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Xiaolan Guo,1 Dansen Wu,1 Xiaoping Chen,2 Jing Lin,1 Jialong Chen,1 Liming Wang,1 Songjing Shi,1 Huobao Yang,1 Ziyi Liu,3 Donghuang Hong1,4 1Department of Critical Care Medicine, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, People’s Republic of China; 2Computer Science and Mathematics, Fujian University of Technology, Fuzhou, Fujian, People’s Republic of China; 3Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Fujian Provincial Key Laboratory of Critical Care Medicine, Fuzhou, Fujian, People’s Republic of ChinaCorrespondence: Ziyi Liu, Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. 160, Pujian Road, Pudong District, Shanghai, 200127, People’s Republic of China, Email liu-ziyi@sjtu.edu.cn Donghuang Hong, Department of Critical Care Medicine, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, No. 134, Dongjie Street, Gulou District, Fuzhou, Fujian, 350001, People’s Republic of China, Email hongdh2003@fjmu.edu.cnPurpose: The objective of this study was to identify the risk factors associated with Carbapenem-resistant Enterobacteriaceae (CRE) colonization in intensive care unit (ICU) patients and to develop a predictive risk model for CRE colonization.Patients and Methods: In this study, 121 ICU patients from Fujian Provincial Hospital were enrolled between January 2021 and July 2022. Based on bacterial culture results from rectal and throat swabs, patients were categorized into two groups: CRE-colonized (n = 18) and non-CRE-colonized (n = 103). To address class imbalance, Synthetic Minority Over-sampling Technique (SMOTE) was applied. Statistical analyses including T-tests, Chi-square tests, and Mann–Whitney U-tests were employed to compare differences between the groups. Feature selection was performed using Lasso regression and Random Forest algorithms. A Logistic regression model was then developed to predict CRE colonization risk, and the results were presented in a nomogram.Results: After applying SMOTE, the dataset included 198 CRE-colonized patients and 180 non-CRE-colonized patients, ensuring balanced groups. The two groups were comparable in most clinical characteristics except for diabetes, previous emergency department admission, and abdominal infection. Eight independent risk factors for CRE colonization were identified through Random Forest, Lasso regression, and Logistic regression, including Acute Physiology and Chronic Health Evaluation (APACHE) II score > 16, length of hospital stay > 31 days, female gender, previous carbapenem antibiotic exposure, skin infection, multi-site infection, immunosuppressant exposure, and tracheal intubation. The risk prediction model for CRE colonization demonstrated high accuracy (87.83%), recall rate (89.9%), precision (85.6%), and an AUC value of 0.877. Patients were categorized into low-risk (0– 90 points), medium-risk (91– 160 points), and high-risk (161– 381 points) groups, with corresponding CRE colonization rates of 1.82%, 7.14%, and 58.33%, respectively.Conclusion: This study identified independent risk factors for CRE colonization and developed a predictive model for assessing the risk of CRE colonization.Keywords: carbapenem-resistant Enterobacteriaceae, intensive care unit, colonization, risk factors, risk prediction model

Zhijie Jiang, Zhujun Fang, Dongsheng Hong, Xiaojuan Wang Department of Clinical Pharmacy, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, People’s Republic of ChinaCorrespondence: Xiaojuan Wang, Email xiaojuanwang1992@zju.edu.cnAbstract: Tumor vessels characterized by abnormal functions and structures hinder the infiltration and immune antigen presentation of immune cells by inducing the formation of an immunosuppressive microenvironment (“cold” environment). Vascular-targeted therapy has been proven to enhance immune stimulation and the effectiveness of immunotherapy by modulating the “cold” microenvironment, such as hypoxia and an acidic microenvironment. Notably, a therapeutic strategy based on “vascular-immune” crosstalk can achieve dual regulation of tumor vessels and the immune system by reprogramming the tumor microenvironment (TME), thus forming a positive feedback loop between tumor vessels and the immune microenvironment. From this perspective, we discuss the factors of tumor angiogenesis and “cold” TME formation. Building on this foundation, some vascular-targeted therapeutic drugs will be elaborated upon in detail to achieve dual regulation of tumor vessels and immunity. More importantly, we focus on cutting-edge nanotechnology in view of “vascular-immune” crosstalk and discuss the rational fabrication of tailor-made nanosystems for efficiently enhancing immunotherapy. Keywords: immunotherapy, nano-delivery systems, anti-angiogenic therapy, “vascular-immune” crosstalk, tumor vessels

Wei Wu,1– 4,* Wenbin Lu,5,* Dongmei Hong,1– 4 Xiya Yu,1– 4 Lize Xiong1– 4 1Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Shanghai, 200434, People’s Republic of China; 2Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200434, People’s Republic of China; 3Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200434, People’s Republic of China; 4Clinical Research Centre for Anesthesiology and Perioperative Medicine, Tongji University, Shanghai, 200434, People’s Republic of China; 5Faculty of Anesthesiology, Changhai Hospital, Naval Medical University/Second Military Medical University, PLA, Shanghai, 200433, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiya Yu; Lize Xiong, Tel +86-21-55603999 ; +86-21-55603002, Fax +86-21-56660851, Email yuxiyash@163.com; mzkxlz@126.com; lizexiong@tongji.edu.cnBackground: The hemoglobin-albumin-lymphocyte-platelet (HALP) index is a novel biomarker reflecting systemic inflammation and nutritional status which are important for coronavirus disease 2019 (COVID-19) mortality. However, the association between HALP and mortality in patients with COVID-19 has yet to be investigated.Methods: A cohort of COVID-19 Omicron BA.2 infected patients admitted to the Shanghai Fourth People’s Hospital, School of Medicine, Tongji University from April 12, 2022 to June 17, 2022 was retrospectively analyzed. Laboratory examinations on hospital admission, including hemoglobin, albumin, and lymphocyte and platelet, were collected. The association between baseline HALP and in-hospital poor overall survival (OS) was assessed using Kaplan–Meier curves, Cox regression models, interaction, and stratified analyses.Results: A total of 2147 patients with COVID-19 Omicron BA.2 infection were included in the final analyses, and mortality in the hospital was 2.65%. Multivariate analysis indicated that low HALP index was independently associated with in-hospital mortality of COVID-19 patients [hazard ratio (HR) = 2.08; 95% confidence interval (CI) = 1.17– 3.73]. Subgroup analysis demonstrated that low HALP index was an independent risk factor for in-hospital mortality in COVID-19 patients with age ≥ 70 (HR = 2.22, CI = 1.18– 4.15) and severe cases (HR = 2.09, CI = 1.13– 3.86).Conclusion: HALP index is independently related to in-hospital poor OS for COVID-19 Omicron BA.2 infected patients, especially for age ≥ 70 and severe cases. HALP index on hospital admission is a useful candidate biomarker for identifying high risk of mortality in COVID-19 Omicron BA.2 infected patients.Keywords: biomarkers, COVID-19, hemoglobin-albumin-lymphocyte-platelet index, mortality, Omicron BA.2

Dongsheng Hong,1,2 Duo Lv,1 Jiaying Wu,1 Xin Li,1 Qingwei Zhao,1 Xiaoyang Lu,1 Lu Li2 1Key Laboratory for Drug Evaluation and Clinical Research of Zhejiang Province, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Social Medicine of school of Public Health, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Xiaoyang Lu, Key Laboratory for Drug Evaluation and Clinical Research of Zhejiang Province, the First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, People’s Republic of China, Email luxiaoyang@zju.edu.cn Lu Li, Department of Social Medicine of school of Public Health, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou, 310058, People’s Republic of China, Email lilu@zju.edu.cnBackground: DIP is a new medical insurance payment system developed in China which was implemented in Guangzhou in January 2018, but few studies have focused on its intervention effect on the drug burden of elderly hypertensive patients.Methods: Nine medical institutions in Guangzhou, China, were selected, among which, daily full medical orders of elderly hypertensive inpatients from 2016 to 2020 were randomly collected. To assess the impact of DIP policy intervention on patient drug burden, we took the data after policy implementation in January 2018, as the intervention data, and applied a segmented regression model with interrupted time series to analyze the trend and changes in average daily drug costs per month and medication structure, stratified by age, sex, and inpatient department.Results: A total of 34,276 elderly hypertensive patients’ daily full medical orders were obtained. The immediate level change of drug costs after intervention was − 23.884 RMB/month (P = 0.652), and the trend change was statistically significant (− 15.642 RMB/month, P = 0.002). The relative cumulative effect at the end of the study was − 78.860% (95% CI: − 86.087% to − 69.076%), and the intervention effect was more significant in surgical and male patients. The analysis of drug structure changes showed that after the implementation of the DIP policy intervention, the proportion of anti-infective drugs, anti-tumor drugs, and biological products all showed a significant downward trend (P < 0.05), while nutritional drugs showed a significant upward trend (P = 0.011), but no immediate horizontal change in slope was observed.Conclusion: The typical practice in China showed that DIP policy intervention can improve the drug burden of elderly hypertensive hospitalized patients and has a stable long-term effect, and the intervention effect is not consistent across different clinical department and populations with different characteristics, and it would also cause changes in the medication structure.Keywords: diagnosis-intervention packet policy, daily drug cost, interrupted time series analysis, elderly hypertension, medication structure

Xiaoxia Tang,1 Yizhuo Zhang,2 Xinyu Dong,2 Guixing Jiang,2 Defei Hong,2,&ast; Xiaolong Liu2,&ast; 1Operating Room, Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2General Surgery, Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaolong Liu; Defei Hong, Email hahapoint1234@sina.com; hongdefi@163.comAbstract: At present, the average five-year survival rate of liver cancer in China is only 12.1%. The reason for this association lies in the diagnosis at its middle or/and advanced stage of liver cancer for lacking special clinical symptoms in almost 70% of patients without the chance of effective surgical resection. Epidemiological studies have shown that there are only 30% of patients with an initial diagnosis of liver cancer have the opportunity to undergo radical surgery. Therefore, systematic and comprehensive treatment would play an important role in liver cancer treatment at its middle or/and advanced stage, and the related therapeutic schedule still needs further improvement and optimization. We applied a gene-targeted drug of Icaritin soft capsule in the treatment of a liver cancer patient at its advanced stage. And the level of AFP was found to decrease to 6.4ng/mL from 10.86ng/mL; meanwhile, MRI showed that the primary tumor significantly reduced in size, with shrinking of the hepatogastric space, hepatic aortic side, and renal artery side lymph nodes. After treatment with TACE and Icaritin, the patient had no discomfort and no longer experienced abdominal pain and bloating and gained three kilograms of weight. The therapeutic effect of Icaritin-targeted drugs was completely demonstrated during the later treatment follow-up. That is to say, the multiple anti-tumor characteristics of Icaritin with good safety were fully displayed in this case, and it can be used in combination with other drugs to treat hepatocellular carcinoma in the clinical setting. The results show that Icaritin can put some effects on the combined treatment of patients with liver cancer.Keywords: HCC, patient, systematic and comprehensive treatment, Icaritin, gene-targeted

Ning Zhao,1,2 Yan Ma,3 Xiaoxue Liang,2 Yu Zhang,4 Dacheng Hong,5 Ying Wang,2 Dong Bai2 1Department of Pharmacy, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Formula-Syndrome Research Center, Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 3Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria; 4Beijing Xiuzheng Pharmaceutical Company, Beijing, People’s Republic of China; 5Department of Pharmaceutical Sciences, University of Vienna, Vienna, AustriaCorrespondence: Dong Bai, Tel +86 13552343081, Fax +8610 64089002, Email baidong2000@126.comPurpose: To study the efficacy of Qianshan Huoxue Gao (QS) in treating acute coronary syndrome (ACS) and to explore the mechanism of action from the perspective of intestinal flora regulation.Methods: Male Sprague–Dawley rats were divided into control, model, QS, and atorvastatin groups; except for the control group, rats underwent ligation of the left anterior descending branch of the coronary artery. Following treatment for 28 days, cardiac function was evaluated using an echocardiographic assay; ELISAs for serum creatine kinase isoenzyme (CK-MB), cardiac troponin I (cTnI), high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-2 (IL-2), IL-6, and tumor necrosis factor-α (TNF-α); assessment of cardiac enzymes and inflammatory response; hematoxylin and eosin (HE) staining for histopathological changes in the heart, skin, and viscera; 16S rRNA gene sequencing for intestinal flora diversity and structural differences analysis; and we further investigated intestinal contents using metabolomics.Results: Compared with controls, CK-MB and cTnI were increased (P< 0.01); ejection factor and fractional shortening were decreased (P< 0.01); left ventricular internal end-diastolic dimension and left ventricular internal end-systolic dimension were increased (P< 0.01); and IL-2, IL-6, TNF-α, and hs-CRP were increased in the model group. Myocardial damage and inflammation were also observed by HE staining. QS improved these indexes, similar to the atorvastatin group; therefore, QS could effectively treat ACS. QS modulates the structure and abundance of the intestinal flora in ACS model rats, among which Bacteroides, Lactobacillus, and Rikenellaceae_RC9_gut_group are associated with cardiovascular disease. Metabolomics revealed that the intestinal metabolite content changed in ACS, with ethanolamine (EA) being the most relevant metabolite for ACS treatment by QS. EA was significantly positively correlated with Eubacterium xylanophilum group, Ruminococcus, unclassified f__Oscillospiraceae, Intestinimonas, Eubacterium siraeum group, Lachnospiraceae NK4A136 group, and norank f__Desulfovibrionaceae.Conclusion: QS can effectively treat ACS and can restore regulation of the intestinal flora. EA may be the primary metabolite of QS, exerting a therapeutic effect in ACS.Keywords: traditional Chinese medicine, acute coronary syndrome, 16S rRNA, ethanolamine, topical paste

Yujie Huang,1 You Zhai,1 Meijia Wu,1 Chengdong Chang,2 Jindan Luo,3 Dongsheng Hong,1 Qingwei Zhao,1 Yao Dai,4 Jian Liu1 1Research Center for Clinical Pharmacy, Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4Department of Radiation Oncology, College of Medicine, University of Florida, Gainesville, FL, USACorrespondence: Jian Liu, Research Center for Clinical Pharmacy, Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China, Tel +86-571-87236560, Fax +86-571-87236531, Email lindaliu87@zju.edu.cn Yao Dai, Department of Radiation Oncology, College of Medicine, University of Florida, Gainesville, FL, USA, Tel +1-352-273-8237, Fax +1-352-273-8252, Email yaodai1111@hotmail.comPurpose: Mammalian Target of rapamycin (mTOR) plays a central role in regulating cell growth, proliferation, and cell cycle. The key component of mTORC2 is highly expressed in docetaxel-resistant prostate cells. However, the underlying molecular effects on prostate cells remain unclear.Methods: A docetaxel-resistant human prostate cell line (PC-3/DTX) was constructed to investigate the role of mTORC2 in docetaxel resistance. The lentivirus was transfected into cells to knock down the expression of Rictor, and cell viability was measured by Cell Counting Kit 8 (CCK-8). Flow cytometry was used to analyze the cell cycle, and the changes in related signal cascades were assessed by immunohistochemistry (IHC) staining and Western blot.Results: Docetaxel showed the lowest IC50 (50% inhibitory concentration) in PC-3/DTX cells with sh-RNA. Decreased Rictor expression resulted in a larger proportion of arrested cells in the G0/G1 phase in PC-3/DTX cells. The IC50 values of the AZD8055 group were lower than in the Rapamycin group when treated with docetaxel again. Furthermore, a larger proportion of PC-3/DTX cells were arrested in the G0/G1 phase in the AZD8055 group compared to the Rapamycin group. The IHC results of the prostate cancer tissues from a CRPC patient revealed the over expression of Rictor only, while Raptor expression was unaffected.Conclusion: We investigated the role of mTORC2 signaling on the acquired docetaxel -resistant PC-3 cells to identify potential methods for clinical treatment. MTORC2 expression is essential for docetaxel drug resistance of PC-3 cells. The mTORC1/2 inhibitor AZD8055 caused more significant disruption of mTORC2 kinase activity than the mTORC1 inhibitor Rapamycin, which lead to decreased docetaxel-mediated resistance. Therefore, reversing docetaxel resistance, may become a therapeutic option in the treatment of mCRPC patients.Keywords: prostate cancer cell, docetaxel, drug resistance, mTORC2, reverse

Link for citation: Van B. Duong, Fomenko I.K., Duc T. Ta, Trung K. Nguyen, Zerkal O.V., Gorobtsov D.N., Hong D. Vu. Influence of digital elevation model resolution on mapping territory susceptibility to landslide development. Bulletin of the Tomsk Polytechnic University. Geo Аssets Engineering, 2023, vol. 334, no. 8, рр. 164-181. In Rus. The relevance. Landslides are one of the most hazardous natural disasters in the world, causing significant economic damage and human deaths. For 20 years (1995–2014), 3876 landslides killed 163658 people and injured 11689 people, as reported by the U. Haque study (2019), based on the data from 128 countries. Excluding events triggered by earthquakes, the total number of fatal landslides from 2004 to 2016 was 4862, and most landslides (75 %) occurred in Asia. In Vietnam, particularly in the northern mountainous regions, landslides frequently caused considerable losses of life and property. The systematic evaluation of landslide hazards is a crucial component of Vietnam's disaster prevention strategy. The main aim of this study is to assess the landslide susceptibility of the Batxat district, Laocai province (Vietnam), using four digital elevation model resolutions (10, 30, 40, and 60 m) and nine landslide causative factors: slope aspect, elevation, slope, distance to roads, distance to faults, distance to drainage, average monthly precipitation, land use, and weathering crust. Object of the study is the landslide susceptibility in Batxat district, Laocai province, Vietnam. Methods: Certainty Factor method, fractal method. Results. The performed analyses indicated a statistically significant relationship between the distribution of landslides and the landslide causative factors in the study area. As a result, the territory was divided into five zones according to its susceptibility to the landslide process: very low, low, moderate, high, and very high. The very low landslide susceptibility zone is less than 10 % of the study area, while the very high susceptibility zone varies from 14,95 to 18,32 %, depending on the digital elevation model spatial resolution. Analysis of the Receiver Operating Characteristics curve revealed that all models, independent of digital elevation model resolution, have good prediction efficiency, with the area under the receiver operating characteristic curve over 70 %. In addition, the Receiver operating characteristic and fractal analysis results indicated that the model with a digital elevation model spatial resolution of 60 m has the highest accuracy. This significant conclusion may be explained by the fact that the accuracy of the landslide susceptibility assessment result is dependent not only on the digital elevation model resolution but also on the ratio of the digital elevation model resolution and the average area of landslides in the study area. This conclusion proves that it is necessary to depict landslide locations and their detailed morphological characteristics on the landslide inventory maps.

Yu Shen,1 Yilei Zheng,1 Daojun Hong1,2 1Department of Neurology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China; 2Department of Medical Genetics, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of ChinaCorrespondence: Daojun Hong, Department of Neurology, The First Affiliated Hospital of Nanchang University, 17# Yongwaizheng St, Nanchang, 330006, People’s Republic of China, Tel/Fax +86-791-8869-2511, Email hongdaojun@hotmail.comAbstract: Over the past decades, advances in genetic sequencing have opened a new world of discovery of causative genes associated with numerous pain-related syndromes. Familial episodic pain syndromes (FEPS) are one of the distinctive syndromes characterized by early-childhood onset of severe episodic pain mainly affecting the distal extremities and tend to attenuate or diminish with age. According to the phenotypic and genetic properties, FEPS at least includes four subtypes of FEPS1, FEPS2, FEPS3, and FEPS4, which are caused by mutations in the TRPA1, SCN10A, SCN11A, and SCN9A genes, respectively. Functional studies have revealed that all missense mutations in these genes are closely associated with the gain-of-function of cation channels. Because some FEPS patients may show a relative treatability and favorable prognosis, it is worth paying attention to the diagnosis and management of FEPS as early as possible. In this review, we state the common clinical manifestations, pathogenic mechanisms, and potential therapies of the disease, and provide preliminary opinions about future research for FEPS.Keywords: familial episodic pain syndromes, voltage-gated sodium channel, transient receptor potential A1, dorsal root ganglia, nociceptive pain

The relevance. Predicting and minimizing the impact of natural disasters are critical tasks for governments worldwide, including Vietnam. Landslides are one of the most frequent types of natural disasters in Vietnam, especially in the northern mountainous provinces, resulting in significant loss of life and property. In this study, the GIS-based bivariate statistical methods were applied for assessing landslide potential in Sapa district, Laocai province, Vietnam. For assessing landslide susceptibility, nine landslide-related factors were selected, including elevation, distance to roads, slope, distance to faults, average monthly precipitation, relative relief, land use, crust weathering, and distance to drainage. The main aim of this study is to prepare landslide potential maps for the study area. In addition, the study also demonstrated the effectiveness of bivariate statistical methods for landslide susceptibility assessment. Object of the study is the landslide susceptibility in Sapa district, Laocai province, Vietnam. Methods: GIS-based bivariate statistical methods including frequency ratio, landslide susceptibility analysis, and statistical index. Results. Landslide potential maps were prepared using GIS-based bivariate statistical methods. The study area is divided into five landslide potential zones: very low, low, moderate, high, and very high. The area under the curve of the receiver operating characteristic (AUCROC) was used to evaluate the performance of these models. The success rates of the models for the training data are 74,60 % frequency ratio, 70,82 % landslide susceptibility analysis and 76,36 % statistical index. The prediction rates of the models for the testing data are 77,01 % frequency ratio, 74,36 % landslide susceptibility analysis and 78,11 % statistical index. The performance evaluation of the models revealed that all three techniques are efficient in assessing landslide potential in the study area. Study results are critical for land use planning and economic development, as well as minimizing landslide-related damage.

Zhiyu Wang, Yaning Wei, lin An, Kunjie Wang, Dan Hong, Yan Shi, Aimin Zang, Shenyong Su, Wenwen Li Department of Medical Oncology, Affiliated Hospital of Hebei University, Baoding, Hebei Province, People’s Republic of ChinaCorrespondence: Wenwen LiDepartment of Medical Oncology, Affiliated Hospital of Hebei University, Baoding, 071000, Hebei Province, People’s Republic of China, Email ww13663129901@yeah.netBackground: Immune cell infiltration plays a critical role in regulating peptic ulcer disease (PUD) and gastrointestinal cancer (GC). However, regulators of the cell signaling hubs remain unclear.Aim: This study characterizes genes that are differentially expressed in PUD and GC tissue samples. Bioinformatics is used to define the immune-associated hub genes associated with the malignant transfer process of PUD to GC.Methods: Total expression data from PUD and early-stage GC tissue samples were obtained from GEO and TCGA. Differentially expressed genes were assessed and immunological enrichment analysis was performed. Protein–protein interaction (PPI) and Cytoscape analysis were used together to identify the hub genes. CIBERSORT and COX analysis were used to analyze the differentially infiltrated immune cell landscapes and determine HR scores of the hub genes.Results: Expression data identified 437 DEGs as common to both GC and PUD tissue. Of these, 49 immune-related DEGs were grouped by function, and seven hub genes were identified by PPI analysis. The NRP2 and SEMA3D genes were then selected for survival analysis. SEMA3D had a higher hazard ratio than NRP2 and was defined as the hub for PUD carcinogenesis.Conclusion: SEMA3D was characterized as the hub gene for PUD carcinogenesis.Keywords: SEMA3D, peptic ulcer disease, gastric cancer, H. pylori, immunological micro-environment

Yao Y, Li C, Qian F, et al. J Inflamm Res. 2021;14:6619–6632. The Editor and Publisher of the Journal of Inflammation Research are retracting the published article. The authors requested to correct errors with images from Figure 3, however it was found that some of the images had been duplicated with those from Yao YY, Li R, Guo YJ, et al. Gastrodin Attenuates Lipopolysaccharide-Induced Inflammatory Response and Migration via the Notch-1 Signaling Pathway in Activated Microglia. Neuromol Med. 2022;24:139–154. https://doi.org/10.1007/s12017-021-08671-1. Specifically, The images for Figure 3C, Control; p-STAT3; Lectin; Merge and LPS+Rg1(60µM); p-STAT3; Lectin; Merge have been duplicated with the images for Figure 3C, Control; NICD, Lectin; Merge and LPS; NICD, Lectin, Merge, respectively, from Yao YY et al (2022). The authors cooperated with our queries and explained the errors were made during the assembly of the figures and discovered following an internal academic review. The authors also provided the journal with original data from their study. However, the errors did raise concerns over the reliability and validity of the findings and the Editor and Publisher made the decision to retract the article and the authors do not agree with this decision. We have been informed in our decision-making by our editorial policies and the COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Yueyi Yao,1 Changyan Li,1 Fusheng Qian,1 Yu Zhao,1 Xiaoyi Shi,1 Dan Hong,1 Qinglong Ai,2 Lianmei Zhong2 1Science and Technology Achievement Incubation Center, Kunming Medical University, Kunming, 650500, People’s Republic of China; 2Department of Neurology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, People’s Republic of ChinaCorrespondence: Lianmei Zhong; Qinglong AiDepartment of Neurology, First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, 650032, Yunnan Province, People’s Republic of ChinaTel/Fax +86-0871-65336015Email 13888967787@163.com; aiqinglong63@163.comPurpose: Neuroinflammation runs through the whole process of nervous system diseases and brain injury. Inflammasomes are thought to be especially relevant to immune homeostasis, and their dysregulation contributes to pyroptosis. The natural compound Ginsenoside Rg1 has been shown to possess anti-inflammatory effects; however, its underlying mechanisms are not entirely clear. Therefore, this study was undertaken to investigate the role and mechanisms of Rg1 in regulating the production of inflammasomes and pyroptosis of microglia in vivo and in vitro.Methods: BV-2 microglial cells were pretreated with Rg1, stattic and interleukin-6 (IL-6), and then stimulated with lipopolysaccharide (LPS) (2μg/mL). Hoechst staining and Annexin V-FITC/PI assay were then carried out. The expression levels of cleaved-caspase-1, pro-caspase-1, interleukin-1β (IL-1β), mature-IL-1β, gasdermin D (GSDMD), activated NH(2)-terminal fragment of GSDMD (GSDMD-N), NOD-, LRR- and pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), absent in melanoma 2 (AIM2), signal transducer and activator of transcription 3 (STAT3) and phosphorylated STAT3 in BV-2 were detected by Western blotting. Additionally, immunofluorescence staining was used to determine the expression of NLRP3 and p-STAT3 in postnatal rat brain and BV-2 microglia subjected to LPS stimulation and Rg1 pretreatment. The targets of transcription factor STAT3 were predicted by hTFtarget and chromatin immunoprecipitation (ChIP) was used to confirm the interaction between STAT3 and AIM2.Results: We showed here that Rg1 effectively inhibited the expression of inflammasomes and microglia pyroptosis induced by LPS. The targets predicted data of Rg1 from Swiss target prediction database showed STAT3 had the highest thresholds of probability score. Rg1 can regulate the phosphorylation of STAT3, which binds to the promoter region of inflammasome AIM2.Conclusion: It is suggested that STAT3 signaling can initiate the transcription activity of AIM2. Rg1 regulates microglia pyroptosis in neuroinflammation induced by LPS through targeting STAT3 signaling.Keywords: neuroinflammation, AIM2, microglia, pyroptosis, Rg1

Zhiyu Wang, Aimin Zang, Yaning Wei, Lin An, Dan Hong, Yan Shi, Jingnan Zhang, Shenyong Su, Guotao Fang Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Department of Medical Oncology, Affiliated Hospital of Hebei University, Baoding 071000, People’s Republic of ChinaCorrespondence: Guotao FangDepartment of Medical Oncology, Affiliated Hospital of Hebei University, No. 648 Dongfeng East Road, Lianchi District, Baoding 071000, Hebei Province, People’s Republic of ChinaTel +86-312-5983042Email fanguotao@protonmail.comBackground: The current approach for treating colorectal cancer favors the use of drug and gene combination therapy, and targeted nano-systems are gaining considerable attention for minimizing toxicity and improving the efficacy of anticancer treatment. The aim of this study was to develop ligand-modified, irinotecan and gene co-loaded lipid-polymer hybrid nanocarriers for targeted colorectal cancer combination therapy.Methods: Hyaluronic acid modified, irinotecan and gene co-loaded LPNs (HA-I/D-LPNs) were prepared using a solvent-evaporation method. Their average size, zeta potential, drug and gene loading capacity were characterized. The in vitro and in vivo gene transfection and anti-tumor ability of this nano-system were evaluated on colorectal cancer cells and mice bearing colorectal cancer model.Results: HA-I/D-LPNs had a size of 182.3 ± 5.1, over 80% drug encapsulation efficiency and over 90% of gene loading capacity. The peak plasma concentration (Cmax) and half-life (T1/2) achieved from HA-I/D-LPNs were 41.31 ± 1.58 μg/mL and 12.56 ± 0.67 h. HA-I/D-LPNs achieved the highest tumor growth inhibition efficacy and the most prominent transfection efficiency in vivo.Conclusion: HA-I/D-LPNs exhibited the most remarkable tumor inhibition efficacy and best gene transfection efficiency in the tumor, which could prove the effects of the drug and gene combination therapy.Keywords: colorectal cancer, combination therapy, lipid-polymer hybrid nanoparticles, hyaluronic acid, irinotecan

The Jiangmen Underground Neutrino Observatory (JUNO) is proposed to determinethe neutrino mass hierarchy using an underground liquid scintillator detector.It is located 53 km away from both Yangjiang and Taishan Nuclear Power Plantsin Guangdong, China. The experimental hall, spanning more than 50 meters, isunder a granite mountain of over 700 m overburden. Within six years of running,the detection of reactor antineutrinos can resolve the neutrino mass hierarchyat a confidence level of 3-4$\sigma$, and determine neutrino oscillationparameters $\sin^2\theta_{12}$, $\Delta m^2_{21}$, and $|\Delta m^2_{ee}|$ toan accuracy of better than 1%. The JUNO detector can be also used to studyterrestrial and extra-terrestrial neutrinos and new physics beyond the StandardModel. The central detector contains 20,000 tons liquid scintillator with anacrylic sphere of 35 m in diameter. $\sim$17,000 508-mm diameter PMTs with highquantum efficiency provide $\sim$75% optical coverage. The current choice ofthe liquid scintillator is: linear alkyl benzene (LAB) as the solvent, plus PPOas the scintillation fluor and a wavelength-shifter (Bis-MSB). The number ofdetected photoelectrons per MeV is larger than 1,100 and the energy resolutionis expected to be 3% at 1 MeV. The calibration system is designed to deploymultiple sources to cover the entire energy range of reactor antineutrinos, andto achieve a full-volume position coverage inside the detector. The veto systemis used for muon detection, muon induced background study and reduction. Itconsists of a Water Cherenkov detector and a Top Tracker system. The readoutsystem, the detector control system and the offline system insure efficient andstable data acquisition and processing.

Tianmei Si,1,2 Jianmin Zhuo,3 Yu Feng,4 Huafei Lu,5 Di Hong,5 Lili Zhang51National Clinical Research Center for Mental Disorders & The Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, People’s Republic of China; 2Peking University Institute of Mental Health/The Sixth Hospital, Beijing, People’s Republic of China; 3Janssen (China) Research & Development Center, Johnson & Johnson (China) Investment Ltd., Shanghai, People’s Republic of China; 4Department of Neuroscience, Janssen Pharmaceutical Companies of Johnson and Johnson, Singapore; 5Medical Affairs, Xi’an Janssen Pharmaceuticals, Beijing, People’s Republic of ChinaBackground: The subgroup analysis of a primary study (NCT01051531) evaluated the effect of long-term paliperidone palmitate once-monthly (PP1M) therapy in Chinese patients with recent-onset schizophrenia responding unsatisfactorily to previous oral antipsychotics.Patients and methods: This 18-month, open-label study consisted of 3 phases – screening (7 days), treatment (18 months) and end-of-study/withdrawal visit. All enrolled patients (18–50 years) received PP1M: 150 mg eq. (day 1), 100 mg eq. (day 8) followed by a once-monthly flexible dose (50, 75, 100 or 150 mg eq.). Efficacy and safety were assessed.Results: Among the 118 enrolled Chinese patients, 68 completed the treatment (mean age: 25.6 years; male: 54.7%). A clinically meaningful change from baseline to day 548 was observed in Positive and Negative Syndrome scale (primary endpoint, mean [SD]: −15.3 [20.76]), Personal and Social Performance scale (15.9 [19.65]), Clinician Global Impression-schizophrenia score (−1.2 [1.54]) and Medication Satisfaction Questionnaire score (0.9 [1.73]). Commonly reported treatment-emergent adverse events (TEAEs) included insomnia (13.9%), injection-site pain (13.9%), upper respiratory tract infection (13.0%), restlessness (13.0%) and akathisia (13.0%). Serious TEAEs were reported in 9.3% patients with schizophrenia being most common (6.5%) and one death (suicide) was observed.Conclusion: Efficacy of PP1M corroborate findings from earlier studies and no new safety concerns emerged in this Chinese subgroup of patients with schizophrenia.Keywords: Chinese patients, long-acting injectable, maintenance therapy, paliperidone palmitate once-monthly, schizophrenia

BackgroundAdrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy without an available effective systemic chemotherapy. Insulin growth factor 2 (IGF-2) overexpression leading to the activation of the IGF-1 receptor (IGF-1R)/mammalian target of rapamycin (mTOR) pathway is well described in ACC. Cixutumumab, a fully human IgG1 monoclonal antibody directed at IGF-1R was combined with temsirolimus on the basis of preclinical data.MethodsPatients received cixutumumab, 3-6 mg kg(-1) intravenously (IV) weekly, and temsirolimus, 25-37.5 mg IV weekly (4-week cycles), with restaging after 8 weeks.ResultsTwenty-six patients were enrolled (13 (50%) men); median age, 47 years; median number of prior therapies, 4. Five patients previously received an IGF-1R inhibitor and one, temsirolimus. The most frequent toxicities, at least possibly drug related, were grade 1-2 thrombocytopenia (38%), mucositis (58%), hypercholesterolaemia (31%), hypertriglyceridemia (35%), and hyperglycaemia (31%). In all, 11 of 26 patients (42%) achieved stable disease (SD) >6 months (duration range=6-21 months) with 3 of the 11 having received a prior IGF-1R inhibitor.ConclusionCixutumumab combined with temsirolimus was well tolerated and >40% of patients achieved prolonged SD.