Predicting who has delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage using machine learning approach: a multicenter, retrospective cohort study.

BACKGROUND: Early prediction of delayed cerebral ischemia (DCI) is critical to improving the prognosis of aneurysmal subarachnoid hemorrhage (aSAH). Machine learning (ML) algorithms can learn from intricate information unbiasedly and facilitate the early identification of clinical outcomes. This study aimed to construct and compare the ability of different ML models to predict DCI after aSAH. Then, we identified and analyzed the essential risk of DCI occurrence by preoperative clinical scores and postoperative laboratory test results. METHODS: This was a multicenter, retrospective cohort study. A total of 1039 post-operation patients with aSAH were finally included from three hospitals in China. The training group contained 919 patients, and the test group comprised 120 patients. We used five popular machine-learning algorithms to construct the models. The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, precision, and f1 score were used to evaluate and compare the five models. Finally, we performed a Shapley Additive exPlanations analysis for the model with the best performance and significance analysis for each feature. RESULTS: A total of 239 patients with aSAH (23.003%) developed DCI after the operation. Our results showed that in the test cohort, Random Forest (RF) had an AUC of 0.79, which was better than other models. The five most important features for predicting DCI in the RF model were the admitted modified Rankin Scale, D-Dimer, intracranial parenchymal hematoma, neutrophil/lymphocyte ratio, and Fisher score. Interestingly, clamping or embolization for the aneurysm treatment was the fourth button-down risk factor in the ML model. CONCLUSIONS: In this multicenter study, we compared five ML methods, among which RF performed the best in DCI prediction. In addition, the essential risks were identified to help clinicians monitor the patients at high risk for DCI more precisely and facilitate timely intervention.

Middle meningeal artery embolization for the treatment of unilateral large chronic subdural hematoma patients with significant midline shift: A single-center experience.

BACKGROUND: The amount of midline shift (MLS) considered safe for middle meningeal artery embolization (MMAE) in patients with chronic subdural hematoma (CSDH) has not been established. Whether MMAE could be used as upfront treatment for unilateral large CSDH patients with significant MLS (>1 cm) has not been reported. OBJECTIVE: To investigate the efficacy and safety of MMAE in unilateral large CSDH patients with MLS > 1 cm. METHODS: Eleven carefully selected CSDH patients with mild or moderate symptoms and significant MLS > 1 cm from 1 May 2021 to 31 August 2022 were included in the study. All patients were treated with MMAE using polyvinyl alcohol (PVA) particles. Outcomes were assessed clinically and with interval imaging studies at follow-up. RESULTS: All 19 MMAs (unilateral embolization in three patients and bilateral embolization in eight patients) were successfully embolized. All 11 patients were followed for subsequent months, and there was no recurrence and enlargement of CSDH. Procedural adverse events, mortality, or complications were not observed. The average time to achieve a 50% reduction in MLS was approximately four weeks, while it took approximately eight weeks to achieve a 50% reduction in maximal volume. All 11 patients showed improvement in their neurological symptoms at three days post-operation, including four hemiplegic patients. CONCLUSIONS: MMAE may demonstrate safety in carefully selected CSDH patients with significant midline shift (MLS > 1 cm), particularly in those who are not suitable for surgery, thus providing a potential alternative approach.

The Influence of Different Levels of Sodium Chloride, Sodium Nitrite, and Glucose on Biogenic Amines and Microbial Communities in Fermented Goat Meat Sausage.

The influence of different levels of sodium chloride, sodium nitrite, and glucose on the quality characteristics of spontaneously fermented goat meat sausage was investigated. The amounts of total biogenic amines in all the sausages ranged from 324.70 to 388.77 mg/kg; among them, spermine was the most abundant, with amounts ranging from 230.96 to 275.78 mg/kg. Increasing sodium chloride from 15 to 35 g/kg, the content of cadaverine, putrescine, tyramine, phenylethylamine, tryptamine, and total amines decreased, and Enterobacteriaceae counts decreased at the same time. Increasing sodium nitrite from 150 to 250 mg/kg, the content of cadaverine, histamine, and total amines decreased, while Enterobacteriaceae counts decreased simultaneously. Increasing glucose from 10 to 40 g/kg, the content of cadaverine, spermidine, and total amines decreased. Enterococcus was the most abundant genus across all the samples, and the relative abundance of Enterococcus was reduced obviously by increasing sodium nitrite and glucose levels. The top 10 differential bacterial taxa for each additive group were respectively obtained, and microbial biomarkers for each level of additive within its group were acquired, respectively. Through Pearson correlation, Lactobacillus was positively correlated with phenylethylamine, tryptamine, tyramine, and cadaverine, Bacteroides and Sediminibacterium were positively correlated with phenylethylamine and putrescine, respectively, suggesting they have the potential to produce biogenic amines. The results provided references for controlling the accumulation of biogenic amines in fermented goat meat sausage via the addition of auxiliary additives during the processing.

miR-194-Loaded Gelatin Nanospheres Target MEF2C to Suppress Muscle Atrophy in a Mechanical Unloading Model.

Muscle atrophy usually occurs under mechanical unloading, which increases the risk of injury to reduce the functionality of the moving system, while there is still no effective therapy until now. It was found that miR-194 was significantly downregulated in a muscle atrophy model, and its target protein was the myocyte enhancer factor 2C (MEF2C). miR-194 could promote muscle differentiation and also inhibit ubiquitin ligases, thus miR-194 could be used as a nucleic acid drug to treat muscle atrophy, whereas miRNA was unstable in vivo, limiting its application as a therapeutic drug. A gelatin nanosphere (GN) delivery system was applied for the first time to load exogenous miRNA here. Exogenous miR-194 was loaded in GNs and injected into the muscle atrophy model. It demonstrated that the muscle fiber cross-sectional area, in situ muscle contractile properties, and myogenic markers were increased significantly after treatment. It proposed miR-194 loaded in GNs as an effective treatment for muscle atrophy by promoting muscle differentiation and inhibiting ubiquitin ligase activity. Moreover, the developed miRNA delivery system, taking advantage of its tunable composition, degradation rate, and capacity to load various drug molecules with high dosage, is considered a promising platform to achieve precise treatment of muscle atrophy-related diseases.

[A Comparative Study of Intraoperative Application of Fluorescein and Indocyanine Green Videoangiography in Intracranial Aneurysm Clipping Surgery].

OBJECTIVE: To compare the application of fluorescein videoangiography (FL-VA) and indocyanine green videoangiography (ICG-VA) in intracranial aneurysm surgery. METHODS: A total of 65 patients who underwent aneurysm clipping in our hospital from January 2019 to January 2020 were included in the study. FL-VA and ICG-VA were used during the surgery to determine whether the aneurysm is completely clipped and the artery bearing the aneurysm and the perforating artery around the aneurysm are unobstructed. RESULTS: All 65 patients underwent both FL-VA and ICG-VA intraoperatively after aneurysm clipping. FL-VA was applied first. In 30 cases, FL-VA and ICG-VA provided the same results. In 10 cases, FL-VA performed obviously better over ICG-VA in visualizing small perforating arteries (2 cases of internal carotid artery-posterior communicating artery aneurysms and 3 cases of anterior communicating artery aneurysm) and evaluating whether the aneurysm was completely clipped (3 cases of middle cerebral artery aneurysm, 1 case of internal carotid artery-posterior communicating artery aneurysms and 1 case of distal anterior cerebral artery aneurysm). In the remaining 25 cases, ICG-VA was repeatedly applied in a short period of time due to quick clearance of indocyanine green from the blood vessels, but this couldn't be done with FL-VA. CONCLUSIONS: Compared with ICG-VA, FL-VA can provide better visualization of perforating artery, and can determine whether the aneurysm was completely clipped more accurately. However FL-VA couldn't be repeatedly applied during a short period of time.

Quercetin prevents bone loss in hindlimb suspension mice via stanniocalcin 1-mediated inhibition of osteoclastogenesis.

Recent studies demonstrate that diet quercetin (Quer) has obvious bone protective effects on ovariectomized rodents but thus far there is no direct evidence to support the inhibitory effect of Quer on bone loss caused by long-term unloading. In the present study, we investigated whether Quer could prevent bone loss induced by unloading in mice. Mice were subjected to hindlimb suspension (HLS) and received Quer (25, 50, 100 mg· kg-1 ·day-1, ig) for 4 weeks. Before euthanasia blood sample was collected; the femurs were harvested and subjected to MicroCT analysis. We showed that Quer administration markedly improved bone microstructure evidenced by dose-dependently reversing the reduction in bone volume per tissue volume, trabecular number, and bone mineral density, and the increase of trabecular spacing in mice with HLS. Analysis of serum markers and bone histometric parameters confirmed that Quer at both middle and high doses significantly decreased bone resorption-related markers collagen type I and tartrate-resistant acid phosphatase 5b, and increased bone formation-related marker procollagen 1 N-terminal propeptide as compared with HLS group. Treatment with Quer (1, 2, 5 µM) dose-dependently inhibited RANKL-induced osteoclastogenesis through promoting the expression of antioxidant hormone stanniocalcin 1 (STC1) and decreasing ROS generation; knockdown of STC1 blocked the inhibitory effect of Quer on ROS generation. Knockdown of STC1 also significantly promoted osteoclastogenesis in primary osteoclasts. In conclusion, Quer protects bones and prevents unloading-caused bone loss in mice through STC1-mediated inhibition of osteoclastogenesis. The findings suggest that Quer has the potential to prevent and treat off-load bone loss as an alternative supplement.

[Effects of high CO2 concentration, drought, and their interaction on different stay-green wheat seedlings]. / 高CO2æµ“åº¦ã€å¹²æ—±åŠå ¶äº’ä½œå¯¹ä¸åŒæŒç»¿åž‹å°éº¦å¹¼è‹—çš„å½±å“.

In this study, a pot experiment was carried out to examine the effects of high CO2 concentration, drought and interaction on seedling growth traits, biomass accumulation and physiological characteristics of different stay-green wheat seedlings, with a stay-green wheat variety Yannong 19 and a non stay-green wheat variety Hanxuan 3 as test materials. There were four treatments in the Open Top Chamber with factorial of CO2 concentration (370 µmol·mol-1 vs 550 µmol·mol-1) and drought (45%-55% vs. 75%-85% of field water-holding capacity). Drought significantly inhibited the growth and development of wheat seedlings, while CO2 concentration significantly increased the number of tillers and promoted the growth and development of wheat seedlings. Under drought condition, high CO2 concentration increased the number of tillers of Hanxuan 3 and Yannong 19 by 61.0% and 42.3%, respectively. Under both water conditions, high CO2 concentration significantly increased the biomass of wheat seedlings, and decreased the content of peroxidase and proline in leaves. Under drought condition, high CO2 concentration showed stronger "fertilizer effect". Furthermore, different varieties had different responses to high CO2 concentration, with higher sensitivity of Hanxuan 3 to enhancement of CO2 concentration. Under the scenario of increasing CO2 concentration, the amount of irrigation water applied to a field can be appropriately reduced for efficient use of water resources. Meanwhile, it is necessary to pay attention to the selection of suitable wheat varieties.

Antitumor Activity and Mechanism Study of Riluzole and Its Derivatives.

To explore novel antitumor agents with high efficiency and low toxicity, riluzole alkyl derivatives (4a-4i) were synthesized. Their anti-proliferative activities against HeLa, HepG2, SP2/0, and MCF-7 cancer cell lines were assessed by the CCK-8 assay and compared with human normal liver (LO2) cells. Most of them showed potent cytotoxic effects against four human tumor cell lines and low toxic to LO2 cells. In particular, 2-(N-ethylamine)-6-trifluoromethoxy- benzothiazole (4a) showed a IC50 value of 7.76 µmol/L in HeLa cells and was found to be nontoxic to LO2 cells up to 65 µmol/L. Furthermore, flow cytometry indicated that 4a could induce remarkable early apoptosis and G2/M cell cycle arrest in HeLa cells. It also impaired the migration ability of HeLa cells in wound healing assays. Western blot results demonstrated that 4a suppressed Bcl-2 protein expression but increased the level of Bax in HeLa cells, and elevated the Bax/Bcl-2 expression ratio. These new findings suggest that 4a exhibited beneficially anti-cervical cancer effect on HeLa cells by inducing HeLa cell apoptosis.

Detachable balloon embolization as the preferred treatment option for traumatic carotid-cavernous sinus fistula?

OBJECTIVE: The purpose of the study was to investigate the treatments and outcomes of patients with traumatic carotid-cavernous sinus fistula (TCCF). METHODS: All patients diagnosed with TCCF at our institution from January 2013 to December 2018 and meeting the inclusion/exclusion criteria were included in the study. RESULTS: A total of 24 patients were included in this study. Of them, 21 (87.5%) were treated with detachable balloon embolization, 1 (4%) with coil embolization, 1 (4%) with balloon-assisted coil embolization, and 1 (4%) with balloon-assisted coil and glue embolization. Among the 21 patients treated with detachable balloon embolization, 10 underwent double-balloon technique embolization including double-detachable balloon embolization (n = 6) and balloon-assisted detachable balloon embolization (n = 4). The fistulas in 17 patients (17/21, 81%) were successfully occluded after the first attempt of detachable balloon embolization, while those in the remaining 4 patients were occluded after a second surgery due to TCCF recurrence or pseudoaneurysm development. Preservation of the internal carotid artery (ICA) was observed in 19 cases after the first treatment by detachable balloon embolization (19/21, 90.4%). ICA was occluded in the remaining two patients, as revealed by a complete angiographic evaluation of the circle of Willis. All patients achieved complete resolution of ocular and orbital manifestations as well as pulsatile bruit, except for three patients whose oculomotorius and/or abducens remained paralyzed during the follow-up period. CONCLUSION: Although several endovascular treatment options are available for TCCF, the detachable balloon embolization is still the preferred method of TCCF, as evidenced in our study. Furthermore, double balloon technique, an improvement upon the conventional detachable balloon embolization, is extremely safe and can effectively treat patients with refractory TCCF.

Treatment of traumatic intracranial aneurysm: Experiences at a single center.

OBJECTIVE: To report the treatment and outcome of traumatic intracranial aneurysm (TICA) cases at the Southwest Hospital, Army Medical University in China. PATIENTS AND METHODS: All patients diagnosed with TICA at our institution from January 1, 1977, to October 31, 2018, and meeting the inclusion/exclusion criteria were included in the study. Cases were reported separately for those diagnosed before 1998 and those after 1998. RESULTS: A total of 25 patients were included in the study. Ten were diagnosed with TICA prior to 1998. Seven of these 10 patients were treated surgically with parent artery sacrificed, including aneurysmectomy, trapping, and bypass. The mean Glasgow Outcome Scale (GOS) score for the 7 patients with surgical treatment was 3.1. Three of the 10 patients died of severe complications, including intracranial infection, delayed bleeding, and deadly injury. After 1998, 15 patients were diagnosed with TICA. Thirteen presented with head trauma and two with iatrogenic TICA following ventricle drainage or sphenoid ridge meningioma resection. Thirteen were treated with endovascular treatment, including coil alone, glue, coil-associated glue, stent alone, stent-assisted coil embolization, one with clipping, and one with conservative treatment. The 13 patients with endovascular treatment achieved a mean GOS score of 4.5. Among the 13 patients, one died from intracranial infection, one suffered recurrence, and one had intraoperative rupture. CONCLUSION: Although the treatment of TICA has traditionally been surgical, endovascular treatment with different techniques, such as endovascular patch, provides a valuable alternative. Currently, the flow diverter is a popular embolization device and may represent another valid treatment option for TICA.

Urokinase, a promising candidate for fibrinolytic therapy for intracerebral hemorrhage.

OBJECTIVE Intracerebral hemorrhage (ICH) is associated with a high rate of mortality and severe disability, while fibrinolysis for ICH evacuation is a possible treatment. However, reported adverse effects can counteract the benefits of fibrinolysis and limit the use of tissue-type plasminogen activator (tPA). Identifying appropriate fibrinolytics is still needed. Therefore, the authors here compared the use of urokinase-type plasminogen activator (uPA), an alternate thrombolytic, with that of tPA in a preclinical study. METHODS Intracerebral hemorrhage was induced in adult male Sprague-Dawley rats by injecting autologous blood into the caudate, followed by intraclot fibrinolysis without drainage. Rats were randomized to receive uPA, tPA, or saline within the clot. Hematoma and perihematomal edema, brain water content, Evans blue fluorescence and neurological scores, matrix metalloproteinases (MMPs), MMP mRNA, blood-brain barrier (BBB) tight junction proteins, and nuclear factor-κB (NF-κB) activation were measured to evaluate the effects of these 2 drugs in ICH. RESULTS In comparison with tPA, uPA better ameliorated brain edema and promoted an improved outcome after ICH. In addition, uPA therapy more effectively upregulated BBB tight junction protein expression, which was partly attributed to the different effects of uPA and tPA on the regulation of MMPs and its related mRNA expression following ICH. CONCLUSIONS This study provided evidence supporting the use of uPA for fibrinolytic therapy after ICH. Large animal experiments and clinical trials are required to further explore the efficacy and safety of uPA in ICH fibrinolysis.

Autophagy activated by duck enteritis virus infection positively affects its replication.

Duck enteritis virus (DEV) is an acute, septic, sexually transmitted disease that occurs in ducks, geese and other poultry. Autophagy is an evolutionarily ancient pathway that is important in many viral infections. Despite extensive study, the interplay between DEV and autophagy of host cells is not clearly understood. In this study, we found that DEV infection triggers autophagy in duck embryo fibroblast (DEF) cells, as demonstrated by the appearance of autophagosome-like double- or single-membrane vesicles in the cytoplasm of host cells and the number of GFP-LC3 dots. In addition, increased conversion of the autophagy marker protein LC3-I and LC3-II and decreased p62/SQSTM1 indicated complete autophagy flux. Heat-inactivated DEV infection did not induce autophagy, suggesting that the trigger of autophagy in DEF cells depended on DEV replication. When autophagy was pharmacologically inhibited by LY294002 or wortmannin, DEV replication decreased. The DEV offspring yield decreased when small interference RNA was used to interfere with autophagy related to the genes Beclin-1 and ATG5. In contrast, after treating DEF cells with rapamycin, an inducer of autophagy, DEV replication increased. These results indicated that DEV infection induced autophagy in DEF cells and autophagy facilitated DEV replication.

Endovascular treatment of distal posterior inferior cerebellar artery aneurysms.

OBJECTIVE: To assess the feasibility and results of endovascular treatment for ruptured distal posterior inferior cerebellar artery (PICA) aneurysms. METHODS: We retrospectively reviewed our experience and results with endovascular treatments for a series of 13 consecutive patients with ruptured distal PICA aneurysms at the Southwest Hospital, Chongqing, China, treated between June 2011 and January 2015. Therapeutic considerations, intraoperative complications, and results were evaluated. RESULTS: Endovascular embolization was performed in all 13 patients including selective coiling (4), stentassisted coiling (2), microcatheter-assisted coiling (1), coiling without adjunctive techniques (1), and parent artery occlusion (5). Planed stent deployment failure occurred in one patients resulting from marked stenosis at the origin of the PICA; the patient`s existing partial Wallenberg`s syndrome became worse after treatment. Another 2 patients treated with parent artery occlusion recovered well without developing obvious neurological deficits, although a small cerebellar infarction of the distal PICA was observed. No patient experienced post procedural hemorrhage during the follow-up period (8-46 months; mean, 26.8 months). CONCLUSION: Distal PICA aneurysms can be managed effectively with various endovascular methods. Protective strategies using a stent or microcatheter for preserving the patency of the proximal PICA segment are a viable treatment option in reducing the potential risk of brain stem ischemia in selected patients.

Endovascular treatment of a traumatic dural arteriovenous fistula of the superior sagittal sinus using dual lumen balloon microcatheter.

Dural arteriovenous fistula (DAVFs) induced by trauma in the superior sagittal sinus (SSS) are rare and difficult to treat because of their unique midline location, multiplicity of arterial feeders, and critical venous drainage. We report a case of an endovascular treatment using dual lumen balloon microcatheter on a patient with post-traumatic SSS DAVF. By the use of dual lumen Scepter balloon microcatheter, proximal Onyx reflux was prevented. In this case, complete embolization of the DAVFs was achieved and the outcome of the patient was fairly good.

Embolization of direct carotid cavernous fistulas with the novel double-balloon technique.

Multiple endovascular management of direct carotid cavernous fistula (CCF) has been widely accepted as a treatment option. Embolization of the fistula with detachable balloons or thrombogenic coil-based occlusion has been the main choice to treat direct CCF, with good safety and efficacy. This study investigated the safety and efficacy of embolization of direct CCF with the novel double-balloon technique. A retrospective review of a prospective database on cerebral vascular disease was performed. We identified a total of five patients presenting with high-flow direct CCF. All patients were managed with transarterial embolization with the novel double-balloon technique. Three of the five patients were treated with two detachable balloons, and a completely occluded fistula with preservation of the internal carotid artery was achieved. Of the remaining two patients treated with more detachable balloons, one patient achieved a perfect outcome and the other one suffered from recurrent fistula due to balloon migration 3 weeks after embolization. During a follow-up period of 12-18 months, no symptoms reoccurred in any patient. Thus, the double-balloon treatment may be a promising method for CCF complete occlusion. This novel technique may bring more benefits in the following two cases: 1). A single inflated detachable balloon fails to completely occlude the CCF, which causing the next balloon can not pass into the fistula. 2). A giant CCF needs more balloons for fistula embolization.

Role of phytochemicals in colorectal cancer prevention.

Although the incidence of colorectal cancer (CRC) has been declining in recent decades, it remains a major public health issue as a leading cause of cancer mortality and morbidity worldwide. Prevention is one milestone for this disease. Extensive study has demonstrated that a diet containing fruits, vegetables, and spices has the potential to prevent CRC. The specific constituents in the dietary foods which are responsible for preventing CRC and the possible mechanisms have also been investigated extensively. Various phytochemicals have been identified in fruits, vegetables, and spices which exhibit chemopreventive potential. In this review article, chemopreventive effects of phytochemicals including curcumin, polysaccharides (apple polysaccharides and mushroom glucans), saponins (Paris saponins, ginsenosides and soy saponins), resveratrol, and quercetin on CRC and the mechanisms are discussed. This review proposes the need for more clinical evidence for the effects of phytochemicals against CRC in large trials. The conclusion of the review is that these phytochemicals might be therapeutic candidates in the campaign against CRC.

Endovascular treatment of posterior communicating artery aneurysms in the presence of the fetal variant of posterior cerebral artery.

Posterior communicating artery (PcomA) aneurysms in the presence of the fetal variant of posterior cerebral artery (PCA) often pose technical challenges for endovascular treatment because of a greater potential for ischemic injury with the fetal PCA compromise. The purpose of this study was to assess the feasibility and results of endovascular treatment for these lesions. We retrospectively reviewed our experience and results of endovascular treatments for a series of nine consecutive patients with PcomA aneurysms occurring at the origin of fetal PCAs at the Department of Neurosurgery of Southwest Hospital, Chongqing, China, between June 2011 and June 2014. Depending on the angiographic findings, location and shape of the aneurysms, various therapeutic strategies were used including coiling by single or double microcatheter, balloon remodeling technique, and single or Y-stenting technique. Overall, fetal PCA was preserved patent in all cases, and complete or near complete occlusion was achieved in 8/9 cases. There was no procedure-related morbidity or mortality. With the exception of one patient who died of pneumonia 6 weeks after treatment, no clinical evidence of neurologic deterioration and hemorrhagic complication was seen during the follow-up period in the remaining 8 patients. Our experience suggests that endovascular treatment is relatively safe and technically feasible in most patients with PcomA aneurysms in the presence of fetal PCA using multiple strategies.