bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bibliometric Analysis of Studies on Neuropathic Pain Associated With Depression or Anxiety Published From 2000 to 2020
Authors: Li Kai-Li-Mi , Chen Yu-Meng , Wang Xue-Qiang , Hu Hao-Yu 
Published: September 2021

Objective: Neuropathic pain (NP) associated with depression or anxiety is highly prevalent in clinical practice. Publications about NP associated with depression or anxiety increased exponentially from 2000 to 2020. However, studies that applied the bibliometric method in analyzing global scientific research about NP associated with depression or anxiety are rare. This work used the bibliometric method to analyze the publications on NP associated with depression or anxiety between 2000 and 2020.Method: Publications from 2000 and 2020 were identified from the Thomson Reuters Web of Science (WoS) database. We employed CiteSpace V to conduct the bibliometric study.Results: A total of 915 articles or reviews were obtained from the WoS database. The number of publications has increased over the last two decades. The USA was the most productive among countries or regions in the field. According to the burst key words, neuroinflammation, hippocampus, safety, and modulation were the hot global research issues in the domain.Conclusion: Publications about NP associated with depression or anxiety have remarkably increased from 2000 to 2020. These historical opinions about NP associated with depression or anxiety could be an important practical basis for further research into potential development trends.
Pharmacological Rescue of the Brain Cortex Phenotype of Tbx1 Mouse Mutants: Significance for 22q11.2 Deletion Syndrome
Authors: Favicchia Ilaria , Flore Gemma , Cioffi Sara , Lania Gabriella , Baldini Antonio , Illingworth Elizabeth 
Published: September 2021

ObjectivesTbx1 mutant mice are a widely used model of 22q11.2 deletion syndrome (22q11.2DS) because they manifest a broad spectrum of physical and behavioral abnormalities that is similar to that found in 22q11.2DS patients. In Tbx1 mutants, brain abnormalities include changes in cortical cytoarchitecture, hypothesized to be caused by the precocious differentiation of cortical progenitors. The objectives of this research are to identify drugs that have efficacy against the brain phenotype, and through a phenotypic rescue approach, gain insights into the pathogenetic mechanisms underlying Tbx1 haploinsufficiency.Experimental ApproachDisease model: Tbx1 heterozygous and homozygous embryos. We tested the ability of two FDA-approved drugs, the LSD1 inhibitor Tranylcypromine and Vitamin B12, to rescue the Tbx1 mutant cortical phenotype. Both drugs have proven efficacy against the cardiovascular phenotype, albeit at a much reduced level compared to the rescue achieved in the brain.MethodsIn situ hybridization and immunostaining of histological brain sections using a subset of molecular markers that label specific cortical regions or cell types. Appropriate quantification and statistical analysis of gene and protein expression were applied to identify cortical abnormalities and to determine the level of phenotypic rescue achieved.ResultsCortical abnormalities observed in Tbx1 mutant embryos were fully rescued by both drugs. Intriguingly, rescue was obtained with both drugs in Tbx1 homozygous mutants, indicating that they function through mechanisms that do not depend upon Tbx1 function. This was particularly surprising for Vitamin B12, which was identified through its ability to increase Tbx1 gene expression.ConclusionTo our knowledge, this is only the second example of drugs to be identified that ameliorate phenotypes caused by the mutation of a single gene from the 22q11.2 homologous region of the mouse genome. This one drug-one gene approach might be important because there is evidence that the brain phenotype in 22q11.2DS patients is multigenic in origin, unlike the physical phenotypes, which are overwhelmingly attributable to Tbx1 haploinsufficiency. Therefore, effective treatments will likely involve the use of multiple drugs that are targeted to the function of specific genes within the deleted region.
Prognostic Score for De Novo Metastatic Breast Cancer With Liver Metastasis and Its Predictive Value of Locoregional Treatment Benefit
Authors: Ji Lei , Fan Lei , Zhu Xiuzhi , Gao Yu , Wang Zhonghua 
Published: September 2021

BackgroundThere is a significant survival difference and lack of effective treatment among breast cancer patients with liver metastasis. This present study aimed to construct a novel prognostic score for predicting the prognosis and locoregional treatment benefit of de novo metastatic breast cancer with liver metastasis (BCLM).MethodsIn total, 2,398 eligible patients between 2010 and 2016 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. They were assigned to the training set including 1,662 patients (2010–2014) and validation set comprising 736 patients (2015–2016) depending on the time of diagnosis. The prognostic score was based on regression coefficients in the multivariate Cox regression analysis. And then, patients were stratified into low-, intermediate-, and high-risk groups by the prognostic score. The discrimination and calibration of prognostic score were evaluated using time-dependent receiver operating characteristic (ROC) curves analysis and calibration curves, respectively. Subgroup analysis was performed to evaluate locoregional surgery and chemotherapy benefit in different risk groups.ResultsAge, race, insurance and marital status, T stage, pathological grade, molecular subtypes, and extrahepatic metastasis were identified as independent prognostic variables in the prognostic score. The prognostic score showed high discrimination power with an area under the curve (AUC) of 0.77 and 0.72 and excellent agreement suggested by calibration plots in the training and validation sets, respectively. Intermediate-risk [hazard ratio (HR) 2.39, 95% confidence interval (CI) 2.09–2.73, P&lt;0.001] and high-risk groups (HR 4.88; 95% CI 4.13–5.76; P&lt;0.001) had significantly worse prognosis in comparison with the low-risk group. The median overall survival (OS) in three prognostic groups were 44, 18, and 7 months, with a 3-year survival rate of 56, 23, and 7%, respectively. Apart from the high-risk group (HR 0.79; 95% CI 0.56–1.10; P=0.157), the low-risk (HR 0.64; 95% CI 0.49–0.84; P=0.001) and intermediate-risk groups (HR 0.68; 95% CI 0.55–0.85; P=0.001) could benefit from the surgery of primary site, while chemotherapy improved prognosis in all risk groups.ConclusionsA prognostic score was developed to accurately predict the prognosis of de novo BCLM patients. Moreover, it may be useful for further subdividing them into different risk groups and helping guide clinicians in treatment decisions.
Patterns of Recurrence and Survival Rate After Complete Resection of Pathological Stage N2 Small-Cell Lung Cancer
Authors: Yu Lian , Xu Jianlin , Qiao Rong , Zhong Hua , Han Baohui , Zhong Runbo 
Published: September 2021

The benefits of surgical resection for patients with stage N2 limited-disease small-cell lung cancer (LD-SCLC) remain controversial. This retrospective study analyzed the survival and recurrence patterns of the patients diagnosed with pathological N2 (p-N2) LD-SCLC after radical resection. A total of 171 p-N2 LD-SCLC patients who underwent radical pulmonary resection and systematic lymphadenectomies at Shanghai Chest Hospital from July 2005 to June 2015 were enrolled. The influence of the mediastinal lymph node status (single or multiple nodes, single- or multiple-station) on the survival and recurrence patterns was retrospectively analyzed. The main recurrence sites were outside the chest cavity (54.8%) and hematogenous metastasis (67.4%). The bone and liver as initial recurrence sites had a poor prognosis, with a median overall survival (OS) of 13.100 months and 11.900 months, respectively. The median disease-free survival (DFS) of patients diagnosed with single and multiple p-N2 after surgery were 19.233 and 9.367 months (P = 0.001), and the median OS were 43.033 and 17.100 months (P &lt; 0.001), respectively. In conclusion, recurrence occurred in the form of hematogenous metastasis mostly in the extra-thoracic part. Interestingly, patients diagnosed with single p-N2 benefited from radical resection. Surgery may be a treatment option regardless of the T stage if N2 SCLC with a single metastatic lymph node can be identified preoperatively.
Enhanced CT-Based Radiomics to Predict Micropapillary Pattern Within Lung Invasive Adenocarcinoma
Authors: Xu Yunyu , Ji Wenbin , Hou Liqiao , Lin Shuangxiang , Shi Yangyang , Zhou Chao , Meng Yinnan , Wang Wei , Chen Xiaofeng , Wang Meihao , Yang Haihua 
Published: September 2021

ObjectiveWe aimed to investigate whether enhanced CT-based radiomics can predict micropapillary pattern (MPP) of lung invasive adenocarcinoma (IAC) in the pre-op phase and to develop an individual diagnostic predictive model for MPP in IAC.Methods170 patients who underwent complete resection for pathologically confirmed lung IAC were included in our study. Of these 121 were used as a training cohort and the other 49 as a test cohort. Clinical features and enhanced CT images were collected and assessed. Quantitative CT analysis was performed based on feature types including first order, shape, gray-level co-occurrence matrix-based, gray-level size zone matrix-based, gray-level run length matrix-based, gray-level dependence matrix-based, neighboring gray tone difference matrix-based features and transform types including Log, wavelet and local binary pattern. Receiver operating characteristic (ROC) and area under the curve (AUC) were used to value the ability to identify the lung IAC with MPP using these characteristics.ResultsUsing quantitative CT analysis, one thousand three hundred and seventeen radiomics features were deciphered from R (https://www.r-project.org/). Then these radiomic features were decreased to 14 features after dimension reduction using the least absolute shrinkage and selection operator (LASSO) method in R. After correlation analysis, 5 key features were obtained and used as signatures for predicting MPP within IAC. The individualized prediction model which included age, smoking, family tumor history and radiomics signature had better identification (AUC=0.739) in comparison with the model consisting only of radiomics features (AUC=0.722). DeLong test showed that the difference in AUC between the two models was statistically significant (P&lt;0.01). Compared with the simple radiomics model, the more comprehensive individual prediction model has better prediction performance.ConclusionThe use of radiomics approach is of great value in the diagnosis of tumors by non-invasive means. The individualized prediction model in the study, when incorporated with age, smoking and radiomics signature, had effective predictive performance of lung IAC with MPP lesions. The combination of imaging features and clinical features can provide additional diagnostic value to identify the micropapillary pattern in IAC and can affect clinical diagnosis and treatment.
Downregulation of GNA15 Inhibits Cell Proliferation via P38 MAPK Pathway and Correlates with Prognosis of Adult Acute Myeloid Leukemia With Normal Karyotype
Authors: Li Mengya , Liu Yu , Liu Yajun , Yang Lu , Xu Yan , Wang Weiqiong , Jiang Zhongxing , Liu Yanfang , Wang Shujuan , Wang Chong 
Published: September 2021

BackgroundThe prognosis of acute myeloid leukemia (AML) with a normal karyotype is highly heterogonous, and the current risk stratification is still insufficient to differentiate patients from high-risk to standard-risk. Changes in some genetic profiles may contribute to the poor prognosis of AML. Although the prognostic value of G protein subunit alpha 15 (GNA15) in AML has been reported based on the GEO (Gene Expression Omnibus) database, the prognostic significance of GNA15 has not been verified in clinical samples. The biological functions of GNA15 in AML development remain open to investigation. This study explored the clinical significance, biological effects and molecular mechanism of GNA15 in AML.MethodsReverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the mRNA expression level of GNA15 in blasts of bone marrow specimens from 154 newly diagnosed adult AML patients and 26 healthy volunteers. AML cell lines, Kasumi-1 and SKNO-1, were used for lentiviral transfection. Cell Counting Kit-8 (CCK8) and colony formation assays were used to determine cell proliferation. Cell cycle and apoptosis were analyzed by flow cytometry. The relevant signaling pathways were evaluated by Western blot. The Log-Rank test and Kaplan-Meier were used to evaluate survival rate, and the Cox regression model was used to analyze multivariate analysis. Xenograft tumor mouse model was used for in vivo experiments.ResultsThe expression of GNA15 in adult AML was significantly higher than that in healthy individuals. Subjects with high GNA15 expression showed lower overall survival and relapse-free survival in adult AML with normal karyotype. High GNA15 expression was independently correlated with a worse prognosis in multivariate analysis. Knockdown of GNA15 inhibited cell proliferation and cell cycle progression, and induced cell apoptosis in AML cells. GNA15-knockdown induced down-regulation of p-P38 MAPK and its downstream p-MAPKAPK2 and p-CREB. Rescue assays confirmed that P38 MAPK signaling pathway was involved in the inhibition of proliferation mediated by GNA15 knockdown.ConclusionsIn summary, GNA15 was highly expressed in adult AML, and high GNA15 expression was independently correlated with a worse prognosis in adult AML with normal karyotype. Knockdown of GNA15 inhibited the proliferation of AML regulated by the P38 MAPK signaling pathway. Therefore, GNA15 may serve as a potential prognostic marker and a therapeutic target for AML in the future.
Overexpression of Circular RNA circ_0013587 Reverses Erlotinib Resistance in Pancreatic Cancer Cells Through Regulating the miR-1227/E-Cadherin Pathway
Authors: Xu Huiting , Chen Runzhi , Shen Qian , Yang Dongmei , Peng Hui , Tong Jin , Fu Qiang 
Published: September 2021

BackgroundErlotinib, a small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, demonstrated therapeutic efficacy against pancreatic cancer. However, acquired resistance to erlotinib in pancreatic cancer is widely observed, and the exact mechanisms have not been fully explored until now. We examined the role of circular RNA circ_0013587 in the acquired resistance to erlotinib in pancreatic cancer cells and explored the underlying mechanisms.MethodsWe selected erlotinib-resistant pancreatic cancer cells from the AsPC-1 cell line. The expression of circ_0013587 was examined by qRT-PCR assays. The effects of circ_0013587 on pancreatic cancer cell proliferation, invasion, and erlotinib resistance were assessed by cell functional assays. Bioinformatic analysis and dual-luciferase reporter assays identified circ_0013587 and E-cadherin as direct targets of miR-1227. Mouse xenograft models were employed to investigate the function of circ_0013587 in erlotinib resistance of tumors in vivo.ResultsCirc_0013587 expression was significantly reduced in erlotinib-resistant AsPC-1 cells. We found that increasing circ_0013587 levels in erlotinib-resistant AsPC-1 cells re-sensitized them, whereas reducing circ_0013587 levels in erlotinib-sensitive AsPC-1 cells made them resistant. Mechanically, circ_0013587 released E-cadherin from the suppression of miR-1227, leading to E-cadherin up-regulation. Rescue assays highlighted that circ_0013587 reversed erlotinib resistance in pancreatic cancer cells by increasing E-cadherin levels through reducing the expression of miR-1227. Furthermore, circ_0013587 overexpression sensitized erlotinib-resistant AsPC-1 cells to erlotinib in xenograft models.ConclusionsOur results demonstrated that down-regulation of circ_0013587 contributes to acquired resistance to erlotinib in pancreatic cancer cells through mediating the miR-1227/E-cadherin pathway and that circ_0013587 is a potential target molecular to overcome erlotinib resistance.
Early Prediction of Tacrolimus-Induced Tubular Toxicity in Pediatric Refractory Nephrotic Syndrome Using Machine Learning
Authors: Mo Xiaolan , Chen Xiujuan , Ieong Chifong , Gao Xia , Li Yingjie , Liao Xin , Yang Huabin , Li Huiyi , He Fan , He Yanling , Chen Yilu , Liang Huiying , Huang Min , Li Jiali 
Published: September 2021

Background and Aims: Tacrolimus(TAC)-induced nephrotoxicity, which has a large individual variation, may lead to treatment failure or even the end-stage renal disease. However, there is still a lack of effective models for the early prediction of TAC-induced nephrotoxicity, especially in nephrotic syndrome(NS). We aimed to develop and validate a predictive model of TAC-induced tubular toxicity in children with NS using machine learning based on comprehensive clinical and genetic variables.Materials and Methods: A retrospective cohort of 218 children with NS admitted between June 2013 and December 2018 was used to establish the models, and 11 children were prospectively enrolled for external validation. We screened 47 clinical features and 244 genetic variables. The changes in urine N- acetyl- β-D- glucosaminidase(NAG) levels before and after administration was used as an indicator of renal tubular toxicity.Results: Five machine learning algorithms, including extreme gradient boosting (XGBoost), gradient boosting decision tree (GBDT), extremely random trees (ET), random forest (RF), and logistic regression (LR) were used for model generation and validation. Four genetic variables, including TRPC6 rs3824934_GG, HSD11B1 rs846910_AG, MAP2K6 rs17823202_GG, and SCARB2 rs6823680_CC were incorporated into the final model. The XGBoost model has the best performance: sensitivity 75%, specificity 77.8%, accuracy 77.3%, and AUC 78.9%.Conclusion: A pre-administration model with good performance for predicting TAC-induced nephrotoxicity in NS was developed and validated using machine learning based on genetic factors. Physicians can estimate the possibility of nephrotoxicity in NS patients using this simple and accurate model to optimize treatment regimen before administration or to intervene in time after administration to avoid kidney damage.
Cardio- and Cerebrovascular Outcomes of Postoperative Acute Kidney Injury in Noncardiac Surgical Patients With Hypertension
Authors: Guangyu Yan , Jingfeng Lou , Xing Liu , Hong Yuan , Yao Lu 
Published: September 2021

Background: The cardiovascular and cerebrovascular risk of postoperative acute kidney injury (AKI) in surgical patients is poorly described, especially in the hypertensive population.Methods: We conducted a retrospective cohort study among all hypertensive patients who underwent elective noncardiac surgery from January 1st, 2012 to August 1st, 2017 at the Third Xiangya Hospital. The primary outcomes were fatal stroke and fatal myocardial infarction (MI). The secondary outcomes were all-cause mortality.Results: The postoperative cumulative mortality within 3 months, 6 months, 1 year, 2 years, and 5 years were 1.27, 1.48, 2.15, 2.15, and 5.36%, for fatal stroke, and 2.05, 2.27, 2.70, 3.37, and 5.61% for fatal MI, respectively, in patients with postoperative AKI. Compared with non-AKI patients, those with postoperative AKI had a significantly higher risk of fatal stroke and fatal MI within 3 months [hazard ratio (HR): 5.49 (95% CI: 1.88−16.00) and 11.82 (95% CI: 4.56−30.62), respectively], 6 months [HR: 3.58 (95% CI: 1.43−8.97) and 9.23 (95% CI: 3.89−21.90), respectively], 1 year [HR: 3.64 (95% CI: 1.63−8.10) and 5.14 (95% CI: 2.50−10.57), respectively], 2 years [HR: 2.21 (95% CI: 1.03−4.72) and 3.06 (95% CI: 1.66−5.64), respectively], and 5 years [HR: 2.27 (95% CI: 1.30−3.98) and 1.98 (95% CI: 1.16−3.20), respectively]. In subgroup analysis of perioperative blood pressure (BP) lowering administration, postoperative AKI was significantly associated with 1-year and 5-year risk of fatal stroke [HR: 9.46 (95% CI: 2.85−31.40) and 3.88 (95% CI: 1.67−9.01), respectively] in patients with ACEI/ARB, and MI [HR: 6.62 (95% CI: 2.23−19.62) and 2.44 (95% CI: 1.22−4.90), respectively] in patients with CCB.Conclusion: Hypertensive patients with postoperative AKI have a significantly higher risk of fatal stroke and fatal MI, as well as all-cause mortality, within 5 years after elective noncardiac surgery. In patients with perioperative administration of ACEI/ARB and CCB, postoperative AKI was significantly associated with higher risk of fatal stroke and MI, respectively.
Salvianolate Ameliorates Osteopenia and Improves Bone Quality in Prednisone-Treated Rheumatoid Arthritis Rats by Regulating RANKL/RANK/OPG Signaling
Authors: Gao Xiang , Wu Qingyun , Zhang Xinle , Tian Jia , Liang Dahong , Min Yalin , Lu Jiaqi , Zhang Xuemei , Cui Liao , Xu Bilian , Liu Yanzhi 
Published: September 2021

Rheumatoid arthritis (RA) is closely associated with periarticular osteopenia and leads to a high risk of generalized osteoporosis. Although glucocorticoid (GC) treatment ameliorates joint degradation and manages inflammation in RA, GC application may induce further bone quality deterioration in RA patients. Current treatments for RA lack relevant strategies for the prevention and treatment of osteopenia in RA. In this study, we aimed to investigate whether salvianolate treatment ameliorated osteopenia in prednisone-treated RA rats. Lewis rats with collagen-induced arthritis (CIA) were administered prednisone (PDN) or PDN plus salvianolate (PDN+Sal) treatment for 90 days. The effects of Sal were investigated in PDN-treated CIA rats. To further evaluate the effects of Sal under inflammatory conditions, we investigated the effects of Sal treatment on the TNF-α-induced inflammatory response in MC3T3-E1 osteoblasts. Bone histomorphometry, bone mineral density (BMD), bone biomechanical properties, micro-computed tomography (micro-CT), immunohistochemistry, RT-PCR and western blot analyses were performed to evaluate the effects of Sal. The results demonstrated that RA induced bone loss and bone quality deterioration, with high bone turnover in CIA rats. PDN+Sal treatment significantly increased BMD and trabecular/cortical bone mass, suppressed inflammation, and improved bone biomechanical properties compared to CIA control and PDN treatment. PDN+Sal treatment significantly suppressed bone resorption and the RANKL and RANKL/OPG ratios compared to PDN. PDN+Sal and PDN treatment significantly inhibited TNF-α by 82 and 83%, respectively, and both suppressed inflammation in CIA rats. However, there was no significant difference between PDN+Sal and PDN treatment alone in regard to bone formation parameters or the management of inflammation and arthropathy. Sal significantly increased Osterix, OPN, and Col1a1 while decreasing RANKL, TRAF6, and TRAIL gene in TNF-α-induced MC3T3-E1 osteoblasts. Sal significantly increased Osterix, OPN and RUNX2 while decreasing NF-κB, TRAF6 and IL-1β protein in TNF-α-induced MC3T3-E1 osteoblasts. The results suggested that salvianolate treatment ameliorated osteopenia and improved bone quality in prednisone-treated RA rats, and the potential mechanism may be related to the regulation of the RANKL/RANK/OPG signaling pathway, TRAIL-TRAF6-NFκB signal axis, and downregulation of inflammatory cytokines. Salvianolate could be used as a promising supplemental therapeutic strategy to ameliorate osteopenia and improve bone quality in GC-treated RA patients.