bluuebunny/crossref_metadata_2025_split huggingface dataset:
The therapeutic mechanism of Compound Lurong Jiangu Capsule for the treatment of cadmium-induced osteoporosis: network pharmacology and experimental verification
Authors: Zhou Ya-shuang , Huang Jian , Cao Wen-xuan , Yu Ao-xue , Li Pan , Liang Jin-ling , Leng Xiang-yang , Jin Jian , Yu Peng , Liu Jia 
Published: July 2024

BackgroundAmong bone diseases, osteoporosis-like skeleton, such as trabecular thinning, fracture and so on, is the main pathological change of cadmium-induced osteoporosis(Cd-OP), accompanied by brittle bone and increased fracture rate. However, the mechanism underlying cadmium-induced osteoporosis has remained elusive. Compound Lurong Jiangu Capsule (CLJC) is an experienced formula for the treatment of bone diseases, which has the effect of tonifying kidney and strengthening bones, promoting blood circulation and relieving pain.ObjectiveNetwork pharmacology and molecular docking technology combined with experiments were used to investigate the potential mechanism of CLJC in treating Cd-OP.MethodThe active compounds and corresponding targets of each herb in CLJC were searched in the TCMSP and BATMAN-TCM databases. The DisGeNet, OMIM, and GeneCards databases searched for Cd-OP targets. The relationship between both of them was visualized by establishing an herb-compound-target network using Cytoscape 3.9.1 software. Gene ontology (GO), and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were performed after determining the intersection of the targets from CLJC and Cd-OP. What’s more, molecular docking was performed to validate the results. All of them were aim to obtain hud signaling pathways for further study. Finally, BAX, BCL-2, and CASPASE-3 were screened and selected for further experiments, which included bone imaging and reconstruction analysis (Micro-CT), hematoxylin-eosin Staining (HE), and western blot (WB).Results106 common targets from CLJC and Cd-OP targets were identified. KEGG pathway analysis suggested that multiple signaling pathways, such as the pathways in cancer, may play roles in treatment. Verification of the molecular docking was successful. Here we showed that Cd-OP displayed Tb.Th and Tb.N significantly reduced and even broke, irregular proliferation of bone cortex, uneven and loose trabecular bone arrangement, changed in apoptosis-related proteins, such as significant upregulation of CASPASE-3, BAX protein and significant downregulation of BCL-2 protein in vivo, while CLJC rescued these phenotypes.ConclusionThis study revealed that CLJC can reduce the expression of apoptosis-related proteins, and multiple components and multiple targets inhibit Cd-OP through apoptosis signaling pathway.
Identification and functional characteristics of a novel splicing heterozygote variant of COL2A1 associated with Stickler syndrome type I
Authors: Gong Yujing , Zhu Weijian , Zhu Mianmian , Chen Dan , Wu Sunke , Hu Sisi , Luo Yi , Jiang Yiyi , Zhu Ting , Wang Dan 
Published: July 2024

BackgroundStickler syndrome type I (STL1) is an autosomal dominant disorder characterized by ocular, auditory, orofacial, and skeletal anomalies. The main causes of STL1 are variants in the COL2A1 gene, which encodes a type II collagen precursor protein. The specific focus of this study was on a newborn from China diagnosed with STL1, with the aim of providing novel insights into the effects of a newly identified intronic variant in the COL2A1 gene on pre-mRNA splicing.MethodsTrio whole exome sequencing was used to identify the causative variant in the family. The identified variant was validated using Sanger sequencing. Bioinformatics programs were used to predict the pathogenicity of the candidate variant. Additionally, an in vitro minigene assay was used to investigate the effects of the identified variant on RNA splicing.ResultsThe proband with STL1 had a novel heterozygous splicing variant in the intron nine acceptor donor site of COL2A1 (c.655-2A&gt;G). This splice junction variant resulted in aberrant COL2A1 mRNA splicing, leading to the skipping of exon 10 and the production of a shorter protein that may lack the last 18 native amino acids.ConclusionThe c.655-2A&gt;G variant in the COL2A1 gene leads to STL1 through abnormal splicing. By expanding the spectrum of variants in the COL2A1 gene, this finding improves the clinical understanding of STL1 and provides guidance for early diagnosis and disease counseling.
The association between IGF-1 levels and four types of osteoarthritis: a bidirectional and two-step mendelian randomization study
Authors: Pan Xiaohan , Cheng Minghuang , Li Dongxu , Liu Zeyu , Yao Qi , Jiang Wei , Zhang Xiaojun , Hao Jie 
Published: July 2024

BackgroundInsulin-like Growth Factor-1 (IGF-1) plays a crucial role in the growth and metabolic functions of various tissues and cells in the body. Recently, there has been increased attention to the association between IGF-1 and osteoarthritis (OA). However, there is controversy in current research regarding the correlation between IGF-1 levels and OA. Furthermore, the specific manner in which Body Mass Index (BMI), a key risk factor for OA, mediates the impact of IGF-1 levels on OA remains unclear.ObjectThis study aimed to investigate the bidirectional causal link between IGF-1 levels and OA in four body regions, and to explore how BMI influences the impact of IGF-1 on these types of OA.MethodTwo-sample Mendelian Randomization (MR) and its combined forms were utilized to investigate the bidirectional relationship between IGF-1 levels and four types of OA, as well as the mediating role of BMI in the impact of IGF-1 levels on OA. Data from various Genome-Wide Association Studies (GWAS) and multiple analytical methods, including inverse variance weighted, MR-Egger regression, and weighted median were utilized. Sensitivity analyses, such as MR-Egger intercept, Cochran Q test, leave-one-out, and MR-PRESSO, were conducted to ensure the robustness of the results.ResultsHigher IGF-1 levels are correlated with an increased risk for knee (OR, 1.07; 95% CI, 1.01–1.03; p = 1.49e-01; q = 9.86e-03), hip (OR, 1.13; 95% CI, 1.06–1.20; p = 7.61e-05; q = 7.44e-05), and hand OA (OR, 1.09; 95% CI, 1.01–1.17; p = 1.88e-02; q = 1.15e-02), but not spine OA but not spine OA (OR, 1.05; 95% CI, 0.99–1.10; p = 9.20e-02; q = 5.52e-02). Different types of OA do not affect IGF-1 levels. BMI mediates the increase in OA risk associated with higher IGF-1, including indirect spine OA risk through BMI.ConclusionThe study elucidates the bidirectional causality between IGF-1 levels and OA in various body parts, highlighting BMI’s mediating role in the impact of IGF-1 levels on OA. This provides valuable insights for OA prevention, diagnosis, and treatment strategies. Future research will expand our study to include a broader spectrum of ethnicities and explore the underlying mechanisms involved.
Identification of shared genetic risks underlying metabolic syndrome and its related traits in the Korean population
Authors: Kim Jun Young , Cho Yoon Shin 
Published: July 2024

Introduction: Observational studies have demonstrated strong correlations between metabolic syndrome (MetS) and its related traits. To gain insight into the genetic architecture and molecular mechanism of MetS, we investigated the shared genetic basis of MetS and its related traits and further tested their causal relationships.Methods: Using summary statistics from genome-wide association analyses of about 72,000 subjects from the Korean Genome and Epidemiological Study (KoGES), we conducted genome-wide multi-trait analyses to quantify the overall genetic correlation and Mendelian randomization analyses to infer the causal relationships between traits of interest.Results: Genetic correlation analyses revealed a significant correlation of MetS with its related traits, such as obesity traits (body mass index and waist circumference), lipid traits (triglyceride and high-density lipoprotein cholesterol), glycemic traits (fasting plasma glucose and hemoglobin A1C), and blood pressure (systolic and diastolic). Mendelian randomization analyses further demonstrated that the MetS-related traits showing significant overall genetic correlation with MetS could be genetically determined risk factors for MetS.Discussion: Our study suggests a shared genetic basis of MetS and its related traits and provides novel insights into the biological mechanisms underlying these complex traits. Our findings further inform public health interventions by supporting the important role of the management of metabolic risk factors such as obesity, unhealthy lipid profiles, diabetes, and high blood pressure in the prevention of MetS.
Generative adversarial networks synthetic optical coherence tomography images as an education tool for image diagnosis of macular diseases: a randomized trial
Authors: Peng Jie , Xie Xiaoling , Lu Zupeng , Xu Yu , Xie Meng , Luo Li , Xiao Haodong , Ye Hongfei , Chen Li , Yang Jianlong , Zhang Mingzhi , Zhao Peiquan , Zheng Ce 
Published: July 2024

PurposeThis study aimed to evaluate the effectiveness of generative adversarial networks (GANs) in creating synthetic OCT images as an educational tool for teaching image diagnosis of macular diseases to medical students and ophthalmic residents.MethodsIn this randomized trial, 20 fifth-year medical students and 20 ophthalmic residents were enrolled and randomly assigned (1:1 allocation) into Group real OCT and Group GANs OCT. All participants had a pretest to assess their educational background, followed by a 30-min smartphone-based education program using GANs or real OCT images for macular disease recognition training. Two additional tests were scheduled: one 5 min after the training to assess short-term performance, and another 1 week later to assess long-term performance. Scores and time consumption were recorded and compared. After all the tests, participants completed an anonymous subjective questionnaire.ResultsGroup GANs OCT scores increased from 80.0 (46.0 to 85.5) to 92.0 (81.0 to 95.5) 5 min after training (p &lt; 0.001) and 92.30 ± 5.36 1 week after training (p &lt; 0.001). Similarly, Group real OCT scores increased from 66.00 ± 19.52 to 92.90 ± 5.71 (p &lt; 0.001), respectively. When compared between two groups, no statistically significant difference was found in test scores, score improvements, or time consumption. After training, medical students had a significantly higher score improvement than residents (p &lt; 0.001).ConclusionThe education tool using synthetic OCT images had a similar educational ability compared to that using real OCT images, which improved the interpretation ability of ophthalmic residents and medical students in both short-term and long-term performances. The smartphone-based educational tool could be widely promoted for educational applications.Clinical trial registration: https://www.chictr.org.cn, Chinese Clinical Trial Registry [No. ChiCTR 2100053195].
Efficacy of sodium hypochlorite in overcoming antimicrobial resistance and eradicating biofilms in clinical pathogens from pressure ulcers
Authors: Fabrizio Giorgia , Sivori Francesca , Cavallo Ilaria , Truglio Mauro , Toma Luigi , Sperati Francesca , Francalancia Massimo , Obregon Francisco , Pamparau Luisa , Kovacs Daniela , Pimpinelli Fulvia , Di Domenico Enea Gino 
Published: July 2024

Sodium hypochlorite (NaOCl) is widely recognized for its broad-spectrum antimicrobial efficacy in skin wound care. This study investigates the effectiveness of NaOCl against a range of bacterial and fungal isolates from pressure ulcer (PU) patients.We analyzed 20 bacterial isolates from PU patients, comprising carbapenem-resistant Klebsiella pneumoniae (CRKP), multidrug-resistant Acinetobacter baumannii (MDRAB), methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible Staphylococcus aureus (MSSA), along with 5 Candida albicans isolates. Antibiotic resistance profiles were determined using standard susceptibility testing. Whole-genome sequencing (WGS) was employed to identify antimicrobial resistance genes (ARGs) and disinfectant resistance genes (DRGs). Genetic determinants of biofilm formation were also assessed. The antimicrobial activity of NaOCl was evaluated by determining the minimum inhibitory concentration (MIC) and the minimal biofilm eradication concentration (MBEC) for both planktonic and biofilm-associated cells.CRKP and MDRAB showed resistance to fluoroquinolones and carbapenems, while MRSA exhibited resistance to β-lactams and levofloxacin. MSSA displayed a comparatively lower resistance profile. WGS identified significant numbers of ARGs in CRKP and MDRAB, with fewer DRGs compared to MRSA and MSSA. All isolates possessed genes associated with fimbriae production and adhesion, correlating with pronounced biofilm biomass production. NaOCl demonstrated substantial antimicrobial activity against both planktonic cells and biofilms. The MIC90 for planktonic bacterial cells was 0.125 mg/mL, and the MBEC90 ranged from 0.225 to 0.5 mg/mL. For planktonic C. albicans, the MIC90 was 0.150 mg/mL, and the MBEC90 was 0.250 mg/mL.These results highlight the challenge in treating biofilm-associated infections and underscore the potential of NaOCl as a robust antimicrobial agent against difficult-to-treat biofilm infections at concentrations lower than those typically found in commercial disinfectants.
Metabolomics highlights biochemical perturbations occurring in the kidney and liver of mice administered a human dose of colistin
Authors: Barla I. , Dagla I. V. , Daskalopoulou A. , Panagiotopoulou M. , Kritikaki M. , Dalezis P. , Thomaidis N. , Tsarbopoulos A. , Trafalis D. , Gikas E. 
Published: July 2024

Introduction: Colistin (CMS) is used for the curation of infections caused by multidrug-resistant bacteria. CMS is constrained by toxicity, particularly in kidney and neuronal cells. The recommended human doses are 2.5–5 mg/kg/day, and the toxicity is linked to higher doses. So far, the in vivo toxicity studies have used doses even 10-fold higher than human doses. It is essential to investigate the impact of metabolic response of doses, that are comparable to human doses, to identify biomarkers of latent toxicity. The innovation of the current study is the in vivo stimulation of CMS's impact using a range of CMS doses that have never been investigated before, i.e., 1 and 1.5 mg/kg. The 1 and 1.5 mg/kg, administered in mice, correspond to the therapeutic and toxic human doses, based on previous expertise of our team, regarding the human exposure. The study mainly focused on the biochemical impact of CMS on the metabolome, and on the alterations provoked by 50%-fold of dose increase. The main objectives were i) the comprehension of the biochemical changes resulting after CMS administration and ii) from its dose increase; and iii) the determination of dose-related metabolites that could be considered as toxicity monitoring biomarkers.Methods: The in vivo experiment employed two doses of CMS versus a control group treated with normal saline, and samples of plasma, kidney, and liver were analysed with a UPLC-MS-based metabolomics protocol. Both univariate and multivariate statistical approaches (PCA, OPLS-DA, PLS regression, ROC) and pathway analysis were combined for the data interpretation.Results: The results pointed out six dose-responding metabolites (PAA, DA4S, 2,8-DHA, etc.), dysregulation of renal dopamine, and extended perturbations in renal purine metabolism. Also, the study determined altered levels of liver suberylglycine, a metabolite linked to hepatic steatosis. One of the most intriguing findings was the detection of elevated levels of renal xanthine and uric acid, that act as AChE activators, leading to the rapid degradation of acetylcholine. This evidence provides a naïve hypothesis, for the potential association between the CMS induced nephrotoxicity and CMS induced 39 neurotoxicity, that should be further investigated.
Retrospective analysis of nystagmus characteristics and clinical applications of positional testing in patients with cupulolithiasis of the posterior semicircular canal in benign paroxysmal positional vertigo
Authors: Wu Jing , Zou Yihuai , Xu Wenyan , Ma Hongming , Huang Lixian , Zhao Bo , Sun Liman 
Published: July 2024

ObjectiveThis study aimed to investigate the characteristics of positional nystagmus in patients with cupulolithiasis of the posterior semicircular canal-benign paroxysmal positional vertigo (PC-BPPV-cu) to improve clinical diagnostic accuracy.MethodsThis study retrospectively analyzed 128 cases of PC-BPPV-cu and 128 cases of canalolithiasis of BPPV (PC-BPPV-ca). General data, intensity, distribution, and the correlation of positional nystagmus were compared between the two groups.ResultsCompared to the PC-BPPV-ca group, more cases from the PC-BPPV-cu group initially presented in the emergency department (P &lt; 0.05). The most frequent positional nystagmus induced by PC-BPPV-cu was torsional-upbeat nystagmus, characterized by the upper pole of the affected eye beating toward the lower ear and vertically upward (387 cases, 59.7%). It was followed by torsional-downbeat nystagmus, characterized by the upper pole of the unaffected eye beating toward the lower ear and vertically downward (164 cases, 25.3%). The former represented posterior canal excitatory nystagmus (PC-EN), while the latter represented posterior canal inhibitory nystagmus (PC-IN). In the PC-BPPV-cu group, PC-EN was most easily caused by the Half Dix–Hallpike (HH) maneuver on the affected side, while PC-IN was most easily induced by a face-down position (FDP) on the unaffected side at approximately 45° angle (45° FDP). The vertical slow phase velocity (v-SPV) of positional nystagmus was more potent in the affected HH than in other positions with PC-EN (all P &lt; 0.05); the v-SPV of positional nystagmus was greater in the 45° FDP than in different positions with PC-IN (all P &lt; 0.05); the v-SPV of the affected Dix–Hallpike (DH) maneuver in the PC-BPPV-ca group was significantly greater than that of the affected HH maneuver in the PC-BPPV-cu group (P &lt; 0.05). The a priori analysis showed that the strongest correlation with HH positional nystagmus was observed in the affected side roll test, followed by the DH maneuver.ConclusionIn the PC-BPPV-cu group, the HH maneuver most easily induced PC-EN on the affected side, and PC-IN was most easily induced by the 45° FDP. In some cases of PC-BPPV-cu, significant nystagmus was not observed to be induced in the DH position on the affected side; however, vertical rotation nystagmus was induced in the roll-test position on the affected side. In such cases, PC-BPPV-cu diagnosis should be considered, and HH and 45° FDP tests should be conducted to support the diagnosis.
Influence of short-term hypoxia exposure on dynamic visual acuity
Authors: Wang Yuchen , Xie Jiaxing , Yu Xinli , Liu Yihe , Wang Zesong , Guo Anqi , Ding Yi , Zhou Xinzuo , Liu Siru , Li Jiaxi , Zhou Chengkai , Li Yuanhong , Liu Ziyuan , Li Xuemin , Ding Li 
Published: July 2024

BackgroundTo quantify the changes in dynamic visual acuity (DVA) and explain the hidden reasons after acute exposure to hypobaric hypoxia status.MethodsThe study group comprised 18 healthy male and 15 healthy female participants aged 20–24 years old. DVA was measured with the self-developed software of Meidixin (Tianjin) Co., Ltd. Measurements were taken at eight altitudes. Data analysis was performed using the Kolmogorov–Smirnov test, paired sample T-test, and two-way repeated measures analysis of variance (ANOVA) for repeated measurements.ResultsAt constant altitude, DVA showed an overall decreasing trend with increasing angular velocity and a fluctuating decrease at the vast majority of altitudes. At constant angular velocities, DVA gradually increased with altitude, with the most pronounced increase in DVA at altitude 5, and thereafter a gradual decrease in DVA as altitude increased. Finally, as altitude decreased, DVA increased again and reached a higher level at the end of the experiment, which was superior to the DVA in the initial state.ConclusionUnder a hypobaric hypoxic environment at high altitude, DVA was affected by the angular velocity and the degree of hypoxia, manifesting as an increase or decrease in DVA, which affects the pilot's observation of the display and control interfaces during the driving process, acquisition of information, and decision-making ability, which in turn may potentially jeopardize the safety of the flight.
Anorexia and bulimia in relation to ulcerative colitis: a Mendelian randomization study
Authors: Su Qiang , Li Jian , Lu Yun , Wu Min , Liang Jiang , An Zhenxiang 
Published: July 2024

BackgroundEvidence for anorexia and bulimia in relation to the risk of ulcerative colitis (UC) is limited and inconsistent. The objective of this research was to utilize bi-directional, two-sample Mendelian randomization (MR) analysis to predict the causal association between anorexia nervosa and bulimia nervosa with UC.MethodsThe genome-wide association studies (GWAS) provided data for anorexia and bulimia from the UK Biobank, utilizing single-nucleotide polymorphisms (SNP) as instrumental variables. Additionally, genetic associations with UC were collected from various sources including the FinnGen Biobank, the UK Biobank and the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). The main analytical approach utilized in this study was the inverse-variance-weighted (IVW) method. To evaluate horizontal pleiotropy, the researchers conducted MR-Egger regression and MR-PRESSO global test analyses. Additionally, heterogeneity was assessed using the Cochran’s Q test.ResultsThis study found a negative association between genetically predicted bulimia (OR = 0.943, 95% CI: 0.893–0.996; p = 0.034) and the risk of UC in the IIBDGC dataset, indicating that individuals with bulimia have approximately a 5.7% lower risk of developing UC. No association was observed in the other two datasets. Conversely, genetically predicted anorexia was not found to be causally associated with UC. In bi-directional Mendelian randomization, UC from the IIBDGC dataset was negatively associated with the risk of anorexia (OR = 0.877, 95% CI: 0.797–0.965; p = 0.007), suggesting that UC patients have approximately a 12.3% lower risk of developing anorexia, but not causally associated with bulimia.ConclusionGenetically predicted bulimia may have a negative association with the onset of UC, while genetically predicted anorexia does not show a causal relationship with the development of UC. Conversely, genetically predicted UC may have a negative association with the development of anorexia.