[Advances in application of Jurkat cell model in research on infectious diseases].

Infectious diseases can be caused by multiple pathogens, which can produce specific immune response in human body. The immune response produced by T cells is cellular immunity, which plays an important role in the anti-infection process of human body, and can participate in immunological protection and cause immunopathology. The outcome of various infectious diseases is closely related to cellular immune function, especially the function of T cells. Jurkat cells belong to the human acute T lymphocyte leukemia cell line. Jurkat cell model can simulate the function T lymphocytes, so it is widely used in the in vitro studies of T cell signal transduction, cytokines, and receptor expression, and can provide reference and guidance for the treatment of various infectious diseases and the research on their pathogenesis. The Jurkat cell model has been widely used in the in vitro studies of viral diseases and atypical pathogens, but parasitic infection studies using the Jurkat cell model are still rare. This article reviews advances in the application of Jurkat cell model in the research on infectious diseases.

[Role of programmed death-1 in viral infectious diseases].

The research on the immunoregulatory effect of programmed death-1 (PD-1) in infectious diseases mainly focuses on chronic viral infection, but there are few studies on acute viral infection. In chronic viral infection, PD-1 is highly expressed on the surface of CD8+ T cells, which is a sign of CD8+ T cell depletion. Recent studies have shown that in chronic viral infection, PD-1 is also highly expressed on the surface of regulatory T cells and binds to programmed death-ligand 1 (PD-L1) on the surface of exhausted CD8+ T cells, resulting in a stronger inhibitory effect on CD8+ T cell immunity. Blocking the PD-1/PD-L1 signaling pathway between exhausted CD8+ T cells and regulatory T cells can significantly reverse the depletion of CD8+ T cells and greatly improve the antiviral effect of CD8+ T cells. However, the role of the PD-1/PD-L1 signaling pathway in acute viral infection remains unknown. This article summarizes the latest research on PD-1 in infectious diseases and discusses its role in acute and chronic viral infection.

[Expression and role of Tc17 cells in mice with neutrophilic asthma].

OBJECTIVE: To determine the proportion of Tc17 cells in the lungs of mice with neutrophilic(NEU) asthma, and to investigate the role of Tc17 cells in the pathogenesis of NEU asthma. METHODS: Thirty-two C57/B6 mice of clean grade were randomly divided into two groups: NEU asthma and control. The mice in the NEU asthma group were sensitized by airway instillation of ovalbumin (OVA) and lipopolysaccharide (LPS), and challenged with an aerosol of OVA, while those in the control group were sensitized and challenged with normal saline. At 24 hours after the final challenge, bronchoalveolar lavage fluid (BALF) was collected, and the total number and differential counts of nucleated cells and percentage of each type were determined. The lung tissues were separated and hematoxylin-eosin staining was performed to observe the pathological changes of lungs; flow cytometry was applied to determine the percentages of Tc17 and Th17 cells in the lung tissues. Enzyme-linked immunosorbent assay was applied to determine the levels of interleukin-6 (IL-6), transforming growth factor β (TGF-β), and interleukin-17 (IL-17) in BALF. RESULTS: The NEU asthma group had a significantly higher total number of nucleated cells, a significantly higher percentage of eosinophils, and a significantly higher percentage of neutrophils in BALF than the control group (P<0.01). The NEU asthma group also had significantly higher percentages of Tc17 and Th17 cells than the control group (P<0.01). In the NEU asthma group, the percentage of Tc17 cells was positively correlated with that of Th17 cells (P<0.05). The NEU asthma group had significantly higher concentrations of IL-6, TGF-β, and IL-17 in BALF than the control group (P<0.05). CONCLUSIONS: The expression of Tc17 cells in the lung tissues increases in mice with NEU asthma, and the increased number of Tc17 cells may be involved in the pathogenesis of NEU asthma. Tc17 cells may play an important role in NEU asthma through IL-17.

Leukotriene receptor antagonists for small-airway abnormalities in asthmatics: a systematic review and meta-analysis.

BACKGROUND: Airway inflammation that occurs in asthma is mainly distributed in the small airways. Leukotriene receptor antagonists (LTRAs) are systemically active drugs that may act on the small airways. OBJECTIVES: The aim of our study was to assess the efficacy of LTRAs for small-airway abnormalities in asthmatics. METHODS: We searched the databases of Cochrane Central, MEDLINE, and EMBASE from the time of the establishment of the databases to December 2012. The data were extracted using a pooled mean difference (MD) or standardized mean difference (SMD) with a 95% confidence interval (CI). RESULTS: Eight studies were included. The outcomes were the conventional parameters for the detection of small-airway abnormalities. Eight studies were included. The outcomes were the conventional parameters for the detection of small-airway abnormalities. LTRAs compared to placebo improved small-airway abnormalities, as indicated by a number of radiological and physiological parameters, such as lung attenuation (MD, 61.00; 95% CI, 26.32 to 95.68) and residual volume (SMD, -0.85; 95% CI, -1.29 to -0.42). Conventional inhaled corticosteroids (ICSs) compared to LTRAs improved small-airway abnormalities, as indicated by the reactance area (p = 0.028). Compared with conventional treatment alone, a combination of LTRAs and conventional treatment improved small-airway abnormalities, as indicated by a number of radiological and physiological parameters, such as airway wall thickness (p < 0.05), alveolar nitric oxide concentration (p = 0.04), a decrease in resistance from 5 to 20 hertz (p = 0.032), reactance area (p = 0.014), eosinophil cationic protein levels (p = 0.045) and number of eosinophils (p = 0.035) in the late-phase induced sputum. However, there was no significant improvement in forced expiratory flow between 25% and 75% of forced vital capacity in any of the comparisons. CONCLUSIONS: LTRAs may improve most of the conventional parameters for the detection of small-airway abnormalities in asthmatics. However, there is no evidence of the superiority of LTRAs over ICSs in improving functional parameters related to the small airways.

[Causes of chronic cough in children: an analysis of 111 cases].

OBJECTIVE: To investigate the causes of chronic cough in children. METHODS: A prospective cohort study was performed on 111 children with chronic cough who were referred to the First Affiliated Hospital of Guangxi Medical University between December 2008 and January 2011. The causes of chronic cough were investigted. RESULTS: Cough variant asthma (45 cases, 40.5%) was the most common cause of chronic cough, followed by upper airway cough syndrome (34 cases, 30.6%), postinfectious cough (19 cases, 17.1%), allergic cough (5 cases, 4.5%), Tourette's syndrome (4 cases, 3.6%), psychogenic cough (1 case, 0.9%) and endobronchial tuberculosis (1 case, 0.9%). The causes were not identified in 2 cases (1.8%). A single cause for chronic cough was noted in 60 patients (54.1%), and multiple potential causes were noted in 49 patients (44.1%), including two coexisting causes in 47 patients (42.3%) and three in 2 patients (1.8%). CONCLUSIONS: The top three causes of chronic cough in children are cough variant asthma, upper airway cough syndrome and postinfectious cough.

Geleophysic dysplasia caused by a mutation in FBN1: A case report.

BACKGROUND: Geleophysic dysplasia (GD) presents the characterized clinical manifestations of acromelic dysplasia, including extremely short stature, short limbs, small hands and feet, stubby fingers and toes, joint stiffness and others. It is clinically distinct from the other acromelic dysplasia in terms of symptoms such as cardiac valvular abnormalities, progressive hepatomegaly and tracheal stenosis. CASE SUMMARY: We report on a Chinese 9-year-old girl with GD with the c.5243G>T (p.C1748F) mutation in FBN1 (fibrillin 1, OMIM 134797). She was born in Guangxi Zhuang Autonomous Region of China. The patient presented with typical clinical features of GD and recurrent respiratory tract infections over 6 years. Laboratory studies and chest computed tomography (CT) scan indicated bronchopneumonia. Her echocardiography revealed mild mitral valve thickening with regurgitation. Laryngopharyngeal CT and electronic bronchoscopy revealed severe glottic stenosis. Echocardiography examination displayed mild mitral valve thickening and regurgitation. Ophthalmic examination did not reveal myopia or lens dislocation. Treated with ceftriaxone sodium and methylprednisolone sodium succinate for injection as well as methylprednisolone orally, patient's symptoms had improved. CONCLUSION: GD is a rare genetic condition that can cause life-threatening cardiovascular and respiratory problems. This study also found that the identified genotype of GD could be related to different clinical phenotypes.

Efficacy and safety of interferon α-2b spray for herpangina in children: A randomized, controlled trial.

OBJECTIVES: The treatment of acute herpangina is inconsistent. We aim to evaluate the effectiveness and safety of interferon α-2b spray versus Ribavirin for this disease. METHODS: A randomized, controlled trial was conducted in eight hospitals in China between 2016 and 2018. 668 patients (1-7 years old) were randomized into an experimental group (treated with Interferon α-2b spray) or control group (received Ribavirin Aerosol). Body temperature returning to normal within 72 h and remaining so for 24 h was the primary outcome; release of oral herpes and adverse events were the secondary outcomes. RESULTS: (1) The average age of onset was 2.5 years old. (2) After 72 h treatment, body temperature of 98.5% patients in experimental group and 94.3% in control group returned to normal and remained so for 24 h (P = 0.004). The differences were greater at 48 h treatment (95.2% vs. 85.9%, P < 0.001) and at 24 h (77.5% vs. 66.5%, P = 0.001). (3) The rate of improved oral herpes in the experimental group was higher than that in control group (46.7% vs.37.1%, P = 0.011). No adverse reaction occurred. CONCLUSIONS: Local application of recombinant interferon α-2b spray showed better efficacy for acute herpangina in children. It was safe for use.

[Primary immunodeficiency diseases in children: clinical analysis of 35 cases].

OBJECTIVE: To summarize clinical features of primary immunodeficiency diseases (PID) in children. METHODS: The clinical data of 35 children with PID from September 2005 to December 2008 were studied retrospectively, including illness history, birth history, family history, clinical manifestations, laboratory findings, diagnosis, treatment and outcome. RESULTS: Of the 35 cases of PID, 6 cases were confirmed with combined T- and B-cell immunodeficiency, 4 cases with X-linked agammaglobulinaemia, 22 cases with selective IgG subclass deficiency, 1 case with common variable immunodeficiency and 2 cases with chronic granulomatous disease. All cases had fever and recurrent infections. Respiratory and digestive tract infections were the most common clinical manifestation. Some of the PID cases lagged behind the normal children of the same age in growth and development. Human gamma-globulin transfusion and anti-infection therapy were administered. Two patients discontinued the therapy, one was transferred to the other hospital and the other 32 patients were discharged following improvement in clinical symptoms. CONCLUSIONS: PID should be considered in children who suffer from recurrent infections and autoimmune diseases or do not respond to long-term use of antibiotics. Immunologic tests should be done as early as possible for the children.

Update on protracted bacterial bronchitis in children.

BACKGROUND: Chronic cough is a common symptom in children and protracted bacterial bronchitis (PBB) is one of the causes of chronic cough. However, the understanding of this disease remains limited. The present study aims to update PBB in children. METHODS: The clinical data of children with PBB from 2014 to 2018 were retrospectively analyzed, and PBB clinical features of published studies were summarized. Electronic databases were searched in May 2019. Clinical studies were included in the present study. Reviews were undertaken in duplicate. RESULTS: Totally 712 cases were analyzed in this study, including 52 cases in our center and 660 cases from 14 studies. In the 52 cases, 88.5% of patients with PBB were less than 6 years old and all of them complained of wet cough. Three cases were confirmed with laryngomalacia, and microbiologically-based-PBB were identified in 13 cases (9 Streptococcus pneumonia, 3 Staphylococcus aureus, and 1 Pseudomonas aeruginosa). Twenty cases were completely remitted after treatment. In the 14 studies, the patients with PBB were typically younger than 3 years old, accompanying wheezing and airway malacia. Co-infection was common in most western cases, Streptococcus pneumonia, Haemophilus influenza and Moraxella catarrhalis were the top three pathogens. Symptoms were improved in most patients, whereas some cases with comorbidities required prolonged antibiotics treatment. CONCLUSIONS: PBB is common in male infants with chronic wet cough and accompanied by wheezing and airway deformities. Most cases are clinically diagnosed PBB in China and microbiologically-based-PBB is common in western countries. Co-infection could be found, Streptococcus pneumoniae and Haemophilus influenza were the most frequent etiology in China and western countries, respectively. Patients with comorbidities may need extended antibiotics treatment for more than 2 weeks.

Diffuse alveolar hemorrhage with histopathologic manifestations of pulmonary capillaritis: Three case reports.

BACKGROUND: Diffuse alveolar hemorrhage (DAH) is a multicause pulmonary capillary hemorrhage or pulmonary vascular small vessel injury (mainly capillaries, including arteries and veins), causing pulmonary microcirculation blood to accumulate in the alveolar space. DAH is classified by the histological absence or presence of pulmonary capillaritis (PC) and is rarely reported in the literature. CASE SUMMARY: This is a report of three girls aged 6-11 years with DAH and PC. Two patients had decreased hemoglobin and one had increased erythrocyte sedimentation rate. High-resolution computed tomography showed bilateral diffuse pulmonary infiltrate, and diagnosis of PC was confirmed by lung biopsy. Immunofluorescence test in one case showed granular IgG and a small amount of granular IgA deposit on the alveolar walls, and was negative in the other two cases, describing isolated pauci-immune PC. Treatment was with glucocorticoid alone or combination with immunosuppressants, and the symptoms resolved in all patients. CONCLUSION: PC is classified as isolated and immune-mediated PC associated with systemic disease. It can be controlled in most children with glucocorticoid alone or combined with immunosuppressants.

Diagnosis and treatment of herpangina: Chinese expert consensus.

BACKGROUND: Herpangina is a common infectious disease in childhood caused by an enterovirus. This consensus is aiming to standardize and improve herpangina prevention and clinical diagnosis. METHODS: The Subspecialty Group of Infectious Diseases, the Society of Pediatric, Chinese Medical Association and Nation Medical Quality Control Center for Infectious Diseases gathered 20 experts to develop the consensus, who are specialized in diagnosis and treatment of herpangina. RESULTS: The main pathogenic serotypes of herpangina include Coxsackievirus-A, Enterovirus-A and Echovirus. Its diagnosis can be rendered on the basis of history of epidemiology, typical symptoms, characteristic pharyngeal damage and virological tests. The treatment is mainly symptomatic, and incorporates topical oral spray with antiviral drugs. The course of herpangina generally lasts 4-6 days with a good prognosis. CONCLUSION: The consensus could provide advices and references for the diagnosis, treatment and management of herpangina in children.

Clinical features for 89 deaths of hand, foot and mouth disease in Guangxi, China, 2014.

OBJECTIVES: The aim of this study is to summarize the risk factors of severe Hand, foot and mouth disease (HFMD) and explore the clinical characteristics of pulmonary edema (PE) and non-PE in the deceased patients with HFMD. METHODS: We identified 89 HFMD deaths which were separated into the PE group or non-PE group. Next, patients were divided based on their initial admission to hospitals as stage 1, 2, 3, or 4; at this point, their clinical manifestations were compared. RESULTS: There were 87 cases in the PE group, and 2 cases in the non-PE group. In the PE group, the difference in median time for patients at different stages from onset to symptoms, showed no significant difference (p>0.05). The etiology was detected as a positive rate for enterovirus 71 (EV71) of 89.19%, which showed a more severe course than other etiologies. The white blood cell (WBC) counts, lymphocyte (LYM) counts and creatine kinase MB (CK-MB) counts of patients admitted in different stages increased significantly with severity (p<0.05). CONCLUSIONS: There may be two clinical subtypes, mostly PE and rarely non-PE, in the deceased patients with HMFD. EV71 and risk factors such as an increased WBC count are associated with a severe course of HMFD.

Addressing parental smoking in pediatric settings of chinese hospitals: a qualitative study of parents.

This study explored factors associated with SHS exposure from parental smoking in Chinese families and assessed nature of antismoking discussions parents had with their children's pediatricians and how pediatricians might best engage with parents in an effort to reduce children's exposure to SHS. Six focus group discussions (FGDs) were conducted among 33 Chinese parents attending six major hospitals in Guangxi province, China. Most participants (32/33) had family members who smoke, and only 21% had strict restriction on smoking at home. Some parents did not know about health consequences of smoking and effects of SHS exposure on children. Situations that made it especially hard to avoid the child's SHS exposure were having an elderly smoker at home and having a visitor who smoked. Only few parents were asked by pediatricians about child's exposure to SHS at home, but only when child's illness was related to smoking. Parents believed that suggestions coming from pediatricians about smoke-free home and parental quitting would be acceptable to parents and other household members. The findings provide insight into SHS exposure reduction effort among Chinese parents and underscore the demand for pediatrician's engagement in addressing parental tobacco use.

[Pulmonary surfactant associated gene variants in mixed ethnic population of Han and Zhuang].

OBJECTIVE: To explore the prevalence of pulmonary surfactant associated pathway genes functional variants in Chinese population. METHOD: Using a cohort of 258 mixed ethnic population of Han and Zhuang, we pooled DNA samples from 146 term male infants and 112 term female infants and then used an Ill umina next generation sequencing platform to perform the complete exonic resequencing in 6 target genes:surfactant protein-B (SFTPB), surfactant protein-C (SFTPC), ATP-binding cassette transporter A3 (ABCA3), lysophospholipid acyltransferase 1 (LPCAT1), choline phosphotransferase 1 (CHPT1), phosphate cytidylyltransferase 1, choline, beta (PCYT1B). Collapsing methods was used to determine the functional allele frequency. RESULT: (1) Altogether, 128 variants were found, including 44 synonymous variants, 66 nonsynonymous variants and 18 insertions-deletions. Of these, 28 variants were predicted to alter protein function. Two of these variants were seen twice, the rest variants were only seen once, for a total of 30 functional alleles; (2) ABCA3 had the most functional variants in both male and female groups with the minor allele frequencies of 0.014 (1.4%) and 0.04 (4%), respectively. The total functional allele frequencies of 6 genes were 0.041 (4.1%) and 0.08 (8%) in the two groups, respectively (P = 0.06). CONCLUSION: (1) Functional variants in pulmonary surfactant associated pathway genes are present in the mixed Han-Zhuang population. (2) ABCA3 contained the most functional variants suggesting that ABCA3 could contribute significantly to neonatal respiratory distress syndrome and other lung disease.

[Airway neutrophils apoptosis in children with severe asthma].

OBJECTIVE: To investigate the changes of neutrophils in airway inflammation in children with severe asthma. METHOD: Children with mild to moderate asthma (n=23), severe asthma (n=16) and healthy control subjects (n=16) underwent lung function tests and sputum induction. The sputum specimens were assayed for cellular differential count, the supernatant and peripheral blood were assayed for the concentrations of IL-8 by "sandwich" enzyme linked immunosorbent assay (ELISA). Sputum supernatant, IL-8 and mifepristone were assessed for their abilities to prolong the in vitro survival of blood-derived neutrophils. RESULT: The percentage of sputum neutrophils was significantly higher in severe asthmatics [59.54 (41.99-74.65)%] than mild-moderate asthmatics [30.03 (15.94-47.71)%] and healthy control subjects [29.72(16.53-45.74)%] (P < 0. 01); the level of IL-8 in sputum was significantly higher in severe asthmatics [2907.78 (331.67 - 3457.93) ng/L] than mild-moderate asthmatics [287.58 (130.75-656.84) ng/L] and healthy control subjects [179.2 (58.55-346.59) ng/L] (P < 0.01); the percentages of neutrophilic apoptosis respectively cultured with LPS [(10.57 +/- 1.97)%], severe asthmatics supernatant [(11.82 +/- 2.96)%], IL-8 [(10.47 +/- 1.93)%], dexamethasone [(9.93 +/- 1.95)%], severe asthma supernatant + mifepristone [(12.15 +/- 2.86)%] in vitro were lower than that cultured with PBS [(17.98 +/- 2.27)%], healthy control supernatant [(17.37 +/- 2.50)%], mild-moderate asthmatics supernatant [(16.35 +/- 3.26)%], mifepristone [(17.89 +/- 2.38)%], and dexamethasone + mifepristone [(17.06 +/- 2.59)%] (P < 0.01). CONCLUSION: Suppression of neutrophilic apoptosis seems to play a potential role in airway neutrophilic inflammation in severe asthmatics, and the level of IL-8 in sputum was significantly higher in patients with severe asthmatics.

[Eosinophils apoptosis in asthmatic children].

UNLABELLED: Prominent eosinophil airway inflammation is important in the pathogenesis of asthma. There is increasing evidence that the disorder of eosinophil apoptosis contributes to the mechanism. But most of the studies have been done in vitro or on animal models, very few were done among the adult asthmatics in vivo. OBJECTIVE: The aim of this study was to elucidate the relationship between the apoptotic eosinophils and Bcl-2 in asthmatic children in vivo. METHODS: Eleven mild to moderate asthmatic patients were recruited and the range of age was 7 - 14 years (9 males, 2 females), meanwhile 7 patients with lower respiratory infection were recruited as control and the range of age was 9 - 14 years (5 males, 2 females). Before and after inhaled glucocorticoid (GC) induced sputum, bronchoalveolar lavage (BAL), bronchial mucosa specimens and peripheral blood were obtained for measuring and comparing the changes of apoptotic EG(2)(+) cell by combining the techniques of TUNEL and immunohistochemistry, meanwhile the expression of Bcl-2 in bronchial mucosa specimens was measured by using the immunohistochemical assay. RESULTS: Before the inhalation of GC, the apoptotic EG(2)(+) cells in asthmatics were significantly lower than that in control group (P < 0.01), and the numbers of EG(2)(+) cell in asthmatics group were significantly higher than that in control group (P < 0.001). After the treatment apoptotic EG(2)(+) cells in asthmatics were increased (P < 0.01), and the numbers of EG(2)(+)cell were decreased (P < 0.01, P < 0.05 and P < 0.05, respectively), FEV(1)% was increased (P < 0.05). Before the inhalation of GC, the numbers of Bcl-2(+) cell in asthmatic airway submucosa were higher than that in control group (P < 0.05) but after the treatment the number of Bcl-2(+) cell did not change significantly. (4) Before and after GC treatment the percentages of apoptotic eosinophils of peripheral blood in vivo had no significant changes compared with those of control subjects (P > 0.05). There was a positive correlation between apoptosis of EG(2)(+) cell in sputum, BAL, airway submucosa and FEV(1)% (P < 0.05). CONCLUSION: Apoptosis of EG(2)(+) cell decreased in the airway of asthmatic children and inducing EOS apoptosis is one of the important mechanism of inhaled GC therapy for asthma.