A Niemann-pick C1 disease child with BCG-itis: a case report and analysis.

BACKGROUND: Niemann-Pick C disease is a rare autosomal recessive lysosomal lipid storage disorder. Some primary immunodeficiency diseases patients developed regional disease or disseminated disease after vaccinating BCG. It is unclear whether NPC gene deficiency is associated with Mycobacteria infection. CASE PRESENTATION: We report and discuss a case of a child who presented at the age of 6 months with NPC1 and BCG-itis. The patient was treated with Miglustat and the symptom of lymphadenopathy was improved. CONCLUSIONS: We reasonably speculate that NPC1 is a susceptibility gene of Mtb infection and mainly affects innate immunity. Once diagnosed, the infant should not be vaccinated with BCG and early treated.

Safety Evaluation of Recombinant Fusion Protein RP22 as a Skin Test Reagent for Tuberculosis Diagnosis: A Phase I Clinical Trial.

INTRODUCTION: This phase I clinical trial was conducted to evaluate the safety of RP22 as a skin test reagent for tuberculosis (TB) diagnosis and to explore the appropriate dosage. METHODS: We used a randomized, double-blind, placebo-controlled identification allergen (IA) skin test. A total of 72 healthy adult volunteers with negative chest X-ray results were randomized into six groups and given a QuantiFERON-TB Gold (QFT) test. Of the 12 participants in each group, eight received RP22 and four received placebo. The doses of RP22 in the six experimental groups ranged from 0.1 to 4.0 µg in a single intradermal injection of 0.1 ml. Skin reactions and adverse events were recorded at intervals. RESULTS: All doses of RP22 except the highest were well tolerated and safe. No serious adverse events associated with the injection were observed in all groups. There were 11 participants who had positive QFT results, eight had a skin reaction with a redness or induration area diameter of greater than 10 mm at 48-72 h, one had no skin reaction. Among the 60 negative-QFT participants, none had a reaction area diameter of greater than 10 mm. CONCLUSION: The RP22 skin test was well tolerated and safe, it could play a key role in screening for latent tuberculosis infection (LTBI) by providing a much-wanted alternative to the tuberculin skin test (TST) and interferon-γ release assays (IGRAs).

Stool-based Xpert MTB/RIF Ultra assay as a tool for detecting pulmonary tuberculosis in children with abnormal chest imaging: A prospective cohort study.

OBJECTIVES: To evaluate the diagnostic efficacy of stool-based Xpert MTB/RIF Ultra assay versus other assays for the detection of paediatric pulmonary tuberculosis (PTB). METHODS: A prospective head-to-head comparative study was conducted from Dec 2017 to May 2019 in Shanghai Public Health Clinical Centre. Samples were collected from children (< 15 years) with abnormal chest imaging (X-ray or CT scan) results for the following tests: Ultra on stool sample (Ultra-Stool), Ultra on respiratory tract sample (Ultra-RTS), Xpert MTB/RIF assay (Xpert) on RTS (Xpert-RTS), acid-fast bacilli smear on RTS (AFB-RTS), and Mycobacterium tuberculosis (Mtb) culture on RTS (Culture-RTS). The results were compared with a composite reference standard. RESULTS: A total of 126 cases with paired results were analysed. Against a composite reference standard, Ultra-RTS demonstrated the highest sensitivity (52%) and specificity (100%). Ultra-Stool showed 84.1% concordance with Ultra-RTS, demonstrating 45.5% sensitivity and 94.7% specificity (kappa = 0.65, 95% CI= 0.51-0.79). The sensitivity of Ultra-Stool was similar to Mtb culture (45.5%, p = 1.000) and higher than AFB-RTS (27.3%, p < 0.05). Assay positivity was associated with age and infiltration range in chest imaging. CONCLUSIONS: When RTS is difficult to obtain, stool sample-based Ultra is a comparable alternative.

Sixty-two severe and critical patients with 2009 influenza A (H1N1) in Shanghai, China.

BACKGROUND: Pandemic influenza A (H1N1) emerged rapidly in China in May 2009. Preliminary comparisons with seasonal influenza suggest that pandemic 2009 influenza A (H1N1) disproportionately affects younger ages and causes generally mild disease. To characterize disease progress, comorbidities, and treatment outcomes among consecutive severe and critically ill patients in a hospital served as a reference center for the care of patients with H1N1 in Shanghai, China. METHODS: A retrospective study on 62 severe and critically ill patients with 2009 influenza A (H1N1) was conducted in Shanghai Public Health Clinical Center. Demographic data, symptoms, comorbidities, disease progression, treatments, and clinical outcomes were collected for analysis. RESULTS: Sixty-two severe or critically ill patients were admitted to the hospital with confirmed 2009 influenza A (H1N1) infection. The median age of the study cohort was 40 years old with a range from 18 years to 75 years, and 67.7% were males. All patients presented with fever and respiratory symptoms. At presentation, 34 patients (54.8%) had comorbidities such as smoking (29.0%), hypertension (29.0%) and hepatitis B virus infection (9.7%). The median time from symptom onset to hospital admission was 6 days (interquartile-range 3 - 14 days) and 23 critically ill patients were admitted to Intensive Care Unit after admission. All the patients received neuraminidase inhibitors (oseltaminir), while 60 patients (96.7%) were treated with antibiotics, and 39 (62.9%) with corticosteroids. Twenty-three critical cases received noninvasive mechanical ventilation on the first day of admission, and 3 of them ultimately required invasive ventilation. Four death reports (6.5%) were filed within the first 14 days from the onset of critical illness with the primary causes of severe acute respiratory distress syndrome, hypoxemia, or complications, secondary infection and sepsis, pyopneumothorax and stroke. CONCLUSIONS: Severe illness from 2009 influenza A (H1N1) infection in Shanghai occurred among young individuals. Critical cases were associated with severe hypoxemia, multisystem organ failure, and a requirement for mechanical ventilation. Most patients had a good prognosis.

[Clinical features and prognosis of the mild cases of pandemic influenza H1N1 virus infection].

OBJECTIVE: Analyze the clinical characteristics of the mild cases of pandemic influenza H1N1 virus infection, as well as the relationship of clinical characteristics and patient genders. METHODS: A total of 245 influenza A (H1N1) patients confirmed by viral nucleic acid detection were included in the study. The patients' personal information, signs and symptoms, lab and iconography data, disease course, negative seroconversion duration of new influenza A (H1N1) viral nucleic acid after antiviral treatment and hospitalization stay were analyzed. Measurement data were analyzed using one-way analysis of variance (ANOVA) by software SPSS 11.5. P < 0.05 was defined as statistically significant. RESULTS: (1) Among the 245 patients, 130 were males and 115 were females, yielding a sex ratio of 1.13:1. Almost 52.0% (127/245) of the patients came from Australia, and 64.5% (158/245) were between 18 and 40 years old. (2) Clinical manifestations included fever (98.4%, 241/245), cough (80.8%, 198/245) and throat congestion (95.9%, 235/245), and lab findings were characterized by elevated C-reaction protein (CRP, 71.0%, 174/245) and neutrophil (52.2%, 128/245). (3) Female patients had significantly lower serum Prealbumin (pre-A) levels than male patients [(245.04 ± 75.3) vs (273.34 ± 92.18) mg/L, F = 5.55, P = 0.019]. (4) The patients' serum CRF levels significantly decreased after the treatment [(4.06 ± 3.47) vs (14.54 ± 14.68) mg/L, F = 6.18, P = 0.016], while the levels of CD3, CD4 and CD8 were significantly increased after treatment [(1451.23 ± 443.97) vs (819.97 ± 375.75) cell/µl, F = 32.61, P = 0.000; (771.33 ± 251.92) vs (435.36 ± 215.35) cell/µl, F = 44.43, P = 0.000; (593.16 ± 237.19) vs (342.47 ± 180.12) cell/µl, F = 28.518, P = 0.000, respectively]. (5) Approximately 30.6% (75/245) of the patients had abnormal signs on chest CT iconography, and 22.0% (54/245) had obvious signs indicating pneumonia. The average disease course was (3.9 ± 1.2) days, the average hospitalization stay was (5.0 ± 1.4) days, and the negative seroconversion duration of the mRNA after antiviral treatment was (3.8 ± 1.4) days. CONCLUSION: The influenza A (H1N1) virus was characterized by fever, cough and throat congestion, with elevated CRP and neutrophil being the most significant lab findings. The influenza A (H1N1) strain was able to affect multiple organs, including being able to affect hepatic synthesis of pre-A as well as immune functioning. The influenza A (H1N1) influenza virus strain was mild clinically, with short disease course and good prognosis.

[Involvement of endoplasmic reticulum stress in development of fatty liver fibrosis induced by methionine-choline-deficient diet in rats].

OBJECTIVE: To study role of endoplasmic reticulum stress in the development of fatty liver fibrosis induced by methionine-choline-deficient diet in rats. METHODS: Non-alcoholic steatohepatitis was induced by 10 weeks- methionine-choline-deficient diet (MCDD), Markers of endoplasmic reticulum stress were determined by immunoblotting and real-time PCR. RESULTS: The number of apoptotic hepatocytes, The expression levels of endoplasmic reticulum stress markers were increased significantly in MCDD group compared to control group (probability value less than 0.05 or probability value less than 0.01), while ratio of hepatocyte proliferation/apoptosis was decreased in MCDD group (probability value less than 0.01). The number of hepatocytes apoptosis, and the expression levels of endoplasmic reticulum stress markers were decreased significantly 2 weeks after the feeding with normal diet in MCDD group (probability value less than 0.05 or probability value less than 0.01). CONCLUSION: MCDD induces endoplasmic reticulum stress and fibrosis in rats.

[Mechanism of hepatocyte regeneration inhibition in rats with liver fibrosis induced by lipogenic methionine-choline- deficient diet].

OBJECTIVE: To obtain the evidence of fibrotic resolution in fatty liver by changing the diet and to clarify the mechanism of hepatocyte proliferation inhibition in rat with fatty liver fibrosis. METHODS: (1) Nonalcoholic steatohepatitis with advanced fibrosis was induced in rats by giving them a methionine-choline-deficient diet (MCDD) for 10 weeks (group M). A methionine-choline-control diet (MCCD) instead of MCDD was given for the last 2 weeks to the experimental group (group R). (2) Fibrosis and inflammation were determined by tissue staining. The activation of hepatic stellate cells and Kupffer cells were determined by immunostaining, immunoblot or quantitative RT-PCR respectively. (3) Hepatocytic apoptosis and proliferation were determined by TUNEL and BrdU staining respectively. Expressions of IL-6, STAT3, JNK-1, c-Jun, p21, C/EBPalpha, HNF6 and HGF-alpha were evaluated by quantitative RT-PCR and immunoblot to clarify the mechanism of hepatocytic proliferation inhibition. RESULTS: (1) Changing the diet from MCDD to MCCD triggered the reduction of fat in hepatocytes and a decrease in inflammatory response. (2) The regression of fibrosis was accompanied by the disappearance of activated stellate cells and macrophages. (3) Compared with control group (group C), hepatocytic apoptotic number increased significantly in group M (68 +/- 16 vs 40 +/- 8, P < 0.05) and the ratio of hepatocytic proliferation/apoptosis decreased markedly in group M (0.10 +/- 0.03 vs 0.19 +/- 0.03, P < 0.01); compared to group M, hepatocytic apoptotic number decreased significantly in group R (48 +/- 6, P < 0.05) and hepatocytic proliferation number and the ratio of hepatocytic proliferation/apoptosis increased markedly in group R (17.2 +/- 4.4 vs 7.5 +/- 3.0, 0.41 +/- 0.09 vs 0.10 +/- 0.03 respectively, P < 0.01). (4) Compared with group C, the mRNA level of IL-6, JNK-1, c-Jun, C/EBPalpha, p21 and HNF6 mRNA decreased significantly (0.34 +/- 0.18 vs 1.33 +/- 0.44, 0.41 +/- 0.11 vs 0.83 +/- 0.26, 0.19 +/- 0.03 vs 1.53 +/- 1.2, 1.94 +/- 0.64 vs 4.51 +/- 1.15, 0.34 +/- 0.20 vs 1.30 +/- 0.75, 0.47 +/- 0.21 vs 0.92 +/- 0.16 respectively, P < 0.05 or P < 0.01), and protein level of IL-6, STAT3, JNK-1, c-Jun, C/EBPalpha, P21 and HNF6 also decreased significantly in liver fibrotic stage (P < 0.05 or P < 0.01) while only IL-6, JNK-1 and p21 recovered immediately after a changed diet from MCDD to MCCD (P < 0.05 or P < 0.01). CONCLUSION: Food intake is a very important factor for controlling the fatty status and pathology of liver. Hepatocytic proliferation inhibition is associated with the arrested G(0)-S phasic transition in fatty liver fibrosis and the up-regulated expression of IL-6, JNK-1 and p21. These factors play a very important role in the recovery of fatty liver fibrosis.