BBIBP-CorV vaccination accelerates anti-viral antibody responses in heterologous Omicron infection: A retrospective observation study in Shanghai.

OBJECTIVES: To investigate how BBIBP-CorV vaccination affecting antibody responses upon heterologous Omicron infection. METHODS: 440 Omicron-infected patients were recruited in this study. Antibodies targeting SARS-CoV-2 spike protein receptor binding domain (RBD) and nucleoprotein of both wild-type (WT) and Omicron were detected by ELISA. The clinical relevance was further analyzed. RESULTS: BBIBP-CorV vaccinated patients exhibited higher anti-RBD IgG levels targeting both WT and Omicron than non-vaccinated patients at different stages. By using a 3-day moving average analysis, we found that BBIBP-CorV vaccinated patients exhibited the increases in both anti-WT and Omicron RBD IgG from the onset and reached the plateau at Day 8 whereas those in non-vaccinated patients remained low during the disease. Significant increase in anti-WT RBD IgA was observed only in vaccinated patients. anti-Omicron RBD IgA levels remained low in both vaccinated and non-vaccinated patients. Clinically, severe COVID-19 only occurred in non-vaccinated group. anti-RBD IgG and IgA targeting both WT and Omicron were negatively correlated with virus load, hospitalization days and virus elimination in vaccinated patients. CONCLUSIONS: BBIBP-CorV vaccination effectively reduces the severity of Omicron infected patients. The existence of humoral memory responses established through BBIBP-CorV vaccination facilitates to induce rapid recall antibody responses when encountering SARS-CoV-2 variant infection.

Retrospective study of characteristics and management of pyogenic liver abscess during 5 years' experience.

Pyogenic liver abscess is a life-threatening disease. It is urgent to review the clinical patterns, risk factors, and management of the disease in order to improve the outcome. We retrospectively analyzed 70 cases of pyogenic liver abscess diagnosed and treated at Shanghai Ninth People's Hospital over five years, including the clinical features, management, and outcome. The average age was 63.06 ± 12.33 y. 71.4% (50/70) were males. 85.7% (60/70) patients presented with fever. The major abnormalities in laboratory were increased CRP and liver dysfunction. 77.8% (14/18) pus cultures came with positive reports, while 26.5% (9/34) blood cultures were positive. K. pneumoniae was the predominant pathogen both in blood (66.7%, 6/9) and pus (64.3%, 9/14) cultures. 42.9% (30/70) patients also had diabetes. Patients with diabetes presented with significantly larger size of abscess (P = 0.014) and were more susceptible to K. pneumoniae infection (P = 0.002). We revealed HbA1c (P = 0.047), accompanying malignancy (P = 0.030), and septic shock (P = 0.045) were three independent risk factors for PLA. In conclusion: pyrogenic liver abscess was atypical; microbiologic positivity of pus culture was higher than that of blood culture; K. pneumoniae was the predominant pathogen in pyrogenic liver abscesses, especially in patients with diabetes; and patients with hyperglycemia had poor outcome.

Noninvasive indicators predict advanced liver fibrosis in autoimmune hepatitis patients.

BACKGROUND: Liver biopsy is the criterion standard for diagnosing liver fibrosis, but it is not widely used to monitor liver fibrosis because of the invasiveness, risk of complications, and sample errors. Therefore, it is necessary to involve other techniques to monitor liver fibrosis or cirrhosis during clinical practice. The objective was to explore noninvasive indicators to predict advanced liver fibrosis in autoimmune hepatitis (AIH) patients. METHODS: A total of 45 AIH patients and 47 healthy controls were recruited to this retrospective study. Complete blood count and liver function tests were performed for all subjects. AIH patients were divided into "no/minimal fibrosis" group and "advanced fibrosis" group based on liver biopsy. RESULTS: AIH patients demonstrated significantly higher monocytes, MCV, RDW-CV, RDW-SD, NLR, RDW-CV/PLT, RDW-SD/PLT, TBIL, DBIL, GLB, ALT, AST, GGT, ALP, and GPR and lower WBC, neutrophils, lymphocytes, RBC, HGB, HCT, LMR, TP, ALB, and AAR compared with healthy controls. Patients with advanced fibrosis showed remarkably higher RDW-CV, RDW-SD, RDW-CV/PLT, RDW-SD/PLT, AAR, and FIB-4 and lower RBC, PLT, PCT, and ALB compared with the no/minimal fibrosis group. Logistic regression analysis showed that RDW-SD/PLT was an independent risk factor for advanced fibrosis with an OR (95% CI) of 2.647 (1.383-5.170). Receiver operating characteristic (ROC) analysis revealed that RDW-SD, RDW-CV/PLT, RDW-SD/PLT, FIB-4, and AAR had an area under the ROC curve (AUC) above 0.700 and RDW-SD/PLT had the largest AUC of 0.785 with a cutoff value of 0.239. CONCLUSION: RDW-SD, RDW-CV/PLT, RDW-SD/PLT, FIB-4, and AAR were excellent noninvasive biomarkers and RDW-SD/PLT was an independent risk factor for predicting advanced fibrosis in AIH patients.

FGF-1/-3/FGFR4 signaling in cancer-associated fibroblasts promotes tumor progression in colon cancer through Erk and MMP-7.

Cancer-associated fibroblasts (CAFs), as the activated fibroblasts in the tumor stroma, are important modifiers of tumour progression. In the present study, we observed that azoxymethane and dextran sodium sulfate treatments induced increasingly severe colorectal mucosal inflammation and the intratumoural accumulation of CAFs. Fibroblast growth factor (FGF)-1 and FGF-3 were detected in infiltrating cells, and FGFR4, the specific receptor for FGF-1 and FGF-3, was detected in colon cancer tissues. The phosphorylation of FGFR4 enhanced the production of metalloproteinase (MMP)-7 and mitogen-activated protein kinase kinase (Mek)/extracellular signal-regulated kinase (Erk), which was accompanied by excessive vessel generation and cell proliferation. Moreover, we separated CAFs, pericarcinoma fibroblasts (PFs), and normal fibroblasts (NFs) from human colon tissue specimens to characterize the function of CAFs. We observed that CAFs secrete more FGF-1/-3 than NFs and PFs and promote cancer cell growth and angiogenesis through the activation of FGFR4, which is followed by the activation of Mek/Erk and the modulation of MMP-7 expression. The administration of FGF-1/-3-neutralizing antibodies or the treatment of cells with FGFR4 siRNA or the FGFR4 inhibitor PD173074 markedly suppressed colon cancer cell proliferation and neovascularization. These observations suggest a crucial role for CAFs and FGF signaling in the initiation and progression of colorectal cancer. The inhibition of the FGF signaling pathway may be a useful strategy for the treatment of colon cancer.

Crucial involvement of tumor-associated neutrophils in the regulation of chronic colitis-associated carcinogenesis in mice.

Ulcerative colitis (UC) is a major form of chronic inflammation that can frequently progress to colon cancer. Several studies have demonstrated massive infiltration of neutrophils and macrophages into the lamina propria and submucosa in the progression of UC-associated colon carcinogenesis. Macrophages contribute to the development of colitis-associated colon cancer (CAC). However, the role of neutrophils is not well understood. To better understand the involvement of tumor-associated neutrophils (TANs) in the regulation of CAC, we used a mouse CAC model produced by administering azoxymethane (AOM), followed by repeated dextran sulfate sodium (DSS) ingestion. This causes severe colonic inflammation and subsequent development of multiple tumors in mice colon. We observed that colorectal mucosal inflammation became increasingly severe with AOM and DSS treatment. Macrophages infiltrated the lamina propria and submucosa, together with a marked increase in neutrophil infiltration. The chemokine CXCL2 increased in the lamina propria and submucosal regions of the colons of the treated mice, together with the infiltration of neutrophils expressing CXCR2, a specific receptor for CXCL2. This process was followed by neoplastic transformation. After AOM and DSS treatment, the mice showed enhanced production of metalloproteinase (MMP)-9 and neutrophil elastase (NE), accompanied by excessive vessel generation and cell proliferation. Moreover, CXCL2 promoted neutrophil recruitment and induced neutrophils to express MMP-9 and NE in vitro. Furthermore, administration of neutrophil-neutralizing antibodies after the last DSS cycle markedly reduced the number and size of tumors and decreased the expression of CXCR2, CXCL2, MMP-9, and NE. These observations indicate a crucial role for TANs in the initiation and progression of CAC and suggest that the CXCL2-CXCR2 axis might be useful in reducing the risk of UC-associated colon cancer.