bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms and technologies in cancer epigenetics
Authors: Sherif Zaki A. , Ogunwobi Olorunseun O. , Ressom Habtom W.
Published: January 2025

Cancer’s epigenetic landscape, a labyrinthine tapestry of molecular modifications, has long captivated researchers with its profound influence on gene expression and cellular fate. This review discusses the intricate mechanisms underlying cancer epigenetics, unraveling the complex interplay between DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs. We navigate through the tumultuous seas of epigenetic dysregulation, exploring how these processes conspire to silence tumor suppressors and unleash oncogenic potential. The narrative pivots to cutting-edge technologies, revolutionizing our ability to decode the epigenome. From the granular insights of single-cell epigenomics to the holistic view offered by multi-omics approaches, we examine how these tools are reshaping our understanding of tumor heterogeneity and evolution. The review also highlights emerging techniques, such as spatial epigenomics and long-read sequencing, which promise to unveil the hidden dimensions of epigenetic regulation. Finally, we probed the transformative potential of CRISPR-based epigenome editing and computational analysis to transmute raw data into biological insights. This study seeks to synthesize a comprehensive yet nuanced understanding of the contemporary landscape and future directions of cancer epigenetic research.
Concurrent versus sequential immunotherapy with chemoradiotherapy for unresectable stage III non-small-cell lung cancer: a retrospective study
Authors: Meng-Xi Zhou , Wen-Jie Fan , Ning Zhang , Li-Yang Zhu , Hong-Yan Wang
Published: January 2025

Background

Immunotherapy combined with chemoradiotherapy has demonstrated promising efficacy in stage III non-small-cell lung cancer (NSCLC). However, the optimal timing for immunotherapy intervention during radiotherapy remains unclear. This study aimed to compare the efficacy and safety of immune checkpoint inhibitors (ICIs) administered concurrently or sequentially with chemoradiotherapy in unresectable stage III NSCLC.

Methods

A retrospective analysis of 98 patients with unresectable stage III NSCLC, treated between January 1, 2019, and June 30, 2023, was conducted. Patients were grouped based on concurrent or sequential administration of ICIs with chemoradiotherapy. Median progression-free survival (mPFS), median overall survival (mOS), 1 and 2-year PFS rates, 2 and 3-year OS rates, objective remission rate (ORR), and disease control rate (DCR) were evaluated. Survival analysis was performed using the Kaplan–Meier method. Univariate and multivariate analyses were conducted using the log-rank test and Cox proportional hazards model. Treatment-related adverse effects were assessed and graded.

Results

A total of 98 patients with unresectable stage III NSCLC treated with chemoradiotherapy and ICIs were included. The mPFS and mOS were 19.0 (14.2-23.8) months and 31.5 (24.3-38.7) months, 12.8 (9.5-16.1) months and 28.5 (19.3-37.7) months in the concurrent and sequential ICI groups, respectively, and mPFS showed a significant difference (P=0.047). The estimated 1 and 2-year PFS rates were 79.6% (95% confidence interval [CI]: 67.6-91.6) and 40.4% (95% CI: 15.8-49.2) for the concurrent group, compared to 51.0% (95% CI: 35.9-66.1) and 31.6% (95% CI: 14.5-48.7) for the sequential group. The estimated 2 and 3-year OS rates were 65.7% (95% confidence interval [CI]: 48.6-82.8) and 40.0% (95% CI: 16.1-63.9) for the concurrent group, compared to 54.6% (95% CI: 35.8-73.4) and 28.7% (95% CI: 4.8-52.6) for the sequential group. The Eastern Cooperative Oncology Group Performance Status Scale (ECOG) score and tumor differentiation were identified as independent factors associated with PFS and OS. Distant metastasis occurred in 13.8% and 25.5% of patients in the concurrent and sequential ICI groups, respectively (P=0.049). The incidence of any grade of pneumonitis was 43.1% and 38.3% in two groups, with grade 3 or higher in 7.8% and 8.5% of patients, respectively. Hematologic toxicity of any grade was observed in 29.4% and 34.0% of the two groups, with grade 3 or higher toxicity identified in 3.9% and 2.1% of patients, respectively.

Conclusions

Concurrent immunotherapy combined with chemoradiotherapy demonstrated superior efficacy than sequential immunotherapy, with good safety and tolerability in patients with unresectable stage III NSCLC.
Real-world evaluation of select adverse drug reactions and healthcare utilization associated with parenteral Ibuprofen and ketorolac in adult and pediatric patients
Authors: Afolabi Mosadoluwa , Rodriguez-Silva Jensy , Chopra Ishveen , Macias-Perez Ines , Makii Jason , Durr Emily , Human Theresa
Published: January 2025

Introduction

Intravenous non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in healthcare settings, but their comparative safety and resource utilization impacts remain understudied. This study aimed to compare adverse drug reactions (ADRs) and healthcare resource utilization (HCRU) between patients receiving IV-ibuprofen versus IV/IM ketorolac.

Methods

A retrospective, longitudinal analysis was conducted using an all-payer database, examining records from January 1, 2014, to June 3, 2023. The study included both adult (≥18 years) and pediatric (<18 years) populations who received one or more doses of either medication. Propensity score matching was applied to both populations, and HCRU was tracked for 29 days post-final dose. The adult cohort included 31,046 IV-ibuprofen and 124,184 ketorolac records, while the pediatric cohort had 5,579 patients per treatment arm.

Results

Both adult and pediatric patients receiving IV-ibuprofen demonstrated lower ADR incidence and reduced HCRU compared to those receiving ketorolac.

Discussion

The findings suggest IV-ibuprofen may be a safer alternative to ketorolac, potentially improving patient care outcomes while reducing healthcare system burden. These results have implications for clinical practice and healthcare resource management.
Construction of a nomogram model to predict the risk of retinopathy of prematurity reactivate after intravitreal anti-vascular endothelial growth factor therapy: a retrospective study
Authors: Shen Ziyun , Hao Qingfei , Yang Tiantian , Cheng Xiuyong
Published: January 2025

Objective

To explore the risk factors for the reactivate of retinopathy of prematurity (ROP) after intravitreal injection of anti-vascular endothelial growth factor (VEGF) and to construct a nomogram model to predict the risk of ROP reactivate.

Methods

A retrospective analysis was conducted on 185 ROP children who underwent anti-VEGF treatment at the First Affiliated Hospital of Zhengzhou University from January 2017 to October 2023. They were randomly divided into a training set (129 cases) and a validation set (56 cases) at a ratio of 7:3. The training set was further divided into a reactivate group (n = 18) and a non-reactivate group (n = 111) based on whether ROP recurred after treatment. Multivariable logistic regression analysis was used to screen for risk factors for ROP reactivate. A nomogram model was constructed using R software and validated using the validation set. The discrimination, calibration, and clinical net benefit of the model were evaluated using the receiver operating characteristic curve (ROC curve), calibration curve, and decision curve analysis, respectively.

Results

Multivariable logistic regression analysis showed that the number of red blood cell transfusions, use of pulmonary surfactant (PS) 2 times or more, and preoperative fundus hemorrhage were independent risk factors for ROP reactivate (P < 0.05). The area under the ROC curve (AUC) of the training set was 0.810 (95% CI: 0.706–0.914), and that of the validation set was 0.756 (95% CI: 0.639–0.873). The Hosmer-Leme show goodness-of-fit test indicated a good fit of the model (P = 0.31). Calibration curve analysis and decision curve analysis suggested high predictive efficacy and clinical application value of the model.

Conclusions

The number of red blood cell transfusions, use of PS 2 times or more, and preoperative fundus hemorrhage are independent risk factors for ROP reactivate. The nomogram model constructed based on these factors has high predictive efficacy and clinical application value.
Effects of physical exercise on anxiety depression and emotion regulation in children with attention deficit hyperactivity disorder: a systematic review and meta-analysis
Authors: Song Yagang , Jia Shuqi , Wang Xing , Wang Aiwei , Ma Tao , Li Shufan , Chen Jiwei , Guo Zhaohui , Ding Feng , Ren Yuxi , Qin Man
Published: January 2025

Objective

This systematic review and meta-analysis aimed to comprehensively evaluate the impact of physical exercise interventions on anxiety, depression, and emotional regulation in children diagnosed with attention deficit hyperactivity disorder (ADHD).

Methods

A comprehensive search was conducted across multiple databases, including Embase, Web of Science (WOS), PubMed, The Cochrane Library, Wanfang Data, VIP Information, and China National Knowledge Infrastructure (CNKI), from their inception up to July 2024. The search aimed to identify randomized controlled trials (RCTs) investigating the impact of physical exercise on anxiety, depression, and emotional regulation in children diagnosed with ADHD. The Physiotherapy Evidence Database (PEDro) scale was employed to assess the quality of the literature, while the revised Cochrane risk-of-bias tool (ROB-2) was used to evaluate the overall risk of bias. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) profiler method was utilized to further assess the quality of evidence. Meta-analysis, sensitivity analysis, and publication bias testing were performed using Stata 18.0 software. Effect sizes were calculated using the standardized mean difference (SMD) and 95% confidence intervals (CI).

Results

The analysis included 18 RCTs, encompassing 830 participants. Physical exercise exhibited a significant positive effect on anxiety (SMD = −0.58, p < 0.05), depression (SMD = −0.57, p < 0.05), and emotional regulation (SMD = 1.03, p < 0.05) in children diagnosed with ADHD. Subgroup analysis revealed that exercise programs with monotypic and mixed modalities, short duration, high frequencies, medium duration, and moderate intensities were the most efficacious in ameliorating anxiety symptoms. The mixed exercise program, when conducted for short duration, with low frequencies, medium duration, and moderate intensity was the most effective in alleviating depression symptoms. Exercise programs featuring mixed modalities, longer duration, moderate to high frequencies, shorter duration, and low intensity yielded the most significant improvements in emotional regulation.

Conclusions

Research demonstrates that physical exercise mitigates anxiety and depression and improves emotional regulation in children with ADHD. A dose-response relationship is evident, correlating with the type, duration, intensity, frequency, and overall exercise duration.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, PROSPERO identifier (CRD42024571577).
The safety of cyclosporine and tacrolimus in pediatric nephrotic syndrome patients: a disproportionate analysis based on the FAERS database
Authors: Liu Yu , Yan Chong , Zhao Yaowang , Deng Sui , Zu Jiancheng
Published: January 2025

Objective

This study aimed to systematically evaluate the safety of cyclosporine (CsA) and tacrolimus (TAC) in pediatric nephrotic syndrome (NS) patients using real-world data from the FDA Adverse Event Reporting System (FAERS).

Methods

We analyzed adverse event (AE) reports from the FAERS database between Q4 2003 and Q2 2024, focusing on AEs associated with CsA and TAC in NS patients aged 18 years and younger. We employed three signal detection methods—Proportional Reporting Ratio (PRR), Relative Reporting Ratio (RRR), and Reporting Odds Ratio (ROR)—to assess the risk of drug-related AEs. Sensitivity analyses were conducted to explore the influence of gender on AE occurrence.

Results

A total of 207 CsA-related and 145 TAC-related AE reports were included. CsA was significantly associated with nephropathy toxic (ROR = 8.26, 95% CI: 4.21–16.20), urine output decreased (ROR = 29.93, 95% CI: 3.66–244.61), and posterior reversible encephalopathy syndrome (ROR = 6.70, 95% CI: 3.17–14.14). TAC was associated with an increased risk of dystonia (ROR = 67.93, 95% CI: 8.63–534.86), kidney fibrosis (ROR = 22.65, 95% CI: 8.16–62.87), and diabetic ketoacidosis (ROR = 46.51, 95% CI: 5.68–380.97). Sensitivity analysis indicated that gender influenced the occurrence of AEs, with CsA showing higher nephrotoxicity in male patients, while TAC was more strongly associated with metabolic disorders and neurological AEs in female patients.

Conclusion

In pediatric NS patients, CsA primarily induces nephrotoxicity and neurological complications, whereas TAC is more likely to cause kidney fibrosis and metabolic disorders. Enhanced monitoring of these AEs and individualized drug adjustments based on patient characteristics are recommended to optimize treatment outcomes and reduce AE incidence.
Prenatal ultrasound phenotype of fetuses with recurrent 1q21.1 deletion and duplication syndrome
Authors: Wang Fengyang , Peng Huijuan , Lou Guiyu , Ren Yanxin , Liao Shixiu
Published: January 2025

Objective

Our study aimed to collect fetuses with recurrent 1q21.1 deletion or duplication syndrome for systematic clinical phenotype analysis to further delineate the intrauterine phenotype features of the two reciprocal syndromes.

Methods

Prenatal samples, including amniotic fluid and chorionic villus samples, were obtained by amniocentesis and chorionic villus sampling at our center, respectively. In total, 43 fetuses were diagnosed with recurrent 1q21.1 deletion or duplication syndrome via array comparative genomic hybridization (array CGH) or copy number variation sequencing (CNV-seq). Prenatal clinical data, pregnancy outcomes, and individual conditions after birth were collected.

Results

In total, 20 fetuses were diagnosed with 1q21.1 deletion syndrome, and 11 had abnormal ultrasound findings. The most common ultrasound features were renal anomalies, musculoskeletal abnormalities, and increased NT. Other less common ultrasound findings encompassed neurologic abnormalities, cardiovascular defects, absence of the gallbladder, intrauterine growth retardation, and cervical cystic hygroma. On the other hand, 23 fetuses had reciprocal 1q21.1 duplication syndrome, 11 of which had abnormal ultrasound findings, mainly nasal bone abnormalities, cardiovascular defects, increased NT, and neurologic abnormalities.

Conclusions

Our case study suggested that the prenatal clinical phenotypes of the recurrent 1q21.1 deletion syndrome and reciprocal duplication syndrome fetuses were highly diverse with incomplete penetrance. Additionally, our findings should expand the intrauterine phenotype associated with the recurrent 1q21.1 region by a series of prenatal ultrasonic anomalies in this work that were described for the first time, which might broaden knowledge of the genotype and phenotype correlation.
Translation and cross-cultural validation of the Lithuanian version of the sleep-related breathing disorder scale of the Pediatric Sleep Questionnaire
Authors: Oboleviciene Gintare , Miseviciene Valdone
Published: January 2025

Introduction

Sleep-disordered breathing (SDB) is considered the second most common chronic health condition in children. Untreated SDB is associated with long-term health consequences. Our objective was to translate the Pediatric Sleep Questionnaire (PSQ) into Lithuanian and culturally adapt and validate the translated version in order to improve the diagnosis of SDB in Lithuanian children.

Methods

Translations and cultural adaptations were performed to generate a Lithuanian version of the PSQ. Psychometric analysis was conducted on 112 Lithuanian children aged 2–17 years. All patients underwent overnight polysomnography.

Results

The Lithuanian PSQ showed good internal consistency (Cronbach's alpha = 0.816). Lithuanian PSQ responses administered 14–30 days apart were strongly correlated (r = 0.924, p < 0.001, 95% CI 0.830–0.967). EFA of the Lithuanian PSQ confirmed four factors (“snoring”, “behavior”, “sleepiness”, and “other”). We found a sensitivity of 72.7% and specificity of 64.6% for a Lithuanian PSQ cutoff score of 8 to predict moderate-to-severe apnea, and a sensitivity of 85.0% and specificity of 62.0% to predict severe apnea. Using a Lithuanian PSQ cutoff ratio of 0.4, a sensitivity of 72.7% and specificity of 63.3% were found to predict moderate-to-severe apnea, and a sensitivity of 85.0% and specificity of 60.9% were found to predict severe apnea.

Conclusions

The Lithuanian version of the PSQ is a reliable, validated, and culturally adapted screening tool for the prediction of moderate-to-severe sleep apnea in children aged 2–17 years. However, polysomnography should be performed to confirm the diagnosis of sleep apnea and other SDB, and to determine the degree of the disorder and the need for treatment.
Bacteriological diagnosis of osteoarticular infections caused by Kingella kingae; a narrative review
Authors: De Marco Giacomo , Vazquez Oscar , Paris Elio , Cochard Blaise , Steiger Christina , Dayer Romain , Ceroni Dimitri
Published: January 2025

In recent years, advancements in modern laboratory diagnostics have identified Kingella kingae (K. kingae) as the major cause of osteoarticular infections in early childhood. The introduction of novel diagnostic methods has ushered in a new era, transitioning from underrated infections to recognizing K. kingae as the primary etiology of skeletal system infections in children. This article provides a new perspective on K. kingae, exploring innovative diagnostic methods that have improved and will continue to transform the management of these infections.
The applications and mechanisms of Rosmarinus officinalis L. in the management of different wounds and UV-irradiated skin
Authors: Xu Jianwen , Li Ting , Li Fei , Qiang Hong , Wei Xiaoxiao , Zhan Ruiwen , Chen Yun
Published: January 2025

Chronic wounds, especially non-healing wounds, significantly affect patients’ quality of life and raise the costs of therapy. Wound healing is a complicated process involving interdependent stages, which may be impaired and delayed by infections with multi-drug resistant pathogens. Current medical strategies for wound healing, especially the treatment of non-healing wounds, exert limited therapeutic effects, thus become a dramatic challenge for modern medicine. There has been growing interest in exploring complementary approaches to enhance the wound healing process, and complementary therapy using herbs and their related products has gained increasing attention. Apart from skin wounds, dermal pathological changes caused by UV irradiation, may also benefit from such complementary therapy. The antimicrobial, anti-inflammatory, antioxidant, analgesic and collagen-promoting properties of extract from Rosmarinus officinalis L. (rosemary) have all been considered to contribute to the beneficial effects on different stages and multiple aspects of skin recovery after various wounds or UV irradiation. This review aims to summarize the applications and their underlying mechanisms of rosemary as part of the complementary therapy for injured and UV-irradiated skin based on the currently available evidence. The medicinal properties of rosemary and its application in wound dressing are first discussed, followed by summarization of its application in different types of wounds. A conclusion is reached and future directions are discussed. As research in this area continue to evolve, rosemary-derived products may become an integral part of holistic wound care strategies, offering a complementary approach to conventional treatments.
Angiopoietin-like protein 4 dysregulation in kidney diseases: a promising biomarker and therapeutic target
Authors: Li Yan , Zhang Yuxin , Cao Mengxia , Yuan Tingting , Ou Santao
Published: January 2025

The global burden of renal diseases is increasingly severe, underscoring the need for in-depth exploration of the molecular mechanisms underlying renal disease progression and the development of potential novel biomarkers or therapeutic targets. Angiopoietin-like protein 4 (ANGPTL4) is a multifunctional cytokine involved in the regulation of key biological processes, such as glucose and lipid metabolism, inflammation, vascular permeability, and angiogenesis, all of which play crucial roles in the pathogenesis of kidney diseases. Over the past 2 decades, ANGPTL4 has been regarded as playing a pivotal role in the progression of various kidney diseases, prompting significant interest from the scientific community regarding its potential clinical utility in renal disorders. This review synthesizes the available literature, provides a concise overview of the molecular biological effects of ANGPTL4, and highlights its relationship with multiple renal diseases and recent research advancements. These findings underscore the important gaps that warrant further investigation to develop novel targets for the prediction or treatment of various renal diseases.
Global research landscape and emerging trends of non-coding RNAs in prostate cancer: a bibliometric analysis
Authors: Zhou Yu-Liang , Yao Wen-Liang , Chen Sheng-Hui , Wang Peng , Fu Jing-Wen , Zhao Jia-Qin , Zhang Jia-Yi
Published: January 2025

Background

Prostate cancer (PC) is the most frequently diagnosed cancer in men and continues to be a major cause of cancer-related mortality worldwide. In recent years, non-coding RNAs (ncRNAs) have emerged as a significant focus in molecular biology research, playing a pivotal role in the development and progression of PC. This study employed bibliometric analysis to explore the global outputs, research hotspots, and future trends in ncRNA-related PC research over the past 20 years.

Methods

Publications on PC-related ncRNAs from 2004 to 2023 were retrieved from Web of Science Core Collection. The co-operation network of countries, institutions, and authors on this topic was analyzed using CiteSpace (version 6.2. R6). In addition, co-occurrence analysis of keywords and co-citation analysis of references were performed using CiteSpace, and emergent detection was also performed.

Results

A total of 2,951 articles on PC-related ncRNAs were finally included in this study for analysis. China contributed the largest number of publications, while the United States was the most influential country in this field, with collaborative ties to 26 other countries. Fudan University was identified as the most active institution in this field. Rajvir Dahiya was the most prolific and influential author. Within the co-citation network, clusters labeled “EVs,” “circRNA,” and “ceRNA” represented current research directions. The cluster labeled “gene” dominated the co-occurrence keywords. “circRNA” showed the highest burst strength among keywords, with “circRNA,” “EVs” and “exosome” maintaining sustained burst strength, suggesting these are the emerging research frontiers in this field.

Conclusion

Investigating ncRNAs as pivotal research subjects in PC is essential for addressing the public health impact of the disease and advancing innovative diagnostic and targeted therapeutic strategies. This study provides a comprehensive bibliometric analysis of research related to PC-associated ncRNAs, delivering a scientific perspective and identifying potential research directions for scholars in this field.
Research hotspots and frontiers of endoplasmic reticulum in glomerular podocytes: a bibliometric and visual analysis from 2005 to 2023
Authors: Junli Wang , Zhihong Hao , Lina Wang , Qiaoqun Ou , Jing Qu , Jiaqi Hu , Yu Shengyou
Published: January 2025

Background

The glomerular podocyte endoplasmic reticulum is a critical component in renal function, yet its research landscape is not fully understood. This study aims to map the existing research on podocyte endoplasmic reticulum by analyzing publications in the Web of Science Core Collection (WOSCC) from the past 19 years.

Methods

We conducted a bibliometric analysis using Citespace, VOSviewer, the Metrology Literature Online platform, and the Bibliometrix software package to visualize and interpret the data from WOSCC. The analysis focused on publication volume, authorship, institutional contributions, and research trends.

Results

The analysis revealed a significant growth in publications, indicating a surge in interest in podocyte endoplasmic reticulum research. Cybulsky, Andrey V, and Papillon, Joan emerge as the most prolific authors, and the Journal of the American Society of Nephrology is the leading journal in this field. China is the top contributor in terms of publications, with McGill University being the most productive institution. The research primarily focuses on endoplasmic reticulum stress, diabetic nephropathy, and apoptosis, with emerging trends in “foot cell apoptosis,” “cell signaling pathways,” and “autophagy.”

Conclusion

The findings highlight the expanding scope of podocyte endoplasmic reticulum research, with a particular emphasis on the mechanisms of endoplasmic reticulum stress and podocyte apoptosis. Future research directions may include the identification of specific therapeutic targets, detailed exploration of podocyte signaling pathways, and the role of autophagy. This study provides a comprehensive overview of the major research areas, frontiers, and trends in podocyte endoplasmic reticulum research, which are pivotal for guiding future investigations.
Efficiency and safety of HAIC combined with lenvatinib and tislelizumab for advanced hepatocellular carcinoma with high tumor burden: a multicenter propensity score matching analysis
Authors: Zhao Zhonghua , Jiang Xiongying , Wen Shiping , Hao Yanzhang
Published: January 2025

Purpose

The present work focused on assessing whether hepatic arterial infusion chemotherapy (HAIC) combined with lenvatinib and tislelizumab was safe and effective on advanced hepatocellular carcinoma (HCC) showing high tumor burden.

Methods

In the present multicenter retrospective study, treatment-naive advanced HCC patients (BCLC stage C) showing high tumor burden (maximum diameter of intrahepatic lesion beyond 7 cm) treated with lenvatinib and tislelizumab with or without HAIC were reviewed for eligibility from June 2020 to June 2023. Baseline differences between groups were mitigated by propensity score matching (PSM). Our primary endpoint was overall survival (OS); and secondary endpoints included adverse events (AEs), progression-free survival (PFS), disease control rate (DCR) and objective response rate (ORR) according to RECIST 1.1 criteria, respectively.

Results

After eligibility reviewed, total 162 patients treated with lenvatinib and tislelizumab were enrolled: 63 patients with HAIC (HTP group), and the remaining 99 patients without HAIC (TP group). After PSM 1:1, 47 cases were evenly divided into each group. Of them, HTP group showed significant prolonged median OS compared with TP group (16.6 versus 21.0 months; hazard ratio [HR]: 0.26, 95% confidence interval [CI]: 0.35–0.98; p = 0.039), and median PFS of HTP group was also prolonged (8.9 versus 11.6 months; HR: 0.55, 95% CI: 0.34–0.87; p = 0.010). Higher DCR and ORR could be observed in HTP relative to TP groups (ORR: 53.2% versus 17.0%, p < 0.001; DCR: 87.2% versus 61.7%, p = 0.004). The severe AEs (grade 3/4) and all grades were comparable between the groups, while all of these AEs could be controlled, and AEs of grade 5 were not reported.

Conclusion

HAIC combined with lenvatinib and tislelizumab is the candidate treatment for advanced HCC patients because of its improved prognosis and acceptable safety.
Hepatotoxicity of statins: a real-world study based on the US Food and Drug Administration Adverse Event Reporting System database
Authors: Wang Bojing , Huang Shu , Li Shiqi , Deng Yaqi , Li Ziyan , Wang Yizhou , Shi Xiaomin , Zhang Wei , Shi Lei , Wang Xiaohong , Tang Xiaowei
Published: January 2025

Background

Statins, as an important class of lipid-lowering drugs, play a key role in the prevention and treatment of cardiovascular diseases. However, with their widespread use in clinical practice, some adverse events have gradually emerged. In particular, the hepatotoxicity associated with statins use has become one of the clinical concerns that require sufficient attention.

Methods

In this study, we conducted a comprehensive and detailed analysis of the hepatotoxicity of statins based on the data of the US Food and Drug Administration Adverse Event Reporting System database from the first quarter (Q1) of 2004 to the Q1 of 2024 and used Reporting Odds Ratios and Empirical Bayes Geometric Mean to mine the signal of adverse events.

Results

In this study, hepatic disorder related seven statins all exhibited positive signals. Through signal mining, we identified a total of 14,511 cases of adverse events associated with hepatic disorder caused by these statin drugs, with atorvastatin, simvastatin, and rosuvastatin occurring at a higher rate. A total of 148 positive signals related to adverse events of hepatic disorder were captured. Autoimmune hepatitis and drug-induced liver injury both presented positive signals across multiple statin drugs. Notably, atorvastatin had the most significant signal strength in cholestatic pruritus and bilirubin conjugation abnormal. Fluvastatin also showed notable signal strength in autoimmune hepatitis, while simvastatin had a relatively weaker signal strength for hepatic enzyme increased.

Conclusion

This study discovered specific adverse event signal values, revealing potential hepatotoxic risks associated with the use of statin drugs. The results provide an important reference for the safe clinical use of drugs, help to improve the understanding of the safety of statins, and also provide a scientific basis for clinicians to make more accurate and safe decisions when making treatment plans.
A randomized sequential allocation study on the optimum programmed intermittent epidural boluses interval time with different concentrations of ropivacaine combined with the dural puncture epidural technique for labor analgesia
Authors: Mao Jingjing , Chen Yi , Sun Linsen , Xu Xiaoxiao , Xu Kai , Ren Tingting , Xiong Xiangsheng , Zhao Weibing
Published: January 2025

Background

The combined technique of programmed intermittent epidural boluses (PIEB) and dural puncture epidural (DPE) is currently considered a more effective mode for labor analgesia. We investigated the optimal interval time for PIEB administration with different concentrations of ropivacaine combined with the DPE for labor analgesia.

Methods

Ninety patients with cervical dilation of <5 cm and a VAS score >5 were randomly assigned to receive labor analgesia with ropivacaine at concentrations of 0.075% (0.075% group), 0.1% (0.1% group), and 0.125% (0.125% group). In each group, an initial administration of a combination of ropivacaine 12 mL and sufentanil 0.3 μg/mL was followed by an additional dose of ropivacaine 10 mL and sufentanil 0.3 μg/mL after 30 min. The initial PIEB interval time was set at 40 min for the first patient in each group, and subsequent interval times for the following patients were adjusted based on meeting analgesic needs (VAS score ≤1) with a gradient of 10 min. The primary outcome was the ED90 of interval time required to achieve analgesic needs during PIEB with different concentrations of ropivacaine, employing an up-and-down sequential allocation method.

Results

The optimal PIEB interval times for ropivacaine concentrations of 0.075%, 0.1%, and 0.125% were determined to be 40.9 (95% CI, 35.3–45.8), 45.3 (95% CI, 39.3–51.5), and 52.9 (95% CI, 46.8–59.3) minutes respectively, while comparable maternal and neonatal outcomes were observed across all groups.

Conclusion

When PIEB is combined with DPE for labor analgesia, the optimal PIEB interval times for ropivacaine concentrations of 0.075%, 0.1%, and 0.125% were determined to be 41, 45, and 53 min respectively.
Cost-effectiveness of tyrosine kinase inhibitor treatment strategies for chronic myeloid leukemia in South Africa
Authors: Woudberg Rochelle , Sinanovic Edina
Published: January 2025

Background

The treatment of chronic myeloid leukemia through tyrosine kinase inhibitors (TKIs) has achieved promising efficacy and safety outcomes, however the costs are associated with a substantial economic burden. The objective of this study was to develop a Markov model with a 20-year time horizon to assess the cost effectiveness of TKIs from a public healthcare system perspective in South Africa.

Methods

We constructed a Markov model to compare three strategies in which treatment was initiated with either imatinib, nilotinib, or dasatinib. Treatment was switched to another TKI in the case of intolerance or resistance to the initial TKI. Effectiveness and utility data were obtained from published literature. Cost data was obtained from local sources for generic imatinib and branded second-generation TKIs and based on national tariffs. Outcomes were reported in total costs and quality-adjusted life years (QALYs). Outcomes were based on calculated incremental cost effectiveness ratios (ICERs) and compared to a willingness-to-pay (WTP) threshold. Sensitivity analyses were conducted to determine the robustness of the model outcomes.

Results

The base-case results showed that imatinib was favored over nilotinib and dasatinib by having the lowest cost at $120 719.55 and providing 5.93 QALYs. Compared to imatinib strategy, nilotinib had an ICER of $26 620.27 per QALY and dasatinib had an ICER of $35 934.94 per QALY, both exceeding the WTP threshold of $18 760 per QALY gained. The sensitivity analysis indicated the robustness of the results.

Conclusion

Imatinib remains the most cost-effective first-line treatment for adults diagnosed with CML in South Africa, with a high probability of being cost-effective across a range of WTP thresholds. Nilotinib and Dasatinib, though offering clinical benefits, their affordability remains a challenge within the current healthcare system and should remain reserved for second-line treatment.
Unlocking the therapeutic mechanism of Caesalpinia sappan: a comprehensive review of its antioxidant and anti-cancer properties, ethnopharmacology, and phytochemistry
Authors: Asevedo Estéfani Alves , Ramos Santiago Livia , Kim Hyo Jeong , Syahputra Rony Abdi , Park Moon Nyeo , Ribeiro Rosy Iara Maciel Azambuja , Kim Bonglee
Published: January 2025

Herbal medicine are an invaluable reservoir of bioactive compounds, offering immense potential for novel drug development to address a wide range of diseases. Among these, Caesalpinia sappan has gained recognition for its historical medicinal applications and substantial therapeutic potential. This review explores the ethnopharmacological significance, phytochemical composition, and pharmacological properties of C. sappan, with a particular focus on its anticancer activities. Traditionally, C. sappan has been utilized for treating respiratory, gastrointestinal, and inflammatory conditions, demonstrating its broad therapeutic scope. The plant’s rich array of bioactive compounds—flavonoids, triterpenoids, phenolic acids, and glycosides—forms the basis of its potent antioxidant, anti-inflammatory, and pharmacological effects. Modern pharmacological research has further substantiated its versatility, revealing anticancer, anti-diabetic, anti-infective, and hepatoprotective properties. However, significant challenges remain, including the need to unravel the precise molecular mechanisms underlying its anticancer effects, refine extraction and isolation methods for bioactive compounds, and validate its safety and efficacy through well-designed clinical trials. Particularly noteworthy is C. sappan’s potential in combination therapies, where it may synergistically target multiple cancer pathways, enhance therapeutic outcomes, and mitigate adverse effects. This review synthesizes the findings from the past decade, providing a comprehensive evaluation of C. sappan’s pharmacological promise while identifying critical areas for future research. By addressing these gaps, C. sappan could serve as a cornerstone for innovative therapeutic strategies, offering hope for improved management of cancer and other complex diseases.
Mechanistic insight of curcumin: a potential pharmacological candidate for epilepsy
Authors: Khatoon Saima , Kalam Nida
Published: January 2025

Recurrent spontaneous seizures with an extended epileptic discharge are the hallmarks of epilepsy. At present, there are several available anti-epileptic drugs (AEDs) in the market. Still no adequate treatment for epilepsy treatment is available. The main disadvantages of AEDs are their associated adverse effects. It is a challenge to develop new therapies that can reduce seizures by modulating the underlying mechanisms with no adverse effects. In the last decade, the neuromodulatory potential of phytoconstituents has sparked their usage in the treatment of central nervous system disorders. Curcumin is an active polyphenolic component that interacts at cellular and molecular levels. Curcumin’s neuroprotective properties have been discovered in recent preclinical and clinical studies due to its immunomodulatory effects. Curcumin has the propensity to modulate signaling pathways involved in cell survival and manage oxidative stress, apoptosis, and inflammatory mechanisms. Further, curcumin can persuade epigenetic alterations, including histone modifications (acetylation/deacetylation), which are the changes responsible for the altered expression of genes facilitating the process of epileptogenesis. The bioavailability of curcumin in the brain is a concern that needs to be tackled. Therefore, nanonization has emerged as a novel drug delivery system to enhance the pharmacokinetics of curcumin. In the present review, we reviewed curcumin’s modulatory effects on potential biomarkers involved in epileptogenesis including dendritic cells, T cell subsets, cytokines, chemokines, apoptosis mediators, antioxidant mechanisms, and cognition impairment. Also, we have discussed the nanocarrier systems for encapsulating curcumin, offering a promising approach to enhance bioavailability of curcumin.
The effect of instability resistance training on balance ability among athletes: a systematic review
Authors: Gao Jianxin , Fu Xinxin , Xu Hang , Guo Qi , Wang Xiaopeng
Published: January 2025

Background

Instability resistance training (IRT) has been the focus of extensive research because of its proven benefits to balance ability, core stability, and sports performance for athletes. However, there is a lack of systematic reviews explicitly evaluating IRT’s impact on athletes’ balance ability. This study aims to conduct a systematic review of the effects of IRT on balance ability among athletes.

Method

This study used guidelines for the systematic review and meta-analysis of PRISMA, Web of Science, EBSCOhost (SPORTDiscus), PubMed, Scopus, and Google Scholar to collect original references in electronic databases. The PICOS method was selected for the inclusion criteria. The physiotherapy evidence database (PEDro) scale was used to assess the scoring for articles’ risk range of bias. The scoring of 20 studies ranges from 4–8, and study quality is moderate to high.

Results

Out of 285 identified studies, only 20 articles fulfilled all the eligibility criteria after screening. IRT could significantly improve reciprocal, static, and dynamic balance ability among judo athletes, basketball players, weightlifters, archery athletes, soccer players, rhythmic gymnasts, badminton players, track and field athletes, handball players, volleyball players, and gymnasts using unstable surfaces or environments (i.e., BOSU, Swiss, Wobble boards, Suspension trainer, Sissel pillows, Inflated disc and foam surface, Airex balance pad, Togu power ball, Thera-Band, Elastic band strap, Sand surface and so on).

Conclusion

The finding suggests that different types of IRT benefit athletes as this training method can effectively enhance reciprocal, static, and dynamic balance ability in athletes. Therefore, this review suggests that IRT should be considered in athletes’ daily training routines for the physical fitness of reciprocal, static, and dynamic balance ability.
A combined diagnostic model including middle rectal artery visualization for predicting lateral lymph node metastasis in rectal cancer
Authors: Wang Ning , Li Yiping , Lu Kun , Wei Kaikai , Jia Shize , Fan Shuhong , Ren Donglin , Fu Yuanji , Liu Zhimin
Published: January 2025

Purpose

This study attempted to establish a combined diagnostic model encompassing visualization of the middle rectal artery (MRA) and other imaging features to improve the diagnostic efficiency of lateral lymph node (LLN) metastasis, which is crucial for clinical decision-making in rectal cancer.

Method

One hundred eleven patients receiving bilateral or unilateral lymph node dissection were enrolled, and 140 cases of LLN status on a certain unilateral pelvic sidewall were selected. Enhanced computed tomography (CT) was used to determine whether MRA was visible. Multivariable regression was used to establish a diagnostic model combining MRA visualization with other imaging features to predict LLN metastasis. Receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) were used to test the diagnostic efficacy for LLN metastasis. Ten-fold cross-validation was completed to internally validate the diagnostic model.

Results

Of the 140 LLNs harvested from 111 patients, 76 were positive and 64 were negative for metastases, respectively. The diagnostic model combining the MRA visualization and lymph node short diameter showed a greater efficiency than a single scale (AUC = 0.945, 95% confidence interval = 0.893–0.976, P < 0.001). The mean cross-validated AUC was 0.869 (95% confidence interval = 0.835–0.903).

Conclusion

Our results establish a combined diagnostic model with the help of MRA visualization to yield a high diagnostic efficiency of LLN metastasis in rectal cancer.
Phosphate rebinding induces force reversal via slow backward cycling of cross-bridges
Authors: Stehle Robert
Published: January 2025

Objective

Previous studies on muscle fibers, myofibrils, and myosin revealed that the release of inorganic phosphate (Pi) and the force-generating step(s) are reversible, with cross-bridges also cycling backward through these steps by reversing force-generating steps and rebinding Pi. The aim was to explore the significance of force redevelopment kinetics (rate constant kTR) in cardiac myofibrils for the coupling between the Pi binding induced force reversal and the rate-limiting transition f– for backward cycling of cross-bridges from force-generating to non-force-generating states.

Methods

kTR and force generation of cardiac myofibrils from guinea pigs were investigated at 0.015–20 mM Pi. The observed force-[Pi], force-log [Pi], kTR-[Pi], and kTR-force relations were assessed with various single-pathway models of the cross-bridge cycle that differed in sequence and kinetics of reversible Pi release, reversible force-generating step and reversible rate-limiting transition. Based on the interpretation that kTR reflects the sum of rate-limiting transitions in the cross-bridge cycle, an indicator, the coupling strength, was defined to quantify the contribution of Pi binding induced force reversal to the rate-limiting transition f– from the [Pi]-modulated kTR-force relation.

Results

Increasing [Pi] decreased force by a bi-linear force-log [Pi] relation, increased kTR in a slightly downward curved dependence with [Pi], and altered kTR almost reciprocally to force reflected by the kTR-force relation. Force-[Pi] and force-log [Pi] relations provided less selectivity for the exclusion of models than the kTR-[Pi] and kTR-force relations. The kTR-force relation observed in experiments with cardiac myofibrils yielded the coupling strength +0.84 ± 0.08 close to 1, the maximum coupling strength expected for the reciprocal kTR–force relationship. Single pathway models consisting of fast reversible force generation before or after rapid reversible Pi release failed to describe the observed kTR–force relation. Single pathway models consistent with the observed kTR-force relation had either slow Pi binding or slow force reversal, i.e., in the consistent single pathway models, f– was assigned to the rate of either Pi binding or force reversal.

Conclusion

Backward flux of cross-bridges from force-generating to non-force-generating states is limited by the rates of Pi binding or force reversal ruling out other rate-limiting steps uncoupled from Pi binding induced force reversal.
Different effects of mechano- and metaboreflex on the central blood pressure waveform
Authors: Nakamura Nobuhiro , Heng Peng , Hayashi Naoyuki
Published: January 2025

Introduction

The effect of mechanoreflex on central blood pressure (BP) is unclear, although the influence of metaboreflex has been investigated. A relatively small contribution of the mechanoreflex to the pressor response to exercise has been considered in humans because many studies have failed to isolate the mechanoreflex-mediated pressor response. In a recent study, we successfully isolated a mechanoreflex-mediated pressor response using static passive stretching (SPS) in the forearm. Thus, it is possible to isolate the effect of the mechanoreflex on the central BP using this recently developed method. We investigated the effect of muscle mechanoreflex on central BP and compared the changes in the shape of the central BP waveform during mechanoreflex and metaboreflex.

Methods

We measured 12 healthy males (age, 26 ± 2 years; height, 171.1 ± 5.2 cm; body mass, 63.3 ± 10.3 kg; body fat, 16.7% ± 3.9%; means ± standard deviation [SD]) in this study. All participants performed static passive stretching (SPS) of the forearm for 60 s to isolate the muscle mechanoreflex. They also performed 120 s of isometric handgrip (IHG) at 30% maximal voluntary contraction and underwent 180 s of post-exercise ischemia (PEI) to isolate the muscle metaboreflex. The carotid BP (cBP) waveform was obtained from the right common carotid artery as the central BP waveform. We evaluated the first systolic peak (P1) and second systolic peak (P2) from the cBP waveform.

Results

SPS increased cBP with an increase in P1 (p < 0.05), whereas PEI increased cBP with an increase in P2 (p < 0.05). SPS did not alter augmentation pressure (AP) (p > 0.05), whereas PEI increased it (p < 0.05). The relative change from rest (Δ) in P1 during SPS was positively correlated with that in stroke volume (r = 0.68; p < 0.05), and the ΔAP during PEI was positively correlated with that in total peripheral resistance TPR (r = 0.61; p < 0.05).

Conclusion

These results suggest different effects of mechano- and metaboreflex on the change in shape of the central BP waveform; mechanoreflex and metaboreflex deform P1 and P2, respectively.