Assistance of next-generation sequencing for diagnosis of disseminated Bacillus Calmette-Guerin disease with X-SCID in an infant: a case report and literature review.

Bacille Calmette-Guérin (BCG) is a live strain of Mycobacterium bovis (M.bovis) for use as an attenuated vaccine to prevent tuberculosis (TB) infection, while it could also lead to an infection in immunodeficient patients. M.bovis could infect patients with immunodeficiency via BCG vaccination. Disseminated BCG disease (BCGosis) is extremely rare and has a high mortality rate. This article presents a case of a 3-month-old patient with disseminated BCG infection who was initially diagnosed with hemophagocytic syndrome (HPS) and eventually found to have X-linked severe combined immunodeficiency (X-SCID). M.bovis and its drug resistance genes were identified by metagenomics next-generation sequencing (mNGS) combined with targeted next-generation sequencing (tNGS) in blood and cerebrospinal fluid. Whole exome sequencing (WES) revealed a pathogenic variant in the common γ-chain gene (IL2RG), confirming X-SCID. Finally, antituberculosis therapy and umbilical cord blood transplantation were given to the patient. He was successfully cured of BCGosis, and his immune function was restored. The mNGS combined with the tNGS provided effective methods for diagnosing rare BCG infections in children. Their combined application significantly improved the sensitivity and specificity of the detection of M.bovis.

Extracorporeal Membrane Oxygenation in Severe Acute Respiratory Distress Syndrome Caused by Chlamydia abortus: A Case Report.

Background: Pneumonia infected by Chlamydia abortus (C. abortus) is rare, especially complicated with severe acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS). Case Presentation: We presented the clinical details of a 44-year-old male who was diagnosed with C. abortus pneumonia, which rapidly progressed and ultimately led to ARDS, sepsis and MODS. Although he was initially diagnosed with pneumonia upon admission, no pathogenic bacteria were detected in sputum by conventional tests. Empirical intravenous infusion of meropenem and moxifloxacin was administered, but unfortunately, his condition deteriorated rapidly, especially respiratory status. On Day 2 after extracorporeal membrane oxygenation (ECMO) initiation, metagenomic next-generation sequencing (mNGS) was performed on the patient's bronchoalveolar lavage fluid, which indicated an infection with C. abortus. The patient's antimicrobial therapy was adjusted to oral doxycycline (0.1g every 12h), intravenous azithromycin (0.5g every day), and imipenem and cilastatin sodium (1g every 6h). The patient's condition improved clinically and biologically. However, the patient was discharged due to financial reasons and unfortunately passed away eight hours later. Conclusion: Infections with C. abortus can result in severe ARDS and serious visceral complications which necessitate prompt diagnosis and active intervention by clinicians. The case highlights the significance of mNGS as an essential diagnostic tool for uncommon pathogens. Tetracyclines, macrolides or their combinations are effective choices for treatment of C. abortus pneumonia. Further study is needed to explore the transmission routes of C. abortus pneumonia and establish precise guidelines for antibiotic treatment.

The Expression and Effect of ABCE1 in Gastric Adenocarcinoma.

ATP-binding cassette E1 (ABCE1) is mainly related to the regulation of viral infection, cell multiplication, and anti-apoptosis. Previous reports confirmed the central role in the regulation of ABCE1 in liver and breast cancer; however, its potential role in gastric adenocarcinoma remains unclear. In our study, siRNA and plasmid were transfected to construct gastric cancer cell lines with low and overexpression of ABCE1, and Western blot, RT-qPCR, and immunohistochemical staining were used to detect ABCE1 expression levels in gastric cancer tissues and cell lines. The effects of ABCE1 on cell growth, metastasis, invasion, cell cycle, and drug resistance were investigated using CCK-8 test, wound healing assay, and clone formation experiment. Functional experiments indicated that si-ABCE1 decreased the proliferation, metastasis, and invasion of gastric adenocarcinoma. Meanwhile, si-ABCE1 has significantly promoted EMT process and enhanced the sensitivity of paclitaxel and cisplatin. In vivo experiments also confirmed that si-ABCE1 group had significantly smaller tumors, and immunohistochemical staining results showed the tumor growth in si-ABCE1 group was reduced obviously. In summary, we found ABCE1 is considered as a crucial role in the evolution of gastric adenocarcinoma and could be a viable therapeutic target for the disease.

Effect of Whole-Brain and Intensity-Modulated Radiotherapy on Serum Levels of miR-21 and Prognosis for Lung Cancer Metastatic to the Brain.

BACKGROUND The goal of the present study was to explore the influence of whole-brain radiotherapy (WBRT) and intensity-modulated radiotherapy (IMRT) on serum levels of miR-21 and prognosis for lung cancer that has metastasized to the brain. MATERIAL AND METHODS Two hundred patients with lung cancer metastatic to the brain were randomized, half to the control group and half to the observation group. The observation group received WBRT and reduced-field IMRT (WBRT+RF-IMRT) and the control group received conventional-field IMRT (CF-IMRT). The total effective rate after treatment was determined. Serum levels of miR-21 were measured before and after radiotherapy with reverse transcriptase-polymerase chain reaction. In addition, tumor marker levels were measured with enzyme-linked immunosorbent assay. The relationship between miR-21 levels and tumor marker levels was assessed with a Pearson correlation coefficient test. Five-year survival was estimated with Kaplan-Meier curves. RESULTS The total effective rate was higher in the observation group (86%) than in the control group (69%). Lower levels of miR-21 and tumor markers were seen in the observation group. Moreover, miR-21 levels were positively correlated with levels of tumor necrosis factor-a, neuron-specific enolase, SCC-Ag, and carcinoembryonic antigen. Low levels of miR-21 were associated with longer overall survival in patients with lung cancer metastatic to the brain. CONCLUSIONS WBRT+RF-IMRT is superior to CF-IMRT for lung cancer metastatic to the brain. MiR-21 may be a marker for prediction of the efficacy of radiotherapy in this disease setting.