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Neolithic-Eneolithic sites in the steppe zone are not so many. Therefore, new settlement excavations are very important. One of them is the Oroshayemoye settlement. The planigraphic observation of the area of this settlement showed that it consists of two sites – Algai and Oroshayemoye I. The scientific novelty of the research is determined by the presence of clear stratigraphic successions on both sites. There are several cultural layers of different ages separated by sterile streaks. The lower level contains the artifacts of the Orlovka Neolithic culture. The finds of the Caspian culture were found in the middle cultural layer. The upper cultural layer contains the inventory of the Eneolithic periods and later epochs. This made it possible to develop the Neolith-Eneolithic cultural periodization in detail for the region. A large series of radiocarbon dates gave the possibility to establish the chronological framework for each culture. The reconstruction of paleogeographical conditions of population development in the Later Stone Age and Eneolithic was provided by the spore-pollen and geochemical analysis. Archaeozoological analysis helped to determine the animal species for each period. Of particular importance are the results related to the appearance of the first signs of a producing economy in the area. In addition, it is possible to provide a more detailed description of ceramic and stone tools for each cultural complex. Technical and technological analysis of pottery revealed characteristic features of various cultures.

New derivatives of the closo-decaborate anion [B10H9–O(CH2)2O(CH2)3C(O)–L–OCH3]2− (An) (1: L = Trp; 2: L = His; 3: L = Met; 4: L = Ala(2-oxopyrrolidin-3-yl) (Pld) were synthesized and isolated as tetraphenylphosphonium salts (Ph4P)2An. Anions 12−; 22−; 32−, and 42− contain a pendant functional group from the L-tryptophan methyl ester, L-histidine methyl ester, L-methionine methyl ester, or methyl 2-amino-3-(2-oxopyrrolidin-3-yl)propanoate (-Trp–OCH3, -His–OCH3, -Met–OCH3, or -Pld–OCH3) residue, respectively, bonded with the boron cluster anion through the oxybis[(ethane-2,1-diyl)oxy] spacer. This pacer is formed as a result of the nucleophilic opening of the attached dioxane molecule in the [B10H9O(CH2)4O]− starting derivative. Sodium salts of the target compounds were isolated and used in biological experiments. It was established that among compounds Na2An (An = 1–4), not all are capable of inhibiting the cytopathic effect of the virus in vitro. Sodium salts Na2An have a low toxic effect on a monolayer of continuous canine embryonic kidney (MDCK) cell line. Compounds Na21 and Na22 had IC50 of 5.0 and 20.0 μg/mL, respectively, while for compounds Na23 and Na24, IC50 values could not be achieved at the concentrations studied. The studies performed for molecular docking of the anionic part of 12− and 22− with the transmembrane domain of viroporin M2 show some differences in the location of these two ligands inside the M2 canal pore.

Brucellosis in animals is an infectious disease caused by bacteria of the genus Brucella. Known methods for diagnosing brucellosis face some challenges, due to the difficulties in isolating and standardizing the natural brucellosis antigen. In this work, we investigated the possibility of using the fluorescence polarization assay (FPA) with synthetic glycoconjugate biosensing tracers to detect antibodies against Brucella as a new methodology for diagnosing brucellosis. Based on the received results, the synthetic fluorescein-labeled trisaccharide tracer is most effective for Brucellosis detection. This tracer is structurally related to the immune determinant fragment of the Brucella LPS buildup of N-formyl-d-perosamine units, connected via α-(1→3)-linkage at the non-reducing end and α-(1→2)-linkage at the reducing end. The sensitivity and specificity in the case of the use of trisaccharide tracer 3b were 71% and 100% (Yuden’s method) and 87% and 88% (Euclidean method), respectively, which is comparable with the diagnostic efficiency of traditionally used serological methods, such as the agglutination test (AT), complement fixation test (CFT), and Rose Bengal test (RBT). Given the known advantages of FPA (e.g., speed, compactness of the equipment, and standard reagents) and the increased specificity of the developed test system, it would be appropriate to consider its widespread use for the diagnosis of brucellosis in animals, including rapid testing in the field.

Hepatocellular carcinoma (HCC) is the third cause of cancer-related mortality worldwide, accounting for more than 800,000 deaths annually. Surgical removal of the neoplasm remains the most effective treatment option. Partial liver resection is an adequate solution for patients without cirrhosis or with well-compensated cirrhosis, orthotopic liver transplantation is necessary in patients with early stage HCC on the background of cirrhosis. Tumor recurrence remains a major limitation of long-term survival of patients after liver transplantation. Posttransplant immunosuppression reduces the body's antitumor defense, which is provided by natural immunity. This contributes to the development and progression of the tumor process. Purpose of the study: to analyze domestic and foreign publications that present treatment options for HCC recurrence after liver transplantation. Literature sources were searched in PubMed, Scopus, Web of Science, MEDLINE, eLibrary databases. The search was conducted in Russian and English by keywords: hepatocellular carcinoma, tyrosine kinase inhibitors, immune checkpoint inhibitors, therapy of HCC relapse, orthotopic liver transplantation, RETREAT index, regorafenib, nivolumab. The authors presented a review of the data on the use of tyrosine kinase inhibitors and immune checkpoint inhibitors to prevent HCC recurrence. The results of the analysis of literature sources showed that the issue of post-transplant immunosuppression is relevant. The large number of studies and clinical case reviews leaves hope that an effective way of immunosuppression for recurrent HCC patients after liver transplantation will soon be found.

Aim of the study: to evaluate prognostic value of baseline lung immune prognostic index (LIPI) and its modification (mLIPI) for metastatic non-small cell lung cancer (mNSCLC) patients treated with immune checkpoint inhibitors (ICI).Material and methods. Baseline neutrophil-to-lymphocyte ratio, lactate dehydrogenase, hemoglobin, platelets, and fibrinogen level were collected from 133 patients treated with ICI in monotherapy or combination between July 2015 and July 2022 in N.N. Blokhin NMRCO. According to evaluating factors patients were divided into three groups of “good” (LIPI 0/mLIPI 0–1), “intermediate” (LIPI 1/mLIPI 2–3) and “poor” prognosis (LIPI 2/mLIPI 4–5). The primary endpoint was progression free survival (PFS).Results. The median PFS for the LIPI groups were 9.7 months (1.4–17.9; 95 % CI), 7.9 months (5.9–9.9; CI 95 %) and 6.0 months (4.07–7.93; 95 % CI) in the “good”, “intermediate” and “poor” prognosis groups, respectively; the hazard ratio (HR) for patients in the “poor” prognosis group (17 patients) was 2.02 (1.06–3.84; 95 % CI) compared with the “good” LIPI group (p=0.03). The median PFS for mLIPI groups were 9.0 months (4.53–13.47; 95 % CI), 8.0 months (5.4–10.6; CI 95 %) and 2.0 months. (1.33–2.67; 95 % CI) in the “good”, “intermediate” and “poor” prognosis groups, respectively. The HR for patients in the “poor” prognosis group (n=12) was 3.12 (1.51–6.46; 95 % CI) compared with the “good” mLIPI group (p=0.002).Conclusion. Baseline LIPI and mLIPI predicts potential resistance to ICI treatment in mNSCLC patients.

Aim: to present a clinical case of a patient with a complicated course of acute pancreatitis.Key points. A 31-year-old patient was admitted to the surgical department with a clinical picture of acute alcoholic pancreatitis. Signs of anemia were regarded as a consequence of gastrointestinal bleeding. Computed tomography with contrast enhancement, along with an increase in the size of the pancreas, the presence of foci of pancreatic necrosis with multiple fluid accumulations in the parapancreatic space, revealed smoothed gaustration and thickening of the walls of the predominantly transverse colon. During colonoscopy, ischemic changes of the colon mucosa were detected in a timely manner. Negative results of analysis for toxins A and B of Clostridioides difficile and pathogenic intestinal flora were obtained. By the means of intensive care, it was possible to achieve complete stabilization of the patient's condition, normalization of laboratory blood parameters and relief of ischemic processes in the colon wall.Conclusion. Ischemic changes of the colon can serve as a complication of acute pancreatitis. A thorough analysis of the results of computed tomography at the first signs of colon lesion and colonoscopy contributed to the rapid detection of complications and prevention of irreversible colon ischemia.

The article presents materials enabling to reconstruct the paleogeographic background of the development of the population of the Volga region steppe in the Neolithic and Eneolithic periods. The relevance of the study comes from the need to develop issues of natural and climatic factors influence on the development of cultures. The novelty is determined by the fact that the research presents materials of the 2014–2019 surveys for the settlement of Oroshaemoe I. The purpose of the article is to reconstruct the paleogeographic background at the time of interest. The tasks of the study also include identification of the chronological framework, reconstruction of natural and climatic conditions, and determination of the faunal component. In order to achieve these goals, archaeological, palynological and geochemical, radiocarbon and faunistic methods were used. The settlement of Oroshaemoe I is characterized by multi-layers and stratification. The site shows successively located layers of the Orlov, Caspian and Khvalynsk cultures, separated by sterile ones. In addition to ceramic and stone implements, faunal remains were found in the cultural layers which makes it possible to identify the species of animals at different stages of the Neolithic-Eneolithic of this region. Clear chronological frameworks are defined for all complexes. For the first time in recent years, the results of spore-pollen analyses were obtained for all cultural layers. An additional source was the results of geochemical analysis for this site. Certain periods of improvement and deterioration of the climatic situation are traced which influenced the vegetation cover of this area. The results of the analysis allow us to conclude that throughout the entire period the vegetation in the surrounding area was similar to modern dry steppes (semi-deserts). An increase in aridity is recorded at a later stage in the development of the Orlov culture. The driest climatic conditions existed during the formation of the Caspian layer; and during the formation of the Khvalyn layer the amount of precipitation began to increase. This resulted in changes in life activity in the Late Stone Age and the Early Metal Age.

Вроджена непрохідність тонкої кишки характеризується наявністю повного або часткового порушення її прохідності, що нерідко супроводжується розвитком синдрому поліорганної недостатності із залученням усіх органів і систем організму, та потребує проведення ургентного хірургічного втручання у новонародженої дитини. Своєчасне виявлення інтестинальної обструкції у новонароджених дітей є необхідною умовою, враховуючи імовірність розвитку важких ускладнень. Досягнення в хірургічному лікуванні, інтенсивній терапії та післяопераційній нутритивній підтримці за останнє десятиріччя призвели до покращення виживаності новонароджених з вродженою непрохідністю тонкої кишки, проте вона і досі пов’язана із значним рівнем захворюваності та летальності. З метою покращення результатів хірургічного лікування вродженої непрохідності тонкої кишки в усьому світі проводяться дослідження факторів, які впливають на летальність, але результати їх різняться і подекуди залишаються суперечливими. Факторами ризику смертності вважають складні вади серця, недоношеність, сепсис, пневмонії та такі хірургічні ускладнення, як синдром короткого кишечника, неспроможність анастомозу та гастродуоденальна дисфункція. У статті проведено аналіз публікацій з актуальних проблем діагностики та лікування вродженої непрохідності тонкої кишки у дітей. Розглянуто основні принципи та методи оперативних втручань окремих дитячих хірургічних клінік, а також реабілітацію дітей у післяопераційному періоді. Автори заявляють про відсутність конфлікту інтересів.

Introduction. Lung cancer remains the one of the most common and fatal cancers in the world. For a long time, chemotherapy was the only treatment option for metastatic lung cancer. Currently, immunotherapy became the one of the preferred options of treatment.The purpose of our work was to evaluate the long-term results of using the PD-1 inhibitor nivolumab in real-world settings.Materials and methods. 108 pretreated patients with metastatic NSCLC were included in this non-randomized, observational study. The median follow-up time was 54.5 months.Results. Median overall survival was 8.8 months (6-12, 95% CI). The five-year overall survival rate was 19.4%. Median progressionfree survival was 3.9 months (3-5, 95% CI). The five-year progression-free survival rate was 7.7%. Overall response rate (ORR) was 18%. In patients with ORR, the median overall survival was not achieved. Prolongation of immunotherapy after disease progression had a positive effect on the overall survival of patients. Clinically significant immuno-related adverse events developed in 21% of patients, but only 7.3% showed the development of adverse events grade 3-4 that required discontinuation of immunotherapy. A rare complication that we met was a case of encephalopathy, to which the patient achieved durable complete response despite discontinuation of immonotherapy.Conclusion. Received survival, efficacy and safety data may inform treatment decisions for patients with metastatic NSCLC in real world settings.

Checkpoint inhibitors, as well as their combinations, are increasingly included in the daily practice of the oncologist. However, given the mechanism of action, its use may be associated with immune side effects that can complicate the clinical course and prognosis of patients. As the number of reported indications for the administration of PD-1, PD-L1, CTLA-4 inhibitors increases, the rate of reports of rare complications associated with immunotherapy increases. Among the complications, it is worth highlighting the group of autoimmune endocrinopathies. Such complications of immunotherapy as hypophysitis, hypo- and hyperthyroidism are quite common, are relatively easy to correct and usually do not lead to discontinuation of therapy. The mechanisms underlying immune damage to target organs remain poorly understood. Primary adrenal insufficiency is a rare and potentially life-threatening complication that, due to non-specific symptoms, may be recognized too late. The development of adrenal insufficiency was noted in only 0.7% of patients in randomized clinical trials. To date, there is no single tactic for identifying and treating this complication. The management of such patients is possible only by a multidisciplinary team that includes an endocrinologist. We present a clinical case of the development of adrenal insufficiency on the background of combined chemo-immunotherapy and the results of the patient’s treatment after its resolution.

The abscopal effect was described more than 50 years ago and is a phenomenon in which radiation therapy promotes the regression of metastatic foci remote from the site of radiation. For decades, this effect has been described as a rare, unexplained phenomenon in patients receiving radiation therapy. Today, the abscopal effect is still an exceptional phenomenon: the mechanism underlying it is still not fully understood. It is believed that the abscopal effect is most likely associated with systemic immune responses that occur under the influence of radiation therapy.We present the case of a 63-year-old patient with advanced peripheral cancer of the upper lobe of the left lung, disease progression in the form of metastatic brain lesions and regression of tumor foci in the lungs after radiation therapy to the brain, while the patient did not receive additional treatment in the form of immunotherapy.The article examines the history of the abscopal effect, an attempt is made to understand the mechanisms of its occurrence, which can help to further improve the results of treatment of patients with NSCLC using radiation therapy and modern approaches to complex cancer treatment.

Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) of the epidermal growth factor receptor (EGFR) that has been approved for the treatment of metastatic non-small cell lung cancer (NSCLC) positive for the secondary T790M mutation of EGFR. Central nervous system (CNS) metastases are a common complication in patients with epidermal growth factor receptor (EGFR)‐mutated non‐small cell lung cancer (NSCLC), resulting in a poor prognosis and limited treatment options. Almost 25% of patients present with accompanying central nervous system (CNS) metastases at the first diagnosis. Treatment of CNS metastases requires a multidisciplinary approach, and the optimal treatment options and sequence of therapies are yet to be established. Many systemic therapies have poor efficacy in the CNS due to the challenges of crossing the blood‐brain barrier (BBB), creating a major unmet need for the development of agents with good BBB‐penetrating biopharmaceutical properties. Although the CNS penetration of first‐ and second‐generation EGFR tyrosine kinase inhibitors (TKIs) is generally low, EGFR‐TKI treatment has been shown to delay time to CNS progression in patients with both in preventing or delaying the onset of CNS metastases, and in leading to intracranial response of preexisting CNS lesions. This is one of the arguments in favor of starting osimertinib upfront rather than initiating treatment with firstor second-generation EGFR-TKIs.

Immunotherapy is the most promising method in the treatment of lung cancer, especially in connection with the rapidly growing development of monoclonal antibodies aimed at inhibiting immune checkpoints: anti-CTLA-4, anti-PD-1, anti-PD-L1. Classic immuno-mediated adverse events that occur with this method of treatment can affect several organs, including the lungs. Pneumonitis is a potentially life-threatening complication and often requires rapid treatment with high doses of corticosteroids and antibacterial drugs. We present the case of a 67-year-old patient with primary multiple malignant tumors of the larynx and left lung after combined treatment and incomplete treatment with Nivolumab, complicated by immuno-mediated pneumonitis. This report highlights the importance of treating patients with contraindications to chemotherapy when specific antitumor treatment is required, as well as timely detection of a rare but dangerous adverse event: immuno-mediated pneumonitis that occurs during treatment with immune checkpoint inhibitors. Thus, knowing the frequency of adverse events when using PD-1 and PD-L1 inhibitors, as well as the possible presence of comorbidities in patients, will make it easier for doctors to make informed decisions in the treatment of patients, and understanding the interaction of the tumor and the immune system will help determine the best predictors of response and further improve the results of treatment of patients with NSCLC.

Recently immune checkpoint inhibitors amazingly changed the landscape of cancer therapy worldwide. The number of immune checkpoint molecules in clinical practice is constantly increasing. There are some monoclonal antibodies recently registered in the Russian Federation: anti-PD1 antibodies (nivolumab, pembrolizumab), anti-PD-L1 (atezolizumab, durvalumab), anti-CTLA-4 (ipilimumab). Immune-mediated endocrinopathies are some of the most common complications of immunotherapy. According to the results of clinical studies, the incidence of serious endocrine immuno-mediated adverse events with anti-PD1 monoclonal antibodies is low (3.5–8%). The use of anti-CTLA4 antibodies, combined regimens, and the use of immunotherapy after chemoradiotherapy significantly increase the incidence of serious adverse events to 30%. In clinical practice of N.N. Blokhin Cancer Research Center among 245 non-small cell lung cancer and hepatocellular carcinoma patients treated with immunotherapy, 22 (8,9%) developed an immune-mediated endocrinopathy. Most patients developed adverse events of 1–2 degrees, in two patients – 3 degrees, requiring discontinuation of treatment. The aim of this article was to provide useful information and recommendations regarding the management of common immuno-related endocrine adverse events (including hypothyroidism, hyperthyroidism, pituitary, adrenal insufficiency) for clinical oncologists.

We report on a comparative analysis of quenched sideband cooling in trapped ions. We introduce a theoretical approach for time-efficient simulation of the temporal cooling characteristics and derive the optimal conditions providing fast laser cooling into the ion’s motional ground state. The simulations were experimentally benchmarked with a single ^172 Yb ^+ ion confined in a linear Paul trap. Sideband cooling was carried out on a narrow quadrupole transition, enhanced with an additional clear-out laser for controlling the effective linewidth of the cooling transition. Quench cooling was thus for the first time studied in the resolved sideband, intermediate and semi-classical regime. We discuss the non-thermal distribution of Fock states during laser cooling and reveal its impact on time dilation shifts in optical atomic clocks.

Non-small cell lung cancer (NSCLC) is the leading cause of death from cancer worldwide. Despite the success over recent years in the treatment of NSCLC it has not yet been able to achieve good long-term survival. The development of immune checkpoint inhibitors has altered the landscape of treatment of advanced cancers, including non-small cell lung cancer (NSCLC). Nivolumab is the PD-1 inhibitor approved for the treatment of NSCLC to show a survival benefit in a randomised phase III trials. The experience of physicians in routine clinical practice is often different from those in a controlled clinical trial setting. The purpose of this analysis is to evaluate nivolumab use in real world setting. Results: The general survival at 76 patients by metastatic NSLC receiving an immunotherapy nivolumab during the period from 2015 to 2019 is analysed. The minimum time of observation was 1.6 months. The median of the general survival made 7.6 months (5.92-9.41. DI 95%). The one-year survival - 35%, at the same time 3-year survival was 25%. At patients with the objective answer the median of the general survival was not reached. Immunomediated adverse events developed in 42% of patients, but only 6.6% showed the development of adverse events of 3-4 degrees, which indicates a favorable toxicity profile. Conclusion: the results received by us correlate with data of clinical trials.

Nowadays neoadjuvant immunotherapy is one of the main research areas in oncology. This interest is supported by the success of check-point inhibitors in treatment of advanced and metastatic lung cancer. The postulate that neoadjuvant immunotherapy achieves tumor devitalization before surgery is confirmed by a morphological assessment of surgical material with a gradation of the antitumor effect. In addition to affecting directly to the tumor, it also affects at potential micrometastases. A morphological assessment with a gradation of the antitumor effect (MPR – a major pathomorphological response, CPR – a complete pathomorphological response) provides a unique opportunity to identify predictors of effectiveness and adjust the treatment tactic. A major morphological response (MPR – less than 10% of viable tumor cells in the tumor tissue) is associated with better overall survival. Currently, there is evidence that the appointment of neoadjuvant immunotherapy in mono mode allows you to achieve MPR in 18–45%, and the use of a combination of immunotherapy with chemotherapy increases it to 32–92%. Neoadjuvant immunotherapy or combination with chemotherapy does not postpone surgical treatment but allows us to achieve the better result.

Molecularly targeted therapy with tyrosine kinase inhibitors (TKI) has been recognized as the optimal treatment option for patients with EGFR-positive non-small-cell lung cancer (NSCLC). At present, 5 drugs of this group are available: first generation – erlotinib and gefitinib, second generation – afatinib and dacomitinib (not registered in Russia), and third generation – osimertinib. The drugs have some peculiarities, this refers to their antitumor activity, safety profile, and resistance mechanisms. Knowledge of these differences is necessary to determine a rational treatment plan. Gefitinib and erlotinib increase the time before progression compared to standard chemotherapy, but do not affect the overall survival rate. Afatinib significantly increases the time before progression, and in the cohort of patients with deletion in the 19th exon – the overall survival rate. Dacomitinib was more effective than gefitinib in terms of time before progression and total survival. On average, the disease progresses after a year and a half of successful treatment. The dominant mechanism of resistance development to TKI of the first and second generation consists in accumulation of mutation of the gatekeeper gene T790M. Most often it is determined in patients with deletion in the 19th exon (Del19). Osimertinib has proved to be effective against tumors not only with activating mutations, but also with T790M resistance mutation, and with minimal activity to EGFR «wild» type receptors. The first indication that it was registered was progression on targeted therapy with first and second generation drugs caused by the secondary mutation of T790M. Later, the advantage of osimertinib compared to gefitinib/erlotinib in untreated EGFR-positive patients was proved. Thus, there are at least two main options for treatment tactics: the consistent use of second and third generation drugs or prescription of osimertinib in the first line with subsequent chemotherapy. Evaluation and consideration of known prognostic factors will allow choosing the optimal tactics for a particular patient.

The urgency of the problem of treating patients with lung cancer is caused by a steady increase in the lung cancer incidence and lung cancer mortality rates in population. Most patients with NSCLC initially present with locally advanced or disseminated disease. Currently, simultaneous chemoradiation therapy (CRT) is the standard for the treatment of locally advanced NSCLC, which appears superior to the single chemotherapy or radiation therapy, while the overall survival (OS) rate remains not high enough. Therefore, the search for optimal combinations of chemotherapeutic drugs and radiation therapy (CRT), as well as fractionation regimens is a promising direction in the treatment of such patients. In this article, we will review the on-topic studies data that are currently available, future directions of the therapy and objectives.

Now the number of patients receiving immunotherapy with checkpoint inhibitors is growing. At the same time, clinicians increasingly encounter such a clinical phenomenon as pseudoprogression. Nowadays we have no radiological evidences of pseudoprogression. The every such case requires an individual decision.

In the open prospective non-randomized single-center study we recruited patients with advanced NSCLC harboring EGFR mutations. Initially there were two months of treatment by gefitinib 250 mg daily. Then, after a 2-week drug-free period, 3 cycles of paclitaxel 175 mg / m2 and carboplatin AUC5 were administrated at days 71-113. Thereafter, gefitinib was re-started on day 135 and continued until disease progression. The primary endpoint was progressive free survival (PFS) time. One-year PFS in all patients group included in the study at the time of the preliminary analysis was 79.8%, median PFS was 17 months (13.5–23, CI 95%). In the group of integrated chemotherapy one-year PFS was 89.3%, median PFS was 19 months (14–23.5, CI 95%).

A new class of atomic interferences using ultranarrow optical transitions are pushing quantum engineering control to a very high level of precision for the next generation of sensors and quantum gate operations. In such context, we propose a new quantum engineering approach to Ramsey-Bordé interferometry introducing multiple composite laser pulses with tailored pulse duration, Rabi field amplitude, frequency detuning and laser phase step. We explore quantum metrology with hyper-Ramsey and hyper-Hahn-Ramsey clocks below the 10^{−18} level of fractional accuracy by fine-tuning control of light excitation parameters leading to spinor interferences protected against light-shift coupled to laser-probe field variation. We review cooperative composite pulse protocols to generate robust Ramsey-Bordé, Mach-Zehnder, and double-loop atomic sensors shielded against measurement distortion related to Doppler and light shifts coupled to pulse area errors. Fault-tolerant autobalanced hyperinterferometers are introduced eliminating several technical laser pulse defects that can occur during the entire probing interrogation protocol. Quantum sensors with composite pulses and ultracold atomic sources should offer a new level of high accuracy in the detection of acceleration and rotation inducing phase shifts, a strong improvement in tests of fundamental physics with hyperclocks while paving the way to a new conception of atomic interferometers tracking space-time gravitational waves with very high sensitivity.

In 1949, Ramsey's method [Phys. Rev. 76, 996 (1949)PHRVAO0031-899X10.1103/PhysRev.76.996] of separated oscillating fields was elaborated boosting over many decades metrological performances of atomic clocks and becoming the standard technique for very high-precision spectroscopic measurements. A generalization of this interferometric method is presented replacing the two single coherent excitations by arbitrary composite laser pulses. The rotation of the state vector of a two-level system under the effect of a single pulse is described using the Pauli matrices basis of the SU(2) group. It is then generalized to multiple excitation pulses by a recursive Euler-Rodrigues-Gibbs algorithm describing a composition of rotations with different rotation axes. A general analytical formula for the phase shift associated with the clock's interferometric signal is derived. As illustrations, hyper-clocks based on three-pulse and five-pulse interrogation protocols are studied and shown to exhibit nonlinear cubic and quintic sensitivities to residual probe-induced light shifts. The presented formalism is well suited to optimize composite phase shifts produced by tailored quantum algorithms in order to design a new generation of optical frequency standards and robust engineering control of atomic interferences in atomic, molecular, and optical physics with cold matter and antimatter.

At the present time, a small group of patients with oligometastases (who have a solitary metastatic lesion in another organ along with the primary tumour of the lung) is differentiated among the patients with metastatic lung cancer. A total of 14 patients of the study citied in this article underwent a comprehensive treatment of oligometastatic non-small cell lung cancer (ONSCLC), which included systemic therapy and local influence on solitary metastasis. The median overall survival for this group was 20 months (16.0–32.6, CI 95%). The 1-year and 2-year overall survival rates accounted for 84.5 and 65.7%, respectively. The findings of the study demonstrate the possibilities of an aggressive approach to the treatment of patients with ONLDLC.

Targeted therapy is the optimal treatment of patients with advanced EGFR-positive NSCLC. The first- and second-generation EGFR tyrosine kinase inhibitors provide a durable antitumor response in most patients during the year. Due to appearance of T790M secondary mutation of resistance at progression of the disease, the administration of osimertinib leads to full control of the tumour for another 10 months. However, this is not the only mechanism of acquired drug resistance. A repeated biopsy of the tumour followed by histological and molecular genetic research makes it possible to clarify the cause of resistance and personalize the further disease management.

Хілоперитонеум (ХП) – патологічний стан, що пов’язаний з накопиченням лімфи у черевній порожнині і характеризується збільшенням розмірів живота та асцитом. Етіологія даного захворювання залишається незрозумілою. Комплексне лікування включає консервативні заходи та оперативне втручання. Метою терапії є зниження вироблення лімфи, осушення порожнин, відновлення втрат рідини. Радикальні способи лікування цієї патології відсутні. У статті наведено клінічний випадок ХП у дитини підліткового віку. Хлопчик хворіє з 2014 р., коли помітили збільшення правої половини калитки. У 2015 р. виникли явища асциту. Лапароскопічно причину асциту не знайдено. 22.10.2015 р. оперований з приводу напруженої водянки правого яєчка, через рік – з приводу пахової грижі зліва та напруженого хілоперитонеуму – проведене видалення грижі, аспірація лімфи. Ознаки накопичення лімфи з’явилися на третю добу після втручання. У віці 17 років дитина була госпіталізована з ознаками напруженого ХП. 08.04.2018 р. проведено операцію – ендовідеохірургічну ревізію органів живота. Екстракція лімфи з черевної порожнини. Видалення двостороннього хілоцеле. Видалення грижі по Шпітці. Дренування черевної порожнини. Під час операції з черевної порожнини було евакуйовано до 12 літрів лімфи. Операція завершилася постановою дренажу у порожнину малого тазу. Післяопераційний період перебігав без хірургічних ускладнень на тлі гіпопротеїнемії (36 г/л), триваючої лімфореї. Хворий виписаний на вимогу батьків у задовільному стані. Діагноз при виписці: «Аномалія розвитку лімфатичної системи. Хвороба Вальдмана? Напружений хілоперитонеум. Пупкова грижа. Двостороннє напружене хілоцеле. Лімфостаз правої нижньої кінцівки».

The article is dedicated to the results of complex diagnostics and treatment (including the new methods of enteroscopy) of gastrointestinal bleeding with unknown source. From 14.02.2007 to 19.04.2017 the source of bleeding was revealed in 173 (82,7%) of 209 patients, including small bowel bleeding in 154 (89,0%) patients. The most frequent sources of bleeding were vessel malformations in 39,6% of patients and small bowel tumors in 30,5% of patients. Endoscopic treatment was performed in 32 (21,7%) cases, surgical treatment - in 41 (27,9%) cases, conservative treatment - in 74 (50,4%) cases.

The aim of the investigation was to study the relationship among adipokines, markers of subclinical inflammation and endothelial dysfunction in patients with metabolic healthy obesity (MHO). The study included 50 persons aged 25-50 years with obesity in the absence of metabolic disorders (International Diabetes Federation criteria, 2005, marked as MHO), the control group consisted of 50 healthy respondents without obesity. We studied clinical and biochemical parameters, insulin resistance index (HOMA-IR), levels of leptin, soluble leptin receptors (sLR), resistin, adiponectin, C-reactive protein (CRP-hs), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), von Willebrand factor, free leptin index was calculated in a formula (FLI = leptin × 100 / sLR). In MHO patients, independently of HOMA-IR index, there was an increase in leptin, FLI, resistin, VEGF, and IL-6 parameters. The concentration of CRP-hs and TNF-α in MHO group with HOMA-IR ≥2.7 was increased. Systolic blood pressure correlated with leptin level (r=0.43, P

We develop a method of synthetic frequency generation to construct an atomic clock with blackbody radiation (BBR) shift uncertainties below 10 ^−19 at environmental conditions with a very low level of temperature control. The proposed method can be implemented for atoms and ions, which have two different clock transitions with frequencies ν _1 and ν _2 allowing to form a synthetic reference frequency ν _syn = ( ν _1 − ɛν _2 )/(1 − ɛ ), which is absent in the spectrum of the involved atoms or ions. Calibration coefficient ɛ can be chosen such that the temperature dependence of the BBR shift for the synthetic frequency ν _syn has a local extremum at an arbitrary operating temperature T _0 . This leads to a weak sensitivity of BBR shift with respect to the temperature variations near operating temperature T _0 . As a specific example, the Yb ^+ ion is studied in detail, where the utilized optical clock transitions are of electric quadrupole ( S → D ) and octupole ( S → F ) type. In this case, temperature variations of ±7 K lead to BBR shift uncertainties of less than 10 ^−19 , showing the possibility to construct ultra-precise combined atomic clocks (including portable ones) without the use of cryogenic techniques.

Timely and accurate diagnosis of tumors of the small intestine remains a clinical challenge. The article presents own experience of the combined use of video capsule and balloon-assisted enteroscopy in the diagnosis and treatment of tumors of the small intestine complicated by hemorrhage.

Immunotherapy presents a new promising approach to the treatment of disseminated lung cancer. Pemriblisumab (Kitruda®) is one of the antiPD-1 drugs registered in Russia, which is used in both the secondand, in the event of high-level PD-L1 expression (≥50%), the first-line therapy. This paper presents a clinical observation of a highly efficient pemribrolizumab treatment of a patient with metastatic adenocarcinoma.

The article tells the short history and describes current trends in the endoscopic treatment of patients with achalasia. The technique, specific equipment and first results of endoscopic operations conducted jointly with Prof. H. Inoue in Russia are demonstrated.

У даному огляді літератури висвітлені питання етіології, патогенезу і клінічних проявів гострого неспецифічного мезаденіту у дітей. До теперішнього часу ця проблема, як і раніше, залишається однією з найактуальніших у дитячій хірургії. Щодо гострого неспецифічного мезаденіту опубліковано досить мало літературних даних, а робіт монографічного характеру - недостатньо. Педіатри і дитячі хірурги постійно цікавляться проблемою цього захворювання, що обумовлено його значимістю для диференціальної діагностики з гострими хірургічними захворюваннями живота, найчастіше з гострим апендицитом. Найбільш частою клінічної "копією" гострого апендициту в дитячому віці є саме неспецифічний мезаденит Описано різні класифікації даної патології. Детально викладені різні лабораторні, патоморфологічні й спеціальні інструментальні дослідження у дітей з гострим неспецифічним мезаденітом. На сучасному науковому рівні висвітлені питання діагностики та диференціальної діагностики, а також методи консервативної терапії і оперативного лікування. Проблема діагностики та лікування гострого неспецифічного мезентеріального лімфаденіту в дітей далека від свого вирішення і вимагає подальшого вивчення й розробки алгоритму дій, як щодо неінвазійної діагностики і спрямованої патогенетичної терапії, так і щодо визначення показань для виконання відеохірургічного втручання.

Recently, system of diagnostic and objective assessment of the state severity of children with acute nonspecific mesenteric adenitis was developed. The clinical material for the study was the observation of 210 patients aged from 3 months to 15 years. Prognostically significant signs were identified on the basis of mathematical analysis of the immediate treatment results (risk factors), which adversely affect the treatment outcome. Their importance is expressed in points. The severity of the patient's condition was determined by number of points they scored. The system allows predicting the treatment effectiveness of acute nonspecific mesenteric adenitis and optimizing the treatment strategy prior complications development.