bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stellera chamaejasme L. extracts in the treatment of glioblastoma cell lines: Biological verification based on a network pharmacology approach
Authors: Wang Kaiyue , Wang Zengyong , Wang Zhiqiang , Xie Xiaoli , Zang Lanlan , Wang Lijuan , Che Fengyuan 
Published: August 2022

BackgroundStellera chamaejasme L (RXLD) has been demonstrated with good clinical effects and medicinal value in the treatment of cancer in vivo and in vitro. Specifically, RXLD can eliminate aggregation accumulation, which is depicted as a vital characteristic feature of intracranial tumors. The potential pharmacological mechanisms of anti-glioblastoma (GBM) have not been adequately identified.MethodsThe 3D structures of the chemical ingredients in RXLD were imported into the PharmMapper database to construct the pharmacophore models. The gene targets of GBM were obtained from databases. The pharmacophore-targets network and the protein-protein interactions (PPI) were constructed using the String database and were visualized by using Cytoscape. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were conducted using Bioconductor software. Cytoscape visualized the relationship of pathways and candidate genes to screen for key target genes. Software packages PyMOL, AutoDock, and Vina acquired the molecular docking results. In vitro experiments were undertaken to characterize RXLD extracts’ effects on A172 cell line proliferation, viability, apoptosis, cell cycle, cell wound healing, cell migration, reactive oxygen species generation, and mitochondrial membrane potential. The expression of core genes in the related pathways was detected by Western blotting.ResultsWe identified 216 potential targets associated with GBM. The core components in RXLD were neochamaejasmin A, wikstrol A, isochamaejasmin, chamaejasmine, and subtoxin A. The undertaken GO enrichment analysis revealed that oxidative stress, cell proliferation, cell cycle, cell invasion, and cell migration were involved in the biological processes. The KEGG enrichment analysis revealed that the crucial pathway was MAPK pathway, while HRAS, PRKCB, MAPK9, CCND1, and TP53 were distributed in core locations. A total of seven RXLD pharmacophores demonstrated strong spontaneous docking activities with MAPK9. In vitro assays indicated that RXLD can induce apoptosis, block the cell cycle in the G2/M and S phases, inhibit cell migration via the Wnt/β-catenin pathway, and inhibited p62/Nrf2 pathway.ConclusionsWe speculate that the RAS/MAPK pathway might be an upstream pathway through which the RXLD exerts its anti-GBM effects and might be able to regulate further the Wnt/β-catenin, the oxidative stress, and the ferroptosis pathways.
An exploratory assessment of the management of pediatric traumatic brain injury in three centers in Africa
Authors: Raees Madiha , Hooli Shubhada , von Saint André-von Arnim Amélie O. , Laeke Tsegazeab , Otupiri Easmon , Fabio Anthony , Rudd Kristina E. , Kumar Rashmi , Wilson Patrick T. , Aklilu Abenezer Tirsit , Tuyisenge Lisine , Wang Chunyan , Tasker Robert C. , Angus Derek C. , Kochanek Patrick M. , Fink Ericka L. , Bacha Tigist 
Published: August 2022

PurposeTraumatic brain injury (TBI) is a leading cause of morbidity and mortality in low- and middle-income countries (LMICs). Hospital care practices of pediatric TBI patients in LMICs are unknown. Our objective was to report on hospital management and outcomes of children with TBI in three centers in LMICs.MethodsWe completed a secondary analysis of a prospective observational study in children (&lt;18 years) over a 4-week period. Outcome was determined by Pediatric Cerebral Performance Category (PCPC) score; an unfavorable score was defined as PCPC &gt; 2 or an increase of two points from baseline. Data were compared using Chi-square and Wilcoxon rank sum tests.ResultsFifty-six children presented with TBI (age 0–17 y), most commonly due to falls (43%, n = 24). Emergency department Glasgow Coma Scale scores were ≤ 8 in 21% (n = 12). Head computed tomography was performed in 79% (n = 44) of patients. Forty (71%) children were admitted to the hospital, 25 (63%) of whom were treated for suspected intracranial hypertension. Intracranial pressure monitoring was unavailable. Five (9%, n = 5) children died and 10 (28%, n = 36) inpatient survivors had a newly diagnosed unfavorable outcome on discharge.ConclusionInpatient management and monitoring capability of pediatric TBI patients in 3 LMIC-based tertiary hospitals was varied. Results support the need for prospective studies to inform development of evidence-based TBI management guidelines tailored to the unique needs and resources in LMICs.
Simultaneous absolute protein quantification of seven cytochrome P450 isoforms in rat liver microsomes by LC-MS/MS-based isotope internal standard method
Authors: Jiang Fulin , Zhang Chang , Lu Zihan , Liu Jingyu , Liu Peiqing , Huang Min , Zhong Guoping 
Published: August 2022

The cytochrome P450 (CYP) enzymes play a pivotal role in drug metabolism. LC-MS/MS-based targeting technology has been applied to the analysis of CYP enzymes, promoting drug development and drug-drug interaction studies. Rat is one of the most commonly used models for drug metabolism assessment, but LC-MS/MS assay quantifying the abundance of CYP enzymes in rats is rarely reported. Herein, an accurate and stable LC-MS/MS based method was developed and validated for the simultaneous quantification of seven major rat CYP isoforms (CYP1A2, 2B1, 2C6, 2C11, 2D1, 2E1, and 3A1) in liver microsomes. The careful optimization of trypsin digestion and chromatography combined with isotope-labeled peptide as internal standard improved the efficiency and accuracy of the analysis. Highly specific surrogate peptides were obtained by a procedure including trypsin digestion for six hours and separated on a Hypersil Gold C18 column (100 × 2.1 mm, 3 μm) using gradient elution for 15 min with a mobile phase of water containing 0.1% formic acid and acetonitrile. In the method validation, linearity, matrix effect, recovery, stability, accuracy, and precision all meet the requirements. Subsequently, this method was applied to detect seven enzymes in rat liver microsomes from four different sources, and the correlation between the abundance and activity of CYP enzymes was further analyzed. The high-throughput detection method provided in this study will provide support for pertinent pharmaceutical research based on rat models.
Astragalus Polysaccharides Alleviate Type 2 Diabetic Rats by Reversing the Expressions of Sweet Taste Receptors and Genes Related to Glycolipid Metabolism in Liver
Authors: Luo Meng-Juan , Wang Ying , Chen Si-Yu , Yang Ze-Min 
Published: August 2022

Sweet taste receptors (STRs) play an important role in glucose metabolism, and type 2 diabetic rats have abnormal expressions of STRs in multiple tissues. Astragalus polysaccharides (APS) has shown a significant therapeutic effect on type 2 diabetes mellitus (T2DM), but its mechanism needs to be further clarified. T2DM rat model was induced by intraperitoneal streptozotocin injection and treated with APS for 8 weeks. Daily indicators of experimental rats were observed, and expression levels of STRs and genes related to glycolipid metabolism were determined by real-time quantitative PCR and western blot. The present study revealed that APS alleviated the symptoms of T2DM rats, improved HOMA-IR and promoted insulin secretion. Gene expression analysis found that APS significantly increased the expressions of signaling molecules in STRs pathways, including taste receptor family 1 member 2 (T1R2), α-gustducin (Gα) and transient receptor potential cation channel subfamily member 5 (TRPM5), and reversed the expressions of genes related to glucolipid metabolism, including glucose transporters 2 and 4 (GLUT2 and GLUT4), pyruvate carboxylase (PC), fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) in the liver of T2DM rats. However, APS had no influences on the expressions of genes, including glycogen synthase kinase-3 beta (GSK-3β), pyruvate kinase (PK) and phosphoenolpyruvate carboxykinase (PEPCK) in the liver of T2DM rats. These results suggested that the physiological roles of STRs in the liver were involved with glucose transport and metabolism. APS alleviated T2DM rats by activating the STRs pathway, and promoted glucose transport and lipogenesis.
The median effective analgesic concentration of ropivacaine in ultrasound-guided interscalene brachial plexus block after arthroscopic rotator cuff repair
Authors: Xu Cheng , Gu Fei , Liu Yang , Chen Rui , Wang Chengyu , Lu Jie 
Published: August 2022

Background: The median effective analgesic concentration (MEAC) of ropivacaine in interscalene brachial plexus block (ISBPB) for postoperative analgesia after arthroscopic rotator cuff repair (ARCR) has not been determined. Therefore, this study aimed to evaluate the MEAC after ARCR using 10 ml ropivacaine.Method: This study was conducted on 40 patients with American Society of Anesthesiologists grade I or II who had selective ARCR. The 10 ml ropivacaine was administered for determined, with an initial concentration of 0.3% using up-and-down sequential allocation. After successful or unsuccessful postoperative analgesia, the concentration of ropivacaine was decreased or increased by 0.05% in the next patient. We defined successful postoperative analgesia as a visual analog scale score of &lt;4 at rest within the initial 8 h after ISBPB. The analytic techniques of linear, linear-logarithmic, exponential regressions and centered isotonic regression were used for calculating MEAC. The secondary outcomes was sufentanil consumption, time to 1st rescue analgesic, onset time of sensory block and motor block.Results: The concentration of ropivacaine administered ranged from 0.1% to 0.35%. The MEAC from the four different methods (linear, linear-logarithmic, exponential regressions and centered isotonic regression) were 0.207% (95% CI, 0.168–0.355%), 0.182% (95% CI, 0.165–0.353%), 0.196% (95% CI, 0.154–0.356%), and 0.163%, respectively. Of the four models, exponential regression had the least residual standard error (0.0990).Conclusion: The MEAC derived from the four statistical models for 10 ml ropivacaine in ultrasound-guided ISBPB for postoperative analgesia was distributed within a narrow range of 0.163%–0.207%. The exponential regression model calculated by the goodness-of-fit test at a concentration of 0.196% best fits the study data.Clinical Trial Registration:http://www.chictr.org.cn/showproj.aspx?proj=127449, identifier ChiCTR2100047978
Integrated bioinformatics analysis uncovers characteristic genes and molecular subtyping system for endometriosis
Authors: Wang Zhaowei , Liu Jia , Li Miaoli , Lian Lishan , Cui Xiaojie , Ng Tai-Wei , Zhu Maoshu 
Published: August 2022

Objective: Endometriosis is a chronic inflammatory estrogen-dependent disease with the growth of endometrial tissues outside the uterine cavity. Nevertheless, the etiology of endometriosis is still unclear. Integrated bioinformatics analysis was implemented to reveal the molecular mechanisms underlying this disease.Methods: A total of four gene expression datasets (GSE7305, GSE11691, GSE23339, and GSE25628) were retrieved from the GEO, which were merged into a meta-dataset, followed by the removal of batch effects via the sva package. Weighted gene co-expression network analysis (WGCNA) was implemented, and endometriosis-related genes were screened under normal and endometriosis conditions. Thereafter, characteristic genes were determined via Lasso analysis. The diagnostic performance was estimated via receiver operating characteristic curves, and epigenetic and post-transcriptional modifications were analyzed. Small molecular compounds were predicted. Unsupervised clustering analysis was conducted via non-negative matrix factorization algorithm. The enriched pathways were analyzed via gene set enrichment analysis or GSVA. Immune features were evaluated according to immune-checkpoints, HLA, receptors, chemokines, and immune cells.Results: In total, four characteristic genes (BGN, AQP1, ELMO1, and DDR2) were determined for endometriosis, all of which exhibited the favorable efficacy in diagnosing endometriosis. Their aberrant levels were modulated by epigenetic and post-transcriptional modifications. In total, 51 potential drugs were predicted against endometriosis. The characteristic genes exhibited remarkable associations with immunological function. Three subtypes were classified across endometriosis, with different mechanisms and immune features.Conclusion: Our study reveals the characteristic genes and novel molecular subtyping of endometriosis, contributing to the early diagnosis and intervention in endometriosis.
Pharmacological suppression of Nedd4-2 rescues the reduction of Kv11.1 channels in pathological cardiac hypertrophy
Authors: Zhang Hua , Fu Tian , Sun Jinglei , Zou Sihao , Qiu Suhua , Zhang Jiali , Su Shi , Shi Chenxia , Li De-Pei , Xu Yanfang 
Published: August 2022

The human ether-á-go-go-related gene (hERG) encodes the pore-forming subunit (Kv11.1), conducting a rapidly delayed rectifier K+ current (IKr). Reduction of IKr in pathological cardiac hypertrophy (pCH) contributes to increased susceptibility to arrhythmias. However, practical approaches to prevent IKr deficiency are lacking. Our study investigated the involvement of ubiquitin ligase Nedd4-2-dependent ubiquitination in IKr reduction and sought an intervening approach in pCH. Angiotensin II (Ang II) induced a pCH phenotype in guinea pig, accompanied by increased incidences of sudden death and higher susceptibility to arrhythmias. Patch-clamp recordings revealed a significant IKr reduction in pCH cardiomyocytes. Kv11.1 protein expression was decreased whereas its mRNA level did not change. In addition, Nedd4-2 protein expression was increased in pCH, accompanied by an enhanced Nedd4-2 and Kv11.1 binding detected by immunoprecipitation analysis. Cardiac-specific overexpression of inactive form of Nedd4-2 shortened the prolonged QT interval, reversed IKr reduction, and decreased susceptibility to arrhythmias. A synthesized peptide containing the PY motif in Kv11.1 C-terminus binding to Nedd4-2 and a cell-penetrating sequence antagonized Nedd4-2-dependent degradation of the channel and increased the surface abundance and function of hERG channel in HEK cells. In addition, in vivo administration of the PY peptide shortened QT interval and action potential duration, and enhanced IKr in pCH. We conclude that Nedd4-2-dependent ubiquitination is critically involved in IKr deficiency in pCH. Pharmacological suppression of Nedd4-2 represents a novel approach for antiarrhythmic therapy in pCH.
Case Report: A good response to furmonertinib second-line treatment of an advanced lung adenocarcinoma patient with a rare EGFR exon 20 N771_P772insH mutation: A case report and literature review
Authors: Zhang Xiao , Han Huan , Zhao Jiuzhou , Liu Xiao , Zhang Jianbo , Sun Rui , Li Shaomei , Liu Baoxing , Zhu Hui , Jiao Shuyue , Li Xiang , Tang Hong 
Published: August 2022

Background: Lung adenocarcinoma with the classical EGFR 19 deletion and exon 21 L858R point mutations has exhibited good responses to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment. However, the sensitivity of uncommon EGFR exon 20 insertion mutation to third-generation EGFR-TKIs has not been determined. Although emerging targeted therapies for EGFR exon 20 insertion mutation have been reported in recent years, such patients still have a poorer prognosis than those with typical or wild-type EGFR mutations.Case summary: Here, we report the case of a 57-year-old man with advanced non-small cell lung cancer (NSCLC) with a rare EGFR exon 20 N771_P772insH mutation. The patient was treated with furmonertinib as second-line therapy. Although his pleural effusion was more than before that during treatment, various examination results showed that the pleural effusion was closely related to hypoproteinemia; thus, local progression was not considered. His cough was significantly alleviated, and the dose was well tolerated. The patient was evaluated for a remarkable progression-free survival (PFS) of 10.0 months, a duration of response (DOR) of 8.0 months, and an overall survival (OS) of 22.0 months, which had not previously been achieved.Conclusion: The present study indicated that furmonertinib might be a good treatment option for first-line progressive NSCLC patients with EGFR exon 20 insertion mutation.
Apatinib for recurrent/progressive glioblastoma multiforme: A salvage option
Authors: Zhang Hong-Hong , Du Xiao-Jing , Deng Mei-Ling , Zheng Lie , Yao Dun-Chen , Wang Zhi-Qiang , Yang Qun-Ying , Wu Shao-Xiong 
Published: August 2022

Purpose: The recurrent/progressive glioblastoma multiforme (GBM) carries a dismal prognosis and the definitive treatment strategy has not yet been established. This study aimed to assess the efficacy and safety of apatinib in recurrent/progressive GBM patients.Materials and methods: The clinical data of 19 recurrent/progressive GBM patients who received apatinib treatment from November 2015 to December 2019 at Sun Yat-sen University Cancer Center were collected retrospectively in this study. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (AEs) were reviewed and assessed.Results: The overall ORR was 52.6%, and the DCR was 73.7%. Median PFS and OS were 5.1 and 10.4 months, respectively. The 6-month PFS and OS rates were 38.9% and 68.4%, respectively. The 12-month PFS and OS rates were 16.7% and 36.8%, respectively. The treatment-related toxicities were generally well-tolerated. The most common grade 3/4 AEs were hand-foot syndrome (36.8%) and hypertension (21.1%).Conclusion: Our study showed that apatinib therapy provided a better salvaging option for recurrent/progressive GBM patients and the toxicity was manageable.
Psychological distress and its influencing factors among psychiatric nurses in China: A cross-sectional study
Authors: Wang Juan , Zheng Zhongren , Tang Yingxue , Zhang Rui , Lu Qinghua , Wang Bin , Sun Qihua 
Published: August 2022

BackgroundPsychiatric nurses often face abuse, attacks, escape, suicides, and other situations related to the care of patients with mental disorders, which are more likely to induce psychological distress.AimsThis study aimed to examine the relationship between coping styles and psychological distress among Chinese psychiatric nurses in Shandong and the significance of sleep quality as a mediating factor.MethodsA total of 812 psychiatric nurses in Shandong, China, were investigated using the Psychological Distress Scale (K10), Simplified Coping Style Questionnaire (SCSQ), Pittsburgh Sleep Quality Index (PSQI) and self-compiled general information questionnaire.ResultsPsychological distress was detected in 571 psychiatric nurses (70.3%). The psychological distress of psychiatric nurses was significantly different with respect to professional title (χ2 = 10.627, P &lt; 0.05) and shift work (χ2 = 9.120, P &lt; 0.01). Psychological distress positively correlated with negative coping style (r = 0.266, P &lt; 0.01) and sleep quality (PSQIT) (r = 0.532, P &lt; 0.01). A significant positive correlation was found between psychological distress and all dimensions of sleep quality (r = 0.158–0.456, P &lt; 0.05). Professional title, positive coping style, negative coping style, sleep quality (PSQIT), subjective sleep quality, sleep disorder and daytime dysfunction predicted psychological distress in psychiatric nurses (R2 = 0.363, F = 65.343, P &lt; 0.01). The relationship between negative coping style and psychological distress was partially mediated by sleep quality, with the mediating effect accounting for 37.97% of the total effect.ConclusionsPsychiatric nurses have a high rate of psychological distress, which is closely related to coping styles, and sleep quality has a certain regulatory effect.
Perceptions of and challenges faced by primary healthcare workers about preconception services in rural India: A qualitative study using focus group discussion
Authors: Chutke Amruta Paresh , Doke Prakash Prabhakarrao , Gothankar Jayashree Sachin , Pore Prasad Dnyandeo , Palkar Sonali Hemant , Patil Archana Vasantrao , Deshpande Aniruddha Vinayakrao , Bhuyan Khanindra Kumar , Karnataki Madhusudan Vaman , Shrotri Aparna Nishikant 
Published: August 2022

BackgroundProviding preconception care through healthcare workers at the primary health care level is a crucial intervention to reduce adverse pregnancy outcomes, consequently reducing neonatal mortality. Despite the availability of evidence, this window of opportunity remains unaddressed in many countries, including India. The public health care system is primarily accessed by rural and tribal Indian population. It is essential to know the frontline healthcare workers perception about preconception care. The study aimed to identify barriers and suggestions for framing appropriate strategies for implementing preconception care through primary health centers.MethodsThe authors conducted a qualitative study using focus group discussions (FGDs) with 45 healthcare workers in four FGDs (8–14 participants in each), in four blocks of Nashik district. The transcribed discussions were analyzed in MAXQDA software using the Socio-Ecological Model as an initial coding guide, including four levels of factors (individual, interpersonal, community, and institutional) that influenced an individual's behavior to use preconception care services.ResultsHealthcare workers had some knowledge about preconception care, limited to adolescent health and family planning services. The interpersonal factors included heavy workload, stress, lack of support and co-operation, and paucity of appreciation, and motivation. The perceived community factors included poverty, migration, poor knowledge of preconception care, lack of felt need for preconception services, the influence of older women in the household decision, low male involvement, myths and misconceptions regarding preconception services. The identified institutional factors were lack of human resources, specialized services, logistics, and challenges in delivering adolescent health and family planning programs. Healthcare workers suggested the need for program-specific guidelines, training and capacity building of human resources, an un-interrupted supply of logistics, and a unique community awareness drive supporting preconception care services.ConclusionMulti-level factors of the Socio-Ecological Model influencing the preconception care services should be considered for framing strategies in the implementation of comprehensive preconception care as a part of a continuum of care for life cycle phases of women.