Neurotoxicity is one common adverse effect caused by many drugs or compounds.In the early phase of new drug development,it is necessary to screen for neurotoxicants.Neurotoxicity studies in nonhuman primates (NHP) are used to evaluate the neurotoxicity of small-molecule drugs or vaccines that may affect the nervous system across the blood-brain barrier during preclinical safety assessment.Toxicologic pathological evaluation or neuropathological examination is the "gold standard" for the evaluation of drug neurotoxicity in preclinical drug safety studies.In this paper,the majory factors influencing the quality of neuropathology evaluation in toxicology,including the general strategy of neuropathology evaluation,the optimal timing of evaluation,the specific blood-brain barrier in the nervous system,the method of sampling in the histopathology of nerve tissue,and the interference of artificial artifacts in diagnosis of neuropathology,were detailly analyzed in order to provide a reference for setting guidelines of neurotoxicity risk assessment in China and pathologists and toxicologists engaged in nonclinical neurotoxicity studies.

AIM To investigate the protective effects of Dahuang Zhechong (DHZC) Pills (Rhei Radix et Rhizoma,Eupolyphaga seu Steleophaga,Hirudo,etc.) against alcoholic liver fibrosis (ALF) injury in mice and to explore the underlying mechanisms.METHODS C57BL/6 male mice were used to build up ALF injury model,intervened with DHZC Pills.The serum of mice was examined for changes in alanine transaminase (ALT),aspartate aminotransferase (AST),interleukin-6 (IL-6),interleukin-10 (IL-10),interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α).Simultaneously,the deposit of collagen 1 (COL-1) and apoptotic cell death in liver tissues were analyzed by immunofluorescent and TUNEL assay,respectively.The expressions of cleaved caspase-3 (CC3) in livers were measured by Western blot.RESULTS Compared with the model group,the levels of serum ALT,AST,IL-6,IFN-γand TNF-α of mice in DHZC group were decreased significantly.And the level of serum IL-10 of mice in DHZC group was increased significantly.Mice in DHZC group had higher rates of COL-1 deposition and apoptotic cell death in liver tissues than those in the model group.Mice treated with DHZC Pills showed lower expression of CC3.CONCLUSION DHZC Pills confers protection against ALF injury in mice by inhibiting the generation of COL-1 and down-regulating apoptosis of liver cells death as a result of adjusting the levels of inflammatory factors.

Objective To analyze the related pathogenicity gene mutations in a sudden death of hypertrophic cardiomyopathy (HCM) on whole exome level.Methods Whole exome sequencing (WES) was been performed on a sudden death case sample with pathological features of HCM by Illumina(R) Hiseq 2500 platform.Using hgl9 as the reference sequences,the sequencing data were analyzed.Suspicious single nucleotide variants (SNV) were screened,and the conservatism and function were analyzed by the software such as PhyloP,PolyPhen-2,SIFT,etc.Results After screening,a heterozygous mutation C719R was finally identified in the gene MYBPC3 of this case.Conclusion The molecular anatomy on whole exome level by second generation sequencing technology can help to define the molecular mechanism of HCM and provide a new mothed and thought for analysis of death cause.

Objective To explore the regularity of time-dependent changes in morphology and biomechanical properties of brain tissues in pigs,and value the feasibility of deducing the postmortem interval (PMI).Methods Brain tissues were taken from 42 pigs and kept in an artificial climate chamber with the temperature of 25 ℃ and humidity of 75％.The samples were collected from telencephalon at sequential time intervals (0,12,24,36,48,60 h;n =6) according to the principle of predefined time,position,direction,ratio,quantity and shape.The samples fixed with formaldehyde were then immediately tested by mechanical testing machine to obtain their biomechanical parameters and the histological sections were prepared.Results With the extension of PMI (0-60 h),brain tissues gradually became discolored,weak,mudding and liquefied under the influence of autolysis and putrefaction.Both clearance area of the white matter and its integrated optical density (IOD) significantly increased during 0-48 h.Biomechanical properties of brain tissues including the limit load,average force,elastic modulus and fracture energy all presented a declining tendency at the interval of 12-60 h.The limit load was considered highly statistically significant,and statistical differences were found in average force,elastic modulus and fracture energy.Conclusions There exists a significantly negative structure-activity relationship between the morphology of brain tissues and biomechanical properties.The limit load of postmortem brain tissues in 60 h is the optimum in the window period,which can be used as a new method for estimating PMI.

Traditional Chinese medicine (TCM) for external use in the treatment of surgical disease has good clinical effect and security,even played a unique effect.At present,surgical department of TCM lack of external application drug.The hospital's own production of external use drug cannot meet the clinical needs,seriously restricting the development of surgical department of TCM.Under the background of attaching great importance to new drug innovation research and development in our country,in the caseof clinical demand of external application drug increases year by year,it is imperative to promote external application drug research and development.This article summarizes the clinical application situation of external application drug,sums up the opportunity and the challenge of new drug research and development,analyses the difficulties and problems in research and development,and the countermeasures were discussed.

Objective:To analyze the incidence and mortality of thyroid cancer among permanent residents in Luwan district of Shanghai from January 2004 to December 2011.Methods:The data of thyroid cancer in permanent residents of Luwan district were collected from the database of cancer registration and management system in Shanghai.The incidence and mortality of thyroid cancer were calculated.The rates were standardized by the demographic composition developed in the Fifth Nationwide Census in the year 2000.The temporal trend in the incidence and mortality of thyroid cancer was assessed using average annual percent change.Results:A total of 413 cases of thyroid cancer were diagnosed from 2004 to 2011,accounting for 3.96％ of the total patients with malignant diseases.During 2004 to 2011,the crude incidence rates ranged from 7.49/105 to 34.86/105,and the standardized incidence rates ranged from 6.02/105 to 23.63/105,displaying a significant increasing trend.The incidence rate in females was significantly higher than that of males.The incidence rate of females peaked at 40-55 years of age.A total of 24 cases died of thyroid cancer during this period.During 2004 to 2011,the crude mortality rates ranged from 0.63/105 to 1.61/105,and the standardized mortality rates ranged from 0.13/105 to 0.46/105.The mortality rate remained stable during the eight year period.Conclusions:There were significant increases of thyroid cancer occurrence from 2004 to 2011 among permanent residents in Luwan district of Shanghai.The mortality rate of thyroid cancer is low.Both the incidence and mortality rates of females were significantly higher than those of males.It is important to identify risk factors of thyroid cancer,so effective control measures can be taken to control its rapid increase.

Diabetic foot ulcer (DFU) is one of the serious complications of diabetes.With high disability,high amputation rate,serious harm to the physical and mental health of diabetes patients.Traditional Chinese medicine drugs for external use has a certain effect and advantages for treatment of DFU.In this paper analyzes the clinical characteristics of DFU and the status of external drug application,and the necessity of research and development of traditional Chinese medicine for DFU treatment.In the article pointed out the difficulties and of the concerns in process of clinical trials for the DFU traditional Chinese medicine research and development.The preliminary recommendations are given in this article.

The external medicine is an indispensable treatment of traditional Chinese medicine (TCM) surgery.The application of Hg is one of the characteristics of TCM surgery medicine for external use.This paper analyzes the present situation of clinical application of Hg and summarizes the common adverse reactions in the literature.The focus of the research on the development of new drugs containing Hg in traditional Chinese medicine is discussed.

ObjectiveTo evaluate the functional changes of stunned myocardium before and after coronary artery bypass graft(CABG) treatment,and clear the meaning of revascularization which CABG has brought to patients with diffused vascular changes.MethodsA total of 36 patients with 99％ diffused coronary artery stenosis in left anterior descending branch underwent non-pump CABG treatment in the Department of Cardiothoracic Surgery the First affiliated hospital of Harbin Medical University.Real-time three-dimensional echocardiography (RT3DE) was repeatedly performed 1 week before operation and 10 days,1 month,and 3 months after CABG.Regional diastolic volumes,systolic volumes,ejection fractions,regional stroke volume to global diastolic volume and the values of abnormal segments before and after CABG were studied.ResultsOne week before operation and 10 days,1 month and 3 months after CABG,the differences of volumes between groups in the last phases of diastole and systolic were statistically significant in anterior wall basement segment,anterior septal basement segment,anterior wall intercalary segment,anterior septal intercalary segment,anterior wall of apex cordis and septation of apex cordis(F =3.51,3.55,4.08,4.05,2.98,3.01,all P ＜ 0.05; F =4.51,4.55,4.08,3.00,2.96,2.99,all P ＜ 0.05).The values of the six segments mentioned above,3 months after operation[(6.74 ± 1.23),(6.64 ± 1.21),(6.02 ± 1.10),(5.95 ± 1.09),(5.82 ± 1.06),(5.10 ± 0.93)ml; (2.74 ± 0.50),(2.69 ± 0.49),(2.51 ± 0.46),(2.32 ± 0.42),(2.36 ± 0.43),(2.03 ± 0.37)ml] were compared with those of 1 week before operation[(8.33 ± 1.52),(8.20 ± 1.50),(7.43 ± 1.36),(7.36 ± 1.34),(7.19 ± 1.31),(6.29 ± 1.15)ml; (4.94 ± 0.90),(4.85 ± 0.88),(4.53 ± 0.83),(4.18 ± 0.76),(4.25 ± 0.78 ),(3.65 ± 0.67)ml],the differences were statistically significant (all P ＜ 0.05); the differences between groups in regional ejection fractions,regional-global ejection fractions were statistically significant(F =4.56,4.88,4.28,3.15,2.93,2.88,P ＜ 0.01 or ＜ 0.05; F =5.56,5.28,4.98,5.15,3.03,2.78,P ＜ 0.01 or ＜ 0.05).Compared with 1 week before the operation, 1 month after the operation in regional ejection fractions,10 days,1 month in regionalglobal ejection fractions after the operation,4 segments of them were significantly improved(all P ＜ 0.05) and 3 months after operation,all the 6 segments had been improved significantly(all P ＜ 0.05).The maximum volume of the sum of group difference of the 6 segments and the 4 segments in the last phase of diastole was statistically significant(F =2.58,5.81,P ＜ 0.05 or ＜ 0.01 ),and the summation began to decrease 10 days after the operation.The values of 3 months after operation[ (36.27 ± 1.10),(25.35 ± 1.16)ml] were compared with that of 1 week before operation[ (44.80 ± 1.36),(31.32 ± 1.43)ml ] the difference was statistically significant (all P＜ 0.05).The maximum volume summafion comparisons of 6 segments and 4 segments in the last phase of systolic had statistical significance(F =5.77,5.57,all P ＜ 0.01 ),and 10 days after the operation,the summation began to decrease.The values of 1 month[(16.4 0 ± 0.48),(11.58 ±0.51 )ml],and 3 months after operation[ (14.65 ± 0.45),(10.26 ± 0.46)ml],were compared with those of 1 week before operation[ (26.40 ± 0.80),(18.50 ± 0.84)ml],the differences were statistically significant (all P ＜ 0.05).ConclusionsStunned myocardium can be improved through CABG in myocardium systolic,diastole function and ejection fractions of the relevant segments and all of this have proved that patients undergoing CABG revascularization can improve the heart function of the ischemic area.

Objective To explore the conception,mechanism,clinical manifestations,diagnosis,treatment and prognosis of ectopic pituitary adenoma. Methods The clinical data of 3 patients with ectopic pituitary adenoma, admitted to our hospital from October 2010 to March 2011, were retrospectively analyzed and discussed by reviewing the relevant literature. Results Clinical manifestations ofectopic pituitary adenoma were as follows:2 had headache,1 had sexual dysfunction and blurred vision, and 1 had acromegalia combined with psychiatric symptom. Endocrinological examination showed that 1 had obviously increased growth hormone (GH) and 1 increased prolactin (PRL).MRI scan indicated that 2 were located in sphenoid sinus and I was located in the sphenoid sinus and clivus.Contrast-enhanced MRI showed enhanced lesions.Total removal was achieved in 2 patients through the trans-sphenoidal approach; partial removal was achieved in the patient with sphenoid sinus and clivus.Pathology examination demonstrated as pituitary adenomas. Conclusion The patients with ectopic pituitary adenoma have neurological dysfunction or/and endocrinological dysfunction; CT and MRI play valuable role in their diagnosis; radical resection of tumor can achieve satisfactory clinical outcomes.