Table of Content

15 March 2018 Volume 36 Issue 3

  

Analysis of the clinical characteristics of late-onset sepsis in very low birth weight infants

　ZHAO Xiaopeng, LYU Hui, LI Xufang, SONG Yanyan, ZHOU Wei

. 2018, 36(3):  161.  doi:10.3969/j.issn.1000-3606.2018.03.001

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　Objective　To explore the clinical characteristics including the morbidity, clinical manifestation, and pathogens of late-onset sepsis (LOS) in very low birth weight (VLBW) infants in neonatal intensive care unit (NICU). Methods　Clinical data of all VLBW infants in NICU from January 2011 to December 2013 were collected. According to the results of blood culture, the VLBW infants diagnosed with LOS were divided into confirmed LOS group and clinical LOS group. The morbidity, clinical manifestations, common pathogens, and drug sensitivity of LOS were retrospectively analyzed. Results　In 226 VLBW infants, there were 117 cases of LOS with the morbidity at 51.8%. Forty-five infants were confirmed to have LOS by blood culture, accounting for 19.9% (45/226); another 72 infants were diagnosed with clinical LOS, accounting for 31.9% (72/226). The rates of tachycardia and temperature fluctuation in confirmed LOS group were higher than those in clinical LOS group, and there were significant differences (P<0.05). There were 51 strains of pathogenic bacteria, with 32 Gram-negative bacteria (62.7%), 16 Gram-positive bacteria (31.4%), and 3 fungi (5.9%). The common pathogenic bacteria were Klebsiella pneumoniae and coagulase negative Staphylococcus, the most of which were multidrug-resistant bacteria. Conclusions　The incidence of LOS in VLBW infants is high. The main clinical manifestations are sudden changes in breathing, heart rate, mental state, and skin color. Although these manifestations are not specific, they could serve as early warning. The common pathogenic bacteria are Klebsiella pneumoniae and coagulase negative Staphylococcus, and both of them are multidrug resistant.

The role of physical examination, pulse oximetry screening, and perfusion index in screening of neonatal congenital heart disease

PAN Cheng, ZOU Xiaoming, CHEN Gang, WANG Tao, JIANG Xianyu, CHEN Jianyong

. 2018, 36(3):  166.  doi:10.3969/j.issn.1000-3606.2018.03.002

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　Objective　To find a reliable, simple, and easily-operated method for the screening of neonatal congenital heart disease (CHD). Methods　A total of 7 105 neonates born from January 2017 to July 2017 were selected. The validity and reliability of physical examination, pulse oximetry screening (POS), and perfusion index (PI) in the screening of neonatal CHD were evaluated according to the diagnosis made by color Doppler echocardiography. Results　When physical examination, POS or PI was used separately in screening for CHD, the sensitivities were in the range of 13.11%~73.77%, specificities 50.20%~99.34%, Youden indexes 0.12~0.70, the total coincidence rates 50.40%~98.86%, positive predictive values 1.27%~40.70%, and negative predictive values 99.29%~99.70%. When physical examination, POS and PI were combined (two or three indexes were positive) for screening, the sensitivities and Youden indexes were 85.25% and 0.82 respectively, which were higher than those of single indicators and suggested that the combination had higher authenticities. The total coincidence rate of the combination was 97.07%, and, although it was lower than POS group (98.86%) and PI screening group (98.58%), it still had a good reliability. Conclusions　The combination of physical examination, POS and PI has a certain clinical value in neonatal CHD screening.

Clinical study on the changes of plasma melatonin and stress factors in neonatal asphyxia

　WANG Ying, MIAO Po, REN Jing, SUN Bin, CHENG Shuai, DING Xin, FENG Xing

. 2018, 36(3):  170.  doi:10.3969/j.issn.1000-3606.2018.03.003

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　Objective　To explore the changes in plasma melatonin (MT) and glucocorticoid (GC) and the expressions of melatonin receptor 1 (MR1) and glucocorticoid receptor alpha (GR alpha) after neonatal asphyxia. Methods　Full-term asphyxia neonates (22 cases of mild asphyxia, 28 cases of severe asphyxia) hospitalized from May 2014 to December 2015 were selected. Another 50 non-asphyxiated full-term newborns hospitalized with single disease such as infection and jaundice at the same time were selected as the control group. Peripheral blood samples were collected within 24 hours after birth and 7 days after birth, and plasma and mononuclear cells were separated. The plasma MT and GC expression levels were detected by ELISA. Realtime PCR was used to detect MR1 and GRα mRNA expression. Results　The plasma GC concentrations in mild and severe asphyxia group increased significantly within 24 hours after birth, higher than that in control group. In addition, the plasma GC concentration in severe asphyxia group was significantly higher than that in mild group (P<0.05). The concentration of plasma GC in mild and severe asphyxia group decreased on the 7th day after birth (P<0.05) and was significantly lower than that at 24 hours after birth, but it was still higher in the severe asphyxia group than that in mild group; both the mild and severe asphyxia group had higher GC level than that in control group; the differences are statistically significant (P<0.05). Within 24 hours after birth, the plasma MT concentration in severe asphyxia group was lower than that in mild asphyxia group and control group, and there were significant differences (P<0.05). Compared with 24 hours after birth, the concentrations of plasma MT in severe and mild asphyxia groups increased significantly, higher than that in control group on the 7th day, and there were significant differences (P<0.05). The level of GR alpha mRNA expression decreased within 24 hours after birth in severe asphyxia group, but  was increased in the mild asphyxia group, and there were significant differences among the three groups (P<0.05). The expression levels of GRα in both mild and severe asphyxia groups recovered on the 7th days after birth, and there were no significant differences compared with control group (P>0.05). Compared with 24 hours after birth , the expression level of MR1 mRNA in severe asphyxia group increased on the 7th day after birth, higher than that in control group and in mild asphyxia group, and there were significant differences (P<0.05). Conclusions　The stress caused by severe asphyxia exceeds the adaptation range in the newborn, and results in the high expressions of MR1 and endogenous MT.
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Congenital nephrotic syndrome with neonatal polycythemia: a case report

HAN Zonglai, YANG Lei, LIN Yi, LI Yongwei, YAN Chaoying

. 2018, 36(3):  175.  doi:10.3969/j.issn.1000-3606.2018.03.004

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Objectives　To investigate the relationship between congenital nephrotic syndrome (CNS) and neonatal polycythemia, and clinical diagnosis and treatment. Methods　The clinical manifestations, diagnosis, and treatment of a case of CNS with neonatal polycythemia were retrospective analyzed, and the related literature were reviewed. Results　A male infant had abdominal distention after his birth, followed by feeding intolerance and poor response. On the third day of birth, he was diagnosed of neonatal polycythemia according to the levels of hemoglobin (249 g/L) and hematocrit (0.714 L/L). And after a partial exchange transfusion, the symptoms were improved. On the sixth day of birth, the infant had edema, urinary protein +++, serum albumin at 12.7 g/L and blood cholesterol at 8.84 mmol/L, and was clinical diagnosed of CNS. Oral hormone therapy was ineffective and he died 32 days after birth. Conclusions　CNS combined with neonatal erythrocytosis is rare in clinic. The coexisting of the two is more likely to induce thromboembolism and organ dysfunction, and the clinical prognosis is poor.

Analyses of the short-term prognostic factors for recovery of independent walking in Guillain Barre syndrome in children

SUN Ruidi, WANG Xiaolu, LIANG Jufang, LUO Xiaoqing, CUI Ling, LI Cheng, LIU Zhisheng, CHEN Juanjuan, JIANG Jun

. 2018, 36(3):  178.  doi:10.3969/j.issn.1000-3606.2018.03.005

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　Objective　To explore the prognostic factors in Guillain Barre syndrome (GBS) in children. Methods　A total of 125 children with GBS were included and grouped according to their independent walking at two and six months after discharge, and their clinical data were analyzed. Results　In 125 children (74 males, 51 females) the average age was 84.49±25.32 months, and 41 were under 6 years old. 102 children had a history of prodromal infections. 32 children had cranial nerve involvement and 35 had autonomic nerve involvement. 12 children need assisted respiration. At 2 and 6 months after discharge, when compared with children who could walk independently, the rates of  functional score > 3, cranial nerve involvement, and neuroelectrophysiology as denervation potential were higher in children who could not walk independently, and the differences were statistically significant (P all<0.05). Conclusions　The factors that affect the short-term prognosis are denervation potential in neuroelectrophysiology, cranial nerve involvement, and functional score > 3. Early identification of uniqueness in patients and subsequent development of targeted rehabilitation training should be carried out to improve the prognosis.

The significance of glomerular fibrinogen deposition in childhood Henoch-Schönlein purpura nephritis

WANG Fengying, LI Xiaozhong, WANG Xingdong, ZHU Xueming

. 2018, 36(3):  182.  doi:10.3969/j.issn.1000-3606.2018.03.006

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Objective　To explore the significance of glomerular fibrinogen (Fib) deposition in Henoch-Schönlein purpura nephritis (HSPN). Methods　The clinical and pathological data of 82 children with HSPN diagnosed by renal biopsy were retrospectively analyzed. The clinical and pathological characteristics of each group were compared according to whether there were glomerular Fib deposition and deposition intensity in the kidney. Results　Glomerular Fib deposition was observed in 63 cases (76.83%) in 82 cases, including Fib+ 23 cases (28.05%), Fib++ 37 cases (45.12%) and Fib+++ 3 cases (3.66%), and no deposition had been found in renal tubules. The levels of high sensitivity C reactive protein (hs-CRP), D-Dimer (DD), CD19+CD23+ lymphocyte subsets, and urinary albumin to creatinine ratio (UMA/Cr) were significantly different among nondeposition group, mild deposition group and severe deposition group (P<0.01). The levels of hs-CRP and CD19+CD23+ in severe deposition groups were significantly higher than those in the mild and non-deposition groups (P<0.05). The level of D-D in the severe and mild deposition group was significantly higher than that in the non-deposition group (P<0.05). The UMA/Cr in the severe deposition group was significantly higher than that in the non-deposition group (P<0.05). Glomerular Fib deposition is positively correlated with IgA deposition (r=0.64, P<0.001). The proportion of glomerular IgG deposition among three groups was significantly different (P<0.05), and the proportion of IgG deposition in the severe group was the highest. Conclusions　When children had glomerular Fib deposition, especially in the case of severe Fib deposition and immune dysfunction, inflammatory response and hypercoagulability are more serious and renal function damage may be more serious.

Changes and significance of serum vitamin A levels in children with community-acquired pneumonia

　YOU Pei, LEI Houxing, WANG Shuanghu, DING Ting, FAN Huisu, LIN Jianjun, LYU Jianfei, LEI Wenfen, WANG Xiaoyu

. 2018, 36(3):  188.  doi:10.3969/j.issn.1000-3606.2018.03.007

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　Objective　To explore the changes and significance of serum vitamin A levels in children with community acquired pneumonia. Methods　A total of 80 children with community-acquired pneumonia (pneumonia group) were selected from October 2015 to March 2016 and were divided into Mycoplasma pneumoniae (MP) infection group, bacteria infection group, MP and bacteria mixed infection group (mixed infection group) according to different pathogens. Thirty healthy children in the same period were selected as the control group. The serum vitamin A concentration was detected by ultra-highperformance liquid chromatography-tandem mass spectrometry. Results　The level of serum vitamin A was (0.567±0.163) μmol/L in pneumonia group, (0.578±0.162) μmol/L in MP infection group, (0.557±0.153) μmol/L in bacteria infection group and (0.554±0.186) μmol/L in mixed infection group, and all of them were lower than that in control group (0.759±0.160) μmol/L, and there were significant differences (P<0.05). There was no difference in serum vitamin A level among MP infection group, bacteria infection group and mixed infection group (P>0.05). There was a significant difference in the distribution of vitamin A deficiency between pneumonia group and control group ( P<0.001). The proportion of suspected subclinical vitamin A deficiency in control group was higher, while vitamin A deficiency and subclinical vitamin A deficiency in pneumonia group were higher. Conclusions　The serum vitamin A level decreased in children with community-acquired pneumonia, But there was no significant differences in serum vitamin A levels among the children with pneumonia caused by different pathogens.

Analysis of the role of paroxysmal nocturnal hemoglobinuria clones in acquired aplastic anemia in children

　SHAO Huijiang, JI Zhenghua, MIAO Meihua, JI Xueqiang, SHAO Xuejun

. 2018, 36(3):  192.  doi:10.3969/j.issn.1000-3606.2018.03.008

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Objective　To analyze the role of paroxysmal nocturnal hemoglobinuria (PNH) clones in children with acquired aplastic anemia (AA). Methods　The relationship between the existence of PNH clones and clinical features in children with AA was retrospectively analyzed. The influence of PNH clones on the efficacy of combined immunosuppressive therapy (IST) of anti-thymocyte globuline (ATG) and cyclosporine A (CSA) was also observed. In addition, multiple factor analysis was used to analyze the main factors affecting the efficacy of AA. Results　One hundred and forty-eight children with AA were enrolled, including 74 cases (50%) of granulocyte PNH clones positive, 68 cases (45.9%) of monocyte PNH clones positive, and 93 cases (62.8%) of total PNH clones (granulocytes and / or monocytes) positive. In 49 children having both granulocytes and monocytes PNH clones, the clone size of monocytes and granulocytes was 0.7% (0.4%-1.5%) and 0.2% (0.1%-0.7%), respectively, and the difference was significant (P<0.001) and there was a significantly positive correlation between them (r=0.65, P<0.001). According to the different PNH positive clones (monocytes, granulocytes, total), children were divide into three groups. And there were no differences in gender, age, concurrent infection, white blood cell count, hemoglobin concentration, platelet count, neutrophil absolute count, reticulocyte percentage in different PNH clones positive and negative groups (P>0.05). The group with monocytes PNH clones positive had a positive effect on the efficacy of IST (P=0.02). Multiple factor logistic regression analysis showed that the concentrations of hemoglobin and the positive PNH clones of monocytes were the main factors affecting the efficacy (P<0.05). Conclusions　The high concentration of hemoglobin and the positive PNH clones of monocytes contribute the better effect of IST in children with AA.

Complex glycerol kinase deficiency: two case report and literature review

　FAN Rui, ZHANG Yining, LI Xiaoping, LU Feiyu, DU Hongwei

. 2018, 36(3):  197.  doi:10.3969/j.issn.1000-3606.2018.03.009

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　Objective　To explore the clinical and genetic characteristics of complex glycerol kinase deficiency (GKD). Methods　The clinical data of 2 cases of complex GKD were analyzed and the related literatures were reviewed. Results　Both cases were male onset in neonatal period, and had hypocorticalism (hyponatremia, hyperkalemia, dehydration), hypercreatine kinasemia, and pseudotriglyceridemia. Gene detection suggested that there was gene deletion in chromosome Xp21 region. In the follow-up, one case had good control of the disease and one died of infection. Conclusions　Complex GKD is an X-linked recessive hereditary disease. It is rare and complicated, and is easily misdiagnosed. Early diagnosis and treatment are beneficial to improve the prognosis.

Diagnosis and treatment of atypical severe combined immunodeficiency disease in 7 children

　HE Jianxin, CHEN Lanqin, ZHAO Yuhong, JIA Xinlei, LIU Gang, XU Baoping, LIU Xiuyun, GUI Jingang, SHEN Kunling, JIANG Zaifang

. 2018, 36(3):  202.  doi:10.3969/j.issn.1000-3606.2018.03.010

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　Objective　To explore the diagnosis and treatment of atypical severe combined immunodeficiency disease (SCID). Methods　The clinical data of atypical SCID in 7 children with IL2RG, JAK3, and RAG1 mutations were reviewed and analyzed from September 2012 to June 2017. Results　In 7 cases (6 males and 1 female), there were 5 infants, 1 toddler and 1 school-age child. Cases 2, 4, and 6 were classic SCID clinical phenotypes. Cases 1, 3, 5, 7 were atypical SCID clinical phenotypes. Case 6 were diagnosed with Omenn syndrome. Cases 2, 5 were classic SCID immune phenotypes, cases 1, 3, 4, 6, 7 were atypical SCID immune phenotypes, and case 1 had maternal chimera. The next generation sequencing indicated that case 1 had a compound heterozygous JAK3 mutation with c.3097-1G>A/ c.946-950GCGGA>ACinsGGT. Cases 2, 3, and 4 had IL2RG mutations, with c. 865C>T/ p.R289X, c.664C>T/R222C, 52delG, respectively. Case 5 had JAK3 mutations with c.2150A>G/p.E717G and c.1915-2A>G. Sanger sequencing indicated that case 6 had a RAG1 mutation of complex heterozygosity with c.994C>T/p.R332X and c.1439G>A/p.S480N. Case 7 had homozygous RAG1 mutation with c.2095C>T/p.R699W. Conclusion　Under certain conditions, gene mutation can lead to atypical clinical and/or immune phenotypic SCID.

The clinical characteristics and gene diagnosis of Rubinstein-Taybi syndrome

CHENG Yanyang, LIU Aojie, WEI Li, ZHANG Jing, XU Zhiliang

. 2018, 36(3):  207.  doi:10.3969/j.issn.1000-3606.2018.03.011

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Objective　To explore the clinical and genetic features of Rubinstein-Taybi syndrome (RSTS). Methods　The clinical data of 2 children with RSTS were reviewed and analyzed. Results　Two male children (3 years old and 4 months old) were admitted to hospital because of growth retardation. Both of them were characterized by short stature, language and motor retardation, excessive hairiness and cryptorchidism. Case 1 had slightly broad thumbs and toes, and case 2 had distinctive facial features of high arched palate, broad nasal bridge, ptosis, and obviously broad thumbs and toes. Cardiac dysplasia was found in both of them by echocardiography. The c.152T>G (L51X) heterozygous mutation was found in case 1 by high throughput sequencing and genomic chip technology, and this mutation has not been reported. Deletion of 2.5 Mb in chromosome 16p13.3 region was found in case 2. Conclusions　The main clinical manifestations of RSTS are excess hair, deformity of thumbs and toes, deformity of the heart development, and growth retardation. Molecular detection can help the clinical diagnosis.

Analysis of genetic defects in the 11p15.5 region in Russell-Silver syndrome

XIA Chaoran, YANG Yongchen, XU Wuhen, LU Zhaoning, WANG Wei

. 2018, 36(3):  210.  doi:10.3969/j.issn.1000-3606.2018.03.012

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　Objective　To explore the pathogenesis of Russell-Silver syndrome (RSS). Methods　Two milliliter peripheral blood samples were collected from 6 male patients aged 6 to 8 years with suspected RSS phenotype, the parents of 2 patients and 5 healthy boys. Mononuclear cells were isolated and genomic DNA was extracted. The methylation level of the H19 imprinting control region (ICR) 1 on chromosome 11p15.5 was detected by pyrosequencing. The methylation status and the copy number variation in the corresponding region of one RSS patient with positive results by pyrosequencing were analysed by methylation-specific multiplex-ligation-dependent probe amplification assay (MS-MLPA). Results　Pyrosequencing analysis revealed that the methylation rates on the 6 CpG targeting sites in H19 differentially methylated region (DMR) in the 6 RSS patients were about 11%~29%, which were significantly lower than those in their parents and normal controls (44%~59%). The MS-MLPA results of one patient with positive pyrosequencing showed that the methylation rates of 4 sites in H19-DMR were about 10%, which was obviously lower than the normal level. The methylation rates of the 4 sites in KCNQ1OT1 gene were about 50%, which was in the normal range. The copy number variations from all samples detected were in the normal range. Conclusion　There is methylation aberration of H19-DMR in ICR1 in children with RSS.

The clinical and genetic analysis of glycogen storage disease type IV in 5 cases

　FANG Di, QIU Wenjuan, YE Jun, HAN Lianshu, ZHANG Huiwen, YU Yongguo, LIANG Lili, GONG Zhuwen, YAN Hui, WANG Jianguo, GU Xuefan

. 2018, 36(3):  216.  doi:10.3969/j.issn.1000-3606.2018.03.013

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　Objective　To investigate the characteristics of glycogen storage disease type IV (GSD IV) clinically, in laboratory tests and in gene mutation. Methods　The clinical manifestations, biochemical indexes, activity of chitotriosidase, and the follow-up of the treatment in 5 cases of GSD IV were analyzed. Results　Five patients (3 boys and 2 girls) aged 4 months - 5 years presented hepatosplenomegaly and elevated liver enzyme levels for 2 months at hospital visit. Two patients had motor developmental delay and weakness but their creatine kinase (CK) level were normal. Glycogen storage and liver fibrosis were observed in the liver biopsy in 4 patients. Target sequencing found that all 5 children carried the complex heterozygous mutation of the GBE1 gene with 2 reported mutations (p.R515C, p.R524Q) and 7 novel mutations. The novel mutation contains 5 missense mutations (p.I460T, p.F76S, p.F538V, p.L650R, p.W455R), one insertion mutations (c.141_142insGCGC), and one large fragment deletion (exon 3-7). Therefore, diagnosis of liver type of GSD IV was confirmed in those children. Two patients died of liver cirrhosis. The liver transplantation was performed due to liver cirrhosis in one patient whose chitotriosidase activity increased obviously before transplantation and decreased significantly after the transplantation and liver enzyme levels were returned to normal 4 months after transplantation. In the other two patients their growth and liver enzyme levels were normal; one had not received special treatments while the other was treated with raw corn starch and level of chitotriosidase was normal. Conclusions　The clinical manifestations of GSD IV are heterogeneous. Target sequencing can be used for fast and noninvasive diagnosis of GSD IV. Chitotriosidase activity is useful in the prognosis assessment for GSD IV.

Research progress in laboratory detection of cytomegalovirus and its feasibility analysis for neonatal screening

WANG Han, LI Tingdong, GUO Xiaoyi

. 2018, 36(3):  221.  doi:10.3969/j.issn.1000-3606.2018.03.014

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　Most of the human cytomegalovirus (HCMV) infection has no obvious clinical symptoms, but it can be latent for life and activated under specific conditions. HCMV active infection during pregnancy can lead to abortion, stillbirth, birthdefect and so on, which causes serious economic and social burdens. Both primary and secondary HCMV infection can lead to congenital infection of newborn, but there is still no effective method for the screening of HCMV secondary infection during pregnancy currently. Therefore, a comprehensive congenital HCMV screening for newborns is implemented for early intervention and thus reducing the consequences of congenital HCMV infection. In this paper, the methods of HCMV laboratory detection and its feasibility for neonatal screening are analyzed, in order to provide a basis for the selection of methods in neonatal congenital HCMV screening.

Correlation between ABCA3 and Pediatric Pulmonary Disease

YUE Xiaofei

. 2018, 36(3):  227.  doi:10.3969/j.issn.1000-3606.2018.03.015

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　Pulmonary surfactant is a lipid-protein complex that lines and stabilizes the respiratory interface in the alveoli, allowing for gas exchange during the breathing cycle. ATP-binding Cassette transporters A3, is a lipid transporter in the limiting membrane of lamellar bodies in alveolar type Ⅱ cells that plays a critical role in the regulation of pulmonary surfactant homeostasis.  Mutations in the ABCA3 gene cause respiratory distress syndrome in new-born and childhood interstitial lung disease.  An updated view on expression of ABCA3 gene and ABCA3 mutation associated with neonatal respiratory distress syndrome,or childhood interstitial lung disease was reviewed.

Advances in research of the pathogenesis of norovirus

ZHU Jing, XIONG Wan

. 2018, 36(3):  231.  doi:10.3969/j.issn.1000-3606.2018.03.016

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Norovirus is one of the main pathogens causing nonbacterial gastroenteritis in infants and young children. Clinical symptoms in norovirus infection include nausea, vomiting, diarrhea, abdominal pain among which vomiting is obvious. Due to the lack of effective research models, the pathogenesis of Norovirus infection is still unclear. This article focuses on the progress in research of the pathogenic mechanism of Norovirus, and mainly discusses the cell phagocytosis and immune response.