bluuebunny/crossref_metadata_2025_split huggingface dataset:
Research on the mechanism of core acupoints in electroacupuncture for functional constipation based on data mining and network acupuncture
Authors: Ong Shun Seng , Tang Ting , Xu Lianjie , Xu Canwei , Li Qi , Deng Xiaoyue , Shen Peihua , Chen Yi , Song Yang , Lu Hai , Fang Ling 
Published: December 2024

AimFunctional Constipation (FC) is a common gastrointestinal disorder that imposes a considerable strain on global health. It negatively impacts the quality of life and results in significant healthcare expenditures. Current treatments, such as lifestyle changes and medications, fail to meet patient satisfaction due to efficacy and safety issues. Electroacupuncture (EA), with its precise stimulation control and standardized protocols, shows promise in FC management. However, optimal EA parameters for FC treatment are yet to be established. Our study reviews EA applications in FC to inform a standardized treatment approach and explore EA’s therapeutic mechanisms.MethodsThis comprehensive study utilized research literature from databases including PubMed, Embase, OVID, Web of Science, the Cochrane Library, CNKI, VIP, and Wanfang to perform a descriptive analysis of acupoint selection and EA parameters. It proceeded to analyze high-frequency acupoint groupings and stimulus parameters, followed by the excavation and analysis of core acupoint prescriptions. Subsequent steps integrated potential target identification for these core formulas, the assembly of a “core acupoint-prescription-target-constipation” network, and the construction of a protein–protein interaction (PPI) network to extract central targets. Additionally, Gene Ontology (GO) and KEGG enrichment analyses were conducted to prognosticate the underlying mechanisms by which EA may exert its therapeutic effects on FC.ResultsIn our study, we analyzed 141EA prescriptions for FC and identified a core set of acupoints including Tianshu (ST25), Fujie (SP14), Shangjuxu (ST37), and Zusanli (ST36) through data mining. The frequency of use was highest for Tianshu (ST25) with 119 occurrences, followed by Fujie (SP14) with 59, Shangjuxu (ST37) with 42, and Zusanli (ST36) with 23. PPI network analysis revealed key targets such as NFKB1, IL6, MyD88, TLR4, TNF, TLR2, and IL1B. GO and KEGG analyses of 49 constipation-associated targets identified 257 BP, 37 CC, and 41 MF terms, and 154 significant pathways, with the top 20 visualized for further analysis.ConclusionThe core acupoint prescription of EA for FC can exert its therapeutic effects by acting on multiple targets and pathways synergistically especially on NFKB1, IL6, MyD88, TLR4, TNF, TLR2, and IL1B. The research findings have preliminarily validated the fundamental effects and related mechanisms of EA parameters and core prescriptions, providing direction for further in-depth exploration of the mechanisms of action.
PCSK9 inhibitor alleviates experimental pulmonary fibrosis-induced pulmonary hypertension via attenuating epithelial-mesenchymal transition by suppressing Wnt/β-catenin signaling in vivo and in vitro
Authors: Lin Jiancheng , Pan Zetao , Sun Jiayan , Wang Xiaowan , Yin Di , Huo Cunyang , Guo Qiang 
Published: December 2024

BackgroundThe co-occurrence of pulmonary hypertension (PH) in patients with pulmonary fibrosis (PF) is linked to a more unfavorable prognosis and increased mortality compared to PF cases without PH. Early intervention and comprehensive management are pivotal for improving survival outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protein essential in cholesterol metabolism. However, the potential for PCSK9 inhibition to alleviate PF-induced PH has not been previously reported.MethodsA mouse model of PF-induced PH was established using intratracheal injection of bleomycin (BLM), followed by administration of a PCSK9 inhibitor every other day. Data on right ventricle (RV) remodeling and changes in pulmonary arteries were collected and analyzed. Transforming growth factor-beta (TGF-β) was also administered to MLE-12 cells as an experimental lung fibrosis model. The mechanisms of PCSK9’s impact on lung fibrosis were examined both in vivo and in vitro.ResultsInhibition of PCSK9 significantly reduced pulmonary artery thickening and RV remodeling in the BLM-induced mouse model. Moreover, the blockage of PCSK9 effectively attenuated the migration and epithelial-mesenchymal transition (EMT) process of TGF-β-induced MLE-12 cells. We also observed that the PCSK9 inhibitor suppressed the expression of the Wnt/β-catenin pathway in both animal and cell experiments.ConclusionPCSK9 plays a crucial role in the progression of PF-induced PH by regulating cell EMT and Wnt/β-catenin signaling. Targeting PCSK9 expression or activity could effectively control lung fibrosis and its PH complication.
Musculoskeletal and body composition response to high-dose testosterone with finasteride after chronic incomplete spinal cord injury—a randomized, double-blind, and placebo-controlled pilot study
Authors: Otzel Dana M. , Nichols Larissa , Conover Christine F. , Marangi Stephen A. , Kura Jayachandra R. , Iannaccone Dominic K. , Clark David J. , Gregory Chris M. , Sonntag Christopher F. , Wokhlu Anita , Ghayee Hans K. , McPhaul Michael J. , Levy Charles E. , Plumlee Charles A. , Sammel Robert B. , White Kevin T. , Yarrow Joshua F. 
Published: December 2024

BackgroundHigh-dose testosterone replacement therapy (TRT), paired with finasteride (type II 5α-reductase inhibitor), improves body composition, muscle strength, and bone mineral density (BMD) in older men, without inducing prostate enlargement—a side effect associated with TRT. Men with spinal cord injury (SCI) exhibit neuromuscular impairment, muscle atrophy, bone loss, and increased central adiposity, along with low testosterone. However, sparse evidence supports TRT efficacy after SCI.MethodsThis parallel-group, double-blind, placebo-controlled, and randomized clinical trial (RCT) is a pilot study that enrolled men (N = 12) with low to low–normal testosterone and gait impairments after chronic motor-incomplete SCI. Participants received high-dose intramuscular TRT (testosterone-enanthate, 125 mg/week) with finasteride (5 mg/day) vs. vehicle+placebo for 12 months. Change relative to baseline was determined for body composition, musculoskeletal outcomes, and prostate size, with effect sizes calculated between groups using Hedges’ g. Adverse events and feasibility were assessed.ResultsTRT + finasteride consistently increased testosterone (g = 1.16–3.08) and estradiol (g = 0.43–3.48), while concomitantly reducing dihydrotestosterone (g = 0.31–2.27). Very large effect sizes at both 6 and 12 months suggest TRT + finasteride increased whole-body fat-free (lean) mass (+3–4% vs. baseline, g = 2.12–2.14) and knee extensor (KE) whole-muscle cross-sectional area (+8–11% vs. baseline, g = 2.06–2.53) more than vehicle+placebo. Moderate-to-large effect sizes suggest TRT + finasteride increased KE maximal voluntary isometric torque (+15–40% vs. baseline, g = 0.47–1.01) and femoral neck and distal femur BMD from 6 months onward (g = 0.51–1.13), compared with vehicle+placebo, and reduced fat mass 9–14% within the whole-body, trunk, and android (visceral) regions at 12 months (g = 0.77–1.27). TRT + finasteride also produced small effect sizes favoring lesser prostate growth than vehicle+placebo (g = 0.31–0.43). The participant retention, drug compliance, and incidence and severity of adverse events were similar among the groups.ConclusionThese data provide proof-of-concept and rationale for larger RCTs aimed at discerning the impact of TRT + finasteride on body composition, musculoskeletal health, and physical function in men with SCI, along with effect sizes and variance of responses to assist in planning subsequent trials.Clinical trial registrationClinicalTrials.gov, identifier NCT02248701.
A machine learning-based predictive model for predicting early neurological deterioration in lenticulostriate atheromatous disease-related infarction
Authors: Jiang Zhuangzhuang , Xu Dongjuan , Li Hongfei , Wu Xiaolan , Fang Yuan , Lou Chen 
Published: December 2024

Background and aimThis study aimed to develop a predictive model for early neurological deterioration (END) in branch atheromatous disease (BAD) affecting the lenticulostriate artery (LSA) territory using machine learning. Additionally, it aimed to explore the underlying mechanisms of END occurrence in this context.MethodsWe conducted a retrospective analysis of consecutive ischemic stroke patients with BAD in the LSA territory admitted to Dongyang People’s Hospital from January 1, 2018, to September 30, 2023. Significant predictors were identified using LASSO regression, and nine machine learning algorithms were employed to construct models. The logistic regression model demonstrated superior performance and was selected for further analysis.ResultsA total of 380 patients were included, with 268 in the training set and 112 in the validation set. Logistic regression identified stroke history, systolic pressure, conglomerated beads sign, middle cerebral artery (MCA) shape, and parent artery stenosis as significant predictors of END. The developed nomogram exhibited good discriminative ability and calibration. Additionally, the decision curve analysis indicated the practical clinical utility of the nomogram.ConclusionThe novel nomogram incorporating systolic pressure, stroke history, conglomerated beads sign, parent artery stenosis, and MCA shape provides a practical tool for assessing the risk of early neurological deterioration in BAD affecting the LSA territory. This model enhances clinical decision-making and personalized treatment strategies.
Navigating the obesity paradox in bladder cancer prognosis—insights from the Taiwan National Health Insurance System Database
Authors: Tseng Wen-Hsin , Chiang Ting-Yi , Ho Chung-Han , Huang Steven K. , Chiu Allen W. , Li Chien-Feng , Shiue Yow-Ling 
Published: December 2024

PurposeThis study investigates the complex relationship between body mass index (BMI) and bladder cancer outcomes, utilizing Taiwan’s national database. Bladder cancer remains a significant health concern, especially in Taiwan, prompting a comprehensive retrospective analysis to explore the impact of obesity on survival outcomes.Materials and methodsA meticulous exclusion process, based on Taiwan National Health Insurance System Database, refined the initial dataset of 15,086 bladder cancer patients to 10,352. Categorizing patients into BMI groups (underweight, normal weight, and obesity), the study examined baseline characteristics, comorbidities, and survival outcomes. The analysis involved Cox regression and subgroup assessments stratified by clinical stage.ResultsAmong our patients, 71.5% are male, 78.5% are over 60 years of age, and 18.8% are between 45 and 60 years old. Despite a higher prevalence of comorbidities, obesity patients exhibited a more favorable prognosis, supporting the obesity paradox. The overall and specific mortality ratio of obesity patients were 0.76 fold and 0.82-fold compared with normal-weight patients (overall: 95% confidence interval [CI], 0.71–0.82, p &lt; 0.0001; specific: 95% CI, 0.75–0.90, p &lt; 0.0001). Conversely, underweight patients displayed an increased risk of both overall and cancer-specific mortality compared to normal-weight patients (p &lt; 0.0001).ConclusionThis study highlights the potential protective role of higher BMI in bladder cancer survival, revealing a more favorable prognosis among obesity patients, highlighting the need for cautious interpretation and suggesting avenues for future research. These insights could guide BMI-targeted intervention strategies, allowing clinicians to consider BMI as a factor in personalized treatment planning for bladder cancer patients.
Dietary caffeine and its negative link to serum Klotho concentrations: evidence from the National Health and Nutrition Examination Survey
Authors: Wu Haimeng , Lu Ping 
Published: December 2024

BackgroundThis is the initial investigation assessing the association between caffeine consumption through diet and circulating Klotho concentrations, with Klotho being recognized as a key biomarker of healthspan and aging.MethodsThis cross-sectional analysis utilized data from 11,169 adults who participated in the National Health and Nutrition Examination Survey (NHANES). Caffeine consumption was evaluated using 24-h dietary recall interviews by trained professionals, and serum Klotho concentrations were measured via an enzyme-linked immunosorbent assay (ELISA). Generalized linear models and threshold effect analysis were employed to examine the relationship between caffeine intake and serum Klotho concentrations. Interaction tests and subgroup analyses were conducted to identify potential effect modifiers.ResultsAfter controlling for covariates, a negative correlation was observed between dietary caffeine consumption and serum Klotho concentrations, with each additional 100 mg of dietary caffeine consumption, Klotho decreased by 3.40 pg./mL (95% confidence interval [CI]: −5.73, −1.07). Participants in the fourth quartile of dietary caffeine consumption showed a 23.00 pg./mL reduction in serum Klotho concentrations (95% CI: −39.41, −6.58) compared to individuals in the first quartile. Threshold effect analysis revealed a threshold point corresponding to natural log-transformed caffeine value &gt;3.74 (equivalent to ~41 mg/day), above which Klotho levels demonstrated a more pronounced decline. Subgroup analyses indicated that this association was more significant in participants with sedentary activity &gt;480 min and without hypertension.ConclusionOur study reveals a significant, dose-dependent negative association linking caffeine intake with serum Klotho concentrations in the United States adults aged 40–79 years, with potential thresholds beyond which the effects become more pronounced. Additional studies are required to verify these results and investigate the underlying biological processes involved.
Octreotide plus IBI-318 plus anlotinib in the treatment of multiple neuroendocrine metastases of unknown primary lesions: a case report
Authors: Qin Haoyue , Yan Huan , Zhang Xing , Huang Zhe , Chen Yangqian , Zhang Yuda , Xiang Siqi , Zhang Yongchang , Yang Nong , Zeng Liang 
Published: December 2024

BackgroundThe second-line treatment of neuroendocrine tumors (NETs) of unknown primary origin remains uncertain. This report presented a patient who received octreotide plus IBI-318 plus anlotinib as a second-line treatment for multiple metastatic NETs of unknown primary lesions after the failure of octreotide plus everolimus.Case presentationA 32-year-old male patient presented with elevated CEA (197.83 ng/ml) without specific symptoms. A contrast-enhanced computed tomography (CT) scan showed multiple metastatic lymph nodes and multiple low-density nodules in the liver of undetermined nature. A right supraclavicular lymph node biopsy indicated NET, but the primary tumor origin remained unknown. PD-L1 expression was negative in tumor tissue according to immunohistochemistry. Immunofluorescence indicated the CD4+ T cells, CD8+ T cells, and Treg cells were gathered around blood vessels, with only a few infiltrating lymphocytes in the tumor tissue. Treatment with octreotide (30 mg/28 d) plus everolimus (5 mg qd) led to disease progression after three cycles. Treatment was changed to octreotide (30 mg/28 d) plus IBI318 (400 mg/28 d) plus anlotinib (10 mg/1-14 d/q3w), leading to partial remission, which was sustained up to the last follow-up (June 20, 2023), with a PFS of 11 months. The patient experienced no treatment-related adverse reactions.ConclusionsOctreotide plus IBI318 plus anlotinib achieved benefits in a patient with advanced NETs of unknown primary lesions after first-line treatment failure, even though with low PD-L1 expression. This case suggests that combining SSAs, TKIs and PD-1/PD-L1 inhibitors could be an alternative second-line treatment for patients with advanced, well-differentiated NETs.
Hotspots and status of Fetal Alpha-Thalassemia from 2009 to 2023: a bibliometric analysis
Authors: Li Qiuying , Li Xinyan , He Sheng , Li Jiao 
Published: December 2024

Objectiveto evaluate the research status and development hotspots of fetal α-thalassemia by quantitatively analyzing the diagnostic status, key areas, related management measures and prospects of the disease by bibliometrics.MethodsThe global literature on fetal α-thalassemia and severe α-thalassemia from 2009–2023 in the Web of Science Core Collection (WOSCC) was visually analyzed by VOSviewer and CiteSpace.Results(1) The examination of the quantity of publications concerning fetal α-thalassemia indicates a rising tendency prior to 2018, followed by a decrease after 2018. (2)The United States, China, Italy, Thailand have published more papers, and the United States has more collaborating countries such as Italy and China. (3) Chiang Mai University and Harvard University are the top two institutions with the highest contribution. However, Chiang Mai University's H index (12) and citation frequency per article (8.05) are relatively low and the NC (6,342), H index (33) and citations per article (75.42) of Harvard University are higher than those of the other institutions. (4) Tongsong T, Gambari R and Fucharoen S are the top three prolific authors. Fucharoen S emerges as the most frequently cited author with 738 citations, excluding self-citations. (5) HEMOGLOBIN leading with 87 published papers (NC:601,IF: 0.82, H-index: 13), followed by BLOOD(58 papers, Nc: 3755, IF: 25.48, H-index: 40) and BLOOD CELLS MOLECULES AND DISEASES(39 papers, Nc: 729, IF: 2.37, H-index: 16). (6) The most cited article was published in science and the second and third cited articles were featured in the Proceedings of the National Academy of Sciences; the top 3 clusters of co-cited literature are “gene editing”, “polymorphisms”, “hydroxyurea”. (7) Keywords analysis showe that the top two categories of keyword cluster focus on the prenatal diagnosis and the current treatment strategy of the disease, which remain the research hotspots.ConclusionsRecent research on this topic has primarily focused on prenatal diagnosis and treatment strategies. A particular area of interest is the ongoing research on gene therapy.The advances in non-invasive diagnosis and therapeutic methods will change the current management approaches for fetal severe α-thalassemia in the future.
Case Report: Primary catastrophic antiphospholipid syndrome in a pediatric patient with cerebral venous sinus thrombosis as the first manifestation
Authors: Xu Lingyang , Wu Jing , Wang Haidong , Yang Baowang 
Published: December 2024

BackgroundAntiphospholipid syndrome (APS) is an autoimmune disease characterized by recurrent vascular thrombotic events. Catastrophic APS (CAPS), which can result in multiple organ failure and even death, is the most severe manifestation of APS. Herein, we report the case of a pediatric patient with CAPS, including the clinical course, diagnosis, and treatment, with the goal of expanding the literature on this condition, as reports of CAPS in pediatric patients are rare.Case presentationA 7-year-old girl presented with cranial hypertension. She was initially admitted to the hospital with a diagnosis of cerebral venous sinus thrombosis (CVST) and was discharged following symptom improvement. However, only 3 days later, the patient was re-presented with cranial hypertension and multiple thromboses and was ultimately diagnosed with CAPS based on multidisciplinary consensus. Despite treatment with a series of anticoagulation and thrombolytic therapies, the child's condition progressed rapidly, and she eventually died of pulmonary embolism.ConclusionCAPS in children is rare and associated with a high mortality rate, making early recognition and diagnosis critical but difficult. Based on the presented case, we recommend routine screening for antiphospholipid antibodies in children with CVST without obvious triggers, or a multidisciplinary collaboration, to facilitate the early diagnosis of CAPS.
Paromomycin targets HDAC1-mediated SUMOylation and IGF1R translocation in glioblastoma
Authors: Min Zhong , Guo Yuejie , Ning Luo 
Published: December 2024

ObjectiveThis study investigates the effects of Paromomycin on SUMOylation-related pathways in glioblastoma (GBM), specifically targeting HDAC1 inhibition.MethodsUsing TCGA and GTEx datasets, we identified SUMOylation-related genes associated with GBM prognosis. Molecular docking analysis suggested Paromomycin as a potential HDAC1 inhibitor. In vitro assays on U-251MG GBM cells were performed to assess Paromomycin’s effects on cell viability, SUMOylation gene expression, and IGF1R translocation using CCK8 assays, qRT-PCR, and immunofluorescence.ResultsParomomycin treatment led to a dose-dependent reduction in GBM cell viability, colony formation, and migration. It modulated SUMO1 expression and decreased IGF1R nuclear translocation, an effect reversible by the HDAC1 inhibitor Trochostatin A (TSA), suggesting Paromomycin’s involvement in SUMO1-regulated pathways.ConclusionThis study highlights Paromomycin’s potential as a therapeutic agent for GBM by targeting HDAC1-mediated SUMOylation pathways and influencing IGF1R translocation, warranting further investigation for its clinical application.
Association between positive youth development and family functioning in the Chinese context: a four-wave longitudinal survey in mainland China
Authors: Li Xiang , Tang Yi-Ting , Shek Daniel T. L. 
Published: December 2024

IntroductionThere is a notable scarcity of research examining the developmental trajectories of positive youth development (PYD) attributes among Chinese preadolescents and adolescents and the predictive effect of family functioning on these trajectories over time.MethodsUsing four waves of data, this longitudinal study investigated preadolescents and adolescents in China in January 2020 (T1), June 2020 (T2), June 2021 (T3), and June 2022 (T4). The study utilized the 90-item “Chinese Positive Youth Development Scale” and the 33-item “Chinese Family Assessment Instrument” to assess PYD and family functioning, respectively. The final matched sample comprised 2,652 Chinese students from grades 4 to 8, with an average age of 10.9 years (SD = 1.32; range 9–15) at the first wave of the survey, and with 51.1% male (n = 1,354).ResultsThe Latent Growth Curve Modeling (LGCM) revealed that the PYD developmental trajectories of preadolescents and adolescents followed a quadratic U-shaped curve, characterized by an initial decline from T1 to T3, followed by a rebound from T3 to T4. Although the time-invariant covariate LGCM indicated no significant gender difference in the initial level of PYD, girls exhibited a slower decline rate and a faster growth rate in PYD over time than did boys. The parallel LGCM demonstrated that initial levels of family functioning significantly and positively predicted both the initial level and the rate of change in PYD over time.DiscussionThis study highlights the critical importance of considering the direct and sustained impact of family functioning within Chinese contexts on positive developmental outcomes among Chinese preadolescents and adolescents. This study also suggests that when designing and formulating specific programs or interventions, it is essential to consider gender differences in the development of competencies to ensure the optimal development of young individuals of different genders.