Aim of the investigation. To study the risk factors of advanced fibrosis in non-alcoholic fatty liver disease (NAFLD) associated with type 2 diabetes mellitus in relation to the vitamin D content in the blood. Materials and methods. 171 patients with NAFLD and type 2 diabetes mellitus (140 women, 31 men), aged from 31 to 69 years, were examined. Serum vitamin D levels were determined by enzyme-linked immunosorbent assay. The severity of liver fibrosis was assessed using transient elastometry. Results. In patients with NAFLD associated with type 2 diabetes mellitus liver fibrosis F3-4 was detected in 14.1% of cases and was associated with parameters of waist circumference ≥ 118 cm, platelets ≤ 225x10⁹/l, total cholesterol ≥ 7.92 mmol/l, triglycerides ≥ 2.5 mmol/L, gammaglutamyltranspeptidase (GGT) ≥ 37 un/l, alkaline phosphatase ≥ 64 u/l, direct bilirubin ≤ 1.3 mmol/l, vitamin D ≤ 13.0 ng/ml, as well as the presence of hypertriglyceridemia. According to multivariate regression analysis, independent predictors of liver fibrosis F3-4 were blood levels of GGT, triglycerides, platelets, and vitamin D. The combination of these parameters in predicting of advanced fibrosis/cirrhosis had a sensitivity of 70.8% and a specificity of 95.6%. Conclusion. Thus, blood levels of triglycerides, platelets, and vitamin D, as well as GGT activity, were associated with fibrosis F3-4 in patients with NAFLD and type 2 diabetes mellitus, that, probably, is connected with their involvement in liver damage, inflammation, and fibrogenesis.

Aim of the investigation. To study the relationship of blood levels of vitamin D-binding protein (VDBP) with clinical and laboratory manifestations of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus. Materials and methods. The study included 80 patients with type 2 diabetes mellitus aged 33 to 69 years (67 women, 13 men). NAFLD was detected in 75.0% patients with type 2 diabetes mellitus. Severe liver steatosis was observed in 40.0% cases of NAFLD, fibrosis F3-4 in 23.3%. Serum levels of VDBP were determined by enzyme-linked immunosorbent assay. Results. The presence of NAFLD in patients with type 2 diabetes mellitus was characterized by lower blood levels of VDBP. Biochemical syndromes of liver pathology, as well as manifestations of diabetes mellitus (except for its duration) did not affect serum levels of VDBP in NAFLD. In patients with NAFLD and obesity, abdominal obesity or dyslipidemia, a lower concentration of VDBP in blood was determined. VDBP values did not depend on the presence of arterial hypertension and metabolic syndrome in NAFLD. Patients with severe liver steatosis or fibrosis F3-4 had lower blood levels of VDBP. Conclusion. Thus, in NAFLD associated with type 2 diabetes mellitus, there is a decrease of blood levels of VDBP, which is associated with the duration of diabetes, the presence of obesity, abdominal obesity and dyslipidemia. Cases of NAFLD with severe steatosis or severe fibrosis/liver cirrhosis are characterized by a lower serum concentration of VDBP.

Background. Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. According to various studies, one of the factors contributing to the development and progression of NAFLD is vitamin D deficiency and insufficiency. Objective. To investigate the interrelationships between clinical and laboratory-instrumental markers of fibrosis activity as well as disturbances in lipid and carbohydrate metabolism in patients with NAFLD before and after completing a course of vitamin D supplementation. Materials and Methods. The study included 121 patients with NAFLD who received vitamin D supplements due to diagnosed deficiency or insufficiency. Anthropometric, laboratory, and instrumental indicators were measured before and after the course of vitamin D therapy. Results. After the treatment, most patients demonstrated a statistically significant increase in vitamin D levels (p < 0.001) and improvement in lipid and carbohydrate metabolism. Mean body mass index, waist circumference, triglyceride levels, and insulin levels decreased significantly (p < 0.05). Additionally, correcting vitamin D deficiency and insufficiency contributed to improvements in liver markers, such as ALT, AST, and composite indices. Conclusion. The obtained data confirm a high prevalence of lipid and carbohydrate metabolic disorders among patients with NAFLD. Vitamin D supplementation significantly improves a range of clinical and laboratory parameters (BMI, WC, AST, albumin, glucose, FLI) in NAFLD patients, emphasizing the need for timely correction of vitamin D insufficiency and deficiency as part of comprehensive NAFLD treatment.

Coronary artery disease (CAD) and metabolic-associated fatty liver disease (MAFLD) through similar pathogenetic mechanisms lead to a high risk of cardiovascular complications and mortality. Objective: To study the level of gamma-glutamyl transferase (GGT) and N-terminal pro b-type natriuretic peptide (NT-proBNP) in patients with CAD and MAFLD. Materials and methods: the study included 96 patients with CAD aged 37-78 years. They were divided into 2 groups: 1 - with CAD and MAFLD (n=48); 2 - with CAD without MAFLD (n=48). General clinical parameters; GGT and NT-proBNP levels; FLI, FIB-4 indices; echocardiography were analyzed. Results: Patients with CAD and MAFLD were more likely to be obese, have type 2 diabetes, FLI ≥60 (p=0,002), FIB-4 ≥3,25 (p=0,01) compared to patients without MAFLD. GGT level was higher in patients of group 1 (p=0,045). In the CAD and MAFLD group, stage 2 CHF (p<0,001) and NYHA classes III-IV (p=0,002) were more common. In group 1, NT-proBNP was higher (p=0,003), and ejection fraction was lower (p<0,001). Patients with MAFLD were more likely to have CHFrEF and CHFrEF (p=0,001) compared to patients without MAFLD. Direct correlations between the level of NT-proBNP and GGT; NT-proBNP and FLI and FIB-4 in patients of group 1 were found. In patients with CAD and MAFLD, a significant increase in the level of GGT and NT-proBNP was detected, which is associated with hepatic steatosis, varying degrees of liver fibrosis and more severe course of CHF, the CHFrEF subtype. Thus, patients with CAD and MAFLD have complex interactions between the heart and liver.

Asthenic syndrome is often present in the clinical picture of non-alcoholic fatty liver disease (NAFLD). The aim of the study was to clarify the clinical manifestations of asthenic syndrome in NAFLD, their severity depending on the stage of the pathological process in the liver. Materials and methods: 64 patients with NAFLD and 15 individuals who do not suffer from this pathology were examined. Clinical examination, ultrasound examination of the abdominal cavity, esophagogastroduodenoscopy, and blood tests were performed. All patients were divided into 3 groups: 49 patients with hepatic steatosis, 15 with steatohepatitis, and 15 with a control group. Results. It was found that at the stage of liver steatosis almost half of the patients had emotional lability, increased anxiety, and irritability. Sleep changes were less frequently detected: daytime and early evening drowsiness (31%), poor sleep (37%). Cognitive impairments were characterized by decreased attention (31%) and memory (29%). In the group of patients with steatohepatitis, 60% of the examined patients had mood instability, increased irritability and anxiety, and 33% had depression. Sleep disorders were often detected, and symptoms such as intermittent sleep, fatigue after sleep, "heavy" awakening, and fatigue in the morning were present. Cognitive impairments in the form of decreased memory and attention were detected in more than half of the patients in this group, and a third of the patients reported an inability to quickly switch attention. Symptoms of asthenic syndrome in patients of the control group occurred in a small percentage of cases or were absent. Conclusion. Asthenic syndrome always been present in patients with NAFLD with greater symptoms of steatohepatitis. Given the somatic nature of asthenic syndrome, treatment should primarily be aimed at correcting the underlying pathology, namely NAFLD with an emphasis on a healthy lifestyle.

Purpose of the study. To evaluate the interaction of polymorphic variants rs1042713 (Arg16Gly) and rs1042714 (Gln27Glu) of the β2-adrenoreceptor (β2-AR) gene with the development of liver cirrhosis (LC). Materials and methods. A total of 137 patients with liver cirrhosis and 143 healthy volunteers, who were Caucasian and unrelated to each other, participated in the observational case-control study. Genotyping of polymorphic variants Arg16Gly and Gln27Glu of the β2-AR gene was performed using the polymerase chain reaction (PCR) method by analyzing restriction fragment length polymorphism of amplicons (PDRF analysis). Results. Genotypes AG, GG and AA of the Arg16Gly polymorphism and genotypes CG, CC and GG of the Gln27Glu polymorphism of the β2-AR gene are not predictors of LC development (OR = 0.86; 95% CI: 0.53-1.37; p=0.52; OR=0.88; 95% CI:0.55-1.41; p=0.59; OR=1.81; 95% CI:0.91-3.62; p=0.09; OR=0.74; 95% CI:0.46-1.19; p=0.22; OR=1.55; 95% CI:0.93-2.58; p=0.09; OR=0.91; 95% CI: 0.52-1.57, p=0.72, respectively, p>0.05). Carrying the Arg16Arg/Gln27Gln haplotype increased the chance of developing LC by 2,4-fold (OR=2.42; 95%DI:1.13-5.18; p=0.02). Arg16ArgGln27Gln haplotype is associated with LC severity according to Child-Pugh classification (χ2=3.27; p=0.007) and severity of liver fibrosis according to APRI index (χ2=4.46; p=0.03). Conclusion. Haplotype Arg16ArgGln27Gln of β2-AR gene is a predictor of LC development, increasing the risk of disease development 2,4 times.

The aim - estimation of hepatocellular apoptosis (HA) in the alcoholic liver disease (ALC) progression from compensation to stable decompensation and acute-on-chronic liver failure (AСLF) and the diagnostic significance of cytokeratin-18 fragments (FCK-18) - marker of HA in different clinical variants of this disease. Materials and methods. 139 patients with ALC were examined: 17 - compensated ALC (men - 10-58,8%; 50.17±9.87 years), 65 - stable decompensated ALC (men - 33-50.8%; 52.13±12.52 years) and 57 with ACLF (men - 30-52,6%; 51.85±13.41 years). FCK-18 (TPS ELISA, Biotech, Sweden), TNF-α (Vector-Best, Russia) were determined, the CLIF-C-AD score and CLIF-C-ACLF score were calculated ((http://www.efclif.com/scientific-activity/score-calculators/clif-c-aclf). Results. The FCK-18 increased from the compensated stage 121.35±23.41 U/l to acute stable decompensation 913.78±312.39 U/l (p<0.001) and to ACLF - 1702.48±502.09 U/l (p<0.001). As the degree of HA, there was an increase in CRP - from 1.23 ± 0.05 mg / l to 20.37 ± 18.35 mg / l and 42.84 ± 19.74 mg / l (p < 0.01) and TNF-α - from 4.89 ± 1.35 pg / ml to 9.87 ± 3.12 pg / ml and 12.49 ± 3.08 pg / ml (p < 0.05), respectively, and organ failure developed - liver, kidney, cerebral, coagulation and circulatory. Short-term death occurred in 19 (33,3%) patients with ACLF. Conclusions. The role of HA in the mechanisms of ALC progression from compensated to stable decompensation and to ACLF and the diagnostic significance of the HA biomarker - FCK-18 in different clinical variants of ALC were shown.

The article provides information on the role of the FTO (A+23525T) fat mass-associated gene polymorphism, the leptin receptor gene LEPR (Arg223Gln) in BEN syndrome in patients with DST. The results of the study of the trophological status of patients with DST and the severity of BEN syndrome are shown. It has been proven that genetic mutations exacerbate genetically determined disorders of the trophological status. In practice, the doctor must take into account the mechanisms of the formation of BEN syndrome in patients with DST and the risks associated with the presence of this syndrome.

Connective tissue dysplasia, being a genetically determined disease, has a number of syndromic manifestations that over time form a chronic pathology, often with chronic abdominal and pelvic pain syndrome. 852 women were examined: 268 primiparous women, 346 reproductive-age patients with pelvic organ prolapse, and 238 patients with postmenopausal POP. The DST syndrome was confirmed phenotypically using international criteria. CTD can be a predictor of the development of abdominal and pelvic pain in women in 25-57%, which can be based on scoliosis (45.5%), osteochondrosis - 54.6%, hernias - 19.4%, chronic gastritis, gastroduodenitis - 52.1%, biliary dyskinesia - 29.4%, chronic colitis and irritable bowel syndrome - 10.8%, concomitant gynecological pathology - 25% of cases, anorectal dysfunction - 50%, varicose veins of the pelvis - 50%. The underlying underlying initial functional and subsequently organic changes in the abdominal and pelvic organs is dysfunction of the smooth muscle component due to decreased expression of the α1C Ca2+ channel subunit protein with subsequent triggering of compensatory mechanisms (increased expression of the ACTA 2 gene), changes in the rigidity of the cell cytoskeleton and remodeling of intercellular matrix elements (changes in the expression of the CPA3 and C1QA and DCN genes). A differentiated and personalized approach to patients with abdominal and pelvic pain syndrome in women with CTD is the leading approach in diagnostic tactics and treatment selection.

Objective: To determine the changes in organs and systems associated with connective tissue dysplasia (CTD) that affect gastric acid production in patients with CTD presenting symptoms of dyspepsia. Materials and Methods: A randomized controlled cross-sectional comparative study was conducted involving a total of 151 participants using a cross-sectional design. Inclusion criteria included presence of dyspeptic symptoms, absence of severe organic pathology capable of manifesting as dyspeptic symptoms (fever, hematemesis, anemia, leukocytosis, elevated ESR, melena), peptic ulcers or erosions in the stomach and duodenum mucosa, age between 18 to 29 years old, no history of Helicobacter pylori eradication therapy, discontinuation of medications affecting gastric acidity according to their half-life period, informed consent for participation in the study. All enrolled subjects underwent general clinical examination (collection of complaints, medical history, physical examination), screening for CTD, assessment of vegetative vascular reactivity (“Nerosoft,” Russia). Since there are no clear reference values for gastric acid-producing function, two additional groups without dyspepsia were formed using the same inclusion criteria except for the presence of dyspeptic symptoms. The research cohort consisted of four groups: Group 1-42 patients with dyspepsia and CTD; Group 2-36 patients with dyspepsia but no CTD; Group 3-37 patients with CTD but no dyspeptic complaints; Group 4-37 healthy volunteers free from both CTD and dyspeptic symptoms. All four groups received comprehensive clinical evaluation including symptom questionnaires using the Gastrointestinal Symptom Rating Scale (GSRS), 24-hour pH-metry (“Gastronscan-24,” Fryazino, Moscow Region, Russia), measurement of serum levels of pepsinogens I and II, gastrin-17, anti-H. pylori IgG antibodies (“Vector-Best,” Novosibirsk, Russia), endoscopic laser Doppler flowmetry (“LAKK-2,” Russia). Results: Among patients with CTD experiencing dyspeptic symptoms, postprandial distress syndrome occurred in 77% of cases. Clinico-functional markers specific to biliary type dysfunction include reflux-gastritis (17.8%) and gallbladder deformation (30%). Markers indicative of hypoacid condition include impaired microcirculation in the gastric wall (26.2%), gastropathy (gastric ptosis, 42%), thoracic cage deformities (23%), hypergastrinemia (25.6%). Conclusion: Decreased gastric acid secretion in patients with CTD is caused by two primary mechanisms. The most common factor involves disturbed gastric motility leading to duodenogastric reflux, resulting in bile entering the stomach and disrupting its secretory activity. In some patients, this process progresses to atrophic changes in the gastric mucosa accompanied by true deficiency in hydrochloric acid production. Both mechanisms significantly reduce the stomach's ability to produce acid, thereby influencing digestive processes and gastrointestinal protective properties.

Objective: to identify the features of clinical symptoms in adolescents with erosive and ulcerative lesions associated with connective tissue dysplasia (CTD), with the proposal of the term "gastrointestinal form of CTD". Materials and methods. The main group consisted of 252 adolescents with external and internal CTD phenomena: 176 children aged 15-17 with erosive gastritis and duodenitis, peptic ulcer disease, examined in the Morozov Children's Clinical Hospital (Moscow); 52 young men aged 16-17 - in the Oblast military registration and enlistment office (Omsk). The comparison group consisted of 47 senior school-age children without signs of CTD (Belgorod). In 54 adolescents, hydroxyproline fractions were analyzed in the serum. The borderline level of statistical significance was p<0.05. Results. In erosive gastritis, there are aching early pains of moderate severity localized in the epigastric region; in erosive duodenitis - severe pains with "Moynigan's rhythm" in the absence of exact localization. For peptic ulcer disease at the age of 15, an atypical painless onset is characteristic, fasting pains of a nagging nature; at the age of 16-17, a classic course with "ulcer-like" pain and dyspeptic syndromes. The lability of nervous processes in the patients is characterized by high personal and situational anxiety, deviations from the autonomic nervous system (vagotonia in erosions, sympathicotonia - ulcers), which is important to take into account, especially in young men of pre-conscription age. With CTD with typical symptoms, the production of defective collagen is observed, determined by the analysis of hydroxyproline fractions: a reliable decrease in the ratio of peptide-bound to free hydroxyproline from 1.1 in erosions to 0.5 in peptic ulcer disease. Conclusions. The gastrointestinal form of CTD is indicated by a combination of erosive gastroduodenitis, peptic ulcer with an asthenic type of constitution, flat feet, myopia, hypermobility of joints, minor anomalies on the part of the heart and lability of the nervous system, which determines the prognosis of a more severe course of the disease. With erosions, there is activation of fibrillogenesis, with peptic ulcer disease - catabolism of connective tissue.

The term “connective tissue dysplasia” has become so ingrained in medical practice in the post-Soviet space that many specialists are reluctant to verify the monogenic syndromes often hidden behind the familiar appearance of a patient with connective tissue dysplasia (CTD). Patients diagnosed with Marfan syndrome and Ehlers-Danlos syndrome have virtually disappeared from clinical practice, while a large number of patients with undifferentiated CTD have emerged. The lack of commitment to clinical and genetic verification of hereditary connective tissue diseases, including analysis and interpretation of the facts, hinders the productive development of this area of scientific knowledge and sometimes leads to disabling and even fatal consequences in such patients. Objective: To evaluate the causes of disability in families with a phenotypic extension of connective tissue dysplasia manifestations and its association with gene mutations. Materials and Methods. A retrospective analysis of the records of 123 patients with syndromic and undifferentiated forms of CTD observed at the department (n = 123) was conducted to assess the causes of disability. A retrospective analysis of outpatient charts and medical records was conducted, along with a family history review of three families and examination of all available first-degree relatives. To establish syndromic forms of CTD, consensus criteria were applied, and genetic testing of the probands was conducted in the Genomed Molecular Pathology Laboratory. Results. Of the 123 patients, disability was noted in 44 cases during an observation period of 3 to 21 years; the average age was 41 ± 12.5 years. The causes of disability were divided into the following groups: osteoarticular and vertebrogenic (n = 9), cardiac and vascular (n = 7), bronchopulmonary (n = 6), neurological (n = 4), ophthalmological (n = 3), audiological (n = 2), nephrological (n = 1), and other (n = 12). Three families with CTD, initially observed with undifferentiated CTD or Ehlers-Danlos syndrome, are presented. The first family presented with hypermobility syndrome and decreased bone mineral density, accompanied by blue sclerae and multiple fractures. Osteogenesis imperfecta was diagnosed in the proband's daughter, and disability due to hearing loss was prevented. The second family presented with bilateral congenital hip dislocation in several generations, hypermobility syndrome, and disabling osteoarthritis. The proband (66 years old), disabled since childhood due to bilateral congenital hip dislocation, bilateral hip replacement, and axonal neuropathy, was found to have new mutations in the type I collagen A1 gene with unknown clinical pathogenicity significance, possibly associated with Ehlers-Danlos syndrome (type I or arthrocholasia type) or osteogenesis imperfecta. A third family with hypermobility syndrome and hyperelastic skin (Ehlers-Danlos syndrome, not confirmed genetically) is described. The proband (45 years old) has disabling kidney disease requiring renal replacement therapy and a kidney transplant, along with hearing loss. Whole-genome sequencing of the proband revealed no mutations in the pathogenic zone. In the proband's daughter, lifestyle modification and nephrological protection slowed the renal impairment (which could have led to disability, as in the proband). The practical significance of these clinical observations is the confirmation of a pronounced phenotypic prevalence of connective tissue dysplasia in families with disabilities arising from various causes associated with connective tissue defects. Conclusion. The presented clinical observations demonstrate the need for early diagnosis upon detection of signs of connective tissue dysplasia, including not only agreed-upon classification criteria for monogenic syndromes but also molecular genetic testing, which ensures the adequacy of treatment at earlier stages. Rehabilitation measures in the third clinical observation demonstrated that lifestyle can influence gene expression, reducing the severity of symptoms and the risk of disability. In our opinion, masking such patients with the term “undifferentiated connective tissue dysplasia,” especially in scientific papers, is unacceptable, especially in cases of disabling and, especially, early fatal events in families with CTD.

The review highlights current understanding of the role of air pollution with particulate matter (PM) in the pathogenesis of chronic non-infectious liver diseases (CLD). For this purpose, the materials of articles indexed in the PubMed and Russian Science Citation Index (RSCI) databases were used. PM with an aerodynamic diameter of ≤2.5 μm are recognized as the most dangerous. It was found that long-term exposure to fine particulate matter (PM2.5), especially those containing metals, significantly increases the risk and mortality from liver cancer, cirrhosis, and non-alcoholic fatty liver disease. Exposure to PM2.5 can contribute to the development of CLD by causing oxidative stress, systemic inflammation, and dysregulation of lipid metabolism. Damage to the intestinal epithelium and disruption of microbiotic homeostasis causes stress to the endoplasmic reticulum of cells, inducing abnormal expression of specific microRNAs or inflammatory factors. The review discusses modern terminology and hypotheses of the pathogenesis of the most common chronic non-infectious liver diseases. Unfortunately, no hypothesis clearly characterizes the role of PM in the pathogenesis of the discussed liver diseases, in particular, at the molecular genetic level. Creating a formalized description of the processes mediating the effect of PM on the human body helps to better understand their role in the pathogenesis of various diseases, in particular CLD, which can contribute to the improvement of early diagnostic methods, treatment, and preventive measures.

Metabolically associated fatty liver disease (MAFLD), formerly known as non-alcoholic fatty liver disease (NAFLD), has become the most prevalent cause of liver disease worldwide. MAFLD is an independent risk factor for cardiovascular diseases and associated mortality. Despite its prevalence, MAFLD is often underestimated and does not receive adequate attention during clinical visits. MAFLD is a hepatic manifestation of metabolic syndrome and affects approximately 55% of individuals living with diabetes. The new definition emphasizes bidirectional connections and raises awareness about identifying fatty liver disease in patients with diabetes and cardiovascular diseases or cardiovascular risk factors, as well as searching for these conditions in patients with MAFLD. Liver dysfunction significantly contributes to the development of diabetes. Although these mechanisms are not fully understood, fat accumulation in the liver leads to changes in energy metabolism and inflammatory signals, which promote insulin resistance. Furthermore, chronic hyperinsulinemia observed in diabetic patients also contributes to fat accumulation in the liver. Diabetes patients may benefit from medications that potentially have a positive impact on MAFLD and liver diseases. This article discusses the potential use of hypoglycemic drugs in MAFLD and their effects on liver fat content, liver enzymes used as markers of steatosis, and tissue inflammation indices, although existing data on structural liver changes are limited, requiring further research in this area.

Heritable and undifferentiated connective tissue disorders (HCTD/UCTD), including Marfan syndrome and related phenotypes, are increasingly recognized as independent risk factors for malignancy. Population-based studies demonstrate a significantly higher incidence of neoplastic diseases among these patients, with a particularly elevated relative risk for gastric adenocarcinoma (~4.6). Clinical observations, including the author’s own data, confirm a tendency toward the early development of tumors of various localizations, indicating a pathogenetic link between connective tissue dysplasia and oncogenesis. A key molecular driver is the constitutive paradoxical activation of the TGF-β signaling pathway: mutations in extracellular matrix genes (e. g., FBN1) and receptor components (TGFBR1/2) do not suppress but rather enhance systemic TGF-β expression and activity - a phenomenon known as the “TGF-β paradox” in HCTD. In oncology, however, TGF-β exhibits a well-known dual role: acting as a tumor suppressor in early carcinogenesis while promoting invasion and metastasis at advanced stages - a context-dependent switch confirmed in both in vitro and in vivo models. The unique pathogenetic background of chronic TGF-β hyperactivation in HCTD (the first paradox), combined with the context-dependent oncologic second paradox, creates a profibrogenic and pro-transforming microenvironment that predisposes connective tissue to neoplastic remodeling. Together, these mechanisms underscore the systemic role of the TGF-β axis in tissue homeostasis and cancer initiation. Part I discusses the clinical and epidemiological evidence for increased cancer risk in HCTD/UCTD and the pathogenetic relationship between the TGF-β paradox and gastric carcinogenesis, focusing on early molecular events within the Correa cascade that establish the groundwork for neoplastic transformation of the gastric mucosa.

A comprehensive review of contemporary Russian and international literature (PubMed, eLibrary, Scopus) is presented, integrating the author’s own observations collected over the past 20 years. The molecular mechanisms underlying the formation of the protumor stroma of the stomach are examined, including cases of hereditary connective tissue disorders (HCTD) such as Marfan syndrome and Marfan-like phenotypes (undifferentiated connective tissue dysplasia). The molecular mechanisms of the TGF-β signaling pathway are discussed, demonstrating a functional shift from tumor-suppressive to pro-oncogenic effects: transdifferentiation of fibroblasts and endothelial cells into tumor-associated fibroblasts (α-SMA⁺ myofibroblasts), activation of epithelial- and endothelial-to-mesenchymal transition, stimulation of angio- and lymphangiogenesis, and the formation of an immunosuppressive tumor microenvironment. A detailed analysis of gastric stromal remodeling toward an HCTD-associated protumor phenotype is provided, including original data (immunohistochemical assessment of TGF-β1, α-SMA, and type III collagen expression) confirming the key role of TGF-β-mediated fibrogenesis in establishing a unique model of the early stage of molecular HCTD-related gastric carcinogenesis. Part II presents evidence that constitutive hyperactivation of the TGF-β signaling pathway in HCTD is accompanied by altered functional activity of major stromal cell populations, leading to impaired epithelial restitution, pathological extracellular matrix remodeling, and early development of fibrotic changes in the gastric mucosa. Overexpression of TGF-β1, predominantly in the subepithelial stroma, correlated with an increase in α-SMA⁺ cells (r≈0.74; p<0.05) and accumulation of type III collagen (r≈0.3; p<0.02). Increased stiffness of the connective tissue matrix enhances mechanotransduction and TGF-β activation, forming a self-perpetuating cycle of stromal activation. The described changes define a morphogenetic variant of chronic gastritis with early signs of neoplastic transformation - multifocal atrophy and intestinal metaplasia - characterized in young HCTD patients by a fibrotic periglandular-subepithelial pattern that promotes accelerated progression along the Correa cascade under H. pylori-negative conditions. Translational research priorities are outlined, emphasizing the need for validation of TGF-β and related biomarkers as risk predictors, which opens perspectives for early screening, prevention, and the development of targeted therapeutic strategies.

Accumulating experimental and clinicopathological evidence supports the concept of an H. pylori-independent variant of the Correa cascade - an alternative pathway of gastric carcinogenesis observed in patients with heritable and undifferentiated connective tissue dysplasias (HCTD/UDCTD). Part III of the review summarizes both literature data and the author’s own findings supporting this concept. According to the proposed model, the initiating event of the pathological process is the chronic hyperactivation of the transforming growth factor-β (TGF-β) signaling pathway against the background of congenital structural deficiency of the extracellular matrix (ECM) - a phenomenon referred to as the “TGF-β paradox.” This condition gives rise to an H. pylori-independent variant of precancerous transformation of the gastric mucosa, characterized by a stepwise morphogenetic evolution from atrophy to intestinal metaplasia and dysplasia. Stromal mechanisms in HCTD/UDCTD create a protumorigenic microenvironment and accelerate neoplastic progression. The proposed concept expands the current etiopathogenetic paradigm of gastric cancer, identifying a distinct cohort of patients with HCTD/UDCTD who require early surveillance and personalized management. Clinical implications include targeted endoscopic risk stratification (OLGA/OLGIM), site-specific biopsy, and morphological verification of atrophic and metaplastic foci in patients with HCTD/UDCTD, irrespective of H. pylori status. Therapeutic implications encompass targeting of the TGF-β axis (TGF-βRI inhibitors, ligand traps, and combinations with immune checkpoint inhibitors), antifibrotic strategies (including sartans), as well as approaches directed toward cancer-associated fibroblasts (CAFs) and the extracellular and extracellular matrix remodeling. Priorities for translational research and evaluation of combined treatment regimens are outlined.

The review article provides information on the mechanisms of functioning of the "gut-brain microbiota" axis, which supports bidirectional communication. The factors influencing this axis are noted, in particular diet, physical activity, and the administration of pre- and probiotic supplements. The results of studies on the effect of changes in the microbiota on the course of neurodegenerative diseases are presented, confirming that the onset and progression of neurodegenerative diseases are partially regulated by the intestinal microbiota. The results of both animal and human studies in Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis are presented, showing an altered composition of the intestinal microbiota and its metabolites. Measures to improve the state of the microbiota using transplantation of fecal microbiota and psychobiotics, presented as potential therapeutic agents for Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, depression and autism spectrum disorders, are considered.

Metabolic dysfunction-associated fatty liver disease (MASLD) is a progressive condition closely linked to metabolic disturbances such as insulin resistance, obesity, dyslipidemia, and arterial hypertension. In recent years, there has been a significant increase in the prevalence of MASLD, highlighting the need for the development of effective therapeutic strategies. This article provides a review of current pharmacological approaches for the treatment of MASLD. Various classes of drugs are discussed, including GLP-1 receptor agonists, SGLT2 inhibitors, and drugs targeting the activation of farnesoid X receptor and peroxisome proliferator-activated receptors. Clinical research data are summarized, demonstrating the effectiveness of these drug classes in reducing steatosis, improving hepatic histological markers, and correcting metabolic abnormalities. GLP-1 receptor agonists have shown improvement in metabolic profiles and histological markers, including a reduction in inflammation and positive changes in fibrosis stage. SGLT2 inhibitors have been shown to not only lower blood glucose levels but also improve liver function, as evidenced by improved imaging and biochemical markers. It has been shown that the effectiveness of hepatoprotective agents is limited in more advanced stages of MASLD. The prospects of using new drugs activating peroxisome proliferator-activated receptors are evaluated, demonstrating their potential in improving metabolic health and hepatic histological characteristics.

This work provides a comprehensive study and systematic review of liver steatometry and elastometry techniques used following traditional ultrasonography (US). The mechanisms and principles of each method are presented along with their comparative characteristics, areas of application, regulatory aspects, and potential directions for development. Special attention is given to improving diagnostic accuracy and reducing risks of false-positive and false-negative results.

Objective - The aim of the study was to experimentally assess the preventive effect of a complex of oxidized pectin and oxymethyluracil on chronic aluminum-induced hepatotoxicity in rats based on molecular and biochemical parameters. Materials and Methods. The experiment was conducted on 56 outbred female rats that received oral administration of aluminum hydroxide at a dose of 15 mg/kg and a chelate complex of oxidized pectin with oxymethyluracil (50 mg/kg) under various preventive and post-exposure regimens for 3-4 months. The expression of metallothionein genes (Mt1, Mt2, Mt3) and zinc transporter genes (Zip1, Zip8) in liver tissue was determined by real-time PCR using specific primers, SYBR Green intercalating dye, and the reference gene Gapdh. Serum activity of AST, ALT, ALP, and LDH was measured; statistical analysis was performed using IBM SPSS Statistics 21 software with one-way ANOVA at a critical significance level of p=0,05. Results. In our study, chronic aluminum exposure was associated with an increase in Zip1 gene expression in the liver, whereas continuous administration of the oxidized pectin-oxymethyluracil complex normalized its expression to control levels. The expression of Zip8 and metallothionein genes (Mt1a, Mt2a, Mt3a) did not change significantly among the experimental groups. At the biochemical level, this complex, when used preventively, contributed to a reduction in AST and LDH activity. Conclusion. The oxidized pectin-oxymethyluracil complex in a rat model of chronic aluminum hydroxide exposure normalizes Zip1 gene expression and reduces AST and LDH activity. Further studies using an expanded set of morphological and molecular markers are required to clarify the organoprotective mechanisms of the complex.

Glycogenic hepatopathy is a rare and often underdiagnosed condition predominantly associated with type 1 diabetes mellitus. This article presents a clinical case of a female patient with liver fibrosis in the context of uncontrolled type 1 diabetes. Examination revealed hyperglycemia, elevated HbA1c (7.28%), and persistently increased transaminase levels (ALT up to 248.9 U/L, AST up to 155.0 U/L). Fibroelastometry and liver biopsy confirmed fibrosis (F0-F4 according to the METAVIR score) and minimally active steatohepatitis. The role of glucose and glycogen metabolism disorders in the development of glycogenic hepatopathy and fibrosis is discussed. Following the optimization of insulin therapy, a decrease in both fibrosis and transaminase levels was observed. Maintaining target HbA1c levels, adhering to dietary recommendations, and regular monitoring of liver function are recommended to prevent disease progression.

The article presents a clinical case of a complicated course of erosive and ulcerative lesions of the colon with the development of phlegmon of the cecum in a patient with HIV infection in the AIDS stage. According to the results of a comprehensive examination, including histological examination, inflammatory bowel diseases and colitis caused by CMVI were excluded. The association with NSAID use was assessed as probable on the Naranjo scale. The outcome of the disease was a dynamic intestinal obstruction caused by phlegmonous colitis, which led to the death of the patient. The purpose of the publication was to draw the attention of specialists to the peculiarities of the course of colitis in HIV-infected patients, the difficulties of differential diagnosis, and risk factors for the development of colon phlegmon.

The purpose of the study: To study the capabilities of the original method of collecting and analyzing complaints “Universal complaint questionnaire” in a pilot study Materials and methods: A continuous one-stage study was conducted, in which 186 young people (men 36.56% and women 63.44%) took part, each of whom completed a survey using a universal questionnaire of complaints of a gastroenterological profile, describing 20 complaints, using CAWI technology. Results: The most common gastrointestinal complaints in adolescence are fatigue and decreased performance (45.16%), general weakness (34.95%), aversion to certain foods (24.19%), decreased appetite (21.51%), belching, aerophagia, regurgitation and heartburn (17.74%), epigastric pain syndrome (16.67%) and abdominal pain (12.5%). A statistically significant difference by gender was obtained for complaints of general weakness, fatigue and decreased performance, epigastric pain syndrome, postprandial distress syndrome and constipation. The earliest complaint is aversion to certain foods (11.95±5.24 years), at 12-14 years, complaints from the upper gastrointestinal tract arise, and at about 16 years, general complaints join in, including abdominal pain. Most complaints at a young age are ongoing. Conclusion: The universal complaint questionnaire can be used by any clinical discipline both in practical activities and in scientific and educational ones, but requires modification for specific tasks.

Francis Kiernan (1800-1874) was an eminent Irish anatomist and physician. He is best known for his detailed work on the anatomy of the liver, for which he received the Copley Medal from the Royal Society in 1836. Kiernan also successfully founded a private course in anatomy in London, establishing himself as an excellent lecturer and teacher, but this later led to resistance from the authorities of the Royal College of Surgeons. In 1836, F. Kiernan was one of the founders of the Senate of the University of London and for several years served as an examiner in anatomy and physiology. He was also a Fellow of the Royal College of Surgeons. His work “The Anatomy and Physiology of the Liver” was published in 1833 and included detailed anatomical descriptions of the structures of the liver with detailed illustrations. Kiernan's studies of the liver brought clarity to problematic aspects of liver morphology and served as a springboard for further study of this organ by subsequent generations of scientists.

This article describes the role of Moritz Hoffmann, anatomist and professor of medicine and surgery, in the history of the discovery of the pancreatic duct, later named after Johann Georg Wirsung. Translations of original texts in Latin are provided, their authors were contemporaries, eyewitnesses, and scientists who were directly acquainted with the participants of those events.