Dynamics of morphological manifestations of the experimental acute aspiration bronchopneumonia development.

Background. Currently, there is a need to create an experimental model for reproducing the main pathogenetic mechanisms of COVID-associated lungs damage. The first stage of such a model may be reproducing acute aspiration bronchopneumonia in rats. Objective. Examine the dynamics of morphological changes in the lungs in the development of experimental acute aspiration bronchopneumonia. Methods. The group of laboratory Wistar rats (n=25) in compliance with bioethical norms under typoental anesthesia was carried out operational intervention with the introduction of a sterile capron thread 2.5 cm long and a thickness of 0.2 mm to a depth of 2.5 cm. In the control group included 5 false-controlled animals. At 7, 14, 21, 28 and 56 days, the animals were derived from the experiment, morphological studies were carried out with the painting serial sections with hematoxylin-eosin. Results. On the 7 day, the morphological picture testified to the development of the acute stage of exudative inflammation with the full-blood of vessels, microtrombosis, dyslectasis, hyperplasia of alveolocytes II type. After 14 days, the proliferative stage was formed with alveolocytes hyperplasia, the epithelium of bronchi, as well as fibroblasts with the formation of sharp peribronchial and alveolar abscesses. After 21 days, the development of the lungs fibrosis with the organization of acute peribronchial and alveolar abscesses was noted, peribronchial and intraalveoli pronounced interstitial edema and the reactive hyperplasia of lymphoid follicles of a mixed nature. After 28 days, bronchopneumonia was organized in the form of fibrosis parenchyma, sections of chronic productive inflammation with the formation of resorbative granuloms; sections of the blood vessels hyalinose. For 56 days, these phenomena were progressed before the development of dense fibrosis (carnification) with sections of chronic abscesses with a formed by a connective tissue capsule, the development of vascular hyalinose. Conclusion. Thus, the model of acute aspiration bronchopneumonia reproduces the dynamics of morphological manifestations of acute lung damage, which is the basis for the development of pathogenetic therapy fields.

Chest CT findings in COVID-19

RT-PCR is the gold standard in the diagnosis of COVID-19 infections, due to its high specificity. However, there are clinical situations in which chest CT may prove vital, for example in patients with high clinical and epidemiologic suspicion towards COVID-19 before positive RT-PCR conversion or in detecting complications. Researchers have developed scales that, based on the findings in chest CT, help predict the severity of the disease. There are three main pathologic patterns of lung injury that correlate with the duration of COVID-19 symptoms. Epithelial pattern with diffuse alveolar damage and desquamation/reactive hyperplasia of pneumocytes; vascular pattern with capillary congestion and (micro)thrombi and fibrotic pattern with interstitial fibrous changes. The epithelial pattern and vascular pattern appear early, even before the symptoms of the disease, whereas the fibrous pattern appears approximately three weeks after the onset of the disease. Typical findings on chest CT in COVID-19 infection are: GGO, consolidation, GGO mixed with consolidation, interlobular septal thickening, air bronchogram sign, crazy paving, bronchial wall thickening and vascular enlargement. Findings that may suggest a different etiology include multiple nodules, tree-in-bud opacities, bronchiectasis, pleural and pericardial effusion, extensive consolidations.

IMMUNOPATHOLOGICAL EFFECT OF SENSITIZED TRANSFER FACTOR ON THE ORGANS OF WHITE MICE AGAINST SALMONELLA TYPHI CHALLENGE INFECTION.

In an experimental study to evaluate the immunopathological effect of transfer factor on the reticuloendothelial organs of white mice and their protection against their challenge infection with Salmonella typhi. The results of this study were showed the followings: 1. Transfer factor recipient group: it was showed an early granulomatous lesions in the liver. Reactive hyperplasia in the T cell regions of the spleen and mediastinal lymph node. The early granulomas were persisted during 7th day and slightly regressed on 14th day postinoculation. 2. Infected group with S. typhi: It was showed a multifocal microabscesses consisted of aggregates of neutrophils in the focal area of necrosis, which was evident during 7th day and gradually transform into granulomas on 14th day postinoculation. 3. Transfer factor recipient and challenge infection group: It was showed well developed granulomatous reactions, which indicate an emergence of cellular immunity (delayed type hypersensitivity reaction). These granulomas were more evident on 7th day and slightly regressed on 14th day postinoculation; providing a transfer factor role in tissue reaction and termination of infection.

Nanoparticle-Based Drug Delivery System—A Target Strategy for Osteoarthritis Treatment

Osteoarthritis (OA) is a bone and joint disease with pathological characteristics such as articular cartilage degeneration injury and synovial and subchondral bone reactive hyperplasia. Once cartilage is damaged, it is difficult to repair it by itself. Current clinical practice is mainly limited to symptomatic treatment, not changing the degenerative process of osteoarthritis. The important goal of nanomedicine is targeted delivery. Nanoparticles (NPs) can provide many unique potential functions for the targeted treatment of arthritis. This review summarizes the research progress of nanomaterials as a drug delivery system in the treatment of osteoarthritis from three aspects: (1) the etiology of OA and the current research status of applying nanoparticles to treat OA, (2) the construction of osteoarthritis models, and (3) the classification of nanoparticle-based drug delivery systems.

Immunophenotyping of non-Hodgkin’s lymphoma by flowcytometry on fine needle aspiration

Background: Lymphoma represents one of the major health problems all over the world. Flow cytometry (FCM) can be used on fine-needle aspiration cytology (FNAC) from lymph node as an ancillary technique. Aim of the study was to assess the utility of flowcytometry (FCM) in diagnosis and differentiation of reactive hyperplasia and non-Hodgkin’s lymphoma (NHL) on FNAC.Methods: The study was carried out on 50 cases, 25 each of reactive hyperplasia and suspicious or confirmed NHL on FNAC. FCI was performed with a complete panel of antibodies on FACS Canto II FCM.Results: All 25 cases of reactive hyperplasia on FNAC were polyclonal on FCM. FCM could be performed in 22 cases (88%) out of 25 suspicious NHL and in three cases the material was inadequate on aspirate. Out of 22 cases of NHL on FNAC 17 cases (77.30%) were diagnosed as B-NHL on FCM. Light chain restriction was demonstrated in 15/17 cases. With the help of FCI, 6 cases were diagnosed as small cell lymphocytic lymphoma, one case as mantle cell lymphoma, one case as follicular lymphoma, and 9 cases as B-NHL-NOS. Histopathology diagnosis was available in nine cases and were in concordance to FCM. Sensitivity of combined FNAC and FCM in sub-classification was 77.30% (17/22). Four cases showed discordance between FNAC and FCM.Conclusion: We concluded that FCM enhances the diagnostic ability of FNAC, playing a crucial role in a rapid and accurate differential diagnosis between reactive hyperplasia, B-NHL and T-NHL.

Flow Cytometry Analysis of Recurrent or Persistent Lymphadenopathy in Patients with Nodular Lymphocyte-Predominant Hodgkin Lymphoma

Objectives: We recently examined the utility of flow cytometric analysis in the diagnosis of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) by examining reactive T-cell features. This study aims to compare these features in sequential biopsies of persistent or recurrent lymphadenopathy in patients with NLPHL. Methods: We reanalysed the histopathology and flow cytometry findings of 9 patients with multiple biopsies for persistent or recurrent lymphadenopathy and either initial or recurrent NLPHL. A flow cytometry signature was considered suggestive of NLPHL if ≥12% of T-cells expressed CD57 or ≥3% of T-cells co-expressed CD4 and CD8. Results: A flow cytometry signature considered suggestive of NLPHL was seen in 18 of 20 specimens. Based on histopathology, 11 were diagnosed as NLPHL, 3 were initially underdiagnosed as atypical lymphoid proliferation, and 4 were initially incorrectly diagnosed as negative or progressive transformation of germinal centers. Flow cytometry showed similar expression patterns of CD57 and CD4/CD8 in T-cells between initial and subsequent biopsies. The remaining 2 specimens lacked the flow cytometry signature suggestive of NLPHL and were histopathologically diagnosed as reactive hyperplasia. Conclusion: Flow cytometry analysis based on our criteria is highly sensitive in detecting NLPHL. Correlation with the cytospin cytology may increase the diagnostic specificity. A negative flow essentially ruled out the possibility of NHLPHL.

Retrospective study of Lymphadenopathy by FNAC in National Institute of Health Islamabad-Pakistan

The objective of the study was to review the pathology of lymph node disorders in adults with peripheral lymphadenopathy. A five year (1998 - 2003) retrospective study of lymph node Fine Needle Aspiration Cytology (FNAC) performed at Histopathlogy department of National Institute of Health Islamabad. Females constitute the major group with 130 cases (64%) in our study. Fifty four percent of the cases were below 20 years of age. Benign lesions were found in 91% of the patients, the majority of which were tuberculous lymphadenitis (52%) followed by nonspecific reactive hyperplasia (39%). Frequency of metastatic carcinoma was 9 (4%), malignant lymphoma 2 (1.0%) and insufficient aspirate in 10 (5%) cases. The commonest site of lymphadenopathy was cervical (71%) followed by submandibular (11%), inguinal 8% and axillary 7%. Reactive hyperplasia was more frequent in female (62%) than male patients (38%), similarly tuberculous lymphadenitis was comparatively more frequent in female (64%) than male patients (36%) in our study. Tuberculous lymphadenitis was the most common pathological diagnosis in young females (15 - 25 years). It is concluded that the pattern of disease is similar to that of other countries of the region.

Recurrent, oral cavity tumor-like exophytic lesions mimicking neoplastic disease in a patient with history of human papillomavirus-mediated squamous cell carcinoma

Reactive hyperplasia is a phenomenon responsible for exophytic lesions in the oral cavity, and may appear to be suspicious, especially in patients who have a significant history of malignancy. Here, we present a case of reactive hyperplasia mimicking recurrence in a patient who was previously treated for tonsillar carcinoma. Physicians who commonly see patients with oral lesions, particularly oral surgeons and otolaryngologists, should be cognizant of the unusual presentation of these lesions as they may mimic the physical characteristics of recurrence.

The Expression and Significance of CyclinD2 and Bcl-2 in Diffuse Large B-cell Lymphoma

Objectives: To study the expression and significance of cyclinD2 and Bcl-2 in diffuse large B-cell lymphoma. Methods: This project used immunohistochemical methods to detect the expression of cyclinD2 and Bcl-2 in 120 cases of diffuse large B-cell lymphoma and 80 cases of reactive hyperplasia of lymphoid tissue. The materials were collected from the hospital from January 2018 to 2020. In March 2015, 120 patients had lymphoma tissue removed during the month of surgery. The postoperative pathological diagnosis was DLBCL. Another 80 cases of lymphoid hyperplasia (RLH) tissues were selected as controls. Results: CyclinD2 and BCL-2 expression were not statistically different in patients with diffuse large B-cell lymphoma in different ages, genders, locations, tissue types, and degree of differentiation; but statistically significant in different Ann Arbor stages, immunotypes, IPI index and first treatment efficacy. Conclusion: This research not only has important theoretical value, but also important economic value and social significance.

Identification of m6a Methyltransferase KIAA1429 As a Potential Prognostic Biomarker in Diffuse Large B-Cell Lymphoma

Introduction N6-methyladenosine (m6A) is the most abundant form of internal modifications in eukaryotic cells. m6A methylation is dynamically modulated by diverse types of regulators, including methyltransferases ('writers'), RNA binding proteins ('readers'), and demethylases ('erasers'). Growing evidence has shown that m6A methylation plays essential role in the development and progression of multiple cancers. However, the functions of m6A methylation in diffuse large B-cell lymphoma (DLBCL) remains undefined. Herein, we aimed to identify novel prognostic biomarker by m6A methylation regulators and explore its underlying mechanism in DLBCL. Methods The available expression data of 48 DLBCL samples and 337 normal samples and the clinical information from 928 DLBCL samples were separately extracted from three databases. The expression level of the m6A methylation regulators was analyzed and the LASSO Cox regression was employed to calculate risk score. Kaplan-Meier survival analysis, univariate and multivariate Cox regression analyses, and ROC curve analysis were conducted. GO and KEGG enrichement were applied to explore the potential function of KIAA1429 in DLBCL. The lymph node biopsies of DLBCL patients and reactive hyperplasia cases were collected with informed consent to detect the expression of KIAA1429. Results We firstly assessed the expression of m6A methylation regulators in DLBCL and found that most of them were dysregulated (p<0.001; Figure 1A-B). Subsequently, we conjectured that the alteration of m6A methylation regulators ratio may be an inherent feature representing individual differences, and discovered that the proportion of diverse m6A RNA methylation regulators was weakly to strongly relevant (p<0.05; Figure 1C). To evaluate the clinical prognostic value of m6A methylation regulators in DLBCL patients, 475 GCB DLBCL patients, which are intimately associated with double-hit lymphoma (DHL) were selected for further analysis. The univariate Cox regression analysis indicated that six genes were high-risk and were significantly associated with OS (p<0.05, HR>1; Figure 2A), including KIAA1429 (p=0.043, HR=1.743). Six genes were selected based on the minimum criteria of LASSO Cox regression to establish the risk signature (Figure 2B-C). The high-risk group had a significantly shorter OS in DLBCL patients (p<0.001; Figure 2D). Furthermore, ROC curve, univariate, and multivariate Cox regression analyses showed that high m6A risk score acted as an independent indicator in DLBCL patients (p<0.001; Figure 2E-G). We further evaluated the correlation between m6A methylation regulators and clinicopathological feature of DHL patients. KIAA1429 was found to be significantly associated with the IPI and DHL (p<0.05; Figure 3A-B). High expression of KIAA1429 resulted in a negative correlation with OS in DHL patients (p=0.018; Figure 3C). However, no significant difference was found in the OS of non-DHL patients (Figure 3D). Univariate analyses indicated that KIAA1429 was an independent indicator in DLBCL patients (p=0.04; Figure 3E). Enhanced expression levels of KIAA1429 mRNA and protein were verified in DLBCL cell lines (Figure 3F-G). Additionally, samples from DLBCL patients also showed significantly high expression of KIAA1429 compared to the reactive hyperplasia group, with the positive rate of 93% (50 of 54) and 25% (5 of 20), respectively (Figure 3H). To investigate the underlying mechanism of KIAA1429, WGCNA was used to divide genes into different modules (Figure 4A-B). Subsequently, We selected the blue module including KIAA1429 to analyze their functions. A significant association between KIAA1429 expression and its module genes was identified (Figure 4C). GO and KEGG enrichment illuminated that KIAA1429 may act as a potential prognostic biomarker by regulating the mRNA processing and MAPK signaling pathways (Figure 4D-F). Conclusions In summary, we identified for the first time that m6A methylation regulators were dysregulated in DLBCL, and its risk score could exert as an independent prognostic indicator in GCB-DLBCL. More importantly, our study demonstrated the prognostic value of KIAA1429 in DHL patients. Further investigations on the mechanism of KIAA1429 in DLBCL may assist clinicians in achieving individualized treatment for this patient population. Keywords: m6A, KIAA1429, prognosis, mechanism, DLBCL Disclosures No relevant conflicts of interest to declare.