New Guaiane-Type Sesquiterpenoids Biscogniauxiaols A-G with Anti-Fungal and Anti-Inflammatory Activities from the Endophytic Fungus Biscogniauxia Petrensis.

Seven undescribed guaiane-type sesquiterpenoids named biscogniauxiaols A-G (1-7) were isolated from the endophytic fungus Biscogniauxia petrensis on Dendrobium orchids. Their structures were determined by extensive spectroscopic analyses, electronic circular dichroism (EC) and specific rotation (SR) calculations. Compound 1 represented a new family of guaiane-type sesquiterpenoids featuring an unprecedented [5/6/6/7] tetracyclic system. A plausible biosynthetic pathway for compounds 1-7 was proposed. The anti-fungal, anti-inflammatory and multidrug resistance reversal activities of the isolates were evaluated. Compounds 1, 2 and 7 exhibited potent inhibitory activities against Candida albicans with MIC values ranging from 1.60 to 6.30 µM, and suppressed nitric oxide (NO) production with IC50 ranging from 4.60 to 20.00 µM. Additionally, all compounds (100 µg/mL) enhanced the cytotoxicity of cisplatin in cisplatin-resistant non-small cell lung cancer cells (A549/DDP). This study opened up a new source for obtaining bioactive guaiane-type sesquiterpenoids and compounds 1, 2, and 7 were promising for further optimization as multifunctional inhibitors for anti-fungal (C. albicans) and anti-inflammatory purposes.

Endovascular treatment achieves better outcomes than best medical management in patients with M2 occlusion and high stroke severity: a meta-analysis.

BACKGROUND: The lack of randomized evidence makes it difficult to establish reliable treatment recommendations for patients with M2 occlusion. This study aims to compare the efficacy and safety of endovascular treatment (EVT) with best medical management (BMM) in patients with M2 occlusion, and to investigate whether the optimal treatment varies according to stroke severity. METHODS: Comprehensive literature retrieval was conducted to identify studies that directly compared the outcomes of EVT and BMM. According to stroke severity, the study population were classified into those with moderate-severe stroke and those with mild stroke. National Institute of Health Stroke Scale (NIHSS) scores ≥ 6 was defined as moderate-severe stroke, and NIHSS scores 0-5 as mild stroke. Random-effects meta-analyses were performed to measure the symptomatic intracranial hemorrhage (sICH) within 72 h, and the modified Rankin Scale (mRS) scores 0-2 and the mortality at 90 days. RESULTS: Totally, 20 studies were identified, including 4358 patients. In the moderate-severe stroke population, the EVT had 82% higher odds for mRS scores 0-2 (OR 1.82, 95% CI 1.34-2.49) and a 43% lower odds for mortality (OR 0.57, 95% CI 0.39-0.82) compared with the BMM. However, no difference was found in the sICH rate (OR 0.88, 95% CI 0.44-1.77). In the mild stroke population, no differences were observed in the mRS scores 0-2 (OR 0.81, 95% CI 0.59-1.10) or mortality (OR 1.23, 95% CI 0.72-2.10) between EVT and BMM, whereas EVT was associated with higher sICH rate (OR 4.21, 95% CI 1.86-9.49). CONCLUSION: EVT may be only beneficial for patients with M2 occlusion and high stroke severity, but not for those with NIHSS scores 0-5.

Neogrisphenol A, a Potential Ovarian Cancer Inhibitor from a New Record Fungus Neohelicosporium griseum.

From the rice fermentation product of a new record fungus, Neohelicosporium griseum, two new polyketides, neogrisphenol A (1) and neogrisphenol B (2), one new isochroman-1-one, (S)-6-hydroxy-7-methoxy-3,5-dimethylisochroman-1-one (3), and four known compounds (4-7) were isolated. Their structures were determined using 1D- and 2D-NMR, mass spectrometry, and chemical calculations. The C-3~C-2' polymerization mode between the two α-naphthalenone derivative moieties is uncommon in compounds 1 and 2. Meanwhile, compounds 1-2 and 5 exhibited antibacterial activity against Bacillus subtilis, Clostridium perfringens, Staphylococcus aureus, and Staphylococcus aureus, with MIC values ranging between 16 and 31 µg/mL. In addition, compound 5 showed antifungal activity against Sclerotinia sclerotiorum and Phytophthora nicotianae var. nicotianae, with respective IC50 values of 88.14 ± 2.21 µg/mL and 52.36 ± 1.38 µg/mL. Compound 1 showed significant cytotoxicity against A2780, PC-3, and MBA-MD-231 cell lines with respective IC50 values of 3.20, 10.68, and 16.30 µM, and the cytotoxicity against A2780 cells was even higher than that of cisplatin (CDDP). With an IC50 value of 10.13 µM, compound 2 also exhibited cytotoxicity against A2780. The in vitro results showed that compound 1 inhibited A2780 cell proliferation, induced apoptosis, and arrested the cell cycle at the S-phase in a concentration-dependent manner.

Endovascular thrombectomy in acute ischemic stroke patients with prestroke disability (mRS ≥2): A systematic review and meta-analysis.

Objective: The effect of endovascular thrombectomy (EVT) in acute ischemic stroke patients with prestroke disability (modified Rankin Scale score, mRS) ≥2) has not been well-studied. This study aimed to assess the safety and benefit of EVT in patients with prestroke disability. Methods: According to PRISMA guidelines, literature searching was performed using PubMed, Embase, and Cochrane databases, for a series of acute ischemic stroke patients with prestroke mRS ≥2 treated by EVT. Random-effects meta-analysis was used to pool the rate of return to prestroke mRS and mortality at 3-month follow-up. Results: In total, 13 observational studies, with 2,625 patients, were analyzed. The rates of return to prestroke mRS in patients with prestroke mRS of 2-4 were 20% (120/588), 27% (218/827), and 31% (34/108), respectively. Patients with prestroke disability treated by EVT had a higher likelihood of return to prestroke mRS (relative risk, RR, 1.86; 95% CI 1.28-2.70) and a lower likelihood of mortality (RR 0.75; 95%CI 0.58-0.97) compared with patients with standard medical treatment. Successful recanalization (Thrombolysis in Cerebral Infarction grade 2b-3) after EVT gave a higher likelihood of return to prestroke mRS (RR 2.04; 95% CI 1.17-3.55) and lower mortality (RR 0.72; 95% CI 0.62-0.84) compared with unsuccessful reperfusion. Conclusions: Acute ischemic stroke patients with prestroke disability may benefit from EVT. Withholding EVT on the sole ground of prestroke disabilities may not be justified.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/.

Environmental toxic metal contaminants and risk of stroke: a systematic review and meta-analysis.

The relationship between toxic metals in the environment and clinical stroke risk remains unclear, although their role as immunotoxicants and carcinogens has been well established. We conducted a systematic review of the relationship between five metals (arsenic, mercury, copper, cadmium, and lead) and stroke. First, we comprehensively searched 3 databases (Pubmed, EMBASE, and Cochrane) from inception until June 2021. Random-effects meta-analyses, pooled relative risks (RR) and 95% confidence intervals (CI) were applied to evaluate the effect value. We finally identified 38 studies involving 642,014 non-overlapping participants. Comparing the highest vs. lowest baseline levels, chronic exposure to lead (RR = 1.07; 95%CI,1.00-1.14), cadmium (RR = 1.30; 95%CI,1.13-1.48), and copper (RR = 1.19; 95%CI,1.04-1.36) were significantly associated with stroke risks. However, the other two metals (arsenic and mercury) had less effect on stroke risk. Further analysis indicated that the association was likely in a metal dose-dependent manner. The results may further support the possibility that environmental toxic metal contaminants in recent years are associated with the increased risk of stroke.

Aspirin and growth, rupture of unruptured intracranial aneurysms: A systematic review and meta-analysis.

OBJECTIVES: Aspirin has been suggested as a potential therapeutic strategy to prevent the growth and rupture of unruptured intracranial aneurysms (UIAs), but there is still controversy. The aim of this systematic review and meta-analysis is to determine the association between aspirin use and growth, rupture of UIAs. METHODS: We performed a systematic literature search of electronic databases to identify cohort and case-control studies investigating the relationship between aspirin use and growth or rupture of UIAs. Pooled odds ratio (OR) with corresponding 95% confidence interval (CI) were calculated using a random effects model. Heterogeneity among studies was quantified using the I2 statistic, and potential publication bias was assessed using funnel plots. Sensitivity analysis was performed to verify the robustness of the intention-to-treat results. Subgroup analysis was conducted according to the frequency of aspirin use. RESULTS: We identified 8 studies comprising 10,518 participants. The risk of bias was low to moderate. The pooled estimate showed that aspirin use was associated with a lower likelihood of growth of UIAs (OR = 0.25, 95% CI = 0.11-0.55; p = 0.0005) without statistical heterogeneity (p for Cochran Q statistic = 0.62, I2 = 0%). Likewise, aspirin intake also significant decreased 58% risk of intracranial aneurysms rupture (OR = 0.42, 95% CI = 0.29-0.60; p < 0.00001) with moderate heterogeneity (p for Cochran Q statistic = 0.005, I2 = 66%). Similar results were observed in the sensitivity analysis. Pooled OR of aspirin frequency subgroup analysis for less than or equal to 2 times per week was 0.82 (95%CI = 0.40-1.72; I2 = 0%), for at least 3 times per week to daily was 0.25 (95%CI = 0.12-053; I2 = 0%), for daily was 0.59 (95%CI: 0.47-0.74; I2 = 0%), and for unknown was 0.26 (95%CI: 0.15-0.45; I2 = 51%). CONCLUSIONS: The results of this systematic review and meta-analysis indicates a beneficial effect of aspirin on growth and rupture of UIAs.

Statin use for the prevention of seizure and epilepsy in the patients at risk: A systematic review and meta-analysis of cohort studies.

OBJECTIVE: Statin use for the prevention of seizure and epilepsy had been suggested but remained controversial. We sought to search existing literature to determine whether prophylactic use of statin reduced the incidence of seizure and epilepsy in the patients at risk. METHODS: Three electronic databases were thoroughly searched to identify clinical studies investigating the effects of statin use on patients at the risk of seizure or epilepsy. Regardless of heterogeneity quantified, a random effects meta-analyses were used to synthesize the evidence, to pool odds ratios (ORs) and corresponding 95 % confidence intervals (CIs). RESULTS: Seven cohort studies involving 26,042 patients with newly-onset epileptogenic brain insults and no history of seizure and epilepsy before were included. Compared with patients didn't receive statin treatment after epileptogenic brain insults, those treated with statin had a lower risk of epilepsy (5 studies; 22,849 patients; pooled OR, 0.48; 95 % CI, 0.31 to 0.73; p = 0.001) and seizure (4 studies; 6076 subjects; pooled OR, 0.35; 95 % CI, 0.25 to 0.48; p = 0.001). CONCLUSIONS: Evidence from this meta-analysis suggested that the use of statin should as primary prevention for patients with risk of seizures and epilepsy. Considering the limited number and quality of available studies, future randomized controlled trials are required to further demonstrate the association between statin use and incident of seizure and epilepsy.

Tranexamic Acid for Acute Spontaneous Intracerebral Hemorrhage: A Meta-Analysis of Randomized Controlled Trials.

Background: The role of tranexamic acid (TXA) in preventing hematoma expansion (HE) in patients with acute spontaneous intracerebral hemorrhage (ICH) remains unclear. We aim to investigate the efficacy and safety of TXA in acute spontaneous ICH with a particular focus on subgroups. Methods: Randomized controlled trials (RCTs) were retrieved from CENTRAL, Clinicaltrials.gov, EMBASE, PubMed, and WHO ICTRP. The primary outcome measurement was HE. The secondary outcome measurements included 3-month poor functional outcome (PFO), 3-month mortality, and major thromboembolic events (MTE). We conducted subgroup analysis according to the CT markers of HE (standard-risk population and high-risk population) and the time from onset to randomization (>4.5 and ≤4.5 h). Results: We identified seven studies (representing five RCTs) involving 2,650 participants. Compared with placebo, TXA may reduce HE on subsequent imaging (odd ratio [OR] 0.825; 95% confidence interval [CI] 0.692-0.984; p = 0.033; I2 = 0%; GRADE: moderate certainty). TXA and placebo arms did not differ in the rates of 3-month PFO, 3-month mortality, and MTE. Subgroup analysis indicated that TXA reduced the risk of HE in the high-risk population with CT markers of HE (OR 0.646; 95% CI 0.503-0.829; p = 0.001; I2 = 0 %) and in patients who were treated within 4.5 h of symptom onset (OR 0.823; 95% CI 0.690-0.980; p = 0.029; I2 = 0%), but this protective effect was not observed in the standard-risk population and patients who were treated over 4.5 h of symptom onset. Conclusions: Tranexamic acid (TXA) may decrease the risk of HE in patients with acute spontaneous ICH. Importantly, the decreased risk was observed in patients who were treatable within 4.5 h and with a high risk of HE, but not in those who were treatable over 4.5 h and in standard-risk population. However, PFO or mortality at 3 months did not significantly differ between patients who received TXA and those who received placebo. TXA is safe for acute spontaneous ICH without increasing MTE.

The effect of tranexamic acid in patients with TBI: a systematic review and meta-analysis of randomized controlled trials.

To conduct a systematic review and meta-analysis and evaluate the effect of tranexamic acid in patients with traumatic brain injury. PubMed, EMBASE, and CENTRAL (Cochrane Central Register of Controlled Trials) were searched to identify randomized controlled trials and evaluate the effect of tranexamic acid in traumatic brain injury patients. The primary outcome was mortality. Two reviewers extracted the data independently. The random effect meta-analysis was used to estimate the aggregate effect size of 95% confidence intervals. Six randomized controlled trials investigating tranexamic acid versus placebo and 30073 patients were included. Compared with placebo, tranexamic acid decreased the mortality (RR = 0.92; 95% CI, 0.87-0.96; p < 0.001) and growth of hemorrhagic mass (RR = 0.78; 95% CI, 0.61-0.99; p = 0.04). However, tranexamic acid could not decrease disability or independent, neurosurgery, vascular embolism, and stroke. Current evidence suggested that compared with placebo, tranexamic acid could reduce mortality and growth of hemorrhagic mass. This finding indicated that patients with traumatic brain injury should be treated with tranexamic acid.

A novel model for predicting the outcome of intracerebral hemorrhage: Based on 1186 Patients.

OBJECTIVE: To establish a model for predicting the outcome according to the clinical and computed tomography(CT) image data of patients with intracerebral hemorrhage(ICH). METHODS: The clinical and CT image data of the patients with ICH in Qinghai Provincial People's Hospital and Xuzhou Central Hospital were collected. The risk factors related to the poor outcome of the patients were determined by univariate and multivariate logistic regression analysis. To determine the effect of factors related to poor outcome, the nomogram model was made by software of R 3.5.2 and the support vector machine operation was completed by software of SPSS Modelor. RESULTS: A total of 8265 patients were collected and 1186 patients met the criteria of the study. Age, hospitalization days, blend sign, intraventricular extension, subarachnoid hemorrhage, midline shift, diabetes and baseline hematoma volume were independent predictors of poor outcome. Among these factors, baseline hematoma volume๥20ml (odds ratio:13.706, 95% confidence interval:9.070-20.709, p < 0.001) was the most significant factor for poor outcome, followed by the volume among 10ml-20ml (odds ratio:11.834, 95% confidence interval:7.909-17.707, p < 0.001). It was concluded that the highest percentage of weight in outcome was baseline hematoma volume (25.0%), followed by intraventricular hemorrhage (23.0%). CONCLUSION: This predictive model might accurately predict the outcome of patients with ICH. It might have a wide range of application prospects in clinical.

Establishment and Verification of the Hematoma Expansion Prediction Score of Intracerebral Hemorrhage in the Qinghai-Tibetan Plateau.

OBJECTIVE: The latest World Health Organization data showed that stroke was the highest mortality in China, accounting for 23.7% of the total mortality from 2000 to 2012. Intracerebral hemorrhage (ICH) was the most deadly and incurable type of stroke. In the Qinghai-Tibetan Plateau, the incidence of stroke was relatively higher. Several studies showed that the shape and heterogeneity of hematoma and image markers on brain computed tomography scan had predictive effects on hematoma expansion (HE). The study aimed to find relative factors and established a nomogram model to predict the HE of ICH. METHODS: All patients with ICH in Qinghai Provincial People's Hospital from January 1, 2012, to May 22, 2018, were continuously collected. A total of 402 patients were included in the study. This was a single-center retrospective study. Univariate and binary logistic regression analysis were performed to screen out the independent predictors that were significantly associated with HE. RESULTS: The total incidence of HE in ICH was 30.9%, whereas the incidence of HE in the basal ganglia and nonbasal ganglia was 36.4% and 17.2%, respectively. Diabetes, basal ganglia hemorrhage, time of onset to baseline computed tomography, island sign, blend sign, black hole sign, and swirl sign were independent predictors of HE. Based on these predictors, a nomogram model was established and the accuracy was 81.6%, the sensitivity was 91.1%, and the specificity was 70.5%. CONCLUSIONS: This model had a high accuracy of predicting HE in the Qinghai-Tibetan Plateau. Because this model is noninvasive, rapid, and low cost, it is easy to promote and has wide application prospects in clinical practice.

Development and Validation of Prognostic Model for Patients with Acute Subdural Hematoma-Reliable Nomogram.

OBJECTIVE: By extracting clinical and computed tomography imaging data of patients with acute subdural hematoma (ASDH), factors that were significantly associated with poor prognosis were screened and a nomogram model was established and validated. METHODS: All patients with ASDH who underwent subdural hematoma removal and decompressive craniectomy from January 2014 to March 2018 in Qinghai Provincial People's Hospital were continuously collected. Finally, 124 patients were included in the study. According to the Glasgow Outcome Scale at 3 months after operation, patients were divided into a good prognosis group and a poor prognosis group. RESULTS: Univariate and binary logistic regression analysis were performed to screen out independent predictors that were significantly associated with poor prognosis of ASDH. On the basis of these factors, a nomogram model was established. CONCLUSIONS: The nomogram model had high accuracy for predicting poor prognosis in patients with ASDH, and it was easy to promote. In the future, large sample and multicenter prospective studies are necessary to complement and identify the results.

Combining Investigation of Imaging Markers (Island Sign and Blend Sign) and Clinical Factors in Predicting Hematoma Expansion of Intracerebral Hemorrhage in the Basal Ganglia.

BACKGROUND AND OBJECTIVE: Intracerebral hemorrhage (ICH) is the most difficult-to-treat form of stroke and accounts for about 10%-30% of all strokes worldwide. Hematoma expansion (HE), which occurs in one third of patients with ICH, is strongly predictive of worse prognosis and potentially preventable if high-risk patients are identified in the early phase of ICH. We summarized data from recent studies on HE prediction and classified those potential indicators into 2 categories: 1) clinical and laboratory and 2) radiographic. Therefore, we aimed to identify the accuracy of L, that is, the value of combining predictors in predicting HE of ICH in basal ganglia. METHODS: We retrospectively investigated the clinical database of Qinghai Provincial People's Hospital for patients with ICH aged >18 years between January 2015 and January 2018. As inclusion criteria, we defined 1) ICH diagnosed on noncontrast computed tomography (CT); 2) noncontrast CT performed on enrollment within 6 hours after onset of symptoms; 3) follow-up CT scan performed within 24 hours after the baseline CT scan; and 4) all of the primary hematoma was located in the basal ganglia. Univariate and multivariate logistic regression analysis were used to analyze the potential HE predictors, and then receiver operating characteristic curves were used to evaluate the L (the value of combining predictors) of imaging markers and clinical factors in predicting HE. RESULTS: Of the 99 patients with HE, island sign was present in 48.48% (48/99) of patients and blend sign was present in 34.34% (34/99) of patients. Multivariate logistic regression analysis identified time to baseline CT scan (odds ratio [OR] 1.574; 95% confidence interval [CI] 1.205-2.054; P = 0.001), baseline hematoma volume (P = 0.001), presence of island sign (OR 11.247; 95% CI 4.701-26.909; P = 0.000), presence of blend sign (OR 3.104; 95% CI 1.425-6.765; P = 0.004), anticoagulants use or international normalized ratio >1.5 (OR 2.755; 95% CI 1.072-7.082; P = 0.035), and intraventricular hemorrhage (OR 2.351; 95% CI 1.066-5.187; P = 0.034) as independent predictors of HE. The sensitivity and specificity of L (value of combining predictors) were 88.89% and 80.84%, respectively; the area under the curve was 0.918. CONCLUSIONS: The findings indicated that the ability of L to predict HE was much more excellent than these 6 predictors alone. L showed a high association with HE, with an accuracy of 91.8%, and was a reliable value of combining predictors in terms of predicting HE. L may serve as a promising, noninvasive tool for clinical therapeutic strategy.

A Reliable Nomogram Model to Predict the Recurrence of Chronic Subdural Hematoma After Burr Hole Surgery.

OBJECTIVE: We established a reliable nomogram model to predict the recurrence of chronic subdural hematoma (CSDH) after burr hole surgery. METHODS: We retrospectively analyzed 514 patients who were treated in our hospital between January 2010 and November 2017 and included 231 patients in this study. We used univariate and binary logistic regression analysis to identify the significantly related predictors for recurrence. Subsequently, we established the nomogram model using these predictors and validated it. RESULTS: The total rate of recurrence after initial surgery for CSDH was 14.29% (33/231) during the following 3 months. We found that preoperative hematoma volume (greater than 121 mL), postoperative residual cavity volume (greater than 72 mL), computed tomography scan imaging type (hyper- and mixed-density type), and age (older than 65 years of age) were significantly related to recurrence. We used 50% recurrence rate as the classification cutoff, with the corresponding points of 252 to validate the nomogram model. The accuracy of predicting the recurrence of CSDH calculated by the binary logistic regression model was 91.7%. The sensitivity and specificity of the nomogram were 87.88% and 84.85%, respectively. CONCLUSIONS: This nomogram model had a high precision to predict the recurrence of CSDH. It needs more external and prospective validation in the future. We expect this model could be used in different neurosurgical problems as well.

Association Between Gray-White Matter Ratio in Computed Tomography and Outcome in Patients with Extra-Axial Hematoma.

OBJECTIVE: To evaluate relationship between gray-white matter ratio (GWR) on computed tomography and prognosis in patients with extra-axial hematoma. METHODS: Patients with extra-axial hematoma who had undergone surgical treatment at Qinghai Provincial People's Hospital from September 2016 to December 2017 were included. GWR values were calculated by measuring values of gray matter and white matter in Hounsfield units in noninjury sites of basal ganglia. According to Glasgow Outcome Scale score at 3 months after operation, patients were divided into good prognosis (Glasgow Outcome Scale score 4-5) and poor prognosis (Glasgow Outcome Scale score 1-3) groups. RESULTS: Of 103 patients who met inclusion criteria and were analyzed, 24 had with a poor outcome, including 5 deaths, and 79 patients had a good outcome. There were significant differences between the 2 groups in terms of age, type of hematoma, admission Glasgow Coma Scale score, and presence of hernia (all P < 0.05). Postoperative HU values of posterior capsule, postoperative GWR values, and difference between preoperative and postoperative GWR values had statistical significance (all P < 0.05). Receiver operating characteristic curve showed that difference between preoperative and postoperative GWR values was the best predictor of poor outcome. CONCLUSIONS: The difference between preoperative or postoperative GWR values has a higher sensitivity and greater area under the curve to predict patient outcome. Measuring the difference between preoperative and postoperative GWR values may be useful as an objective early predictor of outcome in patients with extra-axial hematoma. Larger samples and multicenter prospective studies are still required.