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Kawasaki disease (KD) is a multi-systemic vasculitis of unknown etiology that occurs mainly in children, and the disturbance of gut microbiota is generally believed to cause a hyperimmune reaction triggering KD. The aim of the study was to investigate the alterations in the fecal microbiota and assess its relationship with systemic inflammation. Totally 30 KD children were enrolled and followed up for 6 months, with another group of 30 age- and sex-matched healthy children as controls. Phylotype profiles of fecal microbial communities were analyzed using 16S rRNA gene sequencing. Serum inflammatory markers were detected by flow cytometer. We showed that KD children exhibited a significant reduction in fecal microbial diversity in the acute phase compared with the healthy controls. Enterococcus, Acinetobacter, Helicobacter, Lactococcus, Staphylococcus and Butyricimonas in acute KD children were significantly higher than the healthy children. Levels of systemic inflammation biomarkers, including IL-2, IL-4, IL-6, IL-10, TNF-α, and INF-γ, were significantly elevated in the acute KD children. Altered microbiota genera Enterococcus and Helicobacter abundances were shown to be correlated positively with IL-6, which were never previously reported in KD. This study suggested that gut microbiota alteration is closely associated with systemic inflammation, which provides a new perspective on the etiology and pathogenesis of KD.

Numb is known as a cell fate determinant as it identifies the direction of cell differentiation via asymmetrical partitioning during mitosis. It is considered as a tumour suppressor, and a frequent loss of Numb expression in breast cancer is noted. Numb forms a tri‐complex with p53 and E3 ubiquitin ligase HDM2 (also known as MDM2), thereby preventing the ubiquitination and degradation of p53. In this study, we examined Numb expression in 125 patients with triple‐negative breast cancer (TNBC). The results showed that 61 (48.8%) patients presented with a deficient or decreased Numb expression. The percentage of Ki67 > 14% in the retained Numb group was significantly lower than that in the decreased and deficient Numb groups (86.00% vs. 98.40%, P = .0171). This study aimed to detect the expression and migration of Numb, HDM2 and p53 in the membrane, cytoplasmic and nuclear fractions of normal mammary epithelial cell line MCF‐10A and basal‐like TNBC cell line MDA‐MB‐231. We obtained the cell fractions to identify changes in these three protein levels after the re‐expression of NUMB in the MDA‐MB‐231 cells and the knocking down of NUMB in the MCF‐10A cells. Results showed that Numb regulates p53 levels in the nucleus where the protein levels of Numb are positively correlated with p53 levels, regardless if it is re‐expressed in the MDA‐MB‐231 cells or knocked down in the MCF‐10A cells. Moreover, HDM2 was remarkably decreased only in the membrane fraction of NUMB knock‐down cells; however, its mRNA levels were increased significantly. Our results reveal a previously unknown molecular mechanism that Numb can migrate into the nucleus and interact with HDM2 and p53.

Different cellular constituents of the central nervous system occurring in encephaloceles or neuroglial heterotopias (NGHs) have been reported, but the ependymal morphology has rarely been described in the previous literature, let alone the related histological images. To determine the ependymal morphology in encephaloceles or NGHs, we report a rare case of encephalocele with numerous ependymal components. Radiological examination showed that a 6.2 × 3.1 cm nasal dorsum mass-forming encephalocele in a 24-year-old woman, who had an intracranial connection through a frontal bone defect. This patient underwent a resection of the encephalocele under nasal endoscopy and a reconstruction of the cranial base. The patient had a good prognosis with no postoperative complications during follow-up. Microscopically, the ependymal components entrapped in a collagenized background showed numerous slit-like spaces lined by columnar cells with abundant palely eosinophilic cytoplasm and apical surface microvilli. With immunohistochemistry, in addition to the expression of EMA along with the slit-like spaces, GFAP and S100 were diffusely expressed in the slit-like spaces. In conclusion, the ependymal component in either encephaloceles or NGHs may present slit-like spaces arranged in an anastomosing pattern. The unusual morphology of ependyma continues to be underrecognized by pathologists and is easily misdiagnosed; therefore, an awareness of the morphological change in ependyma is necessary.

BackgroundLymph node inclusions are foci of ectopic tissue in lymph nodes, which were reported in different areas of the body. However, inclusions in the mediastinal lymph node are rare. Here, we report the first case of glandular inclusion within the parenchyma of the intrapulmonary lymph node in a patient with primary lung adenocarcinoma.Case presentationA computed tomography (CT) scan showed a solid pulmonary nodule in the right upper lobe in a 44-year-old man. After a fine needle aspiration biopsy diagnosis of adenocarcinoma, lobectomy and lymph dissection were performed. Histological sections of the lung demonstrated a papillary predominant adenocarcinoma and one intrapulmonary lymph node, which displayed glandular inclusion occupying the node parenchyma. The gland inclusion was very similar to metastasis, but was formed by two layers of epithelial cells, and the abluminal cells were positive for P63, P40, and CK5/6. The patient has remained alive without recurrence and metastasis at the last follow-up before publication.ConclusionsIt is very important to correctly diagnose a lymph node inclusion for proper clinical management.

Purpose Tumors with high mutation load tend to have a stronger immune response in some tumors. The correlation between expression of programmed death ligand-1 (PD-L1), a biomarker of immune response in tumors, and p53, accepted as the most frequently mutated gene in many cancers, in triple-negative breast cancer (TNBC) has not been fully investigated in cancer patients. Materials and methods 132 cases of TNBC and 32 cases of non-TNBC paraffin-embedded tissue sections were selected to detect the expression of PD-L1 and p53 by immunohistochemistry, and results were correlated with clinical data and survival outcomes. The staining of PD-L1 in tumor cells (TCs) and tumor-associated immune cells (TAICs) was assessed separately. Results Strong positive correlations were observed between expression of p53 and PD-L1 both in TCs (r=0.338, P=0.000) and TAICs (r=0.186, P=0.033). The same positive correlation was found in the expression of PD-L1 in TCs and TAICs (r=0.764, P=0.000). Like p53 (P=0.024), positive rate of PD-L1 in TCs was significantly higher in TNBC than in non-TNBC (P=0.02). PD-L1 and p53 in TCs staining were significantly associated with histological grade, tumor size and Ki67 index (P

To assess the diagnostic performance of the H-score of 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) in the histopathological diagnosis of adrenocortical tumors (ACT). We retrospectively evaluated 199 cases of ACT, of which 85 were diagnosed as aldosterone-producing adenoma (APA), 66 as cortisol-producing adenoma (CPA), 9 as aldosterone–cortisol co-secreting adenoma, 30 as nonhyperfunctioning adenoma, and 9 as adrenocortical carcinoma (ACC). Immunohistochemical staining was performed using anti-CYP11B1 and anti-CYP11B2 monoclonal antibodies. The staining was quantified by the McCarty’s H-score system. The diagnostic performance was assessed by the receiver operating characteristic curve (ROC). The H-score of CYP11B1 is highest in the CPA group and lowest in the ACC group. The H-score of CYP11B2 in the APA group is significantly higher than other ACT groups. The area under ROC (AUC) of an increased H-score of CYP11B2 (>65) for the diagnosis of APA was 0.971 (95%CI 0.937–0.990). The AUC of an increased H-score of CYP11B1 (>204) for the diagnosis of CPA was 0.725 (95%CI 0.658–0.786). The AUC of a decreased H-score of CYP11B1 (

Pulmonary extranodal marginal zone lymphoma of the mucosa‐associated lymphoid tissue (MALT) presenting as a progressive pure ground‐glass nodule (GGN) coexisting with lung squamous cell carcinoma has not been reported. A 65‐year‐old male presented with a progressive lung GGN in the left upper lobe identified six and a half years ago but showed no symptoms. The patient had a history of tuberculosis, squamous cell carcinoma, and stomach MALT lymphoma. The patient was diagnosed with lung squamous cell carcinoma coexisting with pulmonary MALT lymphoma through computed tomography (CT)‐guided lung biopsy. A progressive lung GGN presenting in a patient with squamous cell carcinoma does not always indicate multiple primary lung adenocarcinoma, especially when given a specific medical history. The development of MALT lymphoma in the lung presenting as GGNs suggests a possible association between these two entities., Here, we present an extremely rare case of coexistence of lung squamous cell carcinoma with mucosa‐associated lymphoid tissue (MALT) lymphoma presenting as progressive lung ground‐glass nodules.

Background: IgA antibodies against Epstein-Barr virus (EBV) capsid antigen (VCA) and nuclear antigen 1 (EBNA1) have been proposed to facilitate the diagnosis and early detection of nasopharyngeal carcinoma (NPC) in high-incidence regions. However, while new methodologies and new platforms for the detection of VCA-IgA and EBNA1-IgA have become available, proper interassay simultaneous comparisons have not been carried out. The study was to compare the performance of the chemiluminescent immunoassays (CLIA) and enzyme-linked immunosorbent assay (ELISA) for VCA-IgA and EBNA1-IgA antibodies, and to evaluate the levels of EBV antibodies in healthy population from different areas of China. Methods: CLIA and ELISA for VCA-IgA and EBNA1-IgA were performed in NPC and healthy populations from high-incidence areas of NPC in South China (N=555), medium-incidence areas of NPC in Central China (N=318) and low-incidence areas of NPC in North China (N=379), and the results were compared and analyzed. Results: (1) The highest sensitivity in total, early and advanced NPC were 91.5% (CLIA for VCA-IgA), 86.4% (CLIA and ELISA-2 for EBNA1-IgA) and 93.6% (CLIA for VCA-IgA). However, the specificity of EBV-IgA measured by CLIA was relatively lower than ELISA. The top three seromarkers with the largest AUC was CLIA for VCA-IgA (AUC: 0.929, 95% CI: 0.905-0.953), ELISA-2 for EBNA1-IgA (AUC: 0.922, 95% CI: 0.896-0.947) and CLIA for EBNA1-IgA (AUC:0.919, 95% CI: 0.893-0.945), respectively. The positive and negative coincidence rates of the two EBNA1-IgA kits were 69.5% and 91.9%, respectively. However, the coincidence rates of VCA-IgA were relatively low. CLIA kits had good repeatability between different laboratories. (2) The positive rates of EBV-IgA antibodies were relatively high in high-incidence areas of NPC (P < 0.017), while there was no significant difference in the antibody positive rates between medium-incidence areas and low-incidence areas of NPC (P > 0.05). Conclusions: The performance of EBV-IgA antibodies measured by CLIA has good repeatability, higher sensitivity and similar specificity. The higher EBV-IgA positive rate in healthy subjects by CLIA raises concern about its suitability for NPC-risk screening and requires further analysis.

Background Pituicytoma is a rare pituitary non-neuroendocrine tumour. The awareness of pituitary non-neuroendocrine tumours has gradually increased over the past several decades, but the knowledge of some histological variants of the tumours is limited, particularly in clinicopathological significance. Here, we report a rare case of pituicytoma variant. Case presentation A 71-year-old man presented with sudden symptoms of stroke including urinary incontinence, weakness in right lower limb, and trouble speaking. Physical examinations showed a right facial paralysis. The radiological examinations eventually found a 1.7 × 1.4 × 1.3 cm sellar occupied lesion. After symptomatic treatment improved the symptoms, the patient underwent transsphenoidal resection of the pituitary mass. Histologically, the tumour contained hypocellular area and hypercellular area. The hypocellular area showed elongated spindle cells arranged in a fascicular pattern around small vessels and scattered Herring bodies; the hypercellular area showed a large number of pseudorosettes. Immunohistochemistrically, the tumour cells were positive for thyroid transcription factor-1, S100, and neuron-specific enolase. Neurofilament only showed a little positive in the hypocellular area, and silver impregnation was only noted in a perivascular distribution. The patient had no recurrence 4 months after the surgery. Conclusions The rare variant of pituicytoma has a favourable prognosis. Moreover, it needs to be distinguished pituicytomas with pseudorosettes from ependymomas because of different prognosis. Lastly, Herring bodies may occasionally be seen in the pituicytoma, which could be a potential diagnostic pitfall.

Programmed cell death protein 1 (PD-1) and indoleamine 2,3-dioxygenase (IDO) are both immunosuppressive proteins. Here, we investigated the relationship between PD-1 and IDO in the tumor microenvironment (TME) and in tumor-draining lymph nodes (TDLNs) in breast cancer patients. First, the protein and mRNA expression levels of PD-1 and IDO in 20 frozen tissues were examined using Western blotting and real-time polymerase chain reaction. Second, 151 paraffin-embedded breast samples and 52 lymph node samples were analyzed by immunohistochemistry. Third, correlation and survival data for PD-1 and IDO in 963 breast tumor patients were mined using the cBio Cancer Genomics Portal. We found that the protein expression level of IDO was significantly increased in frozen tumor tissues (P = .005). From paraffin-embedded samples in the TME, PD-1+ cells were only located in the stroma, while IDO was expressed in myoepithelial, stromal, and tumor cells. PD-1 and stromal IDO in the TME showed increased expression in tumors (P< .001 and P < .001, respectively). In TDLNs, PD-1+ cells were primarily located in the germinal centers (GCs), and IDO+ cells were primarily located in the paracortex. Normal lymph nodes expressed PD-1 and IDO at the same level as non-metastatic and metastatic lymph nodes (P = .151 and P = .812, respectively). According to cBioPortal, the correlation analysis showed that IDO and PD-1 had high correlation coefficients (r = 0.83). These findings suggest that there is a positive correlation between the expression of PD-1 and IDO and that blocking both PD-1 and IDO pathways may represent an attractive therapeutic strategy in breast cancer treatment.

Background Six Sigma methodology with a zero‐defect goal has long been applied in commercial settings and was utilized in this study to assure/improve the quality of various analytes. Methods Daily internal quality control (QC) and external quality assessment data were collected and analyzed by calculating the sigma (σ) values for 19 analytes based on the coefficient of variation, bias, and total error allowable. Standardized QC sigma charts were established with these parameters. Quality goal index (QGI) analysis and root cause analysis (RCA) were used to discover potential problems for the analytes. Results Five analytes with σ ≥ 6 achieved world‐class performance, and only the Westgard rule (13s) with one control measurement at two QC material levels (N2) per QC event and a run size of 1000 patient samples between QC events (R1000) was needed for QC. In contrast, more control rules (22s/R4s/41s) along with high N values and low R values were needed for quality assurance for five analytes with 4 ≤ σ

Liver plays an essential role in regulating lipid metabolism, and chronically disturbed hepatic metabolism may cause obesity and metabolic syndrome, which may lead to non‐alcoholic fatty liver disease (NAFLD). Increasing evidence indicates long non‐coding RNAs (lncRNAs) play an important role in energy metabolism. Here, we investigated the role of lncRNA H19 in hepatic lipid metabolism and its potential association with NAFLD. We found that H19 was up‐regulated in oleic acid‐induced steatosis and during the development of high‐fat diet (HFD)‐induced NAFLD. Exogenous overexpression of H19 in hepatocytes induced lipid accumulation and up‐regulated the expression of numerous genes involved in lipid synthesis, storage and breakdown, while silencing endogenous H19 led to a decreased lipid accumulation in hepatocytes. Mechanistically, H19 was shown to promote hepatic steatosis by up‐regulating lipogenic transcription factor MLXIPL. Silencing Mlxipl diminished H19‐induced lipid accumulation in hepatocytes. Furthermore, H19‐induced lipid accumulation was effectively inhibited by PI3K/mTOR inhibitor PF‐04691502. Accordingly, H19 overexpression in hepatocytes up‐regulated most components of the mTORC1 signalling axis, which were inhibited by silencing endogenous H19. In vivo hepatocyte implantation studies further confirm that H19 promoted hepatic steatosis by up‐regulating both mTORC1 signalling axis and MLXIPL transcriptional network. Collectively, these findings strongly suggest that H19 may play an important role in regulating hepatic lipid metabolism and may serve as a potential therapeutic target for NAFLD.

Xin Yang,1 Youde Cao,2 Chen Chen,1 Lin Liu,1 Cheng Wang,1 Shengchun Liu1 1Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, 2Department of Pathology, Chongqing Medical University, Chongqing, People’s Republic of China Background: Primary neuroendocrine breast carcinomas (NEBCs) are a rare type of breast carcinomas that lack comprehensive recognition, including the clinicopathological features, therapeutic strategies, and prognostic significance. The aim of this retrospective analysis is to present and analyze our own data of primary NEBCs.Materials and methods: We retrospectively reviewed the medical records from 2005 to 2015 in The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China to obtain a cohort of breast carcinoma patients who were confirmed to have primary NEBC by histopathology. The detailed clinical data along with histopathology, treatment, and follow-up aspects were gathered for analysis.Results: This retrospective analysis included 19 patients with a histopathological diagnosis of primary NEBC from 2005 to 2015. Their mean age was 59.2years (ranging from 17 to 82years). The majority of patients (15/19) focused on stages I and II. Of the 15 patients, 14 were positive for estrogen receptor, and 11 were positive for progesterone receptor. For neuroendocrine markers, the expression rates were 8/19, 14/18, 12/14, and 2/6 for chromogranin A, synaptophysin, neuron-specific enolase, and CD56, respectively. All operable patients except the one stage M1 underwent a surgery and 4/18 had axillary lymph node metastasis. Chemotherapy was performed in 12/19, and endocrine therapy in 8/10. With a median follow-up of 59.2months, only 2 cases progressed after postoperative systemic therapy.Conclusion: The understanding of NEBC is limited due to its rarity. More evidence should be provided to enhance the understanding of NEBC, especially for diagnosis, treatment, and prognosis. Keywords: primary neuroendocrine breast carcinomas, diagnosis, therapy, follow-up

Background: The emergence of vaccine-associated paralytic poliomyelitis has become an ongoing burden of poliomyelitis. During this special period from OPV to IPV-only immunization schedule, we did a meta-analysis to compare the immunogenicity of sequential IPV and OPV versus IPV alone in healthy infants. Methods: This systematic review and meta-analysis was registered at international prospective register of systematic reviews (PROSPERO), and the number was CRD42017054889. We performed it as described. Results: Finally, 6 articles were qualified for our review. The results showed that seroconversion rates against all 3 serotype polioviruses were non-inferior and Geometric mean antibody titers (GMTs) were superior in sequential schedules compared with IPV-only schedule. Thus, the sequential vaccination schedules could induce a stronger immunogenicity. Conclusions: To decrease vaccine-associated and vaccine-derived poliomyelitis, it is a reasonable option to select sequential schedules during this special transition from OPV to IPV-only immunization schedule, which coincides with the current WHO recommendations.