Objective To study the cause of different prognosis in typical medullary carcinoma and atypical medullary carcinoma. Methods The immunohistochemical staining method was used to evaluate the positivity of E cadherin,? catenin, in 30 cases of atypical medullary carcinoma and 18 cases of typical medullary carcinoma and 10 cases of normal breast. Results The positive rate and staining intensity of E cadherin and ? catenin oncoprotein were significantly higher in typical medullary carcinoma than in atypical medullary carcinoma( P

BACKGROUND: Conventional opinions believe tissues of central nervous system(CNS) cannot regenerate after injury when they have been developed and maturated. However, recent researches have validated that neural stem cells exist in human and adult animal nervous system, and most of them are in static status in vivo. The therapeutic effects of neural stem cells in cerebral infarct have been a key point in the researches.OBJECTIVE: To observe the reactive process of endogenous neural stem cells after cerebral infarct to explore the effects of endogenous neural stem cell in CNS traumatic rehabilitation, which provides theoretical gist for the self-restoration after cerebral infarct.DESIGN: A randomized controlled trial by using experimental animals as subjects.SETTING: Department of Neurosurgery of Peking Union Hospital.MATERIALS: The study was conducted in the Laboratory of Neurosurgery Department of Peking Union Hospital from March to October in 2003. Totally 82 healthy male Wistar rats with a body mass between 250 g and 300 g were selected.METHODS: Cerebral infarct model was established in rats by thread-ligation method. Rats were divided into post-infarct 1 day, 3 days, 7 days, 14 days and 28 days groups with 14 rats each. Control group was sham-operation group( n= 12). The expressions of bromodeoxyuridine (BrdU) and Nestin in the brain of the rats were dynamically detected by immunohistochemical method.MAIN OUTCOME MEASURES: The changes of BrdU and Nestin positive cell numbers after cerebral infarct in rats.RESULTS: Only very few BrdU and Nestin positive cells had survived in hippocampal dentate gyrus and subventricular zone(SVZ) area in control group. BrdU positive cell significantly increased compared with control group in hippocampus and SVZ area after 1 day of cerebral infarct( P ＜ 0.05),which reached its peak on the 7th day( P ＜ 0.05), started to reduce after 14 days but still in the level significantly higher than normal( P ＜ 0.05), and closed to normal level after 28 days. And moreover, BrdU and Nestin positive cells were significantly more in infarct side than the opposite side ( P＜ 0.05), which migrated towards the opposite side through callus.CONCLUSION: Cerebral infarct can activate the proliferation in situ and migration of endogenous neural stem cell.

Objective To establish a method for detection folylpolyglutamate syntbetase (FPGS),explore the change of FPGS in the drug-resistant A549 cells induced by methotrexate(MTX) enantiomer,and provide new tools to further investigate drug resistant mechanism. Methods A549 cell lines induced by L-( + )-MTX and D-( - )-MTX (25 μmol/L) were chosen to raise three cell lines as compared with MTX-sensitive cell line. Then FPGS were extracted for the CEIA-LIF and western blot was performed. After validation, FPGS antibodies were labeled by fluoreacein isothiocyanate (FITC) and produced a immune response with former-extracted FPGS. CELA-LIF can separate and detect labeled proteins according ruination time of the protein with different size and detect FPGS in drug resistant cell lines induced with L-(+)-MTX and D-(- )-MTX. The accuracy was evaluated as compared with western blot assay. Results The separation time of CEIA-LIF for labeled FPGS antibody and the immune complexes were7. 1 min and 8.9 min, and the resolving power was 4. 5. The process of protein separation and detection can be accomplished in less than 10 minutes. Western blot analysis showed there was no non-specific bands appears in the extract of these three cell lines after the freeze-thaw in liquid nitrogen. The minimum detection level in sensitive cell strains was 0. 68 mg/μl. The consent of FPGS in L-(+)-MTX and D-( - )-MTX induced cells were 46. 59% and 48. 36% compared with drug sensitive cell strains with CELA-LIF. Conclusions CELA-LIF was established in this experiment. It is efficient and sensitive for detecting of FPGS, which is similar to western blot method. The level of FPGS in L-( + )-MTX and D-( - )-MTX induced drug resistant cell lines is significantly lower, indicating the expression of FPGS is damaged.

Objective Analyzing the construction process and application of health appropriate technology database in Zhejiang province and proposing related considerations and recommendations for the database construction.Methods To design and construct the technology database system,and using excel software to calculate statistic data.Results Established a health appropriate technology database,which contains 826 technologies that can be selected and promoted by the demonstration bases in the whole province.Conclusions The establishment of the technology database increased the efficiency of health appropriate technology transformation at the provincial level,and also provided a reference for the national-wide generalizing of health appropriate technology.

Objective To investigate the correlation between the uptake of 68Ga-DOTATATE in pituitary adenoma and clinical parameters such as hormonal hypersecretion,and to evaluate the curative effect with 68Ga-DOTATATE imaging after octreotide therapy in patients with growth hormone-secreting adenoma (GH adenoma).Methods A total of 34 patients (15 males,19 females) with pituitary adenoma were recruited,including 5 adrenocorticotropic hormone-secreting adenoma (ACTH adenoma),17 GH adenoma,and 12 non-functioning adenoma (NF adenoma).In the 17 patients with GH adenoma,there were 13 patients treated by octreotide intramuscular injection 3 times with a total dose of 60 mg for 3 months.The finial diagnosis was based on histology.68Ga-DOTATATE imaging was performed,and SUV tumor volume and density index (DI) were recorded in all patients.The DI was the ratio of tumor SUVmean to tumor volume.The effective therapy was defined as more than 50％ of hormonal suppression or more than 20％ of tumor shrinkage.Non-parametric Mann-Whitney u test was used.Results NF adenoma showed greater tumor volume than secretory adenoma,((9.10±7.00) cm3 vs (2.92±1.60) cm3,u=43.0,P＜0.05),whereas DI of secretory adenoma was higher than that of NF adenoma (7.16±4.52 vs 1.08±1.40,u=48.5,P＜0.05).Additionally,DI was significantly higher(3.55±0.91 vs 1.38±0.69,u =2.0,P＜0.05) in patients (n =8) with effective treatment than that in patients without effective treatment (n =5).Conclusion 68 Ga-DOTATATE may be a useful probe for PET imaging in patients with pituitary adenoma,and may be valuable for predicting the therapeutic effect of somatostatin analog treatment.

Objective To assess the diagnostic value of 99Tcm-ECD SPECT for hyperacute cerebral ischemia using rats models.Methods A stable and permanent acute cerebral ischemia model using unilateral middle cerebral occlusion was tested in 24 healthy SD rats.The rats were randomly divided into 6 groups according to the time duration between imaging and induced-ischemia (1,2,3,4,5 and 6 h,respectively).The rats were sacrificed immediately after 99Tcm-ECD SPECT/CT imaging and then the brain tissue was dissected for triphenyl tetrazolium chloride (TTC) and HE staining.The count ratio of affected cortex to the contralateral cortex of ＜ 50％ was defined as ischemia on micro SPECT/CT.The volume of the ischemic area was calculated on both SPECT/CT and TTC images.Paired t test was used to determine the statistical difference between the volumes on SPECT/CT and TTC staining.Results The ischemia volume evaluated by TTC staining at 1,2,3,4,5 and 6 h after occlusion was (73.98 ± 27.76),(90.75 ±29.00),(135.00±40.83),(136.25±22.51),(158.50±32.72) and (168.00±32.75) mm3,respectively.The corresponding ischemia volume evaluated by micro SPECT/CT was (98.50 ± 27.77),(110.40±26.80),(157.00±36.82),(165.50±26.54),(175.75±31.16) and (177.25 ±34.33) mm3,respectively,which was concordant with that by TTC staining at each time point (t:-1.681 to-0.390,all P ＞0.05).The ischemic area on micro SPECT/CT imaging was consistent with the pink area by TTC staining.The volume evaluated by micro SPECT/CT tended to be constant 3 h after the occlusion.The ischemia volume showed no significant difference among 3,4,5 and 6 h (all P ＞ 0.05).Conclusions Micro SPECT/CT may have an haemodynamic value for evaluating in vivo cerebral ischemia applied in a rat model.It might have clinical value for the evaluation and decision-making of ultra acute cerebral infarctions.

Objective To grasp the general situation of patent application and authorization of 77 medical and health institutions in Zhejaing,to provide reference and basis for promoting the patent application and conversion.Methods Patent data were searched through Bai Teng net patent database,and SPSS 19.0 was used for statistical analysis.Results The total number of patent application showed a trend of generally rise.There were 1430 valid invention patents in total,among which 264 were invention patents and 1166 utility model patents.The total number of patens as well as invention patents were positive correlated to province GDP GDP and doctors per thousand population (r=0.824,0.812,0.784,0.771 respectively,P＜0.001).The rate of collaborative patent application was 6.28％,and there was a significant difference (α=0.05/3,P＜0.001) in the collaborative patent applications around Hangzhou,provincial and other cities medical and health institutions.Conclusions The total number of patents in 77 medical and health institutions in Zhejaing has reached a certain scale,and the number of patents increase with the economic development and the number of doctors per thousand population.The effective patents present in concentrating in regions,and the proportion of invention patents was low.

Objective:To report the clinical characteristics, diagnosis, and treatment of 2 cases of X-linked acrogigantism(X-LAG).Methods:The clinical information of two patients were retrospectively reported, and peripheral blood DNA was collected for copy number variations detection.Results:Both patients had onset at age of two, with common clinical characteristics including linear growth acceleration, mild facial coarsening, enlargement of hands and feet, increased appetite, and snoring, etc. The heights Z scores of the two patients before treatment were + 6.86 and + 6.53, respectively. Growth hormone(GH) glucose inhibition test showed that GH nadir values were over 1 ng/mL and insulin-like growth factor-Ⅰ(IGF-Ⅰ) were 586.0 ng/mL and 1 042.0 ng/mL, respectively. Patient 1 received three cycles of octreotide microspheres therapy followed by surgery, and achieved clinical and biochemical remission. Patient 2 had lanreotide for 5.5 years but failed biochemical remission. Microduplication of Xq26.3, which contained pathogenic gene G-protein coupled receptor 101(GPR101), was found in germline DNA of two patients through copy number variation detection, leading to the diagnosis of X-LAG.Conclusion:It should be cautious of X-LAG when children below 2 years old presents symptoms such as overgrowth and so on. Medication combined with surgery is effective.

Objective:Cushing′s disease(CD) is caused by the pituitary adrenocorticotroph hormone(ACTH) secreting adenomas, leading to increased serum cortisol levels and various abnormal metabolic processes. Untreated CD is linked to high mortality, thus it is critical to elucidate its pathogenesis. This study aims to explore the pathogenesis of pituitary ACTH adenomas using whole-genome sequencing analysis.Methods:Fresh tumor tissues and peripheral blood samples were collected in 9 confirmed cases of pituitary ACTH adenomas who underwent surgery. Whole genome sequencing was then performed, followed by analysis and verification of single nucleotide mutations, copy number variation(CNV) and chromosome structure variations.Results:Somatic USP8 mutations(p.Ser718del, p. Ser718Pro, p. Pro720Arg, p. Pro720Gln) were found in 5 patients, with a rate of 55.6%; CNV of USP8 was detected in 1 patient; TP53(p.Cys135Tyr), NF1(p.Val1049Glufs*11) and KMT2C(c.3323+ 1G>A) mutations were identified in 1 patient harboring wild-type USP8. CNV analysis showed a loss of heterozygosity in multiple chromosomes in a wild-type USP8 patient. Structural variations were found in 2 with unknown significance. No germline gene mutations were detected in this study.Conclusion:Somatic USP8 mutations, increased copy number of USP8, variations of tumor-related genes such as TP53 and extensive somatic CNV all contribute to pathogenesis of CD. Chromosomal structure variations may suggest high-risk pituitary ACTH adenomas, and call for frequent follow-up and aggressive treatment.

Disorders of sex development (DSD) are a group of rare complex clinical syndromes with multiple etiologies. Distinguishing the various causes of DSD is quite difficult in clinical practice, even for senior general physicians because of the similar and atypical clinical manifestations of these conditions. In addition, DSD are difficult to diagnose because most primary doctors receive insufficient training for DSD. Delayed diagnoses and misdiagnoses are common for patients with DSD and lead to poor treatment and prognoses. On the basis of the principles and algorithms of dynamic uncertain causality graph (DUCG), a diagnosis model for DSD was jointly constructed by experts on DSD and engineers of artificial intelligence. "Chaining" inference algorithm and weighted logic operation mechanism were applied to guarantee the accuracy and efficiency of diagnostic reasoning under incomplete situations and uncertain information. Verification was performed using 153 selected clinical cases involving nine common DSD-related diseases and three causes other than DSD as the differential diagnosis. The model had an accuracy of 94.1%, which was significantly higher than that of interns and third-year residents. In conclusion, the DUCG model has broad application prospects as a computer-aided diagnostic tool for DSD-related diseases.