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About Vladimir Ilyich as a scientist, colleague, teacher and person are told by those who had the opportunity to cooperate with him at different times. His memories reflect his main personal characteristics: passionate devotion to the cause of science, integrity and attitude to people.

Qian Zhou,1 Hao Wang,2 Tianxiang Zhan,2 Xiaofeng Yang,1,2 Liang Wen2 1Department of Emergency and Trauma Center, The International Medical Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310003, People’s Republic of China; 2Department of Neurosurgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310003, People’s Republic of ChinaCorrespondence: Liang WenDepartment of Neurosurgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, Zhejiang Province, People’s Republic of ChinaEmail wenliang@zju.edu.cnXiaofeng YangDepartment of Emergency and Trauma Center, The International Medical Center, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, Zhejiang Province, People’s Republic of ChinaEmail zjcswk@zju.edu.cnBackground: Central nervous system (CNS) infections caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacillus, including carbapenem-resistant Enterobacteriaceae (CRE) and Pseudomonas aeruginosa, are associated with high mortality rates. Clinical trials of ceftazidime/avibactam (CAZ/AVI) on infections of other systems indicate that they are effective against these infections. However, clinical studies on the efficacies of CAZ/AVI in the treatment of CNS infections have not been done.Case Presentation: We evaluated 3 patients diagnosed with MDR/XDR Gram-negative bacillus-associated CNS infections, and effectively treated with CAZ/AVI. Moreover, we performed literature reviews. Before the onset of CNS infections, the 3 patients were subjected to neurosurgical operations, treated with mechanical ventilation, long-term intensive care unit therapy, and various antibiotics. By intravenously administering CAZ/AVI, combined with another antibiotic, the MDR/XDR K. pneumoniae and P. aeruginosa associated ventriculitis was effectively treated in the 3 patients.Conclusion: CAZ/AVI is a viable treatment option for CNS infections caused by MDR/XDR Gram-negative bacteria.Keywords: ceftazidime–avibactam, extensively drug-resistant Gram-negative bacillus, Klebsiella pneumoniae, Pseudomonas aeruginosa, ventriculitis infection

Zhan T, Zhu Q, Han Z, et al. Cancer Manag Res. 2020;12:1483–1492. The authors have advised Figure 4C on page 1490 is incorrect. Due to an error at the time of figure assembly Figure 4D and Figure 4C were inadvertently duplicated. The correct Figure 4 is shown below. Figure 4 miR-455-3p restrains Wnt/β-catenin signaling via TAZ. (A and B) Expression of β-catenin, Cyclin D and C-myc in pancreatic cancer cells transfected with miR-455-3p mimic or miR-455-3p mimic plus TAZ expression vector was detected by qPCR. (C and D) Western blot analysis of β-catenin, Cyclin D and C-myc in PANC1 and MIAPaCa2 cells transfected with miR-455-3p mimic or miR-455-3p mimic plus TAZ expression vector β-actin is used as loading control vs miR-455-3p mimics/mimic control group, miR-455-3p mimics/miR-455-3p mimics+TAZ group. *p

Xia Tian,* Meng Liu,* Xiaodong Huang, Qingxi Zhu, Weijie Liu, Wei Chen, Yanli Zou, Yishan Cai, Shasha Huang, Aifang Chen, Ting Zhan, Min Huang, Xiaoli Chen, Zheng Han, Jie Tan Department of Gastroenterology, Tongren Hospital of Wuhan University (Wuhan Third Hospital), Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zheng Han; Jie Tan Email 422435466@qq.com; 549774892@qq.comBackground: Noscapine is an opium alkaloid that has recently been shown to potentiate anti-cancer therapeutic effects by inducing apoptosis in various malignant cells without any detectable toxicity. However, the mechanism by which noscapine induces apoptosis in colon cancer cells remains unclear.Materials and Methods: In this study, we explored the anti-cancer activity of noscapine in 5-fluorouracil (5-FU)-resistant human colon cancer cell lines HT29/5-FU and LoVo/5-FU and investigated the possible underlying mechanism. The apoptosis and mitochondrial morphology of cells were detected by TUNEL assay and transmission electron microscopy (TEM). The mitochondrial membrane potential (MMP) was determined using JC-1. The mitochondrial permeability transition pore (mPTP) opening was detected by the calcein-AM/cobalt assay. The levels of glucose, lactic, and ATP in cells were evaluated by ELISA kits. Relative protein expression levels were detected by Western blot.Results: We verified that PTEN was involved in noscapine-induced apoptosis in HT29/5-FU and LoVo/5-FU cells. Noscapine greatly increased mitochondrial damage by altering mitochondrial morphology, inducing mitochondrial membrane potential depolarization, and enabling mitochondrial permeability transition pore opening in HT29/5-FU and LoVo/5-FU cells. In addition, noscapine inhibited the Warburg effect by decreasing the levels of glucose, lactic acid, and ATP and inhibiting the protein expression of glucose transporter 1, lactate dehydrogenase-B, hexokinase 2, and pyruvate kinase M2 in HT29/5-FU and LoVo/5-FU cells. However, PTEN interference counteracted the effect of noscapine on mitochondrial damage and the Warburg effect in HT29/5-FU and LoVo/5-FU cells by decreasing the activation of PI3K/mTOR signaling.Conclusion: These results indicated that noscapine induced the apoptosis of HT29/5-FU and LoVo/5-FU human colon cancer cells by regulating mitochondria damage and the Warburg effect via PTEN, and the process is closely related to the PI3K/mTOR signaling pathway.Keywords: colon cancer, noscapine, mitochondrial damage, PTEN, PI3K/mTOR

Ting Zhan, 1,* Qingxi Zhu, 1,* Zheng Han, 1 Jie Tan, 1 Meng Liu, 1 Weijie Liu, 1 Wei Chen, 1 Xiaoli Chen, 1 Xueting Chen, 2 Junsheng Deng, 2 Xia Tian, 1 Xiaodong Huang 1 1Department of Gastroenterology, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan 430060, People’s Republic of China; 2Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaodong Huang; Xia Tian Tel +86 1388619054; +86 13871480868Email 13297056720@163.com; hcwy100@163.comBackground: Pancreatic cancer (PC) is a highly invasive tumor with a poor prognosis, short overall survival rate and few chemotherapeutic choices. Despite the importance of finding ways to treat pancreatic cancer, the mechanisms of tumor progression have not been fully elucidated. microRNA-455-3p (miR-455-3p) has been reported to play an important role in several cancers, but its function in pancreatic cancer remains unclear.Methods: To investigate the biological functions, miRNAs mimics or inhibitors were transfected into pancreatic cancer cells. Flow cytometry was used to detect cell apoptosis. Wound healing and Transwell assays were employed to observe cell invasion and migration abilities. The expression of Bcl-2, Bax, caspase-3, E-cadherin, N-cadherin, Snail, β-Catenin, c-Myc and Cyclin D1 were evaluated by qPCR and Western blot.Results: We confirmed that inhibition of miR-455-3p decreases cell apoptosis and increases cell migration, invasion and EMT of pancreatic cancer, whereas forced overexpression of miR-455-3p has the opposite effect. Furthermore, we demonstrated that the tumor suppression effects of miR-455-3p were partially reversed by TAZ overexpression. In addition, miR-455-3p led to inactivation of Wnt/β-catenin signaling in pancreatic cancer cells, and TAZ overexpression restored the inhibition of Wnt/β-catenin signaling.Conclusion: Taken together, our data demonstrated that miR-455-3p functions as an important tumor suppressor that suppresses the Wnt/β-catenin signaling pathway via TAZ to inhibit tumor progression in pancreatic cancer. We conclude that the miR-455-3p/TAZ/Wnt axis may be a potential therapeutic target for pancreatic cancer.Keywords: miR-455-3p, Wnt, apoptosis, metastasis, EMT

Zhiyu Dong, Junwen Wang, Tingting Zhan, Shuchang Xu Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China Purpose: Esophageal adenocarcinoma (EAC) is the most common type of esophageal cancer in Western countries. It is usually detected at an advanced stage and has a poor prognosis. The aim of this study was to identify key genes and miRNAs in EAC. Methods: The mRNA microarray data sets GSE1420, GSE26886, and GSE92396 and miRNA data set GSE16456 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were obtained using R software. Functional enrichment analysis was performed using the DAVID database. A protein–protein interaction (PPI) network and functional modules were established using the STRING database and visualized by Cytoscape. The targets of the DEMs were predicted using the miRecords database, and overlapping genes between DEGs and targets were identified. The prognosis-related overlapping genes were identified using Kaplan–Meier analysis and Cox proportional hazard analysis based on The Cancer Genome Atlas (TCGA) database. The differential expression of these prognosis-related genes was validated using the expression matrix in the TCGA database. Results: Seven hundred and fifteen DEGs were obtained, consisting of 313 upregulated and 402 downregulated genes. The PPI network consisted of 281 nodes; 683 edges were constructed and 3 functional modules were established. Forty-four overlapping genes and 56 miRNA–mRNA pairs were identified. Five genes, FAM46A, RAB15, SLC20A1, IL1A, and ACSL1, were associated with overall survival or relapse-free survival. FAM46A and IL1A were found to be independent prognostic indicators for overall survival, and FAM46A, RAB15, and SLC20A1 were considered independent prognostic indicators for relapse-free survival. Among them, the overexpression of RAB15 and SLC20A1 and lower expression of ACSL1 were also identified in EAC tissues based on the expression matrix in the TCGA database. Conclusion: These prognosis-related genes and differentially expressed miRNA have provided potential biomarkers for EAC diagnosis and treatment. Keywords: esophageal adenocarcinoma, differential expression genes, functional enrichment analysis, Kaplan–Meier analysis, Cox proportional hazard analysis

Ж.Т. Тощенко: «У нашего журнала — время акме…» / Интервью подготовила Л.А. Козлова

Abstract Sirolimus (SR) is a macrolide with antifungal and antitumor immunosuppressant properties, classified as a selective inhibitor of mammalian target of rapamycin (mTOR). In this study, an ionic in situ gel of SR (SR-SUS-ISG) was formulated using gellan gum, exhibiting stability regardless of temperature and pH variations, causing minimal irritation. Harnessing the physiological conditions of the eye, SR-SUS-ISG underwent gelation upon contact with ions, increasing drug viscosity and prolonging retention on the ocular surface. Concurrently, SR-SUS-ISG displayed favorable shear dilution properties, reducing viscosity at ambient temperature, enhancing fluidity, and facilitating convenient packaging and transport. Biocompatibility assessments on both human corneal epithelial cells and rabbit eyes demonstrated that SR-SUS-ISG could well be tolerated. Pharmacokinetic investigations in rabbit ocular aqueous humor revealed sustained release, improved corneal penetration, and enhanced bioavailability. Additionally, in a rat corneal alkali burn model, SR-SUS-ISG exhibited inhibitory effects on corneal neovascularization, associated with decreased levels of the inflammatory factors VEGF and MMPs. These findings suggested that SR-SUS-ISG held promise as an effective ocular drug delivery system. Graphical Abstract

Abstract The accurate perception of multiple flight parameters, such as the angle of attack, angle of sideslip, and airflow velocity, is essential for the flight control of micro air vehicles, which conventionally rely on arrays of pressure or airflow velocity sensors. Here, we present the estimation of multiple flight parameters using a single flexible calorimetric flow sensor featuring a sophisticated structural design with a suspended array of highly sensitive vanadium oxide thermistors. The proposed sensor achieves an unprecedented velocity resolution of 0.11 mm·s−1 and angular resolution of 0.1°. By attaching the sensor to a wing model, the angles of attack and slip were estimated simultaneously. The triaxial flight velocities and wing vibrations can also be estimated by sensing the relative airflow velocity due to its high sensitivity and fast response. Overall, the proposed sensor has many promising applications in weak airflow sensing and flight control of micro air vehicles.

In view of bottlenecks encountered in the process of turnout laying and replacement on high-speed railways such as substantial construction difficulties, low efficiency, intensive labor workload, and high risk, this paper proposes a control method of intelligent turnout laying and replacement equipment with combined gantry cranes for high-speed railways. It is proposed to utilize a control strategy of asynchronous transverse movement and synchronous tilting of the combined gantry cranes to handle the rotation and longitudinal motion of large components respectively. A theoretical mathematical modeling analysis is performed for the turnout laying and replacement equipment with combined gantry cranes focusing on the rotation and longitudinal movement operations. Moreover, considering the flexible nature of chains in the real construction process of combined gantry cranes, a self-learning algorithm is incorporated to facilitate flexible and highly precise multi-crane cooperative micro-motion control. The experimental results from field operations showcases adopting the control method proposed in this article, stable and reliable rotation and longitudinal movement by the combined gantry cranes, with an operational error of less than 10 mm, achieving full compliance with the requirements of engineering applications demonstrates.