Compound Taxus exerts marked anti-tumor activity and radiosensitization effect on hepatocellular carcinoma cells.

Background: Compound Taxus capsule, as an antineoplastic Chinese patent drug, has been increasingly applied as an adjunctive treatment for the management of non-small-cell lung cancer (NSCLC) and some other malignancies, but research about its antitumor activity and radiosensitization effect on hepatocellular carcinoma (HCC) cells is very rare. Purpose: To investigate the antitumor activity and radiosensitization effect of Compound Taxus on HCC cells and to preliminarily explore the possible molecule mechanisms involved. Methods: Cell viability, cell cycle distribution, apoptosis, DNA damage repair and protein expression levels were detected by CCK-8 assay, flow cytometry, immunofluorescence staining, western blotting analysis and immunohistochemical staining, respectively. The migration and invasion activities and vasculogenic mimicry (VM) formation and angiogenesis were evaluated by tube formation and VM formation assay. Radiation survival curves were obtained from the colony formation assay in human HCC cell lines, Smmc7721 and Bel7402 cells, pretreated with or without Compound Taxus before receiving X-ray irradiation. A Bel7402 tumor-bearing mouse model was established and the radiosensitization effect of Compound Taxus in vivo was evaluated by analyzing tumor volume and tumor weight in different groups receiving different treatments. Results: Compound Taxus decreased viability, induced G2/M arrest, promoted apoptosis, suppressed migration and invasion, and inhibited VM formation and angiogenesis in Smmc7721 and Bel7402 cells. Furthermore, Compound Taxus inhibited irradiation-induced DNA damage repair, enhanced the radiosensitivity of Smmc7721 and Bel7402 cells and improved the anti-tumor therapeutic efficacy of irradiation in Bel7402 tumor-bearing mice. Radiotherapy in combination with Compound Taxus showed the best tumor inhibition compared to that of Compound Taxus alone or irradiation alone. In addition, Compound Taxus significantly down-regulated NF-κB p65, p-NF-κB p65 and Bcl-2, and up-regulated Bax in vitro and in vivo, yet NF-κB p65 overexpression reversed the proapoptotic effect of Taxus on HCC cells, indicating that the NF-κB signaling pathway might be an important signal mediator in the Compound-Taxus-modulated biological responses. Conclusion: Our findings suggest that Compound Taxus shows marked antitumor activity and significant radiosensitization effect on HCC cells, making it possible for Compound Taxus to become a promising auxiliary modality for HCC management and a potential radiosensitizer of HCC in the future.

Urachal Remnant Infection Caused by Actinomyces Turicensis.

BACKGROUND: Urachal remnants (URs) represent uncommon and underdiagnosed entities that are usually detected incidentally at imaging or present clinically different manifestations. METHODS: Here we presented a boy with UR infection. Ultrasonography and bacterial culture and identification were performed. He received antibiotic treatment and underwent surgical excision of the cyst. RESULTS: The patient presented with both a urachal cyst and umbilical-urachal sinus. UR infection was caused by Actinomyces turicensis. He recovered well from the operation without complications. CONCLUSIONS: The present case reminds clinicians to be familiar with imaging features of different types of URs and their potential complications and indicates the necessity of pathogenic microorganism analysis to tailor antibiotic treatment and post-operative follow-up to prevent complications.

Severe Anemia Observed in a Chinese Patient with COVID-19 and Plasmodium Falciparum Malaria Co-Infection.

BACKGROUND: COVID-19 and malaria share some similar symptoms such as fever, difficulty in breathing, fatigue, and headaches of acute onset. With overlapping symptoms and travel history significant for COVID-19 and malaria, healthcare systems and professionals will face a great challenge in the case of COVID-19 and malaria co-infection. METHODS: Here we presented a patient with COVID-19 infection and refractory anemia of unknown reason. A diagnostic test for malaria was later performed. RESULTS: The patient was ultimately diagnosed with COVID-19 and plasmodium falciparum malaria co-infection. He recovered gradually after receiving anti-malaria treatment. CONCLUSIONS: The present case highlights the danger of focusing only on a diagnosis of COVID-19, reminding clinicians to be vigilant about the possibility of co-infections.

A Novel Homozygous VPS13B Splice-Site Mutation Causing the Skipping of Exon 38 in a Chinese Family With Cohen Syndrome.

Background: Cohen syndrome (CS) is a clinically heterogeneous disorder characterized by extensive phenotypic variation with autosomal recessive inheritance. VPS13B was identified to be the disease-causing gene for CS. The objectives of the present study were to screen likely pathogenic mutations of the patient with developmental delay and mental retardation, and to determinate the effect of this splice-site mutation by reverse transcription analysis. Methods: Whole exome sequencing (WES) in combination with Sanger sequencing were performed to identify the causative mutations of this CS family. Subsequently, the impact of the intronic variant on splicing was analyzed by reverse transcription and the construction of expression vector. Results: A novel homozygous splice-site mutation (c.6940+1G>T) in the VPS13B gene was identified in this proband. Sanger sequencing analysis of the cDNA demonstrated that the c.6940+1G>T variant could cause the skipping of entire exon 38, resulting in the loss of 208 nucleotides and further give rise to the generation of a premature in-frame stop codon at code 2,247. Conclusions: The homozygous VPS13B splicing variant c.6940+1G>T was co-segregated with the CS phenotypes in this family and was identified to be the cause of CS after comprehensive consideration of the clinical manifestations, genetic analysis and cDNA sequencing result.

IL-33 facilitates endocrine resistance of breast cancer by inducing cancer stem cell properties.

Breast cancers with estrogen receptor (ER) expressions account for the majority of all clinical cases. Due to hormone therapy with tamoxifen, prognoses of patients with ER-positive breast cancer are significantly improved. However, endocrine resistance to tamoxifen is common and inevitable, leading to compromised efficacy of hormone therapy. Herein, we identify a crucial role of IL-33 in inducing endocrine resistance of breast cancer. IL-33 overexpression in breast cancer cells results in resistance to tamoxifen-induced tumor growth inhibition, while IL-33 knockdown corrects this problem. Mechanistically, IL-33 induces breast cancer stem cell properties evidenced by mammosphere formation and xenograft tumorigenesis, as well as expression of cancer stem cell genes including ALDH1A3, OCT4, NANOG and SOX2. In breast cancer patients, higher serum IL-33 levels portend advanced clinical stages, poorly differentiated cancer cells and tumor recurrence. IL-33 expression levels in patients' freshly isolated breast cancer cells predicts tamoxifen resistance and cancer stem cell features in individual patient. Collectively, IL-33 induces endocrine resistance of breast cancer by promoting cancer stem cell properties. These findings provide novel mechanisms connecting IL-33 with cancer pathogenesis and pinpoint IL-33 as a promising target for optimizing hormone therapy in clinical practice.

IL-33 signaling fuels outgrowth and metastasis of human lung cancer.

IL-33 is a member of IL-1 superfamily that drives production of Th2-related cytokines. Recently, accumulating evidence suggest an involvement of IL-33 in carcinogenesis. Herein, we determine a close correlation of IL-33 expression and cancer progress in patients with non-small-cell lung cancer (NSCLC). Overexpression of IL-33 by transfection with IL-33 expression vector enhances NSCLC outgrowth and metastasis, while genetic knockdown of IL-33 by transfection with IL-33 shRNA limits NSCLC progression. In consistent, IL-33 stimulation of NSCLC cells leads to robust NSCLC outgrowth and metastasis in vitro and in vivo. Mechanically, IL-33-triggered NSCLC progression relies on ST2 receptor and could be abrogated by ST2 blockade. IL-33/ST2 pathway up-regulates membrane glucose transporter 1 (GLUT1) on NSCLC cells, enhancing their glucose uptake and glycolysis. Accordingly, interfering GLUT1 expression dampens IL-33-enhanced glucose uptake and glycolysis in NSCLC cells, thereby abrogates IL-33-induced NSCLC outgrowth and metastasis. In essence, these findings derived from patients' NSCLC cells uncover a new function of IL-33 in NSCLC pathogenesis and identify GLUT1 as a novel target of IL-33 signaling. Block IL-33 is a promising therapeutic strategy to limit NSCLC glycolysis and tumor progression in clinical practice.

Diagnostic Value of D-Dimer Combined with WBC Count, Neutrophil Percentage and CRP in Differentiating Between Simple and.

BACKGROUND: Acute appendicitis is the most common surgical emergency in pediatrics. In this study, we aimed to evaluate the diagnostic value of D-dimer in differentiating between simple and other severe acute appendicitis in children combined with white blood cell (WBC) count, neutrophil percentage, and C-reactive protein (CRP). METHODS: A retrospective study enrolled 327 consecutive patients who underwent appendectomy for acute appendicitis (aged 13 days to 14 years) in Qingdao Women & Children's Hospital from Jan 2013 to Dec 2014. WBC count, neutrophil percentage, CRP, and D-dimer levels were measured. Descriptive analyses, Student's t-test, and receiver operating characteristic (ROC) analyses were used to quantify the correlation between D-dimer level and the severity of appendicitis and to evaluate the differential diagnostic value of D-dimer combined with WBC count, neutrophil percentage and CRP between simple and other severe appendicitis. RESULTS: Compared with simple appendicitis, WBC count, neutrophil percentage, CRP, and D-dimer levels were all significantly higher in other severe appendicitis (p < 0.01). Both CRP and D-dimer levels were positively correlated with the severity of disease. In differentiating between simple and other severe appendicitis, CRP (area under the ROC curve (AUC): 0.841) showed the highest sensitivity (80.7%) and the highest negative predictive value (NPV) (60.0%), while D-dimer (AUC: 0.793) showed the highest specificity (90.0%) and the highest positive predictive value (PPV) (94.9%). Combined CRP and D-dimer had a sensitivity, specificity, PPV, NPV, and accuracy of 87.5%, 94.6%, 97.8%, 72.9%, and 89.4%, respectively. CONCLUSIONS: CRP and D-dimer levels are positively correlated with the severity of acute appendicitis in children. Combined CRP and D-dimer are identified as suitable diagnostic markers for differentiating between simple and other severe appendicitis, which will provide important guidance for clinicians to determine the follow-up management of acute appendicitis.

IL-33 reflects dynamics of disease activity in patients with autoimmune hemolytic anemia by regulating autoantibody production.

BACKGROUND: Autoimmune hemolytic anemia (AIHA), a life-threatening anemia with rapid onset, is caused by autoantibody directed to self red blood cells (RBCs). Currently, mechanisms underlying AIHA pathogenesis are largely undefined. Here we explored the correlation of IL-33 with AIHA disease activity and evaluated IL-33 based therapeutics in AIHA treatment. METHODS: Thirty patients diagnosed with AIHA of warm-type autoantibodies without treatment were enrolled and followed up for 6 months. Levels of cytokines including IL-33, IL-4, IL-6 and IL-13 was determined with ELISA. AIHA disease activity was presented by levels of reticulocyte count, hemoglobin and lactate dehydrogenase. Serum RBC-bound IgG autoantibody was detected using anti-IgG antibody with flow cytometry. To evaluate the effect of IL-33 blockade on AIHA development, groups of B6 mice were immunized with rat RBCs plus recombinant IL-33 protein or IL-33 neutralizing antibody respectively and detected for levels of anti-RBC antibody, frequency of reticulocytes and destruction of transfused syngeneic mouse RBCs. RESULTS: Serum level of IL-33 was higher in AIHA patients compared with healthy individuals. Of interest, serum IL-33 was positively correlated with AIHA disease activity and sensitive to their changes in AIHA patients under clinical management. Mechanistically, IL-33 could promote the production of anti-RBC autoantibody. Serum IL-33 was closely associated with serum anti-RBC autoantibody and sensitive to their changes in AIHA patients. Accordingly, blockade of IL-33 interfered with AIHA incidence and ameliorated disease activity. Vice vasa, enforced IL-33 promoted AIHA incidence and disease activity. CONCLUSIONS: IL-33 was a potential biomarker for monitoring disease activity and therapeutic response in AIHA patients. Targeting IL-33 was a promising strategy for controlling autoantibody production in AIHA patients.