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Duchenne muscular dystrophy (DMD) is a serious and progressive hereditary muscle disease. The DMD gene mutation on the X chromosome causes the loss of dystrophin, causing progressive muscle weakness and muscular atrophy. Most patients die for heart and lung failure. Current gene therapy methods are mainly aimed at restoring the expression of dystrophin, including read-through therapy, exon skipping therapy, vector-mediated gene replacement therapy and gene editing therapy. This article reviews the mechanisms of these different treatments and important advances in clinical research, and analyzes the challenges and application prospects of these treatments.
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Objective:To investigate the correlation between serum CXCL12 and the outcomes after intravenous thrombolytic therapy in patients with acute ischemic stroke.Methods:Consecutve patients with acute ischemic stroke treated with intravenous thrombolytic therapy in the Department of Neurology, the First Affiliated Hospital of Soochow University from January 1, 2020 to August 31, 2021 were enrolled retrospectively. Serum CXCL12 was measured by enzyme-linked immunosorbent assay within 24 h of onset. No improvement in early neurological function was defined as the National Institutes of Health Stroke Scale (NIHSS) 24 h after thrombolysis decreased by <4 compared with the baseline. The clinical outcome was evaluated by the modified Rankin Scale at 90 d after onset, and >2 were defined as a poor outcome. Multivariate logistic regression analysis was used to evaluate the correlation between serum CXCL12 and the outcome after intravenous thrombolysis, and the predictive value of serum CXCL12 for no improvement of early neurological function and poor short-term outcome was analyzed by the receiver operating characteristic (ROC) curve. Results:A total of 66 patients were enrolled, and the serum CXCL12 was 15.72±6.52 g/L. Twenty-seven patients (40.9%) had poor outcomes, and 34 (51.5%) had no improvement in early neurological function. Multivariate logistic regression analysis showed that higher serum CXCL12 was an independent predictor of poor outcome (odds ratio [ OR] 1.245, 95% confidence interval [ CI] 1.093-1.419; P=0.001) and no improvement in early neurological function ( OR 1.250, 95% CI 1.100-1.420; P=0.001). ROC curve analysis showed that the area under the curve of serum CXCL12 for predicting poor outcome was 0.793 (95% CI 0.679-0.908), the best cut-off value was 15.38 μg/L, and the corresponding sensitivity and specificity were 81.5% and 76.9%, respectively. The area under the curve of serum CXCL12 for predicting no improvement of early neurological function was 0.849 (95% CI 0.748-0.951), and the best cut-off value was 15.68 μg/L, and the corresponding sensitivity and specificity were 76.5% and 87.5%, respectively. Conclusion:Serum CXCL12 had a better predictive value for the outcomes of patients with acute ischemic stroke after intravenous thrombolytic therapy.
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Ischemic stroke is one of the primary causes of death and disability worldwide. Neutrophils can release depolymerized chromatin and proteins to form neutrophil extracellular traps (NETs) and participate in intravascular thrombus formation. In recent years, NETs have received increasing attention in the study of acute ischemic stroke. The results indicate that NETs play an important role in the pathogenesis of acute ischemic stroke. This review presented recent advances in the study of NETs in acute ischemic stroke.
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The reperfusion therapies for acute ischemic stroke (AIS) patients in the past have set strict limits on time window. However, with the imaging assessment algorithms for "tissue window" becoming more mature, the time window for reperfusion therapies has been continuously extended. Nowadays the time window of intravenous thrombolysis has been extended to 9 hours after onset of stroke and is expected to be further broadened to 24 hours. At the same time, clinical studies of mechanical thrombectomy for posterior circulation large vessel occlusion (LVO), LVO with large ischemic cores and distal and medium vessel occlusion are all in hot progress. This article summarized diverse imaging assessment algorithms for "tissue window" and the latest advances of clinical research related to different fibrinolytic drugs for intravenous thrombolysis, mechanical thrombectomy for various vascular occlusion and bridging therapy of AIS in the extended time window. The objective of this review was to provide some references for the clinical diagnosis and therapy of stroke beyond time window.
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Endovascular mechanical thrombectomy (EMT) has become the main treatment of acute ischemic stroke, but the pathological study of thrombi retrieved with EMT is still very limited. This article reviews the routine staining, special components, expression of immune factors, electron microscopic morphology, imaging features of the pathological components of thrombi retrieved with EMT, and their correlation with the etiological differentiation and outcomes of stroke.
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AIM: To investigate the efficacy of orbicularis oculi muscle resection combined with orbicularis oculi muscle shortening and lower eyelid retractor reduction in the treatment of elderly lower eyelid entropion.METHODS:A retrospective study was conducted among 97 elderly patients(175 eyes)with lower eyelid entropion who admitted to the hospital from June 2019 to June 2021. According to the treatment method, the patients were divided into control group(47 patients of 82 eyes treated with orbicularis oculi muscle resection)and combination group(50 patients of 93 eyes treated with orbicularis oculi muscle resection combined with orbicularis oculi muscle shortening and lower eyelid retractor reduction). The two groups were compared in terms of short-term curative effect, perioperative indexes, scores of symptoms and signs before and after surgery, width of palpebral fissure before and after surgery, direction of eyelashes, exposure rate of lacrimal caruncle, complications, and patient satisfaction.RESULTS: The total response rate in the combination group was significantly higher than that in the control group(95% vs 80%, P=0.004). The intraoperative blood loss, operation time and hospital stay of the combination group were significantly more/longer than those of the control group(P<0.001). The scores of symptoms and signs such as lacrimation, foreign body sensation, photophobia and irritation in the combination group after the surgery were significantly lower than those in the control group(all P<0.001). After surgery, the width of palpebral fissure, direction of eyelashes and exposure rate of lacrimal caruncle in the combination group were higher than those in the control group(P<0.001). The incidence of postoperative complications in the combination group was lower than that in the control group(8% vs 18%, P=0.032). The patient satisfaction scores of comfort level, trichiasis correction, scar appearance, eyes symmetry and appearance in the combination group were higher than those in the control group(all P<0.001).CONCLUSION: Orbicularis oculi muscle resection combined with orbicularis oculi muscle shortening and lower eyelid retractor reduction is effective and safe in the treatment of elderly lower eyelid entropion, which can meet the requirements of the patients.
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Cardiac stroke is a stroke that occurs when a heart mural thrombus falls off and embolizes in the cerebral arterial system caused by various causes of heart disease, accounting for about 30% of all ischemic strokes. At present, in order to find evidence that emboli may originate from the heart, a large number of auxiliary examinations are needed. Good blood biomarkers are essential for the rapid identification of ischemic stroke in the emergency department. However, there is no breakthrough in this area. Brain natriuretic peptide is secreted in ventricular muscle and hypothalamus. It may be an important bridge between brain and heart diseases. However, the application of brain natriuretic peptide in the diagnosis and treatment of cardiogenic stroke is still very limited. This article reviews the current research status of brain natriuretic peptide levels and cardiogenic stroke and proposes further research trends and prospects.
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Objective:To investigate the predictive value of regional leptomeningeal collateral (rLMC) score on CT angiography (CTA) for the outcome after endovascular therapy in patients with late window anterior circulation stroke.Methods:Patients with acute anterior circulation large vessel occlusive stroke received endovascular treatment 6 to 24 h after onset in the Department of Neurology, the First Affiliated Hospital of Soochow University from January 2018 to July 2021 were enrolled retrospectively. At 3 months after onset, the outcome was evaluated according to the modified Rankin Scale. A score of ≤ 2 was defined as good outcome, and a score of >2 was defined as poor outcome. The clinical data, non-enhanced CT and CTA parameters of the patients were collected. Multivariate logistic analysis was used to determine the independent influencing factors of poor outcomes after endovascular treatment. Results:A total of 74 patients with acute anterior circulation large vessel occlusive stroke treated with endovascular treatment in the late window were enrolled. Their age was 64.41±12.98 years, 43 were males (58.1%). The baseline National Institutes of Health Stroke Scale (NIHSS) score was 13.18±5.22, and the median time from onset to puncture was 527.5 min. Fifty-three patients (71.6%) chose direct thrombectomy and 21 (28.4%) chose intravenous thrombolysis and bridging thrombectomy. Thirty-six patients (48.6%) had a good outcome and 38 (51.4%) had a poor outcome, including 4 (5.4%) died. Univariate analysis showed that there were significant differences in age, atrial fibrillation, fasting blood glucose, NIHSS score, Alberta Stroke Program Early CT Score (ASPECTS), rLMC score and clot burden score between the good outcome group and the poor outcome group (all P<0.05). Multivariate logistic regression analysis showed that higher ASPECTS (odds ratio 0.352, 95% confidence interval 0.157-0.791; P=0.012) and rLMC score (odds ratio 0.550, 95% confidence interval 0.329-0.919; P=0.022) were the independent predictors of good outcomes after endovascular therapy. Conclusion:ASPECTS and rLMC scores were the independent predictors of clinical outcomes after endovascular therapy in patients with late window anterior circulation large vessel occlusive stroke. It had certain guiding value for the decision-making of endovascular treatment in such patients.
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OBJECTIVE@#To observe the clinical therapeutic effect of electroacupuncture (EA) combined with tamsulosin hydrochloride sustained release capsule on chronic prostatitis (CP) of damp and heat stasis.@*METHODS@#A total of 70 patients with CP of damp and heat stasis were randomized into an acupuncture plus medication group (35 cases, 4 cases dropped off) and a medication group (35 cases, 5 cases dropped off). In the medication group, tamsulosin hydrochloride sustained release capsule was given orally, 0.2 mg a time, once each night. On the basis of treatment in the medication group, EA was applied at Guanyuan (CV 4), Sanyinjiao (SP 6) and Yinglingquan (SP 9), with disperse-dense wave, 5 mA in intensity for 30 min. Treatment for 30 days was as one course, and totally 3 courses were required in both groups. Before treatment, 1, 2, 3 months into treatment and at the follow-up of 2 months after treatment, the TCM syndrome score and National Institutes of Health chronic prostatitis symptom index (NIH-CPSI) score were observed, and the clinical efficacy was evaluated in both groups.@*RESULTS@#Compared before treatment, the TCM syndrome scores of 3 months into treatment and follow-up were decreased in the acupuncture plus medication group (@*CONCLUSION@#Acupuncture combined with medication can improve the clinical symptoms in patients with CP of damp and heat stasis, and its therapeutic effect is superior to simple western medication.
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Humans , Male , Acupuncture Points , Acupuncture Therapy , Chronic Disease , Hot Temperature , Prostatitis/drug therapy , Treatment OutcomeABSTRACT
Objective To compare the prognostic value of electronic SOFA (eSOFA) scores and simplified SOFA (sSOFA) scores in evaluating the prognosis of patients with sepsis. Methods A retrospective analysis was conducted of clinical data of 245 patients with sepsis admitted to the Department of Emergency and Critical Care Medicine, Shanghai Pudong Hospital from August 2016 to August 2019. Clinical end points were survival status 28 days after hospital admission. eSOFA score, sSOFA score, qSOFA score and SOFA score were evaluated to predict patient prognosis using the area under the receiver operating characteristic curve (AUC). Results AUC of eSOFA score, sSOFA score, qSOFA score and SOFA score for predicting the prognosis of the patients was 0.757 (95% CI 0.686-0.828), 0.721 (95% CI 0.665-0.787), 0.662 (95% CI 0.586-0.738), 0.806 (95% CI 0.747-0.866, respectively. The eSOFA score was superior to the sSOFA score (Z=2.317, P=0.021) in terms of AUC. Conclusions The eSOFA and sSOFA scores have predictive value for the prognosis of sepsis, and eSOFA score is better than sSOFA score.
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Wake-up stroke (WUS) is clinically defined as ischemic stroke that is associated with neurological deficits on awakening, accounting for approximately one in five individuals presenting with an acute ischemic stroke. At present, the mechanism of WUS onset is still unclear, and whether circadian mechanisms are involved deserves further exploration. Previously, these patients were missed the opportunity of reperfusion therapy due to unknown onset time. Recent studies have changed this concept. Intravenous thrombolysis or mechanical thrombectomy can be performed in appropriate patients after imaging evaluation, thus improving the prognosis of some patients with WUS. This article summarizes the latest research in recent years.
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Three new indole alkaloids, flueindolines A-C (1-3), along with nine known alkaloids (4-12), were isolated from the fruits of Flueggea virosa (Roxb. ex Willd.) Voigt. Compounds 1 and 2 are two new fused tricyclic indole alkaloids possessing an unusual pyrido[1, 2-a]indole framework, and 3 presents a rare spiro (pyrrolizidinyl-oxindole) backbone. Their structures with absolute configurations were elucidated by means of comprehensive spectroscopic analysis, chemical calculation, as well as X-ray crystallography. Chiral resolution and absolute configuration determination of the known compounds 4, 10, and 11 were reported for the first time. The hypothetical biogenetical pathways of 1-3 were herein also proposed.
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Objective:To improve awareness about infratentorial dural arteriovenous fistula (DAVF).Methods:Three cases of DAVF in the First Affiliated Hospital of Soochow University from September 2017 to September 2019 were retrospectively analyzed in terms of clinical features, cerebrospinal fluid (CSF) analysis, brain imaging and treatment, and followed up through telephone call.Results:Case 1: A 43-year-old woman, in chronic but acute aggravated course, presented with weakness of both lower limbs and urination and defecation dysfunction. Brain magnetic resonance imaging (MRI) revealed abnormal signal in medulla. CSF analysis demonstrated aquaporin-4 antibodies positive. Misdiagnosed as neuromyelitis optica spectrum disorders, the treatment was poor. Then digital subtraction angiography (DSA) showed DAVF at the left infratentorial area, and endovascular treatment was operated. Relapse was not observed in two-year follow up. Case 2: A 57-year-old woman, in chronic progressive course, mainly manifested as memory loss, but progressed with dysphagia, fever, coma. Treatment as “central nervous infection” was poor. Then DSA showed DAVF at the bilateral transverse-sigmoid sinus area, and endovascular treatment was operated with embolized partial fistulas. The patient died from lung infection within two months. Case 3: A 52-year-old man, in subacute course, was treated in the Gastroenterology Department with clinical manifestion of stubborn nausea and vomiting. Brain MRI revealed abnormal signal in medulla, with prominent vessel flow voids nearby. Then DSA showed DAVF at the craniocervical junction, and endovascular treatment was operated. Relapse was not observed in six-month follow up.Conclusions:DAVF has a variety of clinical manifestations, and infratentorial DAVF can manifest as acute neurological dysfunction involving the brain stem, cerebellum, spinal cord, which may be easily misdiagnosed. When brain MRI showed intracranial abnormal signal, the possibility of DAVF should be considered. DSA remains the gold standard to diagnose DAVF. Endovascular embolization is the main treatment of infratentorial DAVF at present. Prognosis depends on clinical presentation and fistula classification.
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Wake-up stroke (WUS) is clinically defined as ischemic stroke that is associated with neurological deficits on awakening,accounting for approximately one in five individuals presenting with an acute ischemic stroke.At present,the mechanism of WUS onset is still unclear,and whether circadian mechanisms are involved deserves further exploration.Previously,these patients were missed the opportunity of reperfusion therapy due to unknown onset time.Recent studies have changed this concept.Intravenous thrombolysis or mechanical thrombectomy can be performed in appropriate patients after imaging evaluation,thus improving the prognosis of some patients with WUS.This article summarizes the latest research in recent years.
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@#Background and Objectives: Stroke mimics are medical conditions producing stroke-like symptoms but eventually get diagnosed as non-stroke diseases. Epileptic seizure is a common type of stroke mimic. The purpose of this study is to investigate the application of emergency multimodal computed tomography (CT) in the diagnosis of epileptic seizure. Methods: We retrospectively reviewed the case group of patients with suspected stroke in the emergency stroke care service of the First Affiliated Hospital of Suzhou University from September 2017 to October 2019. We included those who underwent multimodal CT, including non-contrasted cranial CT, CT perfusion with CT angiography, and were ultimately diagnosed as epileptic seizures. Ten patients with acute anterior circulation ischemic stroke were assigned as controls. Results: A total of five cases met the inclusion criteria. Multimodal CT was completed within 2.25 to 3.50h from symptom onset. On CT perfusion, hyperperfusion was shown in four cases and slightly increased perfusion in one case with epileptic seizures. Cerebral blood flow and cerebral blood volume were significantly increased, while time to peak and mean transit time decreased in the regions of interest of the epileptic hemisphere when compared to either the non-affected hemisphere or the ischemic area in the control group (P<0.05). The abnormal perfusion areas did not follow vascular territory supply and CT angiography did not show vessel occlusion in the case group. Conclusion: Emergency multimodal CT could be used effectively to differentiate epileptic seizure from stroke.
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The estimation of postmortem interval （PMI） is a core issue in forensic practice. A large amount of time-dependent data can be produced in the decomposition process of a body, however, such multidimensional data cannot be comprehensively and effectively analyzed and utilized by any existing conventional PMI estimation method. As a rapidly developing information technology, artificial intelligence （AI） has significant advantages in big data processing, due to it's comprehensiveness, efficiency and automation. Some scholars have already applied it to researches on the estimation of PMI, showing it's significant advantages in terms of accuracy and development prospect. This article reviews the significance, mode and progress of application of AI in PMI estimation and provides some suggestions and prospects for future study.
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Humans , Artificial Intelligence , Big Data , Forensic Pathology , Postmortem Changes , Time FactorsABSTRACT
Objective To investigate the relationship between total cerebral small vessel disease (CSVD) burden and intracranial hemorrhage transformation (HT) after intravenous thrombolysis in patients with acute ischemic stroke (AIS).Methods One hundred and fifty-four patients who suffered from ischemic stroke within 4.5 hours of onset and received recombinant tissue plasminogen activator thrombolytic therapy in the emergency green channel of the First Affiliated Hospital of Soochow University from August 2016 to January 2018 were enrolled.HT examined by computed tomography scan within 24 hours after thrombolysis was included.The magnetic resonance imaging examination was performed within 48 hours.The patients were divided into two groups:HT group and control group according to the presence or absence of HT.Periventricular white-matter hyperintensities (WMH) with Fazekas score of 3 or deep WMH with Fasekas score of 2 or 3 was recorded as 1 point,MRI of cerebral microbleeds (CMBs) or lacunar infarction (LI) was recorded as 1 point respectively,and peripheral vascular space (PVS) in basal ganglia graded 2-4 (≥11)was counted 1 point.Single-factor analysis was used to compare total CSVD burden score,baseline data and clinical data between the two groups.Multivariate Logistic regression analysis was performed to explore the relationship between total CSVD burden score and HT.Results The age of the 154 patients was 66.00(59.00,74.25) years,males accounted for 66.9％ (103/154),onset to treatment time (OTT) was 174.50 (131.50,200.00) minutes and the NIHSS score before thrombolytic therapy was 6.00 (3.00,10.25).There were 43 cases (27.9％) with moderate to severe WMH,35 cases (22.7％) with CMBs,52 cases (33.8％) with PVS graded 2-4,and 96 cases (62.3％) with LI.There were 21 enrolled patients (13.6％) who suffered from HT.Symptomatic intracranial hemorrhage occurred in nine cases (5.8％).In the multivariate Logistic regression model,the results demonstrated that baseline diastolic pressure (OR=1.072,95％CI 1.027-1.118,P=0.001)and atrial fibrillation (OR=28.564,95％CI 6.217-131.241,P=0.000) were independently associated with HT.After using the mild CSVD burden score as a reference,moderate CSVD burden (OR=0.810,95％ CI 0.154-4.257,P=0.804) was not associated with HT after thrombolysis,and severe CSVD burden (OR=8.429,95％ CI 1.643-43.227,P=0.011) was independently associated with HT.Conclusions The severity of total CSVD burden in patients with AIS was closely related to HT after thrombolysis.Severe CSVD was an independent risk factor for HT after thrombolysis.
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OBJECTIVE@#To investigate the relationship between Toll-like receptor 4 (TLR4) and collateral circulation in patients with acute cerebral infarction (AIS) after thrombolytic therapy.@*METHODS@#This retrospective, observational cohort study was conducted among 65 patients with AIS receiving thrombolytic therapy, who were divided according to findings by computed tomographic angiography (CTA) into good collateral circulation (group A, = 34) and poor collateral circulation (group B, = 31). Serum samples were collected from all the patients and the levels of TLR4 were measured with ELISA.@*RESULTS@#The patients in group A had significantly better outcomes than those in group B. The NIHSS scores at 24 h and 30 days after thrombolytic therapy, mRS scores at 90 days and serum TLR4 levels were significantly lower in group A than in group B ( < 0.05); the percentages of patients with symptomatic intracerebral hemorrhage were comparable between the two groups. The serum levels of TLR4 were negatively correlated with the rMLC score ( < 0.05). Multivariate logistic regression analysis showed that a high level of TLR4 was associated with a poor collateral circulation after thrombolysis.@*CONCLUSIONS@#Good collateral circulation can increase the benefit of intravenous thrombolysis in patients with ACI, and the level of TLR4 is a predictive factor for the compensation of collateral circulation following ACI.