PD-1/PD-L1-negative tracheal mucoepidermoid carcinoma: A case report and systematic review of the literature

Background: Tracheal mucoepidermoid carcinoma is a rare form of non-small cell lung carcinoma and is defined as a tumor characterized by a combination of squamous, mucus-secreting, and intermediate cell types. This carcinoma is usually located in the lobar or segmental bronchus. Currently, surgery is the preferred treatment for this disease, which includes pneumonectomy, lobectomy, and sleeve lobectomy. Case presentation: A 50-year-old Chinese male presented with cough, shortness of breath and hemoptysis, and the effect of antibiotic therapy was not good. Subsequently, the airway occupied lesion was found by chest CT, and he was transferred to our hospital for surgical resection. Histologically, the tumor contained squamous epidermal cells, mucoepidermoid cells and intermediate cells. Immunohistochemistrically, the tumor cells were positive for p63, CK5/6, CK7 and Ki67. However, the tumor is generally negative for TTF-1 and neuroendocrine markers. The patient had no recurrence 15 months after the surgery. Conclusions: We report a rare case of mucoepidermoid carcinoma in the distal trachea in which the surgery was difficult and could not be performed like a traditional pulmonary resection. We first provide a comprehensive description of airway management and anesthesia intubation. After surgery, we reviewed the literature and found that PD-1/PD-L1 detection had never been reported in tracheal mucoepidermoid carcinoma. Therefore, we studied the PD-1/PD-L1 pathway in this patient, and the results were negative, which may indicate that potential adjuvant therapy with immune checkpoint inhibitors (ICIs) is not useful in this case.

Systematic Characterization of Heterogeneity caused by Neuroinflammation in Alzheimer’s Disease based on Integrative Network Analysis

Background: Alzheimer's disease (AD) is the most common cause of dementia. As a heterogenous disease, there are several clinically and pathobiological defined subtypes with different molecular signatures. Neuroinflammation contributed to AD pathogenesis, however, the roles it played in the heterogeneity of AD was unclear. Objective: We aimed to illustrate the roles neuroinflammation played in the heterogeneity of AD. Method: An integrative network analysis based on transcriptomics, miRNOmics, and proteomics was performed to illustrate the heterogeneous characters of AD. Combined-functional-networks and hypothesis-network were constructed and analyzed to explore the roles neuroinflammation played in AD heterogeneity. Results: Astrocytes, microglia, ‘M2 macrophage-Neuron’, and ‘Microglia- Neuron’ were shown to be enriched in neuroinflammation related functional terms in a cell- and spatial-specific way. The microglia and neurons could interact with each other in three different ways including indirect interactions via intermediate cells, indirect interactions via soluble factors, and direct interactions established localized and functionally distinct signaling, all of which were used to control different biological processes. The combined network analyses exhibited the key roles neuroinflammation plays in the 'AD hypothesis network’. Conclusion : The AD heterogeneity may be caused by the heterogeneous cells involved in neuroinflammation and the crosstalks between spatial-specific molecular signatures.

A Case Report of Mucoepidermoid Carcinoma With Extensive Keratinization in Parotid: Expanding the Morphologic Spectrum

Mucoepidermoid carcinoma (MEC) is the most common malignant tumor of salivary glands in children and young adults. Typically, it is composed of squamoid, mucin-producing and intermediate-types cells. However, overt keratinization is rare. To the best of our knowledge, extensive keratinization or keratin pearls in MEC has never been reported. Keratinization or keratin pearls are regard “practically never seen in low-grade MEC”. Herein, we report a case of a 34-year-old woman who presented with a tumor in right parotid gland for 2 months. Microscopically, the tumor was composed of extensive squamous cells with overt keratin pearls, intermediate cells and few scattered mucous cells. MAML2 gene break-apart and CRTC1-MAML2 gene fusion were detected by fluorescence in situ hybridization. This is the first report to describe a MEC case with extensive squamous metaplasia and overt keratin pearls formation, which expands the morphologic spectrum of MEC.

Label-free imaging to track reprogramming of human somatic cells

The process of reprogramming patient samples to human induced pluripotent stem cells (iPSCs) is stochastic, asynchronous, and inefficient leading to a heterogeneous population of cells. Here, we track the reprogramming status of single patient-derived cells during reprogramming with label-free live-cell imaging of cellular metabolism and nuclear morphometry to identify high-quality iPSCs. Erythroid progenitor cells (EPCs) isolated from human peripheral blood showed distinct patterns of autofluorescence lifetime for the reduced form of nicotinamide adenine dinucleotide (phosphate) [NAD(P)H] and flavin adenine dinucleotide (FAD) during reprogramming. Random forest models classified starting EPCs, partially-reprogrammed intermediate cells, and iPSCs with ~95% accuracy. Reprogramming trajectories resolved at the single cell level indicated significant reprogramming heterogeneity along different branches of cell state. This combination of micropatterning, autofluorescence imaging, and machine learning provides a unique non-destructive method to assess the quality of iPSCs in real-time for various applications in regenerative medicine, cell therapy biomanufacturing, and disease modeling.

Clinico-echographic manifestation of endometritis in cows

Purpose: to study the clinical and echographic manifestation of endometritis.Materials and methods. Clinical and echographic research was carried out on 19 red-and-white cows, in the conditions of the agricultural farm of the Druzhba breeding plant, Pavlovsky district, Voronezh region on the 30-32th day after calving using the Easi-Scan scanner from BCF Technology Ltd, Scotland. Before ultrasound examination to establish the diagnosis, all animals were examined, transrectal palpation of the uterus. Simultaneously with the ultrasound examination, a cytological study of the uterine mucosa was carried out. For this purpose, a probe was constructed from a metal catheter intended for artificial insemination of cows with sequins by the deep cervical method with rectal fixation of the cervix; a cytobrush of the Juno probe was attached to the tip of the instrument. To confirm the diagnosis, a laboratory study of cervical mucus was additionally carried out by the express method according to Whiteside, modified by N. I. Polyantsev and Yu. N. Popov.Results. According to the results of rectal examination and ultrasound diagnostics, the cows were divided into three groups: clinically healthy, animals with clinically pronounced chronic endometritis and with latent endometritis. In the group of healthy animals, individual superficial and vacuolated intermediate cells (6.17 ± 0.51) and single neutrophils (2.31 ± 0.32) were detected in smears. In the group of clinically healthy cows, no gram-positive coccobacillary microorganisms and cells of the basal layer of the uterine mucosa were detected. In the second group, in animals with clinically pronounced chronic endometritis, a large number of segmented neutrophils, lymphocytes and a large number of cocci were detected in smears. Thus, in one visual field, the number of gram-positive cocobacillary microorganisms fluctuated on average 764.45 ± 4.56 microbial bodies, while the number of neutrophils increased in comparison with clinically healthy animals by 20.84 times and averaged 48.14 ± 2 in the group. , 91, the percentage of the score averaged around 12.1%. Simultaneously with an increase in the number of leukocytes in animals, the number of epithelial cells of the uterine mucosa increased by 2.21 times, while individual basal cells were detected simultaneously with superficial and intermediate cells (0.75 ± 0.48). In smears obtained from animals of the third group of cows, there was a significant decrease in the number of coccobacillary microorganisms to 75-360 in one visual field in comparison with similar results in the group with a clinically pronounced form of chronic endometritis. The indicator for segmented neutrophils was 8.05 times higher than in clinically healthy cows, while in relation to clinically sick cows by 61.4% and amounted to 18.60 ± 2.23. In terms of the number of superficial, vacuolated intermediate and basal cells in sick animals with chronic clinically pronounced endometritis and latent endometritis, no significant changes were revealed (1.08 times), while in relation to clinically healthy animals, these indicators were 2.38 times higher. The degree of variation in the number of epithelial cells in the group of cows with latent chronic endometritis was insignificant, which indicates the stability of the trait.Conclusion. Ultrasound scanning allows you to identify the latent form of endometritis and establish degenerative changes in the tissues of the uterus. Ultrasound examination in cows in establishing a diagnosis - endometritis should be the decisive diagnostic method.

Modeling the pathway of breast cancer in the Middle East

This paper proposed an approach for the identification of mutation mechanisms of breast cancer in women in four member countries of the Middle East Cancer Consortium i.e. Egypt, Jordan, Cyprus and Israel (Arabs and Jews). We set up multistage models including both gene mutation and the clonal expansion of intermediate cells. We fit the data-set related to the incidence of female breast cancer in the four member countries. Our simulation results show that the maximum number of driver mutations of breast epithelium stem cells of Egyptian women is 13, whereas there are 14 driver mutations in the genome of stem cells of female patients in Jordan, Cyprus and Israel (Arabs and Jews). In addition, the 3, 10, 5, 5 and 4 stage models are the optimal ones for the tumorigenesis of females in Egypt, Jordan, Cyprus, Israel (Arabs) and Israel (Jews), respectively. The genomic instability is caused by first three driver mutations.

NF-κB determines Paneth versus goblet cell fate decision in the small intestine

ABSTRACT Although the role of the transcription factor NF-κB in intestinal inflammation and tumor formation has been investigated extensively, a physiological function of NF-κB in sustaining intestinal epithelial homeostasis beyond inflammation has not been demonstrated. Using NF-κB reporter mice, we detected strong NF-κB activity in Paneth cells, in ‘+4/+5’ secretory progenitors and in scattered Lgr5+ crypt base columnar stem cells of small intestinal (SI) crypts. To examine NF–κB functions in SI epithelial self-renewal, mice or SI crypt organoids (‘mini-guts’) with ubiquitously suppressed NF-κB activity were used. We show that NF-κB activity is dispensable for maintaining SI epithelial proliferation, but is essential for ex vivo organoid growth. Furthermore, we demonstrate a dramatic reduction of Paneth cells in the absence of NF-κB activity, concomitant with a significant increase in goblet cells and immature intermediate cells. This indicates that NF-κB is required for proper Paneth versus goblet cell differentiation and for SI epithelial homeostasis, which occurs via regulation of Wnt signaling and Sox9 expression downstream of NF-κB. The current study thus presents evidence for an important role for NF-κB in intestinal epithelial self-renewal.

Central mucoepidermoid carcinoma arising directly from a glandular odontogenic cyst of the mandible: a case report

Background Central mucoepidermoid carcinoma (MEC) is a rare salivary gland tumor that affects the jawbone. Glandular odontogenic cyst (GOC) is also a rare odontogenic developmental cyst with glandular differentiation. GOC shares some histological features with central MEC, and a pre-existing GOC can develop into central MEC. Here, we present a rare case of central MEC developed directly from a pre-existing GOC of the mandible. Case presentation A 67-year-old Japanese man presented with a cystic lesion in the right third molar region. Histologically, the biopsy specimen demonstrated both typical findings of a GOC component lined with non-keratinized squamous epithelium and a recognizable component of central MEC consisting of polycystic nests with mucous cells, intermediate cells, and epidermoid cells in the cyst wall. The results from the immunohistochemistry for cytokeratin (CK) profiling demonstrated that, while both central MEC and GOC expressed CKs 7, 14, 18, and 19, CK13 was interestingly exclusively expressed in GOC. Fluorescence in-situ hybridization (FISH) revealed the rearrangement of the Mastermind like (MAML)-2 gene in both the MEC and GOC components. Conclusions Our case suggests that central MEC and GOC may be in the same spectrum of diseases caused by the rearrangement of the MAML-2 gene. However, given that the expression profile of CK13 was completely different between central MEC and GOC, they can be considered as separate tumors. Overall, we demonstrated a rare case in which central MEC may have originated directly from the GOC.

Laboratory Findings, Vaginal Cytology and Histopathology in Bitches with Cystic Endometrial Hyperplasia – Pyometra Complex

Cystic Endometrial Hyperplasia -Pyometra complex, a common pathological condition of uterus in bitches, it is attributed hormonal and bacteriological causes. It is studied in 10 bitches of cross and pure bred and aged from 1-13 years. In this study, the average age of animals was 8.33±1 year. Hematological and biochemical lab findings were evaluated in bitches with or without vaginal discharge. Lab findings were leukocytosis, neutrophilia and normocytic, normocromic anemia. Biochemical results shown increased of ALT and ALKP and a moderate of BUN. An increased number of parabasal and intermediate cells were detected in vaginal cytology. Histopathologic diagnosis confirmed thickness of uteri wall, a lot of cystic glands of it and the pus presented in lumen of uterus and its horns. The purposes of this study were that through different techniques to diagnose earlier Cystic Endometrial Hyperplasia – Pyometra complex in bitches, in order to welfare of animals.

Loss of Adam10 disrupts ion transport in immortalised kidney collecting duct cells

The kidney cortical collecting duct (CCD) comprises of principal cells (PC), intercalated cells (IC) and the recently discovered intermediate cell type. Kidney pathology in a mouse model of the syndrome of apparent aldosterone excess (SAME) revealed plasticity of the cortical collecting duct (CCD), with altered principal cell (PC): intermediate cell: intercalated cell (IC) ratio. The self-immortalized mouse CCD cell line, mCCDcl1, shows functional characteristics of PCs but displays a range of cell types, including intermediate cells, making it ideal to study plasticity. We knocked out Adam10, a key component of the Notch pathway, in mCCDcl1 cells, using CRISPR-Cas9 technology, and isolated independent clones, which exhibited severely affected sodium transport capacity and loss of aldosterone response. Single-cell RNA sequencing revealed significantly reduced expression of major PC-specific markers, such as Scnn1g (γ-ENaC) and Hsd11b2 (11ßHSD2), but no significant changes in transcription of components of the Notch pathway were observed. Immunostaining in the knockout clone confirmed the decrease in expression of γ-ENaC and importantly, showed an altered, diffuse distribution of PC and IC markers, suggesting altered trafficking in the Adam10 knockout clone as an explanation for the loss of polarisation.