Iron metabolism disorder and multiple sclerosis: a comprehensive analysis.

Background: Multiple sclerosis (MS) is the most common chronic inflammatory disease of the central nervous system. Currently, the pathological mechanisms of MS are not fully understood, but research has suggested that iron metabolism disorder may be associated with the onset and clinical manifestations of MS. Methods and materials: The study utilized publicly available databases and bioinformatics techniques for gene expression data analysis, including differential expression analysis, weighted correlation network analysis, gene enrichment analysis, and construction of logistic regression models. Subsequently, Mendelian randomization was used to assess the causal relationship between different iron metabolism markers and MS. Results: This study identified IREB2, LAMP2, ISCU, ATP6V1G1, ATP13A2, and SKP1 as genes associated with multiple sclerosis (MS) and iron metabolism, establishing their multi-gene diagnostic value for MS with an AUC of 0.83. Additionally, Mendelian randomization analysis revealed a potential causal relationship between transferrin saturation and MS (p=2.22E-02; OR 95%CI=0.86 (0.75, 0.98)), as well as serum transferrin and MS (p=2.18E-04; OR 95%CI=1.22 (1.10, 1.36)). Conclusion: This study comprehensively explored the relationship between iron metabolism and MS through integrated bioinformatics analysis and Mendelian randomization methods. The findings provide important insights for further research into the role of iron metabolism disorder in the pathogenesis of MS and offer crucial theoretical support for the treatment of MS.

Chinese clinical practice guidelines for acute infectious diarrhea in children.

BACKGROUND: The guidelines addressed the evidence-based indications for the management of children with acute infectious diarrhea in Chinese pediatric population. DATA SOURCES: The experts group of evidence development put forward clinical problems, collects evidence, forms preliminary recommendations, and then uses open-ended discussions to form recommendations. The literature review was done for developing this guideline in databases including PubMed, Cochrane, EMBASE, China Biomedical Database, and Chinese Journal Full-text Database up to June 2013. Search the topic "acute diarrhea" or "enteritis" and "adolescent" or "child" or "Pediatric patient" or "Baby" or "Infant". RESULTS: For the treatment of mild, moderate dehydration, hypotonic oral rehydration solutions (ORS) are strongly recommended. Intravenous (IV) rehydration is recommended for severe dehydration, with a mixture of alkali-containing dextrose sodium solution. Nasogastric feeding tube rehydration is used for children with severe dehydration without IV infusion conditions with ORS solution. Regular feeding should resume as soon as possible after oral rehydration or IV rehydration. The lactose-free diet can shorten the diarrhea duration. Zinc supplements are recommended in children with acute infectious diarrhea. Saccharomyces boulardii and Lactobacillus Rhamnus are recommended to be used in acute watery diarrhea. Saccharomyces boulardii is recommended in children with antibiotic-associated diarrhea as well. Montmorillonite and Racecadotril (acetorphan) can improve the symptoms of diarrhea or shorten the course of acute watery diarrhea. Antibiotics are recommended with dysenteric-like diarrhea, suspected cholera with severe dehydration, immunodeficiency, and premature delivery children with chronic underlying disease; otherwise, antibiotics are not recommended. CONCLUSION: The principles of the most controversial treatments with of acute infectious disease are reaching to a consensus in China.

Circulating microRNAs as biomarkers for the early diagnosis of childhood tuberculosis infection.

MicroRNAs (miRNAs) are a class of highly conserved, single-stranded RNA molecules (length, 18-25 nt) that regulate the expression of their target mRNAs. Previous studies have demonstrated that miRNAs may be novel biomarkers in the diagnosis of certain diseases. In order to evaluate the diagnostic value of miRNAs in childhood tuberculosis (TB), the circulating miRNA profile was determined using microarray analysis. An miRNA­gene network was constructed to identify closely associated miRNAs and these miRNAs were validated using reverse transcription­quantitative polymerase chain reaction (RT­qPCR). A receiver operational curve (ROC) was used to evaluate the diagnostic sensitivity and specificity of confirmed miRNAs. The microarray data demonstrated that 29 miRNAs were altered with 15 upregulated and 14 downregulated. The network showed indicated 14 miRNAs that are critical in childhood TB. RT-qPCR validated that miR-1, miR-155, miR­31, miR­146a, miR­10a, miR­125b and miR­150 were downregulated in while miR­29 was upregulated in children with TB compared with uninfected children. The ROC curve data indicated the diagnostic value of single miRNA was as follows: miR­150>miR­146a>miR­125b>miR­31>miR­10a>miR­1>miR­155>miR­29. Notably, a combination of these miRNAs exhibited increased diagnostic value compared with any single miRNA. To the best of our knowledge, the present study is the first to identify the expression profile of circulating miRNAs in childhood TB and demonstrated that miRNAs may be a novel, non­invasive and effective biomarker for the early diagnosis of childhood TB.

Epidemiology and Clinical Characteristics of Pediatric Drug-Resistant Tuberculosis in Chongqing, China.

To gain insight into the epidemiology of childhood drug resistant tuberculosis (DR-TB) in China that has the second largest burden of TB and the largest number of multidrug resistant (MDR) TB cases in the world, we performed the cross-sectional study to investigate drug resistance of four first-line anti-TB drugs (isoniazid, rifampicin, streptomycin and ethambutol) using Mycobacterium tuberculosis isolates from 196 culture-confirmed pediatric TB cases diagnosed in the Children's Hospital of Chongqing Medical University, China during 2008-2013. Univariate and multivariate logistic regression analyses were performed to assess the associations between patient demographic and clinical characteristics and DR-and MDR-TB, respectively. Twenty-eight percent (56/196) of the study patients exhibited resistance to at least one of the four first-line anti-TB drugs tested. MDR was found in 4.6% (9/196) of the study patients. More than half (5/9, 55.6%) of the MDR cases were from a single county of Chongqing. A significant association was found between being acid-fast bacilli-smear negative and DR-TB (adjusted OR, 2.33; 95% CI, 1.13-4.80) and between having concurrent thoracic-extrathoracic involvement and MDR-TB (adjusted OR, 9.49; 95% CI, 1.05-85.92), respectively. The findings of this study indicate that the rate of DR is high among pediatric TB patients in Chongqing and suggest an urgent need for studies to identify MDR transmission hotspots in Chongqing, thereby contributing to the control DR- and MDR-TB epidemics in China. The study also generates new insight into the pathogenesis of DR and MDR M. tuberculosis strains and highlights the importance of studying childhood TB to the goal of global TB control.

Clinical and Etiological Characteristics of Atypical Hand-Foot-and-Mouth Disease in Children from Chongqing, China: A Retrospective Study.

BACKGROUND: Hand-foot-and-mouth disease (HFMD) is a disease that had similar manifestations to chickenpox, impetigo, and measles, which is easy to misdiagnose and subsequently causes delayed therapy and subsequent epidemic. To date, no study has been conducted to report the clinical and epidemiological characteristics of atypical HFMD. METHODS: 64 children with atypical HFMD out of 887 HFMD children were recruited, stool was collected, and viral VP1 was detected. RESULTS: The atypical HFMD accounted for 7.2% of total HFMD in the same period (64/887) and there were two peaks in its prevalence in nonepidemic seasons. Ten children (15.6%) had manifestations of neurologic involvement, of whom 4 (6.3%) were diagnosed with severe HFMD and 1 with critically severe HFMD, but all recovered smoothly. Onychomadesis and desquamation were found in 14 patients (21.9%) and 15 patients (23.4%), respectively. The most common pathogen was coxsackievirus A6 (CV-A6) which accounted for 67.2%, followed by nontypable enterovirus (26.6%), enterovirus 71 (EV-A71) (4.7%), and coxsackievirus A16 (A16) (1.5%). CONCLUSIONS: Atypical HFMD has seasonal prevalence. The manifestations of neurologic involvement in atypical HFMD are mild and usually have a good prognosis. CV-A6 is a major pathogen causing atypical HFMD, but not a major pathogen in Chongqing, China.

Host and Microbial Predictors of Childhood Extrathoracic Tuberculosis and Tuberculosis Meningitis.

BACKGROUND: Childhood tuberculosis (TB) is a major infectious disease causing morbidity and mortality in children and yet has been largely ignored until recently. This study is the first study to characterize childhood TB in China incorporating both Mycobacterium tuberculosis genetic characteristics and patient data. METHODS: We analyzed a total of 331 culture-confirmed childhood TB cases and 158 M. tuberculosis isolates from a subset of the study sample. Univariate and multivariate logistic regression analyses were performed to identify host and microbial predictors for having extrathoracic TB alone, concurrent thoracic and extrathoracic TB and TB meningitis (TBM), respectively. RESULTS: Fifty-eight percent (192/331) of the study subjects had extrathoracic TB, and 139 (42.0%) cases had TBM. Both age of less than 5 years [adjusted odds ratio (OR): 4.52; 95% confidence interval (CI): 1.27-16.16] and female sex (adjusted OR: 2.72; 95% CI: 1.03-7.18) were significantly associated with extrathoracic TB alone, whereas living in rural area (adjusted OR: 2.35; 95% CI: 1.06-5.18) was significantly associated with thoracic-extrathoracic TB. Age of less than 5 years was also strongly associated with TBM (adjusted OR: 3.63; 95% CI: 1.64-8.05). Sixty-four percent (101/158) of the study isolates were Beijing lineage strains. Infection with Beijing lineage strains was significantly associated with thoracic-extrathoracic TB (adjusted OR: 2.39; 95% CI: 1.11-5.15) and TBM (adjusted OR: 2.25; 95% CI: 1.10-4.60). CONCLUSIONS: Both microbial and host factors can affect the outcome of M. tuberculosis infection in children. Future studies incorporating host and pathogen data from different populations are warranted to develop new strategies for childhood TB control.

[Research on syndrome distribution features, etiologies, and pathogeneses of Japanese encephalitis].

OBJECTIVE: To explore Chinese medical syndrome distribution features of Japanese encephalitis (JE), and to analyze its correlation between syndromes and features of etiologies and pathogeneses. METHODS: Recruited were 277 patients with confirmative diagnosis of JE from Wuhan Medical Treatment Center, Children's Hospital Affiliated to Chongqing Medical University, Fifth People's Hospital of Guiyang City, Hangzhou Sixth People's Hospital, and Chengdu Hospital of Infectious Diseases between July to September 2012. Chinese medical syndrome distribution features were summarized from their general materials and detailed records of clinical data, including medical history, symptoms and signs, tongue fur, and pulse figures.The frequency of symptoms and signs was calculated according to mild, ordinary, severe, extreme severe degrees. The distribution of Chinese medical syndromes was summarized. And its correlation between syndromes and features of etiologies and pathogeneses were analyzed. RESULTS: After clustering analysis, Chinese medical syndromes of JE could be categorized as four groups: toxicity accumulation in Fei and Wei syndrome (TAFWS), brain collateral impaired by poison syndrome (BCIPS), depression of toxicity in the pericardium syndrome (DTPS), exhaustion of yin and yang syndrome (EYYS). BCIPS and DTPS were dominated, accounting for 74.0% (205 cases). The main causes covered evil of summer heat [accounting for 92.42% (256/277 cases)], heat [accounting for 87.73% (243/277 cases)], and toxin [accounting for 99.64% (276/277 cases)]. CONCLUSIONS: The four Chinese medical syndrome types of JE met Chinese medical clinical features of encephalitis. It is induced by infestation of dampness-heat, resulting in toxicity accumulation in Fei and Wei, brain collateral impaired by poison, depression of toxicity in the pericardium. Yin fluid and blood is exhausted as time goes by. Qi and yin are impaired to form intermingled deficiency and excess, and finally causing exhaustion of yin and yang.

Genomic analysis of a newly isolated of Japanese encephalitis virus strain, CQ11-66, from a pediatric patient in China.

BACKGROUND: Japanese encephalitis virus (JEV) is one of the major causative agents of viral encephalitis in East Asia, Southeast Asia and Australia. However, no clinical JEV strain has yet been isolated from JE patients in Chongqing, China. In this study, we report the genomic analysis of a new JEV strain, CQ11-66, isolated from a pediatric patient in Chongqing, China. FINDINGS: Virus isolation was carried out in BHK-21 cells. Nested PCR was used to detect and isolate the JEV strain, and computer analysis of phylogenetic relationships, nucleic acid homology studies and deduction of the amino acid sequence were conducted using ClustalX (1.8) and Mega5 software. The JEV strain CQ11-66 was isolated from patient cerebrospinal fluid. The sequenced genome of CQ11-66 was 10,863 nucleotides in length, whereas other strains, such as SX09S-01, contain 10,965 nucleotides. Sequence comparison of the CQ11-66 polyprotein open reading frame (ORF) with those of 21 other JEV strains revealed that the nucleotide sequence divergence ranged from 1.68% to 18.46%. Sequence analysis of the full-length CQ11-66 E gene sequence with those of 30 other JEV isolates also identified nucleotide divergence, ranging from 1.69% to 18.74%. Phylogenetic analyses indicated that the CQ11-66 strain belonged to genotype III. CONCLUSIONS: JEV genotype III still circulates in Chongqing and it is therefore important for active surveillance of JEV genotype III to be conducted in the pediatric population.

Children of rural-to-urban migrant workers in China are at a higher risk of contracting severe hand, foot and mouth disease and EV71 infection: a hospital-based study.

The incidence and severity of hand, foot and mouth disease have increased in mainland China since 2008. Therapies and vaccines are currently at different stages of development. This study aimed to determine the social factors associated with the outbreaks and severity of the disease in Chinese children. A multicentre, prospective, case-controlled study was conducted in Shanghai, Chongqing, Guangzhou and Shantou to identify the sociodemographic and behavioural risk factors for hand, foot and mouth disease. Children hospitalized for hand, foot and mouth disease were randomly enrolled from April to November 2011. Stool samples were collected to test for the presence of enterovirus 71 (EV71). A total of 443 children between 1.6 and 68 months of age were enrolled; 304 were uncomplicated cases and 139 were severe cases with central nervous system involvement. The overall detection rate of EV71 was 54.2%, and the positivity rate of EV71 was significantly higher in the severe group than in the uncomplicated group (82.0% versus 40.9%, odds ratio (OR): 8.35, P=0.000). The children of migrant workers (OR: 3.014, P=0.000) and children attending kindergarten (OR: 2.133, P=0.002) were significantly associated with a severe outcome of the disease (OR: 1.765, P=0.026). Our findings indicate that kindergarten attendance and migrant worker parents are the major risk factors associated with severe hand, foot and mouth disease in children <5 years of age. Future public health intervention vaccination campaigns should consider the particular difficulties of achieving high compliance with multiple-dose vaccination regimens in the children of migrant workers.

Screening and comparison of differentially expressed genes between one MDR-TB strain and the virulent M. tuberculosis H37Rv.

To screen and compare the differentially expressed genes between one MDR-TB strain separated from one child patient and the virulent Mycobacterium tuberculosis H37Rv, suppression subtractive hybridization (SSH) technology was used to build a library of cDNAs that were differentially expressed in the MDR and H37Rv. From this cDNA library, genes that were expressed in the MDR-TB but not in the H37Rv were selected for gene sequencing and homology analysis; 113 positive clones were obtained, their cDNA fragments were sequenced, and homology analysis was performed. Four novel sequences were identified. The results provide a partial list of genes differentially expressed in MDR-TB and four novel genes were found. Identification of these genes may contribute to our understanding of MDR-TB development.

Clinical and molecular epidemiology of norovirus infection in childhood diarrhea in China.

A prospective investigation was carried out among pediatric outpatients and inpatients with acute non-dysenteric diarrhea between August, 2008 and July, 2009 in Shanghai, Hangzhou, Chongqing, and Tianjin, China. One step real-time RT-PCR was used for detection of norovirus (NoV) genogroups I and II (GI, GII). The NoV genotypes were classified based on partial capsid sequences. Rotavirus (RV) was detected in parallel. Among 4,123 fecal samples from outpatients, 1,067 (25.9%) were NoV-positive, of which 1,051 (98.5%) belonged to GII and 1,309 (31.7%) were RV-positive. In the inpatient group (n = 317), 25.6% were NoV-positive and 41.6% were RV-positive. Four hundred and fifty-one out of 1,067 NoV-positive strains were sequenced and genotyped and 6 typed strains were GI (3 GI.3, 2 GI.5, 1 GI.4) and 445 typed strains were GII. GII strains clustered into nine genotypes including GII.4 2006b (69.2%), the only GII.4 variant identified in this study, followed by GII.3 (23.8%), GII.6 (3.6%), GII.12 (1.3%), GII.2 (0.9%), GII.13 (0.4%), GII.14 (0.2%), GII.7 (0.2%), and GII.16 (0.2%). A peak of NoV infections was observed during the cold season in Tianjin, while NoV activity was higher between late summer and autumn and lower during winter in Shanghai, Hangzhou, and Chongqing. NoV is a common causative agent of childhood diarrhea in China and the seasons of NoV-associated diarrhea varies between regions. The results show that NoV GII.4 2006b was the predominant strain circulating in China between 2008 and 2009.

[Genotyping of 210 Mycobacterium tuberculosis strains with Spoligotyping and MIRU-VNTR among pediatric tuberculosis patients in Chongqing].

OBJECTIVE: To evaluate the application of spacer oligonucleotide typing (Spoligotyping) and mycobacterial interspersed repetitive unit-variable-number tandem repeat (MIRU-VNTR) analysis in the molecular-epidemiological study of tuberculosis and to discuss the characteristics of pediatric Mycobacterium (M.) tuberculosis strains in Chongqing. METHODS: M. tuberculosis strains isolated and typed by Spoligotyping and MIRU-VNTR respectively, from the children patients in Chongqing and to compare the results from both methods, epidemiologically. RESULTS: By means of Spoligotyping, 210 clinical isolates were divided into 2 gene groups, displaying 44 genotypes. Among them, the biggest group was M. tuberculosis Beijing family, including 130 strains (61.90%), using the Spoligotyping. From the results of MIRU-VNTR, 24 loci showed different polymorphism and the HGI of different loci set (12 old loci, 15 basic loci and 24-loci set) increased accordingly. The subtle difference in HGI was originated from one locus ETR-B, which was included in the 24-locus system. The diversity of each loci and MIRU-VNTR set for non-Beijing genotype strains was higher than that of the Beijing genotype strains. CONCLUSION: In this study, it was preliminarily confirmed the existence of high polymorphism of M. tuberculosis while the Beijing Family was the main genotype and main prevalent strain in children of Chongqing area. Spoligotyping prior to 15-locus with ETR-B combination seemed more suitable for the massive epidemiological investigation of pediatric tuberculosis patients.

DNA polymorphism of Mycobacterium tuberculosis PE_PGRS33 gene among clinical isolates of pediatric TB patients and its associations with clinical presentation.

In vitro and in animal studies have suggested an important role for the Mycobacterium tuberculosis PE_PGRS33 protein in the pathogenesis of TB. A significant level of PE_PGRS33 gene DNA polymorphism among clinical isolates from adult tuberculosis (TB) patients and its association with clinical and epidemiological phenotypes of the disease has been found. To better understand the role of PE_PGRS33 protein in the pathogenesis pediatric TB, we investigated DNA polymorphism of the PE_PGRS33 gene among 101 of pediatric TB patients' isolates and assessed the relationship between the PE_PGRS33 sequence variation and clinical characteristics of TB. Twelve different PE_PGRS33 sequence variations representing 12 different alleles were observed among the 101 M. tuberculosis clinical isolates investigated. Of these 101 isolates, 62(59.41%) had PE_PGRS33 alleles that would result in a change in the amino acid sequence of the PE_PGRS33 protein. The degree of DNA polymorphism within individual M. tuberculosis isolates from pediatric TB patients was remarkably lower than that previously found in M. tuberculosis isolates from adults TB patients. The frequency distribution of isolates having PE_PGRS33 gene sequence variations was similar between Beijing and non-Beijing families of the pathogen. Patients having TB meningitis and negative PPD skin test results appeared to be more likely to be infected by isolates having a mutant type of the PE_PGRS33 gene than patients who had no TB meningitis (OR 2.54, 95% CI [1.11-5.84]) and patients who had positive PPD-skin test results (OR 4.26, 95% CI [1.14-12.86]), respectively. This study provides new insight into the molecular pathogenesis of pediatric TB.

Usefulness of mycobacterial interspersed repetitive-unit locus PCR amplification in rapid diagnosis of Beijing lineage strain infection among pediatric tuberculosis patients.

We assessed the usefulness of mycobacterial interspersed repetitive-unit-variable-number tandem-repeat loci 26, 31, ETR-A, Mtub30, and Mtub02 and a deletion-targeted multiplex PCR in identifying pediatric Mycobacterium tuberculosis Beijing lineage strain infection. We found that the Beijing lineage isolates accounted for ∼ 62% (130/210) of the study isolates.

[Epidemiological surveillance of norovirus and rotavirus diarrhea among outpatient children in five metropolitan cities].

OBJECTIVE: To survey the clinical epidemiological features of norovirus and rotavirus diarrhea among children living in 5 cities. METHOD: A prospective epidemiological investigation was conducted among outpatient children with acute diarrhea between August 2008 and July 2009 in Shanghai, Hangzhou, Guangzhou, Chongqing and Tianjin. The stool samples were randomly collected from children with non-dysentery diarrhea. Group A rotavirus antigen was tested by the kit that applies colloidal gold method in all specimens. GI and GII genogroups of norovirus were detected by one-step real-time reverse-transcription polymerase chain reaction (RT-PCR). The detection rates, seasonality and susceptible age of both viruses-associated diarrhea were analyzed. RESULT: During the one-year period, 5091 fecal samples were obtained, of which 1563 (30.7%) were rotavirus-positive. The detection rates of rotavirus were 29.5% (268/916) in Shanghai, 36.1% (334/926) in Hangzhou, 26.3% (254/968) in Guangzhou, 34.1% (359/1054) in Chongqing and 28.2% (348/1233) in Tianjin, respectively. Among the remaining 3528 rotavirus-negative samples, 1049 (29.7%) were identified to be norovirus-positive. The detection rates of norovirus were 21.2%(136/642) in Shanghai, 31.3% (185/592) in Hangzhou, 24.2% (173/714) in Guangzhou, 31.8% (221/695) in Chongqing and 37.7% (334/885) in Tianjin, respectively. It is estimated that the infection rate of norovirus among outpatients with acute diarrhea is at least more than 20.6% (1049/5092). Of 1049 norovirus strains, 1036 (98.7%) were GII genogroup and 16 (1.5%) were GI genogroup, 3 were mixed with GI and GII genogroups. The 1049 children with norovirus diarrhea aged between 1 month and 14 years with the median age of 10 months (mean: 13.9 ± 16.9 months) and 91.8% were 2 years old or younger. The 1563 children with rotavirus diarrhea aged between 1 month and 11.3 years with the median age of 10 months (mean: 12.9 ± 13.7 months) and 92.5% were 2 years old or younger. The median ages between norovirus-infected children and rotavirus-infected children were significantly different (P < 0.05). The peak seasons of rotavirus diarrhea spanned autumn and winter (from October to February). The peak seasons of norovirus diarrhea presented in the winter and spring (from November to April) in Tianjin. Norovirus became active in April and usually predominantly prevalent in the summer and autumn (from July to October) in Shanghai, Hangzhou and Chongqing. However, norovirus was sporadically prevalent in the spring and detected more commonly in the other seasons in Guangzhou. CONCLUSION: Both rotavirus and norovirus are the major causative agents for childhood diarrhea. The seasonality of rotavirus diarrhea was similar among the 5 cities. Nevertheless, the seasonality of norovirus diarrhea was diverse in the different areas. In Tianjin located in the north of China, norovirus was quite prevalent in the cold season. In the east (Shanghai and Hangzhou) and south-west (Chongqing), norovirus prevailed dominantly in the summer and autumn. In the south (Guangzhou), the activity of norovirus was more obvious in the summer, autumn and winter.

[Monocyte chemotactic protein-1 gene polymorphism and monocyte chemotactic protein-1 expression in Chongqing Han children with tuberculosis].

OBJECTIVE: The aims of this study were to evaluate whether the presence of -2518A/G polymorphism in the distal regulatory region of the monocyte chemotactic protein-1 (MCP-1) was associated with tuberculosis (TB) in Chongqing Han population and to find whether it has a significant impact on the pediatric patient. METHOD: One hundred children [ < or = 15 years old, mean age (7.3+/-4.6) years, 53 male, 47 female] and one hundred adults [51 male, 49 female, age (44.6+/-13.5) years with TB] and 200 healthy controls of comparable age were screened for genotype by PCR-sequence-specific primer (SSP) method. MCP-1 levels in the sera were detected by ELISA. RESULT: (1) TB patients and controls showed different single nucleotide polymorphism (SNP) distribution patterns (58%, 36%). MCP-1 alleles -2518G was associated with increased TB susceptibility (P<0.01). (2) The -2518 GG genotypes was associated with increased TB susceptibility (32% in TB patients and 13% in non-TB controls respectively, P<0.01). (3) The odds of developing TB in genotypes GG were higher than those in homozygous AA, and the risk was higher in children than in adult (7.0-fold in children and 5.1-fold in adults, respectively). (4) Cases of homozygous GG had the highest plasma levels of MCP-1, which increased the likelihood of developing TB. Furthermore, higher levels were observed in children than in adults. CONCLUSION: These findings suggest that persons bearing the MCP-1 genotype GG produce high concentrations of MCP-1, which increases the risk of active TB infection in Chongqing Han people. These findings are more significant in child patients than in adult patients with TB.

[Primary immunodeficiency complicated with Bacillus Calmette-Guerin infection: identification and clinical phenotype of a case of novel interleukin-12Rbeta1 gene mutation].

OBJECTIVE: Interleukin-12 receptor beta1 (IL-12 Rbeta1) deficiency is a rare primary immunodeficiency (PID) characterized by selective susceptibility to weakly virulent organisms, including Mycobacterium bovis, BCG, non-tuberculous environmental mycobacteria and non-typhoidal salmonellosis. The present study was conducted to identify the mutation type and to analyze clinical phenotype. METHODS: Based on the typical clinical manifestations and immunologic tests in this case, a varieties of PIDs were excluded and IL-12Rbeta1 deficiency was suspected. IL-12Rbeta1 chain expressed on Epstein-Barr virus-transformed lymphoblastoid B cell lines were detected by flow cytometric assay. The IL-12Rbeta1 gene sequences of the patient and her parents were analyzed by PCR-directed sequencing. The IL-12Rbeta1 gene sequences of the patient's younger brother also had been analyzed prenatally and after birth. RESULTS: After inoculating BCG, the patient suffered from multiple BCG infectious lymphadenitis. There was no detectable IL-12Rbeta1 on the Epstein-Barr virus-transformed lymphoblastoid B cell lines from the patient, while only mild expression on the cell line from her mother. Sequencing analysis by using sense and antisense primers separately, a novel IL-12Rbeta1 gene mutation was found in the patient which was homozygous single nucleotide substitution, a nonsense mutation with nucleotide substitution of C to T at position 853 (853C-->T) in exon 9 leading the glutamate at position 285 to the stop codon mutation (Q285X). The parents were carriers of the mutated IL-12Rbeta1 gene. But her younger brother has normal IL-12Rbeta1 gene. CONCLUSION: The novel IL-12Rbeta1 gene mutation is responsible for BCG infection in this case and genetic analysis is useful in carrier detection and prenatal diagnosis is feasible when the mother had a baby with identified IL-12Rbeta1 gene mutation before.