CD163-Expressing Porcine Macrophages Support NADC30-like and NADC34-like PRRSV Infections

Porcine reproductive and respiratory syndrome virus (PRRSV) has a strict cell tropism. In addition to the primary alveolar macrophages, PRRSV is strictly cytotropic to African green monkey kidney cells, such as MARC-145 cells; however, MARC-145 cells are not infected by most NADC30-like and NADC34-like PRRSV strains. The essential scavenger receptor CD163 has been proved to mediate productive infection of PRRSV in various non-permissive cell lines. In this study, we systematically tested the porcine CD163 stably expressing 3D4/21 cells for infections with various PRRSV strains. The results showed that the porcine CD163-expressing macrophages support the infections of PRRSV2 of lineages 1, 5, and 8, as evidenced by Western blotting, immunofluorescence assay, quantitative PCR, and virus titration assay. Considering the current prevalence of NADC30-like and NADC34-like PRRSV2 of lineage 1 in China, the CD163-expressing macrophages are very useful for PRRSV research and disease management.     

Early-Adulthood Weight Change and Later Physical Activity in Relation to Cardiovascular and All-Cause Mortality: NHANES 1999–2014

Limited evidence investigated the combined influence of early-adulthood weight change and later physical activity on the risk of cardiovascular (CVD) and all-cause mortality. The aim of this study is to explore the associations of early-adulthood weight change and later physical activity with CVD and all-cause mortality. This is a cohort study of 23,193 US adults aged 40 to 85 years from the National Health and Nutrition Examination Survey (NHANES) 1999 to 2014. Cox proportional hazards regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) of CVD and all-cause mortality associated with early-adulthood weight change and later physical activity. During a median follow-up of 9.2 years, there were 533 and 2734 cases of CVD and all-cause deaths. Compared with being physically inactive, the HRs of the CVD mortality of being physically active were 0.44 (0.26 to 0.73), 0.58 (0.19 to 1.82), 0.38 (0.17 to 0.86) and 0.46 (0.21 to 1.02) among individuals with stable normal, stable obese, non-obese to obese and maximum overweight early-adulthood weight change patterns. Using stable normal patterns that were physically active later as the reference, other early-adulthood weight change patterns did not show a significantly higher risk of CVD mortality when participants were physically active in later life; later physically inactive participants had a significantly increased risk of CVD mortality, with HRs of 2.17 (1.30 to 3.63), 5.32 (2.51 to 11.28), 2.59 (1.29 to 5.18) and 2.63 (1.32 to 5.26) in the stable normal, stable obese, non-obese to obese and maximum overweight groups, respectively. Similar results can be seen in the analyses for all-cause mortality. Our findings suggest that inadequate physical activity worsens the negative impact of unhealthy early-adulthood weight change patterns, which is worthy of being noted in the improvement of public health.     

Local and systemic inflammation triggers different outcomes of tumor growth related to infiltration of anti-tumor or pro-tumor macrophages

Background:Previous evidence suggests inflammation may be a double-edged sword with cancer-promoting and cancer suppressing function. In this study, we explore the impact of local and systemic inflammation on cancer growth.Methods:Female BALB/C mice were subcutaneously implanted with foreign body (plastic plates) to build up a local inflammation and intraperitoneally injected with PolyIC or lipopolysaccharides (LPS) to build up a systemic inflammation, followed by subcutaneous injection of 5 × 10⁵ colon cancer cells. Immunohistochemistry and enzyme linked immunosorbent assay were utilized to detect the Ki67 and interleukin (IL) 6, IL-1β, and monocyte chemoattractant protein-1 expression in the tumor tissues and serum, respectively. The distributions of immune cells and expression of toll-like receptors (TLRs) were evaluated by flow cytometry (FCM) and quantitative real time-polymerase chain reaction.Results:The results showed that local inflammation induced by foreign body implantation suppressed tumor growth with decreased tumor weight (P = 0.001), volume (P = 0.004) and Ki67 index (P < 0.001). Compared with the control group, myeloid-derived suppressive cells sharply decreased (P = 0.040), while CD4⁺ T cells slightly increased in the tumor tissues of the group of foreign body-induced local inflammation (P = 0.035). Moreover, the number of M1 macrophages (P = 0.040) and expression of TLRs, especially TLR3 (P < 0.001) and TLR4 (P < 0.001), were significantly up-regulated in the foreign body group. Contrarily, tumor growth was significantly promoted in LPS or PolyIC-induced systemic inflammation (P = 0.009 and 0.006). FCM results showed M1 type macrophages (P = 0.017 and 0.006) and CD8⁺ T cells (P = 0.031 and 0.023) were decreased, while M2 type macrophages (P = 0.002 and 0.007) were significantly increased in tumor microenvironment of LPS or PolyIC-induced systemic inflammation group. In addition, the decreased expression of TLRs was detected in LPS or PolyIC group.Conclusions:The foreign body-induced local inflammation inhibited tumor growth, while LPS or PolyIC- induced systemic inflammation promoted tumor growth. The results suggested that the different outcomes of tumor growth might be attributed to the infiltration of anti-tumor or pro-tumor immune cells, especially M1 or M2 type macrophages into tumor microenvironment.     

Novel application of the traditional lipid ratios as strong risk predictors of nonsmall-cell lung cancer risk in a Chinese population

Dyslipidemia has been associated with cancer risk, yet the relationship between lipid ratios and nonsmall-cell lung cancer (NSCLC) is still unclear. This study aimed to explore the value of lipid ratios, including total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) and triglyceride/HDL-C (TG/HDL-C) as predictors of NSCLC in a Chinese population. Adult patients with histologically confirmed NSCLC, without a previous history of cancer, concomitant disease associated with lipid metabolism disorders, or usage of lipid-lowering drugs, were enrolled from a single center. Controls without NSCLC, matched for age and sex, were enrolled from the same Center. Lipid profile including TC, TG, HDL-C were measured in all participants. TC/HDL-C and TG/HDL-C were calculated based on the levels of TC, TG, HDL-C. Seven hundred eighty-two NSCLC cases and 599 controls were enrolled. NSCLC patients had significantly higher TG/HDL-C and TC/HDL-C levels than those in the control. After controlling for confounding factors, TG/HDL-C (OR = 4.489, 95% CI: 2.463–6.035, P < .001) and TC/HDL-C (OR = 2.396, 95% CI: 2.086–2.752, P = .001) were independently associated with NSCLC risk. The incidence of NSCLC was increased with rising tertiles of TG/HDL-C and TC/HDL-C. Moreover, patients with TNM II-IV stage NSCLC had higher TG/HDL-C and TC/HDL-C than those in TNM I and Tis stage. TG/HDL-C and TC/HDL-C are positively correlated with NSCLC risk and TG/HDL-C is more predictive than TC/HDL-C in predicting the risk of NSCLC. The highest AUC was that of TG/HDL (0.898), at a cutoff point of 0.62, with 83.6% sensitivity and 83.5% specificity.     

Prognostic factors for squamous cervical carcinoma identified by competing-risks analysis: A study based on the SEER database

Cervical cancer has a high incidence of malignant tumors and a high mortality rate, with squamous cervical carcinoma (SCC) accounting for 80% of cases. A competing-risks model is recommended as being more feasible for evaluating the prognosis and guiding clinical practice in the future compared to Cox regression. Data originating from the Surveillance, epidemiology, and end results (SEER) database during 2004 to 2013 were analyzed. Univariate analysis with the cumulative incidence function was performed to assess the potential risk of each covariate. Significant covariates (P < .05) were extracted for inclusion in a Cox regression analysis and a competing-risks model that included a cause-specific (CS) hazard function model and a sub-distribution (SD) hazard function model. A total of 5591 SCC patients met the inclusion criteria. The three methods (Cox regression analysis, CS analysis, and SD analysis) showed that age, metastasis, American Joint Committee on Cancer stage, surgery, chemotherapy, radiation sequence with surgery, lymph node dissection, tumor size, and tumor grade were prognostic factors affecting survival in patients with SCC. In contrast, race and radiation status were prognostic factors affecting survival in the Cox regression and CS analysis, but the results were different in the SD analysis. Being separated, divorced, or widowed was an independent prognostic factor in the Cox regression analysis, but the results were different in the CS and SD analyses. A competing-risks model was used as a new statistical method to more accurately identify prognostic factors than conventional Cox regression analysis leading to bias in the results. This study found that the SD model may be better suited to estimate the clinical prognosis of a patient, and that the results of an SD model analysis were close to those of a CS analysis.     

Breast Augmentation with Autologous Fat Grafting Immediately after Removal of Polyacrylamide Hydrogel and Fibrotic Capsule in 162 Patients

ObjectiveIn this study, we investigated the feasibility and efficacy of immediate breast augmentation with autologous fat grafting after removal of polyacrylamide hydrogel (PAAG) and fibrotic capsule.MethodsA retrospective study was conducted on 162 female patients who underwent removal of breast filler PAAG and the fibrotic capsule which produced after injection of PAAG via areola omega-shaped incision. Then autologous fat grafting was immediately performed evenly and radially around the areola via the same incision into different layers (subcutaneous, submammary tissue, pectoralis major intramuscular, and inferior pectoralis major space) except the empty cavity. The cavity left by removal of PAAG and fibrous capsule was closed with negative pressure drainage tube and slight external pressure.ResultsAll patients recovered well without severe complications. The average score of postoperative satisfaction with physical well-being: chest was 99.83 (total score: 100) compared with the average satisfaction score of 71.69 (total score: 100) preoperatively by means of BREAST-Q™ evaluation (p < 0.01). All patients were satisfied with their postoperative breast shape.ConclusionsRemoving as much as possible is critical for patients who underwent the PAAG injection. Our experience in immediate breast augmentation with autologous fat grafting after removal of PAAG and fibrotic capsule proved useful and effective to maintain the balance between removing the PAAG as much as possible and retaining soft tissue to reshape breasts.Level of EvidenceIV.     

PRRX1/FOXM1 reduces gemcitabin-induced cytotoxicity by regulating autophagy in bladder cancer

BackgroundBladder cancer (BC) is a common urological malignancy with high mortality worldwide. Many proteins can influence tumorigenesis by participating in cellular processes. Recently, abundant evidence has illustrated that paired related homeobox 1 (PRRX1) is closely related to the progression and development of human cancers. However, the function of PRRX1 in BC remains poorly understood. The aim of our study is to explore the role of PRRX1 in BC progression.MethodsThe expression of genes (PRRX1, FOXM1, LC3B, and Beclin-1) was examined through real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. The expression of proteins (PRRX1, FOXM1, LC3B, and Beclin-1) was measured through immunohistochemistry. Cell viability and the half-maximal inhibitory concentration were detected using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. Cell apoptosis was assessed through flow cytometry. Autophagy was tested by GFP-LC3 immunofluorescence assay. Tumors were grown in nude mice in vivo, and the tumor size, volume, and weight were evaluated.ResultsIn our study, PRRX1 was highly expressed in BC tissues and cells, and high PRRX1 expression resulted in poor overall survival in patients with BC. PRRX1 accelerated the viability and hindered the apoptosis of BC cells. It also weakened gemcitabine-induced cytotoxicity and strengthened gemcitabine-induced autophagy. PRRX1 was found to cooperate with forkhead box protein M1 (FOXM1) to influence downstream genes, and FOXM1 was found to regulate Beclin-1 and microtubule-associated protein 1 light chain 3 (LC3) genes to influence autophagy. PRRX1 up-regulated the expression of LC3 and Beclin-1 by cooperating with FOXM1. In rescue assays, FOXM1 reversed the effects of PRRX1 on gemcitabine-induced cytotoxicity and autophagy. Knockdown of PRRX1 enhanced the inhibitive effects of gemcitabine on tumor growth in vivo.ConclusionsPRRX1 reduces gemcitabine-induced cytotoxicity in BC cells by regulating the expression of the autophagy proteins LC3 and Beclin-1. This discovery suggests that PRRX1 may be a useful therapeutic biomarker for BC.     

Intratumoral PD-1+CD8+ T cells associate poor clinical outcomes and adjuvant chemotherapeutic benefit in gastric cancer

Background Although PD-1 has been reported to be a marker of T-cell exhaustion in several malignancies, the biological role of PD-1⁺CD8⁺ T cells in gastric cancer (GC) remains unclear. Herein, we aimed to investigate the role of PD-1⁺CD8⁺ T cells in the tumour microenvironment and its clinical significance in GC.Designs This study included 441 tumour microarray specimens and 60 Flow cytometry specimens of GC patients from Zhongshan Hospital, and 250 GC patients from the Asian Cancer Research Group.Results Here, we demonstrated that PD-1⁺CD8⁺ T cells functioned as an independent adverse prognosticator in GC. In addition, an abundance of intratumoral PD-1⁺CD8⁺ T cells indicated worse chemotherapeutic responsiveness to fluorouracil in Stage III GC patients. Mechanistically, PD-1⁺CD8⁺ T cell high infiltration indicated an exhausted phenotype of global CD8⁺ T cells in GC tissues, which was characterised by elevated immune checkpoint expression including CTLA-4 and TIM-3, whereas decreased expression of perforin. Furthermore, PD-1⁺CD8⁺ T cell high-infiltration patients with Stage III GC held elevated activity of several therapeutic signal pathways.Conclusions Our study highlighted that PD-1⁺CD8⁺ T cell abundance predicts inferior prognosis in GC, and may serve as a novel predictive biomarker to guide therapeutic option.Subject terms: Gastric cancer, Cancer microenvironment, Tumour immunology