To study the structure and significance of comorbidities and polymorbidity in maternal death. Sixty-five autopsy protocols of maternal deaths in the Novosibirsk Region in the period of 1994 to 2018 were analyzed. Extragenital diseases are the leading diseases in the nosological structure in maternal mortality. Preeclampsia/exlampsia and obstetric hemorrhages lost their leading positions. The increasing role of extragenital pathology in the structure of maternal mortality is due to many factors, such as a larger number of comorbidities and polymorbidity, in pregnant women. Infectious diseases, benign and malignant tumors, and diseases of the heart and blood vessels are the main diseases in the structure of extragenital diseases.

To establish the mechanisms of pathomorphism of transplantable kidney cancer in rats that used flavonoid-containing hedge hyssop (Gratiola officinalis L.) extract in an in vivo experiments. The experiment was carried out on 30 male Wistar rats with transplantable kidney cancer PA. At 72 hours after tumor inoculation, the rats in the experimental groups received hedge hyssop extract at an oral or intramuscular dose of 110 mg/kg/day for 12 days. A comparison group consisted of the animals with a tumor, but without exposure. The investigators used the immunohistochemical markers of apoptosis (p53, bax, bcl-2, Fas-receptor, Fas-ligand), autophagy (LC3B), proliferation (Ki-67), and angiogenesis (VEGF). During statistical data processing, the Shapiro-Wilk test was used to test the normality of the indicator distribution in the groups. Cramer-Welch's t-test was also employed to compare the groups. Histological examination of tumor tissue under the action of hedge hyssop extract showed the emergence of extensive areas of damage (necrosis and apoptotic bodies). With both routes of hedge hyssop extract administration, there was a sharp decrease in the expression of the proliferation markers Ki-67 and the angiogenesis marker VEGF and a high expression of the apoptosis markers p53, bax, CD95 (Fas/APO-1), and FAS-ligand in tumor cells and its absence in the comparison group. All the described changes were more pronounced with intramuscular administration. The expression of the autophagy marker LC3B increased with the oral administration of hedge hyssop extract and decreased with its intramuscular administration. A pronounced pathomorphism of kidney cancer develops due to consumption of hedge hyssop extract. This suppresses the proliferation, angiogenesis, and activation of apoptotic signaling and mitochondrial pathways and blocks protective autophagy. The autophagy marker LC3B can be used as an additional criterion for evaluating the therapeutic pathomorphism of tumors.

To determine the structural changes in the cerebral cortex tissues, which are characteristic of the severe course of chronic obstructive pulmonary disease (COPD) and ischemic cerebral stroke (ICS). The autopsy material of the microcirculatory bed of the cerebral cortex from 18 people aged 48-64 years who had died from COPD, ICS, and a concurrence of these conditions underwent histological examination and morphometric analysis. The state of the brain from the persons who died from ICS was characterized by a decline in the total number of neurons and glial elements, by structural and regional blood flow changes with obvious venous hyperemia, stasis, and red blood cell aggregation in the vessels. There was pericellular and perivascular edema in the perifocal area of the brain from people who died from COPD, as well as morphological signs of cerebral hemodynamic disorders. The brain structural features in ICS concurrent with COPD included a double decrease in the numerical density of capillaries, their hyperemia, perivascular edema, and venous plethora, a substantial change in the diameter of non-muscular venules, parenchymal atrophy, and stromal sclerosis, indicating the presence of a chronic process. Patients with ICS in the presence of COPD versus those who died from the isolated variants of these conditions were recorded to have an obvious decrease in the numerical density of capillaries, their hyperemia, and a pronounced change in the structure of the cerebral vein wall, which is a consequence of multisystem processes associated with COPD.

The paper describes a clinical case of atypical teratoid/rhabdoid tumor with preserved INI1 expression and SMARCA4 gene mutations in an 8-month-old girl. Genome-wide DNA methylation, hierarchical clustering, and next-generation sequencing were used to make a tumor diagnosis. However, BRG1 immunohistochemical examination may be recommended in the routine practice of diagnosis and study of childhood CNS malignant tumors.

Trichilemmal carcinoma is a rare skin tumor that mainly occurs in the elderly (mean age, 71 years) and is localized in the repeatedly sun-exposed areas, most commonly on the face, scalp, neck, and dorsa of the hands. Its differential diagnosis is made with squamous cell skin cancer, clear-cell porocarcinoma, hidradenocarcinoma, and melanoma. The prognosis of trichilemmal carcinoma is most favorable than that of other skin tumors during radical removal. The paper describes a case of an 80-year-old man with long-standing trichilemmal carcinoma of the skin in the area of the shoulder joint, which is concurrent with squamous cell cancer in another area of the skin.

to audit perinatal losses in large regional centers of the Russian Federation with a population of over 1 million inhabitants, such as Chelyabinsk and Novosibirsk. A comprehensive postmortem examination of 309 cases of perinatal losses in 2016 was made, which was supplemented with an assessment of preventability according to the Scandinavian-Baltic classification. The rate of preventable deaths in Chelyabinsk and Novosibirsk amounted to 91 and 81.5% of cases, respectively; the deaths were due to stillbirths at more than 28 weeks' gestation and to dead newborns in almost half of cases. The proportion of intranatal deaths was shown to increase in Chelyabinsk; the number of neonatal deaths at more than 33 weeks' gestation rose in Novosibirsk. Supplementing the traditional clinical and postmortem analysis with an assessment of the preventability of perinatal loss makes it possible to ensure a unified approach to evaluating these conditions and the comparability of autopsy results in different subjects of the Russian Federation and to determine regional reserves for reducing perinatal mortality rates.

to investigate the myocardial expression of some structural proteins and markers of cellular proliferation and innate immunity for assessing their possible diagnostic and prognostic role in patients with chronic myocarditis. The investigation enrolled 23 patients (16 men; mean age, 52.0±12.4 years (range, 27 to 73) with various forms of noncoronarogenic myocardial injury who underwent right ventricular endomyocardial biopsy (n=4), intraoperative left ventricular biopsy (n=17) or autopsy (n=2). Prior to their morphological examination, the patients were divided into two groups: 1) 10 patients with dilated cardiomyopathy and presumptive myocarditis; 2) 13 patients with valvular heart disease, hypertrophic cardiomyopathy, myxoma, and chronic pulmonary thromboembolism, presumptively without myocarditis. Along with myocardial histological and immunohistochemical (IHC) examinations, the expression of vimentin, desmin, c-kit, Ki-67, and Toll-like receptors (TLR) 2 and 9 was determined. Polymerase chain reaction was used to identify whether herpes viruses of and parvovirus B19 genomes were present in the blood and myocardial samples; indirect ELISA was applied to estimate the blood level of antibodies against various cardiac antigens. According to the histological findings, active/borderline lymphocytic myocarditis was diagnosed in all the patients (Group 1) and in 6 patients (Group 2) in conjunction with the underlying disease (only in 9 and 7 patients, respectively), viral genome was detected in the myocardium of 15 patients, including in 5 without morphological signs of myocarditis (parvovirus B19 (n=11), herpesvirus 6 (n=4), herpes simplex virus types 1 and 2 (n=1), Epstein-Barr virus (n=2), and cytomegalovirus (n=1)), and in the blood (n=4). A marked correlation was found between TLR2 and TLR9 expressions and the morphological pattern of active myocarditis in the absence of this correlation with the expression level of other studied markers. The expression level of TLR2 in patients with and without borderline myocarditis was 0 [0; 0,75] and in those with active myocarditis was 1.5 [1; 1,5] points; that of TLR9 was 2 [2; 2] and 4 [3; 4] points, respectively (p<0.001). The expression of TLR2 and TLR9 in patients with borderline myocarditis was lower than in those without myocarditis (0 [0; 0] versus 0 [0; 1] and 2 [1,5; 2] versus 2 [2; 3] points), which can reflect cardiomyocyte destruction/depletion at later stages of the disease. There was also a close correlation between the expression level of TLR2 and that of TLR9 (r=0.824; p<0.001) and with Ki-67 levels (r=-0.531 and r=-0.702; p<0.01). There was also a correlation of the expression of the studied markers with viral persistence (desmin), the degree of myocardial dysfunction and cardiosclerosis (c-kit), which calls for further investigations. Determination of the myocardial expression level of TLR2 and TLR9 may serve as an immunohistochemical marker for myocarditis and preservation of its activity, which is especially valuable in patients with borderline forms. The marked expression of these markers for innate immunity may reflect both one of the mechanisms of genetic predisposition to myocarditis and its severe course and their secondary activation in the pathogenesis of the disease and is a potential target of therapy.

The review of the literature deals with the participation of Clara cells now called club cells (CCs) of the epithelium in the respiratory and terminal bronchioles in the pathogenesis and morphogenesis of chronic inflammatory diseases, precancer, and cancer of the lung, which develop in the respiratory segments. The review summarizes data on the histophysiology of CCs and their participation in the pathogenesis and morphogenesis of chronic interstitial lung diseases, pneumoconiosis, chronic obstructive diseases, adenomatosis, and adenocarcinoma of the lung. In this area, there is a bronchioloalveolar junction area (BAJA), one of the most important stem cell niches. CCs are located in the BAJA; they are progenitor tissue stem cells and play an important role in the regeneration of the epithelium of the respiratory bronchioles and alveoli. Pathology of CCs in the BAJA leads to the maintenance of chronic inflammation, to the destruction of the lung elastic frame, and to impaired epithelial regeneration, interstitial fibrosis, and adenomatosis. In this case, decompensated inflammation, pathological regeneration, and fibrosis develop, which, along with the action of carcinogenic agents, can contribute to the accumulation of mutations and epigenetic rearrangements in the CCs, which subsequently results in atypical adenomatous hyperplasia and adenocarcinoma of the lung.

Liver diseases associated (acute fatty liver of pregnancy) and unassociated (liver hemangioma) with pregnancy and complications due to liver failure are serious conditions and can lead to maternal death. The paper describes two maternal deaths related to liver pathology.

To study endometrial receptivity in infertile women with external genital endometriosis (EGE). Clinical, morphological, immunohistochemical, and molecular genetic examinations of endometrial aspiration pipelle biopsy specimens obtained on days 22-24 of the menstrual cycle from 94 infertile women with endometriosis: 50 women with Stage I-II EGE and 44 women with ovarian endometrioid cysts (OEC). A control group consisted of 54 women with tubal peritoneal factor of infertility (TPFI) and a successful attempt at IVF. Hematoxylin and eosin-stained sections were found to contain a number of endometrial surface epithelial cells containing mature pinopods. The expression levels of leukemia inhibitory factor (LIF), HOXA-10, glycodelin A, avβ3 integrin, estrogen receptors (ER) and progesterone receptors (PR), aromatase in the superficial epithelium, glandular epithelium and endometrial stroma were immunohistochemically revealed. Forty-four patients, including 17 with Stage I-II EGE and 27 with TPFI, showed mRNA expression levels of leukemia inhibitory factor receptor (LIFR), LIF, ER1, PgR, HOXA-10, and PTEN by real-time quantitative polymerase chain reaction (PCR) with a preliminary reverse transcription PCR assay. It was established that in the infertile women with Stage I-II EGE and those with OEC, endometrial receptivity was impaired, which was manifested by a decline in the number of superficial epithelial cells containing mature pinopods, as well as a decrease in the endometrial level of the key receptivity markers: αvβ3 integrin, LIF, glycodelin A, and HOXA10 and increases in the synthesis of aromatase and in the imbalance of endometrial stromal expression of ER and PR detected by immunohistochemistry (IHC). Molecular genetic study showed lower mRNA expression levels of the HOXA-10, LIFR, and PgR genes, which confirms the data obtained by IHC.