LPS-induced sepsis mice with a suppression of p-p65 and p38 signaling that were initially activated by LPS in the brain. In vitro examination confirmed that the protective effect of borneol on both neurons and microglia, and its suppressive effect on p-p65 and p38 pathways were, at least in part, direct. Significance: An early protection of neurons and microglia from bacterial endotoxin during sepsis is beneficial, and borneol has the potential to protect these cells.

AIMS:The accumulation of lipids in macrophages contributes to the development of atherosclerosis. Cholesterol efflux of lipid-loaded macrophages mediated by ATP binding cassette (ABC) cholesterol transporters, on the other hand, has been shown to attenuate atherosclerosis progression in patients with unknown mechanism. We therefore sought to test the effect of metformin that reduced cardiovascular risk in diabetic patients independent of its hypoglycemia effect on cholesterol transport in murine raw264.7 macrophages.MATERIALS AND METHODS:Mouse raw264.7 macrophages were loaded with Ox-LDL (50 μg/ml) for 24 h before incubated with metformin (15 μM) for 24 h. Foam cell formation was assessed by Oil red staining and BIODIPY fluorescent staining as well as cholesterol-ester quantification by commercial kit. Cholesterol uptake and expression of scavenger receptors were detected by flow-cytometry. Cholesterol efflux capacity was measured by fluorescent plate-reader and ABC transporters were detected by Western Blots. Cytokines were detected by ELISA in supernatants and normalized by cellular lysates.KEY FINDINGS:Our results showed that metformin decreased oxidized low-density lipoprotein (Ox-LDL)-induced cholesterol accumulation and foam cell formation by increasing cholesterol efflux to HDL, which was associated with an upregulation of ABC transporter ABCG-1. Moreover, metformin increased Ox-LDL-impaired IL-10 secretion, an important anti-foam cell cytokine in atherosclerosis.SIGNIFICANCE:Our data highlighted the therapeutic potential of targeting macrophage cholesterol efflux with new or existing drugs for the possible reduction of foam cell formation in the prevention and treatment of diabetes-accelerated atherosclerosis.

Background: Macrophage accumulation in the vascular wall is a hallmark of atherosclerosis. Studies showed that shifting of oxidized lipids-induced inflammatory macrophages towards an anti-inflammatory phenotype by promoting oxidative metabolism attenuated atherosclerosis progression. Therefore, this study aimed to investigate whether metformin, which has ameliorated atherosclerosis in animal models and clinical trials, modulated oxidized low-density lipoprotein (Ox-LDL) induced inflammatory status in macrophages by regulating cellular oxidative metabolism. Methods: Murine raw264.7 macrophages were incubated with Ox-LDL (50 mu g/mL) in the presence or absence of metformin (15 mu mol/L) for 24 h. Real-time polymerase chain reaction was used to quantify the transcription of classically activated (M1) pro-inflammatory and alternatively activated (M2) anti-inflammatory markers and mitochondrial DNA copy numbers. Cellular reactive oxygen species (ROS) production and mitochondrial membrane potential were detected by immunofluorescence. Cellular adenosine triphosphate (ATP) synthesis, glucose uptake, and lactic acid production were measured by commercial kit and normalized to cellular lysates. Western blotting analysis was performed to detect the expression of mitochondrial fusion/fission related proteins, enzymes mediating lipid metabolism and signaling pathway of glucose transport. Differences between groups were analyzed using one-way analysis of variance. Results: Metformin improved Ox-LDL-impaired anti-inflammatory phenotype in raw264.7 macrophages as shown by up-regulated transcription of anti-inflammatory markers including interleukin 10 (0.76 +/- 0.04 vs. 0.94 +/- 0.01, P = 0.003) and Resistin-like molecule alpha (0.67 +/- 0.08 vs. 1.78 +/- 0.34, P = 0.030). Conversely, Ox-LDL-diminished phosphorylation of Akt was up-regulated by metformin treatment (0.47 +/- 0.05 vs. 1.02 +/- 0.08, P = 0.040), associated with an improvement of mitochondrial function, characterized by decreased ROS generation (2.50 +/- 0.07 vs. 2.15 +/- 0.04, P = 0.040), increased lipid oxidation, and elevated cellular ATP production (0.026 +/- 0.001 vs. 0.035 +/- 0.003, P = 0.020). Moreover, merformin-mediated Akt activation increased Akt substrate of 160 kDa (AS160) phosphorylation (0.51 +/- 0.04 vs. 1.03 +/- 0.03, P = 0.0041), promoted membrane translocation of glucose transporter 1, and increased glucose influx into the cells (4.78 +/- 0.04 vs. 5.47 +/- 0.01, P < 0.001). Conclusion: This study suggested that targeting macrophage metabolism with new or existing drugs had therapeutic potential for the prevention and treatment of diabetes-accelerated atherosclerosis.

Puerarin, a major active isoflavone extracted from the root of Pueraria lobate, significantly increases plasma β-endorphin and insulin levels and improves impaired insulin signaling in diabetic animals. However, the target tissues and underlying mechanisms in and through which puerarin functions to ameliorating insulin resistance remains largely unclear. In this study, we showed that puerarin enhanced μ-opioid receptor expression and phosphorylation, and increased insulin-stimulated glucose transporter 4 translocation to the plasma membrane in the skeletal muscle of diabetic rats, which were recaptured by a direct application of puerarin in the palmitate-induced insulin-resistant L6 myotubes. Naloxone, an antagonist of μ-opioid receptor, blocked these functions of puerarin. No β-endorphin was detected either in the muscle of diabetic rats or in the palmitate-induced insulin-resistant L6 cells. Furthermore, we presented the evidence to show the interaction between μ-opioid receptor and insulin receptor substrate 1 in the muscle tissues and cells. These results suggested that puerarin improved insulin sensitivity in the skeletal muscle at least in part by its local effects involving μ-opioid receptor function.

AIMS:High level of saturated fatty acids leads to mitochondrial dysfunction and inflammation in the development of insulin resistance in skeletal muscle. We recently found that puerarin improved impaired insulin signaling in skeletal muscle in diabetic animals and in myotubes in vitro. However, whether puerarin can act directly on muscle cells to alleviate lipid-induced mitochondrial dysfunction and inflammation remains obscure. This study was conducted to analyze the attributive properties of puerarin against mitochondrial dysfunction and inflammation in skeletal muscle cells with insulin resistance.MAIN METHODS:The effects of puerarin on mitochondrial biogenesis, oxidative phosphorylation, dynamics of fusion, fission and mitophagy, oxidative stress, as well as inflammatory response and insulin sensitivity in L6 myotubes treated with palmitate were examined.KEY FINDINGS:Puerarin pretreatment improve insulin sensitivity and prevented muscle cells from palmitate-induced mitochondrial dysfunction manifested by the increases of complex I activity, mitochondrial membrane potential and ATP generation, and the decrease of reactive oxygen species (ROS) production. Augmented expression of genes involved in mitochondrial biogenesis, oxidative phosphorylation, and the detoxification of ROS were also observed upon puerarin supplementation. Moreover, puerarin modulated mitochondrial fusion and fission, and rescued palmitate-impaired mitophagy via phosphatase and tensin homolog-induced putative kinase 1(PINK1)/Parkin pathway. In addition, puerarin attenuated palmitate-induced inflammation through the inhibition of toll-like receptor 4/nuclear factor-κB signaling pathway.SIGNIFICANCE:Our findings indicated that puerarin could act directly on muscle cells to attenuate palmitate-induced mitochondrial dysfunction, impaired mitophagy and inflammatory response, thereby contributing to the improvement of insulin sensitivity.

BackgroundS1PR1-STAT3 inter-regulatory loop was initially suggested to be oncogenic in several cancer cells. However, the clinical relevance of this mechanism in tumor progression, disease prognosis and drug response was not established.MethodsThe correlations between S1PR1 transcription, overall survival and chemotherapy response of GC patients were tested using a large clinical database. The relevance of S1PR1 expression and STAT3 activation in both tumor tissues and cancer cell lines was also tested. The effect of S1PR1 high expression achieved by persistent STAT3 activation on tumor cell drug resistance was investigated in vitro and in vivo.FindingsAn enhanced S1PR1 expression was highly related with a reduced overall survival time and a worse response to chemotherapy drug and closer correlation to STAT3 in gastric cancer patients. The issue chip analysis showed that the expressions of S1PR1 and STAT3 activation were increased in higher graded gastric cancer (GC) tissues. Cellular studies supported the notion that the high S1PR1 expression was responsible for drug resistance in GC cells through a molecular pattern derived by constitutive activation of STAT3. The disruption of S1PR1-STAT3 signaling significantly re-sensitized drug resistance in GC cells in vitro and in vivo.InterpretationS1PR1-STAT3 signaling may participate drug resistance in GC, thus could serve as a drug target to increase the efficacy of GC treatment.FundThis work was supported by the National Natural Science Foundation of China (No. 81570775, 81471095), the grant from the research projects in traditional Chinese medicine industry of China (No. 201507004-2).

The etiology of thoracic aortic aneurysm and dissection (TAAD) is complex and heterogeneous. Emerging evidence has demonstrated that genetic causes may be a consideration in early-onset TAAD. Owing to overlapping clinical phenotypes and the genetic heterogeneity of TAAD, it is challenging for clinicians to make a molecular diagnosis of TAAD, particularly in those who present with non-specific syndromic features. In order to identify the causative mutation in two young patients with acute type B aortic dissection without syndromic features, whole exome sequencing (WES) was performed in the present study. A missense mutation (c.G6953A:p.C2318Y) and a nonsense mutation (c.C4786T:p.R1596X) were identified in the fibrillin 1 gene in patients T287 and T267, respectively. The present study emphasized the necessity of genetic testing for young patients with type B aortic dissection. WES is a timely, robust and inexpensive technique for molecular diagnosis, particularly for TAAD caused by numerous genes. Genetic diagnosis of Marfan syndrome could aid in periodic surveillance, prophylactic surgical measures, and genetic counseling.

All phases of disaster management require up-to-date and accurate information. Different in-situ and remote sensor systems help to monitor dynamic properties such as air quality, water level or inundated areas. The rapid emergence of web-based services has facilitated the collection, dissemination, and cartographic representation of spatial information from the public, giving rise to the idea of using Volunteered Geographic Information (VGI) to aid disaster management. In this study, with a brief review on the concept and the development of disaster management, opportunities and challenges for applying VGI in disaster management were explored. The challenges, including Data availability, Data quality, Data management and Legal issues of using VGI for disaster management, were discussed in detail with particular emphasis on the actual needs of disaster management practice in China. Three different approaches to assure VGI data quality, namely the classification and authority design of volunteers, a government-led VGI data acquisition framework for disaster management and a quality assessment system for VGI, respectively, were presented and discussed. As a case study, a prototype of VGI oriented earthquake disaster databank & sharing platform, an open WebGIS system for volunteers and other interested individuals collaboratively create and manage the earthquake disaster related information, was proposed, to provide references for improving the level of earthquake emergency response and disaster mitigation in China.