Sex Differences in Outcomes after Endovascular Thrombectomy for Patients with Acute Ischemic Stroke.

INTRODUCTION: Endovascular thrombectomy (EVT) is the standard of care for patients with large-vessel occlusion acute ischemic stroke (AIS). There may be differing recanalization effectiveness based on patients' sex, and understanding such variations can improve patient outcomes by adjusting for differences. We aimed to assess the sex differences in outcome after EVT for patients with AIS. METHODS: We retrospectively analyzed 250 consecutive AIS patients who underwent EVT from July 2019 to February 2022 across two large comprehensive tertiary care stroke centers in China. Outcomes of male patients were compared to females, where poor outcome was defined as a modified Rankin score (mRS) of 3-6 at 90 days. RESULTS: Male patients had higher rates of symptomatic intracranial hemorrhage (sICH) (12.50% vs. 4.05%, p = 0.042) and higher hospitalization costs (114,541.08 vs. 105,790.27 RMB, p = 0.024). Male patients also had a longer median onset-to-needle time (ONT) (146.00 [104.00, 202.00] versus 120.00 [99.25, 144.75], p = 0.026). However, there were no differences in hospitalization length (p = 0.251), 90-day favorable outcome (p = 0.952), and 90-day mortality (p = 0.931) between the sexes. CONCLUSION: Female patients had lower hospitalization costs and sICH rates than males after EVT for AIS. Identifying such differences and implementing measures, including adaptations to workflow optimization, would help to reduce the ONT and last known normal-to-puncture time seen in males to improve patient outcomes. Despite such variations, favorable outcomes and mortality are similar in female and male AIS patients.

The Impact of Visceral Adiposity on Testosterone Levels in American Adult Men: A Cross-Sectional Analysis.

BACKGROUND Testosterone decline and deficiency importantly affect men's health, and may be associated with excessive deposition of visceral adipose tissue. This study was conducted to explore the association between visceral adiposity index (VAI) and testosterone level. MATERIAL AND METHODS A total of 1551 participants from the NHANES 2013-2013 cycle and 2015-2016 cycle were selected for our analyses. The VAI index was calculated based on waist circumference (WC), body mass index (BMI), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-c), and serum testosterone was measured by isotope dilution liquid chromatography tandem mass spectrometry. Multivariable adjusted linear and logistic regression were utilized to investigate the associations between VAI index and testosterone level and testosterone deficiency, respectively. Additionally, subgroup analyses were performed to identify sensitive populations. RESULTS A total of 1551 participants with mean VAI index of 1.95±0.08 were eligible for our analysis. After adjusting for all potential cofounders, men with higher VAI index displayed a lower level of total testosterone level (ß: -11.74, 95% CI: -17.33, -6.15, P<0.0001), and higher risk of testosterone deficiency (OR: 1.24, 95% CI: 1.09, 1.40, P=0.0022). Comparing to VAI quartile 1, quartile 4 showed the most decreased testosterone level (ß: -94.59, 95% CI: -130.04, -59.14, P<0.0001), and highest risk of testosterone deficiency (OR: 5.07, 95% CI: 2.41,10.63, P<0.0001). Subgroup analysis demonstrated that VAI index was strongly related to testosterone level and testosterone deficiency in aged and obese men. CONCLUSIONS Men with higher VAI index displayed lower testosterone levels and higher risk of testosterone deficiency, especially in aged men and obese men.

Awake craniotomy during pregnancy: A systematic review of the published literature.

Neurosurgical pathologies in pregnancy pose significant complications for the patient and fetus, and physiological stressors during anesthesia and surgery may lead to maternal and fetal complications. Awake craniotomy (AC) can preserve neurological functions while reducing exposure to anesthetic medications. We reviewed the literature investigating AC during pregnancy. PubMed, Scopus, and Web of Science databases were searched from the inception to February 7th, 2023, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Studies in English investigating AC in pregnant patients were included in the final analysis. Nine studies composed of nine pregnant patients and ten fetuses (one twin-gestating patient) were included. Glioma was the most common pathology reported in six (66.7%) patients. The frontal lobe was the most involved region (4 cases, 44.4%), followed by the frontoparietal region (2 cases, 22.2%). The awake-awake-awake approach was the most common protocol in seven (77.8%) studies. The shortest operation time was two hours, whereas the longest one was eight hours and 29 min. The mean gestational age at diagnosis was 13.6 ± 6.5 (2-22) and 19.6 ± 6.9 (9-30) weeks at craniotomy. Seven (77.8%) studies employed intraoperative fetal heart rate monitoring. None of the AC procedures was converted to general anesthesia. Ten healthy babies were delivered from patients who underwent AC. In experienced hands, AC for resection of cranial lesions of eloquent areas in pregnant patients is safe and feasible and does not alter the pregnancy outcome.

Hyperuricemia induces lipid disturbances mediated by LPCAT3 upregulation in the liver.

Potential underlying molecular mechanisms for uric acid-induced lipid metabolic disturbances had not been elucidated clearly. This study investigated the effects and underlying mechanisms of uric acid on the development of lipid metabolic disorders. We collected blood samples from 100 healthy people and 100 patients with hyperuricemia for whom serum lipid analysis was performed. Meanwhile, a mouse model of hyperuricemia was generated, and lipidomics was performed on liver tissues, comparing control and hyperuricemia groups, to analyze lipid profiles and key metabolic enzymes. Uric acid directly induced serum lipid metabolic disorders in both humans and mice based on triglycerides, total cholesterol, and low-density lipoprotein cholesterol. Through lipidomic analysis, 46 lipids were differentially expressed in hyperuricemic mouse livers, and the phosphatidylcholine composition was altered, which was mediated by LPCAT3 upregulation. High-uric acid levels-induced p-STAT3 inhibition and SREBP-1c activation in vivo and in vitro. Moreover, LPCAT3-knockdown significantly attenuated uric acid-induced p-STAT3 inhibition, SREBP-1c activation, and lipid metabolic disorders in L02 cells. In conclusion, uric acid induces lipid metabolic disturbances through LPCAT3-mediated p-STAT3 inhibition and SREBP-1c activation. LPCAT3 could be a key regulatory factor linking hyperuricemia and lipid metabolic disorders. These results might provide novel insights into the clinical treatment of hyperuricemia.

Influence of lactoferrin on Propionibacterium acnes-induced inflammation in vitro and in vivo.

Lactoferrin (LF) is a monomer glycoprotein in the mammalian colostrum that has multiple biological activities and a high affinity for iron ions. Not only does it have strong antibacterial activity, it also can regulate the release of cytokines in inflammatory areas, activate immune cells, and inhibit inflammatory diseases caused by non-pathogenic bacteria and the development of tumors. However, the anti-inflammatory mechanism of LF in inflammatory skin diseases induced by Propionibacterium acnes (P. acnes) has not been elucidated in vitro and in vivo. In this study, we investigated the effects of LF on the generation of inflammatory cytokines in HaCaT cells induced by heat-killed P. acnes. The expression of pro-inflammatory cytokines IL-8 increased after induction of HaCaT by heat-killed P. acnes, but it decreased significantly after LF treatment. Western blotting was used to examine the levels of TLR2, nuclear factor (NF) κB and intercellular cell adhesion molecule 1 protein induced by P. acnes in HaCaT cells, and the results showed that the levels were inhibited by LF. In addition, activated P. acnes (1 × 107 CFU/mL) was injected into the ears of experimental mice, which induced inflammation 24 hours after the injection. However, immunohistochemical analysis showed a significant reduction in the inflammatory response after LF treatment in the right ear relative to the untreated left ear, and the same result was seen with western blotting. In summary, this study revealed the treatment effect of LF on P. acnes-induced inflammation, thus providing support for the anti-acne properties of LF.

Otolaryngology during COVID-19: Preventive care and precautionary measures.

Since the outbreak of novel coronavirus disease (COVID-19) in December 2019, it has spread to various regions and countries, forming a global pandemic. Reducing nosocomial infection is a new issue and challenge for all healthcare systems. Otolaryngology is a high-risk specialty as it close contact with upper respiratory tract mucous, secretions, droplets and aerosols during procedures and surgery. Therefore, infection prevention and control measures for this specialty are essential. Literatures on the epidemiology, clinical characteristics and infection control measures of COVID-19 were reviewed, practical knowledge from first-line otolaryngologists in China, the United States, and Brazil were reviewed and collated. It was recommended that otolaryngology professionals should improve screening in suspected patients with relevant nasal and pharyngeal symptoms and signs, suspend non-emergency consultations and examinations in clinics, and rearrange the working procedures in operating rooms. The guidelines of personal protective equipment for swab sampling, endoscopy and surgery were listed. Indications for tracheotomy during the pandemic should be carefully considered to avoid unnecessary airway opening and aerosol-generation; precautions during surgery to reduce the risk of exposure and infection were illustrated. This review aimed to provide recommendations for otolaryngologists to enhance personal protection against COVID-19 and reduce the risk of nosocomial infection.

Golgi phosphoprotein-3 promotes invasiveness of gastric cancer cells through the mTOR signalling pathway.

PURPOSE: Golgi phosphoprotein-3 (GOLPH3) is an oncogene that is overexpressed in multiple cancers and is associated with poor prognosis. The aim of this study was to examine the impact of GOLPH3 on the migration and metastasis of gastric cancer cells. METHODS: Following the shRNA-mediated knockdown of GOLPH3, we analyzed cytoskeletal reorganization and cell invasion, migration and adhesion, and determined the impact of components of the mammalian target of the rapamycin (mTOR) signalling pathway. RESULTS: The GOLPH3 mRNA and protein expression were significantly lower in both SGC-7901 and MKN-28 cells as compared with poorly-differentiated BGC-823 cells. The GOLPH3 knockdown also significantly reduced cell invasion in all three cell lines through reduced migration as compared with the non-targeting control sequence group. The GOLPH3 knockdown also reduced F-actin in all three cell lines, and decreased cell adhesion in BGC-823 and SGC-7901 cells. Finally, p-mTOR, p70S6K, p-4EBP1 and RhoA protein levels were significantly downregulated in shGOLPH3-1-treated cells. CONCLUSIONS: In conclusion, GOLPH3 increased in poorly-differentiated gastric cancer cells, activating the mTOR-70S6K/4EBP1-RhoA signalling pathway to promote the migration and metastasis of gastric cancer cells.

Cyclin A1 is expressed in mouse ovary.

Cyclin A1 belongs to the type-A cyclins and participates in cell cycle regulation. Since its discovery, cyclin A1 has been shown mostly in testis. It plays important roles in spermatogenesis. However, there were also reports on ovary expression of cyclin A1. Therefore, we intended to revisit the expression of cyclin A1 in mouse ovary. Our study showed that cyclin A1 was expressed at the mRNA level and the protein level in mouse ovary. Tissue staining revealed that cyclin A1 was expressed in maturating oocytes. With the recent data on the functions of cyclins in somatic and stem cells, we also discussed the possibilities of further studies of cyclin A1 in mouse oocytes and perhaps in the oogonial stem cells. Our findings not only add to the supportive evidence of cyclin A1 expression in oocytes, but also may promote more interest in exploring cyclin A1 functions in ovary.

Incidence and prognosis of olfactory and gustatory dysfunctions related to SARS-CoV-2 Omicron strain infection in China: A national multicenter survey of 35,566 individuals.

Objective: This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China. Methods: This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results: Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions: The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.

Higher dosage of HIFU treatment may lead to higher and longer efficacy for moderate to severe perennial allergic rhinitis.

OBJECTIVES: This study was to compare the efficacies and side effects of high intensity focused ultrasound (HIFU) treatment for perennial allergic rhinitis (PAR) with regular and increased dosage. STUDY DESIGN: A prospectively assembled cohort was retrospectively analyzed through visual analogue scale (VAS). METHODS: Regular dosage of HIFU treatment was applied to 56 PAR patients in group A. An increased dosage as twice as the regular one was applied to 48 patients in group B. Nasal obstruction, sneezing, rhinorrhea and rhinocnesmus, which were recognized as the four main symptoms of allergic rhinitis (AR), were evaluated before treatment, 3 months after treatment, and 1 year after treatment. The satisfaction of patients was also evaluated at 1 year postoperatively. Biopsy of the inferior turbinate and morphometric analysis were applied to 11 patients in group A and 10 in group B before HIFU treatment and 3 months after treatment. RESULTS: Comparing the AR symptoms before treatment, There is no statistical difference observed between group A and B (p>0.05). The four main symptoms at 3 months and 1 year after treatment were all significantly improved (p<0.01) in both group A and B. The VAS scores of AR symptoms in Group B were lower than those in Group A at the same stage after treatment, especially at 1 year after treatment (p<0.05). Comparing the results at 3 months and 1 year after treatment, a tendency of recurrence of these symptoms was observed statistically in group A (p<0.05), but not in group B (p>0.05). More cases of nasal dryness and perirhinal swelling were found in group B than those in group A (p<0.05), while all side effects were mild and temporary. Patients in group B were more satisfied than those in group A (p=0.0866 >0.05), though not statistically significant. More reduction of the eosinophils, other inflammatory cells, and the submucosal glands was observed after HIFU treatment in group B than that in group A (p<0.05). CONCLUSIONS: A proper increment of HIFU dosage may be recommended to meet the needs of more improvement of AR symptoms and less recurrence.

Odor familiarity and improvement of olfactory identification test in Chinese population.

Aims: This study aimed to design the Chinese Modified Olfactory Identification (CMOI) test based on the Sniffin' Sticks Olfactory Identification (SSOI) test by changing unfamiliar distractors and odors for more familiar ones for the Chinese population. Materials and methods: We recruited 200 healthy volunteers (103 males and 97 females, aged 18-65 years, mean age 35.04 years, SD 10.96); in a survey, 100 volunteers rated their familiarity with 121 odors, including all the SSOI test odor descriptors and common odors in Chinese daily life. The SSOI test was modified according to the survey results. The other 100 volunteers were tested three times using the SSOI test, the Modified Distractors Olfactory Identification (MDOI) test established by modifying distractors in the SSOI test, and the CMOI test developed by using familiar unpleasant odors to displace the odors with low correct recognition rates in the MDOI test. We compared the test scores of the volunteers during the modification process. Results: Volunteers were unfamiliar with 31 odor descriptors in the SSOI test; 23 distractors with low familiarity were displaced with more familiar distractors. The three odors with the lowest correct recognition rate in the MDOI test (apple, leather, and pineapple) were displaced with familiar unpleasant odors. The test scores were significantly higher in the CMOI test than in others (p < 0.0001); the correct recognition rate in the CMOI test was significantly higher than in the SSOI test (p < 0.01). Conclusion: The test scores in the CMOI test were significantly improved; it prevented choosing wrongly due to unfamiliarity with an odor and its distractors.

Diagnostic and therapeutic strategies of acute invasive fungal rhinosinusitis.

Acute invasive fungal rhinosinusitis (AIFR) is a rare disease, but the prognosis is by no means ideal. Pathologically, fungal infection is not only located in the sinus cavity, but also invades the sinus mucosa and bone wall, the surrounding structures and tissues such as the orbit and anterior skull base are often compromised and are accompanied with intracranial and extracranial complications. Despite decades of efforts, acute invasive fungal rhinosinusitis remains a devastating disease, the mortality of the disease continues to hover around 50%. The main impediments to improving the prognosis of acute invasive fungal rhinosinusitis are the difficulties of early diagnosis and the rapid reversal of immune insufficiency. Moreover, aggressive surgery combined with systemic antifungal therapy are significant positive prognostic factors as well. Progress and standardization of AIFR treatment protocols have been limited by the scarcity of the disease and the absence of published randomized studies. Therewith, how to improve the therapeutic outcome and reduce the mortality rate has always been a challenging clinical discussion. We have summarized the relevant case series and literature from the recent years, management with optimal diagnostic and curative strategies are reviewed.

Phosphatidylserine decarboxylase downregulation in uric acid­induced hepatic mitochondrial dysfunction and apoptosis.

The molecular mechanisms underlying uric acid (UA)-induced mitochondrial dysfunction and apoptosis have not yet been elucidated. Herein, we investigated underlying mechanisms of UA in the development of mitochondrial dysfunction and apoptosis. We analyzed blood samples of individuals with normal UA levels and patients with hyperuricemia. Results showed that patients with hyperuricemia had significantly elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, which may indicate liver or mitochondrial damage in patients with hyperuricemia. Subsequently, lipidomic analysis of mouse liver tissue mitochondria and human liver L02 cell mitochondria was performed. Compared with control group levels, high UA increased mitochondrial phosphatidylserine (PS) and decreased mitochondrial phosphatidylethanolamine (PE) levels, whereas the expression of mitochondrial phosphatidylserine decarboxylase (PISD) that mediates PS and PE conversion was downregulated. High UA levels also inhibited signal transducer and activator of transcription 3 （STAT3） phosphorylation as well as mitochondrial respiration, while inducing apoptosis both in vivo and in vitro. Treatment with allopurinol, overexpression of PISD, and lyso-PE (LPE) administration significantly attenuated the three above-described effects in vitro. In conclusion, UA may induce mitochondrial dysfunction and apoptosis through mitochondrial PISD downregulation. This study provides a new perspective on liver damage caused by hyperuricemia.

Effect of atrial fibrillation on outcomes in patients with anterior circulation occlusion stroke receiving endovascular therapy.

Objective: Atrial fibrillation is one of the major risk factors of ischemic stroke. Endovascular thrombectomy (EVT) has become the standard treatment for acute ischemic stroke with large vessel occlusion. However, data regarding the impact of AF on the outcome of patients with acute ischemic stroke treated with mechanical thrombectomy are controversial. The aim of our study was to determine whether atrial fibrillation modifies the functional outcome of patients with anterior circulation acute ischemic stroke receiving EVT. Methods: We reviewed 273 eligible patients receiving EVT from January 2019 to January 2022 from 3 comprehensive Chinese stroke centers, of whom 221 patients were recruited. Demographics, clinical, radiological and treatment characteristics, safety outcomes, and functional outcomes were collected. Modified Rankin scale (mRS) score ≤ 2 at 90 days was defined as a good functional outcome. Results: In our cohort, 79 patients (35.74%) were eventually found to have AF. Patients with AF were elder (70.08 ± 11.72 vs. 61.82 ± 13.48 years, p = 0.000) and less likely to be males (54.43 vs. 73.94%, p = 0.03). The significant reperfusion rate (modified thrombolysis in cerebral infarction 2b-3) was 73.42 and 83.80% in patients with and without AF, respectively (p = 0.064). The good functional outcome (90-day modified Rankin scale: 0 to 2) rate was 39.24 and 44.37% in patients with and without AF, respectively (p = 0.460) after adjusting multiple confounding factors. There was no difference in the presence of symptomatic intracerebral hemorrhage between the two groups (10.13 vs. 12.68%, p = 0.573). Conclusion: Despite their older age, AF patients achieved similar outcomes as non-AF patients with anterior circulation occlusion treated with endovascular therapy.

[Clinicopathological analysis of aggressive angiomyxoma].

OBJECTIVE: To explore the clinicopathological characteristics of aggressive angiomyxoma (AAM) so as to boost the level of diagnosis and treatment. METHODS: Seven cases of aggressive angiomyxoma were studied with light microscope and immunohistochemistry. Antibody of Vimentin, Desmin, CD34, smooth muscle actin (SMA), estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), S-100, p53 and Ki67 were used. RESULTS: There were 3 males and 4 females with an average age of 43.1 years. Three patients had urinary compressive complaints while others were symptom-free. All underwent surgical resection. Three patients were recurrent after operation. The tumor was generally nodular and its cut surface appeared jelly-like. Histologically, on myxoid stroma background, it was composed of a mixture of spindle and stellar cells without atypical cell and mitosis. There were various-sized vessels with thin to thick walls. The scattered muscle-like cells had a perivascular distribution. Immunohistochemistry showed that tumor cells were positive for Vimentin(+)7/7, Desmin(+)7/7, CD34(+)3/7, SMA(+)2/7, ER(+)6/7, p53(+)4/7, Ki67(+) 1% - 8% and negative for PR, AR and S-100. CONCLUSIONS: As a rare soft tissue tumor, AAM extremely rare in males. Owing to its local invasion and high recurrence, extensive resection and long-term follow-up are necessary.

Endoscope-Assisted Resection of a Vagal Neurofibroma Using a Posterior Styloid Approach.

It is very challenging to expose and remove tumors above the hard palate in the retrostyloid space using the typical cervical approach. Other approaches, such as the cervical-parotid approach, may result in prominent scars, facial paralysis, or masticatory dysfunction. Here, we report a case of a vagal neurofibroma between the internal carotid artery and internal jugular vein in the retrostyloid space. We used a 3D model to design a surgical approach that reduced the risk to the surrounding vessels and nerves. We performed an endoscope-assisted resection of the tumor using a posterior styloid approach. Following surgery, there were no obvious scars on the face or neck, facial paralysis, or dysphagia, but mild hoarseness.

Smoking behavior might affect allergic rhinitis and vasomotor rhinitis differently: A mendelian randomization appraisal.

BACKGROUND: Allergic rhinitis and vasomotor rhinitis are harassing numerous patients and their risk factors have not been well investigated. Here, we try to identify their risk factors and distinguish these 2 diseases. METHODS: A two-sample Mendelian randomization (MR) study was implemented to discover the risk factors of allergic and vasomotor rhinitis. Based on previous studies, we selected 15 potential risk factors and the genome-wide summary statistics were extracted from the non-FinnGen consortium. The genome-wide summary statistics of rhinitis were obtained from the FinnGen consortium. Both univariable MR and multivariable MR analyses were performed to identify the causal risk factors. The Cochrane's Q value was calculated to appraise the heterogeneity. MR-Egger intercept and MR-RPESSO were utilized to appraise the pleiotropy. RESULTS: In the univariable model, the number of cigarettes per day can decrease the risk of allergic rhinitis (IVW OR = 0.29[0.18, 0.47], p-value = 2.70 × 10-7) while increasing the risk of vasomotor rhinitis (IVW OR = 1.30[1.04, 1.62], p-value = 0.022). Besides, no other risk factors could affect the risk of either allergic or vasomotor rhinitis. After adjusting for age of smoking initiation and alcohol intake, the cigarettes per day could still decrease the risk of allergic rhinitis (IVW OR = 4.66 × 10-3 [1.99 × 10-4, 0.11], p-value = 0.003) while not affecting the risk of vasomotor rhinitis (IVW OR = 0.92[0.44, 1.96], p-value = 0.834). CONCLUSION: Smoking can affect the risk of allergic and vasomotor rhinitis differently where it decreases the risk of allergic rhinitis and increases the risk of vasomotor rhinitis.

Neutrophil extracellular traps accelerate vascular smooth muscle cell proliferation via Akt/CDKN1b/TK1 accompanying with the occurrence of hypertension.

OBJECTIVE: Neutrophil extracellular traps (NETs) can trigger pathological changes in vascular cells or vessel wall components, which are vascular pathological changes of hypertension. Therefore, we hypothesized that NETs would be associated with the occurrence of hypertension. METHODS: To evaluate the relationship between NETs and hypertension, we evaluated both the NETs formation in spontaneously hypertensive rats (SHRs) and the blood pressure of mice injected phorbol-12-myristate-13-acetate (PMA) via the tail vein to induce NETs formation in arterial wall. Meanwhile, proliferation and cell cycle of vascular smooth muscle cells (VSMCs), which were co-cultured with NETs were assessed. In addition, the role of exosomes from VSMCs co-cultured with NETs on proliferation signaling delivery was assessed. RESULTS: Formation of NETs increased in the arteries of SHR. PMA resulted in up-regulation expression of citrullinated Histone H3 (cit Histone H3, a NETs marker) in the arteries of mice accompanied with increasing of blood pressure. NET treatment significantly increased VSMCs count and accelerated G1/S transition in vitro . Cyclin-dependent kinase inhibitor 1b (CDKN1b) was down-regulated and Thymidine kinase 1 (TK1) was up-regulated in VSMCs. Exosomes from VSMCs co-cultured with NETs significantly accelerated the proliferation of VSMCs. TK1 was up-regulated in the exosomes from VSMCs co-cultured with NETs and in both the arterial wall and serum of mice with PMA. CONCLUSION: NETs promote VSMCs proliferation via Akt/CDKN1b/TK1 and is related to hypertension development. Exosomes from VSMCs co-cultured with NETs participate in transferring the proliferation signal. These results support the role of NETs in the development of hypertension.

Developing and predicting of early mortality after endovascular thrombectomy in patients with acute ischemic stroke.

Background: Stroke is one of the leading causes of mortality across the world. However, there is a paucity of information regarding mortality rates and associated risk factors in patients with acute ischemic stroke (AIS) undergoing endovascular thrombectomy (EVT). In this study, we aimed to clarify these issues and analyzed previous publications related to mortality in patients treated with EVT. Methods: We analyzed the survival of 245 consecutive patients treated with mechanical thrombectomy for AIS for which mortality information was obtained. Early mortality was defined as death occurring during hospitalization after EVT or within 7 days following hospital discharge from the stroke event. Results: Early mortality occurred in 22.8% of cases in this cohort. Recanalization status (modified thrombolysis in cerebral infarction, mTICI) (p = 0.002), National Institute of Health Stroke Scale Score (NIHSS) score 24-h after EVT (p < 0.001) and symptomatic intracerebral hemorrhage (sICH) (p < 0.001) were independently associated with early mortality. Age, sex, cardiovascular risk factors, NIHSS score pre-treatment, Alberta Stroke Program Early CT Score (ASPECTS), stroke subtype, site of arterial occlusion and timing form onset to recanalization did not have an independent influence on survival. Non-survivors had a shorter hospitalization (p < 0.001) but higher costs related to their hospitalization and outpatient care. Conclusion: The recanalization status, NIHSS score 24-h after EVT and sICH were predictors of early mortality in AIS patients treated with EVT.

The Role of Oxidative Stress in Hyperuricemia and Xanthine Oxidoreductase (XOR) Inhibitors.

Uric acid is the end product of purine metabolism in humans. Hyperuricemia is a metabolic disease caused by the increased formation or reduced excretion of serum uric acid (SUA). Alterations in SUA homeostasis have been linked to a number of diseases, and hyperuricemia is the major etiologic factor of gout and has been correlated with metabolic syndrome, cardiovascular disease, diabetes, hypertension, and renal disease. Oxidative stress is usually defined as an imbalance between free radicals and antioxidants in our body and is considered to be one of the main causes of cell damage and the development of disease. Studies have demonstrated that hyperuricemia is closely related to the generation of reactive oxygen species (ROS). In the human body, xanthine oxidoreductase (XOR) catalyzes the oxidative hydroxylation of hypoxanthine to xanthine to uric acid, with the accompanying production of ROS. Therefore, XOR is considered a drug target for the treatment of hyperuricemia and gout. In this review, we discuss the mechanisms of uric acid transport and the development of hyperuricemia, emphasizing the role of oxidative stress in the occurrence and development of hyperuricemia. We also summarize recent advances and new discoveries in XOR inhibitors.