Food-dependent,exercise-induced anaphylaxis(FDEIA)is a potentially life-threatening disorder that often occurs with exercise,and patients typically have eaten a specific food within hours before disease onset.This dis...Food-dependent,exercise-induced anaphylaxis(FDEIA)is a potentially life-threatening disorder that often occurs with exercise,and patients typically have eaten a specific food within hours before disease onset.This disease is exceedingly rare,with a prevalence of 0.02%.No well-recognized prevention or treatment strategy has been available for FDEIA except avoiding triggers strictly.Here we report an 11-year-old boy with a history of recurrent anaphylaxis of unknown etiology more than 10 times within two years.As the anaphylactic symptoms had not been controlled after traditional treatments,the patient was given subcutaneous injection of dupilumab seven times within 33 weeks.During dupilumab treatments,the patient was exposed to culprit mushrooms plus exercises at least twice a month but without notable anaphylaxis.Thus,dupilumab may improve the allergic reactions in FDEIA patients.展开更多
During the course of chronic hepatitis C virus(HCV)infection,various extrahepatic manifestations of autoimmune disorders may occur,including arthralgia/arthritis,sicca complex,purpura,cutaneous ulcer,and thyroid dysfu...During the course of chronic hepatitis C virus(HCV)infection,various extrahepatic manifestations of autoimmune disorders may occur,including arthralgia/arthritis,sicca complex,purpura,cutaneous ulcer,and thyroid dysfunction.In addition,the prevalence of circulating autoantibodies is high among patients with HCV infection.Commonly detected autoantibodies in HCVinfected patients include rheumatoid factor,antinuclear antibody,anti-SSA/anti-SSB antibody,cryoglobulin,antineutrophil cytoplasmic antibody,anti-smooth muscle antibody,anti-liver and anti-thyroid autoantibodies.These autoantibodies may be associated with underlying autoimmune disorders or liver inflammation in HCV infection.A possible reason for antibody production is overactivation and proliferation of B lymphocytes,via the interaction with the surface protein of HCV.Because immunotherapy can cause HCV flare-up or liver damage,overdiagnosis of HCV-related autoimmune symptoms as primary autoimmune disorders should be avoided.This review describes biomarkers that are useful in clinically evaluating autoimmune manifestations and disorders associated with HCV infection.展开更多
OBJECTIVE: Anti-asthma herbal medicine intervention (ASHMITM), a combination of three tradi- tional Chinese medicinal herbs developed in our laboratory, has demonstrated efficacy in both mouse models of allergic as...OBJECTIVE: Anti-asthma herbal medicine intervention (ASHMITM), a combination of three tradi- tional Chinese medicinal herbs developed in our laboratory, has demonstrated efficacy in both mouse models of allergic asthma, and a double-blind placebo-controlled clinical trial in patients with asthma. This study was designed to determine if the anti-inflammatory effects of individual herbal constituents of ASHMITM exhibited synergy. METHODS: Effects of ASHMI and its components aqueous extracts of Lingzhi (Ganoderma lucidum), Kushen (Sophora flavescens) and Gancao (Glycyrrhiza uralensis), on Th2 cytokine secretion by murine memory Th2 cells (D10.G4.1) and eotaxin-1 secretion by human lung fibroblast (HLF-1) cells were determined by measuring levels in culture supernatants by enzyme- linked immunosorbent assay. Potential synergistic effects were determined by computing interaction indices from concentration-effect curve parameters. RESULTS: Individual Lingzhi, Kushen and Gancao extracts and ASHMI (the combination of individual extracts) inhibited production of interleukin (IL)-4 and IL-5 by murine memory Th2 cells and eotaxin-1 production by HLF-1 cells. The mean 25%-inhibitory-concentration (IC2s) values (mg/mL) forASHMI, Lingzhi, Kushen and Gancao for IL-4 production were 30.9, 79.4, 123, and 64.6, respectively; for IL-5 production were 30.2, 263, 123.2 and 100, respectively; for eotaxin-1 were 13.2, 16.2, 30.2, and 25.1, respectively. The IC50values (mg/mL) for ASHMI, Lingzhi, Kushen and Gancao for IL-4 production were 158.5, 239.9, 446.7, and 281.8, respectively; for eotaxin-1 were 38.1, 33.1, 100, and 158.5, respectively. The interaction indices of ASHMI constituents at IC25 were 0.35 for IL-4, 0.21 for IL-5 and 0.59 for eotaxin-l. The interaction indices at IC^0 values were 0.50 for IL-4 and 0.62 for eotaxin-1 inhibition. Inhibition of IL-5 did not reach IC^0 values. All interaction indices were below 1 which indicated synergy. CONCLUSION: By comparing the interaction index values, we find that constituents in ASHMITM synergistically inhibited eotaxin-1 production as well as Th2 cytokine production.展开更多
Objective This study aimed to compare and analyze the clinical efficacy and safety of late-course and simultaneous integrated dose-increasing intensity-modulated radiation therapy(IMRT) for cervical cancer complicated...Objective This study aimed to compare and analyze the clinical efficacy and safety of late-course and simultaneous integrated dose-increasing intensity-modulated radiation therapy(IMRT) for cervical cancer complicated with pelvic lymph node metastasis. Methods Sixty patients with cervical cancer complicated with pelvic lymph node metastasis who were admitted to our hospital from January 2013 to January 2015 were enrolled. The patients were randomly divided into the late-course dose-increasing IMRT group and the simultaneous integrated dose-increasing IMRT group, with 30 cases included in each group, respectively. All patients were concurrently treated with cisplatin. After treatment, the clinical outcomes of the two groups were compared. Results The remission rate of symptoms in the simultaneous integrated dose-increasing IMRT group was significantly higher than that in the late-course dose-increasing IMRT group(P < 0.05). The follow-up results showed that the overall survival time, progression-free survival time, and distant metastasis time of patients in the simultaneous integrated dose-increasing IMRT group were significantly longer than those in the late-course dose-increasing IMRT group(P < 0.05). The recurrent rate of lymph nodes in the radiation field in the simultaneous integrated dose-increasing IMRT group was significantly lower(P < 0.05) than in the late-course dose-increasing IMRT group. There was no significant difference in the incidence of cervical and vaginal recurrence and distant metastasis between the two groups(P > 0.05). The radiation doses of Dmax in the small intestine, D1 cc(the minimum dose to the 1 cc receiving the highest dose) in the bladder, and Dmax in the rectum in the simultaneous integrated dose-increasing IMRT group were significantly lower(P < 0.05) than in the late-course dose-increasing IMRT group. There was no significant difference in intestinal D2 cc(the minimum dose to the 2 cc receiving the highest dose) between the two groups(P > 0.05). The incidence of bone marrow suppression in the simultaneous integrated dose-increasing IMRT group was significantly lower(P < 0.05) than in the late-course dose-increasing IMRT group.Conclusion The application of simultaneous integrated dose-increasing IMRT in the treatment of cervical cancer patients complicated with pelvic lymph node metastasis can significantly control tumor progression, improve the long-term survival time, and postpone distant metastasis time with high safety.展开更多
AIM: To investigate the role of O-GIcNAcylation of nuclear factor-kappa B (NF-KB) in retinal ganglion cell (RGC) death and analysedthe effect of Aralia elata (AE) on neurodegen- eration in diabetic mice. METH...AIM: To investigate the role of O-GIcNAcylation of nuclear factor-kappa B (NF-KB) in retinal ganglion cell (RGC) death and analysedthe effect of Aralia elata (AE) on neurodegen- eration in diabetic mice. METHODS: C57BL/6mice with streptozotocin-induced diabetes were fed daily with AE extract or control (CTL) diet at the onset of diabetes mellitus (DM). Two months af- tar injection of streptozotocin or saline, the degree of cell death and the expression of O-GIcNAc transferase (OGT), N-acetyl-b-D-glucosaminidase (OGA), O-GIcNAcylated pro- teins, and O-GIcNAcylation of NF-KB were examined. RESULTS: AE did not affect the metabolic status of diabetic mice. The decrease in the inner retinal thickness (P〈0.001 vs CTL, P〈0.01 vs DM) and increases in RGCs with terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (P〈0.001 vs CTL, P〈0.0001 vs DM), glial activation, and active caspase-3 (P〈0.0001 vs CTL, P〈0.0001 vs DM) were blocked in diabetic retinas of AE extract-fed mice. Expression levels of protein O-GIcNAcylation and OGT were increased in diabetic retinas (P〈0.0001 vs CTL), and the level of O-GIcNAcylation of the NF-KB p65 subunit was higher in diabetic retinas than in controls (P〈0.0001 vs CTL). AE extract downregulated O-GIcNAcylation of NF-KB and prevented neurodegeneration induced by hyperglycemia (P〈0.0001 vs DM). CONCLUSION: O-GIcNAcylation of NF-KB is concerned in neuronal degeneration and that AE prevents diabetes-in- duced RGC apoptosis via downregulation of NF-KB O-GI- cNAcylation. Hence, O-GIcNAcylation may be a new object for the treatment of DR, and AE may have therapeutic pos- sibility to prevent diabetes-induced neurodegeneration.展开更多
Objective To compare intra-pleural injection efficacy and safety between Endostar and bevacizumab combined with pemetrexed/cisplatin for the treatment of malignant pleural effusion in patients with epidermal growth fa...Objective To compare intra-pleural injection efficacy and safety between Endostar and bevacizumab combined with pemetrexed/cisplatin for the treatment of malignant pleural effusion in patients with epidermal growth factor receptor(EGFR)-/anaplastic lymphoma kinase(ALK)-lung adenocarcinoma. Methods Sixty-four pCVatients with EGFR-/ALK-lung adenocarcinoma with malignant pleural effusion(MPE) were admitted to the authors' hospital between January 2016 and June 2017. Patients were randomly divided into two groups: Endostar combined with pemetrexed/cisplatin(Endostar group); and bevacizumab plus pemetrexed/cisplatin(Bevacizumab group). They underwent thoracic puncture and catheterization, and MPE was drained as much as possible. Both groups were treated with pemetrexed 500 mg/m^2, intravenous drip(d1), cisplatin 37.5 mg/m^2 per time, intra-pleural injection(d1, d3). Patients in the Endostar group were treated with Endostar 30 mg per time, intra-pleural injection(d1, 3), and patients in the Bevacizumab group were treated with bevacizumab 5 mg/kg per time, intra-pleural injection(d1). Only one cycle of treatment was applied. MPE was extracted before treatment and on day 7 after treatment. The levels of vascular endothelial growth factor(VEGF) were determined using ELISA. Efficacy and side effects were evaluated according to the Response Evaluation Criteria in Solid Tumors(RECIST) version 1.1, and National Cancer Institute Common Terminology Criteria for Adverse Events(CTCAE) version 3.0 criteria. Results The objective response rates in the Endostar and Bevacizumab groups were 50.0% and 56.3%, respectively; there was no statistical difference between the groups(P > 0.05). After one cycle of treatment, the mean VEGF levels in MPE in both groups decreased significantly, and there was no significant difference in the degree of decline between the two groups(P > 0.05). In both groups, pre-treatment VEGF levels for patients achieving complete response were significantly higher than those for patients achieving stable disease + progressive disease(P < 0.05). No specific side effects were recorded. Conclusion Endostar and Bevacizumab demonstrated similar efficacy in controlling MPE in patients with EGFR-/ALK-lung adenocarcinoma through an anti-angiogenesis pathway, with tolerable side effects. The levels of VEGF in MPE could predict the efficacy of intra-pleural injection of anti-angiogenesis drugs.展开更多
Genome-wide association studies(GWASs) have been instrumental in understanding complex phenotypic traits. However, they have rarely been used to understand lineage-specific pathways and functions that contribute to th...Genome-wide association studies(GWASs) have been instrumental in understanding complex phenotypic traits. However, they have rarely been used to understand lineage-specific pathways and functions that contribute to the trait. In this study, by integrating lineage-specific enhancers from mesenchymal and myeloid compartments with bone mineral density loci, we were able to segregate osteoblast-and osteoclast(OC)-specific functions. Specifically, in OCs, a PU.1-dependent transcription factor(TF)network was revealed. Deletion of PU.1 in OCs in mice resulted in severe osteopetrosis. Functional genomic analysis indicated PU.1 and MITF orchestrated a TF network essential for OC differentiation. Several of these TFs were regulated by cooperative binding of PU.1 with BRD4 to form superenhancers. Further, PU.1 is essential for conformational changes in the superenhancer region of Nfatc1. In summary, our study demonstrates that combining GWASs with genome-wide binding studies and model organisms could decipher lineage-specific pathways contributing to complex disease states.展开更多
BACKGROUND Asymptomatic cytomegalovirus(CMV)infection is common in children;in contrast,in children with a weakened immune system,invasive CMV can occur.This is the first case report of a severe manifestation of CMV e...BACKGROUND Asymptomatic cytomegalovirus(CMV)infection is common in children;in contrast,in children with a weakened immune system,invasive CMV can occur.This is the first case report of a severe manifestation of CMV esophagoenterocolitis in a girl diagnosed with anti-N-methyl-D-aspartate-receptor(antiNMDAR)encephalitis who received only a moderate dose of corticosteroid therapy.CASE SUMMARY A 12-year-old-Thai girl presented with acute behavioural change and headache for 6 d.Electroencephalogram and positivity for NMDAR autoantibodies were compatible with anti-NMDAR encephalitis.Hence,she received pulse methylprednisolone 10 mg/kg per day for 4 d and continued with prednisolone 1.2 mg/kg per day.On day 42 of corticosteroid therapy,she developed unremitting vomiting and diarrhoea.Endoscopy showed multiple ulcers and erythaematous mucosa along the gastrointestinal tract.Tissue CMV viral load and viral-infected cells confirmed CMV esophago-enterocolitis.Therefore,the patient received ganciclovir 5 mg/kg per dose every 12 h for 3 wk and then 5 mg/kg per dose once daily for 3 wk.Unremitting diarrhoea slowly improved from stool output 1-4 L per day to 1-2 L per day after 3 wk of treatment.Pulse methylprednisolone 20 mg/kg for 5 d was initiated and continued with prednisolone 1 mg/kg per day.After this repeated pulse methylprednisolone treatment,surprisingly,diarrhoea subsided.Immunologic work-up was performed to rule out underlying immune deficiency with unremarkable results.CONCLUSION Unremitting diarrhoea from CMV esophago-enterocolitis subsided with antiviral and methylprednisolone therapy,implying the immune and NMDAR dysregulation in anti-NMDAR encephalitis.展开更多
Platelet-activating factor (PAF) is a potent inflammatory phospholipid mediator that is known to play a role in early-phase responses in asthma and other diseases. Through its high affinity receptor, PAFR, PAF is know...Platelet-activating factor (PAF) is a potent inflammatory phospholipid mediator that is known to play a role in early-phase responses in asthma and other diseases. Through its high affinity receptor, PAFR, PAF is known to activate multiple signalling pathways contributing to its proinflammatory effects. Of these pathways, the mitogen-activated protein kinase (MAPK) cascade is initiated upon PAF stimulation, leading to the activation of the conventional MAPKs ERK1/2, p38 and JNK. Since dual-specificity phosphatases (DUSP) downregulated MAPK activity, we postulated that PAF could also enhance DUSP expression and thus induced an autoregulatory loop. In this report, we studied the effect of PAF on DUSP mRNA expression in human monocytes. Our results demonstrate that PAF induces DUSP1 and DUSP5 gene expression in a time- and concentration-dependent manner, with maximal effects at PAF 100 nM and at 20 - 30 min of stimulation. In contrast, DUSP2 and DUSP6 gene expression was not enhanced by PAF. Moreover, leukotriene D4, another lipid mediator of inflammation, was unable to modulate DUSP expression. PAF-induced DUSP expression was prevented by the PAFR antagonist WEB2170 and by pretreatment with the transcriptional inhibitor Actinomycin D. Moreover, enhanced DUSP5, but not DUSP1 expression was prevented by pretreatment with the ERK inhibitor PD98059 or the PI3K inhibitor Wortmannin. Taken together, our results indicate that PAF selectively enhances DUSP1 and DUSP5 gene expressions through PAFR activation, and suggest that PAF may have an active role in the resolution of inflammation by its ability to upregulate the two DUSPs and thus provide a negative auto-regulatory signalling mechanism.展开更多
Frequent exposure to water and surfactants is considered to be the main cause of hand eczema from wet work. Ethoxylated surfactants are susceptible to oxidation and some of the oxidation products formed have proved to...Frequent exposure to water and surfactants is considered to be the main cause of hand eczema from wet work. Ethoxylated surfactants are susceptible to oxidation and some of the oxidation products formed have proved to be contact sensitizers in guinea pigs. The question of human sensitization to oxidized surfactants was addressed in a multicentre study in the Stockholm region. 528 consecutive dermatitis patients were patch tested with widely used ethoxylated surfactants in oxidized and non-oxidized form as well as certain identified oxidation compounds. 61 patients presented with mild, clearly irritant reactions to some of the surfactants tested. 18 patients showed not only erythema but also oedema and/or papules and vesicles, using a morphologic descriptive system for reading the patch test reactions. These reactions occurred mostly to oxidized surfactants and oxidation products. When retesting 9 of these 18 patients only an allergic reaction to acetaldehyde was confirmed. We conclude that oxidized ethoxylated surfactants have increased irritant potential compared to non-oxidized material. Our working hypothesis is that oxidized surfactants of technical quality exert a lower risk of sensitization than do oxidized homologous pure surfactants. Among the potential allergens formed during autoxidation, formaldehyde and acetaldehyde must be considered as a source of unexpected exposure.展开更多
Terpenes are widely used fragrance compounds in fine fragrances, but also in domestic and occupational products. Terpenes oxidize easily due to autoxidation on air exposure. Previous studies have shown that limonene, ...Terpenes are widely used fragrance compounds in fine fragrances, but also in domestic and occupational products. Terpenes oxidize easily due to autoxidation on air exposure. Previous studies have shown that limonene, linalool and caryophyllene are not allergenic themselves but readily form allergenic products on air-exposure. This study aimed to determine the frequency and characteristics of allergic reactions to selected oxidized fragrance terpenes other than limonene. In total 1511 consecutive dermatitis patients in 6 European dermatology centres were patch tested with oxidized fragrance terpenes and some oxidation fractions and compounds. Oxidized linalool and its hydroperoxide fraction were found to be common contact allergens. Of the patients tested, 1.3%showed a positive reaction to oxidized linalool and 1.1%to the hydroperoxide fraction. About 0.5%of the patients reacted to oxidized caryophyllene whereas 1 patient reacted to oxidized myrcene. Of the patients reacting to the oxidized terpenes, 58%had fragrance-related contact allergy and/or a positive history for adverse reaction to fragrances. Autoxidation of fragrance terpenes contributes greatly to fragrance allergy, which emphasizes the need of testing with compounds that patients are actually exposed to and not only with the ingredients originally applied in commercial formulations.展开更多
Background: Exposure to plastic fumes can lead to severe occupational hazards due to inhalation, ingestion or direct contact wide variety of potentially harmful by-products during the manufacturing and burning of plas...Background: Exposure to plastic fumes can lead to severe occupational hazards due to inhalation, ingestion or direct contact wide variety of potentially harmful by-products during the manufacturing and burning of plastics. Objectives: To determine the prevalence of respiratory symptoms in plastic factory workers, evaluate the respiratory function of plastic factory workers and the association between respiratory symptoms and the duration of employment. Methods: This was a cross-sectional study done among plastic factory workers. Using a random sampling technique, 190 individuals (95 subjects and 95 control) above 18 years of age were recruited. Data were obtained with a validated questionnaire and Spirometry was done. Result: The mean age of the study group and control were 30.27 ± 7.38 and 25.92 ± 4.63 respectively (t = 4.877;p Conclusion: Workplace exposure to plastic fumes can lead to development of respiratory symptoms and impaired pulmonary function.展开更多
Background:Allergy march refers to progression of allergic diseases from infantile food allergy to the development of asthma and allergic rhinitis (AR).Evidence come mostly from studies in European countries.This stud...Background:Allergy march refers to progression of allergic diseases from infantile food allergy to the development of asthma and allergic rhinitis (AR).Evidence come mostly from studies in European countries.This study aimed to investigate allergy march in Chinese children with infantile food protein allergy (FPA) with a special focus on the effect of different formula interventions.Methods:From 2008 to 2010,153 infants diagnosed with FPA were recruited in five tertiary hospitals across China.They were randomly treated with amino-acid-based formula or soy-protein-based formula for a period of 3 months.Long-term follow-up was performed when they reached early school age,using questionnaires,physical examinations,and serum-specific immunoglobulin E.Results:The overall follow-up rate was 73.20%.In patients who reached their early school years,the prevalence of physician-diagnosed AR and asthma were 43.75% and 23.21%,respectively.Only 40% of the subjects remained positive for food sensitizations upon follow-up.Twenty-six subjects receiving aeroallergen screening tests in infancy all proved negative,but upon follow-up,65.57% were sensitized to aeroallergens (P=0.005).No significant difference between the effects of amino-acid-based formula and soy-protein-based formula on children's allergy march was observed.Conclusions:A high proportion (47.32%) of Chinese infants with early allergic symptoms developed respiratory allergies by their early school years.Most food-sensitized infants outgrew their condition several years later,but then aeroallergen sensitization often occurred.Amino-acid-based formula showed no advantages over soy protein-based formula with respect to arresting the allergy march.展开更多
Background Sphingosine-1-phosphate lyase insufficiency syndrome(SPLIS)or nephrotic syndrome type-14 is caused by biallelic mutations in SGPL1.Here,we conducted a systematic review to delineate the characteristics of S...Background Sphingosine-1-phosphate lyase insufficiency syndrome(SPLIS)or nephrotic syndrome type-14 is caused by biallelic mutations in SGPL1.Here,we conducted a systematic review to delineate the characteristics of SPLIS patients.Methods A literature search was performed in PubMed,Web of Science,and Scopus databases,and eligible studies were included.For all patients,demographic,clinical,laboratory,and molecular data were collected and analyzed.Results Fifty-five SPLIS patients(54.9%male,45.1%female)were identified in 19 articles.Parental consanguinity and positive family history were reported in 70.9%and 52.7%of patients,respectively.Most patients(54.9%)primarily manifested within the first year of life,nearly half of whom survived,while all patients with a prenatal diagnosis of SPLIS(27.5%)died at a median[interquartile(IQR)]age of 2(1.4–5.3)months(P=0.003).The most prevalent clinical feature was endocrinopathies,including primary adrenal insufficiency(PAI)(71.2%)and hypothyroidism(32.7%).Kidney disorders(42,80.8%)were mainly in the form of steroid-resistant nephrotic syndrome(SRNS)and progressed to end-stage kidney disease(ESKD)in 19(36.5%)patients at a median(IQR)age of 6(1.4–42.6)months.Among 30 different mutations in SGPL1,the most common was c.665G>A(p.Arg222Gln)in 11(20%)patients.Twenty-six(49.1%)patients with available outcome were deceased at a median(IQR)age of 5(1.5–30.5)months,mostly following ESKD(23%)or sepsis/septic shock(23%).Conclusion In patients with PAI and/or SRNS,SGPL1 should be added to diagnostic genetic panels,which can provide an earlier diagnosis of SPLIS and prevention of ESKD and other life-threatening complications.展开更多
GATA-3 was first cloned as a T cell specific transcription factor in 1991 and its importance in the transcriptional control of T helper type 2 cell (Th2) differentiation was established in the mid to late 90's. A r...GATA-3 was first cloned as a T cell specific transcription factor in 1991 and its importance in the transcriptional control of T helper type 2 cell (Th2) differentiation was established in the mid to late 90's. A role for GATA-3 during thymic development has long implied by its continuous and regulated expression through out T lineage development, but the absolute requirement for GATA-3 during early T lymphoid commitment/survival previously precluded definitive answers to this question. Several technical breakthroughs have fueled fruitful investigation in recent years and uncovered unexpected and critical roles for GATA-3 in CD4 thymocyte survival, invariant natural killer T cell generation and function, and also in beta selection. Not only does GATA-3 participate in nearly every stage of T cell development from common lymphoid progenitor to Th2, conditional knockout studies have indicated that the influence of GATA-3 also extends beyond the immune system. Cellular & Molecular Immunology. 2007; 4(1): 15-29.展开更多
Background Asthma mortality among children and adolescents at the national level in China was unreported.The aim of this study was to analyze the mortality of asthma among children and adolescents in China using a nat...Background Asthma mortality among children and adolescents at the national level in China was unreported.The aim of this study was to analyze the mortality of asthma among children and adolescents in China using a nationally representative database.Methods This was a descriptive study using data from the Disease Surveillance Points(DSPs)system.All asthma‐related deaths among children and adolescents aged 0–19 years occurring in DSPs across China from 2008 to 2018 were included.Multilevel Poisson regression models were used to compute the total,age-,gender-,region-and residence-specific asthma mortality rates and to investigate the significance of trends and factors associated with asthma mortality.Data from the National Bureau of Statistics were used to estimate the national asthma deaths.Results Total asthma mortality rate among Chinese children and adolescents fluctuated between 0.020(0.009,0.045)and 0.059(0.025,0.137)per 100,000 and showed an overall downward trend(RR,0.909;95%CI 0.854–0.968)during the study period(2008–2018).Asthma mortality rate was higher in the western China(RR 2.356,95%CI 1.513,3.669)and varied over a ninefold range among DSPs in China.The estimated number of deaths decreased by 51.38%from 2008(n=148;95%CI 58,379)to 2018(n=71;95%CI 34,109).Conclusions Asthma mortality rate among children and adolescents in China was at a low level compared to rates worldwide and decreased significantly from 2008 to 2018.Compared with most countries in the world,the number of asthma deaths was higher in China.展开更多
Hypertension is a cardiovascular disease affecting approximately one out of every seven people worldwide. High-sodium consumption has been generally accepted as a risk factor for developing hypertension. Today, global...Hypertension is a cardiovascular disease affecting approximately one out of every seven people worldwide. High-sodium consumption has been generally accepted as a risk factor for developing hypertension. Today, global sodium consumption greatly exceeds guidelines recommended by all medical institutions. This review synthesizes the data of landmark mammalian and human studies which investigated the role of sodium in the pathogenesis of hypertension, along with modern studies questioning this relationship. Recent studies concerning the potential pathways by which high-sodium concentration induces hypertension were reviewed. Human trials and population studies revealed a strong correlation between high blood pressure and average dietary sodium; and animal studies found a dramatic reduction in vascular function in a variety of mammals treated with high-sodium diets. In spite of a few contrarian studies, we found overwhelming evidence that elevated sodium consumption could cause hypertension展开更多
We observed a rare case of invasive mucinous adenocarcinoma (IMA) with a lepidic-predominant pattern accompanied by pulmonary tuberculosis. An 85-year-old man with repeated cough and sputum was admitted to Xinhua Ho...We observed a rare case of invasive mucinous adenocarcinoma (IMA) with a lepidic-predominant pattern accompanied by pulmonary tuberculosis. An 85-year-old man with repeated cough and sputum was admitted to Xinhua Hospital. T-SPOT test result was 212 pg/ml (reference value of negative is 〈 14 pg/ml), Mycobacterium tuberculosis culture was positive, and tuberculin skin test (PPD) was negative (skin induration 〈 5 mm). The patient was treated with several courses of antibiotics and anti-tuberculosis treatments. Repeated chest CT scans showed disease progression. Bronchoscopy yielded negative results. PET-CT scans showed negative results. A percutaneous lung biopsy revealed mucin-secreting cells lining the alveolar walls. IMA with a lepidic- predominant pattern was diagnosed after invasiveness was found after experimental treatments. Simultaneous occurrence of pulmonary tuberculosis and lung cancer are common; however, the present case of IMA having a lepidic-predominant pattern and coexisting with active tuberculosis has not been reported yet.展开更多
A 1-day symposium before the annual meeting of the Global Alliance against Chronic Respiratory Diseases,gathered authorities and researchers from around the world to discuss the impact of air pollution on human and pl...A 1-day symposium before the annual meeting of the Global Alliance against Chronic Respiratory Diseases,gathered authorities and researchers from around the world to discuss the impact of air pollution on human and planetary health.Air quality is a high priority for Global Alliance against Chronic Respiratory Diseases and China,the host country.This article presents a summary,commentary,and amplification of the 17 presentations.Air pollution is closely linked with global warming and harms most body systems even at levels below international standards.Information about the genetic,cellular,and metabolic effects of exposure to air pollution is important for better understanding of individual responses and even potential therapeutic mediation.Reducing air pollution at its source leads to prompt and important benefits and should be the first priority for political and public action.展开更多
Aim: Hypersensitivity reactions to carboplatin are not an infrequent adverse event in ovarian cancer patients. However, reintroduction of platinum-containing schedules is the standard of care in platinum-sensitive rec...Aim: Hypersensitivity reactions to carboplatin are not an infrequent adverse event in ovarian cancer patients. However, reintroduction of platinum-containing schedules is the standard of care in platinum-sensitive recurrent ovarian cancer. Rapid desensitization is a procedure for gradual reintroduction of drug. It allows a safe administration of medications that are beneficial for the management of patients after certain types of hypersensitivity reactions. It is indicated in cases in which there are no reasonable therapeutic alternatives. Methods: We performed a descriptive retrospective study of high-grade ovarian cancer patients with known carboplatin hypersensitivity reactions that were treated with a 13-steps rapid desensitization protocol with 3 different solutions and infusion rates. The procedure followed a mathematic model (gradual increases with a relationship between doses following a geometric series) which is called logarithmic rapid desensitization protocol (LRDP). The aim was to describe the safety of the LRDP in terms of number and severity of infusion reactions and the effectiveness in the rate of cycles completely administered. Results: Four different patients diagnosed with recurrent platinum-sensitive ovarian cancer with a previous infusion reaction were included. LRDP was administered in 19 different cycles. LRDP was administered safety in all 19 cycles, only 2 patients had a mild cutaneous reaction in 4 different cycles during LRDP (21.05%). The foreseen dose of carboplatin was fully administered in all cycles.Conclusion: LRDP with carboplatin is a feasible and safe protocol in patients with previous infusion reaction to carboplatin. The protocol might allow a safe administration of drugs, that are beneficial for the management of patients, after certain types of hypersensitivity reactions, and it is indicated in cases in which there are no reasonable therapeutic alternatives.展开更多
文摘Food-dependent,exercise-induced anaphylaxis(FDEIA)is a potentially life-threatening disorder that often occurs with exercise,and patients typically have eaten a specific food within hours before disease onset.This disease is exceedingly rare,with a prevalence of 0.02%.No well-recognized prevention or treatment strategy has been available for FDEIA except avoiding triggers strictly.Here we report an 11-year-old boy with a history of recurrent anaphylaxis of unknown etiology more than 10 times within two years.As the anaphylactic symptoms had not been controlled after traditional treatments,the patient was given subcutaneous injection of dupilumab seven times within 33 weeks.During dupilumab treatments,the patient was exposed to culprit mushrooms plus exercises at least twice a month but without notable anaphylaxis.Thus,dupilumab may improve the allergic reactions in FDEIA patients.
基金Supported by(In part)the National Science Council,NSC 101-2314-B-182A-103-MY3Chang Gung Memorial Hospi-tal,CMRPG3B1751E
文摘During the course of chronic hepatitis C virus(HCV)infection,various extrahepatic manifestations of autoimmune disorders may occur,including arthralgia/arthritis,sicca complex,purpura,cutaneous ulcer,and thyroid dysfunction.In addition,the prevalence of circulating autoantibodies is high among patients with HCV infection.Commonly detected autoantibodies in HCVinfected patients include rheumatoid factor,antinuclear antibody,anti-SSA/anti-SSB antibody,cryoglobulin,antineutrophil cytoplasmic antibody,anti-smooth muscle antibody,anti-liver and anti-thyroid autoantibodies.These autoantibodies may be associated with underlying autoimmune disorders or liver inflammation in HCV infection.A possible reason for antibody production is overactivation and proliferation of B lymphocytes,via the interaction with the surface protein of HCV.Because immunotherapy can cause HCV flare-up or liver damage,overdiagnosis of HCV-related autoimmune symptoms as primary autoimmune disorders should be avoided.This review describes biomarkers that are useful in clinically evaluating autoimmune manifestations and disorders associated with HCV infection.
基金supported by NIH/NCCAM center grant # 1P01 AT002644725-01"Center for Chinese Herbal Therapy(CHT) for Asthma"to Dr.Xiu-Min Li
文摘OBJECTIVE: Anti-asthma herbal medicine intervention (ASHMITM), a combination of three tradi- tional Chinese medicinal herbs developed in our laboratory, has demonstrated efficacy in both mouse models of allergic asthma, and a double-blind placebo-controlled clinical trial in patients with asthma. This study was designed to determine if the anti-inflammatory effects of individual herbal constituents of ASHMITM exhibited synergy. METHODS: Effects of ASHMI and its components aqueous extracts of Lingzhi (Ganoderma lucidum), Kushen (Sophora flavescens) and Gancao (Glycyrrhiza uralensis), on Th2 cytokine secretion by murine memory Th2 cells (D10.G4.1) and eotaxin-1 secretion by human lung fibroblast (HLF-1) cells were determined by measuring levels in culture supernatants by enzyme- linked immunosorbent assay. Potential synergistic effects were determined by computing interaction indices from concentration-effect curve parameters. RESULTS: Individual Lingzhi, Kushen and Gancao extracts and ASHMI (the combination of individual extracts) inhibited production of interleukin (IL)-4 and IL-5 by murine memory Th2 cells and eotaxin-1 production by HLF-1 cells. The mean 25%-inhibitory-concentration (IC2s) values (mg/mL) forASHMI, Lingzhi, Kushen and Gancao for IL-4 production were 30.9, 79.4, 123, and 64.6, respectively; for IL-5 production were 30.2, 263, 123.2 and 100, respectively; for eotaxin-1 were 13.2, 16.2, 30.2, and 25.1, respectively. The IC50values (mg/mL) for ASHMI, Lingzhi, Kushen and Gancao for IL-4 production were 158.5, 239.9, 446.7, and 281.8, respectively; for eotaxin-1 were 38.1, 33.1, 100, and 158.5, respectively. The interaction indices of ASHMI constituents at IC25 were 0.35 for IL-4, 0.21 for IL-5 and 0.59 for eotaxin-l. The interaction indices at IC^0 values were 0.50 for IL-4 and 0.62 for eotaxin-1 inhibition. Inhibition of IL-5 did not reach IC^0 values. All interaction indices were below 1 which indicated synergy. CONCLUSION: By comparing the interaction index values, we find that constituents in ASHMITM synergistically inhibited eotaxin-1 production as well as Th2 cytokine production.
文摘Objective This study aimed to compare and analyze the clinical efficacy and safety of late-course and simultaneous integrated dose-increasing intensity-modulated radiation therapy(IMRT) for cervical cancer complicated with pelvic lymph node metastasis. Methods Sixty patients with cervical cancer complicated with pelvic lymph node metastasis who were admitted to our hospital from January 2013 to January 2015 were enrolled. The patients were randomly divided into the late-course dose-increasing IMRT group and the simultaneous integrated dose-increasing IMRT group, with 30 cases included in each group, respectively. All patients were concurrently treated with cisplatin. After treatment, the clinical outcomes of the two groups were compared. Results The remission rate of symptoms in the simultaneous integrated dose-increasing IMRT group was significantly higher than that in the late-course dose-increasing IMRT group(P < 0.05). The follow-up results showed that the overall survival time, progression-free survival time, and distant metastasis time of patients in the simultaneous integrated dose-increasing IMRT group were significantly longer than those in the late-course dose-increasing IMRT group(P < 0.05). The recurrent rate of lymph nodes in the radiation field in the simultaneous integrated dose-increasing IMRT group was significantly lower(P < 0.05) than in the late-course dose-increasing IMRT group. There was no significant difference in the incidence of cervical and vaginal recurrence and distant metastasis between the two groups(P > 0.05). The radiation doses of Dmax in the small intestine, D1 cc(the minimum dose to the 1 cc receiving the highest dose) in the bladder, and Dmax in the rectum in the simultaneous integrated dose-increasing IMRT group were significantly lower(P < 0.05) than in the late-course dose-increasing IMRT group. There was no significant difference in intestinal D2 cc(the minimum dose to the 2 cc receiving the highest dose) between the two groups(P > 0.05). The incidence of bone marrow suppression in the simultaneous integrated dose-increasing IMRT group was significantly lower(P < 0.05) than in the late-course dose-increasing IMRT group.Conclusion The application of simultaneous integrated dose-increasing IMRT in the treatment of cervical cancer patients complicated with pelvic lymph node metastasis can significantly control tumor progression, improve the long-term survival time, and postpone distant metastasis time with high safety.
基金Supported by the Basic Science Research Program Through the National Research Foundation(NRF)of Korea Funded by the Ministry of Science,ICT,and Future Planning 2014049413,NRF-2015R1A5A2008833 and NRF-2015R1C1A1A02037702
文摘AIM: To investigate the role of O-GIcNAcylation of nuclear factor-kappa B (NF-KB) in retinal ganglion cell (RGC) death and analysedthe effect of Aralia elata (AE) on neurodegen- eration in diabetic mice. METHODS: C57BL/6mice with streptozotocin-induced diabetes were fed daily with AE extract or control (CTL) diet at the onset of diabetes mellitus (DM). Two months af- tar injection of streptozotocin or saline, the degree of cell death and the expression of O-GIcNAc transferase (OGT), N-acetyl-b-D-glucosaminidase (OGA), O-GIcNAcylated pro- teins, and O-GIcNAcylation of NF-KB were examined. RESULTS: AE did not affect the metabolic status of diabetic mice. The decrease in the inner retinal thickness (P〈0.001 vs CTL, P〈0.01 vs DM) and increases in RGCs with terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (P〈0.001 vs CTL, P〈0.0001 vs DM), glial activation, and active caspase-3 (P〈0.0001 vs CTL, P〈0.0001 vs DM) were blocked in diabetic retinas of AE extract-fed mice. Expression levels of protein O-GIcNAcylation and OGT were increased in diabetic retinas (P〈0.0001 vs CTL), and the level of O-GIcNAcylation of the NF-KB p65 subunit was higher in diabetic retinas than in controls (P〈0.0001 vs CTL). AE extract downregulated O-GIcNAcylation of NF-KB and prevented neurodegeneration induced by hyperglycemia (P〈0.0001 vs DM). CONCLUSION: O-GIcNAcylation of NF-KB is concerned in neuronal degeneration and that AE prevents diabetes-in- duced RGC apoptosis via downregulation of NF-KB O-GI- cNAcylation. Hence, O-GIcNAcylation may be a new object for the treatment of DR, and AE may have therapeutic pos- sibility to prevent diabetes-induced neurodegeneration.
基金Supported by a grant from the Nature Science Foundation of Hubei Province,China(No.2017CFB472)
文摘Objective To compare intra-pleural injection efficacy and safety between Endostar and bevacizumab combined with pemetrexed/cisplatin for the treatment of malignant pleural effusion in patients with epidermal growth factor receptor(EGFR)-/anaplastic lymphoma kinase(ALK)-lung adenocarcinoma. Methods Sixty-four pCVatients with EGFR-/ALK-lung adenocarcinoma with malignant pleural effusion(MPE) were admitted to the authors' hospital between January 2016 and June 2017. Patients were randomly divided into two groups: Endostar combined with pemetrexed/cisplatin(Endostar group); and bevacizumab plus pemetrexed/cisplatin(Bevacizumab group). They underwent thoracic puncture and catheterization, and MPE was drained as much as possible. Both groups were treated with pemetrexed 500 mg/m^2, intravenous drip(d1), cisplatin 37.5 mg/m^2 per time, intra-pleural injection(d1, d3). Patients in the Endostar group were treated with Endostar 30 mg per time, intra-pleural injection(d1, 3), and patients in the Bevacizumab group were treated with bevacizumab 5 mg/kg per time, intra-pleural injection(d1). Only one cycle of treatment was applied. MPE was extracted before treatment and on day 7 after treatment. The levels of vascular endothelial growth factor(VEGF) were determined using ELISA. Efficacy and side effects were evaluated according to the Response Evaluation Criteria in Solid Tumors(RECIST) version 1.1, and National Cancer Institute Common Terminology Criteria for Adverse Events(CTCAE) version 3.0 criteria. Results The objective response rates in the Endostar and Bevacizumab groups were 50.0% and 56.3%, respectively; there was no statistical difference between the groups(P > 0.05). After one cycle of treatment, the mean VEGF levels in MPE in both groups decreased significantly, and there was no significant difference in the degree of decline between the two groups(P > 0.05). In both groups, pre-treatment VEGF levels for patients achieving complete response were significantly higher than those for patients achieving stable disease + progressive disease(P < 0.05). No specific side effects were recorded. Conclusion Endostar and Bevacizumab demonstrated similar efficacy in controlling MPE in patients with EGFR-/ALK-lung adenocarcinoma through an anti-angiogenesis pathway, with tolerable side effects. The levels of VEGF in MPE could predict the efficacy of intra-pleural injection of anti-angiogenesis drugs.
基金supported by NIH-NIAMS Grant 2R01AR044719-15A (M.C.O. and S.M.S.)NIH-NIAMS Grant K08AR062590 (J.F.C.)
文摘Genome-wide association studies(GWASs) have been instrumental in understanding complex phenotypic traits. However, they have rarely been used to understand lineage-specific pathways and functions that contribute to the trait. In this study, by integrating lineage-specific enhancers from mesenchymal and myeloid compartments with bone mineral density loci, we were able to segregate osteoblast-and osteoclast(OC)-specific functions. Specifically, in OCs, a PU.1-dependent transcription factor(TF)network was revealed. Deletion of PU.1 in OCs in mice resulted in severe osteopetrosis. Functional genomic analysis indicated PU.1 and MITF orchestrated a TF network essential for OC differentiation. Several of these TFs were regulated by cooperative binding of PU.1 with BRD4 to form superenhancers. Further, PU.1 is essential for conformational changes in the superenhancer region of Nfatc1. In summary, our study demonstrates that combining GWASs with genome-wide binding studies and model organisms could decipher lineage-specific pathways contributing to complex disease states.
基金The Pediatric Gastroenterology and Hepatology Research Unit,ThailandGrants for Development of New Faculty Staff,Ratchadaphiseksomphot Endowment Fund,Thailand,No.RA63/012Thailand Research Fund Thailand Science Research and Innovation,Thailand,No.MRG6280190。
文摘BACKGROUND Asymptomatic cytomegalovirus(CMV)infection is common in children;in contrast,in children with a weakened immune system,invasive CMV can occur.This is the first case report of a severe manifestation of CMV esophagoenterocolitis in a girl diagnosed with anti-N-methyl-D-aspartate-receptor(antiNMDAR)encephalitis who received only a moderate dose of corticosteroid therapy.CASE SUMMARY A 12-year-old-Thai girl presented with acute behavioural change and headache for 6 d.Electroencephalogram and positivity for NMDAR autoantibodies were compatible with anti-NMDAR encephalitis.Hence,she received pulse methylprednisolone 10 mg/kg per day for 4 d and continued with prednisolone 1.2 mg/kg per day.On day 42 of corticosteroid therapy,she developed unremitting vomiting and diarrhoea.Endoscopy showed multiple ulcers and erythaematous mucosa along the gastrointestinal tract.Tissue CMV viral load and viral-infected cells confirmed CMV esophago-enterocolitis.Therefore,the patient received ganciclovir 5 mg/kg per dose every 12 h for 3 wk and then 5 mg/kg per dose once daily for 3 wk.Unremitting diarrhoea slowly improved from stool output 1-4 L per day to 1-2 L per day after 3 wk of treatment.Pulse methylprednisolone 20 mg/kg for 5 d was initiated and continued with prednisolone 1 mg/kg per day.After this repeated pulse methylprednisolone treatment,surprisingly,diarrhoea subsided.Immunologic work-up was performed to rule out underlying immune deficiency with unremarkable results.CONCLUSION Unremitting diarrhoea from CMV esophago-enterocolitis subsided with antiviral and methylprednisolone therapy,implying the immune and NMDAR dysregulation in anti-NMDAR encephalitis.
文摘Platelet-activating factor (PAF) is a potent inflammatory phospholipid mediator that is known to play a role in early-phase responses in asthma and other diseases. Through its high affinity receptor, PAFR, PAF is known to activate multiple signalling pathways contributing to its proinflammatory effects. Of these pathways, the mitogen-activated protein kinase (MAPK) cascade is initiated upon PAF stimulation, leading to the activation of the conventional MAPKs ERK1/2, p38 and JNK. Since dual-specificity phosphatases (DUSP) downregulated MAPK activity, we postulated that PAF could also enhance DUSP expression and thus induced an autoregulatory loop. In this report, we studied the effect of PAF on DUSP mRNA expression in human monocytes. Our results demonstrate that PAF induces DUSP1 and DUSP5 gene expression in a time- and concentration-dependent manner, with maximal effects at PAF 100 nM and at 20 - 30 min of stimulation. In contrast, DUSP2 and DUSP6 gene expression was not enhanced by PAF. Moreover, leukotriene D4, another lipid mediator of inflammation, was unable to modulate DUSP expression. PAF-induced DUSP expression was prevented by the PAFR antagonist WEB2170 and by pretreatment with the transcriptional inhibitor Actinomycin D. Moreover, enhanced DUSP5, but not DUSP1 expression was prevented by pretreatment with the ERK inhibitor PD98059 or the PI3K inhibitor Wortmannin. Taken together, our results indicate that PAF selectively enhances DUSP1 and DUSP5 gene expressions through PAFR activation, and suggest that PAF may have an active role in the resolution of inflammation by its ability to upregulate the two DUSPs and thus provide a negative auto-regulatory signalling mechanism.
文摘Frequent exposure to water and surfactants is considered to be the main cause of hand eczema from wet work. Ethoxylated surfactants are susceptible to oxidation and some of the oxidation products formed have proved to be contact sensitizers in guinea pigs. The question of human sensitization to oxidized surfactants was addressed in a multicentre study in the Stockholm region. 528 consecutive dermatitis patients were patch tested with widely used ethoxylated surfactants in oxidized and non-oxidized form as well as certain identified oxidation compounds. 61 patients presented with mild, clearly irritant reactions to some of the surfactants tested. 18 patients showed not only erythema but also oedema and/or papules and vesicles, using a morphologic descriptive system for reading the patch test reactions. These reactions occurred mostly to oxidized surfactants and oxidation products. When retesting 9 of these 18 patients only an allergic reaction to acetaldehyde was confirmed. We conclude that oxidized ethoxylated surfactants have increased irritant potential compared to non-oxidized material. Our working hypothesis is that oxidized surfactants of technical quality exert a lower risk of sensitization than do oxidized homologous pure surfactants. Among the potential allergens formed during autoxidation, formaldehyde and acetaldehyde must be considered as a source of unexpected exposure.
文摘Terpenes are widely used fragrance compounds in fine fragrances, but also in domestic and occupational products. Terpenes oxidize easily due to autoxidation on air exposure. Previous studies have shown that limonene, linalool and caryophyllene are not allergenic themselves but readily form allergenic products on air-exposure. This study aimed to determine the frequency and characteristics of allergic reactions to selected oxidized fragrance terpenes other than limonene. In total 1511 consecutive dermatitis patients in 6 European dermatology centres were patch tested with oxidized fragrance terpenes and some oxidation fractions and compounds. Oxidized linalool and its hydroperoxide fraction were found to be common contact allergens. Of the patients tested, 1.3%showed a positive reaction to oxidized linalool and 1.1%to the hydroperoxide fraction. About 0.5%of the patients reacted to oxidized caryophyllene whereas 1 patient reacted to oxidized myrcene. Of the patients reacting to the oxidized terpenes, 58%had fragrance-related contact allergy and/or a positive history for adverse reaction to fragrances. Autoxidation of fragrance terpenes contributes greatly to fragrance allergy, which emphasizes the need of testing with compounds that patients are actually exposed to and not only with the ingredients originally applied in commercial formulations.
文摘Background: Exposure to plastic fumes can lead to severe occupational hazards due to inhalation, ingestion or direct contact wide variety of potentially harmful by-products during the manufacturing and burning of plastics. Objectives: To determine the prevalence of respiratory symptoms in plastic factory workers, evaluate the respiratory function of plastic factory workers and the association between respiratory symptoms and the duration of employment. Methods: This was a cross-sectional study done among plastic factory workers. Using a random sampling technique, 190 individuals (95 subjects and 95 control) above 18 years of age were recruited. Data were obtained with a validated questionnaire and Spirometry was done. Result: The mean age of the study group and control were 30.27 ± 7.38 and 25.92 ± 4.63 respectively (t = 4.877;p Conclusion: Workplace exposure to plastic fumes can lead to development of respiratory symptoms and impaired pulmonary function.
文摘Background:Allergy march refers to progression of allergic diseases from infantile food allergy to the development of asthma and allergic rhinitis (AR).Evidence come mostly from studies in European countries.This study aimed to investigate allergy march in Chinese children with infantile food protein allergy (FPA) with a special focus on the effect of different formula interventions.Methods:From 2008 to 2010,153 infants diagnosed with FPA were recruited in five tertiary hospitals across China.They were randomly treated with amino-acid-based formula or soy-protein-based formula for a period of 3 months.Long-term follow-up was performed when they reached early school age,using questionnaires,physical examinations,and serum-specific immunoglobulin E.Results:The overall follow-up rate was 73.20%.In patients who reached their early school years,the prevalence of physician-diagnosed AR and asthma were 43.75% and 23.21%,respectively.Only 40% of the subjects remained positive for food sensitizations upon follow-up.Twenty-six subjects receiving aeroallergen screening tests in infancy all proved negative,but upon follow-up,65.57% were sensitized to aeroallergens (P=0.005).No significant difference between the effects of amino-acid-based formula and soy-protein-based formula on children's allergy march was observed.Conclusions:A high proportion (47.32%) of Chinese infants with early allergic symptoms developed respiratory allergies by their early school years.Most food-sensitized infants outgrew their condition several years later,but then aeroallergen sensitization often occurred.Amino-acid-based formula showed no advantages over soy protein-based formula with respect to arresting the allergy march.
文摘Background Sphingosine-1-phosphate lyase insufficiency syndrome(SPLIS)or nephrotic syndrome type-14 is caused by biallelic mutations in SGPL1.Here,we conducted a systematic review to delineate the characteristics of SPLIS patients.Methods A literature search was performed in PubMed,Web of Science,and Scopus databases,and eligible studies were included.For all patients,demographic,clinical,laboratory,and molecular data were collected and analyzed.Results Fifty-five SPLIS patients(54.9%male,45.1%female)were identified in 19 articles.Parental consanguinity and positive family history were reported in 70.9%and 52.7%of patients,respectively.Most patients(54.9%)primarily manifested within the first year of life,nearly half of whom survived,while all patients with a prenatal diagnosis of SPLIS(27.5%)died at a median[interquartile(IQR)]age of 2(1.4–5.3)months(P=0.003).The most prevalent clinical feature was endocrinopathies,including primary adrenal insufficiency(PAI)(71.2%)and hypothyroidism(32.7%).Kidney disorders(42,80.8%)were mainly in the form of steroid-resistant nephrotic syndrome(SRNS)and progressed to end-stage kidney disease(ESKD)in 19(36.5%)patients at a median(IQR)age of 6(1.4–42.6)months.Among 30 different mutations in SGPL1,the most common was c.665G>A(p.Arg222Gln)in 11(20%)patients.Twenty-six(49.1%)patients with available outcome were deceased at a median(IQR)age of 5(1.5–30.5)months,mostly following ESKD(23%)or sepsis/septic shock(23%).Conclusion In patients with PAI and/or SRNS,SGPL1 should be added to diagnostic genetic panels,which can provide an earlier diagnosis of SPLIS and prevention of ESKD and other life-threatening complications.
文摘GATA-3 was first cloned as a T cell specific transcription factor in 1991 and its importance in the transcriptional control of T helper type 2 cell (Th2) differentiation was established in the mid to late 90's. A role for GATA-3 during thymic development has long implied by its continuous and regulated expression through out T lineage development, but the absolute requirement for GATA-3 during early T lymphoid commitment/survival previously precluded definitive answers to this question. Several technical breakthroughs have fueled fruitful investigation in recent years and uncovered unexpected and critical roles for GATA-3 in CD4 thymocyte survival, invariant natural killer T cell generation and function, and also in beta selection. Not only does GATA-3 participate in nearly every stage of T cell development from common lymphoid progenitor to Th2, conditional knockout studies have indicated that the influence of GATA-3 also extends beyond the immune system. Cellular & Molecular Immunology. 2007; 4(1): 15-29.
基金supported by grant from the National Key Research and Development Program of China:Cohort Study of Respiratory Diseases-Children-Adult Asthma Cohort Study in China(2016YFC0901103)。
文摘Background Asthma mortality among children and adolescents at the national level in China was unreported.The aim of this study was to analyze the mortality of asthma among children and adolescents in China using a nationally representative database.Methods This was a descriptive study using data from the Disease Surveillance Points(DSPs)system.All asthma‐related deaths among children and adolescents aged 0–19 years occurring in DSPs across China from 2008 to 2018 were included.Multilevel Poisson regression models were used to compute the total,age-,gender-,region-and residence-specific asthma mortality rates and to investigate the significance of trends and factors associated with asthma mortality.Data from the National Bureau of Statistics were used to estimate the national asthma deaths.Results Total asthma mortality rate among Chinese children and adolescents fluctuated between 0.020(0.009,0.045)and 0.059(0.025,0.137)per 100,000 and showed an overall downward trend(RR,0.909;95%CI 0.854–0.968)during the study period(2008–2018).Asthma mortality rate was higher in the western China(RR 2.356,95%CI 1.513,3.669)and varied over a ninefold range among DSPs in China.The estimated number of deaths decreased by 51.38%from 2008(n=148;95%CI 58,379)to 2018(n=71;95%CI 34,109).Conclusions Asthma mortality rate among children and adolescents in China was at a low level compared to rates worldwide and decreased significantly from 2008 to 2018.Compared with most countries in the world,the number of asthma deaths was higher in China.
基金supported in part by grants from the National Heart, Lung, and Blood Institute of the National Institutes of Health, USA (R01HL111656 and K23HL098454 to RFM)the Pulmonary Hypertension Association Proof-of-Concept Research Grant (to J.C.)
文摘Hypertension is a cardiovascular disease affecting approximately one out of every seven people worldwide. High-sodium consumption has been generally accepted as a risk factor for developing hypertension. Today, global sodium consumption greatly exceeds guidelines recommended by all medical institutions. This review synthesizes the data of landmark mammalian and human studies which investigated the role of sodium in the pathogenesis of hypertension, along with modern studies questioning this relationship. Recent studies concerning the potential pathways by which high-sodium concentration induces hypertension were reviewed. Human trials and population studies revealed a strong correlation between high blood pressure and average dietary sodium; and animal studies found a dramatic reduction in vascular function in a variety of mammals treated with high-sodium diets. In spite of a few contrarian studies, we found overwhelming evidence that elevated sodium consumption could cause hypertension
基金The support from National Natural Science Foundation of China (No. 81200017) and Foundation of Traditional Chinese and Western Medicine of General Hospitals in Shanghai (No. ZHYY-ZXYJHZX- 2-201701 ) is gratefully acknowledged.
文摘We observed a rare case of invasive mucinous adenocarcinoma (IMA) with a lepidic-predominant pattern accompanied by pulmonary tuberculosis. An 85-year-old man with repeated cough and sputum was admitted to Xinhua Hospital. T-SPOT test result was 212 pg/ml (reference value of negative is 〈 14 pg/ml), Mycobacterium tuberculosis culture was positive, and tuberculin skin test (PPD) was negative (skin induration 〈 5 mm). The patient was treated with several courses of antibiotics and anti-tuberculosis treatments. Repeated chest CT scans showed disease progression. Bronchoscopy yielded negative results. PET-CT scans showed negative results. A percutaneous lung biopsy revealed mucin-secreting cells lining the alveolar walls. IMA with a lepidic- predominant pattern was diagnosed after invasiveness was found after experimental treatments. Simultaneous occurrence of pulmonary tuberculosis and lung cancer are common; however, the present case of IMA having a lepidic-predominant pattern and coexisting with active tuberculosis has not been reported yet.
文摘A 1-day symposium before the annual meeting of the Global Alliance against Chronic Respiratory Diseases,gathered authorities and researchers from around the world to discuss the impact of air pollution on human and planetary health.Air quality is a high priority for Global Alliance against Chronic Respiratory Diseases and China,the host country.This article presents a summary,commentary,and amplification of the 17 presentations.Air pollution is closely linked with global warming and harms most body systems even at levels below international standards.Information about the genetic,cellular,and metabolic effects of exposure to air pollution is important for better understanding of individual responses and even potential therapeutic mediation.Reducing air pollution at its source leads to prompt and important benefits and should be the first priority for political and public action.
文摘Aim: Hypersensitivity reactions to carboplatin are not an infrequent adverse event in ovarian cancer patients. However, reintroduction of platinum-containing schedules is the standard of care in platinum-sensitive recurrent ovarian cancer. Rapid desensitization is a procedure for gradual reintroduction of drug. It allows a safe administration of medications that are beneficial for the management of patients after certain types of hypersensitivity reactions. It is indicated in cases in which there are no reasonable therapeutic alternatives. Methods: We performed a descriptive retrospective study of high-grade ovarian cancer patients with known carboplatin hypersensitivity reactions that were treated with a 13-steps rapid desensitization protocol with 3 different solutions and infusion rates. The procedure followed a mathematic model (gradual increases with a relationship between doses following a geometric series) which is called logarithmic rapid desensitization protocol (LRDP). The aim was to describe the safety of the LRDP in terms of number and severity of infusion reactions and the effectiveness in the rate of cycles completely administered. Results: Four different patients diagnosed with recurrent platinum-sensitive ovarian cancer with a previous infusion reaction were included. LRDP was administered in 19 different cycles. LRDP was administered safety in all 19 cycles, only 2 patients had a mild cutaneous reaction in 4 different cycles during LRDP (21.05%). The foreseen dose of carboplatin was fully administered in all cycles.Conclusion: LRDP with carboplatin is a feasible and safe protocol in patients with previous infusion reaction to carboplatin. The protocol might allow a safe administration of drugs, that are beneficial for the management of patients, after certain types of hypersensitivity reactions, and it is indicated in cases in which there are no reasonable therapeutic alternatives.