Objective To investigate the effects of insulin on vascular diameter of the peri -infarct region and infarct volume after cerebral infarction in mice. Methods Forty male C57/BL6j mice w ere randomly divided into a control group ( n = 5), a cerebral infarction group ( n = 15), a cerebral insulin resistance group (n = 5), and a cerebral insulin resistance infarction group ( n = 15). A model of cerebral infarction w as induced by the photochemical method. A model of cerebral insulin resistance w as induced by intracerebroventricular injection of streptozocin. Tw o -photon confocal microscope w as used to in vivo evaluate the changes of vascular diameter in the peri-infarct region at 20 min after insulin injection into the cerebelomedulary cistern. After modeling of cerebral infarction, artificial cerebrospinal fluid or insulin (10 ng/ml) w as immediately injected into the cerebelomedulary cistern, and the effect of insulin on cerebral infarct volume w as evaluated at 24 h after infarction. Results Insulin did not have significant effect on various types of cerebral vascular diameters in the normal control group, but it significantly contracted cerebral arteries ( -23.16% ±6.86% and -23.32% ±6.40%, respectively; al P <0.001) and penetrating arteries ( -15.20% ±5.51% and -16.40% ±4.27%, respectively; al P < 0.001) in the cerebral insulin resistance group and the cerebral insulin resistance infarction group, but it did not have any effect on the diameters of the cerebral veins. There w ere no significant differences in the vasoactive effects of insulin betw een the cerebral infarction group and the normal control group, as w el as betw een the cerebral insulin resistance group and the cerebral insulin resistance infarction group. Insulin significantly reduced the volume of cerebral infarction in the cerebral infarction group (9.0 ±1.0 mm3 vs.6.0 ±1.2 mm3; t = 4.294,P =0.002), and it did not have significant effect on the volume of cerebral infarction in the cerebral insulin resistance infarction group ( 12.6 ±2.3 mm3 vs.11.6 ±1.7 mm3; t = 0.782, P = 0.456). Conclusions Insulin can reduce ischemic brain injury in normal mice and can not affect the cerebrovascular diameter of the peri-infarct region. The neuroprotective effect of insulin is not significant in cerebral insulin resistance in mice, and it may be associated w ith the vasoconstrictor effects of insulin in the peri -infarct region.

Objective To examine cerebrovascular reactivity to CO2 inhalation in mice. Methods In vivo Two-Pho?ton imaging technique was used to record the reaction of cerebral cortical vessels including penetrating artery, surface vein and capillary in 5 male C57 mice after CO2 inhalation under a thinned-skull cranial window. Nitric oxide syntheses inhibitor L-NAME and Prostaglandin syntheses inhibitor Indomethacin were used to block different vasodilator pathways, respectively. Results Different mouse cortical vessels displayed different degrees of dilation to 1-minute 5%CO2 inhala?tion. The penetrating artery exhibited the most obvious dilation (45.01%±4.45%). L-NAME intervention significantly di?minished cerebravascular CO2 reactivity(P<0.05). Indomethacin significantly attenuated the dilation of artery but not capillary comparing with L-NAME intervention(P<0.05). Conclusions Different vessels react differently to CO2 inhala?tion in which postaglandins and NO signal pathways are involved.

Objective To explore the effects of Ginkgolide B on the expression of hypoxia inducible factor 1 α (HIF-1α) and P I3K/Akt pathway in the hippocampus of developing rats after pentylenetetrazol(PTZ)-induced status epilepticus,and to investigate the correlation between HIF-1α expression and PI3K/Akt pathway.Methods Ninety-six SD rats aged 21 days were randomly divided into normal saline group(group NS),status epilepticus group (group P),GKB treatment groups (group G+P),GKB +wortmannin treated group (group G+P+W),wortmannin treated group(group P+W).The brain tissue were harvested from the rats at 4 and 8 hours after the inducement,but in the group G+P at 1 h,4 h,8 h,24 h.Immunohistochemistry and Western blot were used respectively to detect HIF-1α and p-Akt protein expression.Results (1) For the group G+P,there were statistical differences in the expression levels of p-Akt protein between 1 h,4 h,8 h and 24 h(P＜0.01),The p-Akt protein reached the peak level at 4 hours (0.85±0.03),there were statistical differences in the expression levels of HIF-1α protein between 1 h,4 h,8 h and 24 h(P＜0.01),the HIF-1α expression reached the peak level at 8 hours(1.00±0.13).(2) The expression of HIF-1α in all the groups at 8 hours time point:the expression levels of HIF-1α in the group P and group G+P were significantly higher than those in the group NS (P＜0.01) and the expression levels of HIF1α in the group G+P were higher than those in the group P(P＜0.01).Using wortmannin,the PI3K/Akt specific inhibitor,HIF-1α protein expression in the group G+P+W and P+W was significantly decreased when compared with the group G+P and P (P＜0.01).(3)The expression of p-Akt in all the groups at 4 hours time point:the expression levels of p-Akt in the group P and group G+P were significantly higher than those in the group NS (P＜0.01) and the expression levels of p-Akt in the group G+P were higher than those in the group P (P＜ 0.01).Using wortmannin,p-Akt protein expression in the group G+P+W and P+W was significantly decreased when compared with the group G+P and P (P＜0.01).Conclusion GKB can activate PI3K/Akt signaling pathway,and the pathway is involved in regulating the expression of HIF-1α.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder primarily occurred in small joints.Our previous studies suggested that sufficient lymphatic drainage was favorable for the recovery of RA.This study aimed at exploring the effect of Er Chen combined with Tao Hong Si Wu Tang (ECSWT) on RA in TNF transgenic (TNF-Tg) mice.Ten-week old TNF-Tg mice and WT littermates were detected with indocyanine green-nearinfrared (ICG-NIR) lymphatic imaging system before and after accepting the 12-week intragastric administration of ECSWT.All ankle joints were assessed by micro-CT scanning.According to three dimensional images of Micro-CT,it was found that the ankle joints in the TNF-Tg group were much eroded compared with the control group.The bone mass and structure were protected after the treatment of ECSWT.ICG-NIR results showed that lymphatic clearance rate of the TNF-Tg group decreased compared with those of the control group.In comparison with the TNF-Tg group,ECSWT promoted the repair of lymphatic function.Compared with the control group,the pulse value of the TNF-Tg group declined;while this condition could be rescued by ERSWT.In conclusion,ECSWT mitigated bone erosion of astragalus bone area in TNF-Tg mice in contrast to the saline mice,while promoted the pulse value and clearance of lymphatic vessels afferent from footpad to popliteal lymph node,implying that ECSWT was a promising agent for treating RA through its promoting lymphatic drainage function effects.

Background and purpose: Natural killer/T cell lymphoma in poor effects, the production of multidrug resistance is one of the reasons to reduce the chemotherapy effect or failure. This study aimed to discuss the multidrug resistance associated protein 4 (ABCC4/MRP4) gene and multidrug resistance associated protein 5 (ABCC5/MRP5) gene expression in NK/T cell lymphoma SNK-6, YTS cell lines and NK/T cell lymphoma tissues, and the relationship between the level of ABCC4/MRP4, ABCC5/MRP5 gene expression and the clinical efifcacy. Methods:Real-time lfuorescence quantitative PCR (Real time-PCR) and immunohistochemical method (IHC) were used to detect the ABCC4/MRP4, ABCC5/MRP5 gene and protein expression. Results:Compared with the normal NK cells, ABCC4/MRP4 and ABCC5/MRP5 gene in SNK-6, YTS cell lines were highly expressed (P<0.05); Compared with rhinitis tissues, the expression of ABCC4/MRP4, ABCC5/MRP5 gene was higher in the NK/T cell lymphoma tissues (P<0.05);The expression level of ABCC4/MRP4 and ABCC5/MRP5 gene was negative correlation with clinical efifcacy (P<0.05). Conclusion: The expression of ABCC4/MRP4 and ABCC5/MRP5 gene affects the of clinical efifcacy of NK/T cell lymphoma.

Objective To observe the efficacy and side effects of exemestane in postmenopausal breast cancer patients with bone metastasis.Methods One hundred and ten postmenopausal breast cancer patients with bone metastasis were treated with exemestane 25 mg.Results In the evaluable data from 110 patients,the complete remission(CR)was encountered in 7 cases,partial remission(PR)in 28 cases,with a total response rate of 31.8％ ;Thirty nine patients had stabled diseases for more than 24 weeks.It produced a clinical benefit (CR + PR + SD)over 24 weeks in 74 cases(67.3％).Diseases progressed in 12 of the cases(10.9％).The patients with positive ER and PR status had a higher chance to be benefited from the treatment than those with negative receptor status.The clinical efficacy was not correlated with treatment history,pathological subtypes and bone,liver,lung and lymph node metastasis(x2 =0.045,0.078,0.200,P ＞ 0.05).No severe adverse effects were observed.Conclusion Exemestane is effective to treat bone metastasis of breast cancer with minor adverse reactions and good tolerability.

Pulmonary veno-occlusive disease (PVOD)/pulmonary capillary hemangiomatosis (PCH) is a rare form of pulmonary vascular disease that causes pulmonary arterial hypertension.The diagnosis of PVOD/PCH can be established by the combination of clinical features,physical examination,radiological findings,lung function,bronchoscopy and other resources.There is no established medical therapy for PVOD/PCH,and the only curative therapy for PVOD/PCH is lung transplantation.A girl with PVOD/PCH was diagnosed in the Second Xiangya Hospital.Combining the characteristics for this case with the relevant literature,we summarized the epidemiology,etiology,diagnosis and treatment for the disease to raise doctors' awareness for this rare disease.

OBJECTIVETo investigate the role of different immunoglobulin- like receptor (KIR)haplotypes in haplo- identical hematopoietic stem cell transplantation (HSCT).

METHODKiller cell KIR genotyping was performed on 468 individuals from 156 unrelated families by PCR-SSP. A total of 624 KIR haplotypes from the parents were used for haplotype analysis. Ninety-two patients received haplo-identical HSCT from one of the parents.

RESULTSThe family study showed segregation of one A haplotype and at least 20 unique B haplotypes. The frequency of haplotype A was 72.92% (455/624). The most commonly observed haplotypes in group B were B1, B2, and B3, present at a frequency of 10.26%, 5.77%, and 4.48%, respectively. Compared to KIR gene matched donors (n=17), grafts from KIR gene mismatched donors (n= 14) had a positive effect on survival after haplo- identical HSCT for AML/MDS patients (OS: 88.2%vs 42.9%,P=0.015; RFS: 88.2%vs 35.7%,P=0.007). No effect was observed for ALL/NHL patients (OS: 76.0%vs 75.0%,P=0.727; RFS: 68.0%vs 65.0%,P=0.866). A significantly lower survival rate was observed for transplants from AA (n=52) and AB1/AB2 donors (n=15), compared to other group Bx donors (n=25) (OS: 53.3%vs 96.0%,P=0.017; RFS: 53.3%vs 92.0%,P=0.019). Meanwhile, the risk of relapse was much higher in AA group (n=52) compared to Bx group (n=40) (25.0%vs 5.0%,P=0.009). A higher risk of TRM was observed in AB1/AB2 group (P=0.012). In addition, transplant from donors carried Cen-B was associated with an increased survival compared with Cen-A homozygous donors (OS: 94.7%vs 68.5%,P=0.036; RFS: 89.5%vs 64.4%,P=0.045).

CONCLUSIONOverall, KIR genotyping and haplotype analyses should be useful for selection of the most optimal donors with favorable KIR gene grafts. KIR gene mismatch donors should be preferred for AML/MDS patients. Selecting donors carried Cen- B and avoiding the selection of donors of KIR genotype AA/AB1/AB2 was strongly advisable for haplo-identical HSCT.

Chronic Disease ; Genotype ; Haplotypes ; Hematopoietic Stem Cell Transplantation ; Humans ; Killer Cells, Natural ; Leukemia, Myeloid, Acute ; therapy ; Neoplasm Recurrence, Local ; Receptors, KIR ; genetics ; Survival Rate ; Tissue Donors

Pulmonary hypertension (PH) is a common complication in patients with end-stage renal disease (ESRD), especially in patients with hemodialysis (HD). Poor prognosis can eventually lead to right heart failure and even death. PH is an independent risk factor for increased mortality in ESRD patients. We should pay attention to these patients in clinic for early detection, prevention and treatment. The pathogenesis of PH in ESRD patients is still unclear so far, which might be related to the increase of pulmonary vascular resistance, pulmonary blood flow, and pulmonary arterial wedge pressure. In addition, the presence of risk factors can promote the development of PH, such as chronic hypoxia, vascular calcification, and inflammation.
Heart Failure ; Humans ; Hypertension, Pulmonary ; Kidney Failure, Chronic ; Renal Dialysis ; Risk Factors

Objective:To study the application effect of scenario simulation teaching combined with mini-clinical evaluation exercise (Mini-CEX) in the standardized residency training of general surgery.Methods:The study included in 62 trainees who had standardized residency training in the Department of General Surgery of the Affiliated Hospital of Xuzhou Medical University From July 2019 to July 2020. The subjects were randomly divided into traditional teaching group (control group) and scenario simulation teaching combined with Mini-CEX teaching group (experimental group), with 31 students in each group. The scores of the entrance examination, Mini-CEX scores and the evaluation of teaching effect were compared between the two groups. SPSS 21.0 was used to perform t test on the test scores, Mini-CEX scores and teaching effective evaluation scores of the two groups. Results:①The theoretical scores of the experimental group [(82.48 ± 6.02) points] were significantly higher than those of the control group [(77.32±6.25) points], with significant differences ( t=3.31, P<0.01). The clinical practice scores of the experimental group [(88.96 ± 2.93) points] were significantly higher than those of the control group [(80.87±5.41) points], with significant differences ( t=7.33, P<0.01). ②Mini-CEX scores of the experimental group were higher than those of the control group ( P<0.01). ③Through the teaching questionnaire, the scores of the experimental group were higher than those of the control group ( P<0.01). Conclusion:Scenario simulation teaching combined with Mini-CEX has achieved good results in the standardized residency training of general surgery, which could be used as a new clinical teaching mode.