Inducible costimulatory molecule(ICOS)is a member of the CD28 family,which can be expressed on the tumor tissues and immune cells in the tumor microenvironment. ICOS enhances its anti-tumor activity through participating in CD4 + T and CD8 + T cell immune response and enhancing the secretion of cyto-kines on the activated T cells and NK cells. While the curative effect of cytotoxic T lymphocyte-associated anti-gen-4(CTLA-4)monoclonal antibody is relevant with CD4 + T cells expressing ICOS,which suggesting ICOS may become a novel anti-tumor therapeutic target in the future.

OBJECTIVE:To investigate clinical efficacy and safety of recombinant human tissue type plasminogen activator (rt-PA) intravenous thrombolytic in the treatment of elderly patients (over 75 years old) with acute cerebral infarction (ACI). METHODS:78 elderly ACI patients,on the basis of routine treatment,were divided into thrombolysis group (40 cases) and non-thrombolysis group (38 cases) according to the will of patients or family members. Non-thrombolysis group received aspirin 200 mg,qd;thrombolysis group was given rt-PA 0.9 mg/kg(maximum dose of 90 mg)by intravenous push of 10% dose within 1 min,and intravenous dripping of residue dose within 60 min;receiving aspirin 200 mg,qd,24 h after thrombolytic therapy with-out contraindications. Both groups were treated for 14 days. The effective rate,NIHSS score before treatment and 24 h,7 d and 14 d after treatment,prognosis after 90 d were compared between 2 groups,and the occurrence of ADR was observed in 2 groups. RE-SULTS:The total effective rate was 67.50% in thrombolysis group and 52.63% in non-thrombolysis group,with statistical signifi-cance(P<0.05);there was significant difference in NIHSS score between 2 groups 24 h,7 d,14 d after treatment(P<0.05);90 d prognosis of thrombolysis group was superior to that of non-thrombolysis group,there was statistically significance (P<0.05);there was no statistical significance in the incidence of ADR between 2 groups (P>0.05). CONCLUSIONS:4.5 h time window rt-PA intravenous thrombolytic therapy is safe and effective for elderly patients with ACI,and can reduce disability and fatality,im-prove prognosis.

Objective To investigate the effect and mechanism of liver X receptor ( LXR ) agonist on expression of fatty acid synthase( FAS) in diabetic kidney. Methods In the part of in vivo study, immunostaining was used to detect the FAS protein expression in kidney. 16-week-old male db/db mice on C57BL/6 background were administered via gavage a LXR synthetic agonist, TO901317, at a dose of 3 mg · kg-1 · d-1 or vehicle ( 0. 5%Carboxymethyl Cellulose Sodium, CMC-Na) alone for 7 d;Quantitative RT-PCR and Western blot were used to detect mRNA and protein levels of FAS and SREBP-1. In the part of in vitro study, MCT cell(a mouse murine proximal tubule cell line)was treated with 10μmol/L TO901317 for 24 h or transfected with active SREBP-1c expression vector (SREBP-1cN). HEK293 cells(a human renal tubule cell line)were transfected with mFAS-(1. 7 kb)-luc, LXR expression vector or SREBP-1cN for 12 h. Quantitative RT-PCR and luciferase reproter assay were utilized to examine FAS mRNA level and FAS promoter activity. Results FAS was abundantly expressed in renal cortex, with low expresson in renal glomeruli. The mRNA and protein expressious of FAS in kidney of db/db mice were lowered compared with db/m mice. TO90137 treatment increased FAS mRNA expression by 1. 3-fold. TO901317 increased expression of SREBP-1 in kidneys of db/m and db/db mice by 5. 1-fold and 17-fold, respectively. TO901317 and overexpression of SREBP-1c increased expression of FAS in MCT cells by 1. 5-fold and 1. 8-fold. Transcription activity of FAS were induced by TO901317, LXR, and SREBP-1cN overexpressions in HEK293 cells. Conclusions Both direct(LXRE)and indirect(SREBP-1c)mechanisms may contribute to the up-regulation of FAS expression by LXR in renal proximal tubule cells.

Objective To analyze the follow-up results and clinical characteristics of one case of highly sensitized recipient after combined kidney transplantation and splenic fossa auxiliary heterotopic liver transplantation.Methods This patient was diagnosed as having chronic renal insufficiency in the uremia period 10 years ago,subjected to kidney transplantation 9 years ago,and got renal allograft loss 8 years ago.The recipient was positive for PRA (for class Ⅰ,31％,and for class Ⅱ,63％).Under the general anesthesia,the patient was given combined kidney transplantation and splenic fossa auxiliary heterotopic liver transplantation.The ATG was used for immune induction.Rituximab and plasma exchange were applied to prevent acute rejection.Regular follow-up was done after discharge.Results On the postoperative day (POD) one,ALT was 256 IU/L,AST was 342 IU/L and serum creatinine was 502 μmol/L.On the POD 6,ALT and AST levels were normal and serum creatinine was 141 μmol/L.Serum creatinine increased to 202 μmol/L and the volume of urine reduced on the POD 7.The ultrasound displayed graft size increased slightly,substantial echogenicity enhanced,artery blood flow RI increased to 0.8,suggesting the occurrence of acute rejection.A single dose of Rituximab,intravenous IG,and plasma exchange were given.On the POD 60,serum creatinine was reduced to 131 μmol/L.During a follow-up period of 28 months,imrnunosuppresants were given:Tac + MMF + Pred.FK506 valley concentration was maintained at 6-8 μg/L.The function of the transplanted kidney and liver was normal,and the general conditions were good.Conclusion Combined kidney transplantation and splenic fossa auxiliary heterotopic liver transplantation is safe.Individualized medication and regular follow-up are the important factors for long-term survival of recipients.

Angiostrongylus cantonensis invades the central nervous system (CNS) of humans to induce eosinophilic meningitis and meningoencephalitis and leads to persistent headache, cognitive dysfunction, and ataxic gait. Infected mice (nonpermissive host), admittedly, suffer more serious pathological injuries than rats (permissive host). However, the pathological basis of these manifestations is incompletely elucidated. In this study, the behavioral test, histological and immunohistochemical techniques, and analysis of apoptotic gene expression, especially caspase-3, were conducted. The movement and motor coordination were investigated at week 2 post infection (PI) and week 3 PI in mice and rats, respectively. The cognitive impairs could be found in mice at week 2 PI but not in rats. The plaque-like lesion, perivascular cuffing of inflammatory cells, and dilated vessels within the cerebral cortex and hippocampus were more serious in mice than in rats at week 3 PI. Transcriptomic analysis showed activated extrinsic apoptotic pathway through increased expression of TNFR1 and caspase-8 in mice CNS. Immunohistochemical and double-labeling for NeuN and caspase-3 indicated the dramatically increased expression of caspase-3 in neuron of the cerebral cortex and hippocampus in mice but not in rats. Furthermore, western-blotting results showed high expression of cleaved caspase-3 proteins in mice but relatively low expression in rats. Thus, extrinsic apoptotic pathway participated in neuronal apoptosis might be the pathological basis of distinct behavioral dysfunctions in rodents with A. cantonensis infection. It provides the evidences of a primary molecular mechanism for the behavioral dysfunction and paves the ways to clinical diagnosis and therapy for A. cantonensis infection.
Angiostrongylus cantonensis* ; Angiostrongylus* ; Animals ; Apoptosis* ; Behavior Rating Scale ; Caspase 3 ; Caspase 8 ; Central Nervous System ; Cerebral Cortex ; Diagnosis ; Eosinophils ; Gait ; Gene Expression ; Headache ; Hippocampus ; Humans ; Meningitis ; Meningoencephalitis ; Mice ; Neurons* ; Rats ; Receptors, Tumor Necrosis Factor, Type I ; Rodentia*

Background/Aims: The incidence and prevalence of inflammatory bowel disease (IBD) is rising in Asia recently. The study aimed to obtain a comprehensive understanding of the current status of drug therapy and monitoring for IBD in Asia. Methods: A questionnaire investigation on drug therapy and monitoring for IBD was conducted right before the 6th Annual Meeting of Asian Organization for Crohn’s & Colitis. Questionnaires were provided to Asian physicians to fill out via emails between March and May 2018. Results: In total, responses of 166 physicians from 129 medical centers were included for analysis. Among the surveyed regions, the most average number of IBD specialist gastroenterologists and nurses was 4.8 per center in Taiwan and 2.5 per center in Mainland China, respectively. 5-Aminosalicylic acid/sulfasalazine (99.4%) was the most preferred first-line choice for mild-moderate ulcerative colitis (UC), meanwhile corticosteroid (83.7%) was widely applied for severe UC. The first-line medication for Crohn’s disease (CD) markedly varied as corticosteroid (68.1%) was the most favored in Mainland China, Japan, and South Korea, followed by infliximab (52.4%) and azathioprine (47.0%). Step-up strategy was preferred in mild-moderate UC (96.4%), while 51.8% of the physicians selected top-down treatment for CD. Only 25.9% and 17.5% of the physicians could test blood concentration of infliximab and antibody to infliximab in their hospitals, respectively. Conclusions The current status of drug therapy and monitoring for IBD in Asia possesses commonalities as well as differences. Asian recommendations, IBD specialist teams and practice of therapeutic drug monitoring are required to improve IBD management in Asia.

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.
Brain Ischemia ; drug therapy ; Humans ; Prognosis ; Retrospective Studies ; Stroke ; drug therapy ; Thrombolytic Therapy ; Time Factors

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.
Administration, Intravenous ; Brain Ischemia ; drug therapy ; Fibrinolytic Agents ; therapeutic use ; Hospitals ; statistics & numerical data ; Humans ; Prognosis ; Stroke ; drug therapy ; Thrombolytic Therapy ; statistics & numerical data ; Time Factors ; Treatment Outcome

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.
Antifibrinolytic Agents ; adverse effects ; pharmacology ; Atrial Fibrillation ; complications ; Brain Ischemia ; complications ; drug therapy ; Humans ; Retrospective Studies ; Stroke ; complications ; drug therapy ; Thrombolytic Therapy ; adverse effects ; Treatment Outcome

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.
Brain Ischemia ; drug therapy ; Fibrinolytic Agents ; therapeutic use ; Humans ; Reperfusion ; Retrospective Studies ; Stroke ; drug therapy ; Thrombolytic Therapy ; Time Factors ; Treatment Outcome