bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioinformatics study of the potential therapeutic effects of ginsenoside Rh3 in reversing insulin resistance
Authors: Wang Yayun , Wu Dongming , Wang Yongxin , Sun Jingwen , Wang Xiaona , Huang Yanqin , Sun Mingliang 
Published: May 2024

BackgroundIn recent years, the incidence of insulin resistance is increasing, and it can cause a variety of Metabolic syndrome. Ginsenosides have been clinically proven to improve fat metabolism and reduce insulin resistance, but their components and mechanism of action are still unclear.ObjectiveGinsenoside, a bioactive compound derived from ginseng, exhibits significant potential in treating obesity, diabetes, and metabolic disorders. Despite evidence supporting its efficacy in ameliorating insulin resistance (IR) in obesity, the specific bioactive components and underlying mechanisms remain obscure. In this study, we endeavored to elucidate the potential molecular targets and pathways influenced by ginsenoside Rh3 (GRh3) to ameliorate IR in liver tissue. We employed a comprehensive approach that integrates system pharmacology and bioinformatics analysis.Materials and methodsOur methodology involved the identification of candidate targets for GRh3 and the profiling of differentially expressed genes (DEGs) related to IR in individuals with insulin resistance. The coalescence of candidate targets and DEGs facilitated the construction of a “GRh3-targets-disease” network for each tissue type, ultimately yielding 38 shared target genes. Subsequently, we conducted pathway enrichment analysis, established protein-protein interaction (PPI) networks, and identified hub targets among the GRh3 targets and IR-related DEGs. Additionally, we conducted animal experiments to corroborate the role of these hub targets in the context of GRh3.ResultsOur investigation identified a total of 38 overlapping targets as potential candidates. Notably, our analysis revealed crucial hub targets such as EGFR, SRC, ESR1, MAPK1, and CASP3, alongside implicated signaling pathways, including those related to insulin resistance, the FoxO signaling pathway, the PPAR signaling pathway, and the IL-17 signaling pathway. This study establishes a robust foundation for the mechanisms underlying GRh3’s efficacy in mitigating IR. Furthermore, these results suggest that GRh3 may serve as a representative compound within the ginsenoside family.ConclusionThis study elucidates the potential molecular targets and associated pathways through which GRh3 ameliorates IR, showcasing its multifaceted nature, spanning multiple targets, pathways, and mechanisms. These findings establish a robust foundation for subsequent experimental inquiries and clinical applications.
Global trends and hotspots in pain associated with bipolar disorder in the last 20 years: a bibliometric analysis
Authors: Zhao Hong Qing , Zhou Mi , Jiang Jia Qi , Luo Zhi Qiang , Wang Yu Hong 
Published: May 2024

PurposeThe prevalence of comorbid pain and Bipolar Disorder in clinical practice continues to be high, with an increasing number of related publications. However, no study has used bibliometric methods to analyze the research progress and knowledge structure in this field. Our research is dedicated to systematically exploring the global trends and focal points in scientific research on pain comorbidity with bipolar disorder from 2003 to 2023, with the goal of contributing to the field.MethodsRelevant publications in this field were retrieved from the Web of Science core collection database (WOSSCC). And we used VOSviewer, CiteSpace, and the R package “Bibliometrix” for bibliometric analysis.ResultsA total of 485 publications (including 360 articles and 125 reviews) from 66 countries, 1019 institutions, were included in this study. Univ Toront and Kings Coll London are the leading research institutions in this field. J Affect Disorders contributed the largest number of articles, and is the most co-cited journal. Of the 2,537 scholars who participated in the study, Stubbs B, Vancampfort D, and Abdin E had the largest number of articles. Stubbs B is the most co-cited author. “chronic pain,” “neuropathic pain,” “psychological pain” are the keywords in the research.ConclusionThis is the first bibliometric analysis of pain-related bipolar disorder. There is growing interest in the area of pain and comorbid bipolar disorder. Focusing on different types of pain in bipolar disorder and emphasizing pain management in bipolar disorder are research hotspots and future trends. The study of pain related bipolar disorder still has significant potential for development, and we look forward to more high-quality research in the future.
Neurologic music therapy for non-fluent aphasia: a systematic review and meta-analysis of randomized controlled trials
Authors: Gu Jiayi , Long Wei , Zeng Siqin , Li Chengjuan , Fang Cuini , Zhang Xiaoying 
Published: May 2024

IntroductionThe efficacy of neurologic music therapy (NMT) techniques for the treatment of non-fluent aphasia has been widely accepted by the rehabilitation medical community. However, consensus on which dimensions of speech function can be improved by NMT techniques and standardized intervention dosage remains elusive. This study aimed to provide evidence regarding the efficacy of NMT in improving speech function and explore the optimal intervention dose. A systematic review and meta-analysis were conducted to search for randomized clinical trials and open-label trials that evaluated speech functions after NMT.MethodsWe searched all papers and reviews published from database inception to July 2023, including PubMed, Cochrane Library, Web of Science, Embase, and CNKI. Statistical analyses were mainly carried out on RevManV5.4.1 and pooled using a random-effects model. The primary outcome was the standardized mean difference (SMD) in speech functions, determined by calculating the change in speech functions score from baseline to the primary endpoint in the NMT group versus the control arm.ResultsA total of 11 studies with 329 patients were included. NMT had a positive effect on repetition ability (SMD = 0.37, 95%CI [0.12, 0.62], p  &lt; 0.05), but did not lead to significant differences in naming, comprehension, spontaneous speech, or communication. When the intervention time was &gt;20 h, NMT exhibited a significant advantage at improving repetition ability (SMD = 0.43, 95%CI [0.06, 0.79], p  &lt; 0.05).DiscussionThis study provides evidence supporting the NMT enhancement of repetition ability in patients with non-fluent aphasia. Future large-sample studies are required to determine the optimal intervention dose of music therapy for different subtypes of non-fluent aphasia.Systematic review registrationPROSPERO, identifier CRD42023470313.
State- and frequency-dependence in autonomic rebalance mediated by intradermal auricular electroacupuncture stimulation
Authors: Yang Sen , Wu Yu-Rui , Zhan Zheng , Pan Yan-Hong , Jiang Jin-Feng 
Published: May 2024

BackgroundVagus nerve stimulation (VNS) improves diseases such as refractory epilepsy and treatment-resistant depression, likely by rebalancing the autonomic nervous system (ANS). Intradermal auricular electro-acupuncture stimulation (iaES) produces similar effects. The aim of this study was to determine the effects of different iaES frequencies on the parasympathetic and sympathetic divisions in different states of ANS imbalance.MethodsWe measured heart rate variability (HRV) and heart rate (HR) of non-modeled (normal) rats with the treatment of various frequencies to determine the optimal iaES frequency. The optimized iaES frequency was then applied to ANS imbalance model rats to elucidate its effects.Results30 Hz and 100 Hz iaES clearly affected HRV and HR in normal rats. 30 Hz iaES increased HRV, and decreased HR. 100 Hz iaES decreased HRV, and increased HR. In sympathetic excited state rats, 30 Hz iaES increased HRV. 100 Hz iaES increased HRV, and decreased HR. In parasympathetic excited state rats, 30 Hz and 100 Hz iaES decreased HRV. In sympathetic inhibited state rats, 30 Hz iaES decreased HRV, while 100 Hz iaES decreased HR. In parasympathetic inhibited rats, 30 Hz iaES decreased HR and 100 Hz iaES increased HRV.Conclusion30 Hz and 100 Hz iaES contribute to ANS rebalance by increasing vagal and sympathetic activity with different amplifications. The 30 Hz iaES exhibited positive effects in all the imbalanced states. 100 Hz iaES suppressed the sympathetic arm in sympathetic excitation and sympathetic/parasympathetic inhibition and suppressed the vagal arm and promoted the sympathetic arm in parasympathetic excitation and normal states.
Atrophy patterns in hippocampal subregions and their relationship with cognitive function in fibromyalgia patients with mild cognitive impairment
Authors: Long Yingming , Xie Xinyan , Wang Yingwei , Xu Jinping , Gao Ziyi , Fang Xiaokun , Xu Tong , Zhang Nan , Lv Dongling , Wu Ting 
Published: May 2024

ObjectivesFibromyalgia (FM) has been associated with decreased hippocampal volume; however, the atrophy patterns of hippocampal subregions have not yet been identified. We therefore aimed to evaluate the volumes of hippocampal subregions in FM patients with mild cognitive impairment (MCI), and to explore the relationship between different subregional alterations and cognitive function.MethodsThe study included 35 FM patients (21 with MCI and 14 without MCI) and 35 healthy subjects. All subjects performed the Montreal Cognitive Assessment (MoCA) to assess cognitive function. FreeSurfer V.7.3.2 was used to calculate hippocampal subregion volumes. We then compared hippocampal subregion volumes between the groups, and analyzed the relationship between hippocampal subregion volume and cognitive function using a partial correlation analysis method.ResultsCompared with the healthy subjects, FM patients with MCI had smaller hippocampal volumes in the left and right CA1 head, Molecular layer head, GC-DG head, and CA4 head, and in the left Presubiculum head. Poorer executive function, naming ability, and attention were associated with left CA1 head and left Molecular layer head atrophy. By contrast, hippocampal subregion volumes in the FM patients without MCI were slightly larger than or similar to those in the healthy subjects, and were not significantly correlated with cognitive function.ConclusionSmaller volumes of left CA1 head and left Molecular layer head were associated with poorer executive function, naming ability, and attention in FM patients with MCI. However, these results were not observed in the FM patients without MCI. These findings suggest that the hippocampal subregions of FM patients might present compensatory mechanisms before cognitive decline occurs.
Construction and validation of an endoscopic ultrasonography-based ultrasomics nomogram for differentiating pancreatic neuroendocrine tumors from pancreatic cancer
Authors: Mo Shuangyang , Huang Cheng , Wang Yingwei , Zhao Huaying , Wei Haixiao , Qin Haiyan , Jiang Haixing , Qin Shanyu 
Published: May 2024

ObjectivesTo develop and validate various ultrasomics models based on endoscopic ultrasonography (EUS) for retrospective differentiating pancreatic neuroendocrine tumors (PNET) from pancreatic cancer.MethodsA total of 231 patients, comprising 127 with pancreatic cancer and 104 with PNET, were retrospectively enrolled. These patients were randomly divided into either a training or test cohort at a ratio of 7:3. Ultrasomics features were extracted from conventional EUS images, focusing on delineating the region of interest (ROI) for pancreatic lesions. Subsequently, dimensionality reduction of the ultrasomics features was performed by applying the Mann-Whitney test and least absolute shrinkage and selection operator (LASSO) algorithm. Eight machine learning algorithms, namely logistic regression (LR), light gradient boosting machine (LightGBM), multilayer perceptron (MLP), random forest (RF), extra trees, k nearest neighbors (KNN), support vector machine (SVM), and extreme gradient boosting (XGBoost), were employed to train prediction models using nonzero coefficient features. The optimal ultrasomics model was determined using a ROC curve and utilized for subsequent analysis. Clinical-ultrasonic features were assessed using both univariate and multivariate logistic regression. An ultrasomics nomogram model, integrating both ultrasomics and clinical-ultrasonic features, was developed.ResultsA total of 107 EUS-based ultrasomics features were extracted, and 6 features with nonzero coefficients were ultimately retained. Among the eight ultrasomics models based on machine learning algorithms, the RF model exhibited superior performance with an AUC= 0.999 (95% CI 0.9977 - 1.0000) in the training cohort and an AUC= 0.649 (95% CI 0.5215 - 0.7760) in the test cohort. A clinical-ultrasonic model was established and evaluated, yielding an AUC of 0.999 (95% CI 0.9961 - 1.0000) in the training cohort and 0.847 (95% CI 0.7543 - 0.9391) in the test cohort. Subsequently, the ultrasomics nomogram demonstrated a significant improvement in prediction accuracy in the test cohort, as evidenced by an AUC of 0.884 (95% CI 0.8047 - 0.9635) and confirmed by the Delong test. The calibration curve and decision curve analysis (DCA) depicted this ultrasomics nomogram demonstrated superior accuracy. They also yielded the highest net benefit for clinical decision-making compared to alternative models.ConclusionsA novel ultrasomics nomogram was proposed and validated, that integrated clinical-ultrasonic and ultrasomics features obtained through EUS, aiming to accurately and efficiently identify pancreatic cancer and PNET.
Blood cell indices and inflammation-related markers with kidney cancer risk: a large-population prospective analysis in UK Biobank
Authors: He Qingliu , Wei Chengcheng , Cao Li , Zhang Pu , Zhuang Wei , Cai Fangzhen 
Published: May 2024

BackgroundKidney cancer is a prevalent malignancy with an increasing incidence worldwide. Blood cell indices and inflammation-related markers have shown huge potential as biomarkers for predicting cancer incidences, but that is not clear in kidney cancer. Our study aims to investigate the correlations of blood cell indices and inflammation-related markers with kidney cancer risk.MethodsWe performed a population-based cohort prospective analysis using data from the UK Biobank. A total of 466,994 participants, free of kidney cancer at baseline, were included in the analysis. The hazard ratios (HRs) and 95% confidence intervals (CIs) for kidney cancer risk were calculated using Cox proportional hazards regression models. Restricted cubic spline models were used to investigate nonlinear longitudinal associations. Stratified analyses were used to identify high-risk populations. The results were validated through sensitivity analyses.ResultsDuring a mean follow-up of 12.4 years, 1,710 of 466,994 participants developed kidney cancer. The Cox regression models showed that 13 blood cell indices and four inflammation-related markers were associated with kidney cancer incidence. The restricted cubic spline models showed non-linear relationships with kidney cancer. Finally, combined with stratified and sensitivity analyses, we found that the mean corpuscular hemoglobin concentration (MCHC), red blood cell distribution width (RDW), platelet distribution width (PDW), systemic immune-inflammation index (SII), and product of platelet count and neutrophil count (PPN) were related to enhanced kidney cancer risk with stable results.ConclusionOur findings identified that three blood cell indices (MCHC, RDW, and PDW) and two inflammation-related markers (SII and PPN) were independent risk factors for the incidence of kidney cancer. These indexes may serve as potential predictors for kidney cancer and aid in the development of targeted screening strategies for at-risk individuals.
Current landscape of primary small bowel leiomyosarcoma: cases report and a decade of insights
Authors: Zhou Junjie , Xu Houyun , Hu Jibo , Hong Qiang , Yu Xiping , Liu Wei , Zhao Jiaxin , Hu Hongjie 
Published: May 2024

The incidence of leiomyosarcoma (LMS) is about 4–5/100,000 individuals per year. LMSs occurring in the small bowel are even rarer, and their preoperative diagnosis is very difficult. We described two patients with pathologically confirmed small bowel LMS and analyzed their clinical and medical imaging features. Similar cases reported in English in Pubmed database over the past decade were reviewed and summarized. These tumors were categorized by the growth direction and relationship with the intestinal lumen into three types: intraluminal (n = 10), intermural (n = 3), and extraluminal (n = 7). Notably, among the three types of LMS, the intramural leiomyosarcoma stands out as a noteworthy subtype. Emerging evidence suggests that smaller tumor size (&lt; 5 cm) and the intraluminal type may serve as favorable prognostic indicators, while the extraluminal type is associated with relatively poor prognosis. Furthermore, the integration of imaging features with CA125 and LDH biomarkers holds promise for potential diagnostic value in LMS.
Causal relationship between iron deficiency anemia and asthma: a Mendelian randomization study
Authors: Li Mengchun , Chen Zhengdong , Yang Xin , Li Wanwei 
Published: May 2024

BackgroundObservational studies have suggested an association between iron deficiency anemia (IDA) and asthma, which may affect the occurrence of asthma. However, whether IDA is a new management goal for asthma remains to be determined.ObjectiveWe conducted a two-sample Mendelian randomization(MR)analysis to assess the association between IDA and asthma.MethodsWe performed a two-sample MR study to assess a causal relationship between IDA (ncase = 12,434, ncontrol = 59,827) and asthma (ncase = 20,629, ncontrol = 135,449). Inverse variance weighted (IVW) was used as the primary method for the analyses. Furthermore, we used weighted medians and MR-Egger to enhance robustness. Data linking genetic variation to IDA and asthma were combined to assess the impact of IDA on asthma risk.ResultsThere are five single nucleotide polymorphisms (SNPs) were used as genetic tool variables for exposure factors. Genetically determined IDA was significantly associated with an increased risk of asthma (OR = 1.37, 95% CI: 1.09–1.72, p = 0.007). There was little heterogeneity in the MR studies and no evidence of level pleiotropy was found.ConclusionsIn our MR study, our findings emphasize that IDA may be associated with a high risk of asthma, indicating a potential role for IDA in the development of asthma. Future research needs to elucidate its potential mechanisms to pave the way for the prevention and treatment of asthma.
Pharmacokinetic assessment of tacrolimus in combination with deoxyschizandrin in rats
Authors: Sun Jianguo , Wang Zhipeng , Liu Na , Liu Zhijun , Cui Lili , Tao Xia , Chen Wansheng , Gao Shouhong , Wu Zhijun 
Published: May 2024

BackgroundTacrolimus (Tac) is commonly used for postoperative immunosuppressive therapy in transplant patients. However, problems, for example, low bioavailability and unstable plasma concentration, persist for a long time, Studies have reported that the deoxyschizandrin could effectively improve these problems, but the pharmacokinetic parameters (PKs) of Tac combined with deoxyschizandrin are still unknown.MethodIn this study, an UHPLC-MS/MS method has been established for simultaneous quantitation of Tac and deoxyschizandrin. The PKs of Tac influenced by different doses of deoxyschizandrin after single and multiple administrations were analyzed, and the different impact of deoxyschizandrin and Wuzhi capsule on PKs of Tac were compared.ResultThe modified UHPLC-MS/MS method could rapid quantification of Tac and deoxyschizandrin within 2 min using bifendatatum as the internal standard (IS). All items were successfully validated. The Cmax of deoxyschizandrin increased from 148.27 ± 23.20 to 229.13 ± 54.77 ng/mL in rats after multiple administrations for 12 days. After co-administration of 150 mg/mL deoxyschizandrin, Tac had an earlier Tmax and greater Cmax and AUC0–t, and the Cmax and AUC0–t of Tac increased from 14.26 ± 4.73 to 54.48 ± 14.37 ng/mL and from 95.10 ± 32.61 to 315.23 ± 92.22 h/ng/mL, respectively; this relationship was positively proportional to the dosage of deoxyschizandrin. In addition, compared with Wuzhi capsule, the same dose of deoxyschizandrin has a better effective on Tac along with more stable overall PKs.ConclusionAn UHPLC-MS/MS method was established and validated for simultaneous detection of deoxyschizandrin and Tac. Deoxyschizandrin could improve the in vivo exposure level and stability of Tac, besides, this effect is better than Wuzhi capsule in same dose.
Ephedra sinica polysaccharide regulate the anti-inflammatory immunity of intestinal microecology and bacterial metabolites in rheumatoid arthritis
Authors: Ma Yanmiao , Wei Xiuhong , Peng Jiehao , Wei Fuxia , Wen Ya , Liu Mingran , Song Bo , Wang Yonghui , Zhang Yumin , Peng Tao 
Published: May 2024

IntroductionEphedra sinica polysaccharide (ESP) exerts substantial therapeutic effects on rheumatoid arthritis (RA). However, the mechanism through which ESP intervenes in RA remains unclear. A close correlation has been observed between enzymes and derivatives in the gut microbiota and the inflammatory immune response in RA.MethodsA type II collagen-induced arthritis (CIA) mice model was treated with Ephedra sinica polysaccharide. The therapeutic effect of ESP on collagen-induced arthritis mice was evaluated. The anti-inflammatory and cartilage-protective effects of ESP were also evaluated. Additionally, metagenomic sequencing was performed to identify changes in carbohydrate-active enzymes and resistance genes in the gut microbiota of the ESP-treated CIA mice. Liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry were performed to observe the levels of serum metabolites and short-chain fatty acids in the gut. Spearman’s correlational analysis revealed a correlation among the gut microbiota, antibiotic-resistance genes, and microbiota-derived metabolites.ResultsESP treatment significantly reduced inflammation levels and cartilage damage in the CIA mice. It also decreased the levels of pro-inflammatory cytokines interleukin (IL)-6, and IL-1-β and protected the intestinal mucosal epithelial barrier, inhibiting inflammatory cell infiltration and mucosal damage. Here, ESP reduced the TLR4, MyD88, and TRAF6 levels in the synovium, inhibited the p65 expression and pp65 phosphorylation in the NF-κB signaling pathway, and blocked histone deacetylase (HDAC1 and HDAC2) signals. ESP influenced the gut microbiota structure, microbial carbohydrate-active enzymes, and microbial resistance related to resistance genes. ESP increased the serum levels of L-tyrosine, sn-glycero-3-phosphocholine, octadecanoic acid, N-oleoyl taurine, and decreased N-palmitoyl taurine in the CIA mice.ConclusionESP exhibited an inhibitory effect on RA. Its action mechanism may be related to the ability of ESP to effectively reduce pro-inflammatory cytokines levels, protect the intestinal barrier, and regulate the interaction between mucosal immune systems and abnormal local microbiota. Accordingly, immune homeostasis was maintained and the inhibition of fibroblast-like synoviocyte (FLS) proliferation through the HDAC/TLR4/NF-κB pathway was mediated, thereby contributing to its anti-inflammatory and immune-modulating effects.