bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcatheter Arterial Chemoembolization in Combination With High-Intensity Focused Ultrasound for Intermediate and Advanced Hepatocellular Carcinoma: A Meta-Analysis
Authors: Wang Yun-Bing , Ma Rong , Wang Zhi-Biao , Shi Qiu-Ling , Zhang Lian , Chen Wen-Zhi , Gong Jian-Ping , Bai Jin 
Published: March 2022

BackgroundThe study was conducted to explore whether high-intensity focused ultrasound (HIFU) can improve the effect of transcatheter arterial chemoembolization (TACE) in intermediate and advanced hepatocellular carcinoma (HCC).MethodsPubMed, Embase, Cochrane Library, Web of Science, Wanfang Data, CQVIP, China National Knowledge Infrastructure (CNKI), and Chinese Biomedical (CBM) databases were searched for randomized controlled trials (RCTs) comparing the effect of TACE in combination with HIFU group (group A) to TACE alone group (group B) in treating intermediate and advanced HCC. The primary outcomes were overall survival (OS) rate and tumor response rate. The odds ratio (OR) and 95% confidence interval (CI) for each study were calculated and then pooled with fixed effects model or random effects model. Sensitivity analyses and subgroup analyses were conducted. A publication bias was also evaluated.ResultsAfter literature selection, eleven RCTs involving 803 patients were included in this meta-analysis. This meta-analysis revealed that group A was associated with an increased 6-month OS rate (OR = 0.20), 12-month OS rate (OR = 0.23), 24-month OS rate (OR = 0.32), and overall response rate (WHO criterion, OR = 0.22; RECIST criterion, OR = 0.30). Furthermore, subgroup analyses showed no bias in the result. Given the limited number of studies that reported major complications, no additional meta-analysis of complication was conducted. Despite no special treatment, any complication following HIFU treatment was found to subside within 3-7 days.ConclusionTACE in combination with HIFU is associated with increased OS and tumor response in intermediate and advanced HCC. Current evidence supports the use of HIFU after TACE treatment in intermediate and advanced HCC.
Chemoradiotherapy Versus Chemotherapy Alone for Advanced Esophageal Squamous Cell Carcinoma: The Role of Definitive Radiotherapy for Primary Tumor in the Metastatic Setting
Authors: Li Li-Qing , Fu Qing-Guo , Zhao Wei-Dong , Wang Yu-Dan , Meng Wan-Wan , Su Ting-Shi 
Published: March 2022

IntroductionThe role of definitive radiotherapy in advanced esophageal squamous cell carcinoma (ESCC), especially in the metastatic setting, remains unclear. Therefore, we aimed to investigate the efficacy of chemoradiotherapy (CRT) versus chemotherapy (CT) alone in these selected patients.MethodsWe retrospectively evaluated 194 newly diagnosed advanced ESCC who underwent definitive CRT or CT alone, including 97 patients with locally advanced and 97 patients with distant metastatic disease. Cumulative overall survival (OS) and progression-free survival (PFS) were evaluated with a log-rank test. Propensity score matching was used to simulate random allocation. In addition, we performed subgroup analysis in the locally advanced and metastatic disease.ResultsAfter matching, 63 well-paired patients were selected. The adjusted median OS (12.5 vs. 7.6 months, p = 0.002) and PFS (9.0 vs. 4.8 months, p = 0.0025) in the CRT group were superior to that in the CT-alone group. Further subgroup analysis revealed that CRT conferred survival benefits to both locally advanced and metastatic cohorts. For patients with distant metastasis, median OS (12.9 vs. 9.3 months, p = 0.029) and PFS (9.9 vs. 4.0 months, p =0.0032) in the CRT group were superior to that in the CT-alone group. In a multivariate Cox regression analysis of the entire cohort, additional definitive radiotherapy was independently associated with better OS (p = 0.041) and PFS (p = 0.007).ConclusionsIn both locally advanced and metastatic ESCC, additional definitive-dose radiotherapy was associated with improved clinical outcomes. Therefore, more consideration should be given to its application in the metastatic setting.
Integrated Network Pharmacology and Experimental Verification to Explore the Molecular Mechanism of Hedysarum Multijugum Maxim–Curcumae Rhizoma Herb Pair for Treating Non-Small Cell Lung Cancer
Authors: Hu Shaopu , Ge Mengxue , Zhang Shuixiu , Jiang Min , Hu Kaiwen , Gao Lei 
Published: March 2022

BackgroundHedysarum Multijugum Maxim–Curcumae Rhizoma (HMMCR), a well-known herb pair in traditional Chinese medicine (TCM), has been widely used for the treatment of various cancers. However, the active components of HMMCR and the underlying mechanism of HMMCR for non-small-cell lung carcinoma (NSCLC) remain unclear.MethodsActive ingredients of HMMCR were detected by liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). On this basis, potential targets of HMMCR were obtained from SwissTargetPrediction database. NSCLC-related targets were collected from four public databases (GeneCards, OMIM, TTD, and PharmGkb). The drug ingredients–disease targets network was visualized. The hub targets between HMMCR and NSCLC were further analyzed by protein–protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Subsequently, the results predicted by network pharmacology were further validated via in vitro experiments.ResultsA total of 181 compounds were identified from the aqueous extract of HMMCR. Through network analysis, a compound–target network including 153 active ingredients of HMMCR and 756 HMMCR-NSCLC co-targets was conducted; 6 crucial compounds and 62 hub targets were further identified. The results of KEGG enrichment analysis showed that PI3K/Akt signaling pathway may be the critical pathway of HMMCR in the treatment of NSCLC. The in vitro experiments indicated that HMMCR inhibits the proliferation and migration of NSCLC cells via inactivation of the PI3K/Akt signaling pathway, consistent with the results predicted by network pharmacology.ConclusionIntegrating LC-ESI-MS/MS, network pharmacology approach, and in vitro experiments, this study shows that HMMCR has vital therapeutic effect on NSCLC through multi-compound, multi-target, and multi-pathway, which provides a rationale for using HMMCR for the treatment of NSCLC.
Risk Stratification and Distribution of Hepatocellular Carcinomas in CEUS and CT/MRI LI-RADS: A Meta-Analysis
Authors: Zhou Yan , Qin Zhengyi , Ding Jianmin , Zhao Lin , Chen Ying , Wang Fengmei , Jing Xiang 
Published: March 2022

BackgroundCEUS LI-RADS and CT/MRI LI-RADS have been used in clinical practice for several years. However, there is a lack of evidence-based study to compare the proportion of hepatocellular carcinomas (HCCs) in each category and the distribution of HCCs of these two categorization systems.PurposeThe purpose of this study was to compare the proportion of HCCs between corresponding CEUS LI-RADS and CT/MRI LI-RADS categories and the distribution of HCCs and non-HCC malignancies in each category.MethodsWe searched PubMed, Embase, and Cochrane Central databases from January 2014 to December 2021. The proportion of HCCs and non-HCC malignancies and the corresponding sensitivity, specificity, accuracy, diagnostic odds ratio (DOR), and area under the curve (AUC) of the LR-5 and LR-M categories were determined using a random-effect model.ResultsA total of 43 studies were included. The proportion of HCCs in CEUS LR-5 was 96%, and that in CECT/MRI LR-5 was 95% (p &gt; 0.05). The proportion of non-HCC malignancy in CEUS LR-M was lower than that of CT/MRI LR-M (35% vs. 58%, p = 0.01). The sensitivity, specificity, and accuracy of CEUS LR-5 for HCCs were 73%, 92%, and 78%, respectively, and of CT/MRI LR-5 for HCCs, 69%, 92%, and 76%, respectively.ConclusionWith the upshift of the LI-RADS category, the proportion of HCCs increased. CEUS LR-3 has a lower risk of HCCs than CT/MRI LR-3. CEUS LR-5 and CT/MRI LR-5 have a similar diagnostic performance for HCCs. CEUS LR-M has a higher proportion of HCCs and a lower proportion of non-HCC malignancies compared with CT/MRI LR-M.
Comparison of Effectiveness of Two Different Doses of Propranolol on Kaposiform Hemangioendothelioma
Authors: Wei Li , Li Li , Xu Zigang , Zhang Bin , Han Xiaofeng , Wang Chen , Liu Yuanxiang , Xiu Bingyu , Qiu Lei , Sun Yujuan , Ma Lin 
Published: March 2022

ObjectiveTo compare the clinical efficacy and safety of two different doses of propranolol in the treatment of cutaneous kaposiform hemangioendothelioma (KHE).MethodsThe cohort of this prospective case–control study comprised 11 children with KHE treated from October 2015 to August 2018 in our institution. All participants were clinically and pathologically diagnosed as having cutaneous KHE. The children were allocated to two groups: six children in Group A (low-dose group) received oral propranolol 1.5 mg/kg/d, whereas five in Group B (high-dose group) received oral propranolol 2 mg/kg/d. The children were checked and photographed before and after treatment. Changes in the tumors were tracked by clinical and ultrasound examination. Follow-up visits to monitor for adverse reactions occurred regularly.ResultsGrade I, Grade II, and Grade IV improvements in tumors were each noted in one child in Group A (three improved in total) and Grade III in two and Grade IV in another two children in Group B (four improved in total). Oral propranolol was effective in 50 and 80% of children in Groups A and B, respectively; this difference is statistically significant (P &lt; 0.01). Minor adverse reactions occurred in eight of the 11 children.ConclusionsPropranolol treatment is effective against cutaneous KHE. There were no serious adverse reactions, and the treatment was safe in the long term. A dose of 2 mg/kg/d was more effective than 1.5 mg/kg/d in the treatment of KHE and did not increase the rate of adverse reactions. Children with KHE should be treated with propranolol 2 mg/kg/d orally.
Liver Involvement in Acute Respiratory Infections in Children and Adolescents – Results of a Non-interventional Study
Authors: Kamin Wolfgang , Adams Ortwin , Kardos Peter , Matthys Heinrich , Meister Norbert , Strassburg Christian P. 
Published: March 2022

BackgroundIn children and adults with acute respiratory tract infections (ARTI), elevations of serum liver enzyme activities are frequently observed in clinical practice. However, epidemiological data particularly in the pediatric population are very limited. The aim of this study was to assess the incidence of hepatic involvement, to identify the viruses and to analyze risk factors in children and adolescents with ARTI in a real-world setting.MethodsWe report on a prospective, multicenter, non-interventional study with 1,010 consecutive patients aged 1–17 years with ARTI who consulted a physician within 5 days after onset of symptoms. Laboratory blood tests and PCR virus detection in nasopharyngeal lavage were performed at first presentation and after 3–7 days. Patients with elevated activities of serum liver enzymes (ASAT, ALAT, and γ-GT) were determined in local laboratories and values were normalized by dividing by the individual upper limit of the normal range (ULN). The resulting index (&lt;1 means below ULN, &gt;1 means above ULN) allowed to compare results from laboratories with different reference ranges.ResultsLaboratory test results of 987 patients were available at first visit. 11.1% (95% CI: 9.2–13.3%) exhibited an elevation of ASAT, ALAT, and/or γ-GT activities. Virus DNA or RNA was identified in nasopharyngeal lavages of 63% of the patients. 12.2% of patients with positive PCR and 9.7% of those with negative PCR (p = 0.25) had elevated serum liver enzyme activities. The highest rates were observed in patients with a positive result for influenza B virus (24.4%) followed by human metapneumovirus (14.6%), and human coronavirus (others than SARS-CoV-2) (13.6%). The rate of children and adolescents with ARTI and elevation of serum liver enzyme activities correlated with the virus species and with overweight of the patients but did not differ in patients with or without previous medication intake.ConclusionElevated enzyme activities are present in about 10% of children and adolescents with ARTI. In our cohort, these elevations were mild to moderate; probably resulting from an inflammation process with hepatic involvement.
Qingda Granule Attenuates Angiotensin II-Induced Renal Apoptosis and Activation of the p53 Pathway
Authors: Long Linzi , Zhang Xiuli , Wen Ying , Li Jiapeng , Wei Lihui , Cheng Ying , Liu Huixin , Chu Jianfeng , Fang Yi , Xie Qiurong , Shen Aling , Peng Jun 
Published: March 2022

Background: Qingda granules (QDG) exhibit antihypertension and multiple-target-organ protection. However, the therapeutic potential of QDG on hypertensive renal injury remains unknown. Therefore, the main objective of the current study is to explore the effects and underlying mechanisms of QDG treatment on renal injury in angiotensin (Ang) II-infused mice.Methods and results: Mice were infused with Ang II (500 ng/kg/min) or saline for 4 weeks with subcutaneously implanted osmotic pumps. After infusion, mice in the Ang II + QDG group were intragastrically administrated with QDG daily (1.145 g/kg/day), whereas the control group and Ang II group were intragastrically administrated with the same amount of double-distilled water. Blood pressure of the mice monitored using the CODA™ noninvasive blood pressure system revealed that QDG treatment significantly attenuated elevated blood pressure. Moreover, hematoxylin–eosin staining indicated that QDG treatment ameliorated Ang II-induced renal morphological changes, including glomerular sclerosis and atrophy, epithelial cell atrophy, and tubular dilatation. RNA-sequencing (RNA-seq) identified 662 differentially expressed transcripts (DETs) in renal tissues of Ang II-infused mice, which were reversed after QDG treatment. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis based on DETs in both comparisons of Ang II vs. Control and Ang II + QDG vs. Ang II identified multiple enriched pathways, including apoptosis and p53 pathways. Consistently, terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) staining and Annexin V staining revealed that QDG treatment significantly attenuated Ang II-induced cell apoptosis in renal tissues and cultured renal tubular epithelial cell lines (NRK-52E). Furthermore, western blot analysis indicated that Ang II infusion significantly upregulated the protein expression of p53, BCL2-associated X (BAX), cle-caspase-9, and cle-caspase-3, while downregulating the protein expression of BCL-2 in renal tissues, which were attenuated after QDG treatment.Conclusion: Collectively, QDG treatment significantly attenuated hypertensive renal injury, partially by attenuating renal apoptosis and suppressing p53 pathways, which might be the underlying mechanisms.
Asthma Therapies on Pulmonary Tuberculosis Pneumonia in Predominant Bronchiectasis–Asthma Combination
Authors: Yeh Jun-Jun , Lin Hui-Chuan , Yang Yu-Cih , Hsu Chung-Y. , Kao Chia-Hung 
Published: March 2022

Background: It is sometimes difficult to distinguish between asthma and bronchiectasis as their symptoms overlap, and these two diseases are associated with pulmonary tuberculosis (PTB) or pneumonia.Objective: The purpose of this study is to determine the effects of bronchodilator drugs, steroids, antidepressants drugs, and antianxiety drugs on the risks of PTB or pneumonia in patients with bronchiectasis–asthma combination or bronchiectasis–asthma–chronic obstructive pulmonary disease combination—BCAS cohort.Methods: After propensity score matching, we retrospectively studied patients with BCAS (N = 620) and without BCAS (N = 2,314) through an analysis. The cumulative incidence of PTB or pneumonia was analyzed through Cox proportional regression. After adjustment for sex, age, comorbidities, and medications [including long-acting beta2 agonist/muscarinic antagonists (LABAs/LAMAs), short-acting beta2 agonist/muscarinic antagonists (SABAs/SAMAs), leukotriene receptor antagonist, montelukast, steroids (inhaled corticosteroids, ICSs; oral steroids, OSs), anti-depressants (fluoxetine), and anti-anxiety drugs (benzodiazepines, BZDs)], we calculated the adjusted hazard ratios (aHR) and their 95% confidence intervals (95% CI) for these risks. Similar to OSs, ICSs are associated with an increased risk of PTB or pneumonia, lumping these two as steroids (ICSs/OSs).Results: For the aHR (95% CI), with non-LABAs/non-OSs as the reference 1, the use of LABAs [0.70 (0.52–0.94)]/OSs [0.35 (0.29–0.44)] was associated with a lower risk of PTB or pneumonia. However, the current use of LABAs [2.39 (1.31–4.34)]/SABAs [1.61 (1.31–1.96)], steroids [ICSs 3.23 (1.96–5.29)]/OSs 1.76 (1.45–2.14)], and BZDs [alprazolam 1.73 (1.08–2.75)/fludiazepam 7.48 (1.93–28.9)] was associated with these risks. The current use of LAMAs [0.52 (0.14–1.84)]/SAMAs [1.45 (0.99–2.11)] was not associated with these risks.Conclusion: The current use of LAMAs/SAMAs is relatively safe with respect to PTB or pneumonia risks, but LABAs/SABAs, steroids, and BZDs could be used after evaluation of the benefit for the BCAS cohort. However, we must take the possible protopathic bias into account.
Prescription Appropriateness of Drugs for Peptic Ulcer and Gastro-Esophageal Reflux Disease: Baseline Assessment in the LAPTOP-PPI Cluster Randomized Trial
Authors: Ardoino Ilaria , Casula Manuela , Molari Giulia , Mucherino Sara , Orlando Valentina , Menditto Enrica , Franchi Carlotta 
Published: March 2022

Background: Drugs for peptic ulcer and gastro-esophageal reflux disease (GERD) are among the most widely prescribed, frequently without appropriate indications. This represents an important issue, as it leads to risk of adverse events for patients and unnecessary costs for National Health Service.Aim: To assess the prescription appropriateness of drugs for GERD, in the frame of the “Evaluation of the effectiveness of a Low-cost informative intervention to improve the Appropriate PrescripTiOn of Proton PumP Inhibitors in older people in primary care: a cluster-randomized controlled study” (LAPTOP-PPI) (Clinicaltrial.gov: NCT04637750).Methods: The appropriateness of drug prescription was assessed on data collected in administrative databases, by integrating information on concomitant medications, outpatient medical and laboratory procedures and hospital discharge diagnoses, according to the reimbursement criteria provided by the Italian Medicine Agency. We analyzed data of community-dwelling people aged 65 years and over, living in the areas of Bergamo (Northern Italy) and Caserta (Southern Italy), from July 1 to 31 December 2019.Results: Among 380,218 patients, 175,342 (46.1%) received at least one prescription of drugs for GERD. All in all, we found that only 41.2% of patients received appropriate prescriptions.Conclusion: Given the potential risk of adverse drug reactions, especially in older people, educational interventions should be prompted for physicians, in order to improve the quality of prescription of drugs for GERD and, in turn, avoid unfavorable health outcomes and unnecessary costs.
Absorption, Metabolism, and Excretion of ACT-1004-1239, a First-In-Class CXCR7 Antagonist: In Vitro, Preclinical, and Clinical Data
Authors: Huynh Christine , Seeland Swen , Segrestaa Jerome , Gnerre Carmela , Hogeback Jens , Meyer zu Schwabedissen Henriette E. , Dingemanse Jasper , Sidharta Patricia N. 
Published: March 2022

ACT-1004-1239 is a potent, selective, first-in-class CXCR7 antagonist, which shows a favorable preclinical and clinical profile. Here we report the metabolites and the metabolic pathways of ACT-1004-1239 identified using results fromin vitroandin vivostudies. Two complementaryin vitrostudies (incubation with human liver microsomes in the absence/presence of cytochrome P450- [CYP] specific chemical inhibitors and incubation with recombinant CYPs) were conducted to identify CYPs involved in ACT-1004-1239 metabolism. For thein vivoinvestigations, a microtracer approach was integrated in the first-in-human study to assess mass balance and absorption, distribution, metabolism, and excretion (ADME) characteristics of ACT-1004-1239. Six healthy male subjects received orally 100 mg non-radioactive ACT-1004-1239 together with 1 μCi14C-ACT-1004-1239. Plasma, urine, and feces samples were collected up to 240 h post-dose and14C-drug-related material was measured with accelerator mass spectrometry. This technique was also used to construct radiochromatograms of pooled human samples. Metabolite structure elucidation of human-relevant metabolites was performed using high performance liquid chromatography coupled with high resolution mass spectrometry and facilitated by the use of rat samples. CYP3A4 was identified as the major CYP catalyzing the formation of M1in vitro. In humans, the cumulative recovery from urine and feces was 84.1% of the dose with the majority being eliminated via the feces (69.6%) and the rest via the urine (14.5%). In human plasma, two major circulating metabolites were identified, i.e., M1 and M23. EliminationviaM1 was the only elimination pathway that contributed to ≥25% of ACT-1004-1239 elimination. M1 was identified as a secondary amine metabolite following oxidative N-dealkylation of the parent. M23 was identified as a difluorophenyl isoxazole carboxylic acid metabolite following central amide bond hydrolysis of the parent. Other metabolites observed in humans were A1, A2, and A3. Metabolite A1 was identified as an analog of M1 after oxidative defluorination, whereas both, A2 and A3, were identified as a reduced analog of M1 and parent, respectively, after addition of two hydrogen atoms at the isoxazole ring. In conclusion, CYP3A4 contributes to a relevant extent to ACT-1004-1239 disposition and two major circulating metabolites were observed in humans.Clinical Trial Registration:(https://clinicaltrials.gov/ct2/show/NCT03869320) ClinicalTrials.gov Identifier NCT03869320.