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this paper presents data on the study of the cultural properties of the genetic variant Omicron of the SARS-CoV-2 virus of the coronavirus infection COVID-19. The most permissive biological systems for the reproduction of this virus variant are Vero, MA-104, MARC-145, PK-15, and SPEV cell cultures. The productive conditions for cultivating the genetic variant Omicron of the SARS-CoV-2 virus in the studied cell lines turned out to be the following parameters: seeding concentration of cells 200 thousand/cm3, multiplicity of infection – 0.01 TCD50/cell, virus cultivation period – 2 days, cell lesion area monolayer before collecting the virus – 75-80%, the biological activity of the virus in the range from 4.14±0.31 to 6.66±0.22 lg TCD50/cm 3.

BACKGROUND: Non-pharmacological treatments are an integral part of the treatment of all patients with type 2 diabetes (T2D). However, due to many factors, doctors and patients themselves tend to underestimate or completely neglect such effective methods in managing the course of the disease. Despite the high level of evidence of the effectiveness of this type of treatment for T2D, every year scientists around the world continue to actively study the effect of various non-drug methods on the course of the disease.AIM: To study the effect of a 24-week structured non-pharmacological treatment program on glycated hemoglobin reduction and weight loss in middle-aged patients with compensated T2D taking metformin.MATERIALS AND METHODS: A two-group, randomized, parallel-group, blinded trial was designed. Patients with an established diagnosis of T2D in the stage of compensation (HbA1c ≤7%), aged 45–59 years, taking metformin, were randomized to receive either standard non-pharmacological treatment of diabetes according to clinical protocol of T2D treatment in Kazakhstan, or an intensive course of non-pharmacological treatment according to a structured program developed by researchers. The duration of the intervention was 24 weeks. Primary outcomes were glycated hemoglobin, body weight. Secondary outcomes: blood pressure, waist circumference, insulin resistance index (HOMA-IR), lipid profile: total cholesterol, high and low density lipoproteins, triglycerides. The outcomes of the participants in both groups were assessed at baseline, 12 and 24 weeks after randomization. The study is registered with ClinicalTrials.gov NCT04632823.RESULTS: The study included 200 patients, 67 patients completed the study: intervention group n=33, control group n=34. After 24 weeks of observation, patients in the intervention group showed a significant decrease in HbA1c from 6.34% to 6.22%, p1c remained the same at 6.5% (p=0.703). Patients in both groups significantly reduced body weight, however, the decrease in the intervention group was more significant: by 6.7% of the initial level, while in the control group, only 1.1%. LDL, triglycerides, cholesterol level, HOMA-IR 2, and diastolic blood pressure did not decline significantly in the control group. All biochemical characteristics except triglycerides and LDL decreased significantly in the intervention group.CONCLUSION: The use of a structured program of non-pharmacological treatment of type 2 diabetes mellitus among compensated (HbA1c ≤7%) middle-aged patients who took metformin significantly reduced body weight and glycated hemoglobin in 24 weeks.

The problem of "new" infectious diseases has now acquired particular relevance for national and international health systems. One of these infections is the SARS-CoV-2 coronavirus. Due to the rapid spread of a new type of coronavirus in the world, molecular genetic studies of this virus are of great importance. This will help to understand the nature of the virus and develop antiviral drugs to prevent the disease. The aim is to identify a missense mutation in the ORF3 gene of the studied coronavirus strain SARS-CoV-2/human/KAZ/Britain. This paper presents the results of the development and sequencing of the ORF3 gene of the coronavirus strain SARS-Cov-2/human/KAZ/Britain. For the development and sequencing by the Sanger method of the ORF3 gene, 4 pairs of primers were developed, with an overlap of 100-150 bp. The changes in the ORF3 gene compared to other strains whose data were obtained from the GISAID database were analyzed. As a result, the obtained amino acid sequences of the ORF3a gene of variant B.1.1.7 were compared with the reference strain HCoV-19/Wuhan/Hu-1/2019, where one mutation was determined at position 149: W (tryptophan) → L (leucine). The phylogenetic affiliation of the studied virus strain was also determined, where the genetic distance between the studied strains of the SARS-CoV-2 virus was determined. Thus, the greatest similarity with the studied strain were: HCoV-19/Wuhan/Hu-1/2019, HCoV-19/England/MILK-9E05B3/2020, HCoV-19/Japan/IC-0446/2020, HCoV-19/Germany/NI-IOV-MHH15/2020, and the strain HCoV-19/Argentina/PAIS-F0418/2021 significantly distanced itself from the SARS-CoV-2/human/KAZ/Britain strain.

The paper presents the results of the development and manufacture, as well as assembly and installation of a test device for testing miniature samples by the SPT method. The results of mechanical tests by tensile and SPT methods of 35X steel material after heat treatment (quenching + tempering) at different tempering temperatures. The evaluation of changes in the strength characteristics of steel grade 35X, depending on the heat treatment mode. The correlation equations between the t/10 method and the yield strength of each 35X steel sample obtained during tensile tests were determined and obtained.

Purpose. Development of a calculation methodology for three-layer cylindrical shell stability, which will significantly improve the calculation practice for these structures regarding the determination of critical external pressure. Methodology. When determining the critical external pressure, the method of variational calculation using the Euler equation of the mixed variational problem was used. To determine three-layer cylindrical shell stability, the factors of significant influence on its strength and stability were taken into consideration, namely the reduced modulus of a three-layer wall elasticity. Bending stiffness Dh was substituted with flexural stiffness of three-layer shell with account for the shear deformation. Findings. The current situation of the three-layer cylindrical shell stability issue is investigated. Using the variational calculation methods via the Euler equation of the mixed variational problem an equation is composed of equality condition of inner and external force action of an orthotropic structure, which is under the state of neutral equilibrium with radial displacement. The previously obtained equation for radial displacements having been taken and applied to the system potential energy per unit of length equation, an equation for the critical pressure determination is determined. The analytical solution obtained was proposed for the structure of the crane travelling wheel with an elastic insert. Pcr 1267MPa was obtained. The allowable wheel pressure on rail for the crane travelling wheels is adopted to be within 250 MPa, i.e. the available stability margin is nc 1267/250 5.1. As we can see, the stability margin is more than sufficient. Originality. A new methodology for the three-layer cylindrical shell under external pressure calculation is developed. A quantitative assessment of the crane travelling wheel with flexible insert critical pressure is carried out. Practical value. A determination methodology for critical pressure of a three-layer cylindrical structure under external pressure is created.

The relationship of age and date of birth (DOB) in the data

Background: Barrett's esophagus is often asymptomatic and only a small portion of Barrett's esophagus patients are currently diagnosed and under surveillance. Therefore, it is important to develop risk prediction models to identify high-risk individuals with Barrett's esophagus. Familial aggregation of Barrett's esophagus and esophageal adenocarcinoma, and the increased risk of esophageal adenocarcinoma for individuals with a family history, raise the necessity of including genetic factors in the prediction model. Methods to determine risk prediction models using both risk covariates and ascertained family data are not well developed.Methods: We developed a Barrett's Esophagus Translational Research Network (BETRNet) risk prediction model from 787 singly ascertained Barrett's esophagus pedigrees and 92 multiplex Barrett's esophagus pedigrees, fitting a multivariate logistic model that incorporates family history and clinical risk factors. The eight risk factors, age, sex, education level, parental status, smoking, heartburn frequency, regurgitation frequency, and use of acid suppressant, were included in the model. The prediction accuracy was evaluated on the training dataset and an independent validation dataset of 643 multiplex Barrett's esophagus pedigrees.Results: Our results indicate family information helps to predict Barrett's esophagus risk, and predicting in families improves both prediction calibration and discrimination accuracy.Conclusions: Our model can predict Barrett's esophagus risk for anyone with family members known to have, or not have, had Barrett's esophagus. It can predict risk for unrelated individuals without knowing any relatives' information.Impact: Our prediction model will shed light on effectively identifying high-risk individuals for Barrett's esophagus screening and surveillance, consequently allowing intervention at an early stage, and reducing mortality from esophageal adenocarcinoma. Cancer Epidemiol Biomarkers Prev; 25(5); 727–35. ©2016 AACR.

Supplementary Methods of imputation of age and estimating the parameters of the prediction model. Supplementary Table S1 Missing rates on the 8 covariates in the training and validation datasets. Supplementary Table S2 Stepwise removal of covariates in the MLM model on the basis of LRT tests and AIC. Supplementary Table S3. Description of the eight predictor covariates. Supplementary Table S4 Number of informative pedigrees without missing covariate data.

The joint linearity of the categorical covariates on the logit scale

The linear relationship between the continuous covariates and susceptibility on the logit scale

The consistency of true age and the corresponding imputed age that was imputed according to the family structure and the known ages of family members

The article provides information about green microalga Chloroidium saccharophilum (Trebouxiophyceae) whose history of study dates back to more than 100 years. The issues of its intraspecific variability are considered. We also studied the strain of C. saccharophilum IRK–A 230 isolated from a small puddle on the southeastern shore of Lake Baikal (Republic of Buryatia, Russia). Light and electron microscopy and molecular phylogeny methods establish the species identity of the strain. The alga has an ellipsoidal cell shape, parietal chloroplast and visible pyrenoid with starch sheath; reproduction by equal and unequal autospores in even and odd numbers; the ability to form spherical cells; and accumulated yellow pigments in old non-heterotrophic cultures. The data obtained by us complement the species characteristics, and its biology and geography. The amended description of C. saccharophilum is provided.

Weifeng Zou,1 Dong Ye,2 Sha Liu,3 Jinxing Hu,1 Tao Zhu,1 Fang He,4 Pixin Ran5 1State Key Laboratory of Respiratory Disease, Guangzhou Chest Hospital, Guangzhou, Guangdong, People’s Republic of China; 2State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 3The Second Hospital, University of South China, Hengyang, Hunan, People’s Republic of China; 4School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 5State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Pixin RanState Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Road, Yuexiu District, Guangzhou, Guangdong, 510120, People’s Republic of ChinaTel +86 13922765811Email pxran@gzhmu.edu.cnBackground and Purpose: PM2.5-associated airway inflammation has recently been recognized as pivotal to the development of COPD. Aberrant glycogen synthase kinase (GSK)-3β signaling is linked to the inflammatory response. Therefore, we investigated the effects of GSK-3β inhibitors on the PM2.5-induced inflammatory response in bronchial epithelial cells.Methods: The production of phosphorylated GSK-3β (p-GSK-3β) was analyzed by immunohistochemistry with PM2.5-induced mice. HBECs were treated with various inhibitors targeting GSK-3β or JNK before PM2.5 stimulation. The production of GSK-3β signaling was analyzed by Western blotting. Inflammatory cytokine production was detected by qRT–PCR and ELISA.Results: PM2.5 exposure caused lung inflammation, upregulated serum concentrations of HMGB1 and IL-6, decreased IL-10 expression, and significantly attenuated p-GSK-3β production in mice. HBECs exposed to PM2.5 showed significantly reduced p-GSK-3β production, an increased ratio of p-JNK/JNK, increased NF-κB activation and IκB degradation, and upregulated the inflammatory cytokines HMGB1 and IL-6. Intervention with GSK-3β inhibitors TDZD-8 and SB216763 significantly suppressed PM2.5-induced outcomes. Moreover, the JNK inhibitor SP600125 also reduced the level of NF-κB phosphorylation induced by PM2.5. The differences in the levels of inflammation-related cytokines in the TDZD-8 groups were greater than those in the SB216763 groups.Conclusion: Inhibition of GSK-3β weakens the PM2.5-induced inflammatory response by regulating the JNK/NF-κB signaling pathway in bronchial epithelial cells.Keywords: PM2.5, COPD, GSK-3β, inflammatory response, HBECs

Chenchen Wang,1,2 Demei Ye,1 Zuoling Xie,1,2 Xi Huang,1 Zheng Wang,2 Haiyan Shangguan,2,3 Wenwen Zhu,2 Shaohua Wang1 1Department of Endocrinology, The Affiliated ZhongDa Hospital of Southeast University, Nanjing, 210009, People’s Republic of China; 2School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of China; 3Nanjing Central Hospital, Nanjing, 210008, People’s Republic of ChinaCorrespondence: Shaohua WangDepartment of Endocrinology, The Affiliated ZhongDa Hospital of Southeast University, Nanjing, 210009, People’s Republic of ChinaTel +86 25 83262810Fax +86 25 83285132Email gyjwsh@126.comPurpose: In addition to hyperglycemia and hyperlipidemia, obesity and hypertension are important cardiovascular risk factors for coronary heart disease (CHD) in patients with type 2 diabetes mellitus (T2DM). This study aims to explore the interaction of these risk factors.Patients and Methods: Data of hospitalized patients with T2DM from 2013 to 2018 were collected. A multivariate logistic regression model was established. Patients with normal weight and blood pressure were recruited as controls. The interaction on the risk of CHD was evaluated by relative excess risk due to interaction (RERI).Results: Among the 30,693 patients with T2DM, 7202 (23.5%) had CHD. In the low weight group, the prevalence of CHD in patients with hypertension was nearly four times higher than that in patients without hypertension (42.7% vs 11.3%, P < 0.01). The OR value of hypertension alone on CHD increased from 1.29 (95% CI 1.06– 1.56) in the body mass index (BMI) 30.0– 34.9 kg/m2 group to 1.35 (95% CI 1.11– 1.62) in the BMI ≤ 18.5 kg/m2 group. Additive interaction was observed between hypertension and BMI in CHD risk, especially in the low weight group (RERI:2.2, 95% CI 0.9– 3.5). BMI and CHD risk showed a smile curve relationship. The attributive proportion in the low weight group was higher than that in the severe obesity group, that is, 0.52 (95% CI 0.35– 0.69) vs 0.18 (95% CI − 0.59 to 0.95).Conclusion: Maintaining normal weight and avoiding low weight are particularly important for patients with co-occurring diabetes and hypertension to prevent the risk of CHD.Keywords: type 2 diabetes, cardiovascular, hypertension, body mass index, interaction

We present a review of current literature and findings of our own surveys of 35 children and 182 adults with ankylosing spondylitis. Compared with the disease in adults, juvenile ankylosing spondylitis has a number of clinical features, which occurs only in boys, manifests by a more frequent lesion of axial joints (shoulder, hip), development of systemic bone deficiency (osteopenia, osteoporosis), enthesitis (in particular, of the femoral condyles and the vertebral joints, but not achillodynia), uveitis, and cardiopathy, proliferation (and not destruction) of bone sections during the onset of spondylopathy and a rare involvement in the process of the lumbar spine and the formation of epiphyseal osteoporosis, higher blood concentrations of interleukin-8 and -17, but lower values of interleukin-1β, circulating immune complexes, fibrinogen, immunoglobulins А and G. It may be desirable to separate ankylosing spondylitis as a nosological form, such as juvenile idiopathic arthritis (in the recent past, juvenile rheumatoid arthritis)., Представлены обзор современной литературы и данные собственных обследований 35 детей и 182 взрослых, страдающих анкилозирующим спондилитом. По сравнению с заболеванием у взрослых людей ювенильный анкилозирующий спондилит (ЮАС) имеет целый ряд особенностей клинического течения, который возникает исключительно у мальчиков, проявляется более частым поражением осевых суставов (плечевых, тазобедренных), развитием системного остеодефицита (остеопении, остеопороза), энтезитов (в частности, мыщелков бедренной кости и позвонковых сочленений, но не ахиллодинитов), увеита и кардиопатии, пролиферацией (а не деструкцией) участков кости в дебюте спондилопатии и редким вовлечением в процесс поясничного отдела позвоночника и формированием эпифизарного остеопороза, более высокими концентрациями в крови интерлейкинов-8 и -17, но меньшими значениями интерлейкина-1β, циркулирующих иммунных комплексов, фибриногена, иммуноглобулинов А и G. Возможно, будет целесообразным выделение ЮАС в отдельную нозологическую форму, как, например, ювенильного идиопатического артрита (в недавнем прошлом — ювенильного ревматоидного артрита)., Наведено огляд сучасної літератури і дані власних обстежень 35 дітей та 182 дорослих, що страждають від анкілозуючого спондиліту. Порівняно із захворюванням у дорослих людей ювенільний анкілозуючий спондиліт (ЮАС) має низку особливостей клінічного перебігу, що виникає виключно у хлопчиків, виявляється частішим ураженням вісьових суглобів (плечових, кульшових), розвитком системного остеодефіциту (остеопенії, остеопорозу), ентезитів (зокрема, виростків стегнової кістки й хребцевих зчленувань, але не ахіллодинітів), увеїту і кардіопатії, проліферацією (а не деструкцією) ділянок кістки в дебюті спондилопатії та рідкісним залученням до процесу поперекового відділу хребта й формуванням епіфізарного остеопорозу, більш високими концентраціями в крові інтерлейкінів-8 і -17, але меншими значеннями інтерлейкіну-1β, циркулюючих імунних комплексів, фібриногену, імуноглобулінів А і G. Можливо, буде доцільним виділення ЮАС в окрему нозологічну форму, як, наприклад, ювенільного ідіопатичного артриту (в недавньому минулому — ювенільного ревматоїдного артриту).

Jing Zhao,1,&ast; Qing Zhao,1,&ast; Jing-Ze Lu,1 Dan Ye,1 Sheng Mu,1 Xiao-Di Yang,2 Wei-Dong Zhang,3,4 Bing-Liang Ma1 1Department of Pharmacology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 3Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 4School of Pharmacy, Second Military Medical University, Shanghai, 200433, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei-Dong Zhang; Bing-Liang Ma Email wdzhangy@hotmail.com; bingliang.ma@hotmail.comPurpose: This study aimed to evaluate the pharmaceutical and pharmacokinetic effects of the natural nanoparticles (Nnps) isolated from Coptidis Rhizoma extract on berberine hydrochloride (BBR) and systematically explore the related mechanisms.Methods: Firstly, Nnps were isolated from Coptidis Rhizoma extract and then an Nnps-BBR complex was prepared. After qualitative and quantitative analysis in terms of size, Zeta potential, morphology, and composition of the Nnps and the Nnps-BBR complex, the effects of the Nnps on the crystallization of BBR were characterized. The effects of the Nnps on the solubility and dissolution of BBR were then evaluated. In addition, the effects of the Nnps on BBR in terms of cellular uptake, transmembrane transport, metabolic stability, and pharmacokinetics in mice were studied.Results: The Nnps had an average size of 166.6 ± 1.3 nm and Zeta potential of − 12.5 ± 0.2 mV. The Nnps were formed by denaturation of co-existing plant proteins with molecular weight < 30 kDa. The Nnps adsorbed or dispersed BBR, thereby promoting BBR transformation from crystal to amorphous form and improving its solubility and dissolution. The Nnps carried and promoted BBR uptake by human colonic adenocarcinoma (Caco-2) cells via caveolae-mediated endocytosis, reducing P-gp-mediated efflux of BBR in mice gut sacs and Madin-Darby canine kidney cells stably expressing the transporter P-gp (MDCK-MDR1) cells. Moreover, the Nnps improved BBR metabolic stability in mouse intestinal S9, promoting BBR intestinal absorption in mice, as shown by increased peak BBR concentration (Cmax, 1182.3 vs 310.2 ng/mL) and exposure level (AUC0– 12 h, 2842.8 vs 1447.0 ng·h/mL) in mouse portal vein. In addition, the Nnps increased BBR exposure level in mouse livers (95,443.2 vs 43,586.2 ng·h/g liver).Conclusion: The proteinaceous nanoparticles isolated from Coptidis Rhizoma extract can form a natural nano-drug delivery system with BBR, thereby significantly improving the pharmacokinetics of oral BBR.Keywords: natural nanoparticles, drug delivery system, pharmacokinetic synergy, berberine hydrochloride, herbal extract

Yingli Tao,1 Bin Liu,2 Ying Chen,2 Yiduoduo Hu,2 Rui Zhu,3 Ding Ye,2 Yingying Mao,2 Xiaohui Sun2 1Department of Reproductive Immunology, Tongde Hospital, Hangzhou, 310012, People’s Republic of China; 2Department of Epidemiology and Biostatistics, School of Public Health, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 3Institute of Pharmacology, College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of ChinaCorrespondence: Xiaohui Sun; Yingying MaoDepartment of Epidemiology and Biostatistics, School of Public Health, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310053, People’s Republic of ChinaTel +86-571-8663-3143; +86-571-8661-3603Fax +86-571-8663-3143; +86-571-8661-3693Email 20191030@zcmu.edu.cn; myy@zcmu.edu.cnBackground: Evidence from observational studies has suggested a link between cigarette smoking and the risk of polycystic ovary syndrome (PCOS). However, it remains uncertain whether the observed relationship is causal or due to biases inherent in observational studies. Therefore, we adopted two-sample Mendelian randomization (MR) design to assess the potential causal association between smoking and the risk of PCOS.Methods: Summary level data of PCOS was obtained from a genome-wide association study (GWAS) meta-analysis including 4,138 cases and 20,129 controls of European ancestry. Single-nucleotide polymorphisms (SNPs) associated with smoking initiation (n=360) were selected and used as genetic instrumental variables (IVs). MR analysis was performed using inverse-variance weighted (IVW) method, supplemented with the likelihood-based method, weighted median method, MR pleiotropy residual sum and outlier (MR-PRESSO) test, and MR-Egger regression.Results: Genetically predicted smoking initiation was associated with an increased risk of PCOS in the primary analysis (odds ratio (OR) =1.38, 95% confidence interval (CI) =1.12– 1.69). MR-Egger regression did not detect the horizontal pleiotropy. Sensitivity analyses using alternative MR methods and restricted IVs produced similar results.Conclusion: Our study provided evidence to support a potential causal association between smoking initiation and an increased risk of PCOS, providing a better understanding of the etiology and prevention of PCOS. Further studies are warranted to clarify the underlying biological mechanisms of smoking in the development of PCOS.Keywords: causal inference, cigarette smoking, Mendelian randomization, polycystic ovary syndrome, single-nucleotide polymorphism

Dong Ye,1 Yongqin Deng,2 Zhisen Shen1 1Department of Otorhinolaryngology-Head and Neck Surgery, Lihuili Hospital of Ningbo University, Ningbo, 315040, Zhejiang, People’s Republic of China; 2Department of Otorhinolaryngology-Head and Neck Surgery, Ningbo University School of Medicine, Ningbo, 315211, People’s Republic of ChinaCorrespondence: Dong Ye; Zhisen ShenDepartment of Otorhinolaryngology-Head and Neck Surgery, Lihuili Hospital of Ningbo University, Ningbo, 315040, People’s Republic of ChinaTel +86-13819861213; +86-13906687216Fax +86-574-87392232Email yedong518@sina.com; szs7216@sina.comAbstract: Head and neck squamous cell carcinoma (HNSCC) is the most common malignant tumor of the head and neck. HNSCC mainly affects the oral cavity and the laryngeal, laryngopharyngeal, and oropharyngeal tracts. The high incidence, hidden onset, low survival rate, and unsatisfactory effects of treatment effect underscore the importance of identify the mechanisms of HNSCC occurrence and development. Although there is a very urgent need for early diagnosis and treatment, there are currently no reliable early HNSCC diagnosis biomarkers or effective treatment targets. Long non-coding RNA (lncRNA) is widely involved in biological processes, especially as a key regulator of tumorigenesis and development. Lung adenocarcinoma metastasis-associated transcript 1 (MALAT1) is an important member of the lncRNA family that can regulate the occurrence and development of a variety of malignant tumors and is anticipated to be an ideal marker for early tumor diagnosis and an effective therapeutic target. Here, we review the research progress into the role of MALAT1 in the diagnosis and treatment of HNSCC and its regulatory mechanism.Keywords: head and neck squamous cell carcinoma, MALAT1, diagnosis, treatment, mechanism

Yongqin Deng, Yujie Cao, Liuqian Wang, Dong Ye Department of Otorhinolaryngology-Head and Neck Surgery, Lihuili Hospital of Ningbo University, Ningbo, Zhejiang, 315040, People’s Republic of ChinaCorrespondence: Dong YeDepartment of Otorhinolaryngology-Head and Neck Surgery, Lihuili Hospital of Ningbo University, Ningbo, Zhejiang, 315040, People’s Republic of ChinaTel +86-138 1986 1213Fax +86-574-8739 2232Email yedong518@sina.comAbstract: The study of salivary exosomes in malignant neoplasms has attracted widespread attention in the clinical setting. Although a variety of diagnostic and treatment approaches have been proposed, there are some limitations to their application. In recent years, the role of salivary exosomes in cancer has been increasingly studied. Salivary exosomes not only renew and regulate the biological behavior of tumor cells, such as malignant proliferation, migration, and invasion, but they also serve as ideal markers for early diagnosis of diseases and may represent an effective therapeutic target. This article reviews the current research on salivary exosomes in malignant neoplasms.Keywords: liquid biopsy, exosome, malignant neoplasm, diagnosis, treatment

Objectives. Catalytically active materials are required in different chemical engineering processes. This makes the development of new materials with high efficiency and original ways in which to obtain them of significant interest. The present work investigates the synthesis of catalytically active material including electrode materials, as well as their improved efficiency due to the nanodecoration of their surface.Methods. An aluminum folio was nanoperforated (nanoscalloped) by high-voltage anodization in an acidic medium. The effective electrode material was obtained as a metallic nickel replica rather than an oxide layer of the product. To study the surface state of aluminum obtained in this manner, a scanning electron microscope (Hitachi-SU8200) was used. The elementary composition of the aluminum was determined by back-scattered X-ray irradiation.Results. The nickel replica obtained in the above-described process exceeded the catalytic activity estimated by methanol oxidation of the unprocessed nickel 70–150 times.Conclusions. The present paper demonstrates the potential of creating effective catalytically active nanopillar materials using the metallic rather than metal-oxide part of a layer of anodized aluminum as a matrix template.

Adama Ouattara,1 Abdoul-Karim Pare,1 Fasnewinde Aristide Kabore,2 Clotaire Yameogo,2 Desire Ky,2 Dramane Bayané,1 Delphine Ye,1 Timothee Kambou1 1Division of Urology, Souro Sanou Teaching Hospital, Bobo-Dioulasso, Burkina Faso; 2Division of Urology, Yalgado Ouedraogo Teaching Hospital, Ouagadougou, Burkina FasoCorrespondence: Adama OuattaraDivision of Urology, P.O. Box:1465, Bobo-Dioulasso, Burkina-FasoEmail adamsouat1@hotmail.comAim: To describe the epidemiological aspects, etiology and outcome of iatrogenic ureteral injury repair at the urology division of Souro Teaching Hospital of Bobo Dioulasso (Burkina-Faso).Patients and Methods: This was a retrospective descriptive study of consecutive patients with iatrogenic ureteric injuries who were referred and managed in the urology division of Souro Sanou Teaching Hospital (Bobo-Dioulasso) from January 2012 to December 2017. Variables studied were age, the time at the diagnosis, the causative event, the method of repair, and the outcome of the management.Results: The mean age was 37.72± 3.5 years coming from the rural population in most cases. The mean time at the diagnosis was 15 days. The injuries were due to gynecologic surgeries with hysterectomy (66%) and caesarian section (33%). Ureteric reimplantation with anti-reflux system was performed in seventeen patients. The rate of treatment success was 94% and the postoperative course was uneventful for all the patients.Conclusion: Iatrogenic ureteric lesions at the department of urology of Sanou Sourou teaching hospital of Bobo Dioulasso were mainly caused by gynecologic and obstetric surgeries like hysterectomy and caesarian section.Keywords: iatrogenic, ureter, injury, pelvic surgery

Xiaohong Quan,1,* Huihui Liu,1,* Dongmei Ye,2 Xinling Ding,3 Xiulan Su4 1Experiment & Teaching Center for Basic Medicine, Chifeng University School of Basic Medical Sciences, Chifeng, Inner Mongolia, 024000, People’s Republic of China; 2Core Facility Center for Functional Experiments, CUSBMS, Chifeng University School of Basic Medical Sciences, Chifeng, Inner Mongolia, 024000, People’s Republic of China; 3Department of Human Anatomy, CUSBMS, Chifeng University School of Basic Medical Sciences, Chifeng, Inner Mongolia, 024000, People’s Republic of China; 4Clinical Research Center for Medical Sciences, IMMU, Chifeng University School of Basic Medical Sciences, Chifeng, Inner Mongolia, 024000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaohong QuanExperiment & Teaching Center for Basic Medicine, Chifeng University School of Basic Medical Sciences, No. 1 Yingbin Road, Chifeng City, Inner Mongolia, 024000, People’s Republic of ChinaEmail quanxiaohongxh@163.comBackground: Podocyte injury serves an important role during the progression of diabetic nephropathy (DN). The aim of this study was to investigate the effects of forsythoside A (FA) on high glucose (HG)-induced podocyte injury and to identify the possible mechanisms.Methods: MPC-5 podocytes were cultured under HG conditions. After exposure to different doses of FA, cell viability and apoptosis were respectively evaluated with CCK-8 assay and flow cytometry. Then, the levels of oxidative stress-related markers and inflammatory factors were examined by corresponding kits. Western blot analysis was employed to detect the expression of Nox2, Nox4, COX-2, iNOS and matrix metalloproteinases 12 (MMP12). Subsequently, MMP12 was overexpressed to assess whether the effects of FA on HG-stimulated podocyte injury were mediated by MMP12 and MAPK signaling.Results: Results indicated that FA dose-dependently elevated cell viability, reduced cell apoptosis in HG-induced MPC-5 cells. Additionally, FA significantly inhibited oxidative stress, which could be certified by decreased content of malondialdehyde (MDA), enhanced activities of superoxide dismutase (SOD) and catalase (CAT), and downregulated expression of Nox2 and Nox4. Moreover, notably reduced levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were observed in FA-treated MPC-5 cells under HG conditions, accompanied by decreased COX-2 and iNOS expression. Remarkably, FA suppressed MMP12 expression in a dose-dependent manner, and the effects of FA on MPC-5 cells exposed to HG were partially counteracted by MMP12 overexpression. Mechanically, FA inactivated the expression of phospho-ERK (p-ERK), p-p38 and p-JNK, which was restored after MMP12 overexpression.Conclusion: These findings demonstrate a protective mechanism of FA by inactivating MAPK signaling via MMP12 inhibition in HG-induced podocyte injury, providing a promising therapeutic candidate for the treatment of DN.Keywords: diabetic nephropathy, high glucose, oxidative stress, inflammation, apoptosis

Ding Ye,1 Bin Liu,1 Zhixing He,2 Lin Huang,2 Yu Qian,1 Keding Shao,2 Chengping Wen,2 Yingying Mao1 1Department of Epidemiology and Biostatistics, Zhejiang Chinese Medical University School of Public Health, Hangzhou, Zhejiang, 310053, People’s Republic of China; 2Institute of Basic Research in Clinical Medicine, Zhejiang Chinese Medical University School of Basic Medical Sciences, Hangzhou, Zhejiang, 310053, People’s Republic of ChinaCorrespondence: Yingying MaoDepartment of Epidemiology and Biostatistics, Zhejiang Chinese Medical University School of Public Health, Hangzhou, Zhejiang, 310053, People’s Republic of ChinaTel +86-571-8661-3536Email myy@zcmu.edu.cnChengping WenInstitute of Basic Research in Clinical Medicine, Zhejiang Chinese Medical University School of Basic Medical Sciences, Hangzhou, Zhejiang, 310053, People’s Republic of ChinaTel +86-571-8663-3377Email wengcp@163.comObjective: To investigate the potential causal associations of circulating levels of growth differentiation factor 15 (GDF-15) with the risk of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) using a Mendelian randomization (MR) design.Methods: A genome-wide association study (GWAS) of GDF-15 among 5,440 individuals of European ancestry was used to identify genetic instruments. Summary statistics of SLE, RA and IBD were obtained from publicly available GWASs. We conducted an MR study using the inverse-variance weighted (IVW) method, supplemented with simple-median and weighted-median methods. Cochran Q test and MR-Egger regression were used to detect potential heterogeneity and directional pleiotropy. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated.Results: We found that genetically predicted high circulating GDF-15 levels were associated with a decreased risk of SLE (OR 0.80, 95% CI 0.68– 0.92 by IVW), with similar results in sensitivity analyses. In replication analysis using summary data from another SLE GWAS, the results were consistent (OR 0.82, 95% CI 0.71– 0.93 by IVW). Moreover, no evidence of heterogeneity or pleiotropy was detected. However, genetically determined circulating levels of GDF-15 were not associated with risk of RA or IBD in the primary analysis and subsequent sensitivity analyses.Conclusions: Our study suggested an inverse association between circulating GDF-15 levels and risk of SLE, and further studies are warranted to elucidate the underlying biological mechanisms. There was limited evidence supporting a causal association of circulating GDF-15 levels with risk of RA and IBD.Keywords: growth differentiation factor 15, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, Mendelian randomization, single nucleotide polymorphism

Enthesitis is a common clinical feature of spondyloarthritis (SpA), characterized by inflammation of the tendon or ligament attachment site to a bone or joint capsule. The importance of detecting enthesitis for the diagnosis of SpA is confirmed by its inclusion in the classification criteria for psoriatic arthritis (PsA) – CASPAR – and in the classification criteria for SpA of the international group for the study of spondyloarthritis – ASAS. Enthesitis may be the first clinical sign of SpA, as well as the leading symptom that significantly influences the therapeutic choice. Enthesitis occurs in 30–50% of patients with SpA and is associated with high disease activity, more severe pain and worse quality of life. The frequency of enthesitis detected by ultrasound in patients with PsA is approximately 4 times higher than in patients with ankylosing spondylitis and is associated with the severity of the disease. The review presents current data on the pathophysiology, diagnosis and treatment of enthesitis. Recent studies emphasize the role of imaging methods for the diagnosis of enthesitis due to their higher sensitivity and specificity compared to clinical examination. There is very limited information on the effect of synthetic disease-modifying antirheumatic drugs on enthesitis, while targeted drugs and biologic therapy have shown high efficacy in its treatment compared to placebo. Preliminary evidence suggests that targeting interleukin (IL) 17 or IL12/23 may be more effective in enthesises inflammation suppression than tumor necrosis factor α inhibition.

Qingquan Liu,1,* Yiru Wang,1,* Xuecheng Zhao,2 Lixuan Wang,2 Feng Liu,3 Tao Wang,4 Dawei Ye,5 Yongman Lv1,2 1Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China; 2Department of Health Management Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China; 3Department of Urology, Shaoyang Central Hospital, Shaoyang 422000, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China; 5Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yongman Lv; Dawei YeTongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan 430030, People’s Republic of ChinaTel +86-2783662848; +86-2783663409Fax + 86-2783662848Email lvyongman@126.com; dy0711@gmail.comBackground: The novel coronavirus disease (COVID-19) is leading to high morbidity and mortality. This aim of this study was to test whether blood urea nitrogen-to-creatinine ratio (BCR) is a predictor for mortality in patients with COVID-19.Methods: Ranges of “normal” BCR values were calculated from 9165 healthy subjects, and 337 and 79 COVID-19 patients were randomly assigned to the training cohort and the validation cohort, respectively. Prognostic factor of death incidence was selected by LASSO regression analyses. The prognostic ability of BCR range was assessed by logistic regression analysis. A nomogram for predicting in-hospital mortality based on BCR was developed. The performance of the nomogram was evaluated with respect to its calibration, discrimination, and clinical usefulness.Results: Among 337 COVID-19 patients, 13.4% and 11.3% were classified into higher and lower than normal range group, respectively. Kaplan–Meier curves for all-cause mortality showed that patients with higher BCR group had worse prognosis (P< 0.0001). BCR above the normal range was independently associated with death in COVID-19 patients (OR: 7.54; 95%CI: 1.55– 36.66; P=0.012). The nomogram had good discrimination in the training cohort (C-index 0.838; 0.795– 0.880) and the validation cohort (C-index 0.929; 0.869– 0.989), and good calibration. Using maximum Youden index, the cutoff values of 59.8 points, the sensitivity and specificity were 75.4% and 81%. Decision curve and clinical impact curve analysis demonstrated that the nomogram was clinically useful.Conclusion: BCR was a useful prognostic factor for COVID-19 patients. Development of an individualized BCR-based prediction nomogram can effectively predict the risk of mortality and help clinicians to make individual treatment early.Keywords: blood urea nitrogen, creatinine, coronavirus, COVID-19

The moss flora of the Kondinskie Lakes Natural Park named after L.F. Stashkevich (Khanty-Mansi Autonomous Okrug - Yugra, Russia) currently in-cludes 114 species. Fifty-four species (47.4%) are rare for the natural park, of which eleven species, such as Dichelyma capillaceum, Dicranum septen-trionale, Sphagnum annulatum, S. mirum, S. subfulvum, S. tenellum, are rare for the Khanty-Mansi Autonomous Okrug and Western Siberia. The phytocenotic association and the frequency of oc-currence of the studied species was analyzed. The paper discusses the reasons for the high proportion of rare mosses in the park’s brioflora and the fea-tures of their distribution over the territory of the park.

A comparative analysis has been performed in this work for low temperature strength of 31 types of the conventional (non-modified) and modified road asphalt concretes. The neat bitumens of the grades BND 70/100, BND 100/130 and BND 130/200 have been produced by the Pavlodar petrochemical plant from the crude oil of the Western Siberia (Russia) by the method of direct oxidation and they satisfy the requirements of the standard ST RK 1373-2013. The polymers Elvaloy 4170, Elvaloy AM, Kraton, Calprene 501, Butonal NS, SBS (L 30-01 A), KUMHO KTP and crumb rubber have been used for the modification of the bitumens. The modification of the bitumens has been performed in the laboratory of Kazakhstan Highway Research Institute. The modified bitumens satisfy the requirements of the standard ST RK 2534-2015. The conventional and modified asphalt concretes satisfy the requirements of the standards ST RK 1225-2019, ST RK 1223-2019, ST RK 2028-2010, ST RK 2373-2019 and GOST 31015-2002. The strength of the asphalt concretes at uniaxial direct tension at a constant strain rate of 1 mm/min at the temperatures of -10 °С, -20 °С and -30 °С determined in the device TRAVIS under the standard EN 2697-46 has been accepted as a characteristic of their low temperature strength. It is found out that various modifiers affect the asphalt concrete strength in different ways: a degree of impact depends both on a type of an asphalt concrete and a modifier, as well as on a negative temperature value. Some modifiers increase, and some of them decrease the strength of the asphalt concretes at low temperatures compared with the original asphalt concretes. Among the modifiers the polymer Elvaloy AM has been found to be the most efficient at low temperatures. The asphalt concretes of type B with the bitumens of grades BND БНД 100/130 and BND 130/200 at modification by the polymer Elvaloy AM had the biggest strength at all the considered low temperatures: at -10 ºC – 6.79 MPa and 6.43 MPa; at -20 ºC – 7.57 MPa and 7.87 MPa; at -30 ºC – 7.35 MPa and 8.86 MPa. The stone mastic asphalt concretes 15 and 20 with the polymers and without them at all the considered low temperatures practically had the strength not higher than the basic asphalt concretes of type B with neat (original) bitumens of grades BND 100/130 and BND 130/200.

Еру primary Sjogren’s Syndrome (PSS) is a chronic autoimmune disease of unknown etiology with the specific predisposition to the occurrence of exocrine gland inflammation. This disease is characterized by the presence of the sicca syndrome and systemic manifestations, including inflammatory arthritis, skin lesions, hematological disorders, neuropathies, interstitial lung disease. Systemic manifestations occur in 70 % of patients with PSS. In addition, such patients are characterized by a high risk of developing B-cell lymphoma, comprising 5 — 10 %. Over the past decade, a series of practical guidelines for managing patients with PSS have been published, based on the systematic reviews involving both experts and patients. This literature review on the treatment of PSS is based on an analysis of current recommendations, systematic reviews, and clinical studies. Treatment stratification aims to alleviate symptoms, stimulate secretion, prevent damage, and suppress the activity of a systemic disease. The first-line therapy for treating dry eye syndrome should be volume replacement and lubrication using artificial tear preparations and eye gels, the main components of which should be lubricants with a polymer base or agents. With systemic involvement, glucocorticoids (GC) should be used in the minimum dose and for the period of time necessary to control an active systemic disease, pulse therapy with methylprednisolone followed by 0.5 mg/kg per day or less can be considered as induction therapy for severe manifestations, and doses

Dan Ye, Hao-Ran Shen, Liangqing Yao Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, People’s Republic of ChinaCorrespondence: Liangqing YaoObstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, People’s Republic of ChinaTel/Fax +86-021-33189900Email sherryye1217@163.comBackground: Thinking of the rarity and malignancy of gynecologic tract carcinosarcomas (GTCS), the aim of the study was to investigate the possible predictors of relapse-free survival (RFS) and overall survival (OS) for GTCS patients.Methods: We performed a retrospective cohort study of women with GTCS at our hospital between January 2009 and December 2013. We used the Kaplan–Meier method to calculate RFS and OS, and Cox regression analysis to define the survival effects of risk factors.Results: A total of 45 GTCS patients were included in the study. The median follow-up time was 46 months. Cox regression analysis showed that lymph node metastasis was significantly associated with worse RFS (HR: 3.145; 95%CI: 1.181– 8.378; P=0.022) and OS (HR: 4.065; 95%CI: 1.57– 10.524; P=0.004). Pelvic lymphadenectomy had a favorable RFS (HR: 0.213; 95%CI: 0.057– 0.796; P= 0.021).Conclusion: Lymph node metastasis significantly affected the prognosis of uterine carcinosarcoma. Pelvic lymphadenectomy could reduce the relapse rate of GTCS patients.Keywords: pelvic lymphadenectomy, relapse-free survival, overall survival, gynecologic tract carcinosarcomas

Background: Innovations in treatments, imaging, and molecular characterisation in advanced prostate cancer have improved outcomes, but various areas of management still lack high-level evidence to inform clinical practice. The 2021 Advanced Prostate Cancer Consensus Conference (APCCC) addressed some of these questions to supplement guidelines that are based on level 1 evidence. Objective: To present the voting results from APCCC 2021. Design, setting, and participants: The experts identified three major areas of controversy related to management of advanced prostate cancer: newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC), the use of prostate-specific membrane antigen ligands in diagnostics and therapy, and molecular characterisation of tissue and blood. A panel of 86 international prostate cancer experts developed the programme and the consensus questions. Outcome measurements and statistical analysis: The panel voted publicly but anonymously on 107 pre-defined questions, which were developed by both voting and non-voting panel members prior to the conference following a modified Delphi process. Results and limitations: The voting reflected the opinions of panellists and did not incorporate a standard literature review or formal meta-analysis. The answer options for the consensus questions received varying degrees of support from panellists, as reflected in this article and the detailed voting results reported in the Supplementary material. Conclusions: These voting results from a panel of experts in advanced prostate cancer can help clinicians and patients to navigate controversial areas of management for which high-level evidence is scant. However, diagnostic and treatment decisions should always be individualised according to patient characteristics, such as the extent and location of disease, prior treatment(s), comorbidities, patient preferences, and treatment recommendations, and should also incorporate current and emerging clinical evidence and logistic and economic constraints. Enrolment in clinical trials should be strongly encouraged. Importantly, APCCC 2021 once again identified salient questions that merit evaluation in specifically designed trials. Patient summary: The Advanced Prostate Cancer Consensus Conference is a forum for discussing current diagnosis and treatment options for patients with advanced prostate cancer. An expert panel votes on predefined questions focused on the most clinically relevant areas for treatment of advanced prostate cancer for which there are gaps in knowledge. The voting results provide a practical guide to help clinicians in discussing treatment options with patients as part of shared decision-making. © 2022 The Author(s)

This PhD thesis focuses on the non-intrusive and semi-intrusive uncertainty quantification (UQ) analysis of the in-stent restenosis (ISR) multiscale model. We study the uncertainty forward propagation problems and apply various surrogate modelling techniques, such as reduced-order modelling and Gaussian process to reduce the expensive computational cost of the multiscale model in the UQ. In Chapter 2, a comparison of non-intrusive and semi-intrusive UQ methods based on the ISR2D model is presented and discussed. The results on uncertainty propagation allow us to draw conclusions on the advantages and limitations of these methods. A UQ of ISR3D with four biological uncertain parameters is studied in Chapter 3. A surrogate model, based on Gaussian process regression with proper orthogonal decomposition, was developed and subsequently used for model response evaluation in the UQ. A detailed analysis of the uncertainty propagation and sensitivity analysis is presented. Chapter 4 presents a data-driven surrogate model for blood flow simulations in unparameterised vessels. The surrogate model is based on non-intrusive reduced-order modelling and surface registration. Two examples of blood flow through a stenosis and a bifurcation are analysed. Chapter 5 introduces a series of UQ patterns for efficient UQ of multiscale models, and categorises them by the level of intrusiveness and optimization method. We demonstrate how these patterns can be implemented in multiscale models, using the formalism of the multiscale modelling and simulation framework.

The authors regret that Axel Heidenreich was added to the author list in error. The author list is now corrected as above, however the affiliations of remaining authors have been retained. The authors would like to apologise for any inconvenience caused. © 2022 The Author(s)

In multi-agent reinforcement learning, transfer learning is one of the key techniques used to speed up learning performance through the exchange of knowledge among agents. However, there are three challenges associated with applying this technique to real-world problems. First, most real-world domains are partially rather than fully observable. Second, it is difficult to pre-collect knowledge in unknown domains. Third, negative transfer impedes the learning progress. We observe that differentially private mechanisms can overcome these challenges due to their randomization property. Therefore, we propose a novel differential transfer learning method for multi-agent reinforcement learning problems, characterized by the following three key features. First, our method allows agents to implement real-time knowledge transfers between each other in partially observable domains. Second, our method eliminates the constraints on the relevance of transferred knowledge, which expands the knowledge set to a large extent. Third, our method improves robustness to negative transfers by applying differentially exponential noise and relevance weights to transferred knowledge. The proposed method is the first to use the randomization property of differential privacy to stimulate the learning performance in multi-agent reinforcement learning system. We further implement extensive experiments to demonstrate the effectiveness of our proposed method.

With extensive applications and remarkable performance, deep reinforcement learning is becoming one of the most important technologies that researchers have been focusing on. Many applications have used reinforcement learning, such as robotics, recommendation systems, and healthcare systems. These systems could collect data about the environment or users, which may contain sensitive information that posed a real risk when these data were disclosed. In this work, we aim to preserve the privacy of the data used in deep reinforcement learning with Double Deep-Q-Network in continuous space by adopting the differentially private SGD method to inject a noise to the gradient. In our experiment, we used a different amount of noise on two separate settings to demonstrate how effective of using this method.

Liping Li, Dan Ye, Liang Liu, Xiaoju Li, Jun Liu, Shengtian Su, Wenjing Lu, Zhigao Yu Department of Oncology, Xiantao First People’s Hospital, Xiantao, Hubei, People’s Republic of ChinaCorrespondence: Zhigao YuDepartment of Oncology, Xiantao First People’s Hospital, No. 29, Middle Section of Mianzhou Avenue, Xiantao, Hubei 433000, People’s Republic of ChinaTel +86 13477410999Email zhongjiyi330108@126.comPurpose: Non-small cell lung cancer (NSCLC) is a typical epithelial lung cancer with high metastasis, incidence and mortality. In recent years, long noncoding RNA small nucleolar RNA host gene 7 (SNHG7) has been identified as significant regulator in different cancer types, including NSCLC. However, the underlying molecular mechanism of SNHG7 during NSCLC tumorigenesis and progression remains largely unclear.Methods: SNHG7 and miR-181a-5p expression in NSCLC tumors and cells were detected by qRT-PCR. Cell viability, migration, invasion and apoptosis were evaluated by CCK-8, transwell and flow cytometry assay, respectively. A549 and NCI-H1299 xenograft mice model was constructed by subcutaneously injecting cells stably transfected with sh-SNHG7 and sh-NC. The interaction between SNHG7 and miR-181a-5p was validated by luciferase reporter system, RIP and RNA pull down assay. Protein expression of cleaved caspase 3, proliferating cell nuclear antigen (PCNA), AKT, p-AKT, mammalian target of rapamycin (mTOR) and p-mTOR was analyzed by Western blot.Results: SNHG7 expression was up-regulated while miR-181a-5p expression was down-regulated in NSCLC tumors, especially those from patients at Phase III+IV, compared with normal tissues. However, SNHG7 depletion attenuated tumor growth in vitro and in vivo. Moreover, miR-181a-5p inhibitor abolished SNHG7 silencing induced inhibition on proliferation, migration and invasion in NSCLC. Subsequently, we found SNHG7 modulated cell progression by targeting miR-181a-5p and activating AKT/mTOR signaling pathway.Conclusion: SNHG7 accelerates proliferation, migration and invasion of NSCLC by suppressing miR-181a-5p through AKT/mTOR signaling pathway, thus presenting desirable biomarkers for NSCLC therapy.Keywords: NSCLC, SNHG7, miR-181a-5p, AKT/mTOR pathway, progression

Yichun Wang,1,* Dongmei Ye,2,* Mei Kang,1 Liyang Zhu,1 Shuhao Pan,1 Fan Wang1 1Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, People’s Republic of China; 2Department of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fan Wang Tel +86-055162923541Email wangfan1965@126.comBackground: We aimed to identify the suitable indication and delineate the target volume based on the pattern of abdominal lymph node recurrence (ALNR) after radical surgery for guiding postoperative radiotherapy in thoracic esophageal squamous cell cancer (TESCC).Methods: Clinical data of patients with locally advanced TESCC after radical surgery without perioperative anti-tumor therapies from June 2011 to June 2016 were reviewed. Logistic regression analysis was used to find out the high-risk factors of ALNR. The pattern of ALNR was analysed and a template CT in the Pinnacle treatment plan system was used to reconstruct the distribution of the sites of ALNR.Results: A total of 63 (19.57%) patients with 276 lymph nodes of ALNR were identified in 322 patients. Univariate logistic regression indicated that pathological tumor location, width of tumor, T stage, N stage, TNM stage, ratio of lymph node metastasis (LNM), vessel carcinoma embolus, cancerous node, LNM in the middle and lower mediastinum, LNM in the abdominal region, ratio of LNM in the abdominal region were risk factors of ALNR. Multivariate logistic regression analysis showed that only LNM in the abdominal region was an independent risk factor. The odds ratio was 7.449 (95% CI=2.552– 22.297, P< 0.001). Station 16a2, station 9, station 16b1, and station 8 were the major regions of ALNR. The recurrence rates were 10.56%, 9.63%, 7.14% and 5.28% in these stations, respectively.Conclusion: Positive pathological abdominal lymph nodes should be the major indication for abdominal irradiation in postoperative radiotherapy for locally advanced TESCC. We recommended that the target volume includes station 8, station 9, station 16a2 and station 16b1 and proposed a specific delineation of the clinical target volume based on the distribution of ALNR on template CT images.Keywords: esophageal carcinoma, clinical target volume, recurrence, postoperative radiotherapy, abdominal lymph nodes

Extensive experience in operating nuclear power plants convincingly proves that fast liquid metal cooled reactors are among the most promising. The advantages of using liquid lead coolants in nuclear power industry are shown. In Russia, lately, much attention has been paid to the natural safety of fast reactors. At the stage of testing materials for components of reactor plants, a number of problems arose for basic systems. An experimental lead-cooled installation was developed for testing large structures, continuous monitoring and maintaining specified technical parameters. For reliable coolant circulation (lead coolant circulation speed up to 200 kg/s), a magnetohydrodynamic pump (MHD pump) has been developed, which is distinguished by high efficiency and reliability, it is also ease in operation and maintenance. Currently, the experimental setup is successfully used in scientific research of materials for RU BREST-OD-300. All its systems showed high reliability, maintainability and the possibility of further modernization.

Yao Zhu,1,2 Dingwei Ye1,2 On behalf of the Expert Group1Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical School, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Dingwei YeDepartment of Oncology, Shanghai Medical School, Fudan University, No. 270 Dongan Road, Shanghai 200032, People’s Republic of ChinaTel +86 13 701663571Email dwyeli@163.comAbstract: Currently, the basic treatment of advanced prostate cancer is still endocrine therapy, but almost all patients eventually progress to castration-resistant prostate cancer (CRPC). In 2016, the Chinese Expert Consensus on the Diagnosis and Treatment of CRPC which aimed to help Chinese clinicians formulate treatment plans for CRPC was published. In this 2019 update, the 2016 version was updated with the aim of providing a more appropriate reference for clinical practice, standardizing CRPC patient management, and facilitating decision-making. The consensus is evidence-based and reviews the optimal therapeutic recommendations for CRPC management in China by taking into consideration the clinical characteristics of Chinese patients; drug availability, efficacy and safety; and recent advancements and developments in the international medical arena.Keywords: prostate cancer, castration-resistant, metastases, treatment, expert consensus

The term cryoglobulinemia (CG) is used when detecting serum immunoglobulins that reversibly precipitate and form a gel at a temperature below 37 °C and dissolve when the temperature rises above 37 °C. Type I CG consists of only one isotype or a subclass of monoclonal immunoglobulins, while types II and III are classified as mixed CG (MCG) that is primarily characterized by the presence of immunoglobulins G and M. Types II and II-III MCG can result in cryoglobulinemic vasculitis (CGV) more frequently, whereas type III can lead to this condition less frequently. The presence of type I cryoglobulins is always associated with B-cell lymphoproliferative diseases. On the contrary, type II or type III MCG is more commonly associated with systemic autoimmune diseases and chronic infections. Thus, hepatitis C virus infection contributes to the development of MCG in 80–90% of cases. CGV is considered a rare disease worldwide (

Wen Liu,1 Wenxian Li,1 Zhankun Wang,2 Yao Zhu,3 Dingwei Ye,3 Guiming Zhang1 1Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2Department of Urology, Qingdao Eighth People’s Hospital, Qingdao, People’s Republic of China; 3Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of ChinaCorrespondence: Guiming ZhangDepartment of Urology, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Qingdao 266003, People’s Republic of ChinaTel +86-532 82913056Fax +86-532 82911999Email zhangguiming9@126.comBackground: To investigate the pathological risk of prostate cancer (PCa) according to the obesity and metabolic status of Chinese patients undergoing radical prostatectomy.Materials and Methods: We performed a retrospective cross-sectional study of 1016 patients with PCa who underwent radical prostatectomy and whose metabolic status and body mass index were examined. Multivariate logistic regression analysis was performed to examine the relationship between different metabolic obesity phenotypes and the pathological outcomes of PCa.Results: Among 1016 men, 551 (54.2%), 106 (10.4%), 238 (23.4%), and 121 (11.9%) were assigned to the metabolically healthy and normal weight (MHNW) group, metabolically abnormal but normal weight (MANW) group, metabolically healthy but overweight or obese (MHO) group, and metabolically abnormal and overweight or obese (MAO) group, respectively. Compared with the MHNW group, the MAO group had a significantly greater risk of a higher prostatectomy Gleason score [odds ratio (OR), 1.907; 95% confidence interval (95% CI), 1.144– 3.182], pathological stage (OR, 1.606; 95% CI, 1.035– 2.493), and seminal vesicle invasion (OR, 1.673; 95% CI, 1.041– 2.687). In contrast, the ORs were not increased in the MHO or MANW group. In the context of normal weight, metabolic disorders were associated with lymph node involvement. The metabolic status and body mass index were not associated with extracapsular extension or surgical margins in any of the four groups.Conclusion: The MAO phenotype is associated with aggressive PCa, including a higher prostatectomy Gleason score, pathological stage, and seminal vesicle invasion and might also be associated with disease progression. Obesity and metabolic disorders act synergistically to increase the pathological risk of PCa.Keywords: prostate cancer, obesity, metabolic syndrome, pathology, Gleason score

Si-si Wang, Dao-xiong Ye, Bo Wang, Chao Xie Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, The People’s Republic of ChinaCorrespondence: Dao-xiong YeDepartment of General Surgery, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, Fujian Province 350001, The People’s Republic of ChinaTel/Fax +86-591-86218015Email daoxiongy@163.comPurpose: Primary squamous cell carcinoma is a rare malignancy in the thyroid gland (SCCTh). The overall prognosis of this carcinoma is poor. This study aimed to explore the application of Raman spectroscopy in investigating the expression of CK5/6 and P63 in SCCTh.Patients and Methods: Tissues of the SCCTh and adjacent normal thyroid, as well as blood serum, were collected from a patient with pathology-confirmed SCCTh. Whole genome sequencing analysis was performed with the tissue of the SCCTh. The expressions of keratins and TP53 family gene were investigated by the Raman spectroscopy in tissues of the SCCTh and adjacent normal thyroid. The serum was also investigated by the Raman spectroscopy for the expression of keratins and TP53 family gene.Results: The whole genome sequencing analysis identified the mutation of the TP53 gene (42%) in the tissues of SCCTh. Accordingly, the Raman spectra analyses showed higher expression of keratins and TP53 family gene in the tissues of SCCTh compared with that in the adjacent normal thyroid. Raman spectra analyses of the serum of the patient also showed the expressions of the keratins and TP53 family gene.Conclusion: The expressions of the keratins and TP53 are different in the tissues of SCCTh and adjacent normal thyroid, and the difference could be identified with high sensitivity by the Raman spectra analyses.Keywords: SCCTh, thyroid neoplasms, CK5/6, P53, Raman spectrum analysis

The article discusses experimental studies of the formation of vibration accelerations in the axial direction on axles with driven and driven standard cylindrical double-flange travel wheels. The study of the formation of vibration signs was carried out during the movement of the cargo carriage of an overhead crane, both without load and with a load of various weights. Traveling wheels are the fastest wearing parts of an overhead crane. A decrease in the time of their operation leads to an increase in the monetary costs of repair work to restore the running wheels or replace them. Therefore, for modern crane construction, a very urgent task is to increase the service life of crane traveling wheels due to their modernization. The designs of crane traveling wheels are currently quite rigid and do not perceive distortions and shocks that arise when the rail track deviates from the recommended values. This leads to significant wear on the rails, as well as on the flanges of the crane traveling wheels. To check the previously obtained theoretical data, an experimental study was carried out on an overhead crane with a lifting capacity of 5 tons, a span of 22.5 m, a lifting height of 8 m, an operating mode of 7 K. drive standard running wheels of the overhead crane trolley. Also, the analysis of the regularity of the formation of vibration signs during the movement of the cargo trolley of an overhead crane at various speeds, as well as in its various operating modes, is carried out. The level of vibration accelerations in the axial direction on the axles of the wheels with an increase in the weight of the load demonstrates multidirectional tendencies. For the drive wheel, the RMS vibration is reduced compared to a smaller load case (30% between 0.5 tones and 2.0 tones), and approaches the value of vibration levels at idle speed.

Xuan Zhou, 1,* Huihui Ji, 2,* Dongxue Ye, 2 Hong Li, 1 Fen Liu, 2 Haiyan Li, 2 Jin Xu, 1 Yujun Li, 1 Fenggang Xiang 1, 2 1Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao 266000, People’s Republic of China; 2Department of Pathology, School of Basic Medicine, Qingdao University, Qingdao 266071, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fenggang XiangDepartment of Pathology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao 266000, People’s Republic of ChinaEmail xiangfenggang0532@163.comIntroduction: The aim of the present study was to examine the expression of ATAD2 in gastric cancer (GC) specimens and to evaluate its correlation with clinicopathologic features, including survival of GC patients. The potential roles of ATAD2 in the GC cell proliferation, apoptosis, and tumour growth were further explored.Materials and Methods: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting and immunohistochemistry (IHC) were applied to determine the mRNA and protein expression of ATAD2 in GC and corresponding adjacent non-tumourous specimens. The relationship between ATAD2 expression and clinicopathological features of GC patients was analysed. Kaplan-Meier analysis was performed to assess the prognostic value of ATAD2 expression levels. The proliferation, colony formation, apoptosis and tumorigenesis roles of ATAD2 were measured using in vitro and in vivo experiments.Results: The expression of ATAD2 mRNA and protein was overexpressed in GC tissues compared with corresponding adjacent non-tumourous tissues. ATAD2 expression was significantly correlated with tumour size, tumour differentiation, and clinical tumour-node-metastasis (TNM) stage. Patients with high ATAD2 expression were likely to experience significantly shorter postoperative overall survival (OS) and disease-free survival (DFS). Multivariate Cox analysis suggested ATAD2 as an independent variable for OS and DFS. Knockdown of ATAD2 significantly suppressed cell proliferation, colony formation in vitro and tumorigenicity in vivo. Cell cycle and apoptotic assays showed that the anti-proliferative effect of pLV-ATAD2 shRNA was mediated by arresting cells in the G1 phase and inducing cell apoptosis. Silencing of ATAD2 reduced the expression of cyclinD1, ppRb, E2F1 and cyclinE and upregulated the expression of cleaved-PARP and cleaved-Caspase 3.Conclusion: Our study indicated that ATAD2 plays an important role in the process of tumorigenesis and progression in GC, and it could serve as a novel prognostic biomarker and a therapeutic target for the treatment of GC patients.Keywords: ATAD2, gastric cancer, proliferation, apoptosis, prognosis