Immunization with Hypoallergens of Shrimp Allergen Tropomyosin Inhibits Shrimp Tropomyosin Specific IgE Reactivity

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Chinese herbal medicine for functional dyspepsia: systematic review of systematic reviews

© The Author(s), 2018. Background: Pharmacotherapy, including prokinetics and proton pump inhibitors for functional dyspepsia (FD) have limited effectiveness, and their safety has been recently questioned. Chinese herbal medicine (CHM) could be considered as an alternative. A systematic review (SR) of SRs was performed to evaluate the potential effectiveness and safety of CHM. Method: We conducted a comprehensive literature search for SRs with meta-analyses in eight international and Chinese databases. Pooled effect estimation from each meta-analysis was extracted. The AMSTAR instrument was used to assess the methodological quality of the included SRs. Results: A total of 14 SRs of mediocre quality assessing various CHMs, alone or in combination with conventional pharmacotherapy, were included. Meta-analyses showed that CHM was more effective than prokinetic agents for the alleviation of global dyspeptic symptoms. Three specific CHM formulae appeared to show superior results in the alleviation of global dyspeptic symptoms, including Si Ni San, modified Xiao Yao San and Xiang Sha Liu Jun Zi decoction. No significant difference in the occurrence of adverse events in using CHM or pharmacotherapy was reported. Conclusion: CHM can be considered as an alternative for the treatment of FD symptoms when prokinetic agents and proton pump inhibitors are contraindicated. Future trial design should focus on measuring changes in individual dyspeptic symptoms and differentiate the effectiveness of different CHM for postprandial distress syndrome and epigastric pain syndrome. A network meta-analysis approach should be used to explore the most promising CHM formula for FD treatment in the future

HLA alleles associated with asparaginase hypersensitivity in Chinese children

Asparaginase is an important drug to treat childhood haematological malignancies. Data on the association between human leukocyte antigens (HLA) and asparaginase hypersensitivity among Chinese are lacking. We conducted a retrospective study to identify HLA alleles associated with asparaginase hypersensitivity among Chinese children with acute lymphoblastic leukaemia (ALL), mixed phenotype leukaemia and non-Hodgkin lymphoma (NHL), who received asparaginases with HLA typing performed between 2009 and 2019. 107 Chinese patients were analysed. 66.3% (71/107) developed hypersensitivity to at least one of the asparaginases. HLA-B*46:01 (OR 3.8, 95% CI 1.4-10.1, p < 0.01) and DRB1*09:01 (OR 4.3, 95% CI 1.6-11.4, p < 0.01) were significantly associated with L-asparaginase hypersensitivities, which remained significant after adjustment for age, gender and B cell ALL [HLA-B*46:01 (adjusted OR 3.5, 95% 1.3-10.5, p = 0.02) and DRB1*09:01 (OR 4.4, 95% CI 1.6-13.3, p < 0.01)]

Intermediate-term evaluation of a pratical chelation protocol based on stratification of thalassemic patients by serum ferritin and magnetic resonance imaging cardiac T2*

A standardized chelation protocol was applied by stratifying transfusion-dependent thalassemic patients into three groups, namely well chelated group (A), inadequately chelated group without (B) or with (C) risk of cardiac complications based on serum ferritin (SF) levels and magnetic resonance imaging (MRI) cardiac T2* measurements. Group A patients were advised to continue with deferoxamine (DFO) (Regimen Ic). Group B patients were given options of either intensification of DFO alone (Regimen Ii), deferiprone (L1) alone (Regimen II) or combined therapy with L1 and DFO (Regimen III). Group C patients were advised to take either Regimen Ii or Regimen III. The 1-year result showed that the combined therapy (Regimen III) significantly reduced SF level, cardiac and liver iron in the groups of inadequately chelated patients. The same set of outcome parameters was repeated at 2.5 years of treatment so as to evaluate the intermediate-term effects of this risk stratified chelation protocol. The number of patients with cardiac T2* <20 ms decreased from 34 (60%) at baseline to 17 (30%) of the whole cohort of 57 patients at the end of the study. There were further improvements in SF, cardiac and liver T2* in Group C patients. Significant improvement in left ventricular ejection fraction (LVEF) was demonstrated after 2.5 years of the combined therapy group in which the change was not initially apparent after the first year of assessment. Copyright © Informa Healthcare USA, Inc.link_to_subscribed_fulltex

A practical chelation protocol based on stratification of thalassemic patients by serum ferritin and magnetic resonance imaging cardiac t2 *

Proceedings of the 17th International Conference on Chelation (ICOC), Shenzhen, PR China 23-27 November 2007.Our previous study showed that combined therapy with deferiprone (L1) and deferoxamine (DFO) was safe and efficacious in reducing iron overload in poorly-chelated thalassemia major patients for the short-term but the magnetic resonance imaging (MRI) T2* evaluation was not available at that time. Since October 2006, we applied a standardized chelation protocol by stratifying transfusion-dependent thalassemic patients into three groups, namely well-chelated group (A), poorly-chelated group without (B) or with (C) risk of cardiac complications, based on their serum ferritin (SF) levels and magnetic resonance imaging (MRI) cardiac T2* measurements. The patients in each group were given options of chelation regimens to improve their iron overload status. Chelation regimens included continuation or intensification of DFO alone (Regimen Ic or Ii, respectively), L1 alone (Regimen II), and combined therapy with L1 and DFO (Regimen III). Group A patients continued with Regimen Ic. Group B patients could opt for either Regimen Ii or IIIII. Group C patients could opt for either Regimen Ii or III. Serum ferritin levels and MRI cardiac and liver T2* measurements were evaluated after 1 year of treatment. Fifty-seven patients (27 males, 30 females; age range 534 years, median: 25 years) were categorized into Group A (n = 3), B (n = 20) and C (n = 34). All Group A patients continued with DFO treatment. In Group B, seven were on Regimen Ii, five on Regimen II and five on Regimen III. In Group C, five were on Regimen Ii, two on Regimen II and 26 on Regimen III. Significant improvement was noted only for Group C patients using Regimen III (combined therapy) in SF levels, cardiac T2* and liver T2* measurements. © Informa UK, Ltd.link_to_subscribed_fulltex

Penicilliosis in children without HIV infection-are they immunodeficient?

Background. Penicillium marneffei infection is indigenous to Southeast Asia. Majority of penicilliosis occurs in patients with AIDS, and less commonly with secondary immunodeficiencies. Penicilliosis is rare in otherwise healthy persons, but information on their immunological status is often lacking.Methods.From 1996 to 2009, we diagnosed penicilliosis in 5 children. Their clinical features, immunological findings, and genetic studies were analyzed. A systematic review of the English and Chinese literature was performed. Case reports/series on patients <18 years with penicilliosis were included, and patients stated to be human immunodeficiency virus (HIV)-positive excluded. Results. All of our 5 patients were HIV negative. Presentations included fungemia (n = 2), multifocal lymphadenopathy (n = 2), and necrotizing pneumonia (n = 1). Four patients had recurrent mucocutaneous candidiasis. Hyperimmunoglobin E syndrome was diagnosed in 1 patient, while another had functional defect in interleukin-12/interferon-γ axis. Three patients were lymphopenic with low natural killer cell counts, but a specific immune defect was not identified. Systematic review of 509 reports on human penicilliosis identified 32 patients aged 3 months to 16 years with no known HIV infection. Twenty-four patients (75%) had disseminated disease, and 55% died of penicilliosis. Eight patients had primary immunodeficiencies or blood disorders, while 4 others had abnormal immune functions. Immune evaluations of the remaining patients were unstated.Conclusion.Penicilliosis is a severe disease causing high mortality in children. As an AIDS-defining illness, penicilliosis should be regarded as an indicator for underlying immunodeficiency in HIV-negative individuals. Immunological investigations should be performed, especially in those with recurrent infections. Multicentered collaborative studies are needed to collect information on long-term prognosis and define immune defects underlying penicilliosis. © 2011 The Author.link_to_OA_fulltex

The genetics of macrocephaly, autistic spectrum disorders and developmental delay in Chinese children

Poster PresentationsObjective: Macrocephaly is a common dysmorphic feature in children with autistic spectrum disorders and developmental problems. Previous studies showed that 14–34% of autistic children had head circumference >97 percentile. The aim of this study was to investigate the genetic causes of children with macrocephaly, autistic spectrum disorders and/ or global developmental delay. Method: Chinese children diagnosed with macrocephaly with head circumference >2 S.D. with either autistic spectrum disorders and/ or global developmental delay were recruited prospectively from 1st January 2010 to 31st December 2014. After obtaining informed consent, whole exome sequencing was done on the patients’ blood and buccal DNA. There were total of 18 patients and 27 family members. Coding exons in DNA samples from the patients and the family members were captured by Illumina Truseq Exome Enrichment Kit (64mb) and sequenced by Illumina Hiseq 2000 machine. The whole sequencing data analysis follows the best practice of GATK 3.2 (The Genome Analysis Toolkit, Broad Institute). Results: Out of the 18 patients with macrocephaly, autistic spectrum and/ or global developmental delay, 5 patients (27%) were identified to have genetic mutations (3 de novo mutations, 1 autosomal dominant and 1 was X-linked inherited). 4 out of the 5 mutations were linked to the PI3KAKT- mTOR pathway. Interestingly, one of these patients with biallelic PTEN mutations had the most severe clinical features of macrocephaly, global developmental delay and early death. Conclusion: Children with macrocephaly, autistic spectrum disorders and/ or global developmental delay should be offered genetic evaluations to rule out megalencephaly syndromes related to the PI3K-AKT-mTOR pathway. Early recognition will help to identify and treat complications such as increased cancer risks and early lethality

Molecular diagnosis of severe combined immunodeficiency - Identification of IL2RG, JAK3, IL7R, DCLRE1C, RAG1, and RAG2 mutations in a cohort of Chinese and Southeast Asian children

Severe combined immunodeficiencies (SCID) are a group of rare inherited disorders with profound defects in T cell and B cell immunity. From 2005 to 2010, our unit performed testing for IL2RG, JAK3, IL7R, RAG1, RAG2, DCLRE1C, LIG4, AK2, and ZAP70 mutations in 42 Chinese and Southeast Asian infants with SCID adopting a candidate gene approach, based on patient's gender, immune phenotype, and inheritance pattern. Mutations were identified in 26 patients, including IL2RG (n=19), IL7R (n=2), JAK3 (n=2), RAG1 (n=1), RAG2 (n=1), and DCLRE1C (n=1). Among 12 patients who underwent hematopoietic stem cell transplantation, eight patients survived. Complications and morbidities during transplant period were significant, especially disseminated bacillus Calmette-Guérin disease which was often difficult to control. This is the first cohort study on SCID in the Chinese and Southeast Asian population, based on a multi-centered collaborative research network. The foremost issue is service provision for early detection, diagnosis, management, and definitive treatment for patients with SCID. National management guidelines for SCID should be established, and research into an efficient platform for genetic diagnosis is needed. © 2010 Springer Science+Business Media, LLC.link_to_subscribed_fulltex