bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression analysis of cytokines IL-5, IL-6, IL-8, IL-17 and VEGF in breast cancer patients
Authors: Liu Gang , Chen Xiang-Ting , Zhang Hao , Chen Xin 
Published: December 2022

ObjectiveTo investigate the relationship between changes in peripheral blood vascular endothelial growth factor (VEGF), interleukin-5 (IL-5), interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-17 (IL-17) concentrations in breast cancer patients and their significance and clinical value in breast cancer staging and invasive metastasis.MethodsFrom September 2021 to April 2022, 60 breast cancer patients from Chongqing Medical University Hospital No. 2022 were enrolled in the breast breast cancer surgery group, while 30 patients with benign breast disease were enrolled in the control group during the same period. Venous blood samples were collected at admission and 1 week after surgery to determine the expression of these factors in serum. Statistical methods such as Wilcoxon test and Spearman correlation analysis were used to analyze the relationship between the above factors and the clinicopathological characteristics of the patients.ResultsBy analyzing data from patients with benign and malignant breast tumors, an association was found with serum levels of IL-6, IL-17 and VEGF. Their respective areas under the operating characteristic curve were 0.649, 0.734 and 0.656 (P &lt; 0.05). There were significant differences in the cytokine expression levels of IL-17 and VEGF in different molecular typing (P values were 0.008 and 0.040, respectively). The expression levels of IL-17 and VEGF were higher in HER-2 receptor-positive and triple-negative patients than in hormone receptor-positive patients (P &lt; 0.05). Also, no significant correlation was found between the various cytokines mentioned in the article and breast cancer lymph node metastasis and Tumor Node Metastasis stage (TNM stage). In addition, in the breast cancer surgery group, postoperative VEGF levels were lower (P &lt; 0.05) and IL-6 levels were higher (P &lt; 0.05) compared to preoperative levels.ConclusionsSerum IL-6, IL-17, and VEGF are strongly associated with breast cancer development and can be used as a reference indicators for breast cancer diagnosis. In addition, post-operative VEGF levels decreases and IL-6 levels increases compared to pre-operative levels, which can also be used as an a postoperative follow-up indicator. In contrast, IL-5 and IL-8 have not found to be significantly associated with breast cancer patients in this study, which requires further study.
En bloc resection of huge primary tumors with epidural involvement in the mobile spine using the “rotation–reversion” technique: Feasibility, safety, and clinical outcome of 11 cases
Authors: Lu Ming , Zhou Zhongxin , Chen Wei , Lei Zixiong , Dai Shuangwu , Hou Changhe , Du Shaohua , Jin Qinglin , Jin Dadi , Boriani Stefano , Li Haomiao 
Published: December 2022

BackgroundEn bloc resection of spinal tumors provides better local control and survival outcomes than intralesional resection. Safe margins during en bloc resection of primary spinal tumors with epidural involvement are required for improved outcomes. The present study describes a “rotation–reversion” technique that has been used for en bloc resection of huge primary tumors in the mobile spine with epidural involvement and reported the clinical outcomes in these patients.MethodsAll patients with primary spinal tumors who were treated with the rotation–reversion technique at our institution between 2015 and 2021 were evaluated retrospectively. Of the patients identified, those with both huge extraosseous soft-tissue masses and epidural involvement were selected for a case review. Clinical and radiological characteristics, pathologic findings, operative procedures, complications, and oncological and functional outcomes of these patients were reviewed.ResultsOf the 86 patients identified with primary spinal tumors who underwent en bloc resection using the rotation–reversion technique between 2015 and 2021, 11 had huge extraosseous soft-tissue masses with epidural involvement in the mobile spine. The average maximum size of these 11 tumors was 8.1 × 7.5 × 9.7 cm. Median follow-up time was 28.1 months, mean operation time was 849.1 min (range 465–1,340 min), and mean blood loss was 6,972.7 ml (range 2,500–17,700 ml), with 10 (91%) of the 11 patients experiencing perioperative complications. The negative margin rate was 91%, with only one patient (9%) experiencing local recurrence. Ten patients were able to walk normally or with a crutch at the last follow-up, whereas one was completely paralyzed preoperatively.ConclusionThe rotation–reversion technique is an effective procedure for the en bloc resection of huge primary spinal tumors, with the extension of invasion in selected patients including not only the vertebral body but also the pedicle and part of the posterior arch.
Glutathione levels are associated with methotrexate resistance in acute lymphoblastic leukemia cell lines
Authors: Canevarolo Rafael Renatino , Melo Carolina Pereira de Souza , Cury Nathalia Moreno , Artico Leonardo Luiz , Corrêa Juliana Ronchi , Lau Yanca Tonhasca , Mariano Samara Sousa , Sudalagunta Praneeth Reddy , Brandalise Silvia Regina , Zeri Ana Carolina de Mattos , Yunes José Andrés 
Published: December 2022

IntroductionMethotrexate (MTX), a folic acid antagonist and nucleotide synthesis inhibitor, is a cornerstone drug used against acute lymphoblastic leukemia (ALL), but its mechanism of action and resistance continues to be unraveled even after decades of clinical use.MethodsTo better understand the mechanisms of this drug, we accessed the intracellular metabolic content of 13 ALL cell lines treated with MTX by 1H-NMR, and correlated metabolome data with cell proliferation and gene expression. Further, we validated these findings by inhibiting the cellular antioxidant system of the cells in vitro and in vivo in the presence of MTX.ResultsMTX altered the concentration of 31 out of 70 metabolites analyzed, suggesting inhibition of the glycine cleavage system, the pentose phosphate pathway, purine and pyrimidine synthesis, phospholipid metabolism, and bile acid uptake. We found that glutathione (GSH) levels were associated with MTX resistance in both treated and untreated cells, suggesting a new constitutive metabolic-based mechanism of resistance to the drug. Gene expression analyses showed that eight genes involved in GSH metabolism were correlated to GSH concentrations, 2 of which (gamma-glutamyltransferase 1 [GGT1] and thioredoxin reductase 3 [TXNRD3]) were also correlated to MTX resistance. Gene set enrichment analysis (GSEA) confirmed the association between GSH metabolism and MTX resistance. Pharmacological inhibition or stimulation of the main antioxidant systems of the cell, GSH and thioredoxin, confirmed their importance in MTX resistance. Arsenic trioxide (ATO), a thioredoxin inhibitor used against acute promyelocytic leukemia, potentiated MTX cytotoxicity in vitro in some of the ALL cell lines tested. Likewise, the ATO+MTX combination decreased tumor burden and extended the survival of NOD scid gamma (NSG) mice transplanted with patient-derived ALL xenograft, but only in one of four ALLs tested.ConclusionAltogether, our results show that the cellular antioxidant defense systems contribute to leukemia resistance to MTX, and targeting these pathways, especially the thioredoxin antioxidant system, may be a promising strategy for resensitizing ALL to MTX.
Prognostic biomarker MCP-4 triggers epithelial-mesenchymal transition via the p38 MAPK pathway in ovarian cancer
Authors: Li Siting , Hu Yuexin , Liu Ouxuan , Li Xiao , Lin Bei 
Published: December 2022

BackgroundMonocyte chemoattractant protein-4 (MCP-4/CCL13) is a proinflammatory factor that is overexpressed in various malignant tumors and may play an important role in tumor progression and metastasis. However, its role and mechanism of action in ovarian cancer remains unknown.MethodsImmunohistochemistry (IHC) was performed to detect the expression of MCP-4 in ovarian cancer tissues, and the effect of MCP-4 on patient survival and prognosis was analyzed. Overexpression and suppression of MCP-4 in ovarian cancer cell lines were then established, and their effects on cell invasion, migration, and apoptosis were studied. ES-2 cell lines were employed to establish a peritoneal dissemination model in nude mice. Western blotting was performed to detect the expression of epithelial mesenchymal transition (EMT) markers and the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway.ResultsMCP-4 was highly expressed in ovarian cancer tissues and its expression level was related to the prognosis of patients with ovarian cancer. MCP-4 overexpression promoted the migration and invasion of ovarian cancer cells but inhibited apoptosis. MCP-4 overexpression increased the expression of MMP-2, MMP-9, N-cadherin, vimentin and Bcl2/Bax and decreased the expression of E-cadherin. MCP-4 overexpression increased the phosphorylation of the p38 MAPK pathway. The inhibition of MCP-4 expression indicated an opposite trend. In vivo experiments have also confirmed that MCP-4 overexpression can promote metastasis of ovarian cancer.ConclusionMCP-4 promotes ovarian cancer progression through the p38 MAPK signaling pathway, and may be a potential biomarker and therapeutic target for ovarian cancer.
Inflammation-related citrullination of matrisome proteins in human cancer
Authors: Rappu Pekka , Suwal Ujjwal , Siljamäki Elina , Heino Jyrki 
Published: December 2022

IntroductionProtein arginine deiminases (PADs) are intracellular enzymes that may, especially in pathological conditions, also citrullinate extracellular substrates, including matrisome proteins such as structural proteins in extracellular matrix (ECM). PADs are abundantly expressed in human cancer cells. Citrullination of matrisome proteins has been reported in colon cancer but the phenomenon has never been systematically studied.MethodsTo gain a broader view of citrullination of matrisome proteins in cancer, we analyzed cancer proteomics data sets in 3 public databases for citrullinated matrisome proteins. In addition, we used three-dimensional cell cocultures of fibroblasts and cancer cells and analyzed citrullination of ECM.Results and discussionOur new analysis indicate that citrullination of ECM occurs in human cancer, and there is a significant variation between tumors. Most frequently citrullinated proteins included fibrinogen and fibronectin, which are typically citrullinated in rheumatoid inflammation. We also detected correlation between immune cell marker proteins, matrix metalloproteinases and ECM citrullination, which suggests that in cancer, citrullination of matrisome proteins is predominantly an inflammation-related phenomenon. This was further supported by our analysis of three-dimensional spheroid co-cultures of nine human cancer cell lines and fibroblasts by mass spectrometry, which gave no evidence that cancer cells or fibroblasts could citrullinate matrisome proteins in tumor stroma. It also appears that in the spheroid cultures, matrisome proteins are protected from citrullination.
Case Report: A case of radioactive iodine-refractory thyroid cancer accompanying cervical lymph node metastasis treated with US-guided RFA combined with 125I seed implantation
Authors: Zhai Yuanpeng , Shao Yu , Li Qian 
Published: December 2022

BackgroundLocal control of metastases is critical to improving the life quality of patients with radioactive iodine-refractory (RAIR) thyroid cancer accompanying regional lymph node metastasis.Case reportThe reported patient suffered from RAIR thyroid cancer accompanying poorly controlled cervical lymph node metastasis. The patient’s lesions were controlled through 125I seed implantation combined with ultrasound-guided radio-frequency ablation (US-guided RFA). Such a combination therapy has not been reported to date.ConclusionThis study found US-guided RFA combined with 125I seed implantation to be safe and effective for the control of cervical local metastases in patients with RAIR thyroid cancer.
Effects of dehydroabietic acid on nontarget lipidomics and proteomics of HepG2
Authors: Xiahou Zhikai , Han Jun 
Published: December 2022

Objective: Studies of the effects of dehydroabietic acid on the multiomics of HepG2 hepatoma carcinoma cells are currently lacking. In this study, the molecular mechanism of the influence of dehydroabietic acid on HepG2 cells was disclosed by studying lipidomics and proteomics. Correlations among multiomics conjoint analysis results were verified.Methods: First, proteomics analysis of HepG2 cells was carried out using dehydroabietic acid. Differentially expressed proteins were screened and analyzed. Pathway enrichment analyses of differential proteins were compared, and the molecular mechanism was disclosed. Second, lipidomics analysis of HepG2 cells was conducted using dehydroabietic acid. The influence of dehydroabietic acid on HepG2 cells was determined on the lipid molecular level. Finally, a conjoint analysis of data related to differentially expressed proteins of ferroptosis and differentially changing lipid molecules was implemented.Results: A total of 260 upregulated and 961 downregulated proteins were screened in the proteomics analysis. The top five significantly enriched pathways included ferroptosis, oxidative phosphorylation, and protein processing in the endoplasmic reticulum. In the lipidomics analysis, 30 significantly differential metabolites with upregulated and downregulated expression were identified, and differentially expressed lipids were mainly related to the metabolism of glyceryl phosphatide. According to the comprehensive multiomics analysis results, real-time quantitative PCR and the enzyme-linked immunosorbent assay (ELISA), ACSL3 participated in cardiolipin metabolism.Conclusion: Dehydroabietic acid influences HepG2 cells through the above biological pathways.
A novel biflavone from Reineckia carnea induces apoptosis of human renal cancer 786-O cells
Authors: Yang Jianqiong , Xiao Bang , Li Yamei , Liu Xiaoxuan , Zhang Minhong , Luo Yaoling , Wang Biao , Liu Hai 
Published: December 2022

Renal cell carcinoma (RCC) is a common malignant tumor of the urinary system, which is highly invasive, metastatic, and insensitive to radiotherapy and chemotherapy. Chinese herbal medicine has always been an important source of anti-tumor drug development. Reineckia carnea Kunth is a traditional herb commonly used by the Miao nationality in southwest China. In this study, the extract of Reineckia carnea was isolated and purified by reverse phase preparative chromatography and other chromatographic techniques. According to the physicochemical properties and spectral data, the structure of the compound was identified, and a novel biflavone compound named Reineckia-biflavone A (RFA) was obtained. The result of antiproliferative activity showed that RFA had cytotoxicity on 786-O cells with an IC50 value of 19.34 μmol/L. The results of CCK-8 and hemolysis assays showed that RFA was not significantly cytotoxic to both red blood cells (RBC) and peripheral blood mononuclear cells (PBMC). By Hoechst 33258 apoptosis staining, typical apoptotic morphology was observed under fluorescence microscope. RFA could induce the apoptosis of 786-O cells with the increase of apoptosis rate. The cell cycle tests showed that the cell proportion was obviously arrested in the S phase. At the same time, RFA could decrease the mitochondrial membrane potential and increase the intracellular free Ca2+ concentration. Western blot showed that the expression levels of pro-apoptotic proteins (Bax, Caspase-3, Cleaved Caspase-3, and Cytochrome c) in cells rose, while the expression level of anti-apoptotic proteins (Bcl-2) declined significantly. In conclusion, this study suggests that the RFA is a new biflavone determined by SciFinder retrieval. The apoptosis may be triggered by RFA through the mitochondrial pathway, which is mediated by up-regulating the intracellular calcium ion, down-regulating the mitochondrial membrane potential, and changing the apoptosis-related proteins.
Post-marketing safety of immunomodulatory drugs in multiple myeloma: A pharmacovigilance investigation based on the FDA adverse event reporting system
Authors: Jiang Tingting , Su Hui , Li Yanping , Wu Yuanlin , Ming Yue , Li Chen , Fu Ruoqiu , Feng Lu , Li Ziwei , Li Li , Ni Rui , Liu Yao 
Published: December 2022

Objective: In recent years, the emergence of immunomodulatory drugs (IMiDs) has significantly improved clinical outcomes in patients with multiple myeloma (MM); however, serious adverse events (AEs) have hindered their safe clinical application. This study aimed to characterize the safety profiles and differences in IMiDs through a disproportionality analysis using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS), a post-marketing surveillance database.Methods: This study filtered reports of thalidomide, lenalidomide, and pomalidomide as primary suspect drugs in FAERS files from January 2013 to December 2021. AEs in the reports were retrieved according to the preferred terms (PTs) of the Medical Dictionary for Regulatory Activities. Furthermore, we detected safety signals using the reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian belief propagation neural network (BCPNN). When all three algorithms showed an association between the target drug and the AE, a positive signal was generated.Results: We extracted 9,968 thalidomide, 231,926 lenalidomide, and 55,066 pomalidomide AE reports. AEs were more common in male patients and in those &gt;44 years old. Important safety signals were detected based on the system organ classes (SOC), including thalidomide (cardiac disorders: ROR, 2.87; PRR, 2.79; IC 1.22), lenalidomide (gastrointestinal disorders: ROR, 2.38; PRR, 2.27; IC 0.75), and pomalidomide (respiratory, thoracic, and mediastinal disorders: ROR, 2.14; PRR, 2.09; IC 0.85). Within the PT level, we identified novel risk signals: the thalidomide-induced second primary malignancy (SPM) signal was significant; lenalidomide reduced the success rate of hematopoietic stem cell collection; and three IMiDs may cause human chorionic gonadotropin increase, but this needs to be proven by clinical data. Pneumonia, sepsis, and renal failure are common risk factors for death due to IMiDs. Compared with thalidomide and lenalidomide, pomalidomide has a lower risk of venous thromboembolism (VTE) and is beneficial to patients with renal insufficiency.Conclusion: Mining data from FAERS resulted in novel AE signals, including adenocarcinoma of colon, harvest failure of blood stem cells, and increased levels of human chorionic gonadotropin. Further investigation is required to verify the significance of these signals. Moreover, IMiDs showed differences in safety reports, which should be emphasized by clinicians.
Study on external cavity diode laser with a wide mode-hopping free tuning range
Authors: Zhang Aiguo , Qiao Shan , Sheng Liwen , Huang Lin , Liu Zhiming , Ju Junwei , Zhang Zhihui , Yin Bingqi , Li Peng , Liu Jiaqing , Wei Yu 
Published: December 2022

A wide mode-hopping free and narrow linewidth tunable laser diode source with a Littman-Metcalf arrangement based on a diffraction grating is presented. Several experiments are carried out to demonstrate the tuning characteristics and spectral linewidth of the proposed external-cavity diode laser source. A wide no mode-hopping continuous wavelength tuning range about 59.13 nm in ultra-C-band with a narrow spectral linewidth of less than 100 kHz is obtained. An optical signal to noise ratio of more than 65 dB and an output power more than 14.8 dBm over the whole tuning range can also be realized in a long-term free running condition. The proposed tunable laser allows simultaneously mode-hopping free and narrow linewidth tunable radiation, thus opening a door for practical application such as coherent detection.
Cerebral multimodality monitoring in adult neurocritical care patients with acute brain injury: A narrative review
Authors: Tas Jeanette , Czosnyka Marek , van der Horst Iwan C. C. , Park Soojin , van Heugten Caroline , Sekhon Mypinder , Robba Chiara , Menon David K. , Zeiler Frederick A. , Aries Marcel J. H. 
Published: December 2022

Cerebral multimodality monitoring (MMM) is, even with a general lack of Class I evidence, increasingly recognized as a tool to support clinical decision-making in the neuroscience intensive care unit (NICU). However, literature and guidelines have focused on unimodal signals in a specific form of acute brain injury. Integrating unimodal signals in multiple signal monitoring is the next step for clinical studies and patient care. As such, we aimed to investigate the recent application of MMM in studies of adult patients with traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), acute ischemic stroke (AIS), and hypoxic ischemic brain injury following cardiac arrest (HIBI). We identified continuous or daily updated monitoring modalities and summarized the monitoring setting, study setting, and clinical characteristics. In addition, we discussed clinical outcome in intervention studies. We identified 112 MMM studies, including 11 modalities, over the last 7 years (2015–2022). Fifty-eight studies (52%) applied only two modalities. Most frequently combined were ICP monitoring (92 studies (82%)) together with PbtO2 (63 studies (56%). Most studies included patients with TBI (59 studies) or SAH (53 studies). The enrollment period of 34 studies (30%) took more than 5 years, whereas the median sample size was only 36 patients (q1- q3, 20–74). We classified studies as either observational (68 studies) or interventional (44 studies). The interventions were subclassified as systemic (24 studies), cerebral (10 studies), and interventions guided by MMM (11 studies). We identified 20 different systemic or cerebral interventions. Nine (9/11, 82%) of the MMM-guided studies included clinical outcome as an endpoint. In 78% (7/9) of these MMM-guided intervention studies, a significant improvement in outcome was demonstrated in favor of interventions guided by MMM. Clinical outcome may be improved with interventions guided by MMM. This strengthens the belief in this application, but further interdisciplinary collaborations are needed to overcome the heterogeneity, as illustrated in the present review. Future research should focus on increasing sample sizes, improved data collection, refining definitions of secondary injuries, and standardized interventions. Only then can we proceed with complex outcome studies with MMM-guided treatment.
College students’ learning perceptions and outcomes in different classroom environments: A community of inquiry perspective
Authors: Hu Yan , Huang Jinyan , Kong Fanzhe 
Published: December 2022

IntroductionThis study examined the significant differences in Chinese college students’ learning perceptions and outcomes between the “quasi smart” and smart classrooms under the perspective of the community of inquiry (CoI) framework.MethodsThe participants were 275 freshmen students who took the “college physics” hybrid course in the spring of 2022 at a four-year university in central China. Data were collected from the CoI survey, a follow-up focus group interview with ten randomly selected student participants, and a semi-structured interview with the instructor.Results and discussionThe results indicated that the students’ perceptions of the teaching, social, and cognitive presences were significantly higher in the smart classroom than in the “quasi smart” classroom; further, students in the smart classroom achieved significantly higher course marks than those in the “quasi smart” classroom. The pros and cons of these two different classroom environments were identified by the participating students and their course instructor.