Objective To investigate the efficacy and safety of intravenous thrombolysis with low-dose and standard-dose recombinant tissue plasminogen activator(rt-PA)in the elderly patients(aged over 80 years)with acute ischemic stroke(AIS).Methods A total of 201 elderly patients with AIS treated at Tianjin Fourth Central Hospital from February 2019 to February 2023 were prospectively included and randomly assigned to the rt-PA low-dose group(n=93,0.6 mg/kg)and rt-PA standard-dose group(n=108,0.9 mg/kg).The incidence of intra-cranial hemorrhage,symptomatic intracranial hemorrhage,fatal intracranial hemorrhage,neurologic deterioration within 7 days and mortality within 90 days were observed to evaluate the safety.The neurologic improvement rate and good prognosis rate at 90 days were used to evaluate the effectiveness.A stratified analysis of 90-day outcomes was performed based on stroke severity and age.Results The incidence of intracranial hemorrhage,symptomatic intracranial hemorrhage and fatal intracranial hemorrhage within 7 days in rt-PA low-dose group was lower than that in rt-PA standard-dose group(P＜0.05).There were no statistically significant differences between the two groups concerning the residual safety index and the effectiveness index.The 90-day good prognosis rate of moderate stroke sub-group and of≥90 years of age sub-group in rt-PA low-dose group were both higher than that of rt-PA standard-dose group(P＜0.05).Conclusions For AIS patients with moderate stroke and aged over 90 years,intravenous thrombolytic therapy with rt-PA 0.6 mg/kg is recommended.

Acute ischemic stroke (AIS) is a kind of central nervous system disease that seriously threatens human health and life. Current treatment for AIS is mainly reperfusion. However, the time-sensitive of reperfusion limits its clinical application, and a considerable part of patients within the time window cannot achieve the expected effect after reperfusion; related complications of reperfusion have not been completely solved. So far, some clinical trials have confirmed that neuroprotectants are useful supplements and adjuncts to reperfusion. This paper reviews the recent advance in neuroprotectants combined with reperfusion in AIS to provide references for AIS treatment.

This study aimed to observe the protective effect of momordicine I, a triterpenoid compound extracted from momordica charantia L., on isoproterenol (ISO)-induced hypertrophy in rat H9c2 cardiomyocytes and investigate its potential mechanism. Treatment with 10 μM ISO induced cardiomyocyte hypertrophy as evidenced by increased cell surface area and protein content as well as pronounced upregulation of fetal genes including atrial natriuretic peptide, β-myosin heavy chain, and α-skeletal actin; however, those responses were markedly attenuated by treatment with 12.5 μg/ml momordicine I. Transcriptome experiment results showed that there were 381 and 447 differentially expressed genes expressed in comparisons of model/control and momordicine I intervention/model, respectively. GO enrichment analysis suggested that the anti-cardiomyocyte hypertrophic effect of momordicine I may be mainly associated with the regulation of metabolic processes. Based on our transcriptome experiment results as well as literature reports, we selected glycerophospholipid metabolizing enzymes group VI phospholipase A 2 (PLA2G6) and diacylglycerol kinase ζ (DGK-ζ) as targets to further explore the potential mechanism through which momordicine I inhibited ISO-induced cardiomyocyte hypertrophy.Our results demonstrated that momordicine I inhibited ISO-induced upregulations of mRNA levels and protein expressions of PLA2G6 and DGK-ζ. Collectively, momordicine I alleviated ISO-induced cardiomyocyte hypertrophy, which may be related to its inhibition of the expression of glycerophospholipid metabolizing enzymes PLA2G6 and DGK-ζ.

Objective:To investigate the efficacy and safety of recombinant tissue plasminogen activator (rt-PA) intravenous thrombolysis combined with edaravone dexborneol at different timing in super elderly patients (aged≥85 years) with moderate to severe acute ischemic stroke (AIS).Methods:A prospective study was performed. Seventy-one super elderly patients with moderate to severe AIS treated with rt-PA intravenous thrombolysis combined with edaravone dexborneol from December 2020 to March 2023 in Department of Neurology, Affiliated Fourth Central Hospital of Nankai University were selected and randomly divided into early group ( n=35) and advanced group ( n=36); patients in the early group were given edaravone dexborneol immediately after rt-PA intravenous thrombolysis, and patients in the advanced group were given edaravone dexborneol 24 h after rt-PA intravenous thrombolysis. In addition, 31 patients with moderate to severe AIS received rt-PA intravenous thrombolysis only in Department of Neurology of the hospital from August 2018 to December 2020 were selected as control group. Differences in efficacy and safety indexes among the 3 groups were compared. Results:After 7 d of treatment, the improvement rate of neurological function in early group was significantly higher than that in control group and advanced group ( P<0.05). After 90 d of treatment, modified Rankin scale (mRS) scores in early group were statistically lower than those in control group and advanced group ( P<0.05); good prognosis rate in early group was statistically higher than that in control group and advanced group ( P<0.05). The incidences of intracranial hemorrhage and symptomatic intracranial hemorrhage in early group were significantly lower than those in control group and advanced group ( P<0.05). After 30 and 90 d of treatment, the advanced group had significantly lower mortality than the control group, but significantly higher mortality than the early group ( P<0.05). Conclusion:Edaravone dexborneol immediately after rt-PA intravenous thrombolysis is the optimal timing for super elderly patients with moderate to severe AIS, which can improve the efficacy and safety.

Background/Aims: PF-00547659 is a monoclonal antibody against human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) that prevents the binding of α4β7+ lymphocytes to MAdCAM-expressing sites in the gastrointestinal tract with high affinity and selectivity, and is being developed for the treatment of Crohn’s disease (CD). Methods: OPERA is a randomized, multicenter, double-blind, placebo-controlled study to investigate the efficacy, safety, and pharmacokinetics of PF-00547659 following subcutaneous administration in subjects with active CD, a history of failure or intolerance to anti-tumor necrosis factor and/or immunosuppressants, high-sensitivity C-reactive protein > 3.0 mg/L, and ulcers on colonoscopy. The primary endpoint was Crohn’s Disease Activity Index-70 response at week 8 or 12. Subpopulation analyses for Asian subjects were performed as some differences are observed in genetics and clinical phenotypes in Asian CD patients compared with Western patients. Results: In this study, 265 CD subjects were randomized, with a subpopulation of 21 subjects (8 Japanese and 13 Korean) defined as the Asian population. In the overall and Asian populations; PF-00547659 was pharmacologically active as evidenced by soluble MAdCAM and circulating β7+ central memory CD4+ T-lymphocytes, although no clear evidence of efficacy was observed in any clinical endpoints; pharmacokinetics of PF-00547659 in the Asian subpopulation was generally comparable to the overall population; and the safety profile of PF-00547659 appeared acceptable up to 12 weeks of treatment. Conclusions In the overall and Asian populations, efficacy of PF-00547659 could not be demonstrated using any clinical endpoints compared with placebo. Pharmacokinetics and safety of PF-00547659 were generally comparable. Further studies with larger numbers of patients are required to confirm our results. (Trial Registration Number: NCT01276509)

Objective To reveal the virulence genes and the polymorphisms of chromosomal 16S rRNA gene of Yersinia enterocolitic strains isolated from different districts in Jiangsu Province,2015. Methods Five virulence genes(ail,virF,yadA,ystA and ystB)of Yersinia enterocolitic strains isolated from different districts in Jiangsu Province were detected by using polymerase chain reaction(PCR),and phylogenetic analysis of chromosomal 16S rRNA gene was performed by amplification and sequencing. Results In this study,73 Yersinia enterocolitic strains were collected in Jiangsu Province in 2015.Among them,56(76.7%)strains carried virulence genes,and ail-virF-yadA -ystA -ystB+were the dominate types in diarrhea patients and other hosts.All strains can be clustering into 4 groups according to the phylogenetic analysis of chromosomal 16S rRNA gene.Conclusions The non-pathogenic Yersinia enterocolitic(ystB+)is the dominant strain in Jiangsu province,and the pathogenic strains are also found in this region.The result of phylogenetic analysis of chromosomal 16S rRNA gene and the profiles of virulence genes are highly consistent.

Objective:To explore the effects of HIF-1α on the growth of transplanted oral cancer and on the expression of CEACAM1 and VEGF-C in the tumor.Methods:Nude mouse model of oral cancer was established by transplantation of Tca8113 cells respectively treated by HIF-1α siRNA and negative control siRNA subcutaneously into right axillary region of nude mice.3 weeks after transplantation the mice were sacrificed,the tumor volum and weight were measured.The tumor tissue was examined by ELISA method for the detection HIF-1α protein expression,by real-time quantitative PCR and western blot for the detection of mRNA and protein expression of HIF-1α,CEACAM1 and VEGF-C respectively.Results:The volume and weight of the transplanted tumor in HIF-1 α siRNA group were significantly less than those in the control group(P＜0.05),CEACAM1 and VEGF-C mRNA and protein were down-regulate in HIF-1α siRNA group (P＜0.05).Conclusion:HIF-1α expression is positively related to the expression of CEACAM1 and VEGF-C in the regulation of oral tumor growth.

OBJECTIVETo retrospectively evaluate the HER2 status of 1 501 invasive breast cancer (IBC) by immunohistochemistry (IHC) and fluorescent in situ hybridizaion (FISH), and to compare and analyze the changes and their effects, using the 2007 and 2013 American Society of Clinical Oncology/College of American Pathologist(ASCO/CAP) HER2 testing guidelines.

METHODSTissue handling and HER2 testing were performed according the 2007 ASCO/CAP guideline recommendations. The HER2 status of all newly diagnosed IBC were routinely assessed by IHC, and reflex FISH assay was done on all the IHC equivocal (IHC 2+) cases. The HER2 status of 1 501 cases of IBC was re-evaluated according to these two criteria.

RESULTSUsing the 2007 and 2013 ASCO/CAP criteria, the overall positive, equivocal and negative rates of HER2 over-expression and/or amplification in the 1 501 IBCs were 23.05% and 23.52%, 11.59% and 12.52%, and 65.36% and 63.96%, respectively. The positive and equivocal rates increased by 0.47% and 0.93% respectively, but the negative rate decreased by 1.40% when using the new criteria. For HER2 IHC staining using the 2007 and 2013 guidelines, the positive, equivocal and negative rates were 17.99% and 18.13% (+0.13%), 32.51% and 32.91% (+0.40%) and 49.50% and 48, 97% (-0.53%), respectively. FISH for HER2 amplification was done in 348 of the 1 501 IBCs, and using the 2007 and 2013 guidelines, the positive, equivocal and negative rates were 27.59% and 29.02% (+1.43%), 1.15% and 3.74% (+2.59%) and 71.26% and 67.24% (-4.02%), respectively.

CONCLUSIONSThe application of 2013 ASCO/CAP guideline could lead to an increase in positive and equivocal rates, and a decrease in negative rate. The influence could be more prominent for the evaluation of FISH result, and would raise the positive and equivocal rates since a mean HER2 copy number is used in the new criteria. Our re-estimation of IHC result was concordant with the prediction of the guideline.

Breast Neoplasms ; chemistry ; Female ; Guideline Adherence ; Humans ; Immunohistochemistry ; Medical Oncology ; Receptor, ErbB-2 ; analysis ; Retrospective Studies ; Societies, Medical ; standards

Objective To identify the relationship between impaired glucose regulation of neuronal apoptosis in hip-pocampus and the ability of learning/memory in rats.Methods The model rats were made by high fat and sugar diet;The morris water maze was used to detect the learning and memory function;The TUNEL method was used to detect neuronal apoptosis in hippocampus .Expression of Bcl-2/Bax and Bcl-2 mRNA/Bax mRNA factor in hippo-campus neurons was detected with immunohistochemistry and in situ hybridization .Results Compared with NGT group, in IGR group the learning and memory ability were meaningfully decreased (P<0.05);the number of neuro-nal apoptosis in hippocampus was increased significantly ( P<0.05 ); the expression of Bcl-2 and Bcl-2 mRNA in hippocampus decreased significantly ( P<0.05);the expression of Bax and Bax mRNA in hippocampus increased sig-nificantly ( P<0.05 );The ability of learning and memory was positively correlated with expression of Bcl -2 ( P<0.05) and negatively correlated to the expression of Bax (P<0.05).Conclusions There is a relationship between impaired glucose regulation and the ability of learning and memory in rats , its mechanism may be potentially related to hippocampal neuronal apoptosis .

Objective To investigate the effect of CT perfusion (CTP) imaging guidance in the treatment of acute cere?bral infarction. Methods Patients (n=200) with acute cerebral infarction who visited our clinic within 6 hours underwent CTP examination and were divided into two groups:penumbra group and non-penumbra group according to their CTP imag?ing (presence of penumbra or not). Recombinant tissue plasminogen activator (rt- PA) was administrated for intravenous thrombolysis in both groups. NIHSS (The NIH Stroke Scale), BI (Barthel Index), mRS (modified Rankin Scores) and hemor?rhagic transformation events of two groups were determined before and after thrombolysis to evaluate its effect and prognosis in these two group. Results Compared with non penumbra group, NIHSS was reduced in penumbra group from 7 days after rt-PA (6.67±3.46 vs 4.76±2.04), and this decrease became obvious at 4 weeks after rt-PA (6.67±3.46 vs 3.68±1.93). Effi?ciency rate at 4 week (60.3%) and good prognosis rate at 3 months(71.7%)were both significantly improved in penumbra group than those in non penumbra group(34.7%,56.8%). Conclusion rt-PA under CTP guidance is effective and safe in the treatment of acute cerebral infarction. The thrombolytic therapy window can be enlarged according to the presence of pen?umbra or not and the bleeding conversion rate remains at low level.