Protective effects of histone deacetylase 6 specific inhibitor tubastatin A on subarachnoid hemorrhage in rats and the underlying mechanisms / 中南大学学报(医学版)

OBJECTIVES@#Subarachnoid hemorrhage (SAH) is a serious cerebrovascular disease. Early brain injury (EBI) and cerebral vasospasm are the main reasons for poor prognosis of SAH patients. The specific inhibitor of histone deacetylase 6 (HDAC6), tubastatin A (TubA), has been proved to have a definite neuroprotective effect on a variety of animal models of acute and chronic central nervous system diseases. However, the neuroprotective effect of TubA on SAH remains unclear. This study aims to investigate the expression and localization of HDAC6 in the early stage of SAH, and to evaluate the protective effects of TubA on EBI and cerebral vasospasm after SAH and the underlying mechanisms.@*METHODS@#Adult male SD rats were treated with modified internal carotid artery puncture to establish SAH model. In the first part of the experiment, rats were randomly divided into 6 groups: a sham group, a SAH-3 h group, a SAH-6 h group, a SAH-12 h group, a SAH-24 h group, and a SAH-48 h group. At 3, 6, 12, and 24 h after SAH modeling, the injured cerebral cortex of rats in each group was taken for Western blotting to detect the expression of HDAC6. In addition, the distribution of HDAC6 in the cerebral cortex of the injured side was measured by immunofluorescence double staining in SAH-24 h group rats. In the second part, rats were randomly divided into 4 groups: a sham group, a SAH group, a SAH+TubAL group (giving 25 mg/kg TubA), and a SAH+TubAH group (giving 40 mg/kg TubA). At 24 h after modeling, the injured cerebral cortex tissue was taken for Western blotting to detect the expression levels of HDAC6, endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS), terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining to detect apoptosis, and hematoxylin and eosin (HE) staining to detect the diameter of middle cerebral artery.@*RESULTS@#The protein expression of HDAC6 began to increase at 6 h after SAH (P<0.05), peaked at 24 h (P<0.001), and decreased at 48 h, but there was still a difference compared with the sham group (P<0.05). HDAC6 is mainly expressed in the cytoplasm of the neurons. Compared with the sham group, the neurological score was decreased significantly and brain water content was increased significantly in the SAH group (both P<0.01). Compared with the SAH group, the neurological score was increased significantly and brain water content was decreased significantly in the SAH+TubAH group (both P<0.05), while the improvement of the above indexes was not significant in the SAH+TubAL group (both P>0.05). Compared with the sham group, the expression of eNOS was significantly decreased (P<0.01) and the expressions of iNOS and HDAC6 were significantly increased (P<0.05 and P<0.01, respectively) in the SAH group. Compared with the SAH group, the expression of eNOS was significantly increased, and iNOS and HDAC6 were significantly decreased in the SAH+TubA group (all P<0.05). Compared with the SAH group, the number of TUNEL positive cells was significantly decreased and the diameter of middle cerebral artery was significantly increased in the SAH+TubA group (both P<0.05) .@*CONCLUSIONS@#HDAC6 is mainly expressed in neurons and is up-regulated in the cerebral cortex at the early stage of SAH. TubA has protective effects on EBI and cerebral vasospasm in SAH rats by reducing brain edema and cell apoptosis in the early stage of SAH. In addition, its effect of reducing cerebral vasospasm may be related to regulating the expression of eNOS and iNOS.

Expression and significance of L1 cell adhesion molecule and transforming growth factor-β1 in pancreatic cancer tissue / 临床肝胆病杂志

ObjectiveTo investigate the expression of L1 cell adhesion molecule (L1CAM) and transforming growth factor-β1 (TGFβ1) in pancreatic cancer tissue and their association with the prognosis of pancreatic cancer. MethodsHistological specimens were collected from 125 patients with pancreatic cancer who underwent surgical resection in The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University Cancer Hospital, and Wuming Hospital of Guangxi Medical University from January 2015 to January 2018. Immunohistochemistry was used to measure the expression of L1CAM and TGFβ1 in all specimens, and the association of the expression of L1CAM and TGFβ1 with clinical indices, survival, and prognosis was analyzed. The t-test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups; the Cox proportional-hazards regression model was used to investigate the influencing factors for the survival of patients with pancreatic cancer; the Kaplan-Meier survival analysis was used to evaluate the survival of patients with different expression levels of L1CAM and TGFβ1. ResultsThe high protein expression rate of L1CAM in pancreatic cancer tissue was significantly higher than that in adjacent tissue (75.20% vs 20.00%, χ2=76.352, P＜0.001). The high protein expression rate of TGFβ1 in pancreatic cancer tissue was significantly higher than that in adjacent tissue (8160% vs 23.20%, χ2=85.461, P＜0.001). The protein expression of L1CAM was positively correlated with that of TGFβ1 in pancreatic cancer (r=0.492, P＜0.001). The protein expression of L1CAM and TGFβ1 were associated with tumor size, degree of tumor differentiation, TNM stage, lymph node metastasis, intravascular tumor thrombus, and perineural invasion (all P＜0.05). The patients with high protein expression of L1CAM or TGFβ1 had a significantly lower overall survival rate than those with low expression (χ2=54661 and 39597, both P＜0.001). ConclusionL1CAM and TGFβ1 proteins are highly expressed in pancreatic cancer tissue and may be associated with poor prognosis by promoting lymphatic metastasis and hematogenous metastasis. L1CAM and TGFβ1 proteins play an important role in the development, progression, and metastasis of pancreatic cancer.

Serum expression of angiopoietin-like protein 2 in pancreatic cancer patients with or without diabetes and its association with prognosis / 临床肝胆病杂志

ObjectiveTo investigate the expression level of angiopoietin-like protein 2 (ANGPTL2) in pancreatic cancer patients with or without diabetes and the clinical value of ANGPTL2 as a prognostic marker in patients with pancreatic cancer. MethodsSerum samples were collected from 125 pancreatic cancer patients who were treated in The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University Cancer Hospital, and Wuming Hospital of Guangxi Medical University from January 2015 to January 2018, among whom 64 had pancreatic cancer alone and 61 had pancreatic cancer and diabetes, and 66 individuals who underwent physical examination were enrolled as control group. ELISA was used to measure the serum level of ANGPTL2, and the association of the expression level of ANGPTL2 with clinical indices, survival, and prognosis was analyzed. A one-way analysis of variance was used for comparison of normally distributed continuous data between three groups, and the Bonferroni test was used for comparison between two groups. The independent-samples Kruskal-Wallis H test was used for comparison of continuous data with skewed distribution between three groups and the one-way ANOVA analysis was used for comparison between two groups. The chi-square test was used for comparison of categorical data between groups. Spearman correlation analysis was also performed to investigate correlation. The Kaplan-Meier method was used to plot survival curves, and the log-rank test was used for comparison of survival rate. The Cox risk model was used to perform univariate and multivariate analyses to determine independent risk factors for the prognosis of pancreatic cancer. ResultsThe pancreatic cancer+diabetes group had a significantly higher serum concentration of ANGPTL2 than the pancreatic cancer group and the control group ［7.79 (7.12-8.17) ng/ml vs 5.74 (508-6.40) ng/ml and 3.72 (3.25-4.16) ng/ml, χ2=126.367, P＜0.001］. Serum ANGPTL2 concentration was positively correlated with carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) (r=0.560 and 0.731, both P＜0.001). The univariate analysis showed that tumor size, distant organ metastasis, degree of tumor differentiation， CEA, ANGPTL2, and HbA1c were closely associated with the long-term survival of pancreatic cancer patients, and the multivariate analysis showed that tumor size (HR=2.657,P=0.005), distant organ metastasis (HR=5.000,P=0.014), degree of tumor differentiation (HR=2.466,P=0.004), CEA(HR=1.110,P＜0.001) and ANGPTL2(HR=1.901,P=0.001) were independent risk factors for the prognosis of pancreatic cancer patients. For all pancreatic cancer patients, the high ANGPTL2 expression group had a significantly lower 2-year survival rate than the low ANGPTL2 expression group (8.51% vs 25.81%, χ2=5.651, P=0.017). For the pancreatic cancer patients with diabetes, the high ANGPTL2 expression group had a significantly lower 2-year survival rate than the low ANGPTL2 expression group (2.20% vs 32.70%, χ2=24.895, P＜0.001).ConclusionANGPTL2 can be used as an effective clinical index to evaluate the prognosis of pancreatic cancer patients, especially those with diabetes.

Establishment of a mouse model of cutaneous squamous cell carcinoma induced by 7,12-DMBA, croton oil and narrow-band ultraviolet B irradiation / 中国比较医学杂志

Objective To establish a mouse model of cutaneous squamous cell carcinoma induced by 7,12-dimethylbenz(a)anthracene (7,12-DMBA)/croton oil and narrow-band ultraviolet B (NB-UVB) irradiation.Methods A total of fifty 6-8-week old BALB/c mice (male:female 1:1) were randomly divided into three experimental groups.The group A was treated with chemical carcinogens alone, group B was treated with NB-UVB alone, and group C was treated with chemical carcinogens plus NB-UVB.The general status and skin appearance of mice were observed during the experiment.The survival rate and tumor formation rate of each group was calculated at weeks 5, 10, 15, and 20. Pathological examination was carried out to observe the histological changes of skin lesions.Results Papules measuring≥l mm in diameter began to develop in some mice of the group C at 5 weeks after the first treatment with chemical carcinogens.The tumor formation rates at 20 weeks after treatment were 86.67%, 7.14%, 94.12%in the groups A, B, C, respectively.Pathological examination revealed characteristic changes of squamous cell carcinoma in 13.34%, 0%, 70.59%of the mice in the group A, B, C, respectively.Conclusions Establishment of a mouse model of cutaneous squamous cell carcinoma induced by 7,12-DMBA/croton oil and NB-UVB is a better method than treated with chemical carcinogens alone or NB-UVB alone.This method can increase the tumor formation rate and incidence rate of SCC, and within a shorter period.

Effect of the Combination of Xiyanping and Cefazolin on the Function of Neutrophils in Mice / 生物医学工程学杂志

Xiyanping is used to treat infectious diseases with antibiotics in clinic. The aim of this study is to investigate the mechanism of Xiyanping through studying the effect of the combination of Xiyanping with Cefazolin on the chemotaxis and phagocytic function of peripheral blood neutrophils in mice. Ten healthy mice were in control group. Forty healthy mice in experimental group were infected with staphylococcus aureus, and were randomly divided further into four groups, i. e. model group, Xiyanping group, Cefazolin group and combination group (Xiyanping with Cefazolin). Mice in the control group and model group were given normal saline (NS) through abdomen while those in other groups were given Xiyanping, Cefazolin, and Xiyanping with Cefazolin, respectively. The chemotaxis of peripheral blood neutrophils was detected with the transwell method, and the phagocytic function of peripheral blood neutrophils was analyzed with flow cytometry (FCM). In the present study, there was no significance on the chemotactic index of peripheral blood neutrophils in all the groups (P > 0.05). The actual phagocytotic rate and index of peripheral blood neutrophils in the blank group, Xiyanping group, and the combination group were significantly higher than those of the model group and Cefazolin group (P < 0.05). However, those were not significant in the blank group, Xiyanping group, and the combination group (P > 0.05) or between the model group and Cefazolin group (P> 0.05). Our results suggested the combination of Xiyanping and Cefazolin could enhance the therapeutic effect by improving the phagocytic function of peripheral blood neutrophils.

The relationship between expression of Id-2 and MMP-9 and clinical pathology index in rectal cancer / 重庆医学

Objective To observe the expression level of inhibitor of differentiation 2 (Id‐2) and matrix metalloproteinases‐9 (MMP‐9) in rectal cancer ,analysis the correlation of the expression level of them ,to study the relationship between the expression level of them and the clinical pathology indicators of rectal cancer .Methods Rectal cancer tissues and normal tissue adjacent to rec‐tal cancer were obtained from the rectal cancer resection of 56 patients with rectal cancer ,using immunohistochemical method to ob‐serve the expression level of Id‐2 and MMP‐9 in normal tissue adjacent to rectal cancer and rectal cancer and Spearman correlation test to detect the correlation between the expression level of Id‐2 and MMP‐9 ;then we analyzed the relationships between the ex‐pression level of Id‐2 and MMP‐9 and the index of rectal cancer clinical pathology .Results The positive expression rate of Id‐2 in the in rectal cancer tissues is more higher than that of normal tissue of adjacent to rectal cancer (73 .21% vs .48 .21% ,P0 .05) .Conclusion There is a close relationship between the expression levels of Id‐2 and MMP‐9 in rectal cancer and the occurrence and development of rectal cancer .Rectal cancer with the higher Id‐2 expression level may be the ways to achieve tumor invasion and metastasis through MMP‐9 as a facilitator .

Compensation mechanism in public hospitals and path optimization system changes / 中华医学科研管理杂志

The compensation mechanism reform is the key and difficult point of the public hospital reform.Although current health care reform has been carried out including strengthening public welfare of public hospitals and adjusting the compensation mechanism,the effect is not very obvious.How to conduct the compensation mechanism reform orderly and smoothly has become an important topic.I have analyzed the historical evolution,the status and problems of the hospital compensation mechanism.On the basis I have made views and suggestions about the current drive and the path optimization for the compensation mechanism reform.

International experience of the management system of public hospitals and public welfare system / 中华医学科研管理杂志

There are three kinds mainly of the present government worldwide management of public hospital management system and public service system.This paper compares the management system of public hospitals of the United States of America,Britain,Singapore and other countries,discussion of foreign public hospital public welfare system arrangement.With a view to put forward effective suggestions for the reform of public hospitals in China and public hospital regression public.

Statins and intracerebral hemorrhage / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To briefly review the literature regarding the impact of statins on the prevention and treatment of stroke, especially on intracerebral hemorrhage (ICH). We described statins' effects, mechanism of ICH, serum total cholesterol and ICH, and the relationship between statins and ICH.</p><p><b>DATA SOURCES</b>All articles used in this review were mainly searched from the PubMed database with no limitations of language and year of publication.</p><p><b>STUDY SELECTION</b>Randomized controlled studies, prospective cohort studies, animal experiments, and meta-analysis articles related to this topic in the past decade were selected.</p><p><b>RESULTS</b>Statins play an important role in the primary and secondary prevention of cardiovascular diseases and also have an impact on the treatment of vascular diseases. There still exist controversies about the relationship between statins and ICH. More clinical and experimental trials indicate that statins do not increase the risk of ICH.</p><p><b>CONCLUSION</b>A low or a regular dose of statins would not increase the risk of ICH.</p>

Study on the strategies of hospital crisis management / 中华医学科研管理杂志

critical incidents are significant for the management of hospitals,and it may even be critical to the survival and development of the hospital.This article introduces a series of practices adopted by the First People's Hospital of Changzhou conducted in cases of crisis,and discusses the strategies and measures in hospital crisis management.