Objective: Hepatitis C virus (HCV), being reported to be associated with a high prevalence of serological markers of autoimmunity in HCV-infected patients, and possibly sharing partial sequences in amino acid segments with thyroid tissue antigens, may be associated with interferon-a (IFN-a)-induced thyroid dysfunction in chronic hepatitis C patients. We conducted this study to clarify the issue. Design and Methods: One hundred and fifty chronic hepatitis C patients with normal baseline thyroid function were treated with IFN-a 2a, 2b and n1 (3-6 million Units three times weekly for 24 weeks). Pretreatment sera were tested for HCV genotype and HCV RNA levels. Serum thyrotropin, total thyroxine and free thyroxine index were performed every 4 weeks for 24 weeks followed by every 8 weeks for another 24 weeks. Results: Twenty-one (14.0%) patients developed early thyroid dysfunction (abnormal thyroid function during the first 3 months of therapy). Female gender, lower HCV RNA levels, IFN-a n1 and a lower IFN-a dose were significantly associated with early thyroid dysfunction. On multivariate analysis, gender, IFN-a preparation and HCV RNA levels were the significant factors associated with early thyroid dysfunction. Seven (4.7%) patients developed thyroid dysfunction during the second 3 months of IFN-a therapy. Taken together, 18.7% patients developed thyroid dysfunction. Female, mixed HCV genotype infection and lower HCV RNA levels were significantly associated with thyroid dysfunction. However, only gender remained significantly associated with IFN-a-induced thyroid dysfunction in multivariate analysis. Conclusions:The virologic features of HCV may be associated with thyroid dysfunction in chronic hepatitis C patients treated with IFN-a. Nevertheless, gender still plays the most important role in IFN-a-induced thyroid dysfunction.

Nod-like receptor family, CARD domain-containing 4 (NLRC4) inflammasome activation is required for efficient clearance of intracellular pathogens through caspsase-1-dependent pyroptosis in macrophages. Although neutrophils have a critical role in protection from Pseudomonas aeruginosa infection, the mechanisms regulating inflammasome-mediated pyroptosis in neutrophils and its physiological role are largely unknown. We sought to determine the specific mechanisms regulating neutrophil pyroptosis in P. aeruginosa strain PAO1 (PAO1) lung infection and to identify the pathological role of this process. Nox2 models with reduced neutrophil antibacterial activity exhibited increased neutrophil pyroptosis, which was mediated by flagellin, a pathogenic PAO1 component. We also demonstrate that PAO1-induced pyroptosis depended on NLRC4 and Toll-like receptor 5 (TLR5) in neutrophils generated from Nlrc4 or Tlr5 mice. Our study reveals previously unknown mechanisms and physiological role of neutrophil pyroptosis during P. aeruginosa lung infection. Furthermore, our findings regarding neutrophil pyroptosis in the context of neutrophil dysfunction may explain the causes of acute and/or chronic infectious diseases discovered in immune-compromised patients.

PS of 0 (n¼39, 15.18%) or 1 (n¼203, 78.99%). The treatment of apatinib was mainly first-line treatment (n¼103, 40.08%), second-line treatment (n¼64, 24.90%), and adjuvant treatment (n¼42, 16.34%). The starting dose of apatinib was 250mg in 132 patients and 500mg in 125 patients. The treatment regimens were: apatinib combined with chemotherapy drugs (178/257), apatinib monotherapy (64/257), apatinib combined with chemotherapy drugs plus PD-1 antibody drug (8/275), and apatinib combined with PD-1 antibody drug (7/275). Thirty-three patients achieved partial response, 69 patients achieved stable disease, and 26 patients had progressive disease, and no CR was achieved, illustrating an ORR of 25.78% and a DCR of 79.69%. During the treatment, the overall incidence of adverse events was 70.82%. The most common adverse events were hypertension (32.68%), leukopenia (26.46%), hand-foot syndrome (25.29%), neutropenia (20.23%), etc.Conclusions: This real-world research showed current treatment status and provided preliminary evidence for the efficacy and safety of apatinib in the treatment of gastric cancer in China. More data would be analyzed and reported in future.[ChiCTR2000035597]Legal entity responsible for the study: The authors.

A 77-year-old woman with cirrhosis was admitted with a one-week history of altered sensorium. A prior evaluation of her liver disease disclosed only a serum alpha 1 -antitrypsin level of 30 mg per deciliter (reference range, 93 to 224). The patient had no evidence of pulmonary disease. Eventually, she died of liver failure and complications of gram-negative sepsis. At autopsy the liver weighed 725 g (reference range, 1500 to 1800) and had extensive micronodular cirrhosis (Panel A). Trichrome staining of histologic sections demonstrated prominent fibrosis (blue staining in Panel B, ¬100). Multiple diastase-resistant periodic acid-Schiff-positive cytoplasmic eosinophilic globules of various sizes were present within the hepatocytes (Panel C, ¬400) -a characteristic of alpha 1 -antitrypsin deficiency. The diagnosis was supported by immunohistochemical studies, which showed intense staining of these globules with alpha 1 -antitrypsin antibody (Panel D, ¬200). The patient's 45-year-old daughter was subsequently evaluated and found to have a mildly decreased serum level of alpha 1 -antitrypsin (86 mg per deciliter) and the MZ phenotype of alpha 1 -antitrypsin deficiency on high-resolution electrophoresis.