简介：AbstractIn modern society, subarachnoid hemorrhage, mostly caused by intracranial aneurysm rupture, is accompanied by high disability and mortality rate, which has become a major threat to human health. Till now, the etiology of intracranial aneurysm has not been entirely clarified. In recent years, more and more studies focus on the relationship between hemodynamics and intracranial aneurysm. Under the physiological condition, the mechanical force produced by the stable blood flow in the blood vessels keeps balance with the structure of the blood vessels. When the blood vessels are stimulated by the continuous abnormal blood flow, the functional structure of the blood vessels changes, which becomes the pathophysiological basis of the inflammation and atherosclerosis of the blood vessels and further promotes the occurrence and development of the intracranial aneurysm. This review will focus on the relationship between hemodynamics and intracranial aneurysms, will discuss the mechanism of occurrence and development of intracranial aneurysms, and will provide a new perspective for the research and treatment of intracranial aneurysms.

简介：AbstractMany factors can cause inner ear injury, such as noise exposure, chemicals, viral infection, and radiation. The main pathological manifestations of inner ear injury are local hypoxia-ischemia, micro-trauma, and an increased level of reactive oxygen species and inflammatory mediators. The contribution of the inflammatory response to the mediation of cochlear and vestibular pathologies has received increasing attention in recent years. Aseptic inflammation can devastate audition and balance, which can lead to many typical clinical inner ear diseases. In this review, we will discuss the most pertinent and recent research on inflammatory mechanisms in inner ear injury. We will also discuss the pathophysiology of some common and significant ear diseases, such as sudden sensorineural hearing loss, age-related hearing loss, noise-induced hearing loss, and Meniere’s disease.

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简介：AbstractMammalian follicles are composed of oocytes, granulosa cells, and theca cells. Theca cells form in the secondary follicles, maintaining follicular structural integrity and secreting steroid hormones. Two main sources of theca cells exist: Wilms tumor 1 positive (Wt1+) cells native to the ovary and Gli1+ mesenchymal cells migrated from the mesonephros. Normal folliculogenesis is a process where oocytes, granulosa cells, and theca cells constantly interact with and support each other through autocrine and paracrine mechanisms. The proliferation and differentiation of theca cells are regulated by oocyte-derived factors, including growth development factor 9 and bone morphogenetic protein 15, and granulosa cell-derived factors, including desert hedgehog, Indian hedgehog, kit ligand, insulin-like growth factor 1, as well as hormones such as insulin and growth hormones. Current research on the origin of theca cells is limited. Identifying the origin of theca cells will help us to systematically elaborate the mechanisms of follicular formation and development.

简介：AbstractLung cancer is a malignant tumor characterized by a rapid proliferation rate, less survivability, high mortality, and metastatic potential. This review focuses on updated research about the clinical application of traditional Chinese medicine (TCM) as an adjuvant therapy to lung cancer treatment and the mechanisms of TCM effect on lung cancer in vitro and in vivo. We summarized the recent 5 years of different research progress on clinical applications and antitumor mechanisms of TCM in the treatment of lung cancer. As a potent adjuvant therapy, TCM could enhance conventional treatments (chemotherapy, radiation therapy, and epidermal growth factor receptors [EGFRs] tyrosine kinase inhibitors [TKIs]) effects as well as provide synergistic effects, enhance chemotherapy drugs chemosensitivity, reverse drug resistance, reduce adverse reactions and toxicity, relieve patients’ pain and improve quality of life (QOL). After treating with TCM, lung cancer cells will induce apoptosis and/or autophagy, suppress metastasis, impact immune reaction, and therapeutic effect of EGFR-TKIs. Therefore, TCM is a promisingly potent adjuvant therapy in the treatment of lung cancer and its multiple mechanisms are worthy of an in-depth study.

简介：AbstractCell death occurs in various tissues and organs in the body. It is a physiological or pathological process that has different effects. It is of great significance in maintaining the morphological function of cells and clearing abnormal cells. Pyroptosis, apoptosis, and necrosis are all modes of cell death that have been studied extensively by many experts and scholars, including studies on their effects on the liver, kidney, the heart, other organs, and even the whole body. The heart, as the most important organ of the body, should be a particular focus. This review summarizes the mechanisms underlying the various cell death modes and the relationship between the various mechanisms and heart diseases. The current research status for heart therapy is discussed from the perspective of pathogenesis.

简介：AbstractPost-traumatic osteomyelitis (PTO) is a worldwide problem in the field of orthopaedic trauma. So far, there is no ideal treatment or consensus-based gold standard for its management. This paper reviews the representative literature focusing on PTO, mainly from the following four aspects: (1) the pathophysiological mechanism of PTO and the interaction mechanism between bacteria and the body, including fracture stress, different components of internal fixation devices, immune response, occurrence and development mechanisms of inflammation in PTO, as well as the occurrence and development mechanisms of PTO in skeletal system; (2) clinical classification, mainly the etiological classification, histological classification, anatomical classification and the newly proposed new classifications (a brief analysis of their scope and limitations); (3) imaging diagnosis, including non-invasive examination and invasive examination (this paper discusses their advantages and disadvantages respectively, and briefly compares the sensitivity and effectiveness of the current examinations); and (4) strategies, including antibiotic administration, surgical choices and other treatment programs. Based on the above-mentioned four aspects, we try to put forward some noteworthy sections, in order to make the existing opinions more specific.

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简介：AbstractBackground:Acute mural dissection of the anterior wall of the internal carotid artery which may contribute to the development of blood blister-like aneurysms (BBLAs) was postulated, and stenting or flow diversion treatment across the soi-disant aneurysm was reported in this study.Methods:From December 2016 to December 2018, 8 patients presenting with subarachnoid hemorrhage (SAH) due to BBLA were subjected to endovascular treatment with stent-assisted coiling. Clinical outcomes were evaluated using a clinical outcome score scale.Results:Based on angiograms, pathologic change involving the supraclinoid segments of the internal carotid artery (ICA) adjacent to BBLA was found in all patients. This pathologic change meant a focal dissection of the supraclinoid segment of the ICA which constituted the pathogenesis of BBLAs. Closed-cell, open-cell, and braided stents were used in 1, 1, and 6 patients, respectively. Complete obliteration was achieved following endovascular treatment among all 8 patients harboring BBLA. One re-bleeding successive to a closed-cell stent across the aneurysmal neck was observed. Follow-up angiograms revealed stable complete exclusion of all BBLAs from the parent vessel at 3 to 8 months. All patients had a favorable clinical outcome score of 0-1.Conclusions:Acute dissection of a focal point of the intracranial vessels underlies the development of BBLAs. Open-cell and braided-cell stent-assisted coiling may constitute appropriate treatment due to good apposition against the vascular walls. Adjunctive coils may facilitate immediate complete occlusion of BBLAs.

简介：AbstractCoronavirus disease 2019 is a major threat to public health globally. Though its pathogenesis has not been fully elucidated, angiotensin-converting enzyme 2 (ACE2) has been recently identified as a receptor for the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the cell. Here, we aimed to clarify the potential role of ACE2 in SARS-CoV-2-induced acute lung injury and its underlying mechanism. As a receptor for coronavirus, ACE2 mediates the entry of SARS-CoV-2 into cells in a similar way as for severe acute respiratory syndrome coronavirus (SARS-CoV). The high binding affinity of SARS-CoV-2 to ACE2 correlates with its efficient spread among humans. On the other hand, ACE2 negatively regulates the renin-angiotensin-aldosterone system (RAAS) primarily by converting angiotensin II to angiotensin 1-7, which exerts a beneficial effect on coronavirus-induced acute lung injury. Human recombinant ACE2 has been considered as a potential therapy for SARS-CoV-2 by blocking virus entry and redressing the imbalance of RAAS in SARS-CoV-2 infection. The level of ACE2 expression can be upregulated by treatment with an ACE inhibitor (ACEI) or angiotensin II type 1 receptor blocker (ARB). To date, no evidence shows that ACEIs or ARBs increase the susceptibility and mortality of patients infected with SARS-CoV-2, and hence, it is not advisable to discontinue such drugs in patients with cardiovascular disease.

简介：AbstractPurpose:Injuries are one of the leading causes of death and lead to a high social and financial burden. Injury patterns can vary significantly among different age groups and body regions. This study aimed to evaluate the relationship between mechanism of injury, patient comorbidities and severity of injuries. Methods: The study included trauma patients from July 2016 to June 2018, who were admitted to Sina Hospital, Tehran, Iran. The inclusion criteria were all injured patients who had at least one of the following: hospital length of stay more than 24 h, death in hospital, and transfer from the intensive care unit of another hospital. Data collection was performed using the National Trauma Registry of Iran minimum dataset.Results:The most common injury mechanism was road traffic injuries (49.0%), followed by falls (25.5%). The mean age of those who fell was significantly higher in comparison with other mechanisms (p < 0.001). Severe extremity injuries occurred more often in the fall group than in the vehicle collision group (69.0% vs. 43.5%, p < 0.001). Moreover, cases of severe multiple trauma were higher amongst vehicle collisions than injuries caused by falls (27.8% vs. 12.9%, p = 0.003).Conclusion:Comparing falls with motor vehicle collisions, patients who fell were older and sustained more extremity injuries. Patients injured by motor vehicle collision were more likely to have sustained multiple trauma than those presenting with falls. Recognition of the relationship between mechanisms and consequences of injuries may lead to more effective interventions.

简介：AbstractObjective:Premature ovarian failure (POF) is a disease characterized by irregular menstruation and results in infertility which markedly affects the reproductive health of women. The Salvia miltiorrhiza-Codonopsis pilosula drug pair is effective at treating POF; however, knowledge of the mechanisms of S. miltiorrhiza-C. pilosula in the treatment of POF is lacking. Thus, we carried out network pharmacology and molecular docking to clarify the mechanisms of this drug pair.Methods:The core components and targets of S. miltiorrhiza-C. pilosula were obtained using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database and UniProt database, and the disease targets related to POF were searched using different tools to obtain the overlapping target genes of S. miltiorrhiza and C. pilosula. A protein interaction network of the intersection target was constructed using STRING database, and the network of "traditional Chinese medicine-active ingredient-intersection target-disease" and "pathways-targets" was constructed using Cytoscape 3.8.0. The DAVID online tool was also used to determine the gene ontology functions and Kyoto Encyclopedia of Genes and Genomes pathways associated with the intersection target genes. Finally, the binding ability of the drug to the active components and potential targets were predicted using molecular docking.Results:S. miltiorrhizae-C. pilosula had 72 active components, 128 targets, 3,775 POF targets, and 106 common targets. The potential targets were mainly related to the biological processes of DNA-binding transcription factor binding, RNA polymerase II-specific DNA-binding transcription factor binding, transcription factor activity, steroid receptor activity, and hypoxia response. Further, the Kyoto Encyclopedia of Genes and Genomes enrichment pathways included PI3K-Akt signaling pathway, apoptosis, interleukin (IL)-17 signaling pathway, relaxin signaling pathway, and other biological pathways.Conclusion(s):S. miltiorrhiza-C. pilosula can inhibit ovarian granulosa cell apoptosis and improve ovarian hemodynamics through multiple targets and multiple pathways and help treat POF.

简介：AbstractBackground:Depression is a common mental illness in childhood and adolescence, with an incidence of 4%-5%; it can lead to impairments in learning and social functioning. Transcutaneous auricular vagus nerve stimulation (taVNS) is a commonly used method of auricular acupuncture point stimulation, which is regarded as an effective treatment for adults with depression. The aim of this study was to investigate the efficacy and mechanism of taVNS for adolescents with mild to moderate depression.Methods:This randomized controlled clinical trial will include 120 patients aged 12-16 years, all of whom are diagnosed with mild to moderate depression. Patients will be randomly assigned to a taVNS group and a drug control group (sertraline hydrochloride) at a ratio of 1:1. Patients will be evaluated using the 17-item Hamilton Depression Scale, Hamilton Anxiety Rating Scale, Self-Rating Depression Scale, Self-Rating Anxiety Scale, and Pittsburgh Sleep Quality Index scores at baseline, as well as at the 2nd, 4th, 6th, 8th, and 12th weeks. To investigate the underlying neural mechanisms of taVNS treatment from the perspective of the default mode network, multimodal magnetic resonance imaging (MRI; i.e., structural MRI [sMRI], resting state MRI [rsMRI], and pseudocontinuous arterial spin-labeled [pcASL] MRI) will be used to compare cerebral images among groups. MRI data will also be collected from 40 healthy volunteers to assess whether the participants exhibit normal development of structural and functional components.Discussion:Depression is the most common mental disorder in adolescence. Drug treatment can improve depression symptoms; however, the side effects of drug treatments are often severe. This study proposes a simple physiotherapy that aims to treat adolescents with mild to moderate depression. The mechanism of taVNS in the treatment of depression will also be investigated. The results of this study will provide evidence to guide the application of taVNS in adolescents with depression.

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简介：AbstractBackground:Non-coding RNAs have attracted considerable attention for their vital role in cancer. The purpose of this study was to determine the effects of non-coding RNAs on hepatocellular carcinoma (HCC) and reveal their regulatory mechanism in the pathophysiological process.Methods:We measured the expression of mucin 1 (MUC1) and miR-485-5p in tissues from 15 HCC patients and in liver cancer cell lines by quantitative real-time polymerase chain reaction and Western blot, screened for aberrantly expressed microRNAs (miRNAs) by miRNA microarrays. Bioinformatics tools were used to find the miRNA and circular RNA that regulated MUC1, which were validated by RNA immunoprecipitation assay and luciferase reporter assay. Cell counting kit-8, Transwell assays, and flow cytometry were used to conduct functional experiments. Proteins were examined by western blot and immunohistochemical staining assays. Significant differences between groups were estimated using the one-way analysis of variance. A P < 0.05 was considered statistically significant.Results:MUC1 was overexpressed in HCC tissues compared with that in paratumor tissues (normal vs. tumor, 1.007 ± 0.215 vs. 75.213 ± 18.403, t = 18.401, P < 0.001) while miR-485-5p was down-regulated (normal vs. tumor, 4.894 ± 0.684 vs. 1.586 ± 0.398, t= 16.191, P < 0.001). Inhibition of miR-485-5p promoted cell proliferation (73.33% ± 5.13% vs. 41.33% ± 3.51%, t= 8.913, P < 0.001), migration (102 ± 8 cells vs. 46 ± 8 cells, t= 8.681, P < 0.001), invasion (59 ± 7 cells vs. 28 ± 2 cells, t = 8.034, P < 0.01), and suppressed apoptosis (22.64% ± 6.97% vs. 36.33% ± 3.96%, t = 2.958, P < 0.05) of HepG2 cells with which MUC1 is knocked down. Mechanically, miR-485-5p binds to MUC1, while circHECTD1 binds to miR-485-5p, resulting in the indirect up-regulation of the MUC1 level.Conclusions:Our findings reveal that circHECTD1 facilitates HCC progression by sponging miR-485-5p to up-regulate MUC1.