Prognostic significance and value of further classification of lymphovascular invasion in invasive breast cancer: a retrospective observational study.

PURPOSE: To investigate the prognostic significance of lymphovascular invasion in invasive breast cancer and the value of using specific vascular endothelial markers to further classify lymphovascular invasion. METHODS: We collected 2124 patients with invasive breast cancer who were hospitalized at the First Hospital of Dalian Medical University from 2012 to 2020. Statistical methods were used to investigate the relationship between lymphovascular invasion and clinicopathological characteristics of breast cancer, and the correlation between lymphovascular invasion on overall survival (OS) and disease-free survival (DFS) of various categories of breast cancers. Immunohistochemical staining of breast cancer samples containing lymphovascular invasion using specific vascular endothelial markers D2-40 and CD34 was used to classify lymphovascular invasion and to investigate the relationship between lymphovascular invasion and breast cancer progression. RESULTS: There was a high correlation between lymphovascular invasion and T stage, N stage and nerve invasion. Survival analyses showed that patients with lymphovascular invasion, especially luminal B, triple-negative, and Her-2 overexpression breast cancer patients, had poorer OS and DFS prognosis, and that lymphovascular invasion was an independent prognostic factor affecting OS and DFS in breast cancer. The immunohistochemical staining results showed that positive D2-40 staining of lymphovascular invasion was linked to the N stage and localized recurrence of breast cancer. CONCLUSION: Lymphovascular invasion is associated with aggressive clinicopathological features and is an independent poor prognostic factor in invasive breast cancer. Breast cancer localized recurrence rate and lymph node metastases are influenced by lymphatic vessel invasion. Immunohistochemical techniques should be added to the routine diagnosis of lymphovascular invasion.

[Repaired four cases of hypopharyngeal combined neck skin defects using a folded supraclavicular flap].

Objective:To evaluate the outcomes following the use of folded supraclavicular flap repaired hypopharyngeal combined neck skin defects. Methods:Folded supraclavicular flap were designed to repaired four cases of hypopharyngeal combined neck skin defects patients. Evaluate their repair effect （3 men,1 woman; mean age:66 years）. Hypopharyngeal fistula from 3.2 cm×1.8 cm to 4.5 cm×3.8 cm,skin defects in the neck from 3.8 cm×2.2 cm to 5.1 cm×4.5 cm. The folded supraclavicular flap from 8 cm×5 cm to 13 cm×9 cm. Results:All flaps survived, head and neck appearance was satisfactory, and no patient experienced a major complication. All patients resumed an oral diet function. No fistula recurrence or stricture developed after 6-19 months of follow-up. Conclusion:The folded supraclavicular flap is a safe and effective flap Repaired for hypopharyngeal combined neck skin defects.

Comparisons of drug-eluting balloon versus drug-eluting stent for the treatment of cancer patients presenting with acute myocardial infarction.

BACKGROUND: Treatment for cancer patients presenting with acute myocardial infarction (AMI) remains challenging. The objective of the study was to investigate the safety and efficiency of drug eluting balloon (DEB) versus drug eluting stent (DES) in this high-risk group. METHODS: Between 1st January 2017 and 1st January 2022, cancer patients admitted to Beijing Chaoyang Hospital with AMI were retrospectively enrolled. The primary endpoint was major adverse cardiovascular event (MACE). The secondary endpoints included major bleeding events, heart failure and cardiac complications. RESULTS: A total of 164 cancer patients presenting with AMI were included in the final analysis. Patients treated with DEB had a numerically lower rate of MACE than those treated with DES during a median follow-up of 21.8 months (22.9% vs. 37.1%, p = 0.23). Patients treated with DEB had a trend towards lower rate of major bleeding events than patients treated with DES (6.3% vs. 18.1%, HR 2.96, 95% CI [0.88, 9.92], p = 0.08). There were no significant differences between the two groups with regards to the rate of heart failure (4.2% vs. 9.5%, p = 0.32) and cardiac complications (0.0% vs. 2.6%, p = 0.56). CONCLUSIONS: The present study demonstrated that in cancer patients with AMI, DEB had a trend towards lower rate of major bleeding events and a numerically lower rate of MACE compared with DES.

Comparisons of different new-generation transcatheter aortic valve implantation devices for patients with severe aortic stenosis: a systematic review and network meta-analysis.

BACKGROUND: Whether there are differences among the new-generation transcatheter aortic valve implantation (TAVI) devices for patients with aortic stenosis remains unclear. The aim of the study was to compare the efficiency and safety of different new-generation TAVI devices for patients with aortic stenosis. MATERIALS AND METHODS: A comprehensive search of PubMed, Embase and Web of Science from their inception to 1 February 2022. Randomized clinical trials and observational studies that compared two or more different TAVI devices were enroled. Pairwise meta-analysis and frequentist network meta-analysis were conducted to pool the outcome estimates of interest. RESULTS: A total of 79 studies were finally included. According to the surface under the cumulative ranking, the top two ranked valves for lower rates of events were as follows: direct flow medical (DFM) (4.6%) and Lotus (48.8%) for lower rate of device success; Sapien 3 (16.8%) and DFM (19.7%) for lower mortality; DFM (8.6%) and Sapien 3 (25.5%) for lower rates of stroke; Evolut (27.6%) and DFM (35.8%) for lower rates of major and life-threatening bleeding; Portico (22.6%) and Sapien 3 (41.9%) for lower rates of acute kidney injury; Acurate (8.6%) and DFM (13.2%) for lower rates of permanent pacemaker implantation; Lotus (0.3%) and Sapien 3 (22.7%) for lower rates of paravalvular leak; Evolut (1.4%) and Portico (29.1%) for lower rates of mean aortic valve gradients. CONCLUSIONS: The findings of the present study suggested that the device success rates were comparable among these new-generation valves except for DFM. After excluding DFM, Sapien 3 might be the best effective for decreased mortality and stroke; Lotus might be the best effective for decreased paravalvular leak; Evolut might be the best effective for decreased major and life-threatening bleeding and mean aortic valve gradients; Acurate and Portico might be the best effective for decreased permanent pacemaker implantation and acute kidney injury, respectively.

Diagnostic value of ultrasound elastography in triple negative breast cancer: A meta-analysis.

BACKGROUND: The purpose of this study was to determine the value of ultrasound elastic imaging (UE) in the differential diagnosis of the 3 negative breast cancer (TNBC) and non-TNBC. METHODS: We searched the PubMed, Cochrane Library, and CBM databases from inception to July 20, 2022 and used STATA version 14.0 and Meta-Disc version 1.4 software. We computed summary statistics for sensitivity (Sen), specificity, positive and negative likelihood ratio (LR+/LR-), diagnostic odds ratio, and summary receiver operating characteristic curves. Cochran Q-statistic and I2 test were used to assess potential heterogeneity between studies. Sen analysis was carried out to evaluate the effect of a single study on overall estimation. We also conducted a meta regression analysis to investigate potential sources of heterogeneity. RESULTS: Nine studies that fulfilled all the criteria for acceptance were incorporated into the meta-analysis. TNBC 317 and non-TNBC 1055 cases were evaluated. All breast tumors were histologically confirmed. The pooled Sen was 0.78 (95% confidence interval [CI] = 0.58-0.90); the pooled specificity was 0.86 (95%CI = 0.78-0.91). The pooled LR+ was 5.46 (95%CI = 3.07-9.73); the pooled negative LR- was 0.26 (95%CI = 0.12-0.55). The pooled diagnostic odds ratio of UE was 21.00 (95% CI = 6.14-71.78). The area under the summary receiver operating characteristic curve was 0.89 (SE = 0.0378). No evidence was found to reveal bias (t = 0.10, P = .92). CONCLUSION: Our meta-analysis showed that UE could have high diagnostic accuracy in distinguishing TNBC and non-TNBC.

Metabolic reprogramming enables the auxiliary diagnosis of breast cancer by automated breast volume scanner.

Breast cancer is the leading cause of female cancer-related deaths worldwide. New technologies with enhanced sensitivity and specificity for early diagnosis and monitoring of postoperative recurrence are in critical demand. Automatic breast full volume scanning system (ABVS) is an emerging technology used as an alternative imaging method for breast cancer screening. Despite its improved detection rate of malignant tumors, ABVS cannot accurately stage breast cancer preoperatively in 30-40% of cases. As a major hallmark of breast cancer, the characteristic metabolic reprogramming may provide potential biomarkers as an auxiliary method for ABVS. Objective: The objective of this study was to identify differential metabolomic signatures between benign and malignant breast tumors and among different subtypes of breast cancer patients based on untargeted metabolomics and improve breast cancer detection rate by combining key metabolites and ABVS. Methods: Untargeted metabolomics approach was used to profile serum samples from 70 patients with different subtypes of breast cancer and benign breast tumor to determine specific metabolomic profiles through univariate and multivariate statistical data analysis. Results: Metabolic profiles correctly distinguished benign and malignant breast tumors patients, and a total of 791 metabolites were identified. There were 54 different metabolites between benign and malignant breast tumors and 17 different metabolites between invasive and non-invasive breast cancer. Notably, the missed diagnosis rate of ABVS could be reduced by differential metabolite analysis. Moreover, the diagnostic performance analyses of combined metabolites (pelargonic acid, N-acetylasparagine, and cysteine-S-sulfate) with ABVS performance gave a ROC area under the curve of 0.967 (95% CI: 0.926, 0.993). Conclusions: Our study identified metabolic features both in benign and malignant breast tumors and in invasive and non-invasive breast cancer. Combined ultrasound ABVS and a panel of differential serum metabolites could further improve the accuracy of preoperative diagnosis of breast cancer and guide surgical therapy.

Evaluation of left atrial function and mechanical dispersion in breast cancer patients after chemotherapy.

BACKGROUND: Left atrial (LA) function and mechanical dispersion changes in breast cancer patients treated with chemotherapy remain unclear. HYPOTHESIS: LA function and LA mechanical dispersion in breast cancer patients would be impaired after chemotherapy. METHODS: This single-center retrospective study included 91 consecutive breast cancer patients treated with chemotherapy and 30 controls. Patients were examined by echocardiography three times at intervals. Conventional parameters, left ventricular strain, LA strain, and LA mechanical dispersion were evaluated and compared. RESULTS: LA strain during reservoir phase (LASr), conduit phase (LAScd), and contraction phase (LASct) all decreased markedly after chemotherapy and were lower than those of the controls (all p < .01). The standard deviation of time to peak positive strain during LA reservoir phase corrected by R-R interval (LA SD-TPSr) was significantly increased after chemotherapy and was higher than that of the controls (p < .001). The change of LA function was expressed as Δ. Multivariate linear regression analyses showed that LAVIp (0.399, 95% confidence interval [CI]: 0.610, 1.756, p = .000) was independently associated with ΔLASr, LAPEF (-0.325, 95% CI: -45.123, -10.676, p = .002) and age (0.227, 95% CI: 0.021, 0.350, p = .027) were independently associated with ΔLAScd, and LAVImax (0.341, 95% CI: 0.192, 0.723, p = .001) was independently associated with ΔLASct. LAVImax (0.505, 95% CI: 0.000, 0.001, p = .039) and mitral E (-0.256, 95% CI: 0.000, 0.000, p = .024）were independently associated with ΔLA SD-TPSr. CONCLUSIONS: Mechanical function of LA declined after chemotherapy in breast cancer patients. With the decrease of LA mechanical function, LA mechanical dispersion assessed by two-dimensional speckle-tracking echocardiography increased significantly, and its clinical value needs to be further studied.

Oncolytic Zika virus promotes intratumoral T cell infiltration and improves immunotherapy efficacy in glioblastoma.

Glioblastoma (GBM) is the deadliest primary brain tumor and is generally resistant to immunotherapy because of severe dysfunction of T cells. Novel treatment options are critically needed to overcome the immunotherapy resistance of GBM. Here we demonstrate that Zika virus (ZIKV) treatment improves the efficacy of anti-PD ligand 1 (PD-L1) immunotherapy in GBM. We found that ZIKV induces a strong pro-inflammatory response and increases CD4+ and CD8+ T cell intratumoral infiltration and activation in GBM mouse models. ZIKV treatment of mice bearing GBM tumors inhibits tumor growth and prolongs survival. These therapeutic effects of ZIKV on GBM tumors are negated in mice depleted of T cells. Moreover, ZIKV dramatically promotes activation of the type I interferon signaling pathway in GBM cells. ZIKV treatment potently sensitizes GBM to PD-L1 blockade and provides significant and durable survival benefits. Our findings reveal that ZIKV overcomes the resistance of GBM to immune checkpoint blockade, which may lead to therapeutic applications of ZIKV in individuals with GBM receiving immunotherapy.

Traditional uses, phytochemistry, pharmacology and toxicology of the genus Gynura (Compositae): A comprehensive review.

ETHNOPHARMACOLOGICAL RELEVANCE: Gynura cass., belonging to the tribe Senecoineae of the family Compositae, contains more than 40 accepted species as annual or perennial herbs, mainly distributed in Asia, Africa and Australia. Among them, 11 species are distributed in China. Many of the Gynura species have been used as traditional herbal medicines for the treatment of diabetes mellitus, rheumatism, eruptive fever, gastric ulcer, bleeding, abscesses, bruises, burning pains, rashes and herpes zoster infection in tropical Asia countries such as China, Thailand, Indonesia, Malaysia, and Vietnam. Some of the species have been used as vegetables, tea beverage or ornamental plants by the local people. AIM OF THE STUDY: A more comprehensive and in-depth review about the geographical distribution, traditional uses, chemical constituents and pharmacological activities as well as safe and toxicity of Gynura species has been summarized, hoping to provide a scientific basis for rational development and utilization as well as to foster further research of these important medicinal plant resources in the future. MATERIALS AND METHODS: A review of the literature was performed based on the existing peer-reviewed researches by consulting scientific databases including Web of Science, PubMed, Elsevier, Google Scholar, SciFinder and China National Knowledge Infrastructure. RESULTS: Many of the Gynura species have been phytochemically studied, which led to the isolation of more than 338 compounds including phenolics, flavonoids, alkaloids, terpenoids, steroids, cerebrosides, aliphatics and other compounds. Pharmacological studies in vitro and in vivo have also confirmed the various bioactive potentials of extracts or pure compounds from many Gynura plants, based on their claimed ethnomedicinal and anecdotal uses, including antioxidant, anti-inflammation, anticancer, antidiabetic, antihypertension, antibacterial and other activities. However, pyrrolizidine alkaloids (PAs) pose a threat to the medication safety and edible security of Gynura plants because of toxicity issues, requiring the need to pay great attention to this phenomenon. CONCLUSION: The traditional uses, phytochemistry and pharmacology of Gynura species described in this review demonstrated that these plants contain a great number of active constituents and display a diversity of pharmacological activities. However, the mechanism of action, structure-activity relationship, potential synergistic effects and pharmacokinetics of these components need to be further elucidated. Moreover, further detailed research is urgently needed to explain the mechanisms of toxicity induced by PAs. In this respect, effective detoxification strategies need to be worked out, so as to support the safe and reasonable utilization of Gynura plant resources in the future.

Immune-related gene data-based molecular subtyping related to the prognosis of breast cancer patients.

BACKGROUND: Breast cancer (BC), which is the most common malignant tumor in females, is associated with increasing morbidity and mortality. Effective treatments include surgery, chemotherapy, radiotherapy, endocrinotherapy and molecular-targeted therapy. With the development of molecular biology, immunology and pharmacogenomics, an increasing amount of evidence has shown that the infiltration of immune cells into the tumor microenvironment, coupled with the immune phenotype of tumor cells, will significantly affect tumor development and malignancy. Consequently, immunotherapy has become a promising treatment for BC prevention and as a modality that can influence patient prognosis. METHODS: In this study, samples collected from The Cancer Genome Atlas (TCGA) and ImmPort databases were analyzed to investigate specific immune-related genes that affect the prognosis of BC patients. In all, 64 immune-related genes related to prognosis were screened, and the 17 most representative genes were finally selected to establish the prognostic prediction model of BC (the RiskScore model) using the Lasso and StepAIC methods. By establishing a training set and a test set, the efficiency, accuracy and stability of the model in predicting and classifying the prognosis of patients were evaluated. Finally, the 17 immune-related genes were functionally annotated, and GO and KEGG signal pathway enrichment analyses were performed. RESULTS: We found that these 17 genes were enriched in numerous BC- and immune microenvironment-related pathways. The relationship between the RiskScore and the clinical characteristics of the sample and signaling pathways was also analyzed. CONCLUSIONS: Our findings indicate that the prognostic prediction model based on the expression profiles of 17 immune-related genes has demonstrated high predictive accuracy and stability in identifying immune features, which can guide clinicians in the diagnosis and prognostic prediction of BC patients with different immunophenotypes.

HRD1 inhibits fatty acid oxidation and tumorigenesis by ubiquitinating CPT2 in triple-negative breast cancer.

Dependence on glutamine and acceleration of fatty acid oxidation (FAO) are both metabolic characteristics of triple-negative breast cancer (TNBC). With the rapid growth of tumors, accelerated glutamine catabolism depletes local glutamine, resulting in glutamine deficiency. Studies have shown that the use of alternative energy sources, such as fatty acids, enables tumor cells to continue to proliferate rapidly in a glutamine-deficient microenvironment. However, the detailed mechanisms behind this metabolic change are still unclear. Herein, we identified HRD1 as a regulatory protein for FAO that specifically inhibits TNBC cell proliferation under glutamine-deficient conditions. Furthermore, we observed that HRD1 expression is significantly downregulated under glutamine deprivation and HRD1 directly ubiquitinates and stabilizes CPT2 through K48-linked ubiquitination. In addition, the inhibition of CPT2 expression dramatically suppresses TNBC cell proliferation mediated by HRD1 knockdown in vitro and in vivo. Finally, we found that the glutaminase inhibitor CB839 significantly inhibited TNBC cell tumor growth, but not in the HRD1 knock-downed TNBC cells. These findings provide an invaluable insight into HRD1 as a regulator of lipid metabolism and have important implications for TNBC therapeutic targeting.

Levonorgestrel Ameliorates Adenomyosis via lncRNA H19/miR-17/TLR4 Pathway.

PURPOSE: To explore the mechanism of levonorgestrel (LNG)-ameliorating adenomyosis through long non-coding RNA H19 (lncRNA H19)/miR-17/Toll-like receptor 4 (TLR4) pathway. PATIENTS AND METHODS: A total of 71 cases of adenomyosis and 54 cases of normal endometrium were sampled. Quantitative polymerase chain reaction (qPCR) was employed to quantify lncRNA H19, miR-17, and TLR4 mRNA, while Western blot (WB) was used to quantify TLR4 protein. Effects of LNG on normal endometrial stromal cells (ESCs) were evaluated. Suppression/over-expression vectors of lncRNA H19, miR-17, and TLR4 were constructed to observe their effects on ESCs. RESULTS: MiR-17 and TLR4 mRNA were up-regulated and lncRNA H19 was down-regulated in adenomyosis. After LNG treatment, lncRNA H19 was up-regulated while miR-17 and TLR4 were down-regulated. LNG, up-regulation of lncRNA H19, and down-regulation of miR-17 and TLR4 portend increased apoptosis, G1-arrested cells, as well as inhibited inflammation. Dual-luciferase reporter (DLR) assay conformed the targeting relation of lncRNA H19/miR-17/TLR4 pathway. CONCLUSION: LNG ameliorates adenomyosis via lncRNA H19/miR-17/TLR4 pathway.

Concordance of Genomic Alterations between Circulating Tumor DNA and Matched Tumor Tissue in Chinese Patients with Breast Cancer.

PURPOSE: Circulating tumor DNA (ctDNA) served as a noninvasive method with less side effects using peripheral blood. Given the studies on concordance rate between liquid and solid biopsies in Chinese breast cancer (BC) patients were limited, we sought to examine the concordance rate of different kinds of genomic alterations between paired tissue biopsies and ctDNA samples in Chinese BC cohorts. MATERIALS AND METHODS: In this study, we analyzed the genomic alteration profiles of 81 solid BC samples and 41 liquid BC samples. The concordance across 136 genes was evaluated. RESULTS: The median mutation counts per sample in 41 ctDNA samples was higher than the median in 81 tissue samples (p=0.0254; Wilcoxon rank sum test). For mutation at the protein-coding level, 39.0% (16/41) samples had at least one concordant mutation in two biopsies. 20.0% tissue-derived mutations could be detected via ctDNA-based sequencing, whereas 11.7% ctDNA-derived mutations could be found in paired tissues. At gene amplification level, the overall concordant rate was 68.3% (28/41). The concordant rate at gene level for each patient ranged from 83.8% (114/136) to 99.3% (135/136). And, the mean level of variant allele frequency (VAF) for concordant mutations in ctDNA was statistically higher than that for the discordant ones (p < 0.001; Wilcoxon rank sum test). Across five representative genes, the overall sensitivity and specificity were 49.0% and 85.9%, respectively. CONCLUSION: Our results indicated that ctDNA could provide complementary information on genetic characterizations in detecting single nucleotide variants (SNVs) and insertions and deletions (InDels).

LncRNA AK045171 protects the heart from cardiac hypertrophy by regulating the SP1/MG53 signalling pathway.

Hearts often undergo abnormal remodelling and hypertrophic growth in response to pathological stress. Long non-coding RNAs (LncRNAs) can change cardiac function and participate in regulation of cardiac hypertrophy. The present study aims to identify the role of AK045171 in cardiac hypertrophy and the underlying mechanism in hypertrophic cascades. Mice with cardiac hypertrophy were established through transverse aortic constriction (TAC). Cardiac hypertrophy in cardiomyocytes was induced by angiotensin II (angII). The expression of AK045171 and its target gene SP1 was examined in cardiomyocytes transfected with miRNA. The AK045171 expression level was downregulated in mice after TAC surgery. Overexpression of AK045171 attenuated cardiac hypertrophy both in vitro and in vivo. The mechanism study indicated that AK045171 binds with SP1, which promotes transcription activation of MEG3. It is suggested that overexpression of AK045171 might have clinical potential to suppress cardiac hypertrophy and heart failure.

Effects of antidiabetic drugs on left ventricular function/dysfunction: a systematic review and network meta-analysis.

BACKGROUND: Although a variety of antidiabetic drugs have significant protective action on the cardiovascular system, it is still unclear which antidiabetic drugs can improve ventricular remodeling and fundamentally delay the process of heart failure. The purpose of this network meta-analysis is to compare the efficacy of sodium glucose cotransporter type 2 (SGLT-2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) agonists, metformin (MET), sulfonylurea (SU) and thiazolidinediones (TZDs) in improving left ventricular (LV) remodeling in patients with type 2 diabetes (T2DM) and/or cardiovascular disease (CVD). METHODS: We searched articles published before October 18, 2019, regardless of language or data, in 4 electronic databases: PubMed, EMBASE, Cochrane Library and Web of Science. We included randomized controlled trials in this network meta-analysis, as well as a small number of cohort studies. The differences in the mean changes in left ventricular echocardiographic parameters between the treatment group and control group were evaluated. RESULTS: The difference in the mean change in LV ejection fraction (LVEF) between GLP-1 agonists and placebo in treatment effect was greater than zero (MD = 2.04% [0.64%, 3.43%]); similar results were observed for the difference in the mean change in LV end-diastolic diameter (LVEDD) between SGLT-2 inhibitors and placebo (MD = - 3.3 mm [5.31, - 5.29]), the difference in the mean change in LV end-systolic volume (LVESV) between GLP-1 agonists and placebo (MD = - 4.39 ml [- 8.09, - 0.7]); the difference in the mean change in E/e' between GLP-1 agonists and placebo (MD = - 1.05[- 1.78, - 0.32]); and the difference in the mean change in E/e' between SGLT-2 inhibitors and placebo (MD = - 1.91[- 3.39, - 0.43]). CONCLUSIONS: GLP-1 agonists are more significantly associated with improved LVEF, LVESV and E/e', SGLT-2 inhibitors are more significantly associated with improved LVEDD and E/e', and DPP-4 inhibitors are more strongly associated with a negative impact on LV end-diastolic volume (LVEDV) than are placebos. SGLT-2 inhibitors are superior to other drugs in pairwise comparisons.

Relapsing granulomatosis with polyangiitis provoked by trauma: A case report.

RATIONALE: The precise cause of granulomatosis with polyangiitis (GPA) remains unclear. Herein we present a case of refractory GPA occurring after trauma. PATIENT CONCERNS: A 43-year-old man suffered fractures of the left orbital in an accident, and then received surgical repair. At a postoperative follow-up, he developed maxillary sinusitis. Seven months later, he was hospitalized with symptoms of cough, high-grade fever, and loss of weight. DIAGNOSIS: He was diagnosed with GPA based on the symptoms of upper and lower respiratory tract involvement, granulomas in a lung biopsy specimen, and presence of PR3-ANCA. INTERVENTIONS: Initially the patient responded well to the treatment of glucocorticoids and cyclophosphamide (CYC). Forty days later, he was hospitalized again with symptoms of fever, cephalgia, and recurrent ulcerated subcutaneous nodules, due to the vasculitic manifestations of GPA. This time he was treated with cyclophosphamide and glucocorticoids with no improvement, and then switched to rituximab. OUTCOMES: After 4 doses of rituximab, the symptom of cephalgia disappeared and subcutaneous ulcerations and conjunctival congestion diminished. LESSONS: Trauma may act as an inflammatory stimulus to affect the course of disease in GPA. The combination of glucocorticoids and cyclophosphamide is the standard therapy for GPA. Nevertheless, patients who have no response to CYC, especially with predominantly vasculitic manifestations, could resort to rituximab.

IL-17A/IL-17RA promotes invasion and activates MMP-2 and MMP-9 expression via p38 MAPK signaling pathway in non-small cell lung cancer.

The present study is to investigate the effect and mechanism of action of interleukin (IL)-17A and its receptor IL-17RA on non-small cell lung cancer (NSCLC). A total of 139 NSCLC patients were included in the study. NSCLC tissues and tumor-adjacent tissues were collected from the patients. Human NSCLC cell lines H157, H1975, and A549 were used for in vitro studies. MTT assay was performed to determine cell proliferation. Wound healing assay was used to determine cell motility. Transwell assay was carried out to detect migration and invasion. Quantitative real-time polymerase chain reaction was conducted to measure mRNA expression, while Western blotting was used for determine protein expression. Immunohistochemistry was employed to evaluate IL-17RA expression in 139 primary human NSCLC tissues. Levels of IL-17RA in NSCLC tissues were higher than tumor-adjacent normal tissues, and associated with clinical outcomes. Kaplan-Meier survival analysis indicated that NSCLC patients with positive IL-17RA expression had a poor survival. In addition, IL-17A/IL-17RA affected NSCLC cell migration and invasion in vitro. Treatment with IL-17A/IL-17RA increased the expression of MMP-2 and MMP-9 in NSCLC cells. Furthermore, phosphorylation of p38 was enhanced in IL-17RA-overexpressing NSCLC cells. P38 MAPK-specific inhibitor SB203580 suppressed the migration and invasion of NSCLC cells. MMP-2 and MMP-9 were downstream effectors of IL-17RA and p38 signaling pathways. The present study demonstrates that P38 MAPK activity is crucial for IL-17A/IL-17RA to promote NSCLC metastasis. In addition, IL-17A/IL-17RA signaling may be a novel and promising cancer therapeutic target for the treatment of NSCLC.

A single mutation in the prM protein of Zika virus contributes to fetal microcephaly.

Zika virus (ZIKV) has evolved into a global health threat because of its unexpected causal link to microcephaly. Phylogenetic analysis reveals that contemporary epidemic strains have accumulated multiple substitutions from their Asian ancestor. Here we show that a single serine-to-asparagine substitution [Ser139→Asn139 (S139N)] in the viral polyprotein substantially increased ZIKV infectivity in both human and mouse neural progenitor cells (NPCs) and led to more severe microcephaly in the mouse fetus, as well as higher mortality rates in neonatal mice. Evolutionary analysis indicates that the S139N substitution arose before the 2013 outbreak in French Polynesia and has been stably maintained during subsequent spread to the Americas. This functional adaption makes ZIKV more virulent to human NPCs, thus contributing to the increased incidence of microcephaly in recent ZIKV epidemics.

Immunization with truncated envelope protein of Zika virus induces protective immune response in mice.

The global spread of Zika virus (ZIKV) as well as its unexpected link to infant microcephaly have resulted in serious public health concerns. No antiviral drugs against ZIKV is currently available, and vaccine development is of high priority to prepare for potential ZIKV pandemic. In the present study, a truncated E protein with the N-terminal 90% region reserved (E90) from a contemporary ZIKV strain was cloned and expressed in Escherichia coli, purified by a Ni-NTA column, and characterized by Western blotting assays. Immunization with recombinant E90 induced robust ZIKV-specific humoral response in adult BALB/c mice. Passive transfer of the antisera from E90-immunized mice conferred full protection against lethal ZIKV challenge in a neonatal mice model. Our results indicate that recombinant ZIKV E90 described here represents as a promising ZIKV subunit vaccine that deserves further clinical development.

Lighting-up breast cancer cells by a near-infrared fluorescent probe based on KIAA1363 enzyme-targeting.

The first NIR KIAA1363-targeting probe, NB-AX, specifically and instantly featured an "off-on" switch upon gradual addition of KIAA1363 over all kinds of other biomolecules, and its detection limit was initially calculated to be 0.58 µg mL-1 (3δ/k). The probe was also able to be used in ultrafast distinguishing of breast cancer cells from normal cells in fluorescence imaging and applied in tissue imaging and tumor imaging in vivo.