bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between pretracheal and/or prelaryngeal lymph node metastasis and paratracheal and lateral lymph node metastasis of papillary thyroid carcinoma: A meta-analysis
Authors: Wang Bin , Zhu Chun-Rong , Liu Hong , Yao Xin-Min , Wu Jian
Published: September 2022

Objective

We conducted a meta-analysis to study the relationship between pretracheal and/or prelaryngeal lymph node metastasis and paratracheal and lateral lymph node metastasis in papillary thyroid carcinoma.

Method

A systematic literature search was conducted using PubMed, Embase, and the Cochrane Library electronic databases for studies published up to February 2022. The reference lists of retrieved articles were also reviewed. Two authors independently assessed the methodological quality and extracted the data. A random-effects model was used to calculate the overall pooled relative risk. Publication bias in these studies was evaluated using Egger’s test and Begg’s test.

Results

Twenty-five independent studies involving 10,525 patients were included in the meta-analysis. The pooled relative risk for ipsilateral and contralateral paratracheal lymph node metastasis was 3.01 (95% confidence interval [CI]: 1.66, 5.45) and 5.68 (95% CI: 2.50, 12.88), respectively, in patients with pretracheal lymph node metastasis. Among patients with prelaryngeal lymph node metastasis, the pooled relative risk for ipsilateral paratracheal and/or pretracheal contralateral paratracheal, and lateral lymph node metastasis was 2.02 (95% CI: 1.90, 2.14), 2.22 (95% CI: 1.34, 3.67), and 3.85 (95% CI: 2.89, 5.14), respectively.

Conclusion

Pretracheal lymph node metastasis and prelaryngeal lymph node metastasis were significantly associated with an increased likelihood of both ipsilateral lymph node metastasis and contralateral paratracheal lymph node metastasis in papillary thyroid carcinoma. Prelaryngeal lymph node metastasis was positively correlated with the incidence of lateral lymph node metastasis.
A systematic review on intra-arterial cerebral infusions of chemotherapeutics in the treatment of glioblastoma multiforme: The state-of-the-art
Authors: Pinkiewicz Mateusz , Pinkiewicz Milosz , Walecki Jerzy , Zawadzki Michał
Published: September 2022

Objective

To provide a comprehensive review of intra-arterial cerebral infusions of chemotherapeutics in glioblastoma multiforme treatment and discuss potential research aims. We describe technical aspects of the intra-arterial delivery, methods of blood-brain barrier disruption, the role of intraoperative imaging and clinical trials involving intra-arterial cerebral infusions of chemotherapeutics in the treatment of glioblastoma multiforme.

Method

159 articles in English were reviewed and used as the foundation for this paper. The Medline/Pubmed, Cochrane databases, Google Scholar, Scielo and PEDro databases have been used to select the most relevant and influential papers on the intra-arterial cerebral infusions of chemotherapeutics in the treatment of glioblastoma multiforme. Additionally, we have included some relevant clinical trials involving intra-arterial delivery of chemotherapeutics to other than GBM brain tumours.

Conclusion

Considering that conventional treatments for glioblastoma multiforme fall short of providing a significant therapeutic benefit, with a majority of patients relapsing, the neuro-oncological community has considered intra-arterial administration of chemotherapeutics as an alternative to oral or intravenous administration. Numerous studies have proven the safety of IA delivery of chemotherapy and its ability to ensure higher drug concentrations in targeted areas, simultaneously limiting systemic toxicity. Nonetheless, the scarcity of phase III trials prevents any declaration of a therapeutic benefit. Given that the likelihood of a single therapeutic agent which will be effective for the treatment of glioblastoma multiforme is extremely low, it is paramount to establish an adequate multimodal therapy which will have a synergistic effect on the diverse pathogenesis of GBM. Precise quantitative and spatial monitoring is necessary to guarantee the accurate delivery of the therapeutic to the tumour. New and comprehensive pharmacokinetic models, a more elaborate understanding of glioblastoma biology and effective methods of diminishing treatment-related neurotoxicity are paramount for intra-arterial cerebral infusion of chemotherapeutics to become a mainstay treatment for glioblastoma multiforme. Additional use of other imaging methods like MRI guidance during the procedure could have an edge over X-ray alone and aid in selecting proper arteries as well as infusion parameters of chemotherapeutics making the procedure safer and more effective.
Clinicopathological and CT features of tumor spread through air space in invasive lung adenocarcinoma
Authors: Qin Lili , Sun Yubing , Zhu Ruiping , Hu Bo , Wu Jianlin
Published: September 2022

Objective

Tumor spread through air spaces (STAS) has recently been reported as a novel invasive pattern in lung adenocarcinoma. Thus, this study aimed to investigate the clinicopathological and radiological features in invasive lung adenocarcinoma with tumor STAS.

Methods

Data of 503 invasive lung adenocarcinoma patients who underwent surgery between 1 January 2015 and 31 December 2021 were collected. The correlations between STAS presence and clinicopathological and radiological characteristics were analyzed. Statistical analysis was performed using SPSS 22.0.

Results

Among the 503 patients with invasive adenocarcinoma, 247 (47.9%) and 262 (52.1%) patients were positive and negative for STAS, respectively. Compared to STAS-negative adenocarcinoma, STAS was more common in papillary, micropapillary, and solid tumors (p < 0.01); STAS was associated with advanced pT (p = 0.024), pN (p < 0.001), and pTNM (p < 0.001) stage, more lymph node metastases (p < 0.01), more pleural invasion (p < 0.01), and more neurovascular invasion (p = 0.025). The maximum diameter (p < 0.01), the maximum diameters of the solid component (p < 0.01), and the consolidation/tumor ratio (CTR, p < 0.01) were significantly larger in STAS-positive than in STAS-negative adenocarcinoma. Other common computed tomography (CT) features of adenocarcinomas, i.e., lobulation (p < 0.01), spiculation (p < 0.01), vacuole (p < 0.01), air bronchogram (p = 0.020), vascular convergence (p < 0.01), and pleural indentation (p < 0.01) were significantly associated with STAS. In a multivariable analysis, the maximal diameter of the solid component (odds ratio [OR], 2.505; 95% confidence interval [CI], 1.886–3.329), vacuole (OR, 3.301; 95% CI, 1.822–5.980), and spiculation (OR, 2.162; 95% CI, 1.221–3.829) were independent predictors of STAS. The area under the curve (AUC) of the maximal diameter of the solid component was 0.757 (95% CI, 0.714–0.799; p < 0.001), the sensitivity was 73.9%, and the specificity was 69.1% at a cutoff value of 1.18 cm.

Conclusion

STAS was significantly correlated with several invasive clinicopathological and radiological characteristics, and the maximal diameter was an independent predictor of STAS. These results will prove helpful in identifying STAS-positive adenocarcinoma by CT before surgical resection.
Role of hypoxia in the tumor microenvironment and targeted therapy
Authors: Chen Gaoqi , Wu Kaiwen , Li Hao , Xia Demeng , He Tianlin
Published: September 2022

Tumor microenvironment (TME), which is characterized by hypoxia, widely exists in solid tumors. As a current research hotspot in the TME, hypoxia is expected to become a key element to break through the bottleneck of tumor treatment. More and more research results show that a variety of biological behaviors of tumor cells are affected by many factors in TME which are closely related to hypoxia. In order to inhibiting the immune response in TME, hypoxia plays an important role in tumor cell metabolism and anti-apoptosis. Therefore, exploring the molecular mechanism of hypoxia mediated malignant tumor behavior and therapeutic targets is expected to provide new ideas for anti-tumor therapy. In this review, we discussed the effects of hypoxia on tumor behavior and its interaction with TME from the perspectives of immune cells, cell metabolism, oxidative stress and hypoxia inducible factor (HIF), and listed the therapeutic targets or signal pathways found so far. Finally, we summarize the current therapies targeting hypoxia, such as glycolysis inhibitors, anti-angiogenesis drugs, HIF inhibitors, hypoxia-activated prodrugs, and hyperbaric medicine.
PIWI-interacting RNAs in cancer: Biogenesis, function, and clinical significance
Authors: Yao Jie , Xie Mei , Ma Xidong , Song Jialin , Wang Yuanyong , Xue Xinying
Published: September 2022

PIWI-interacting RNAs (piRNAs) are a less-studied class of small non-coding RNAs approximately 24–31 nucleotides in length. They express in germline and somatic cells and form complexes with PIWI proteins to exert regulatory effects. New studies show that piRNAs are aberrantly expressed in various cancers. In this review, we focus on those piRNAs that are associated with cancer hallmarks such as proliferation, invasion, and chemoresistance and discuss their potential as biomarkers for cancer diagnosis and prognosis.
Computed tomography-based deep-learning prediction of lymph node metastasis risk in locally advanced gastric cancer
Authors: Zhang An-qi , Zhao Hui-ping , Li Fei , Liang Pan , Gao Jian-bo , Cheng Ming
Published: September 2022

Purpose

Preoperative evaluation of lymph node metastasis (LNM) is the basis of personalized treatment of locally advanced gastric cancer (LAGC). We aim to develop and evaluate CT-based model using deep learning features to preoperatively predict LNM in LAGC.

Methods

A combined size of 523 patients who had pathologically confirmed LAGC were retrospectively collected between August 2012 and July 2019 from our hospital. Five pre-trained convolutional neural networks were exploited to extract deep learning features from pretreatment CT images. And the support vector machine (SVM) was employed as the classifier. We assessed the performance using the area under the receiver operating characteristics curve (AUC) and selected an optimal model, which was compared with a radiomics model developed from the training cohort. A clinical model was built with clinical factors only for baseline comparison.

Results

The optimal model with features extracted from ResNet yielded better performance with AUC of 0.796 [95% confidence interval (95% CI), 0.715-0.865] and accuracy of 75.2% (95% CI, 67.2%-81.5%) in the testing cohort, compared with 0.704 (0.625-0.783) and 61.8% (54.5%-69.9%) for the radiomics model. The predictive performance of all the radiological models were significantly better than the clinical model.

Conclusion

The novel and noninvasive deep learning approach could provide efficient and accurate prediction of lymph node metastasis in LAGC, and benefit clinical decision making of therapeutic strategy.
Photodynamic therapy for prostate cancer: Recent advances, challenges and opportunities
Authors: Xue Qin , Zhang Jingliang , Jiao Jianhua , Qin Weijun , Yang Xiaojian
Published: September 2022

Over the past two decades, there has been a tendency toward early diagnosis of prostate cancer due to raised awareness among the general public and professionals, as well as the promotion of prostate-specific antigen (PSA) screening. As a result, patients with prostate cancer are detected at an earlier stage. Due to the risks of urine incontinence, erectile dysfunction, etc., surgery is not advised because the tumor is so small at this early stage. Doctors typically only advise active surveillance. However, it will bring negative psychological effects on patients, such as anxiety. And there is a higher chance of cancer progression. Focal therapy has received increasing attention as an alternative option between active monitoring and radical therapy. Due to its minimally invasive, oncological safety, low toxicity, minimal effects on functional outcomes and support by level 1 evidence from the only RCT within the focal therapy literature, photodynamic treatment (PDT) holds significant promise as the focal therapy of choice over other modalities for men with localized prostate cancer. However, there are still numerous obstacles that prevent further advancement. The review that follows provides an overview of the preclinical and clinical published research on PDT for prostate cancer from 1999 to the present. It focuses on clinical applications of PDT and innovative techniques and technologies that address current problems, especially the use of nanoparticle photosensitizers in PDT of prostate cancer.
Do body composition parameters correlate with response to targeted therapy in ER+/HER2- metastatic breast cancer patients? Role of sarcopenia and obesity
Authors: Kripa Endi , Rizzo Veronica , Galati Francesca , Moffa Giuliana , Cicciarelli Federica , Catalano Carlo , Pediconi Federica
Published: September 2022

Purpose

To investigate the association between body composition parameters, sarcopenia, obesity and prognosis in patients with metastatic ER+/HER2- breast cancer under therapy with cyclin-dependent kinase (CDK) 4/6 inhibitors.

Methods

92 patients with biopsy-proven metastatic ER+/HER2- breast cancer, treated with CDK 4/6 inhibitors between 2018 and 2021 at our center, were included in this retrospective analysis. Visceral Adipose Tissue (VAT), Subcutaneous Adipose Tissue (SAT) and Skeletal Muscle Index (SMI) were measured before starting therapy with CDK 4/6 inhibitors (Palbociclib, Abemaciclib or Ribociclib). Measurements were performed on a computed tomography-derived abdominal image at third lumbar vertebra (L3) level by an automatic dedicated software (Quantib body composition®, Rotterdam, Netherlands). Visceral obesity was defined as a VAT area > 130 cm2. Sarcopenia was defined as SMI < 40 cm2/m2. Changes in breast lesion size were evaluated after 6 months of treatment. Response to therapy was assessed according to RECIST 1.1 criteria. Spearman’s correlation and χ2 analyses were performed.

Results

Out of 92 patients, 30 were included in the evaluation. Of the 30 patients (mean age 53 ± 12 years), 7 patients were sarcopenic, 16 were obese, while 7 patients were neither sarcopenic nor obese. Statistical analyses showed that good response to therapy was correlated to higher SMI values (p < 0.001), higher VAT values (p = 0.008) and obesity (p = 0.007); poor response to therapy was correlated to sarcopenia (p < 0.001). Moreover, there was a significant association between sarcopenia and menopause (p = 0.021) and between sarcopenia and the persistence of axillary lymphadenopathies after treatment (p = 0.003), while the disappearance of axillary lymphadenopathies was associated with obesity (p = 0.028).

Conclusions

There is a growing interest in body composition, especially in the field of breast cancer. Our results showed an interesting correlation between sarcopenia and progression of disease, and demonstrated that VAT can positively influence the response to targeted therapy with CDK 4/6 inhibitors. Larger-scale studies are needed to confirm these preliminary results.

Clinical Relevance

Sarcopenia and obesity seem to predict negative outcomes in many oncologic entities. Their prevalence and impact in current breast cancer care are promising but still controversial.
Early economic modeling of magnetic resonance image-guided high intensity focused ultrasound compared to radiotherapy for pain palliation of bone metastases
Authors: Simões Corrêa Galendi Julia , Yeo Sin Yuin , Grüll Holger , Bratke Grischa , Akuamoa-Boateng Dennis , Baues Christian , Bos Clemens , Verkooijen Helena M. , Shukri Arim , Stock Stephanie , Müller Dirk
Published: September 2022

Introduction

Magnetic Resonance Image-guided High Intensity Focused Ultrasound (MR-HIFU) is a non-invasive treatment option for palliative patients with painful bone metastases. Early evidence suggests that MR-HIFU is associated with similar overall treatment response, but more rapid pain palliation compared to external beam radiotherapy (EBRT). This modelling study aimed to assess the cost-effectiveness of MR-HIFU as an alternative treatment option for painful bone metastases from the perspective of the German Statutory Health Insurance (SHI).

Materials and methods

A microsimulation model with lifelong time horizon and one-month cycle length was developed. To calculate the incremental cost-effectiveness ratio (ICER), strategy A (MR-HIFU as first-line treatment or as retreatment option in case of persistent pain or only partial pain relief after EBRT) was compared to strategy B (EBRT alone) for patients with bone metastases due to breast, prostate, or lung cancer. Input parameters used for the model were extracted from the literature. Results were expressed as EUR per quality-adjusted life years (QALYs) and EUR per pain response (i.e., months spent with complete or partial pain response). Deterministic and probabilistic sensitivity analyses (PSA) were performed to test the robustness of results, and a value of information analysis was conducted.

Results

Compared to strategy B, strategy A resulted in additional costs (EUR 399) and benefits (0.02 QALYs and 0.95 months with pain response). In the base case, the resulting ICERs (strategy A vs. strategy B) are EUR 19,845/QALY and EUR 421 per pain response. Offering all patients MR-HIFU as first-line treatment would increase the ICER by 50% (31,048 EUR/QALY). PSA showed that at a (hypothetical) willingness to pay of EUR 20,000/QALY, the probability of MR-HIFU being cost-effective was 52%. The expected value of perfect information (EVPI) for the benefit population in Germany is approximately EUR 190 Mio.

Conclusion

Although there is considerable uncertainty, the results demonstrate that introducing MR-HIFU as a treatment alternative for painful bone metastases might be cost-effective for the German SHI. The high EVPI indicate that further studies to reduce uncertainty would be worthwhile.
Is preoperative ultrasound tumor size a prognostic factor in endometrial carcinoma patients?
Authors: Ambrosio Marco , Raffone Antonio , Alletto Andrea , Cini Chiara , Filipponi Francesco , Neola Daniele , Fabbri Matilde , Arena Alessandro , Raimondo Diego , Salucci Paolo , Guerrini Manuela , Travaglino Antonio , Paradisi Roberto , Mollo Antonio , Seracchioli Renato , Casadio Paolo
Published: September 2022

Objective

We aimed to assess the prognostic value of preoperative ultrasound tumor size in EC through a single center, observational, retrospective, cohort study.

Methods

Medical records and electronic clinical databases were searched for all consecutive patients with EC, preoperative ultrasound scans available to ad hoc estimate tumor size, and a follow-up of at least 2-year, at our Institution from January 2010 to June 2018. Patients were divided into two groups based on different dimensional cut-offs for the maximum tumor diameter: 2, 3 and 4 cm. Differences in overall survival (OS), disease specific survival (DSS) and progression-free survival (PFS) were assessed among the groups by using the Kaplan–Meier estimator and the log-rank test.

Results

108 patients were included in the study. OS, DSS and PFS did not significantly differ between the groups based on the different tumor diameter cut-offs. No significant differences were found among the groups sub-stratified by age, BMI, FIGO stage, FIGO grade, lymphovascular space invasion status, myometrial invasion, lymph nodal involvement, histotype, and adjuvant treatment.

Conclusions

Preoperative ultrasound tumor size does not appear as a prognostic factor in EC women.
Risk factors and predictive nomograms for early death of patients with pancreatic cancer liver metastasis: A large cohort study based on the SEER database and Chinese population
Authors: Zhang Haidong , Dong Hui , Pan Zheng , Du Xuanlong , Liu Shiwei , Xu Wenjing , Zhang Yewei
Published: September 2022

Background

The liver is the most common organ for distant metastasis of pancreatic cancer, and patients with pancreatic cancer liver metastases (PCLM) often die in a short period of time. As such, the establishment of an effective nomogram to predict the probability of early death (survival time ≤3 months) in PCLM patients is of considerable significance.

Methods

Patients diagnosed with PCLM in the Surveillance, Epidemiology, and End Result (SEER) database between 2010 and 2015 were included for model construction and internal validation. A data set was obtained from the Chinese population for external validation. Risk factors that contributed to all-cause and cancer-specific early death were determined by means of univariable and multivariable logistic regression. The accuracy of the nomogram was verified by means of receiver operating characteristic (ROC) curves, and the true consistency of the model was assessed by calibration curves. The clinical applicability of the model was evaluated by means of decision curve analysis (DCA).

Results

A total of 12,955 patients were included in the present study, of whom 7,219 (55.7%) experienced early death and 6,973 (53.8%) patients died of PCLM. Through multivariable logistic regression analysis, 11 risk factors associated with all-cause early death and 12 risk factors associated with cancer-specific early death were identified. The area under the curves (AUCs) for all-cause and cancer-specific early death were 0.806 (95% CI: 0.785- 0.827) and 0.808 (95% CI: 0.787- 0.829), respectively. Internal validation showed that the C-indexes of all-cause and cancer-specific early death after bootstrapping (5,000 re-samplings) were 0.805 (95% CI: 0.784-0.826) and 0.807 (95% CI: 0.786-0.828), respectively. As revealed by the calibration curves, the constructed nomograms exhibited good consistency. The decision curve analysis (DCA) indicated the nomograms had significant clinical applicability.

Conclusion

In the present study, reliable nomograms were developed for predicting the early death probability in patients with PCLM. Such tools can help clinicians identify high-risk patients and develop individualized treatment plans as early as possible.
Prevalence of hypertension and related risk factors among children and adolescents at three separate visits: A large school-based study in China
Authors: Hu Jia , Ding Ziyao , Han Di , Hai Bo , Lv Huiling , Yin Jieyun , Shen Hui , Gu Aihua , Yang Haibing
Published: September 2022

Objective

We aimed to demonstrate characteristics of hypertension at three separate visits and its risk factors among children and adolescents based on a large school-based study in China.

Materials and methods

Based on a large-scale ongoing monitoring program conducted in Suzhou, China, 59,679 children and adolescents aged 7–17 years from 60 public schools were enrolled during 2020 to 2021. Height, weight, and blood pressure (BP) were measured. Additional BP would be measured for hypertensive students at least 2 weeks later. Confirmed hypertension was defined as simultaneously BP meeting above or equal to 95th percentile for age, sex, and height at three separate visits. Odds ratio (ORs), and 95% CIs were calculated by logistic regression to identify risk factors for hypertension.

Results

Prevalence of hypertension at three separate visits were 20.4, 6.3, and 3.1%, respectively. Prevalence of confirmed isolated systolic hypertension, isolated diastolic hypertension, and systolic and diastolic hypertension were 1.9, 0.3, and 0.9%, respectively. Hypertension prevalence for stages 1 and 2 were 2.6 and 0.6%. Different hypertension prevalence were found among various age and gender groups. Boys [OR, 1.137 (95% CI, 1.033–1.251)], high age [OR, 3.326 (95% CI, 2.950–3.751)], urban residents [OR, 1.579 (95% CI, 1.417–1.760)], high-socioeconomic status [OR, 1.156 (95% CI, 1.039–1.286)] and body mass index category including overweight [1.883 (95% CI, 1.665–2.129)], obesity [4.049 (95% CI, 3.625–4.523)], and thinness [OR, 0.457 (95% CI, 0.306–0.683)] were associated with confirmed hypertension.

Conclusion

A single BP measurement would overestimate hypertension prevalence, about 3% Chinese children were hypertensive, early, and effective intervention around risk factors for hypertension should be taken.
Exosomes in the f ield of reproduction: A scientometric study and visualization analysis
Authors: Shen Yifeng , You Yaodong , Zhu Kun , Fang Chunyan , Chang Degui , Yu Xujun
Published: September 2022

Background: The diagnostic capabilities of exosomes in the field of reproductive biomedicine have attracted much attention. The aim of this scientometric study was to statistically and qualitatively assess the knowledge structure, hot issues, and research trends of papers about exosomes in the field of reproduction using visualization methods.

Methods: The Web of Science Core Collection was searched for studies on exosomes in the field of reproduction. We performed bibliometric and visual analyses using VOSviewer, CiteSpace, and Microsoft Excel.

Results: After database search, 1,011 articles were included, with number of studies being published every year continually increasing. These publications came from 61 nations or regions, with the US having the highest number. The University of Queensland was the main institution in which the research was conducted. The journal Placenta contained the highest number studies. There were 5,247 authors in total. Carlos Salomon had the highest number of papers with co-citations. Exosomes, extracellular vesicles, pregnancy, microRNAs, preeclampsia, placenta, microvesicles, gene expression, biomarkers, and first trimester were the most frequently used terms.

Conclusion: Exosome research is booming in reproductive biomedicine. Future studies will likely focus on exosomes as biomarkers in gamete formation and fertilization, pregnancy, and cancers associated with reproduction. In addition to focusing on fundamental research, we should concentrate on the application of the results and the investigation of exosomes in infertile patients.
Identification of kaempferol as an OSX upregulator by network pharmacology-based analysis of qianggu Capsule for osteoporosis
Authors: Huang Ann Yehong , Xiong Zhencheng , Liu Kuankuan , Chang Yanan , Shu Li , Gao Guolan , Zhang Chi
Published: September 2022

Osteoporosis is the most common metabolic disease of skeleton with reduced bone density and weaker bone. Qianggu Capsule as a traditional chinese medicine has been widely used to treat osteoporosis. The potential pharmacological mechanism of its active ingredient Gusuibu is not well understood. The purpose of this work is to analyze the anti-osteoporosis function of Gusuibu based on network pharmacology, and further explore the potential mechanism of Qianggu Capsule. The active compounds and their corresponding targets of Gusuibu were obtained from TCMSP, TCMID, and BATMAN-TCM databases. Potential therapeutic targets for osteoporosis were obtained through DisGeNET, TTD, GeneCards, MalaCards, CTD, and OMIM databases. The overlapping targets of Gusuibu and osteoporosis were obtained. GO and KEGG pathway enrichment analysis were performed. The “Gusuibu-active compounds-target genes-osteoporosis” network and protein-protein interaction (PPI) network were constructed, and the top hub genes were screened by using the plug-in CytoHubba. Molecular docking was used to verify the binding activity of hub genes and key compounds. We identified 21 active compounds and 140 potential therapeutic targets that may be related to Gusuibu and 10 hub genes (AKT1, IL6, JUN, TNF, MAPK3, VEGFA, EGFR, MAPK1, CASP3, PTGS2). Molecular docking analysis demonstrated that four key active small molecules in Gusuibu (including Luteolin, Naringenin, Kaempferol, and Beta-sitosterol) have excellent binding affinity to the target proteins encoded by the top 10 hub genes. Our new findings indicated that one key active compound kaempferol activated the expression of osteoblast specific transcription factor OSX through JNK kinase pathway.
Network pharmacology and computer-aided drug design to explored potential targets of Lianhua Qingwen and Qingfei Paidu decoction for COVID-19
Authors: Li Liyuan , Wang Xiaoying , Guo Xiao , Li Yikun , Song Qiuhang , Li Aiying
Published: September 2022

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2, has spread globally, affecting people’s lives worldwide and hindering global development. Traditional Chinese Medicine (TCM) plays a unique role in preventing and treating COVID-19. Representative prescriptions for the COVID-19 treatment, Lianhua Qingwen (LHQW) and Qingfei Paidu Decoction (QFPD), effectively alleviate COVID-19 symptoms, delaying its progression and preventing its occurrence. Despite the extensive similarity in their therapeutic effects, the mechanisms and advantages of LHQW and QFPD in in treating mild-to-moderate COVID-19 remain elusive. To characterize the mechanisms of LHQW and QFPD in treating COVID-19, we used integrated network pharmacology and system biology to compare the LHQW and QFPD components, active compounds and their targets in Homo sapiens. LHQW and QFPD comprise 196 and 310 active compounds, some of which have identical targets. These targets are enriched in pathways associated with inflammation, immunity, apoptosis, oxidative stress, etc. However, the two TCM formulas also have specific active compounds and targets. In LHQW, arctiin, corymbosin, and aloe-emodin target neurological disease-related genes (GRM1 and GRM5), whereas in QFPD, isofucosterol, baicalein, nobiletin, oroxylin A, epiberberine, and piperlonguminine target immunity- and inflammation-related genes (mTOR and PLA2G4A). Our findings indicate that LHQW may be suitable for treating mild-to-moderate COVID-19 with nervous system symptoms. Moreover, QFPD may effectively regulate oxidative stress damage and inflammatory symptoms induced by SARS-CoV-2. These findings may provide references for the clinical application of LHQW and QFPD.
The Efficacy and Safety of Roxadustat for Anemia in Patients With Chronic Kidney Disease: A Meta-Analysis
Authors: Wang Lijun , Yin Heng , Yang Liling , Zhang Fenglian , Wang Song , Liao Dan
Published: September 2022

Background: Chronic kidney disease (CKD) is a global public health problem, and anemia is a common complication in CKD patients. Roxadustat (FG-4592) is an oral hypoxia-inducible factor (HIF) stabilizer. Roxadustat has been shown in studies to keep up with and increase hemoglobin better than placebo or erythropoietin. The purpose of this meta-analysis was to assess the efficacy and safety of roxadustat.

Methods: We searched CBM, CNKI, VIP, Wanfang Database, PubMed, Cochrane Library, Embase, and Web of Science for randomized controlled trials of roxadustat for the treatment of anemia in CKD patients. The papers were screened using rigorous criteria and their quality was assessed using the Cochrane 5.1.0 assessment manual for randomized controlled trials (RCTs). RevMan 5.3 was used to extract and synthesize data for meta-analysis.

Results: There were 8 RCTs (7 articles) in all, and 1,364 patients with chronic kidney disease anemia were involved. The overall quality of the studies included was satisfactory. The meta-analysis findings revealed that roxadustat can considerably enhance hemoglobin, transferrin, and total iron binding capacity (TIBC) in both dialysis-dependent (DD) and non-dialysis-dependent (NDD) patients: Hemoglobin (Hb): DD: [SMD = 0.23, 95% CI (0.01, 0.44), p = 0.04], NDD: [SMD = 2.08, 95% CI (1.23, 2.93) p < 0.000001]; transferrin: DD: [SMD = 0.78, 95% CI (0.24, 1.32), p = 0.004], NDD: [SMD = 1.37, 95% CI (0.76, 1.98), p < 0.0001]; TIBC: DD [SMD = 0.97, 95% CI (0.64, 1.29), p < 0.00001], NDD [SMD = 1.34, 95% CI (0.9, 1.78), p < 0.00001]. After roxadustat therapy, patients’ serum iron levels were considerably higher in the dialysis group than in the control group, but there was no significant change in the NDD group [SMD = 0.42, 95% CI (0.27, 0.57), p < 0.00001]. In the NDD group, hepcidin, ferritin, and transferrin saturation (TSAT) were significantly reduced after roxadustat treatment: Hepcidin [SMD = −1.59, 95% CI (−2.69, −0.49), p = 0.005], ferritin [SMD = −0.51, 95% CI (−0.72, 0.3) p < 0.00001], TSAT [SMD = −0.41, 95% CI (−0.62, 0.2), p < 0.0001]. In terms of safety, adverse events (AE) [SMD = 1.08, 95% CI (0.98, 1.18) p = 0.11] and serious adverse events (SAE) [SMD = 1.32, 95% CI (0.97, 1.9) p = 0.08] were not significantly different between the two groups.

Conclusion: Roxadustat can improve anemia in NDD patients with chronic kidney disease, and its short-term safety was comparable to that of the comparison group.
Saponins from Panax notoginseng ameliorate steroid resistance in lupus nephritis through regulating lymphocyte-derived exosomes in mice
Authors: Chen Jia , Zhou Qingyun , Lu Ying
Published: September 2022

Lupus nephritis (LN) is the most common and severe type of organ damage and an important primary disease in end-stage renal failure in patients with systemic lupus erythematosus (SLE). Clinical guidelines recommend steroid treatment, but steroid resistance has become a major factor leading to treatment failure and affecting prognosis. Our previous study demonstrated that Saponins from Panax Notoginseng (Panax ginseng saponins, PNS) could reverse steroid resistance of lymphocytes by downregulating P-glycoprotein (P-gp) expression and provide renal protection in LN mice, but the mechanism by which lymphocytes transmit these related messages to renal lamina propria cells is not clear. Therefore, we further elucidated this mechanism through holistic experiments. In this study, low-dose methylprednisolone (0.8 mg/kg/day, MP) was used to induce a steroid-resistant lupus nephritis (SR-LN) mouse model in weeks one to four, and a therapeutic steroid dosage (MP 12 mg/kg/day) or a combined PNS (PNS 100 mg/kg/day) treatment was administered from week five to eight. Lymphocyte-derived exosomes (Lyme-Exos) were isolated from the spleens of mice and injected into untreated homozygous LN mice for 14 days via the tail vein. At the end of the experiment, the efficacy and mechanism of action of different groups of Lyme-Exos on LN mice were observed. The results revealed that exogenously injected Lyme-Exos were effectively taken up by the kidney and affected the progression of kidney disease. Steroid-resistant lymphocyte-derived exosomes intervented with PNS significantly downregulated the levels of silent information regulator-related enzyme 1 (Sirt1), multidrug resistance gene 1 (MDR1), and P-gp in the renal cortex and glomerular endothelial cells (GECs); reduced serum autoantibody [antinuclear antibody (ANA) and anti-double-stranded DNA (dsDNA)] levels and inflammatory markers (WBC, PCR, and PCT); improved renal function; and attenuated urinary microalbumin excretion. Additionally, renal histopathological damage (HE staining) and fibrosis (Masson staining) were improved, and immune complex (IgG) deposition and membrane attack complex (C5b-9) production were significantly reduced; the gene levels of inflammatory factors (INF-γ, MCP-1, IL-8, IL-17, vWF, VCAM-1, IL-1β, IL-6, PTX3) in the renal cortex were downregulated. Taken together, this study showed that PNS may alleviate steroid resistance in GEC by interfering with steroid-resistant Lyme-Exos to ameliorate LN progression, which will likely provide insights into developing a new LN treatment.
Potential application of traditional Chinese medicine in cerebral ischemia—Focusing on ferroptosis
Authors: Zhao Fengyan , Peng Caiwang , Sun Yang , Li Hengli , Du Ke , Liu Fang
Published: September 2022

Traditional Chinese medicine (TCM) has attracted a great deal of attention in the treatment of cerebral ischemia is credited with the remarkable neuroprotective effects. However, the imperfect functional mechanism of TCM is a major obstacle to their application. Many studies have been conducted to illustrate the pathophysiology of post-ischemic cerebral ischemia by elucidating the neuronal cell death pathway. Meanwhile, a new type of cell death, ferroptosis, is gradually being recognized in various diseases and is becoming a new pathway of therapeutic intervention strategy to solve many health problems. Especially since ferroptosis has been found to be closely involved into the pathogenesis of cerebral ischemia, it has been considered as a key target in the treatment of cerebral ischemia. Therefore, this paper reviews the latest research findings about the treatment of cerebral ischemia with TCM focused on ferroptosis as a target. Also, in order to explores the possibility of a new approach to treat cerebral ischemia with TCM, we discusses the correlation between ferroptosis and other cell death pathways such as apoptosis and autophagy, which would provide references for the following researches.
Effects and mechanisms of 6-hydroxykaempferol 3,6-di-O-glucoside-7-O-glucuronide from Safflower on endothelial injury in vitro and on thrombosis in vivo
Authors: Wang Li-Wei , He Jiang-Feng , Xu Hai-Yan , Zhao Peng-Fei , Zhao Jie , Zhuang Cong-Cong , Ma Jian-Nan , Ma Chao-Mei , Liu Yong-Bin
Published: September 2022

Background: The florets of Carthamus tinctorius L. (Safflower) is an important traditional medicine for promoting blood circulation and removing blood stasis. However, its bioactive compounds and mechanism of action need further clarification.

Objective: This study aims to investigate the effect and possible mechanism of 6-hydroxykaempferol 3,6-di-O-glucoside-7-O-glucuronide (HGG) from Safflower on endothelial injury in vitro, and to verify its anti-thrombotic activity in vivo.

Methods: The endothelial injury on human umbilical vein endothelial cells (HUVECs) was induced by oxygen-glucose deprivation followed by reoxygenation (OGD/R). The effect of HGG on the proliferation of HUVECs under OGD/R was evaluated by MTT, LDH release, Hoechst-33342 staining, and Annexin V-FITC apoptosis assay. RNA-seq, RT-qPCR, Enzyme-linked immunosorbent assay and Western blot experiments were performed to uncover the molecular mechanism. The anti-thrombotic effect of HGG in vivo was evaluated using phenylhydrazine (PHZ)-induced zebrafish thrombosis model.

Results: HGG significantly protected OGD/R induced endothelial injury, and decreased HUVECs apoptosis by regulating expressions of hypoxia inducible factor-1 alpha (HIF-1α) and nuclear factor kappa B (NF-κB) at both transcriptome and protein levels. Moreover, HGG reversed the mRNA expression of pro-inflammatory cytokines including IL-1β, IL-6, and TNF-α, and reduced the release of IL-6 after OGD/R. In addition, HGG exhibited protective effects against PHZ-induced zebrafish thrombosis and improved blood circulation.

Conclusion: HGG regulates the expression of HIF-1α and NF-κB, protects OGD/R induced endothelial dysfunction in vitro and has anti-thrombotic activity in PHZ-induced thrombosis in vivo.
The efficacy of mesalazine on nonspecific terminal ileal ulcers: A randomized controlled trial
Authors: Li Junrong , Ling Fangmei , Guo Di , Zhao Jinfang , Cheng Ling , Chen Yidong , Xu Mingyang , Zhu Liangru
Published: September 2022

Background: Nonspecific terminal ileal ulcers are one of the common ulcerative diseases in terminal ileum. However, the studies about treatment efficacy are scarce. We aimed to investigate the efficacy of mesalazine in the treatment of this disease.

Methods: Eighty-two patients with nonspecific terminal ileal ulcers who sought outpatient medical treatment in the Division of Gastroenterology, Wuhan Union Hospital, from April 2016 to January 2019 were enrolled and randomly divided into two groups. The experimental group took mesalazine orally, 4.0 g/d, once a day for 3 months. The control group was followed up without special intervention. The primary endpoint was the endoscopic remission rate at the 6th and 12th month. Secondary endpoints included the clinical remission rate at the 1st, 6th and 12th month and adverse events (ChiCTR1900027503).

Results: About the endoscopic efficacy, the remission rate of the experimental group and control group was 73.2 versus 61.0% at the 6th month (RR = 1.20, 95%CI 0.88∼1.63, p = 0.24) and 87.8 versus 78.0% at the 12th month (RR = 1.13, 95%CI 0.92∼1.37, p = 0.24). About the clinical efficacy, the remission rate was 70.3 versus 43.8% at the 1st month (RR = 1.61, 95%CI 1.03∼2.51, p = 0.03), 83.8 versus 68.8% at the 6th month (RR = 1.22, 95%CI 0.93∼1.60, p = 0.14) and 91.9 versus 81.3% at the 12th month (RR = 1.13, 95%CI 0.93∼1.37, p = 0.34). During follow-up, no patients were diagnosed with Crohn’s disease or intestinal tuberculosis, and no patients developed significant complications.

Conclusion: For patients with nonspecific terminal ileal ulcers, there is no disease progression over a short term. In addition, there is no significant difference in clinical or endoscopic efficacy between patients who received mesalazine and patients who are followed up without special intervention.
Experimental and population balance model interpretation of foam physics in porous media
Authors: Zhao Jing , He Yanfeng , Yang Jun
Published: September 2022

Foam has been used as an effective displacing fluid for gas mobility control in enhanced oil recovery (EOR) and subsurface remediation. In this study, a series of core flooding experiments are performed on cores with a wide permeability ranging from 3.3 to 2749 mD to evaluate the impact of foam quality and permeability on foam performance. It is found that the steady-state foam mobility control factor is related to permeability in a non-linear, non-monotonic manner. A full physics, mechanistic foam model is proposed by incorporating a novel flowing foam fraction relation grounded-up from pore-level observations, and a new kinetic expression of foam coalescence rate by oil based on pinch-off foam rupture mechanism into the population-balance framework of Almajid et al. (Advances in Water Resources, 2021, 150: 103877). The proposed model is applied to match foam flow experimental results in the absence and in the presence of oil. Results show that our model captures the high-quality and low-quality foam regimes observed in previous oil-free foam flow experiments. Within the medium permeability range, in the absence of oil, lower gas mobility is observed in the lower permeability core due to faster foam film thinning at higher capillary pressure, while in the presence of residual oil, the difference in foam mobility fades away due to the insignificant impact of capillary pressure on the stability of pseudoemulsion films.
Preconditioned Pseudo-Spectral Gradient Flow for Computing the Steady-State of Space Fractional Cahn-Allen Equations With Variable Coefficients
Authors: Alzahrani Saleh Mousa , Chokri Chniti
Published: September 2022

The aim of this paper is to propose some efficient and accurate numerical methods to compute the steady-state of variable coefficients space fractional Cahn-Allen equations. The approach combines an adaptive time stepping semi-implicit gradient flow method to minimize the fractional energy functional and pseudo-spectral approximation schemes. Based on the use of a preconditioned GMRES, the space fractional Cahn-Allen equation is then solved efficiently. The full methodology is supported by the numerical solution of a one-dimensional problem.
Chiral flow in a binary mixture of two-dimensional active disks
Authors: López-Castaño Miguel A. , Rodríguez-Rivas A. , Vega Reyes F.
Published: September 2022

In this article, we, experimentally, studied the dynamics of a binary mixture of air-fluidized disks. The disks are chiral since they incorporate a set of blades with constant tilt. Both species are identical except for their blade tilt angle, which is rotated by 180° in the second species. We analyzed the phase behavior of the system. Our analysis reveals a wide range of different fluid dynamics, including chiral flow. This chiral flow features in its base state a large vortex. We reported, for certain ranges of relative particle density of each species, inversion of the vorticity of this vortex. We discussed the possible mechanisms behind these chiral flow transitions.
Vascular smooth muscle ion channels in essential hypertension
Authors: Daghbouche-Rubio Nuria , López-López José Ramón , Pérez-García María Teresa , Cidad Pilar
Published: September 2022

Hypertension is a highly prevalent chronic disease and the major risk factor for cardiovascular diseases, the leading cause of death worldwide. Hypertension is characterized by an increased vascular tone determined by the contractile state of vascular smooth muscle cells that depends on intracellular calcium levels. The interplay of ion channels determine VSMCs membrane potential and thus intracellular calcium that controls the degree of contraction, vascular tone and blood pressure. Changes in ion channels expression and function have been linked to hypertension, but the mechanisms and molecular entities involved are not completely clear. Furthermore, the literature shows discrepancies regarding the contribution of different ion channels to hypertension probably due to differences both in the vascular preparation and in the model of hypertension employed. Animal models are essential to study this multifactorial disease but it is also critical to know their characteristics to interpret properly the results obtained. In this review we summarize previous studies, using the hypertensive mouse (BPH) and its normotensive control (BPN), focused on the identified changes in the expression and function of different families of ion channels. We will focus on L-type voltage-dependent Ca2+ channels (Cav1.2), canonical transient receptor potential channels and four different classes of K+ channels: voltage-activated (Kv), large conductance Ca2+-activated (BK), inward rectifiers (Kir) and ATP-sensitive (KATP) K+ channels. We will describe the role of these channels in hypertension and we will discuss the importance of integrating individual changes in a global context to understand the complex interplay of ion channels in hypertension.
Rapid Weight Loss of Up to Five Percent of the Body Mass in Less Than 7 Days Does Not Affect Physical Performance in Official Olympic Combat Athletes With Weight Classes: A Systematic Review With Meta-Analysis
Authors: Mauricio Clóvis De Albuquerque , Merino Pablo , Merlo Rodrigo , Vargas José Jairo Narrea , Chávez Juan Ángel Rodríguez , Pérez Diego Valenzuela , Aedo-Muñoz Esteban Ariel , Slimani Maamer , Brito Ciro José , Bragazzi Nicola Luigi , Miarka Bianca
Published: September 2022

Given the relevance of the effects that weight loss can generate on the physical performance in athletes, this study performed a systematic review with meta-analysis of the published literature on rapid weight loss (RWL) and examined its impact on the physical performance in Official Olympic combat sports athletes. The “Preferred Reporting Items for Systematic Reviews and Meta-Analysis” (PRISMA) guidelines were followed to ensure an ethical and complete reporting of the findings. PubMed, SPORT Discus, and EBSCO were the electronic databases explored for article retrieval and selection. The following string was applied: “RWL” OR “weight loss” OR “weight reduction” AND “judo” OR “wrestling” or “taekwondo” or “boxing” AND “performance.” Based on the quality analysis, conducted according to the “Tool for the assessment of study quality and reporting in exercise training studies” (TESTEX), ten articles achieved a score >6 points. The meta-analysis showed a significant difference in pre- vs. post-weight loss (p = 0.003) and no effects in pre- vs. post-power and strength performance analysis (p > 0.05 for both results). Based on our systematic review and meta-analysis of the literature, RWL up to ≤5% of the body mass in less than 7 days does not influence performance outcomes in Official Olympic combat athletes with weight classes, considering the strength and power measures.