Application of a nomogram model for the prediction of 90-day poor outcomes following mechanical thrombectomy in patients with acute anterior circulation large-vessel occlusion.

Background: The past decade has witnessed advancements in mechanical thrombectomy (MT) for acute large-vessel occlusions (LVOs). However, only approximately half of the patients with LVO undergoing MT show the best/independent 90-day favorable outcome. This study aimed to develop a nomogram for predicting 90-day poor outcomes in patients with LVO treated with MT. Methods: A total of 187 patients who received MT were retrospectively analyzed. Factors associated with 90-day poor outcomes (defined as mRS of 4-6) were determined by univariate and multivariate logistic regression analyzes. One best-fit nomogram was established to predict the risk of a 90-day poor outcome, and a concordance index was utilized to evaluate the performance of the model. Additionally, 145 patients from a single stroke center were retrospectively recruited as the validation cohort to test the newly established nomogram. Results: The overall incidence of 90-day poor outcomes was 45.16%, affecting 84 of 186 patients in the training set. Moreover, five variables, namely, age (odds ratio [OR]: 1.049, 95% CI [1.016-1.083]; p = 0.003), glucose level (OR: 1.163, 95% CI [1.038-1.303]; p = 0.009), baseline National Institute of Health Stroke Scale (NIHSS) score (OR: 1.066, 95% CI [0.995-1.142]; p = 0.069), unsuccessful recanalization (defined as a TICI grade of 0 to 2a) (OR: 3.730, 95% CI [1.688-8.245]; p = 0.001), and early neurological deterioration (END, defined as an increase of ≥4 points between the baseline NIHSS score and the NIHSS score at 24 h after MT) (OR: 3.383, 95% CI [1.411-8.106]; p = 0.006), were included in the nomogram to predict the potential risk of poor outcomes at 90 days following MT in LVO patients, with a C-index of 0.763 (0.693-0.832) in the training set and 0.804 (0.719-0.889) in the validation set. Conclusion: The proposed nomogram provided clinical evidence for the effective control of these risk factors before or during the process of MT surgery in LVO patients.

Cytotoxicity sesquiterpenoids from the leaves of Datura stramonium L.

Four new sesquiterpenoids, dstramonins A-D (1-4), and one new natural product (5), together with three known compounds (6-8), were isolated from the leaves of Datura stramonium L. The structures of new compounds were elucidated by extensive spectroscopic analysis and comparison with the literature. The cytotoxicity of isolates against LN229 cells was assessed and compounds 2-4, and 7 displayed cytotoxic activity with IC50 values ranging from 8.03 to 13.83 µM.

Bisphenol A exposure decreases sperm production and male fertility through inhibition PCBP2 expression.

Growing evidence suggests that the exposure of bisphenol A (BPA), an endocrine disruptor that commonly present in the environment, can impair reproduction. However, conflicting results have been reported, and the underlying mechanism has not been fully understood. In this study, 3-week-old male mice were oral exposed to 50 mg/kg/d BPA or equivalent corn oil for 28 days. Their testis and epididymis were then collected for morphology examination by HE stains. The number of sperm was counted, and the morphology was analyzed by PNA (peptide nucleic acid) and pap staining. Fertilization capacity and successful rate were analyzed after mating with wide-type females. Spermatid DNA damage and apoptosis were evaluated by DFI, γH2AX stain, and TUNEL assay. RNA sequencing analysis was conducted to identify differentially expressed genes in testicular tissue of mice exposed to BPA. RNA interference was used to verify the regulatory mechanism of BPA exposure on gene expression in GC-2 cells. Our data showed that the total number of sperm was decreased and the morphology was impaired in BPA-exposed mice. In addition, the serum testosterone level and fertilization efficiency were also reduced. Mechanism studies showed that BPA could suppress the expression of PCBP2, a key regulatory gene in spermatid development, by activating the EZH2/H3K27me3. In conclusion, we found that BPA exposure can impair spermatid development via affecting key gene expression that is at least partially due to epigenetic modification.

Overexpressing Runx2 of BMSCs Improves the Repairment of knee Cartilage Defects.

BACKGROUND: Recruitment of gene modifying bone marrow mesenchymal stem cells (BMSCs) has been considered an alternative to single-cell injection in articular cartilage repair. PURPOSE: This study aimed to investigate whether the effect of runt-related transcription factor 2(Runx2) overexpression bone marrow mesenchymal stem cells in vivo could improve the quality of repaired tissue of a knee cartilage defect in a rabbit model. METHODS: Thirty-two New Zealand rabbits were randomly divided into four groups. The blank group (Con) did not receive anything, the model group (Mo) was administered saline, the simple stem cell group (MSCs) received MSCs injection, and the Runx2 transfection group (R-MSCs) received Runx2 overexpression MSCs injection. After adapting to the environment for a week, a 5 mm diameter cylindrical osteochondral defect was created in the center of the medial femoral condyle. Cell and saline injections were performed in the first and third weeks after surgery. The cartilage repair was evaluated by macroscopically and microscopically at 4 and 8 weeks. RESULTS: Macroscopically, defects were filled and surfaces were smoother in the MSCs groups than in the Mo group at 4th week. Microscopically, the R-MSCs group showed coloration similar to surrounding normal articular cartilage tissue at 8 weeks in masson trichrome staining. The COL-II, SOX9, and Aggrecan mRNA expressions of MSCs were enhanced at 4 weeks compared with R-MSCs, then the expression reduced at 8 weeks, but was still higher than Mo group level (P<0.05). The western blot examination revealed that the COL-IIand SOX9 expression of MSCs was higher than R-MSCs at 4 weeks, then the expression reduced at 8 weeks, but was still higher than the Mo level (P<0.05). The IL-1ß content in the joint fluid also revealed that cartilage repair with R-MSCs was better than that with MSCs at 8 weeks (P<0.05). CONCLUSION: The R-MSCs group showed cellular morphology and arrangement similar to surrounding normal articular cartilage tissue, and Runx2 overexpression of MSCs resulted in overall superior cartilage repair as compared with MSCs at 8 weeks.

Dissection-related carotid-cavernous fistula (CCF) following surgical revascularization of chronic internal carotid artery occlusion: a new subtype of CCF and proposed management.

BACKGROUND: The development of carotid-cavernous fistulas (CCFs) during surgical recanalization of chronic internal carotid artery occlusion (ICAO) may be secondary to severe ICA dissection rather than a focal tear of the cavernous ICA seen in typical traumatic CCFs. The purpose of this study is to investigate the causal relationship between the CCFs and severe ICA dissections and to characterize technical outcomes after treatment with stenting. METHODS: Five patients underwent treatment with self-expanding stents due to intraprocedural CCF and ICA dissection following surgical removal of ICAO plaque. The stents were telescopically placed via true channel of the dissection. Safety of the procedure was evaluated with 30-day stroke and death rate. Procedural success was determined by the efficacy of CCF obliteration and ICAO recanalization with angiography. RESULTS: All CCFs were associated with spiral and long segmental dissection from the cervical to cavernous ICA. After stenting, successful dissection reconstruction with TICI 3 was achieved in all patients, with complete (n = 4) or partial CCF (n = 1) obliteration. No patient had CCF syndrome, stroke, or death during follow-up of 6 to 37 months; but one patient had pulsatile tinnitus, which resolved 1 year later. Angiography at 6 to 24 months demonstrated CCF obliteration in all 5 patients and durable ICA patency in 4 patients. CONCLUSIONS: Intraprocedural CCFs with spiral and cervical-to-cavernous ICA dissection during ICAO surgery are dissection-related because of successful obliteration after stenting for dissection reconstruction. Self-expanding stenting through true channel of the dissection, serving as implanting stent-autograft, may be an optimal therapy for the atypical CCF complication from ICAO surgery.

Diagnostic value of contrast-enhanced harmonic endoscopic ultrasonography in predicting the malignancy potential of submucosal tumors: a systematic review and meta-analysis.

OBJECTIVES: Contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) utilizes the second-harmonic signals from contrast microbubbles located in the vessels to improve the detectability of microcirculation. Many studies have used CH-EUS to stratify the malignancy risk of submucosal tumors (SMTs), discriminate gastrointestinal stromal tumors (GISTs) from benign SMTs, and predict the malignancy of GISTs based on the regularity of vessels or enhancing patterns. The aim of this study was to conduct a meta-analysis to evaluate the diagnostic performance of CH-EUS in the differential diagnosis of SMTs. METHODS: After searching the Medline, Embase, and Cochrane databases systematically, studies that evaluated the diagnostic accuracy of CH-EUS for the prediction of the malignancy potential of SMTs were pooled. The diagnostic accuracy was computed using a stochastic effect model. The overall test performance was summarized with the summary receiver operating characteristic curve. RESULTS: Six studies discriminated GISTs from benign lesions, and three studies discriminated low-risk from high-risk GISTs, covering a total of 354 cases of SMT. The overall accuracy of CH-EUS in predicting malignancy risk can be assessed as follows: sensitivity 0.87 (95% CI 0.82-0.91), specificity 0.82 (95% CI 0.74-0.89), positive likelihood ratio of 3.55 (95% CI 2.39-5.27), negative likelihood ratio of 0.21 (95% CI 0.13-0.33), and diagnostic odds ratio of 22.17 (95% CI 10.43-47.10). The overall area under the curve was 0.89. Subgroup analysis of the sensitivity and specificity for studies discriminating low-risk from high-risk GISTs were 0.93 (95% CI 0.77-0.99) and 0.81 (95% CI 0.63-0.93), respectively. There was evidence of significant heterogeneity, but no proof of publication bias. CONCLUSIONS: CH-EUS is an effective tool for improving the diagnostic accuracy of conventional EUS for discriminating SMTs and is superior to other imaging techniques. However, due to the limited number of well-designed control studies, we should take into consideration the uncertainty of this method when altering a treatment plan.

Covered Stenting Is an Effective Option for Traumatic Carotid Pseudoaneurysm with Promising Long-Term Outcome.

OBJECTIVE: Covered stenting is an optional strategy for traumatic carotid pseudoaneurysm, especially in malignant conditions of potential rupture, but the long-term outcomes are not clear. Our aim was to determine if covered stenting is an effective option for traumatic carotid pseudoaneurysm with promising long-term outcomes. METHODS: Self-expanding Viabahn and balloon-expandable Willis covered stents were separately implanted for extra- and intracranial traumatic carotid pseudoaneurysm. The covered stent was placed across the distal and proximal pseudoaneurysm leakage under roadmap guidance. Procedural success was defined as technical success (complete exclusion of the pseudoaneurysm and patency of the parent artery) without a primary end point (any stroke or death within 30 days after the procedure). Long-term outcomes were evaluated as ischemic stroke in the territory of the qualifying artery by clinical follow-up through outpatient or telephone consultation and as the exclusion of the pseudoaneurysm and patency of the parent artery by imaging follow-up through angiography. RESULTS: Five patients with traumatic carotid pseudoaneurysm who underwent covered stenting were enrolled. The procedural success rate was 100%. No ischemic stroke in the territory of the qualifying artery was recorded in any of the five patients during a mean clinical follow-up of 44±16 months. Complete exclusion of the pseudoaneurysm and patency of the parent artery were maintained in all five patients during a mean imaging follow-up of 39±16 months. CONCLUSION: Satisfactory procedural and long-term outcomes were obtained, suggesting that covered stenting is an effective option for traumatic carotid pseudoaneurysm.

Identification of key transcription factors associated with cerebral ischemia­reperfusion injury based on gene­set enrichment analysis.

Cerebral ischemia­reperfusion injury (CIRI) usually causes detrimental complications following reperfusion therapy in stroke patients. The present study systematically investigated the regulatory mechanism involved in the pathogenesis of CIRI using gene set enrichment analysis of the transient middle cerebral artery occlusion mouse stroke model. The results revealed a total of 13 CIRI­related transcription factors (TFs), including CCAAT enhancer binding protein b (Cebpb), Cebpa, early growth response­1, Fos, Rela, Jund, signal transduction and activator of transcription 5a/b, transformation related protein 53, GLI family zinc finger 2 (Gli2), Sp3, TF AP­2 α (Tfap2a) and spleen focus forming virus proviral integration oncogene (Spi1). To the best of our knowledge, five TFs (Cebpa, Gli2, Sp3, Tfap2a and Spi1) were the first to be reported associated with CIRI in the present study. The five novel CIRI­related TFs were mainly associated with pathways of inflammation and responses to reperfusion, including the tumor necrosis factor signaling pathway (Gli2, Spi1 and Tfap2a, P=0.0035, 0.0035 and 0.048, respectively), interleuking­17 signaling pathway (Cebpa, Gli2, Sp3, Spi1 and Tfap2a, P=0.019, 0.047, 0.019, 0.035 and 0.005, respectively) and fluid shear stress and atherosclerosis (Gli2, Sp3, Spi1 and Tfap2a, P=0.047, 0.046, 0.013 and 0.003, respectively). These results may improve understanding of the potential molecular mechanism underlying the pathogenesis of CIRI at the genome­wide level.

Outcomes of Multimodality In situ Recanalization in Hybrid Operating Room (MIRHOR) for symptomatic chronic internal carotid artery occlusions.

BACKGROUND: An in situ recanalization procedure of endovascular therapy (ET) or carotid endarterectomy (CEA) has been attempted in patients with symptomatic chronic internal carotid artery occlusions (ICAOs), though the recanalization rates of both are low. OBJECTIVE: To investigate the outcomes of Multimodality In situ Recanalization for ICAOs in a Hybrid Operating Room (MIRHOR) at the same session. METHODS: Symptomatic chronic ICAOs were classified into type A or B (short occlusion with or without a tapered residual root [TRR]), and C or D (long occlusion with or without TRR), and managed in a hybrid operating room with ET, CEA, or both, as needed. Primary efficacy outcome was technical success of recanalization with Thrombolysis in Myocardial Infarction 3. Secondary efficacy outcome was any stroke or death within 30 days (primary safety outcome) plus an ipsilateral ischemic stroke after 30 days. RESULTS: Technical success was finally achieved in 35 (83.3%) of 42 consecutively enrolled patients with ICAO, which was significantly higher than 35.7% (15/42, p<0.001) from the initial ET or CEA alone. Furthermore, the success rate was in descending order: 100% (18/18) for type A and B occlusions, 75% (6/8) for type C occlusions, and 69% (11/16) for type D occlusions (p=0.017). Two secondary efficacy outcome events (5.1%) without mortality, including one (2.4%) primary safety outcome, were observed during a mean follow-up of 10.5 months. CONCLUSION: The MIRHOR for symptomatic chronic ICAOs at the same session significantly improves technical success, with low periprocedural complications and favorable clinical outcomes. The ICAO classification appears valuable in predicting technical success.

The safety of triple antiplatelet therapy under thromboelastography guidance in patients undergoing stenting for ischemic cerebrovascular disease.

OBJECTIVE: To investigate the safety of triple antiplatelet therapy (TAT) with cilostazol in patients undergoing stenting for extracranial and/or intracranial artery stenosis. METHODS: A prospectively collected database was reviewed to identify patients who underwent stenting for extracranial and/or intracranial artery stenosis and showed resistance to aspirin and/or clopidogrel as assessed by pre-stenting thromboelastography (TEG) testing. Patients were assigned to a TAT group and a dual antiplatelet therapy (DAT) group. Major complications were defined as thromboembolic events (transient ischemic attack (TIA), ischemic stroke, and stent thrombosis) or major bleeding events within 30 days, and minor complications were defined as extracranial bleeding that did not require vascular surgery or transfusion within 30 days. RESULTS: A total of 183 patients were identified. The incidence of major complications was significantly lower in the TAT group than in the DAT group (TAT group vs. DAT group, 1/110 vs. 6/73; P=0.017). TIAs occurred in four patients, with one in the TAT group and three in the DAT group (1/110 vs. 3/73; P=0.303). Ischemic strokes occurred in three patients in the DAT group (TAT group vs. DAT group, P=0.062). No major bleeding events or stent thrombosis was recorded in either group. Two patients (one in each group) experienced minor complications that resolved without additional treatment (1/110 vs. 1/73; P>0.999). CONCLUSIONS: TAT under TEG guidance appears to be a safe antiplatelet strategy in patients undergoing stenting for extracranial and/or intracranial artery stenosis. By employing TAT under TEG guidance, favorable outcomes can be achieved in these patients.