Diagnostic Value of Immunological Biomarkers in Children with Asthmatic Bronchitis and Asthma.

Background and Objectives: This study aimed to investigate the diagnostic value of immunological biomarkers in children with asthmatic bronchitis and asthma and to develop a machine learning (ML) model for rapid differential diagnosis of these two diseases. Materials and Methods: Immunological biomarkers in peripheral blood were detected using flow cytometry and immunoturbidimetry. The importance of characteristic variables was ranked and screened using random forest and extra trees algorithms. Models were constructed and tested using the Scikit-learn ML library. K-fold cross-validation and Brier scores were used to evaluate and screen models. Results: Children with asthmatic bronchitis and asthma exhibit distinct degrees of immune dysregulation characterized by divergent patterns of humoral and cellular immune responses. CD8+ T cells and B cells were more dominant in differentiating the two diseases among many immunological biomarkers. Random forest showed a comprehensive high performance compared with other models in learning and training the dataset of immunological biomarkers. Conclusions: This study developed a prediction model for early differential diagnosis of asthmatic bronchitis and asthma using immunological biomarkers. Evaluation of the immune status of patients may provide additional clinical information for those children transforming from asthmatic bronchitis to asthma under recurrent attacks.

Rapid diagnosis of Talaromyces marneffei infection by metagenomic next-generation sequencing technology in a Chinese cohort of inborn errors of immunity.

Talaromyces marneffei (T. marneffei) is an opportunistic pathogen. Patients with inborn errors of immunity (IEI) have been increasingly diagnosed with T. marneffei in recent years. The disseminated infection of T. marneffei can be life-threatening without timely and effective antifungal therapy. Rapid and accurate pathogenic microbiological diagnosis is particularly critical for these patients. A total of 505 patients with IEI were admitted to our hospital between January 2019 and June 2022, among whom T. marneffei was detected in 6 patients by metagenomic next-generation sequencing (mNGS), and their clinical and immunological characteristics were summarized. We performed a systematic literature review on T. marneffei infections with published immunodeficiency-related gene mutations. All patients in our cohort were confirmed to have genetic mutations in IL12RB1, IFNGR1, STAT1, STAT3, and CD40LG. T. marneffei was detected in both the blood and lymph nodes of P1 with IL12RB1 mutations, and the clinical manifestations were serious and included recurrent fever, weight loss, severe anemia, splenomegaly and lymphadenopathy, all requiring long-term antifungal therapy. These six patients received antifungal treatment, which relieved symptoms and improved imaging findings. Five patients survived, while one patient died of sepsis after hematopoietic stem cell transplantation. The application of mNGS methods for pathogen detection in IEI patients and comparison with traditional diagnosis methods were investigated. Traditional diagnostic methods and mNGS tests were performed simultaneously in 232 patients with IEI. Compared to the traditional methods, the sensitivity and specificity of mNGS in diagnosing T. marneffei infection were 100% and 98.7%, respectively. The reporting time for T. marneffei detection was approximately 26 hours by mNGS, 3-14 days by culture, and 6-11 days by histopathology. T. marneffei infection was first reported in IEI patients with IL12RB1 gene mutation, which expanded the IEI lineage susceptible to T. marneffei. For IEI patients with T. marneffei infection, we highlight the application of mNGS in pathogenic detection. mNGS is recommended as a front-line diagnostic test for rapidly identifying pathogens in complex and severe infections.

Application value of gray-scale ultrasound and shear wave elastography in differential diagnosis of thyroid nodules.

BACKGROUND: The global prevalence of thyroid cancer has increased significantly in recent years. Ultrasonography is the preferred method for differentiating benign and malignant thyroid nodules preoperatively and is recommended by guidelines. OBJECTIVE: To assess the application value of gray-scale ultrasound and shear wave elastography in distinguishing small thyroid nodules. METHODS: A retrospective analysis of 228 thyroid nodules, all of which were confirmed by pathology after surgery or FNA from January 2019 to January 2020, was carried out. All nodules were divided into a ⩽ 5 mm group and a > 5 mm group according to their maximum size. We compared the differences in the gray scale and elastography of the nodules between the two groups and the accuracy of different diagnostic methods. RESULTS: The accuracies of gray-scale ultrasound and shear wave elastography in the ⩽ 5 mm group were found to be lower than those in the > 5 mm group, and the gray-scale accuracy was slightly higher than that of shear wave elastography in both groups (p< 0.05). The largest AUC (area under the curve) of elastic parameters in the ⩽ 5 mm and > 5 mm groups was found for Emax and Esd, respectively. Based on a combination of these two parameters, the accuracies of the two groups were significantly higher than those of the parameters or gray scale alone (p< 0.05) and were 84.62% and 85.48%, respectively. CONCLUSION: Shear wave elastography is valuable in the diagnosis of benign and malignant thyroid nodules using ultrasonography. When combining gray-scale ultrasound and shear wave elastography, the diagnostic accuracy is obviously improved, especially for ⩽ 5 mm small thyroid nodules.

Ultrasound May Help Detect Chest Wall Recurrence After Mastectomy at an Early Stage.

OBJECTIVES: To define ultrasound (US) features that help diagnose local recurrence (LR) and differentiate benign masses from LR chest wall masses after mastectomy in patients with breast cancer. METHODS: The US and surgical records of 119 pathologically confirmed chest wall masses in 101 patients were reviewed from 4634 patients with breast cancer who underwent mastectomies. The chest wall masses were divided into 2 groups depending on their longitudinal diameter (LD; ≤10 and > 10 mm). The US features of the subgroups, depending on their nature (benign and LR), were analyzed and compared. RESULTS: Among 119 masses, 58 (48.74%) were benign masses, and 61 (51.26%) were LR masses. For LR, the mean area under the curve ± SD, sensitivity, and specificity of US were 0.849 ± 0.033, 85.25%, and 84.48% (P < .001), respectively. Among the US characteristics, vascularity, an irregular shape, and a location in deep layers were the top 3 factors related to LR (odds ratios, 4.0, 2.6, and 2.2). To diagnose LR by US, judging the anatomic layer of the locations of masses with an LD of 10 mm or less and the presence of vascularity in masses with an LD of greater than 10 mm were helpful. CONCLUSIONS: Ultrasound is a relatively accurate and objective method to differentiate LR from a benign mass after mastectomy with follow-up. Judging the anatomic layer of the mass location with US likely increases the accuracy of LR diagnosis at an early stage.

LIG4 syndrome: clinical and molecular characterization in a Chinese cohort.

BACKGROUND: DNA Ligase IV (LIG4) syndrome is a rare disease with few reports to date. Patients suffer from a broad spectrum of clinical features, including microcephaly, growth retardation, developmental delay, dysmorphic facial features, combined immunodeficiency, and malignancy predisposition. There may be a potential association between genotypes and phenotypes. We investigated the characteristics of LIG4 syndrome in a Chinese cohort. RESULTS: All seven patients had growth restriction. Most patients (6/7) had significant microcephaly (< - 3 SD). Recurrent bacterial infections of the lungs and intestines were the most common symptoms. One patient had myelodysplastic syndromes. One patient presented with an inflammatory bowel disease (IBD)-like phenotype. Patients presented with combined immunodeficiency. The proportions of naïve CD4+ and naïve CD8+ T cells decreased notably in five patients. All patients harbored compound heterozygous mutations in the LIG4 gene, which consisted of a missense mutation (c.833G > T, p.R278L) and a deletion shift mutation, primarily c.1271_1275delAAAGA (p.K424Rfs*20). Two other deletion mutations, c.1144_1145delCT and c.1277_1278delAA, were novel. Patients with p.K424Rfs*20/p.R278 may have milder dysmorphism but more significant IgA/IgM deficiency compared to the frequently reported genotype p.R814X/p.K424Rfs*20. One patient underwent umbilical cord blood stem cell transplantation (UCBSCT) but died. CONCLUSIONS: The present study reported the clinical and molecular characteristics of a Chinese cohort with LIG4 syndrome, and the results further expand the phenotypic and genotypic spectrum and our understanding of genotype-to-phenotype correlations in LIG4 syndrome.

Low-Dose Pioglitazone does not Increase ROS Production in Chronic Granulomatous Disease Patients with Severe Infection.

PURPOSE: We sought to further investigate the efficacy and safety of pioglitazone for chronic granulomatous disease (CGD) patients with severe infection. METHODS: CGD patients with severe infection were enrolled and treated with pioglitazone for 90 days. The degree of improvement in infection and the changes of dihydrorhodamine-123 (DHR) were used to evaluate the efficacy of pioglitazone. The adverse reaction of pioglitazone was also investigated. RESULTS: We planned to enroll 30 patients at first in the study. However, the study was terminated due to negative results from all 3 enrolled patients. The 3 patients were diagnosed with CGD by clinical characteristics, DHR analysis, and genetics analysis. Mutations were CYBB (c.177C>A; p.C59X) in P1, CYBB (c.1498G>T; p.D500Y) in P2, and NCF2 (c.137T>G; p.M46R) in P3, respectively. The age of onset of the 3 patients was within 2 years after birth. The most common sites of infection were lung, lymph node, skin, and soft tissue, which were experienced in all 3 patients. The age of administration with pioglitazone was 5.2 years, 16 years and 11.1 years, respectively. The 3 patients experienced no improvement in severity of infection and stimulation index of the DHR did not also improve after receiving pioglitazone 10, 45 and 90 days, respectively. No drug-related adverse reaction was found during the period of pioglitazone. CONCLUSIONS: Low dose of pioglitazone did not improve the severity of infection and production of ROS in CGD patients with severe infection.

A dominant autoinflammatory disease caused by non-cleavable variants of RIPK1.

Activation of RIPK1 controls TNF-mediated apoptosis, necroptosis and inflammatory pathways1. Cleavage of human and mouse RIPK1 after residues D324 and D325, respectively, by caspase-8 separates the RIPK1 kinase domain from the intermediate and death domains. The D325A mutation in mouse RIPK1 leads to embryonic lethality during mouse development2,3. However, the functional importance of blocking caspase-8-mediated cleavage of RIPK1 on RIPK1 activation in humans is unknown. Here we identify two families with variants in RIPK1 (D324V and D324H) that lead to distinct symptoms of recurrent fevers and lymphadenopathy in an autosomal-dominant manner. Impaired cleavage of RIPK1 D324 variants by caspase-8 sensitized patients' peripheral blood mononuclear cells to RIPK1 activation, apoptosis and necroptosis induced by TNF. The patients showed strong RIPK1-dependent activation of inflammatory signalling pathways and overproduction of inflammatory cytokines and chemokines compared with unaffected controls. Furthermore, we show that expression of the RIPK1 mutants D325V or D325H in mouse embryonic fibroblasts confers not only increased sensitivity to RIPK1 activation-mediated apoptosis and necroptosis, but also induction of pro-inflammatory cytokines such as IL-6 and TNF. By contrast, patient-derived fibroblasts showed reduced expression of RIPK1 and downregulated production of reactive oxygen species, resulting in resistance to necroptosis and ferroptosis. Together, these data suggest that human non-cleavable RIPK1 variants promote activation of RIPK1, and lead to an autoinflammatory disease characterized by hypersensitivity to apoptosis and necroptosis and increased inflammatory response in peripheral blood mononuclear cells, as well as a compensatory mechanism to protect against several pro-death stimuli in fibroblasts.

Current Status of the Management of Mendelian Susceptibility to Mycobacterial Disease in Mainland China.

PURPOSE: Although many studies have investigated Mendelian susceptibility to mycobacterial disease (MSMD) worldwide, there is no report of the long-term clinical management and prognosis for MSMD in China. METHODS: This is a cohort study from January 2000 to June 2018. Three hundred and twenty-four patients with bacillus Calmette-Guérin (BCG) infection were diagnosed during this period, and those with MSMD diagnosed by genetic and functional experiments were enrolled in the study. The clinical and genetic characteristics and management of these MSMD patients were summarized. RESULTS: Thirty patients diagnosed with MSMD were followed up. The age at the follow-up end point ranged from 5 to 173 months. Among the patients, IL12RB1 mutations were identified in 22, IFNGR1 mutations in 5, STAT1 mutations in 2, and IFNGR2 mutation in 1. The medium age at onset was 3 months. BCG infection involved multiple organs, including regional infection (8/30; 26.7%) or distant or disseminated infection (22/30; 73.3%). Ten percent (30/324) of patients with BCG infection had a confirmed MSMD diagnosis. Protein expression of IL12RB1 or IFNGR1 was decreased in all patients with IL12RB1 or IFNGR1 mutation, respectively, as indicated by flow cytometry. In addition, 77.8% of patients received rhIFN-γ treatment, which can improve the prognosis of patients with IL12RB1 deficiency. Two patients received stem cell transplantation. Twenty-five patients remained alive at the time of publication. CONCLUSION: MSMD is an important cause of BCG infection. Flow cytometric detection of IL12RB1 and IFNGR1 expression is very useful for rapid MSMD diagnosis. rhIFN-γ therapy is effective in patients with MSMD, particularly improving prognosis in those with IL12RB1 deficiency.

Residue levels and health risk of pesticide residues in bell pepper in Shandong.

The purpose of this study was to investigate pesticide residues in bell peppers from Shandong Province, China. A total of 299 samples were collected from 17 cities in 2016. The concentrations of 26 pesticide residues were determined by gas chromatography with mass spectrometry (GC-MS). The results showed that there were 25 pesticides (15 OPs, 7 PYs, 3 CBs) found in 86 bell pepper samples, and the total number of positives was 120. The total frequency was 28.76%. The detection frequency for OPs, PYs and CBs was 16.39%, 12.37% and 3.01%, respectively. The most frequently detected pesticide was bifenthrin, with the frequency of 5.02%. 5.35% of samples contained pesticide residues above the maximum residue limits (MRLs) set by China. 7.36% of samples contained more than one pesticide. The values of %ADI were below 100, while the %ARfD of carbofuran and methidathion exceeded 100 for children. The cumulative risk was highest for OPs. From the public health point of view, the levels of pesticide residues in bell peppers do not pose a serious health risk to adults, but the acute health risk to children should be paid more attention.

Association between serum magnesium and blood count: influence of type 2 diabetes and central obesity.

The relationship between serum Mg and blood cell counts in Chinese adult diabetes or central obesity was assessed by investigating 8163 subjects with China Health and Nutrition Survey (mean age 59⋅6 years, 54⋅9 % men). Participants were classified according to blood Mg (below 0⋅65 mmol/l, or 0⋅66-0⋅94 mmol/l or above 0⋅95 mmol/l), type 2 diabetes (yes/no) and central obesity (yes/no). Leucocytes, erythrocytes, platelets (PLT), Hb and glycated Hb (HbA1c) were determined using standardised methods and conditions. HbAc1, leucocytes and PLT were significantly higher among subjects with central obesity than without central obesity (P < 0⋅05). A significant increase for Hb, erythrocytes, PLT, but not leucocytes, across progressive Mg groups was observed in subjects without diabetes (P < 0⋅05). Hb, erythrocytes and HbAc1 were significantly higher among subjects with higher Mg than in subjects with lower Mg with diabetes (P < 0⋅05). Central obesity disturbed the positive association between PLT count and serum Mg. Type 2 diabetes caused metabolism disorder in serum Mg, blood sugar and blood cell count. Hb, erythrocytes and PLT, but not leucocytes, are positively correlated with serum Mg, but this association is somehow disturbed by type 2 diabetes or central obesity.

Report of a Chinese Cohort with Leukocyte Adhesion Deficiency-I and Four Novel Mutations.

PURPOSE: We aimed to report the characteristics of leukocyte adhesion deficiency-I (LAD-I) and four novel mutations in the ITGB2 gene in a Chinese cohort. METHODS: Seven patients with LAD-I were reported in our study. Clinical manifestations and immunological phenotypes were reviewed. The expression of CD18 was detected by flow cytometry. Next-generation sequencing (NGS) and Sanger sequencing were performed to identify gene mutations. RESULTS: The mean onset age of all the patients was 1.3 months. Recurrent bacterial infections of the skin and lungs were the most common symptoms. Most patients (6/7) had delayed cord separation. The number of white blood cells (WBC) was increased significantly, except that two patients had a mild increase in the number of WBC during infection-free periods. The expression of CD18 was very low in all patients. Homozygous or compound heterozygous mutations in the ITGB2 gene were identified in each patient. Four mutations were novel, including c.1794dupC (p.N599Qfs*93), c.1788C>A (p.C596X), c.841-849del9, and c.741+1delG. Two patients had large deletions of the ITGB2 gene. Five patients were cured by hematopoietic stem cell transplantation (HSCT). CONCLUSIONS: This study reported the clinical and molecular characteristics of a Chinese patient cohort. It is helpful in understanding the current status of the disease in China.

Novel Heterogeneous Mutation of TNFAIP3 in a Chinese Patient with Behçet-Like Phenotype and Persistent EBV Viremia.

PURPOSE: Tumor necrosis factor alpha-induced protein 3 (TNFAIP3, A20) is a negative regulator of the nuclear factor-κB (NF-κB) pathway. It has recently been recognized that TNFAIP3 deficiency leads to early onset of autoinflammatory and autoimmune syndrome resembling Behçet's disease. Here, we report a novel mutation in TNFAIP3 in a Chinese patient, who had Behçet-like phenotype and persistent Epstein-Barr virus (EBV) viremia. METHODS: The clinical data were collected. Immunological function was detected. Gene mutation was detected by whole-exome sequencing (WES) and confirmed by Sanger sequencing. mRNA and protein levels were detected in the patient under lipopolysaccharide (LPS) stimulation by real-time PCR and Western blot. RESULTS: The patient is a 13-year-old boy, presenting with intermittent fever for 5 months, who also experienced diffuse lymphadenopathy, arthritis, and recurrent multiple gastrointestinal ulcers. EBV DNA was detected in the serum and peripheral blood mononuclear cells of the patient. The immunological phenotype showed increased proportion of double-negative T cells (CD3+CD4-CD8-). A novel missense mutation (c.1428G > A) locating at the zinc fingers 2 (ZF2) domain of TNFAIP3 inherited from his mother was confirmed. Compared with age-matched healthy controls, decrease expression of A20 was observed in the patient. The NF-κB pathway was found to be overactivated, and the synthesis of TNF-α was upregulated in the patient-derived cells. However, cells from the mother showed a milder response to LPS than cells from the patient. CONCLUSIONS: The present research indicated that the TNFAIP3 mutation of c.1428G > A (p.M476I) leads to the reduced suppression of NF-κB activation and accounted for the autoinflammatory phenotype and persistent EBV viremia in the patient.

A Chinese DADA2 patient: report of two novel mutations and successful HSCT.

Deficiency of adenosine deaminase 2 (DADA2) is an autoinflammatory disease caused by autosomal recessive mutations in Cat Eye Syndrome Chromosome Region 1 (CECR1) gene. In this report, we aimed to describe the clinical manifestations, immunological features, genotype, and treatments of one Chinese patient with novel CECR1 gene mutations. This patient initially presented with recurrent fever and rashes from the age of 3 months, but no pathogen was found. She then developed dry gangrene of the fingers at 5 months of age. Laboratory examinations revealed elevated levels of C-reactive protein and thrombocytes. The expression of interleukin-6 (IL-6) and IL-8 were both elevated. Sequencing results revealed that she had compound heterozygous mutations in CECR1 gene (c.1211T>C, p.Phe404Ser and c.1114 G>A, p.Val372Met). Subsequently, treatment with anti-IL-6 (tocilizumab) was started. However, she developed blurred vision in the right eye with occlusion of the central retinal artery, accompanied by unsteady gait. Magnetic resonance imaging (MRI) showed infarction of the right thalamus. Finally, she underwent hematopoietic stem cell transplantation (HSCT) and is currently in remission. Our findings suggest that HSCT could cure this disease.

Report of a Chinese Cohort with Activated Phosphoinositide 3-Kinase δ Syndrome.

PURPOSE: We aimed to report the clinical manifestations and immunological features of activated phosphatidylinositol 3-kinase δ syndrome 1 (APDS1) in a Chinese cohort. Moreover, we investigated the efficacy and safety of rapamycin therapy for Chinese patients with APDS1. METHODS: Fifteen Chinese patients with APDS1 from 14 unrelated families were enrolled in this study. These patients were diagnosed based on clinical features, immunological phenotype, and whole-exome sequencing. Four patients were treated with rapamycin, and the clinical efficacy and safety of rapamycin were observed. The changes of phosphorylation of Akt and mammalian target of rapamycin (mTOR) signaling pathway after rapamycin treatment were detected by flow cytometry and real-time PCR. RESULTS: The common clinical manifestations of the patients included lymphadenopathy (93%), recurrent sinopulmonary infections (93%), hepatosplenomegaly (93%), and diarrhea (78%). Epstein-Barr virus (EBV) (80%) and fungus (Aspergillus) (47%) were the most common pathogens. Immunological phenotype included elevated Immunoglobulin (Ig) M levels (100%), decreased naive T cells, increased senescent T cells, and expanded transitional B cells. Whole-exome sequencing indicated that 13 patients had heterogeneous PIK3CD E1021K mutations, 1 patient had heterogeneous E1025G mutation and 1 patient had heterogeneous Y524N mutation. Gain-of-function (GOF) PIK3CD mutations increased the phosphorylation of the Akt-mTOR signaling pathway. Four patients underwent rapamycin therapy, experiencing substantial improvement in clinical symptoms and immunological phenotype. Rapamycin inhibited the activated Akt-mTOR signaling pathway. CONCLUSIONS: We described 15 Chinese patients with APDS1. Treatment with the mTOR inhibitor rapamycin improved patient outcomes.

A Cohort of 169 Chronic Granulomatous Disease Patients Exposed to BCG Vaccination: a Retrospective Study from a Single Center in Shanghai, China (2004-2017).

PURPOSE: Clinical diagnosis and treatment for chronic granulomatous disease (CGD) have advanced greatly in recent years. However, CGD patients in China have unique clinical features and infection spectrums, which are challenging to their caretakers. Here, we summarized the clinical characteristics, genetic features, treatment, and prognosis of CGD in a single center in Shanghai. METHODS: One hundred sixty-nine CGD patients were recruited between January 2004 and May 2017 based on clinical diagnosis. Electronic medical charts were reviewed to collect clinical data. RESULTS: Among the 169 patients recruited, CYBB mutations were identified in 150 cases, whereas CYBA mutations were identified in 7 cases, NCF1 in 5, and NCF2 in 7. The medium age at onset was 1 month (interquartile range 1-3). The medium age at diagnosis was 8 months (interquartile range 3-19). The most common infection sites were the lung (95.9%), lymph node (58.5%), skin (45.4%), intestinal (43.1%), and perianal (38.5%). Bacillus Calmette-Guérin (BCG) infections were common (59.2%). In addition, other non-infectious complications were also common, including anemia (55.4%) and impaired liver functions (34.6%). Thirty-one patients received stem cell transplantation. By the end of this study, 83/131 patients survived. CONCLUSIONS: Similar to other non-consanguineous populations, X-linked CGD accounted for the majority of the cases in China. However, BCG infections were a clinical challenge unique to China. In addition, severe infections were the major cause of death and the overall mortality was still high in China.

The three CYBA variants (rs4673, rs1049254 and rs1049255) are benign: new evidence from a patient with CGD.

BACKGROUND: Chronic granulomatous disease (CGD) is an inherited immunodeficiency disease caused by the defect of NADPH oxidase. Mutations in CYBB or CYBA gene may result in membrane subunits, gp91phox or p22phox, expression failure respectively and NADPH oxidase deficiency. Previous study showed that three variants, c.214 T > C (rs4673), c.521 T > C (rs1049254) and c.*24G > A (rs1049255), in CYBA gene form a haplotype, which are associated with decreased reactive oxygen species generation. The study aims to confirm the three above mentioned variants are benign and report a novel mutation in CYBB gene. METHODS: A patient with CGD and his family members were enrolled in the study. NADPH oxidase activity and gp91phox protein expression of neutrophils were analyzed by flow cytometry. Direct sequencing was used to detect CYBB and CYBA gene mutations. RESULTS: The patient was diagnosed with CGD according to clinical and immune phenotype. The case has a novel homozygous mutation in CYBB gene and the above mentioned three variants in CYBA gene. The mutation in CYBB gene was confirmed to be pathogenic, and the three variants in CYBA gene to be benign. CONCLUSIONS: The study not only reported a novel mutation in CYBB, which results in CGD, but also confirmed the above mentioned three variants in CYBA are benign.

Concentrations and health risk assessment of rare earth elements in vegetables from mining area in Shandong, China.

To investigate the concentrations of rare earth elements in vegetables and assess human health risk through vegetable consumption, a total of 301 vegetable samples were collected from mining area and control area in Shandong, China. The contents of 14 rare earth elements were determined by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). The total rare earth elements in vegetables from mining and control areas were 94.08 µg kg-1 and 38.67 µg kg-1, respectively, and the difference was statistically significant (p < 0.05). The leaf vegetable had the highest rare earth elements concentration (984.24 µg kg-1 and 81.24 µg kg-1 for mining and control areas, respectively) and gourd vegetable had the lowest rare earth elements concentration (37.34 µg kg-1 and 24.63 µg kg-1 for mining and control areas, respectively). For both areas, the rare earth elements concentration in vegetables declined in the order of leaf vegetable > taproot vegetable > alliaceous vegetable > gourd vegetable. The rare earth elements distribution patterns for both areas were characterized by enrichment of light rare earth elements. The health risk assessment demonstrated that the estimated daily intakes (0.69 µg kg-1 d-1 and 0.28 µg kg-1 d-1 for mining and control areas, respectively) of rare earth elements through vegetable consumption were significantly lower than the acceptable daily intake (70 µg kg-1 d-1). The damage to adults can be neglected, but more attention should be paid to the effects of continuous exposure to low levels of rare earth elements on children.

Efficacy of allergen-specific immunotherapy for peanut allergy: a meta-analysis of randomized controlled trials.

Peanut allergy is one of the most common food allergies. Allergen-specific oral immunotherapy (OIT) and sublingual immunotherapy (SLIT) for peanut allergy aim to induce desensitization and then tolerance to peanuts. However, there is still considerable uncertainty about the safety of these two approaches and if the risk is justified by the benefit of the therapy. We performed a systematic review and meta-analysis to assess the efficacy and safety of OIT and SLIT in patients with peanut allergy. We performed searches of the MEDLINE, CINAHL, EMBASE, ISI Web of Science, and Cochrane databases (through March 18, 2013) for randomized controlled trials (RCTs) that compared OIT or SLIT with a placebo in patients with peanut allergy. The study selection and data extraction were independently performed by two reviewers. The primary outcome was the proportion of patients whose condition improved. We also analyzed immunologic changes and adverse events. A meta-analysis was performed using a random effects model. Three RCTs that comprised a total of 86 subjects were analyzed. OIT or SLIT had a significantly positive effect on peanut allergy (odds ratio [OR], 38.44; 95% confidential interval [CI], 6.01-245.81). Several immunologic changes associated with the induction of tolerance were improvements. There is no difference between the OIT or SLIT group and placebo group in the number of patients who required epinephrine during the study (OR, 0.51; 95% CI, 0.03-10.20). This study showed a statistically significant benefit of peanut immunotherapy in patients with peanut allergy. However, these findings are based on an analysis of a small number of RCTs. Additional larger, well-designed and double-blind RCTs are needed.

Clinical characteristics and immunogenetics of BCGosis/BCGitis in Chinese children: a 6 year follow-up study.

In this study, the clinical and immunogenetical features in a cohort of Chinese patients with BCGosis/BCGitis were investigated. For the patients with abnormal immunological functions, Sanger sequencing was used to identify the involved genes. There were 74 confirmed cases of BCGosis/BCGitis during 2007-2012. Classified by infected tissues and organs, no cases only had local infection, 39 patients had a regional infection, 21 patients had a distant infection and 14 patients had a disseminated infection. Thirty-two patients (43.2%) had definitive primary immunodeficiency diseases (PID) and chronic granulomatous disease (CGD) is the most common PID (n = 23, accounted for 71.9% of all PID patients). For CGD patients, based on the anti-tuberculosis treatment, administration of rhIFN-γ resulted in better control of BCGosis/BCGitis. The results indicate that PIDs are associated with susceptibility to BCG disease. For children with BCGosis/BCGitis, immune function evaluation is necessary, and IFN-γ treatment for BCGosis/BCGitis patients with CGD is effective.