Schizandrin A attenuates early brain injury following subarachnoid hemorrhage through suppressing neuroinflammation.

BACKGROUND: Early brain injury (EBI) is the vital factor in determining the outcome of subarachnoid hemorrhage (SAH). Schizandrin A (Sch A), the bioactive ingredient extracted from Schisandra chinensis, has been proved to exert beneficial effects in multiple human diseases. However, the effect of Sch A on SAH remains unknown. The current study was designed to explored role and mechanism of Sch A in the pathophysiological process of EBI following SAH. METHOD: A total of 74 male C57BL/6 J mice were subjected to endovascular perforation to establish the SAH model. Different dosages of Sch A were administrated post-modeling. The post-modeling assessments included neurological test, brain water content, RT-PCR, immunofluorescence, Nissl staining. Oxygenated hemoglobin was introduced into microglia to establish a SAH model in vitro. RESULT: Sch A significantly alleviated SAH-induced brain edema and neurological impairment. Moreover, application of Sch A remarkably inhibited SAH-induced neuroinflammation, evidenced by the decreased microglial activation and downregulated TNF-α, IL-1ß and IL-6 and expression. Additionally, Sch A, both in vivo and in vitro, protected neurons against SAH-induced inflammatory injury. Mechanismly, administration of Sch A inhibited miR-155/NF-κB axis and attenuated neuroinflammation, as well as alleviating neuronal injury. CONCLUSION: Our data suggested that Sch A could attenuated EBI following SAH via modulating neuroinflammation. The anti-inflammatory effect was exerted, at least partly through the miR-155/NF-κB axis, which may shed light on a possible therapeutic target for SAH.

A Systematic Review of Application Progress on Machine Learning-Based Natural Language Processing in Breast Cancer over the Past 5 Years.

Artificial intelligence (AI) has been steadily developing in the medical field in the past few years, and AI-based applications have advanced cancer diagnosis. Breast cancer has a massive amount of data in oncology. There has been a high level of research enthusiasm to apply AI techniques to assist in breast cancer diagnosis and improve doctors' efficiency. However, the wise utilization of tedious breast cancer-related medical care is still challenging. Over the past few years, AI-based NLP applications have been increasingly proposed in breast cancer. In this systematic review, we conduct the review using preferred reporting items for systematic reviews and meta-analyses (PRISMA) and investigate the recent five years of literature in natural language processing (NLP)-based AI applications. This systematic review aims to uncover the recent trends in this area, close the research gap, and help doctors better understand the NLP application pipeline. We first conduct an initial literature search of 202 publications from Scopus, Web of Science, PubMed, Google Scholar, and the Association for Computational Linguistics (ACL) Anthology. Then, we screen the literature based on inclusion and exclusion criteria. Next, we categorize and analyze the advantages and disadvantages of the different machine learning models. We also discuss the current challenges, such as the lack of a public dataset. Furthermore, we suggest some promising future directions, including semi-supervised learning, active learning, and transfer learning.

Natural Language Processing Applications for Computer-Aided Diagnosis in Oncology.

In the era of big data, text-based medical data, such as electronic health records (EHR) and electronic medical records (EMR), are growing rapidly. EHR and EMR are collected from patients to record their basic information, lab tests, vital signs, clinical notes, and reports. EHR and EMR contain the helpful information to assist oncologists in computer-aided diagnosis and decision making. However, it is time consuming for doctors to extract the valuable information they need and analyze the information from the EHR and EMR data. Recently, more and more research works have applied natural language processing (NLP) techniques, i.e., rule-based, machine learning-based, and deep learning-based techniques, on the EHR and EMR data for computer-aided diagnosis in oncology. The objective of this review is to narratively review the recent progress in the area of NLP applications for computer-aided diagnosis in oncology. Moreover, we intend to reduce the research gap between artificial intelligence (AI) experts and clinical specialists to design better NLP applications. We originally identified 295 articles from the three electronic databases: PubMed, Google Scholar, and ACL Anthology; then, we removed the duplicated papers and manually screened the irrelevant papers based on the content of the abstract; finally, we included a total of 23 articles after the screening process of the literature review. Furthermore, we provided an in-depth analysis and categorized these studies into seven cancer types: breast cancer, lung cancer, liver cancer, prostate cancer, pancreatic cancer, colorectal cancer, and brain tumors. Additionally, we identified the current limitations of NLP applications on supporting the clinical practices and we suggest some promising future research directions in this paper.

Radiological classification of meningiomas with hemorrhagic onset and its clinical significance.

Meningiomas are the most common benign intracranial tumors and frequently present with a gradual onset of neurological deficits; conversely, their acute presentation with hemorrhagic onset appears to be a rare event. Nonetheless, as early surgical evacuation is the foundation of treatment, a timely diagnosis of this rare type of intracranial hemorrhage is necessary. The purpose of the present single-center study was to investigate the radiological characteristics and propose a new bleeding classification for guiding the diagnosis and treatment. A total of 19 patients consecutively diagnosed with hemorrhagic meningioma were enrolled in this retrospective study. Intracranial extra-axial mass, tumor-associated hemorrhage and peritumoral brain edema were the three main radiological features of the hemorrhagic meningiomas. The site of tumor-associated hemorrhage included the peritumoral space, subarachnoid space, subdural space, brain parenchyma and/or intratumor region. Based on the anatomical relationship between meningioma and hematoma, the spontaneous hemorrhage stemming from meningiomas was further summarized into three bleeding patterns involving purely intratumoral hemorrhage (type I), purely extratumoral hemorrhage (type II) and combined intra/extratumoral hemorrhage (type III); furthermore, the type III hemorrhage usually came from type I bleeding that extended into the surrounding regions. The symptoms in type I patients were generally mild and early surgery was performed following adequate preoperative evaluations. The symptoms in type II patients were mild in certain cases and moderate to severe in others, so early or emergency surgery was chosen according to the clinical status of the patient. Almost all type III patients had moderate to severe symptoms and these patients usually required emergency surgery. In addition, patients with different bleeding types may have different pathological mechanisms underlying the tumor bleeding. Apart from being convenient for diagnosis, this concise and practical bleeding classification may aid in the selection of the treatment strategy and facilitate the understanding of the associated mechanisms.

First-line contact aspiration versus first-line stent retriever for acute posterior circulation strokes: an updated meta-analysis.

BACKGROUND: Both stent retriever (SR) and contact aspiration (CA) are widely used as first-line strategies for acute posterior circulation strokes (PCS). However, it is still unclear how CA and SR compare as the first-line treatment of acute PCS. Several new studies have been published recently, so we aimed to perform an updated meta-analysis. METHODS: The meta-analysis was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement. Random-effects models were performed to pool the outcomes and the value of I2 was calculated to assess the heterogeneity. RESULTS: Ten observational studies with 1189 patients were included, among whom 492 received first-line CA and 697 received first-line SR. The pooled results revealed that first-line CA could achieve a significantly higher proportion of modified Thrombolysis In Cerebral Infarction (mTICI) 2b/3 (OR 1.90, 95% CI 1.33 to 2.71, I2=0%), mTICI 3 (OR 1.95, 95% CI 1.15 to 3.31, I2=59.6%), first-pass effect (OR 2.91, 95% CI 1.51 to 5.58, I2=0%), lower incidence of new-territory embolic events (OR 0.20, 95% CI 0.05 to 0.83, I2=0%), and shorter procedure time (mean difference -29.4 min, 95% CI -46.8 to -12.0 min, I2=62.8%) compared with first-line SR. At 90-day follow-up, patients subjected to first-line CA showed a higher functional independence (modified Rankin Scale score 0-2; OR 1.38, 95% CI 1.01 to 1.87, I2=23.5%) and a lower mortality (OR 0.71, 95% CI 0.50 to 1.00, p=0.050, I2=0%) than those subjected to first-line SR. CONCLUSIONS: This meta-analysis suggests that the first-line CA strategy could achieve better recanalization and clinical outcomes for acute PCS than first-line SR. Limited by the quality of included studies, this conclusion should be drawn with caution.

LncRNA SOX2-OT regulates miR-192-5p/RAB2A axis and ERK pathway to promote glioblastoma cell growth.

Glioblastoma (GBM) is the most frequent tumor in the central nervous system. Long non-coding RNAs (lncRNAs) have been widely accepted as essential participators in cancer progression. Nonetheless, the specific role and mechanism of lncRNA SRY-box transcription factor 2 overlapping transcript (SOX2-OT) in GBM have not been studied. We evaluated expression levels of SOX2-OT, miR-192-5p and Ras-related protein Rab-2A (RAB2A) in GBM cells via qRT-PCR. To investigate the roles of SOX2-OT in GBM cells, CCK-8, JC-1, EdU, and western blot assays were performed. The connection among SOX2-OT, miR-192-5p and RAB2A in GBM cells was explored through pull down, luciferase reporter, and RIP assays. Western blot and qRT-PCR were employed to analyze the activity of extracellular-signal-regulated kinase (ERK) signaling pathway. SOX2-OT expression was higher in GBM cell lines than in normal cells. SOX2-OT knockdown repressed proliferation and promoted apoptosis of GBM cells. Mechanism assays revealed that SOX2-OT could sponge miR-192-5p. Moreover, RAB2A was certified to be the target gene of miR-192-5p. Overexpression of RAB2A reversed the repressive function of SOX2-OT knockdown on GBM cell growth. Furthermore, SOX2-OT activated ERK signaling pathway in GBM cells. SOX2-OT regulated miR-192-5p/RAB2A axis and ERK pathway to promote GBM cell growth.

Lumican silencing alleviates tumor necrosis factor-α-induced nucleus pulposus cell inflammation and senescence by inhibiting apoptosis signal regulating kinase 1/p38 signaling pathway via inactivating Fas ligand expression.

A recent study has reported that lumican (LUM) is expressed at a high level in the nucleus pulposus specimens from herniated lumbar disc, without description of the specific mechanism. This study was designed to investigate the function and mechanism of LUM in intervertebral disc degeneration (IDD). In this study, human nucleus pulposus cells (hNPCs) cells were challenged with tumor necrosis factor (TNF)-α to establish the IDD in vitro model. After LUM silencing, cell viability was detected using CCK-8 kit, and the expression of inflammatory factors was evaluated using RT-qPCR and ELISA. Flow cytometry and ß-galactosidase staining were used to determine cell cycle and cell senescence. The expression of cycle and senescence-related proteins was evaluated with western blotting. Then, Fas ligand (FasL) was overexpressed and proteins in apoptosis signal regulating kinase 1 (ASK1)/p38 signaling were tested. Finally, GS-4997, an inhibitor of ASK1, was used to explore the regulatory effects of LUM on ASK1/p38 signaling in TNF-α-induced hNPCs. Results indicated that LUM expression was upregulated in TNF-α-challenged hNPCs. LUM gene interference mitigated TNF-α-induced inflammatory response, cell cycle arrest, and senescence of hNPCs. It was then found that LUM silencing could inhibit ASK1/p38 signaling in TNF-α-treated hNPCs, which was reversed by FasL overexpression. Additionally, ASK1/p38 participated in the mediation by LUM of TNF-α-induced inflammation, cell cycle arrest, and senescence of hNPCs. To conclude, interference with LUM effectively mitigated TNF-α-induced inflammatory response, cell cycle arrest, and cell senescence. Further experiments showed the involvement of ASK1/p38 pathway in LUM-mediated NP cell phenotypes through FasL.

Hemorrhagic abdominal pseudocyst following ventriculoperitoneal shunt: a case report.

BACKGROUND: Abdominal cerebrospinal fluid (CSF) pseudocyst is an uncommon but important complication of ventriculoperitoneal (VP) shunts. While individual articles have reported many cases of abdominal CSF pseudocyst following VP shunts, no case of a hemorrhagic abdominal pseudocyst after VP shunts has been reported so far. CASE PRESENTATION: This article reports a 68-year-old woman with a 4-month history of progressive abdominal pain and distention. She denied any additional symptoms. A VP shunt was performed 15 years earlier to treat idiopathic normal pressure hydrocephalus and no other abdominal surgery was performed. Physical examination revealed an elastic palpable mass in her right lower abdomen, which was dull to percussion. Abdominal computed tomography (CT) scan indicated a large cystic collection of homogenous iso-density fluid in the right lower abdominal region with clear margins. The distal segment of the peritoneal shunt catheter was located within the cystic mass. Abdominal CSF pseudocyst was highly suspected as a diagnosis. Laparoscopic cyst drainage with removal of the whole cystic mass was performed, 15-cm cyst which found with thick walls and organized chronic hematic content. No responsible vessel for the cyst hemorrhage was identified. No further shunt revision was placed. Histological examination showed that the cyst wall consisted of outer fibrous tissue and inner granulation tissue without epithelial lining, and the cystic content was chronic hematoma. The patient had an uneventful postoperative course and remained asymptomatic for 8-mo follow-up. CONCLUSION: To the best of our knowledge, this is the first report of hemorrhagic onset in the abdominal pseudocyst following VP shunt. Such special condition can accelerate the appearance of clinical signs of the abdominal pseudocyst after VP shunts, and its mechanisms may be similar to the evolution of subdural effusion into chronic subdural hematoma (CSDH).

Long-term application of hydroxychloroquine could not prevent the infection of COVID-19.

INTRODUCTION: Current pandemic of the coronavirus induced disease 2019 (COVID-19) presents an urgent issue to the world due to lack of vaccine and medication. Hydroxychloroquine (HCQ) has generated a lot of controversies whether it is effective in prevention and treatment of COVID-19. Current report presents a 63-year-old woman who has taken HCQ for many years but still infected by COVID-19. CASE PRESENTATION: A patient with rheumatoid arthritis came to the clinic with fever and sore throat. The patient has been treated with 200 mg HCQ per day since 2016. Laboratory tests showed that the patient had lymphopenia, increased levels of high-sensitive C-reactive protein (hs-CRP) and serum Interleukin-6 (IL-6). Chest radiography showed that the patient had pneumonia. Throat swab test confirmed COVID-19 positive. On admission, she was treated with nebulized interferon alfa-2b, oral Lopinavir/Ritonavir, and ceftriaxone sodium for the COVID-19 in addition to HCQ. The patient stayed in hospital for 18 days, recovered from oxygen intake, and eventually discharged from hospital. Follow up investigation showed the patient developed antibody against COVID-19. CONCLUSIONS: Long-term application of HCQ could not prevent COVID-19 infection, but whether HCQ exerts benefit to alleviation of clinical symptoms and duration of hospital stays remains to be further investigated.

Neuroprotective effect of berberine against learning and memory deficits in diffuse axonal injury.

The aim of the present study was to assess the neuroprotective effect of berberine against learning and memory deficits in diffuse axonal injury (DAI). DAI rats were orally gavaged with berberine at a dose of 200 mg/kg of body weight for 4 weeks. Behavioral tests were used to analyze the neuroprotective effect of berberine against DAI-induced learning and memory deficits. In the present study, treatment with berberine significantly protected against DAI-induced inhibition of learning and memory in rats. Notably, berberine significantly suppressed the levels of tumor necrosis factor, interleukin-1ß and monocyte chemoattractant protein-1, as well as reduced the protein expression levels of nuclear factor-κB, Bcl-2-associated X protein and cytochrome c in DAI rats. In addition, berberine significantly suppressed the protein expression of p38 mitogen-activated protein kinase, activating transcription factor 2 and vascular endothelial growth factor in DAI rats. These results suggested that berberine exhibited a neuroprotective effect against learning and memory deficits in severe DAI through the suppression of inflammation, angiogenesis and apoptosis in a rat model.

An Underlying Pathological Mechanism of Meningiomas with Intratumoral Hemorrhage: Undifferentiated Microvessels.

BACKGROUND: Meningiomas usually present with a gradual onset of symptoms, and their acute presentation with a hemorrhagic event appears to be a rare condition. Although many clinical features of such a condition have been characterized, pathophysiological mechanisms underlying the bleeding remain unclear, and some contradictory results have been reported. The value of tumor vascularity as an index for the bleeding propensity of meningiomas is inconsistent. We sought to identify whether meningiomas have different types of blood vessels, and to explore the association of the different tumor vessels with intratumoral hemorrhage. METHODS: Six patients with meningioma with acute onset due to intratumoral hemorrhage were identified, and 12 nonhemorrhagic meningiomas were matched according to specific clinical data. The characteristics of tumor vessels were examined through immunohistochemical staining of CD31, CD34, and smooth muscle actin (SMA). The number of stained vessels was counted and compared between the 2 groups. RESULTS: Two distinct types of blood vessels were determined in all meningiomas: undifferentiated (CD31+/CD34-) and differentiated (CD31+/CD34+) vessels, and most differentiated vessels were covered by pericytes marked by SMA. However, only the mean number of undifferentiated vessels in hemorrhagic meningiomas was significantly higher than that in controls (15.3 ± 4.9 vs. 6.4 ± 3.6; P < 0.01). Neither the number of differentiated vessels nor the total number of tumor vessels were significantly different between the 2 groups (P > 0.05). CONCLUSIONS: Our results suggest that tumor vasculature in meningiomas is heterogeneous, and that the undifferentiated vessels may play a pivotal role in the spontaneous intratumoral hemorrhage from meningiomas.

Where are we in the modelling of traumatic brain injury? Models complicated by secondary brain insults.

BACKGROUND: Traumatic brain injury (TBI) contributes to a substantial number of deaths and cases of disability. Despite well-established experimental models and years of carefully conducted research, a clinical therapeutic breakthrough in TBI has lagged. This may be due, in part, to the discrepancies between commonly used experimental models and clinical scenarios. METHOD: Secondary insults, such as hypotension and hypoxemia, have been well demonstrated as powerful determinants of outcomes from TBI. Despite the frequency of secondary insults in patients with TBI, they are rarely incorporated into most existing models of TBI. This review focuses on the combined injury models, especially coupled with systemic secondary insults, and aims to provide a new view to guiding future research endeavors in this field. RESULTS: A growing number of experimental models of TBI complicated by certain secondary insult have been gradually introduced and characterized. Correspondingly, the pathophysiological changes following combined injuries and the interactive effects of primary injury with secondary insults can be studied more in-depth. CONCLUSION: A more complete understanding of the interactions between the injured brain and secondary insults represents a potentially fruitful avenue that may increase the likelihood of developing effective therapies. Experimental models of TBI should not only attempt to model the focal or diffuse changes resulting from external forces, but also integrate, when appropriate, secondary insults reminiscent of human situations.

[Effect of gefinitib on airway mucus hypersecretion induced by acrolein in rats].

OBJECTIVE: To test the effect of gefinitib, an EGFR-TKI, on airway mucus hypersecretion induced by acrolein in rats. METHODS: Thirty six rats were randomly divided into six groups, each with six rats. Group A did not get any intervention; group B had airway mucus hypersecretion induced by inhaled acrelein; Gefitinib intervention was given to group C, D, and E, with a dose of 10 mg/kg,20 mg/kg, and 30 mg/kg of gefitnib administered by gavage, respectively, 30 min before exposure to acrolein inhalation; group F served as a control group, with gefitinib (30 mg/kg) administered by gavage 30 min before exposure to saline inhalation. After three weeks, the rats were sacrificed. The lung tissue sections were obtained. The immunohistochemistry and RT-PCR were performed to detect the MUC5AC and its mRNA expression. The EGFR was detected by immunohistochemical staining. The goblet cells were identified with Alician Blue-periodic Acid Schiff (AB-PAS). RESULTS: Overexpression of MUC5AC, EGFR and increased goblet cells in the lungs of the rats were found in the rats exposed to acrolein inhalations. Gefitinib intervention inhibited the expression of MUC5AC and the increase of goblet cells induced by acrolein. Gefitinib also reduced the expression of EGFR in the lungs. CONCLUSION: Acrolein increases the expression of MUC5AC through activating EGFR, which indicates that EGFR-TKI such as gefitinib can be useful in the treatment of mucus hypersecretion by regulating the signal transduction pathways of EGFR.

[Transnasal-sphenoided endosurgical and microsurgical technique of pituitary adenometomies].

OBJECTIVE: To evaluate the surgical technique of pituitary adenomas by naso-sphenoid way and the prevention of complication. METHOD: The pituitary adenomas in 19 cases were removed under endoscope and microscope by the transnasosphenoided way. Sphenoid-saddle base was restructed with lip-tendon-membrane and the nasal separate bone. RESULT: Seventeen cases had entire resection in the 19 patients. Two cases had subtotal resection. The symptoms were improved with no sever complications in 19 cases during the period of 3-36 months follow-up and no recovery in 17 cases. CONCLUSION: lt is a effective surgical technique that the pituitary neoplasms are removed by nasosphenoidal way under the endoscope and microscope with the alcohol for preventing the tumor recovery and with the lip-tendon-membrane and nasal separate bone for restructing the saddle base.