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BACKGROUND: Maternal-fetal immunology is intricate, and the effects of mRNA-S maternal vaccination on immune regulation at the maternal-fetal interface require further investigation. Our study endeavors to elucidate these immunological changes, enhancing our comprehension of maternal and fetal health outcomes. By analyzing immune profiles and cytokine responses, we aim to provide valuable insights into the impact of mRNA-S vaccination on the delicate balance of immune regulation during pregnancy, addressing critical questions in the field of reproductive pharmacology. OBJECTIVES: This investigation sought to examine the prospective influence of mRNA-S-based vaccines and extracellular vesicles (EVs) containing the Spike (S) protein at the maternal-fetal interface. Our primary emphasis was on evaluating their effects on maternal decidua cells and fetal chorion trophoblast cells (hFM-CTCs). METHODS: We validated the generation of EVs containing the S protein from small human airway epithelial cell lines (HSAECs) following mRNA-S vaccine exposure. We assessed the expression of angiotensin-converting enzyme 2 (ACE2) gene and protein in fetal membranes and the placenta, with specific attention to decidual cells and fetal membrane chorion cells. To assess cellular functionality, these cells were exposed to both recombinant S protein and EVs loaded with S proteins (eSPs). RESULTS: Our findings revealed that cells and EVs subjected to mRNA-S-based vaccination exhibited altered protein expression levels of S proteins. At the feto-maternal interface, both placental and fetal membrane tissues demonstrated similar ACE-2 expression levels. Among individual cellular layers, syncytiotrophoblast cells in the placenta and chorion cells in the fetal membrane exhibited elevated ACE-2 expression. Notably, EVs derived from HSAECs activated the MAPK pathway in decidual cells. Additionally, decidual cells displayed a substantial increase in gene expression of chemokines like CXCL-10 and CXCL-11, as well as proinflammatory cytokines such as IL-6 in response to eSPs. However, the levels of Ccl-2 and IL-1ß remained unchanged in decidual cells under the same conditions. Conversely, hFM-CTCs demonstrated significant alterations in the proinflammatory cytokines and chemokines with respect to eSPs. CONCLUSION: In conclusion, our study indicates that mRNA-S-based maternal vaccination during pregnancy may influence the maternal-fetal interface's COVID-19 interaction and immune regulation. Further investigation is warranted to assess safety and implications.
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Vesículas Extracelulares , Trofoblastos , Humanos , Feminino , Gravidez , Trofoblastos/imunologia , Vesículas Extracelulares/imunologia , Vesículas Extracelulares/metabolismo , Decídua/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Citocinas/metabolismo , Vacinação , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/genética , Troca Materno-Fetal , SARS-CoV-2/imunologia , COVID-19/prevenção & controle , COVID-19/imunologia , Linhagem Celular , Vacinas contra COVID-19/imunologia , RNA Mensageiro/metabolismo , RNA Mensageiro/genéticaRESUMO
Objective:To investigate the predictive value of serum proenkephalin A 119-159 (penKid) on incidence and the 28-day mortality in patients with sepsis-associated acute kidney injury (SA-AKI).Methods:This study was a single center, observational cohort study. Sepsis/septic shock patients admitted to Department of Critical Care Medicine of Taizhou People's Hospital Affiliated to Nanjing Medical University from September 2021 to September 2022 were selected and divided into the SA-AKI group and the non-SA-AKI group according to whether acute kidney injury (AKI) occurred within 28 days. Patients in the SA-AKI group were subdivided into the death group and the survival group according to whether death occurred within 28 days. Baseline data and laboratory indicators such as penKid concentration were compared among different groups. COX regression analysis was used to explore the risk factors of death within 28 days in the SA-AKI patients, And Kaplan-Meier curve was used to analyze patient prognosis.Result:A total of 161 patients were included in this study, of whom 66 (41.0%) developed AKI. The baseline penKid concentration in the SA-AKI group was significantly higher than that in the non-SA-AKI group [(2.99 ± 0.68) μg/L vs. (1.86±0.75) μg/L, P<0.05]. Multivariate COX regression analysis showed that the baseline penKid ( HR=5.608, 95% CI: 3.507-8.967, P<0.001) and lactate (LA) ( HR=1.089, 95% CI: 1.003-1.183, P=0.043) were independent risk factors for AKI in sepsis/septic shock patients. Of the 66 SA-AKI patients, 27 (40.9%) died within 28 days, and the baseline penKid concentration in the death group was significantly higher than that in the survival group [ (3.55 ± 0.54) μg/L vs. (2.60±0.47) μg/L, P<0.05]. COX regression analysis showed that penKid ( HR=5.892, 95% CI: 2.457-14.132, P<0.001) was an independent risk factor for mortality in SA-AKI patients. Kaplan-Meier curve showed that the 28-day mortality of patients with baseline penKid ≥ 3.24 μg/L was significantly higher than that of patients with baseline penKid <3.24 μg/L ( P<0.001). Conclusions:In sepsis/septic shock patients, the penKid concentration measured on the first day in the SA-AKI group is significantly higher than that in the non-SA-AKI group. In SA-AKI patients, the penKid concentration measured in patients who survived within 28 days is significantly lower than that in the death group. PenKid is an independent risk factor for the occurrence and death of SA-AKI.
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Emergence of SARS-CoV-2 variants of concern (VOC), including the highly transmissible delta strain, has posed challenges to current COVID-19 vaccines that principally target the viral spike protein (S). Here, we report a nucleoside-modified mRNA vaccine that expresses the more conserved viral nucleoprotein (mRNA-N). We show that mRNA-N alone was able to induce a modest but significant control of SARS-CoV-2 in mice and hamsters. Critically, by combining mRNA-N with the clinically approved S-expressing mRNA vaccine (mRNA-S-2P), we found that combinatorial mRNA vaccination (mRNA-S+N) led to markedly enhanced protection against the SARS-CoV-2 delta variant compared to mRNA-S. In a hamster model, we demonstrated that while mRNA-S alone elicited significant control of the delta strain in the lungs ([~]45-fold reduction in viral loads compared to un-vaccinated control), its effectiveness in the upper respiratory tract was weak, whereas combinatorial mRNA-S+N vaccination induced markedly more robust control of the delta variant infection in the lungs ([~]450-fold reduction) as well as in the upper respiratory tract ([~]20-fold reduction). Immune analyses indicated that induction of N-specific immunity as well as augmented S-specific T-cell response and neutralizing antibody activity were collectively associated the enhanced protection against SARS-CoV-2 delta strain by combinatorial mRNA vaccination. These findings suggest that the combined effects of protection in the lungs and upper respiratory tract could both reduce the risk of severe disease as well as of infection and transmission.
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Objective:To explore the risk factors of acute kidney injury (AKI) in acute respiratory distress syndrome (ARDS) patients with mechanical ventilation.Methods:A retrospective analysis was conducted. ARDS patients with mechanical ventilation admitted to ICU of Taizhou People's Hospital from January 2019 to December 2019 were enrolled. Patients were divided into the AKI group and non-AKI group according to whether the patients had AKI. Clinical characteristics and laboratory indicators of the two groups were compared. Risk factors of incidence of AKI in ARDS patients were analyzed. The Kaplan-Meier survival curve was drawn to evaluate the survival rates of the two groups.Results:A total of 120 ARDS patients with mechanical ventilation were included, and 57 patients (47.5%) developed AKI. Procalcitonin, increased basal creatinine, decreased pH and impaired consciousness were independent risk factors for AKI in ARDS patients with mechanical ventilation. Fifty-seven of the 120 patients died with a mortality of 38.3%. The Kaplan-Meier survival curve showed that the survival rate of the AKI group was significantly lower than that of the non-AKI group ( P<0.001). Conclusions:The incidence and mortality of AKI is high in ARDS patients with mechanical ventilation. Procalcitonin, increased basal creatinine, decreased pH and impaired consciousness are independent risk factors for AKI in ARDS patients with mechanical ventilation.
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The outbreak of novel coronavirus pneumonia occurred in Wuhan, Hubei province of China, at the end of 2019, and spread rapidly across the country. After the outbreak of this disease, the overwhelming majority of cities have launched the "first level response" and the regular diagnosis and treatment of cancer patients are greatly affected. The digestive systemic cancer is the most common malignancy. Most patients are diagnosed in the advanced stage with poor prognosis. The epidemic of novel coronavirus pneumonia poses new challenges to diagnosis and treatment of the patients with digestive system malignancies. Based on the fully understanding of the characteristics of digestive system tumors, we should change the treatment strategy and adopt more reasonable treatment strategy timely during the epidemic period to minimize the adverse effects of the epidemic of novel coronavirus pneumonia on the treatment.
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OBJECTIVE@#To investigate the effect of working time on the prognosis of patients with ischemic stroke undergoing intravenous thrombolysis.@*METHODS@#Clinical data of 3050 patients with ischemic stroke received intravenous thrombolysis from 71 hospitals in Zhejiang Province during June 2017 and September 2018 were retrospective analyzed. Whole day of Saturday and Sunday were defined as weekend; whole day of Monday to Friday were defined as weekdays; Monday to Friday 8:00-17:00 were defined as daytime of weekdays; Monday to Friday 17:01-07:59 on next day were defined as nights of weekdays; unconventional working time were defined as weekend and nights of weekdays. Good outcome was defined as mRS 0-2 at 3 months. Univariate analyses of baseline and prognostic variables in group of weekend and weekdays, nights of weekdays and daytime of weekdays, unconventional working time and daytime of weekdays were performed. Binary logistic regression was used to investigate whether weekend, nights of weekdays and unconventional working time were independent predicting factors of outcome after intravenous thrombolysis, respectively.@*RESULTS@#There was no difference in 7-day mortality, 3-month mortality and good outcome at 3-month between weekend group and weekdays group, nights of weekdays group and daytime of weekdays group, unconventional working time group and daytime of weekdays group (all >0.05). Binary logistic regression results showed that weekends, nights of weekdays and unconventional working time were not independent predicting factors for outcome after intravenous thrombolysis (all >0.05).@*CONCLUSIONS@#The working time has not affected the outcomes of patients with ischemic stroke undergoing intravenous thrombolysis in studied hospitals of Zhejiang province.
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Humanos , Isquemia Encefálica , Tratamento Farmacológico , Prognóstico , Estudos Retrospectivos , Acidente Vascular Cerebral , Tratamento Farmacológico , Terapia Trombolítica , Fatores de TempoRESUMO
OBJECTIVE@#To compare the time delay between in-hospital stroke and out-of-hospital stroke patients, and to explore the influence factors for the prognosis of in-hospital stroke patients treated by intravenous thrombolysis.@*METHODS@#Clinical data of 3050 patients with ischemic stroke who received intravenous thrombolysis in 71 hospitals in Zhejiang province from June 2017 to September 2018 were analyzed. Differences of time delay including door to imaging time (DIT), imaging to needle time (INT) and door to needle time (DNT) between in-hospital stroke (=101) and out-of-hospital stroke (=2949) were observed. The influencing factors for the outcome at 3 month after intravenous thrombolysis in patients with in-hospital stroke were analyzed using binary logistic regression analysis.@*RESULTS@#Patients with in-hospital stroke had longer DIT[53.5 (32.0-79.8) min vs. 20.0 (14.0-28.0) min, <0.01], longer IDT[47.5(27.3-64.0)min vs. 36.0(24.0-53.0)min, <0.01], and longer DNT[99.0 (70.5-140.5) min vs. 55.0 (41.0-74.0) min, <0.01], compared with patients with out-of-hospital stroke; patients in comprehensive stroke center had longer DIT[59.5(44.5-83.3) min vs. 37.5(16.5-63.5) min, <0.01], longer DNT[110.0(77.0-145.0) min vs. 88.0 (53.8-124.3) min, <0.05], but shorter INT[36.5(23.8-60.3)min vs. 53.5 (34.3-64.8) min, <0.05], compared with patients in primary stroke center. Age (=0.934, 95% 0.882-0.989, <0.05) and baseline National Institute of Health Stroke Scale score (=0.912, 95% 0.855-0.973, <0.01) were independent risk factors for prognosis of in-hospital stroke patients.@*CONCLUSIONS@#In-hospital stroke had longer DIT and DNT than out-of-hospital stroke, which suggests that a more smooth thrombolysis process of in-hospital stroke should be established.
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Humanos , Administração Intravenosa , Isquemia Encefálica , Tratamento Farmacológico , Fibrinolíticos , Usos Terapêuticos , Hospitais , Prognóstico , Acidente Vascular Cerebral , Tratamento Farmacológico , Terapia Trombolítica , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE@#To investigate the association of atrial fibrillation (AF) with hemorrhagic transformation (HT) in patients with ischemic stroke treated by intravenous thrombolysis.@*METHODS@#Clinical data of 3272 patients treated by intravenous thrombolysis from 71 hospitals in Zhejiang Province during June 2017 and December 2018 were retrospectively reviewed. Intracranial HT was defined as intracranial hemorrhage suggested by imaging examination 24 hours after intravenous thrombolysis. Patients were dichotomized into HT group (=533) and non-HT group (=2739). The association of AF and HT was analyzed by univariate analysis and binary logistic regression.@*RESULTS@#Compared with the non-HT group, the HT group were older, had longer onset to needle time (ONT), higher baseline National Institute of Health Stroke Scale (NIHSS) score, higher baseline glucose level, and higher AF rate (<0.05 or <0.01). Binary logistic regression analysis revealed that AF was independently associated with HT (=2.527, 95%:2.030-3.146, <0.01).@*CONCLUSIONS@#AF is independently associated with the occurrence of HT in ischemic stroke patients treated with intravenous thrombolysis.
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Humanos , Antifibrinolíticos , Farmacologia , Fibrilação Atrial , Isquemia Encefálica , Tratamento Farmacológico , Estudos Retrospectivos , Acidente Vascular Cerebral , Tratamento Farmacológico , Terapia Trombolítica , Resultado do TratamentoRESUMO
OBJECTIVE@#To investigate the effect of treatment time on the outcome of patients with ischemic stroke undergoing reperfusion therapy.@*METHODS@#The clinical data of 3229 ischemic stroke patients who received intravenous thrombolysis with or without arterial thrombolysis from 71 hospitals in Zhejiang province from June 2017 to September 2018 were retrospectively reviewed. The good outcome was defined as modified Rankin Scale (mRS) ≤ 2. Binary logistic regression analysis was used to investigate the association of door to needle time (DNT), or door to reperfusion time (DRT) with the outcomes in patients treated by intravenous thrombolysis or bridging arterial thrombolysis, respectively.@*RESULTS@#Binary logistic regression showed that DNT (=0.994, 95%:0.991-0.997, <0.01) or DRT (=0.989, 95%:0.983-0.995, <0.01) were independently associated with good outcomes, respectively. Every hour decreases in DNT resulted in a 4.7%increased probability of functional independence (mRS 0-2) in patients treated by intravenous thrombolysis; Every hour decreases in DRT was associated with a 11.4%increased probability of functional independence in patients treated by intravenous thrombolysis with arterial thrombolysis.@*CONCLUSIONS@#Good outcomes are associated with lower DNT in ischemic stroke patients treated by intravenous thrombolysis or lower DRT in patients treated by intravenous thrombolysis bridging arterial thrombolysis.
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Humanos , Isquemia Encefálica , Tratamento Farmacológico , Fibrinolíticos , Usos Terapêuticos , Reperfusão , Estudos Retrospectivos , Acidente Vascular Cerebral , Tratamento Farmacológico , Terapia Trombolítica , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE@#To investigate the effect of emergency medical service (EMS) on the prognosis of ischemic stroke patients treated with intravenous thrombolysis.@*METHODS@#Clinical data of 2123 ischemic stroke patients treated with intravenous thrombolysis in 70 hospitals in Zhejiang province were retrospectively analyzed. There were 808 patients sent to the hospital by ambulance (EMS group) and 1315 patients by other transportations (non-EMS group). Good outcome was defined as modified Rankin Scale (mRS) ≤ 2 at 3-month. The onset to needle time (ONT), onset to door time (ODT), door to needle time (DNT) and outcome were compared between EMS group and non-EMS group. Binary logistic regression was used to explore the influencing factors for the outcome at 3-month.@*RESULTS@#Compared with the non-EMS group, patients in the EMS group were older, with higher baseline National Institute of Health Sroke Scale (NIHSS) score, and had a higher proportion of atrial fibrillation (all 0.05). Binary logistic regression showed that EMS was not independently associated with good outcome (=0.856, 95%:0.664-1.103, >0.05).@*CONCLUSIONS@#EMS had not improve the outcome of patients receiving intravenous thrombolysis in Zhejiang province.
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Humanos , Administração Intravenosa , Isquemia Encefálica , Tratamento Farmacológico , Serviços Médicos de Emergência , Fibrinolíticos , Usos Terapêuticos , Prognóstico , Estudos Retrospectivos , Acidente Vascular Cerebral , Tratamento Farmacológico , Terapia Trombolítica , Resultado do TratamentoRESUMO
Objective To verify the feasibility and effectiveness of modified gastric bypass surgery in the treatment of non-obese type 2 diabetic mellitus(T2DM ) GK rats .Methods Forty male GK rats were randomly divided into four groups (n=10) ,the group A served as the modified gastric bypass ,group B as the Roux-en-Y gastric bypass ,group C as the sham operation and group D as the blank control group .Fasting blood glucose(FBG) ,glycosylated hemoglobin(HbA1c) and fasting serum insulin(FINS) in each group were detected at preoperative 1 week ,postoperative 1 ,2 ,4 ,8 ,12 weeks .Results The rat body mass at postoperative 1 week in the group A and B was significantly decreased compared with the group D ,and began to recover at postoperative 4 weeks , the rat body mass at the same time point had no statistical difference between the group A and B (P>0 .05) .FPG ,FINS and HbA1c at preoperative 1 week had no statistical difference among various groups (P>0 .05) .FPG and FINS at postoperative 1 week had no statistical difference among various groups (P>0 .05) .FPG and FINS at postoperative 2 ,4 ,8 ,12 weeks had no statistical difference between the group A and B(P>0 .05) ,which had no statistical difference between the group A with the group C and D (P>0 .05) . HbA1c at postoperative 4 weeks had no statistical difference among various groups (P>0 .05);which at postoperative 12 weeks had no statistical difference between the group A and B (P>0 .05) ,while which had no statistical difference between the group A with the group C and D(P>0 .05) .Conclusion The modified gastric bypass surgery has the improvement effect on glycometabolism of rat non-obese T2DM ,which is similar to that of Roux-en-Y gastric bypass surgery .
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Uveitic glaucomas (UG) are complex in cause or disease and response to treatment.UG typically is associated with very high intraocular pressure and more intense optic nerve damage than other glaucoma types.This secondary glaucoma requires an early diagnosis and adequate management of both uveitis and glaucoma.Recently,a multitude of novel medical therapies and surgical techniques have been added to the armamentarium of existing therapeutic modalities.This article reviews the surgical treatment of UG,including Trabeculectomy,laser peripheral iridotomy,nonperforating deep sclerectomy,glaucoma drainage implants,minimally invasive glaucoma surgery,and also briefly discusses the application and effect of these surgical treatments.
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Objective To discuss the ultrasonic anatomy of gastrocnemius and its substructures in normal population. Methods Eighty gastrocnemius in 40 volunteers were scanned by real time high frequency ultrasound. Sonograms of medial and lateral heads of gastrocnemius were acquired. Plume angles between medial and lateral heads of gastrocnemius were measured at condition of rest, 5 kg and 10 kg isometric contraction. Both dominant and non-dominant legs were evaluated. Differences of plume angles were compared by ANOVA in different conditions and by t test in different legs. Results At the upper part of the muscle, both medial and lateral heads of gastrocnemius could be divided into muscular compartment, shallow compartment and deep compartment by hyperechoic intra-muscular septa with clear margin. The septa of lateral heads presented as hyperechoic side-lying′T′, while the septa of medial heads presented as hyperechoic side-lying-′T′. Vascular signals could be detected in these hyperechoic septa. The plume angle at the distal part of the lateral head of gastrocnemius was composed of shallow compartment attaching to the Achilles tendon, and that of the medial head was composed of medial muscular compartment attaching to the tendon. At rest, 5 kg and 10 kg isometric contraction, plume angles of lateral heads were (13.36±3.20)°, (13.32±3.30)° and (12.75±3.20)°, and plume angles of medial heads were (8.69±3.30)°, (8.59±2.99)° and (8.65±3.20)°. Under the same condition, plume angles of medial heads were larger than those of lateral heads and the difference was statistically signiifcant (t=9.09, 9.50 and 8.10, all P<0.01). Changes of plume angles between rest and different weight bearing conditions were small, and differences were not statistically signiifcant (F=0.89 and 0.02, P=0.41 and 0.98). Plume angles of medial heads in dominant legs and non-dominant legs were (13.66±3.60)° and (13.30±2.84)°, and those of lateral heads were (8.71±3.48)° and (8.80±3.35)°. The plume angles of medial heads were larger in dominant legs than those in non-dominant legs, while the plume angles of lateral heads were smaller in dominant legs than those in non-dominant legs. However, both differences were not statistically signiifcant (t=0.70 and 0.87, P=0.48 and 0.17). Conclusions The anatomical characteristics of medial and lateral heads and compartments of gastrocnemius can be clearly depicted by high frequency ultrasound. Plume angles can also be accurately measured.
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Objective To investigate the correlation of homoeysteine (Hcy) and blood glucose level with type 2 diabetic fundus lesions.Methods Sixty patients with type 2 diabetic fundus lesions were selected and grouped as the diabetic fundus lesions group from February of 2011 to October of 2012,and 40 patients with type 2 diabetes were recruited as the diabetes group,40 healthy volunteer were recruited as the control group.Glycosylated hemoglobin Alc(HbAlc),fasting blood glucose(FBG),homocysteine(Hcy) and total cholesterol (TC),triglyceride (TG),high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) of the three groupwere measured and compared.Results Compared with the control group,Hcy in the diabetic fundus lesions group and the diabetic group were significantly higher than the control group ((17.6 ± 4.7) μmol/L,(13.3 ± 2.9) μmol/L vs.(7.3 ± 1.8) μmol/L),and as well as HbA1 c ((11.3 ±2.7)%,(9.2±1.4)% vs.(4.0±1.1)%),FBG ((11.5 ±3.4) μmol/L,(10.1 ±2.1) μmol/Lvs.(4.2 ±1.7) μmol/L)and TC((6.7 ±1.1) mmol/L,(5.1 ±1.0) mmol/L vs.(4.4±0.8) mmol/L) (F=5.091,5.107,6.017,5.813,P =0.043,0.036,0.032,0.040 respectively).The Hcy,TC,TG,FBG and HbAlc of type 2 diabetic fundus lesions with I stage were the lowest,and the stage of type 2 diabetic fundus lesions was relevant with the level of Hcy,TC,TG,FBG and HbAlc,which were different significantly (F =5.418,5.524,4.971,5.713 respectively,P =0.038,0.041,0.042,0.040 respectively).Conclusion The serum Hcy and blood glucose are risk factors to type 2 diabetic nephropathy.Lowering Hcy concentration and reducing the glucose may be a new way to prevent the occurrence of type 2 diabetic nephropathy.
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Objective To investigate the safety and efficacy of intravenous thrombolytic therapy with recombinant tissue plasminogen activator(rtPA)in patients with isolated penetrating artery territory infarct (IPAI).Methods Data of retrospectively collected clinical,laboratory,and radiological from 75 consecutive patients with acute ischemic stroke treated with intravenous rtPA therapy from June 2009 to April 2011.Etiological classification was carried out according to the Chinese Ischemic Stroke Classification of Subgroups(CISS).The rates of hemorrhagic transformation(HT)and clinical outcomes of patients were compared between IPAI group and non-IPAI group.Results All 75 patients with mean age of 67.4years and 25(33.3%)fenale,were treated with intravenous rtPA.Before treatment,their average score of the National Institutes of Health Stroke Scale(NIHSS)was 12.3 ± 6.4,and mean length of time from onset to treatment was 239.6 ±97.5 minutes.After thrombolytic therapy,the radiological HT was found in 24 patients(32%).Symptomatic intracraneal hemorrhage(ICH)occurred in 4 patients(5.3%).Of 22 (29.3%)patients with IPAI,only one experienced HT.Logistic regression analysis suggested that IPAI wasan individualized predictor used alone for determining the low risk of HT.In the patients with IPAI,82% of them had an individual clinical outcome(mRS < 2)one month after onset,and the neurological outcomes were better in patients with IPAI than those in patients with non-IPAI(P < 0.01).Conclusions The risk of hemorrhagic complication was low and the clinical outcome was good in patients with isolated penetrating artery territory infarct after intravenous thrombolytic therapy with rtPA.Imaging diagnosis of IPAI might facilitate the treatment with rtPA in this cohort of patients.
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Objective To investigate the impact of the pretreatment perfusion weighted imaging (PWI)-diffusion weighted imaging (DWI) mismatch on reperfusion and early neurological improvement after intravenous thrombolysis in acute ischemic stroke.Methods We retrospectively reviewed our collected clinical,laboratory,and radiologic data in patients receiving intravenous recombinant tissue plasminogen activator therapy,who had performed multimodal MRI in both pretreatment and 24 h post-treatment in our hospital..The target mismatch of PWI-DWI was defined as a PWI lesion that was 10 ml or more and 120% or more of the DWI lesion,with DWI lesion less than 70 ml and PWI lesion less than 140 ml.The smalllesion was defined as a DWI and PWI volume both less than 10 ml.The others were termed non-target mismatch.Reperfusion required a 30% or greater reduction in PWI lesion volume on the 24-hour follow-up scar.The early neurological improvement was defined as the patients with an NIHSS score of 0 to 4 or 6-point or greater improvement at 7 days.Results Among 45 patients analyzed,19(41%) patients presented target mismatch,of which 8 patients were treated over 4.5 h.The rate of reperfusion and early neurological improvement after thrombolysis in target mismatch group were both significantly increased comparing with non-target mismatch group( 16/19 vs 5/12,x2 =6.092,P <0.05 and 13/19 vs 2/12,x2 =7.888,P < 0.05,respectively ),although the recanalization rate demonstrated no significant difference between two groups.The pooled OR for reperfusion was 6.4(95% CI 1.156-35.437,P =0.034),and the pooled OR for favorable clinical response was 21.7 ( 95% CI 2.234-210.110,P =0.008 ) in target mismatch patients.Among the target mismatch group,13/16 of patients with reperfusion had early neurological improvement,while no patients without reperfusion had neurological improvement.The rate of recanalization,reperfusion and neurological improvement after thrombolysis demonstrated no significant difference between target mismatch group treated within 4.5 h and beyond 4.5 h.Conclusion Patients with target mismatch profile before thrombolysis had a high reperfusion rate and were prone to get early neurological improvement,indicating that the evaluation of PWI-DWI mismatch may facilitate the selection of patients who may benefit from thrombolysis beyond the time window.
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Objective To investigate the expression of neuroprotective peptide [Gly14]-Humanin (HNG) in eukaryotic cells by gene engineering technique and analyze its biological activity. Methods By means of asymmetrical primer/template, double stranded cDNA of HNG with FLAG in its C-terminal was obtained, which was cloned into the plasmid pcDNA3.1(-), and the resultant recombinant vector pcDNA3.1(-)/HNG-FLAG was transfected into PC12 cells. At the same time, the recombinant vector pcDNA3.1(-)/EGFP was transfected to control the efficiency of transfection. The expression of HNG in the cells was determined by immunocytochemistry. In order to analyze the biological activity of the expressed HNG, 25μM Aβ25-35 peptide was added to the culture medium of the transfected cells for 24h, then cell morphology, MTT assay and Hoechst 33258 staining were observed. Results The eukaryotic expression vector of pcDNA3.1(-)/HNG-FLAG was identified by enzyme digestion and sequencing. HNG was highly expressed in PC12 cells. After exposure of PC12 cells to 25μM Aβ25-35 for 24h, cell viability decreased to (65.8±5.3)%, and the dystrophic changes of neuritis and nuclei condensation were obvious. When cells were pre-transfected with pcDNA3.1(-)/HNG-FLAG, Aβ25-35-induced cell death and morphological changes of cells and nuclei were suppressed. In contrast, pre-transfected with empty vector did not protect cells from Aβ25-35-induced toxicity. Conclusion The eukaryotic expression vector for FLAG-tagged HNG was successfully constructed and expressed in PC12 cells. Expressed HNG has biological activity.
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The human brain-derived neurotrophic factor (hBDNF) gene was cloned by polymerase chain reaction and the recombinant adeno-associated viral vector inserted with hBDNF gene (AAV-hBDNF) was constructed. Cultured rat hippocampal neurons were treated with Abeta(25-35) and serued as the experimental Abeta-induced neuronal damage model (AD model), and the AD model was infected with AAV-hBDNF to explore neuroprotective effects of expression of BDNF. Cell viability was assayed by MTT. The expression of bcl-2 anti-apoptosis protein was detected by immunocytochemical staining. The change of intracellular free Ca ion ([Ca2+]i) was measured by laser scanning confocal microscopy. The results showed that BDNF had protective effects against A-induced neuronal damage. The expression of the bcl-2 anti-apoptosis protein was raised significantly and the balance of [Ca2+]i was maintained in the AAv-hBDNF treatment group as compared with AD model group. These data suggested that recombinant AAV mediated a stable expression of hBDNF in cultured hippocampal neurons and resulted in significant neuron protective effects in AD model. The BDNF may reduce neuron apoptosis through increasing the expression of the bcl-2 anti-apoptosis protein and inhibiting intracellular calcium overload. The viral vector-mediated gene expression of BDNF may pave the way of a novel therapeutic strategy for the treatment of neurodegenerative diseases such as Alzheimer's disease.
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Objective To explore the effect of β-amyloid protein (Aβ) on S100β expression in rat hippocampus and its mechanisms. Methods At 7 days after bilateral stereotaxis injection of different dose of fibrillar Aβ 25-35 and interluekin-1 receptor antagonist (IL-1ra) into the rat CA1 region, the learning and memory abilities of rats were tested with passive avoidance task. Amyloid deposition was detected by using Congo red staining technique. Nissl staining and immunohistochemical techniques were used to analyze the number of neurons, and GFAP and the S100β expression in hippocampal CA1 region , respectively. Results After fibrillar Aβ injection, the step-through latency of rats was significantly shortened compared to that of the control group. The GFAP positive astrocytes were found surrounding amyloid deposition. Neuronal loss occurred in the pyramidal cell layer of CA1 region. The number of S100β positive cells in Aβ-treated group was significantly increased compared with that in the control group. After IL-1ra injection, the number of S100β positive cells was significantly decreased. Conclusion Intrahippocampal injection of Aβ 25-35 could cause similar pathologic changes of Alzheimer's disease. Aβ 25-35 was capable of up-regulating S100β expression in a dose-dependent manner. The injection of IL-1ra could attenuate the effect of Aβ on S100β expression.
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The human brain-derived neurotrophic factor (hBDNF) gene was cloned by polymerase chain reaction and the recombinant adeno-associated viral vector inserted with hBDNF gene (AAV-hBDNF) was constructed. Cultured rat hippocampal neurons were treated with Aβ25-35 and serued as the experimental Aβ-induced neuronal damage model (AD model), and the AD model was infected with AAV-hBDNF to explore neuroprotective effects of expression of BDNF. Cell viability was assayed by MTT. The expression of bcl-2 anti-apoptosis protein was detected by immunocytochemical staining. The change of intracellular free Ca ion ([Ca2+]i) was measured by laser scanning confocal microscopy. The results showed that BDNF had protective effects against Aβ-induced neuronal damage. The expression of the bcl-2 anti-apoptosis protein was raised significantly and the balance of [Ca2+]i was maintained in the AAV-hBDNF treatment group as compared with AD model group. These data suggested that recombinant AAV mediated a stable expression of hBDNF in cultured hippocampal neurons and resulted in significant neuron protective effects in AD model. The BDNF may reduce neuron apoptosis through increasing the expression of the bcl-2 anti-apoptosis protein and inhibiting intracellular calcium overload. The viral vector-mediated gene expression of BDNF may pave the way of a novel therapeutic strategy for the treatment of neurodegenerative diseases such as Alzheimer's disease.