bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppression of Tumorigenicity 5 Ameliorates Tumor Characteristics of Invasive Breast Cancer Cells via ERK/JNK Pathway
Authors: Cheng Jianghong , Li Mingli , Tzeng Chi-Meng , Gou Xingchun , Chen Shuai 
Published: July 2021

BackgroundSuppression of tumorigenicity 5 (ST5) has been considered as a tumor suppressor gene in HeLa tumor cells. However, its role in the progression of breast cancer remains vague.MethodsOnline database analysis was determined by Oncomine and Breast Cancer Gene-Expression Miner v4.4 (bc-GenExMiner v4.4). Tumor biology behaviors were measured by MTT assay, wound healing model, Transwell and Flow cytometry assays. Methylation-specific PCR (MSP) was employed to detect promoter methylation.ResultsLow level of ST5 was observed in breast cancer specimens, particularly in recurrent, invasive breast cancer cases compared to para-carcinoma tissue or non-invasive breast cancer. The downregulation of ST5 was also proved in MDA-MB-231 and SKBR3 cell lines with a high invasive capability as compared to MCF-7 cell with a low invasive capability. ST5 was negatively associated with pathological stages of breast cancer. ST5-downregulation promoted, while ST5-upregulation inhibited the progression of cell proliferation, cell cycle and migration of MDA-MB-231 cells. Additionally, ST5 knockdown inhibited, whereas ST5 overexpression promoted apoptosis of MDA-MB-231 cells. However, ST5 modification, either upregulation or downregulation, had no significant impact on tumor behaviors of MCF-7 cells. Mechanistically, ST5 protein ablation activated, while ST5-upregulation repressed the activities of phosphorylated ERK1/2 and JNK, and subsequently the expression of c-Myc. PD98059-mediated ERK1/2 inhibition abolished the stimulatory effects of ST5-depletion on ERK1/2/JNK/c-Myc signaling axis, and ST5 depletion-mediated cell over-proliferation and migration. Of note, ST5 reduction in invasive breast cancer cells should implicate in the hypermethylation of ST5 promoter region.ConclusionOur findings suggest that ST5 potentially acts as a tumor suppressor gene in invasive breast cancer through regulating ERK/JNK signaling pathway and provide a novel insight for breast cancer treatment.
The Survival Effect of Radiotherapy on Stage II/III Rectal Cancer in Different Age Groups: Formulating Radiotherapy Decision-Making Based on Age
Authors: Li Yuqiang , Liu Heli , Zhou Yuan , Zhou Zhongyi , Liu Wenxue , Zhao Lilan , Güngör Cenap , Wang Dan , Pei Qian , Pei Haiping , Tan Fengbo 
Published: July 2021

IntroductionTotal mesorectal excision (TME), chemotherapy (CT), and radiotherapy (RT) are usually integrated into the comprehensive treatment of stage II/III rectal cancer (RC). Neoadjuvant radiotherapy (nRT) has become the standard treatment for stage II/III RC patients to help reduce the size of a tumor or kill cancer cells that have spread. Adjuvant RT is delivered after the resection to destroy remaining cancer cells and used mainly in stage II/III RC patients who have not received preoperative radiotherapy, such as those who suffered from a bowel obstruction before surgery. It is controversial whether radiotherapy can improve the survival of stage II/III RC patients. An increasing number of studies have reported that rectal cancer exhibited mismatched biology, epidemiology, and therapeutic response to current treatment strategy in different age groups. It is necessary to investigate whether radiotherapy exhibits disparate effects in different age groups of patients with stage II/III RC.MethodsData from the Surveillance, Epidemiology, and End Results (SEER) Program was extracted to identify stage II/III RC diagnosed in the periods of 2004–2016. The statistical methods included Pearson’s chi-square test, log-rank test, Cox regression model, and propensity score matching.ResultsNeoadjuvant radiotherapy (nRT) cannot improve the prognosis, and postoperative RT may even reduce the survival time for early onset stage II/III RC. Postoperative RT was not able to improve the overall survival (OS), while nRT may provide limited survival improvement for middle-aged stage II/III RC patients. In addition, radiotherapy can significantly improve the prognosis for elderly stage II/III RC.ConclusionsThis study indicated the inconsistent survival effect of radiotherapy on stage II/III rectal cancer patients in different age groups. Hence, we formulated a novel flow chart of radiotherapy decision-making based on age in stage II/III RC patients.
Association of Preoperative Coagulability With Incidence and Extent of Portal Vein Tumor Thrombus and Survival Outcomes in Hepatocellular Carcinoma After Hepatectomy: A Large-Scale, Multicenter Study
Authors: Zhang Xiu-Ping , Zhou Teng-Fei , Feng Jin-Kai , Sun Zi-Yang , Zhen Zuo-Jun , Zhou Dong , Zhang Fan , Hu Yi-Ren , Zhong Cheng-Qian , Chen Zhen-Hua , Chai Zong-Tao , Wang Kang , Shi Jie , Guo Wei-Xing , Wu Meng-Chao , Lau Wan Yee , Cheng Shu-Qun 
Published: July 2021

BackgroundOccurrence of portal vein tumor thrombus (PVTT) worsens the outcomes of hepatocellular carcinoma (HCC) and imparts high economic burden on society. Patients with high risks of having hypercoagulation are more likely to experience thrombosis. Herein, we examined how preoperative international normalized ratio (INR) was related to the incidence and extent of PVTT, and associated with survival outcomes in HCC patients following R0 liver resection (LR).MethodsPatients with HCC and PVTT were enrolled from six major hospitals in China. The overall survival (OS) and recurrence-free survival (RFS) rates of individuals with different INR levels were assessed with Cox regression analysis as well as Kaplan-Meier method.ResultsThis study included 2207 HCC patients, among whom 1005 patients had concurrent PVTT. HCC patients in the Low INR group had a significantly higher incidence of PVTT and more extensive PVTT than the Normal and High INR groups (P&lt;0.005). Of the 592 HCC subjects who had types I/II PVTT following R0 LR, there were 106 (17.9%), 342 (57.8%) and 144 (24.3%) patients in the High, Normal and Low INR groups, respectively. RFS and OS rates were markedly worse in patients in the Low INR group relative to those in the Normal and High INR groups (median RFS, 4.87 versus 10.77 versus 11.40 months, P&lt;0.001; median OS, 6.30 versus 11.83 versus 12.67 months, P&lt;0.001).ConclusionPreoperative INR influenced the incidence and extent of PVTT in HCC. Particularly, patients with HCC and PVTT in the Low INR group had worse postoperative prognosis relative to the High and Normal INR groups.
Access to Aboriginal Community-Controlled Primary Health Organizations Can Explain Some of the Higher Pap Test Participation Among Aboriginal and Torres Strait Islander Women in North Queensland, Australia
Authors: Dasgupta Paramita , Condon John R. , Whop Lisa J. , Aitken Joanne F. , Garvey Gail , Wenitong Mark , Baade Peter D. 
Published: July 2021

BackgroundAboriginal and Torres Strait Islander Community-Controlled Health Organisations (ACCHOs) provides culturally appropriate primary care for Aboriginal and Torres Strait Islander people in Australia. The population of North Queensland has a higher proportion of Aboriginal and Torres Strait Islander people, a greater population coverage of ACCHOs, and higher cervical screening participation than the Rest of Queensland. The association between regional differences in the use of ACCHOs for cervical screening and variations in screening participation among Aboriginal and Torres Strait Islander women is currently unknown.MethodsThis is a population-based study of 1,107,233 women, aged 20–69 years who underwent cervical screening between 2013 and 2017. Of these women, 132,972 (12%) were from North Queensland, of which 9% were identified as Aboriginal and Torres Strait Islander women (2% Rest of Queensland) through linkage to hospital records. Regional differentials in screening by Aboriginal and Torres Strait Islander status were quantified using participation rate ratios (PRRs) with 95% confidence intervals (CIs) from negative binomial regression models. Logistic regression was used to identify factors associated with Aboriginal and Torres Strait Islander women being screened at ACCHOs.ResultsAboriginal and Torres Strait Islander women from North Queensland (versus) Rest of Queensland had higher odds of screening at ACCHOs after adjusting for age and area-level variables. After adjustment for non-ACCHO variables, the regional differential in screening among Aboriginal and Torres Strait Islander women was significantly higher (PRR 1.28, 95% CI 1.20–1.37) than that among other Australian women [PRR = 1.11 (1.02–1.18)], but was attenuated on further adjustment for ACCHO variables, [PRR = 1.15, (1.03–1.28)] to become similar to the corresponding point estimate for other Australian women [PRR = 1.09, (1.01–1.20)]. However, the significant interaction between Aboriginal and Torres Strait Islander status and region (p &lt; 0.001) remained, possibly reflecting the large cohort size. Screening participation increased with better access to health services for all women.ConclusionsImproving access to primary health care for Aboriginal and Torres Strait Islander women, especially through ACCHOs, may reduce existing disparities in cervical screening participation. Further gains will require greater levels of local community engagement and understanding of the experiences of screened Aboriginal and Torres Strait Islander women to inform effective interventions.
Feasibility and Mechanism Analysis of Shenfu Injection in the Treatment of Idiopathic Pulmonary Fibrosis
Authors: Liu Peipei , Yang Shengnan , Wang Zai , Dai Huaping , Wang Chen 
Published: July 2021

Background: Idiopathic pulmonary fibrosis (IPF) is disease with high mortality, and its effective treatment is limited. Shenfu injection is a traditional Chinese medicine which can improve circulation and protect cells. In this study, we aimed to investigate the feasibility and mechanism of Shenfu injection in the treatment of IPF.Methods: The components and targets of Shenfu injection were mainly retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. The targets of Shenfu injection were standardized by UniProt database. The Genecards and OMIM databases was used to search for IPF-related genes. The Venn diagram of gene intersection was drawn using the OmicStudio tools, and the protein-protein interaction network was visualized using the Cytoscape 3.7.2 software. Moreover, the metascape online software was applied to explore the enriched Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and the Cytoscape 3.7.2 software was used to construct the target-pathway network. Molecular docking was used to visualize the interactions between the main active compounds and targeted proteins. Animal experiments were performed to validate the effects and mechanisms of Shenfu injection.Results: We obtained 46 co-targets of Shenfu injection and IPF. Among the hub target genes, several genes with important functions were enriched, including TNF, IL-6, IL-1B, TP53, JUN, CASP3 and CASP8. The pathway enrichment analysis for the hub target genes identified pathways in infection/inflammation, apoptosis and cancer. Molecular docking results showed that the main active compound Ginsenoside Re had high affinity to the core target proteins. These results suggested that Shenfu injection may have a positive effect in the treatment of IPF. Consistent with this finding, animal experiments showed that Shenfu injection significantly reduced pulmonary fibrosis in a mouse model with inhibition of apoptosis and inflammation by downregulating IL-1β, caspase-3 and phosphorylated NF-κB.Conclusion: Our results demonstrated that Shenfu injection efficiently alleviate bleomycin-induced pulmonary fibrosis through multi-targets in inflammation-, apoptosis- and cancer-related pathways, which provided first evidence and reference to the feasibility of Shenfu injection in the treatment of IPF.
Tetramethylpyrazine Preserves the Integrity of Blood-Brain Barrier Associated With Upregulation of MCPIP1 in a Murine Model of Focal Ischemic Stroke
Authors: Jin Zhuqing , Liang Jian , Kolattukudy Pappachan E. 
Published: July 2021

Tetramethylpyrazine (TMP), a prominent ingredient of Chinese herb Ligusticum chuanxiong Hort, is known to suppress neuroinflammation and protect blood-brain barrier (BBB) integrity. We investigated whether monocyte chemotactic protein-induced protein 1 (MCPIP1, also known as Regnase-1), a newly identified zinc-finger protein, plays a role in TMP-mediated anti-inflammation and neuroprotection. Male C57BL/6 mice were subjected to focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO) for 2 h, followed by reperfusion for 24 h. TMP (25 mg/kg or 50 mg/kg) or vehicle was administered intraperitoneally 12 h before and post MCAO. The TMP significantly upregulated MCPIP1 in the ischemic brain tissues and effectively inhibited extravasation of fluorescein isothiocyanate (FITC)-dextran, resulting in attenuation of brain edema. These effects of the TMP were associated with a significant reduction in levels of inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and MMP-9 in the ischemic brain tissues. The TMP upregulated the expression of MCPIP1 in primary cultures of neurons and protected against oxygen–glucose deprivation-induced neuron death, while this neuroprotective effect of TMP was abolished by knockdown of MCPIP1 using MCPIP1-specific siRNA. These results suggest that preservation of BBB integrity by TMP is associated with its anti-inflammatory activity. The effect of TMP is mediated, at least in part, via upregulation of MCPIP1 in the ischemic brain.
Adaptive Capacities and Complexity of Heart Rate Variability in Patients With Chronic Obstructive Pulmonary Disease Throughout Pulmonary Rehabilitation
Authors: Hognon Louis , Heraud Nelly , Varray Alain , Torre Kjerstin 
Published: July 2021

IntroductionThe complexity of bio-signals, like R-R intervals, is considered a reflection of the organism’s capacity to adapt. However, this association still remains to be consolidated. We investigated whether the complexity of R-R intervals at rest and during perturbation [6-minute walking test (6MWT)], yielded information regarding adaptive capacities in Chronic Obstructive Pulmonary Disease (COPD) patients during pulmonary rehabilitation (PR).MethodsIn total, 23 COPD patients (64 ± 8 years, with forced expiratory volume in 1 s of 55 ± 19% predicted) were tested three times at the start (T1), middle (T2), and end (T3) of 4 weeks PR. Each time, R-R intervals were measured at rest and during 6MWT. The complexity of R-R intervals was assessed by evenly spaced Detrended Fluctuations Analysis and evaluated by the fractal exponent α and deviation from maximal complexity |1-α|.ResultsThe 6MWT distance was significantly increased at T2 and T3 compared to T1. Neither α nor |1-α| at rest and during perturbation significantly changed throughout PR, nor were they consistently associated with 6MWT distances at each time. Throughout the PR program, complexity during the 6MWT was significantly lower compared to the rest. The level of α during 6MWT at T1 was positively correlated with the improvement of the 6MWT distance throughout the PR program.DiscussionReduced complexity in COPD patients during acute perturbation at the beginning of PR supports a decreased improvement of the 6MWT distance throughout PR. This result seems consistent with the notion that the complexity reflects the patients’ adaptive capacities and could therefore become a clinical indicator in an applied perspective.
Effects of Lung Injury on Regional Aeration and Expiratory Time Constants: Insights From Four-Dimensional Computed Tomography Image Registration
Authors: Herrmann Jacob , Gerard Sarah E. , Shao Wei , Xin Yi , Cereda Maurizio , Reinhardt Joseph M. , Christensen Gary E. , Hoffman Eric A. , Kaczka David W. 
Published: July 2021

Rationale: Intratidal changes in regional lung aeration, as assessed with dynamic four-dimensional computed tomography (CT; 4DCT), may indicate the processes of recruitment and derecruitment, thus portending atelectrauma during mechanical ventilation. In this study, we characterized the time constants associated with deaeration during the expiratory phase of pressure-controlled ventilation in pigs before and after acute lung injury using respiratory-gated 4DCT and image registration.Methods: Eleven pigs were mechanically ventilated in pressure-controlled mode under baseline conditions and following an oleic acid model of acute lung injury. Dynamic 4DCT scans were acquired without interrupting ventilation. Automated segmentation of lung parenchyma was obtained by a convolutional neural network. Respiratory structures were aligned using 4D image registration. Exponential regression was performed on the time-varying CT density in each aligned voxel during exhalation, resulting in regional estimates of intratidal aeration change and deaeration time constants. Regressions were also performed for regional and total exhaled gas volume changes.Results: Normally and poorly aerated lung regions demonstrated the largest median intratidal aeration changes during exhalation, compared to minimal changes within hyper- and non-aerated regions. Following lung injury, median time constants throughout normally aerated regions within each subject were greater than respective values for poorly aerated regions. However, parametric response mapping revealed an association between larger intratidal aeration changes and slower time constants. Lower aeration and faster time constants were observed for the dependent lung regions in the supine position. Regional gas volume changes exhibited faster time constants compared to regional density time constants, as well as better correspondence to total exhaled volume time constants.Conclusion: Mechanical time constants based on exhaled gas volume underestimate regional aeration time constants. After lung injury, poorly aerated regions experience larger intratidal changes in aeration over shorter time scales compared to normally aerated regions. However, the largest intratidal aeration changes occur over the longest time scales within poorly aerated regions. These dynamic 4DCT imaging data provide supporting evidence for the susceptibility of poorly aerated regions to ventilator-induced lung injury, and for the functional benefits of short exhalation times during mechanical ventilation of injured lungs.
Anxiety and Depression in Patients With Physical Diseases and Associated Factors: A Large-Scale Field Survey in General Hospitals in China
Authors: Yang Wanlin , Xiao Ling , Yuan Zhiyong , Huang Huan , Xiang Yilei , Liu Zhongchun , Nan Cai , Wang Huiling , Wang Gaohua 
Published: July 2021

Introduction: To investigate the characteristic of anxiety and depression among patients in general hospitals, and explore the degree of the clinical symptoms and correlated social economic factors.Methods: This is a cross-sectional survey of anxiety and depression in patients with physical diseases, who were suspected of depression and anxiety based on their clinical performance by their physicians and PHQ ≧ 8, from various clinical departments of 57 general hospitals in China. Data regarding demographic characteristics and clinical characteristics were collected. Social and psychological factors and the severity of anxiety or depression were collected through self-rating scales. Finally, we used multivariate logistic regression to identify the factors associated with anxiety and depression in patients with physical diseases.Results: A total of 2,105 (84.6%) valid and completed questionnaires were returned. The proportion of anxiety, depression, combined depression and anxiety, either anxiety or depression among the patients with physical diseases from all clinical departments was 63.3, 75.1, 57.1, and 81.2% respectively. Further regression analysis indicated that gender, monthly income, specific physical diseases, personality traits, social supports and life negative events were related factors of both anxiety and depression.Conclusions: Anxiety and depression were common in patients with physical diseases, with a high proportion of co-morbidity of anxiety and depression. Females, patients with cancer, poor social support and negative life events reported more severe anxiety and depression. The results may help to understand the present situation of anxiety and depression in general hospitals in china, and identify the patients with high risk of depression and anxiety.
Variations in the Density and Distribution of Cajal Like Cells Associated With the Pathogenesis of Ureteropelvic Junction Obstruction: A Systematic Review and Meta-Analysis
Authors: Samaranayake U. M. J. E. , Mathangasinghe Y. , Liyanage U. A. , de Silva M. V. C. , Samarasinghe M. C. , Abeygunasekera S. , Lamahewage A. K. , Malalasekera A. P. 
Published: July 2021

Introduction: Cajal like cells (CLCs) in the upper urinary tract have an ability to generate coordinated spontaneous action potentials and are hypothesized to help propel urine from renal pelvis into the ureter. The objective of this review was to describe the variations in the density and distribution of CLCs associated with ureteropelvic junction obstruction (UPJO).Materials and Methods: Studies comparing the density and distribution of CLCs in the human upper urinary tract in patients with UPJO and healthy controls were included in this systematic review. We searched online electronic databases; Ovid MEDLINE, Scopus, PubMed and Cochrane reviews for the studies published before October 31, 2020. A meta-analysis was conducted to compare the density of CLCs at the ureteropelvic junction (UPJ) in patients with UPJO and matched controls.Results: We included 20 and seven studies in the qualitative and quantitative synthesis, respectively. In majority (55%) CLCs were located between the muscle layers of the upper urinary tract. The CLC density in the UPJ gradually increased with aging in both healthy subjects and patients with UPJO. The pooled analysis revealed that the density of CLCs at the UPJ was significantly low in patients with UPJO compared to the controls (SMD = −3.00, 95% CI = −3.89 to −2.11, p &lt; 0.01).Conclusions: The reduction in CLC density at the UPJ in patients with UPJO suggests a contribution from CLCs in the pathogenesis of UPJO. Since age positively correlates with CLC density, it is imperative to carefully match age when conducting case control studies comparing the CLC density and distribution.Protocol Registration Number: CRD42020219882.