bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is fracture management merely a physical process? Exploring the psychological effects of internal and external fixation
Authors: Jia Qiyu , Peng Zhenlei , Huang Anqi , Jiang Shijie , Zhao Wen , Xie Zengru , Ma Chuang 
Published: April 2024

Abstract
Background
Internal and external fixation are common surgical procedures for treating fractures. However, the impact of different surgical approaches (including internal and external fixations) on patients’ psychological status and Quality of Life (QoL) is rarely examined. Herein, we aimed to investigate the effects of internal and external fixation on anxiety, depression, insomnia, and overall mental and physical health in Distal Radius Fractures (DRF) patients.

Methods
We performed a retrospective study on 96 fracture patients who underwent internal fixation (57 patients) or external fixation (39 patients). The Visual Analog Scale (VAS), the Hospital Anxiety and Depression Scale (HADS), the Athens Insomnia Scale (AIS), and the Medical Outcomes Study Short Form 36 (SF-36) questionnaire were used to assess the patients’ pain, anxiety, depression, sleep, and QoL before surgery and at seven days, one month, and three months post-surgery.

Results
The VAS scores were significantly lower in the Internal Fixation Group (IFG) than in the External Fixation Group (EFG) on the seventh day and one month postoperatively (P < 0.05). Although both groups showed no significant anxiety, depression, or insomnia before surgery (P > 0.05), the EFG showed significantly higher HADS-A, HADS-D, and AIS scores than the IFG at seven days and one and three months postoperatively (P < 0.05). Additionally, changes in HADS-A, HADS-D, and AIS scores were most significant at day seven post-surgery in the EFG (P < 0.05). Furthermore, no significant difference was found between the two groups in the average Physical Component Summary (PCS) and Mental Component Summary (MCS) scores before surgery (P > 0.05). However, both groups showed positive changes in PCS and MCS scores at postoperative day seven and one and three months postoperatively, with the IFG having significantly higher average PCS and MCS scores compared to the EFG (P < 0.05).

Conclusion
Compared to external fixation, internal fixation did not significantly impact patients’ emotions regarding anxiety and depression in the early postoperative period, and physical and mental health recovery was better during the postoperative rehabilitation period. Furthermore, when there are no absolute indications, the impact on patients’ psychological well-being should be considered as one of the key factors in the treatment plan during surgical approach selection.
SP1 transcriptionally activates HTR2B to aggravate traumatic spinal cord injury by shifting microglial M1/M2 polarization
Authors: Xu Qifei , Kong Fanguo , Zhao Guanghui , Jin Junwei , Feng Shengkai , Li Ming 
Published: April 2024

Abstract
Background
Spinal cord injury (SCI) can result in structural and functional damage to the spinal cord, which may lead to loss of limb movement and sensation, loss of bowel and bladder control, and other complications. Previous studies have revealed the critical influence of trans-acting transcription factor 1 (SP1) in neurological pathologies, however, its role and mechanism in SCI have not been fully studied.

Methods
The study was performed using mouse microglia BV2 stimulated using lipopolysaccharide (LPS) and male adult mice subjected to spinal hitting. Western blotting was performed to detect protein expression of SP1, 5-hydroxytryptamine (serotonin) receptor 2B (HTR2B), BCL2-associated x protein (Bax), B-cell lymphoma-2 (Bcl-2), inducible nitric oxide synthase (iNOS), clusters of differentiation 86 (CD86), Arginase 1 (Arg-1) and clusters of differentiation 206 (CD206). Cell viability and apoptosis were analyzed by MTT assay and TUNEL assay. mRNA levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-4 (IL-4) and tumor necrosis factor-β (TNF-β) were quantified by quantitative real-time polymerase chain reaction. The association of SP1 and HTR2B was identified by chromatin immunoprecipitation assay and dual-luciferase reporter assay. HE staining assay was performed to analyze the pathological conditions of spinal cord tissues.

Results
LPS treatment induced cell apoptosis and inhibited microglia polarization from M1 to M2 phenotype, accompanied by an increase of Bax protein expression and a decrease of Bcl-2 protein expression, however, these effects were relieved after SP1 silencing. Mechanism assays revealed that SP1 transcriptionally activated HTR2B in BV2 cells, and HTR2B knockdown rescued LPS-induced effects on BV2 cell apoptosis and microglial M1/M2 polarization. Moreover, SP1 absence inhibited BV2 cell apoptosis and promoted microglia polarization from M1 to M2 phenotype by decreasing HTR2B expression. SCI mouse model assay further showed that SP1 downregulation could attenuate spinal hitting-induced promoting effects on cell apoptosis of spinal cord tissues and microglial M1 polarization.

Conclusion
SP1 transcriptionally activated HTR2B to aggravate traumatic SCI by shifting microglial M1/M2 polarization.
Aspiration of thrombus for intermediate-risk subacute pulmonary embolism
Authors: He Jiahao , Liu Chunli 
Published: April 2024

AbstractPulmonary embolism is the most common cardiovascular disease after myocardial infarction and stroke. Konstantinides (Eur Heart J 41(4):543–603, 2020) Current guidelines categorize patients with PE as being at low, intermediate, and high risk of early death, with the intermediate-risk group experiencing the greatest uncertainty regarding treatment recommendations. Rapid reduction of the thrombus load by thrombolysis significantly reduces symptoms and decreases mortality, but is accompanied by a high risk of bleeding. Meyer (N Engl J Med 370(15):1402-11, 2014) Mechanical thrombectomy (CDTE) have been proven safe and efficient, yet current ESC guidelines suggest the utilization of catheter interventions only for hypotensive patients with high bleeding risk, failed systemic thrombolysis, and cardiogenic shock or if a patient does not respond to conservative therapy Konstantinides (Eur Heart J 41(4):543–603, 2020). Here, we report a case of an intermediate-risk patient with pulmonary embolism who underwent thrombus aspiration and showed significant improvement in symptoms after treatment.
Experience with aortic arch inclusion technique using artificial blood vessel for type A aortic dissection: an application study
Authors: Li Qingfeng , Li Bin , Xi Shuqiang , Li Zhaobin , Zhu Zhe , Jin Zeyue , Yang Fan , Liu Lei 
Published: April 2024

Abstract
Background
This study aimed to elucidate the methodology and assess the efficacy of the aortic arch inclusion technique using an artificial blood vessel in managing acute type A aortic dissection (ATAAD).

Methods
We conducted a retrospective review of 18 patients (11 males and 7 females, average age: 56.2 ± 8.6 years) diagnosed with ATAAD who underwent total aortic arch replacement (TAAR) using an artificial vascular “inclusion” between June 2020 and October 2022. During the operation, deep hypothermic circulatory arrest (DHCA) and selective antegrade cerebral perfusion (ACP) of the right axillary artery were employed for brain protection. The ‘inclusion’ total aortic arch replacement and stented elephant trunk (SET) surgery were performed.

Results
Four patients underwent the Bentall procedure during the study, with one additional patient requiring coronary artery bypass grafting (CABG) due to significant involvement of the right coronary orifice. Three patients died during postoperative hospitalization. Other notable complications included two cases of postoperative renal failure necessitating continuous renal replacement therapy (CRRT), one case of postoperative double lower limb paraplegia, and one case of cerebral infarction resulting in unilateral impairment of the left upper limb. Eleven patients underwent computed tomography angiography (CTA) examinations of the aorta three months to one-year post-operation. The CTA results revealed thrombosis in the false lumen surrounding the aortic arch stent in seven patients and complete thrombosis of the false lumen around the descending aortic stent in eight patients. One patient had partial thrombosis of the false lumen around the descending aortic stent, and another patient’s false lumen in the thoracic and abdominal aorta completely resolved after one year of follow-up.

Conclusions
Incorporating vascular graft in aortic arch replacement simplifies the procedure and yields promising short-term outcomes. It achieves the aim of total arch replacement using a four-branch prosthetic graft. However, extensive sampling and thorough, prolonged follow-up observations are essential to fully evaluate the long-term results.
Oleuropein alleviates myocardial ischemia–reperfusion injury by suppressing oxidative stress and excessive autophagy via TLR4/MAPK signaling pathway
Authors: He Jia , Huang Liting , Sun Kaili , Li Jilang , Han Shan , Gao Xiang , Wang Qin-Qin , Yang Shilin , Sun Wen , Gao Hongwei 
Published: April 2024

Abstract
Background
Myocardial ischemia/reperfusion injury (MIRI) is an important complication of reperfusion therapy, and has a lack of effective prevention and treatment methods. Oleuropein (OP) is a natural strong antioxidant with many protective effects on cardiovascular diseases, but its protective effect on MIRI has not yet been studied in depth.

Methods
Tert-Butyl hydroperoxide (tBHP) was used to establish an in vitro oxidative stress model. Cell viability was detected by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and lactate dehydrogenase (LDH). Flow cytometry and fluorescence assays were performed for evaluating the ROS levels and mitochondrial membrane potential (MMP). Immunofluorescence analysis detected the NRF2 nuclear translocation and autophagy indicators. Further, Western blotting and quantitative real-time PCR were performed to evaluate the expression levels of proteins and mRNAs. Molecular docking, CETSA, and molecular interaction analysis explored the binding between OP and TLR4. The protective effects of OP in vivo were determined using a preclinical MIRI rat model.

Results
OP protected against tBHP-treated injury, reduced ROS levels and reversed the damaged MMP. Mechanistically, OP activated NRF2-related antioxidant pathways, inhibited autophagy and attenuated the TLR4/MAPK signaling pathway in tBHP-treated H9C2 cells with a high binding affinity to TLR4 (KD = 37.5 µM). The TLR4 inhibitor TAK242 showed a similar effect as OP. In vivo, OP could alleviate cardiac ischemia/reperfusion injury and it ameliorated adverse cardiac remodeling. Consistent with in vitro studies, OP inhibited TLR4/MAPK and autophagy pathway and activated NRF2-dependent antioxidant pathways in vivo.

Conclusion
This study shows that OP binds to TLR4 to regulate oxidative stress and autophagy for protecting damaged cardiomyocytes, supporting that OP can be a potential therapeutic agent for MIRI.
NBR1-p62-Nrf2 mediates the anti-pulmonary fibrosis effects of protodioscin
Authors: Zeng Qian , Wen Bin-bin , Liu Xin , Luo Yong-yu , Hu Zhen-gang , Huang Lei , Zhang Xiao-hua , Huang Xiao-ting , Zhou Ting-ting , Sang Xiao-xue , Luo Yu-yang , Xiong Da-yan , Luo Zi-qiang , Liu Wei , Tang Si-yuan 
Published: April 2024

Abstract
Background
Idiopathic pulmonary fibrosis is a persistent disease of the lung interstitium for which there is no efficacious pharmacological therapy. Protodioscin, a steroidal saponin, possesses diverse pharmacological properties; however, its function in pulmonary fibrosis is yet to be established. Hence, in this investigation, it was attempted to figure out the anti-pulmonary fibrosis influences of protodioscin and its pharmacological properties related to oxidative stress.

Methods
A mouse lung fibrosis model was generated using tracheal injections of bleomycin, followed by intraperitoneal injection of different concentrations of protodioscin, and the levels of oxidative stress and fibrosis were detected in the lungs. Multiple fibroblasts were treated with TGF-β to induce their transition to myofibroblasts. It was attempted to quantify myofibroblast markers’ expression levels and reactive oxygen species levels as well as Nrf2 activation after co-incubation of TGF-β with fibroblasts and different concentrations of protodioscin. The influence of protodioscin on the expression and phosphorylation of p62, which is associated with Nrf2 activation, were detected, and p62 related genes were predicted by STRING database. The effects of Nrf2 inhibitor or silencing of the Nrf2, p62 and NBR1 genes, respectively, on the activation of Nrf2 by protodioscin were examined. The associations between p62, NBR1, and Keap1 in the activation of Nrf2 by protodioscin was demonstrated using a co-IP assay. Nrf2 inhibitor were used when protodioscin was treated in mice with pulmonary fibrosis and lung tissue fibrosis and oxidative stress levels were detected.

Results
In vivo, protodioscin decreased the levels of fibrosis markers and oxidative stress markers and activated Nrf2 in mice with pulmonary fibrosis, and these effects were inhibited by Nrf2 inhibitor. In vitro, protodioscin decreased the levels of myofibroblast markers and oxidative stress markers during myofibroblast transition and promoted Nrf2 downstream gene expression, with reversal of these effects after Nrf2, p62 and NBR1 genes were silenced or Nrf2 inhibitors were used, respectively. Protodioscin promoted the binding of NBR1 to p62 and Keap1, thereby reducing Keap1-Nrf2 binding.

Conclusion
The NBR1-p62-Nrf2 axis is targeted by protodioscin to reduce oxidative stress and inhibit pulmonary fibrosis.

Graphical Abstract
Molecular and phenotypic characteristics of Bardet-Biedl syndrome in Chinese patients
Authors: Gao Shiyang , Zhang Qianwen , Ding Yu , Wang Libo , Li Zhiying , Hu Feihan , Yao Ru-en , Yu Tingting , Chang Guoying , Wang Xiumin 
Published: April 2024

Abstract
Background
Bardet-Biedl syndrome (BBS) is a type of non-motile ciliopathy. To date, 26 genes have been reported to be associated with BBS. However, BBS is genetically heterogeneous, with significant clinical overlap with other ciliopathies, which complicates diagnosis. Disability and mortality rates are high in BBS patients; therefore, it is urgent to improve our understanding of BBS. Thus, our study aimed to describe the genotypic and phenotypic spectra of BBS in China and to elucidate genotype–phenotype correlations.

Methods
Twenty Chinese patients diagnosed with BBS were enrolled in this study. We compared the phenotypes of Chinese BBS patients in this study with those from other countries to analyze the phenotypic differences across patients worldwide. In addition, genotype–phenotype correlations were described for our cohort. We also summarized all previously reported cases of BBS in Chinese patients (71 patients) and identified common and specific genetic variants in the Chinese population.

Results
Twenty-eight variants, of which 10 are novel, in 5 different BBS-associated genes were identified in 20 Chinese BBS patients. By comparing the phenotypes of BBSome-coding genes (BBS2,7,9) with those of chaperonin-coding genes (BBS10,12), we found that patients with mutations in BBS10 and 12 had an earlier age of onset (1.10 Vs. 2.20, p < 0.01) and diagnosis (4.64 Vs. 13.17, p < 0.01), whereas patients with mutations in BBS2, 7, and 9 had a higher body mass index (28.35 Vs. 24.21, p < 0.05) and more vision problems (p < 0.05). Furthermore, in 91 Chinese BBS patients, mutations were predominant in BBS2 (28.89%) and BBS7 (15.56%), and the most frequent variants were in BBS2: c.534 + 1G > T (10/182 alleles) and BBS7: c.1002delT (7/182 alleles), marking a difference from the genotypic spectra of BBS reported abroad.

Conclusions
We recruited 20 Chinese patients with BBS for genetic and phenotypic analyses, and identified common clinical manifestations, pathogenic genes, and variants. We also described the phenotypic differences across patients worldwide and among different BBS-associated genes. This study involved the largest cohort of Chinese patients with BBS, and provides new insights into the distinctive clinical features of specific pathogenic variants.
The concept of resilience to Alzheimer’s Disease: current definitions and cellular and molecular mechanisms
Authors: de Vries Luuk E. , Huitinga Inge , Kessels Helmut W. , Swaab Dick F. , Verhaagen Joost 
Published: April 2024

AbstractSome individuals are able to maintain their cognitive abilities despite the presence of significant Alzheimer’s Disease (AD) neuropathological changes. This discrepancy between cognition and pathology has been labeled as resilience and has evolved into a widely debated concept. External factors such as cognitive stimulation are associated with resilience to AD, but the exact cellular and molecular underpinnings are not completely understood. In this review, we discuss the current definitions used in the field, highlight the translational approaches used to investigate resilience to AD and summarize the underlying cellular and molecular substrates of resilience that have been derived from human and animal studies, which have received more and more attention in the last few years. From these studies the picture emerges that resilient individuals are different from AD patients in terms of specific pathological species and their cellular reaction to AD pathology, which possibly helps to maintain cognition up to a certain tipping point. Studying these rare resilient individuals can be of great importance as it could pave the way to novel therapeutic avenues for AD.
Role of viscoelasticity in the appearance of low-Reynolds turbulence: considerations for modelling
Authors: Pajic-Lijakovic Ivana , Milivojevic Milan , McClintock Peter V. E. 
Published: April 2024

AbstractInertial effects caused by perturbations of dynamical equilibrium during the flow of soft matter constitute a hallmark of turbulence. Such perturbations are attributable to an imbalance between energy storage and energy dissipation. During the flow of Newtonian fluids, kinetic energy can be both stored and dissipated, while the flow of viscoelastic soft matter systems, such as polymer fluids, induces the accumulation of both kinetic and elastic energies. The accumulation of elastic energy causes local stiffening of stretched polymer chains, which can destabilise the flow. Migrating multicellular systems are hugely complex and are capable of self-regulating their viscoelasticity and mechanical stress generation, as well as controlling their energy storage and energy dissipation. Since the flow perturbation of viscoelastic systems is caused by the inhomogeneous accumulation of elastic energy, rather than of kinetic energy, turbulence can occur at low Reynolds numbers.This theoretical review is focused on clarifying the role of viscoelasticity in the appearance of low-Reynolds turbulence. Three types of system are considered and compared: (1) high-Reynolds turbulent flow of Newtonian fluids, (2) low and moderate-Reynolds flow of polymer solutions, and (3) migration of epithelial collectives, discussed in terms of two model systems. The models considered involve the fusion of two epithelial aggregates, and the free expansion of epithelial monolayers on a substrate matrix.
Mosaic derivative chromosomes at chorionic villi (CV) sampling are expression of genomic instability and precursors of cryptic disease-causing rearrangements: report of further four cases
Authors: Vitetta Giulia , Desiderio Laura , Baccolini Ilaria , Uliana Vera , Lanzoni Giulia , Ghi Tullio , Pilu Gianluigi , Ambrosini Enrico , Caggiati Patrizia , Barili Valeria , Trotta Anna Carmela , Liuti Maria Rosaria , Malpezzi Elisabetta , Pittalis Maria Carla , Percesepe Antonio 
Published: April 2024

AbstractMosaic chromosomal anomalies arising in the product of conception and the final fetal chromosomal arrangement are expression of complex biological mechanisms. The rescue of unbalanced chromosome with selection of the most viable cell line/s in the embryo and the unfavourable imbalances in placental tissues was documented in our previous paper and in the literature. We report four additional cases with mosaic derivative chromosomes in different feto-placental tissues, further showing the instability of an intermediate gross imbalance as a frequent mechanism of de novo cryptic deletions and duplications. In conclusion we underline how the extensive remodeling of unbalanced chromosomes in placental tissues represents the ‘backstage’ of de novo structural rearrangements, as the early phases of a long selection process that the genome undergo during embryogenesis.
Perioperative versus adjuvant S-1 plus oxaliplatin chemotherapy for stage II/III resectable gastric cancer (RESONANCE): a randomized, open-label, phase 3 trial
Authors: Wang Xinxin , Lu Canrong , Wei Bo , Li Shuo , Li Ziyu , Xue Yingwei , Ye Yingjiang , Zhang Zhongtao , Sun Yihong , Liang Han , Li Kai , Zhu Linghua , Zheng Zhichao , Zhou Yanbing , He Yulong , Li Fei , Wang Xin , Liang Pin , Huang Hua , Li Guoli , Shen Xian , Ji Jiafu , Tang Yun , Xu Zekuan , Chen Lin ,   on behalf of RESONANCE study group
Published: April 2024

AbstractEvidence from Europe shows that perioperative chemotherapy may be beneficial for the treatment of locally advanced gastric cancer, but reliable and robust data is lacking. To rectify this, the phase 3 RESONANCE trial investigated the efficacy and safety of S-1 plus oxaliplatin (SOX) as a perioperative chemotherapy regimen for gastric cancer. This randomized, open-label trial enrolled patients from 19 medical centers with stage II/III resectable gastric cancer who were centrally randomly assigned to either perioperative chemotherapy (PC) arm or adjuvant chemotherapy (AC) arm. Patients in the PC arm received two to four cycles of SOX followed by surgery and four to six cycles of SOX. Patients in the AC arm received upfront surgery and eight cycles of SOX. 386 patients in each group were enrolled and 756 (382 in PC and 374 in AC) were included in the mITT population. The three-year DFS rate was 61.7% in the PC arm and 53.8% in the AC arm (log-rank p = 0.019). The R0 resection rate in the PC arm was significantly higher than that in the AC arm (94.9% vs. 83.7%, p < 0.0001). There was no difference between two arms in surgical outcomes or postoperative complications. Safety-related data were like the known safety profile. In conclusion, from a clinical perspective, this trial indicated a trend towards higher three-year disease-free survival rate with perioperative SOX in stage II/III resectable gastric cancer with well-tolerated toxicity compared to adjuvant SOX, which might provide a theoretical basis for applying perioperative SOX in advanced gastric cancer patients. (ClinicalTrials.gov NCT01583361)