Volume 90  ·   Issue 08  ·  2010

The incidence rate of breast cancer has been the highest among female malignant tumors. Data published by the World Health Organization (WHO) in 2004~ ([1]) showed that there were 1.1 million new cases worldwide every year, with the highest incidence rate in North America and Europe. In 2009, there were 254,000 new cases in the United States and 326,000 new cases in Europe.

Medical laboratory produces data, and the accuracy of the data directly affects the medical level and the vital interests of patients. The first element of medical laboratory management is the quality of inspection reports, and quality is the eternal theme of discipline construction.

Objective To investigate the efficacy and safety of goserelin pins anastrozole in advanced premenopausal breast cancer patients. Methods We summarized a single-centre experience with goserelin plus anastrozole in 32 premenopausal women with metastatic breast cancer (MBC). All patients received goserelin 3.6 mg by subcutaneous injection every 4 weeks concurrently with anastrozole 1 mg daily.The median duration of treatment was 12 months. Results No patient achieved complete remission (CR)(0%), 6 partial remissions (PR) (18.8%), 21 stable diseases (SD) (65.6%) and 5 progressive diseases (PD) ( 15. 6% ). Objective response rate (ORR) was achieved in 18. 8% and clinical benefit ( CR + PR + SD>6 months) in 68.8%. The median progression-free survival (PFS) was 12 ( 2 - 57 )months. One-year overall survival rate (OS) was 87.4% and two-year OS 66. 9%. The OS of patients without visceral metastasis was significantly longer than that of patients with visceral metastasis (P = 0. 04).Hot flushes and nausea were predominant toxicities. ConclusionThe combination of goserelin and anastrozole appears to be an efficient and well-tolerated regimen in premenopausal MBC women.

Objective To explore the breast fiber endoscopy for the diagnosis of nipple discharge.Methods FV-2OOOE Japanese ultra-fine fiber-optic duct endoscopy system was employed in 3267 cases of patients with nipple discharge. And the findings were correlated with pathological examinations. Results There were normal lumen (n =499) (15.27%), duct dilation with chronic inflammation (n = 1750)(53. 57% ) and intraductal lesions ( n = 1018 ) (31.16% ). Conclusion Breast fiber endoscopy is a safe and effective method of examination in patients with nipple discharge. It should be used as the preferred method of etiological diagnosis.

Objective To investigate the expression of proto-oneogene Wip1 in breast cancer tissue and its clinical significance. Methods Through the uses of semi-RT-PCR, immunohistochemieal technique and Western blot, the specimens from 70 patients of breast cancer and 20 normal controls were detected for Wip1 mRNA and protein expression. At the same time, the authors analyzed the relations between the expression of Wip1 in human breast cancer and different clinical pathologic parameters. Results RT-PCR:The values of gene expression of Wip1 mRNA in breast cancer tissue, perieaneerous tissue and normal breast tissue were 0. 715±0. 087, 0. 175± 0. 021 and 0. 154±0. 022 respectively. Thus the value of gene expression in breast cancer tissue was significantly higher than that in perieaneerous tissue or normal breast tissue (P<0. 01 ). Immunohistochemistry:The high expression rates of Wip1 protein in breast cancer tissue, perieancerous tissue and normal breast tissue were 62. 9% (44/70), 2. 9% (2/70) and 0(0/20)respectively and there was a significant difference among these three different tissues ( P<0. 01 ). Western blot:The relative contents of Wip1 protein in breast cancer tissue, perieaneerous tissue and normal breast tissue were 0. 688±0. 151, 0. 251±0. 043 and 0. 234±0. 044 respectively. The relative content of Wip1 protein in breast cancer tissue was significantly higher than that in pericaneerous tissue or normal breast tissue (P <0. 01 ). The high expression of Wip1 protein was negatively correlated with the expression of p53, but it had nothing to do with tumor size, age, tumor staging, axillary lymph node metastasis and expressions of ER and PR. Conclusion The high expression of Wip1 mRNA and its protein in breast cancer tissue may promote the growth of breast cancer. Wip1 may become a new target for therapy of breast cancer.

Objective To explore the association between polymorphism of dopamine 1 transporter variable number tandem repeat ( DAT1 VNTR) and breast cancer with abnormal Hilit in Chinese Han population from Xinjiang. Methods The breast caner patients were divided into four body fluids according to Uighur medicine theory. And polymerase chain reaction and VNTR polymorphism technique were employed to detect genotypie and allelie frequencies of a 40 bp VNTR polymorphism situated in 3'untranslated region of DAT1 gene in 144 breast cancer patients with abnormal Hilit and 104 normal control subjects in Han population of Xinjiang province. Results In our sample, the repeat numbers of 40 bp were 7 and 9-11 (PCR product length of 360 bp and 440 bp to 520 bp) and 10-repeat allele (480 bp) detected was the dominant allele of DAT1 gene polymorphisms with an allelic frequency of 90. 9% ; Seven kinds of genotype were detected and genotype 10/10 was the most common genotype with a genotypic frequency of 83. 1%. The frequency of 10-repeats allele and 10/10 genotype was significantly higher in breast caner patients with abnormal balgham Hilit than in controls (OR =0. 127, 95% CI 0.016 -0.988, P =0.026;OR=0. 134, 95% CI 0.018 -1.016, P =0.020) and breast caner patients with abnormal Sapra Hilit (OR =0. 132, 95% CI 0.016 - 1.075, P =0.049; OR =0. 132, 95% CI 0.017 - 1.042, P =0.033).Conclusion The 10-repeats allele and 10/10 genotype of 40 bp VNTR polymorphism of DAT1 may increase the risk of breast cancer with Uighur medicine abnormal Hilit in Chinese Han population from Xinjiang province and it is not correlated with the susceptibihty to breast cancer with Uighur medicine abnormal Sapra Hilit.

Objective To investigate the correlation between change of tumor size after 2 cycles of neoadjuvant chemotherapy and pathological evaluation after 4 cycles of neoadjuvant chemotherapy. And to evaluate the feasibility of predicting pathological evaluation by ultrasonic evaluation in the initial stage of neoadjuvant chemotherapy for primary breast cancer. MethodsRetrospective analysis was performed in women with primary breast cancer,including 138 patients receiving 4 cycles of anthracycline-based neuadjuvant chemotherapy (CTX500 mg/m~2, D1, D8 Q28D; THP35 mg/m~2, D1, D8 Q28D; 5-Fu200 mg/m~2/day, ci D1-D28), and 84 patients receiving 4 cycles of taxane-based neoadjuvant chemotherapy (PTX60-80mg/m~2, D1, D8, D15 Q21D). The ROC (receiver operating characteristic) curve was employed to evaluate whether the product change of 2 largest perpendicular diameters of tumor as observed by ultrasonography after 2 cycles of neoadjuvant chemotherapy could exactly predict the pathologic evaluation by the Miller & Payne grading system criteria after 4 cycles of neoadjuvant chemotherapy. Results When no response, excellent response or pathologic complete remission to neoadjuvant chemotherapy were predicted by ultrasonic evaluation. And the areas under the curve ROC were 0. 689, 0. 655 and 0. 647 respectively (all P values <0. 05). It was predicted as no response by using the traditional standard of ultrasonic evaluation of <50% or excellent response at ≥ 50% ( kappa<0. 40 ). ConclusionPathological evaluation after 4 cycles of anthracycline- or taxane-basecl primary chemotherapy in breast cancer can't be predicted reliably only by the product change of 2 largest perpendicular diameters of tumor as observed by ultrasound after 2 cycles of neoadjuvant chemotherapy.

Objective To study the difference in prevalence of major risk factors of coronary heart disease (CHD) in resident from Beijing communities in different age groups so as to offer suggestions for prevention of CHD in Beijing. Methods The samples were selected by random cluster multistage method.Serum lipid level and CHD factors were determined through questionnaire, physical examination and biochemical detection for 10 054 subjects in Beijing communities during June 2007 to August 2007.According to age, the subjects were divided into 3 groups:20 -44 yr group, 45 -59 yr group and ≥60 yr group, Results After age and sex standardization the prevalence of hypercholesterolemia, hypertension,diabetes, smoking and obesity was 9. 30%, 41.57%, 10. 18%, 35.81% and 22. 89% respectively. The prevalence of hypercholesterolemia, hypertension and diabetes showed an rising trend with advancing age (trend χ~2:15.6, 31.7 and 18.0, all P <0.001). The group of 45-59 yr had the highest prevalence in smoking and obesity 28% and 25.27% respectively. Over 30% in the groups of 45-59 yr and ≥60 yr were in the borderline of hypercholesterolemia and hypertension and over 40% were overweight. After age and sex standardization, 67. 15% of community residents had at least 1 CHD risk factor, 21.37% and 8. 50% 2 or over 3 CHD risk factors. As compared with group 20 -44 yr, the odds ratio (95%CI) for clustering of CHD risk factors in groups 45 - 59 yr and ≥60 yr were 2.63 (95 % CI 2. 371 - 2. 924) and 4. 3 (95 % CI 3. 764 -4. 913) respectively. The odds ratio (95% CI) for clustering of CHD risk factors for male vs female was 4.392(95% CI 3.938-4.899).Conclusion The prevalence of CHD major risk factors of Beijing community residents is high.Groups of 45-59 yr and ≥60 yr have a higher prevalence and clustering of CHD major risk factors than 20-44 yr group.So these age groups deserve a higher priority of comprehensive prevention and control strategies of CHD.

Objective To evaluate the clinical value of flexible endoscopic realignment for posterior urethral disruption as compared with traditional open realignment. Methods A total of 58 patients suffering posterior urethral disruption in Beijing Jishuitan Hospital from January 2003 to May 2009 were examined.Twenty-three patients( Group A) were performed with flexible endoscopic realignment and 35 patients( Group B) were performed with traditional open realignment. The operation duration and post-operative complications were compared between two groups. Results All operations were successfully performed .The operative duration was significantly shorter in Group A than that in Group B[(29±10)min vs(58 ±11 )min, P =0. 000]. Also, the patients in Group A had a significantly decreased rate of stricture and false urethral passages formation ( 17.4% vs 42. 9%, 0 vs 20%, both P<0. 05 ). There were no significant difference in urinary infection , repeat procedures, incontinence and impotence between two groups ( P >0. 05 ). Conclusion As compared with traditional open realignment, flexible endoscopic realignment has the advantages of short operation duration, lesser trauma and fewer comphcations. Therefore it is an excellent method for the treatment of urethral injury.

Objective To investigate the clinical manifestations and to characterize mutations of the GLA gene in Chinese patients with Fabry disease so to enhance the diagnosis of Fabry disease. Methods Sixteen Chinese affected males (from 16 unrelated families) with the classic phenotype of Fabry disease were investigated. The patients were diagnosed by a deficiency of α-galactesidase A(α-Gal A) activity. All seven exons and the neighboring intronic sequences of GLA gene were analyzed by PCR amplification and automated sequencing. ResultsA total of 14 mutations were identified including 12 single-base substitutions( 11 missense and 1 nonsense mutations) ,1 small deletion and 1 splicing mutation. Eight novel mutations( c. 119 C>A, c. 275 A>T, c. 520T>C, c. 547G>C, c. 647A>G, c. 929T>G, c. 1045T>A,IVS1-1G>A)were identified. The novel mutations were not tested by RFLP on 100 GLA alleles in Chinese population, and were highly conservative in mammalian species. ConclusionFabry disease is often misdiagnosed in China. There is no hot spot for mutations in Chinese patients. GLA gene mutation analysis is a reliable method to diagnosis for Fabry disease.

Objective To extensively evaluate the method of simultaneous determination of intra gastric pressure (IGP) in liquid load test (LLT) in healthy subjects (HS) and patients with functional dyspepsia (FD). Methods Forty HS and 67 FD patients ( Rome Ⅲ criteria) were recruited. All subjects were surveyed with regards to demographic characteristics,features of FD symptom spectrum and psychological status (Zung anxiety and depression scale). And the test of simultaneous determination of IGP in LLT was conducted. Finally all the data were collected and analyzed. Results HS group:no statistical difference was found in IGP divided by gender, age and body mass index (P >0.05). The coefficient of variation of IGP at 15.3% was less than that of maximal intake volume (MIV). Twice repeated studies showed quite similar results and the linear interclass correlation coefficient of IGP was 0. 806 (P = 0. 002).As to the range of normal value from HS, the proportion of gastric hypersensitivity accounted for 35.0% and impaired aceommodatian for 25.0%. FD group:no statistical difference was found in IGP and MIV divided by gender, age and FD symptom subtype (P >0. 05). FD patients with abnormal psychological status had a lower IGP (4. 2±1.2 mm Hg vs 4. 8±1.1 mm Hg, P =0. 042) and MIV (450±138 ml vs 526±121 ml,P =0. 034 ) than those with normal status. IGP was not related to epigastric pain, epigastric burning,postprandial fullness or early satiation (F = 1. 635, P =0. 190). Early satiation was significantly related to MIV ( F = 4. 682, P = 0. 031 ; correlation coefficient was - 6. 8, P = 0. 033 ). No statistical difference was found in gastric compliance among HS,all FD patients,patients with hypersensitivity or impaired accommodation (P>0. 05). The test had an excellent safety and tolerability. Condusions The method of simultaneous determination of IGP in LLT can differentiate gastric hypersensitivity from impaired aeeommodation. And it has an excellent feasibility, safety and reliability.

Objective To evaluate the efficacy and safety of oral theophylline versus placebo in patients with stable chronic obstructive pulmonary disease (COPD). Methods The databases Medline,Embase, Web of Science, Cochrane Central Register of Controlled Trials and Chinese Biomedical Database were retrieved by using the key words " Uniphyl or Theophylline or Theo-Dur or theo or Theotrim or Elixophylline or Elixophyllin or PhyUocontin or aminophylline or Methylxanthine or nuelin or doxofylline"and "obstructive or bronchitis or pulmonary emphysema or bronchial hyperreactivity or COPD or COLD or emphysema" so as to search the materials about the randomized controlled clinical trials comparing the effectiveness of stable COPD treated by oral theophylline and placebo. A meta-analysis was conducted. For continuous variables, the results of individual studies were pooled using fixed-effect weighted mean difference (WMD) with a corresponding 95% confidence interval (CI). Where the results were expressed as dichotomous variables, the relative risk (RR) with 95% CI was calculated. Results Thirty-four documents about randomized controlled clinical trials, including a total of 2087 patients, from the retrieved 2010 documents accorded to the demand of enrollment. The results of meta-analysis showed that theophylline significantly improved the forced expiratory volume in 1 s, forced vital capacity and peak expiratory flow rate (WMD 0.09 L, 95%CI0. 09 -0.09; WMD0. 14 L, 95% CI0. 13 -0. 14; WMD 17.0 L/min and 95% CI 6. 9-27.2 respectively). Arterial oxygen tension and arterial carbon dioxide tension at rest both improved with treatment (WMD 2. 89 mm Hg, 95% CI 1.11 -4.66; WMD -2.05 mm Hg and 95%CI -3.59 to - 1.42 respectively). Six-minute walk distance significantly improved ( WMD 38. 89 meters, 95% CI 21.55- 56. 22) in treatment group. The RR of acute exacerbations was smaller between both groups ( RR 0. 74,95% CI0. 59-0.93). The RR of total adverse events was similar (RR 1.05, 95% CI 0.95 -1.16) while RR of drug-related adverse events was greater (RR 2. 54, 95% CI 1.37 -4. 70). And there was significant statistical difference. Conclusion Compared with the placebo, theophylline can improve lung function,arterial blood gas tensions and walking distance while the incidence of drug-related adverse events is higher.

Objective To investigate the characteristics of APC gene germline mutation in Chinese patients with familial adenomatous polyposis ( FAP). Methods The genomic DNA was extracted from peripheral venous blood drawn from probands of 14 Chinese FAP families from Beijing, Hebei, Henan,Anhui, Inner Mongolia, Shanxi and Fujian. The APC gene was amplified by PCR and underwent direct sequencing. Large fragment deletion was detected by multiplex ligation-dependent probe amplification (MLPA) only in micromutation-negative samples found by sequencing. Results APC gene micromutations were found in 9 probands and the mieromutation detection rate was 64. 3%, including 6 frameshift mutations, 2 splicing mutations and 1 nonsense mutation. Large fragment deletions of APC gene were detected in 2 probands ( 14. 3% ). The total mutation detection rate of micromutation and large fragment deletion was 78. 6%. Four novel micmromutations and 2 novel large fragment deletions were found, including c. 2336-2337insT, c. 3923-3929delAAGAAAA, c. 532-2A>T, c. 4179-4180GAdelinsT, large fragment deletions of exons 11 and 10A and large fragment deletion of exon 15 start. Conclusions In Chinese FAP patients, the germline mutation type of APC gene is variable; the majority is of frameshift mutation. The most common mutation site is exon 15. The mutation detection rate of APC gene can be boosted effectively by direct sequencing in combination with MLPA.

：Objective To explore thepathogenesis of irritable bowel syndrome (IBS) and the regulation of the networkrelationship between differential proteins. MethodsSixteen female SD rats of clean gradewere randomly divided into IBS group ( n = 8) and control group ( n = 8). A rat model ofIBS was established by a special odor of mothball as a conditional stimulation andeolorectal distension plus the classic conditions of physical restraint as anon-conditional stimulation in turn. The total proteins were extracted from colon mucosaof two different rat groups. After preparation of total proteins, selubilized proteinswere separated by two-dimensional differential gel electrophoresis. Those differentialprotein spots were identified by matrix-assisted laser desorption/ionization time offlight mass spectrometry ( MALDI-TOF MS). The identified proteins were classified throughan online web gene ontology tool. Some of the valuable differently expressed proteins werechosen for further verification by Western blotting. ResultsIntensity changes of 19 spotswere detected among 1396 protein spots. A total of 13 different proteins were identifiedby MALDI-TOF MS successfully ; eight of these were up-regulated and five down-regulated incolon mueosa of IBS rat. The eight over-expressed proteins were cytokeratin 8, proteindisulfide isomerase A3 ( PDIA3 ),peroxiredoxin-6, cathepsin S, heterogeneous nuclearribonueleoprotein F, eukaryotic translation initiation factor, earbonyl reductase 1,glyoxalase I; five under-expressed proteins were alpha-enolase, transgelin,serpinB5,cardiac α-actin1 and 40S ribosomal protein SA. The results of Western blotting confirmed that PDIA3 wasindeed over-expressed in colonic mucosa of IBS rat. ConclusionsSome proteins related toimmunity of intestinal tract, inflammation and nerve are differently expressed in colonicmueosa of IBS rat. It is suggested that immunity, inflammation and neuro-endocrine networkin gut are associated with the pathogenesis of IBS.

Objective To determine the role of extraceilular signal-regulated kinases1/2 ERK1/2) signaling pathway in regulating myocardial inflammation and cardiac function in a rat model of coronary microembolization (CME). Methods The Sprague-Dawley rats were randomly divided into three groups:sham-operated group( n = 15 ), coronary microcmbolization group ( n = 15 ) and PD98059 group ( n = 15 ).CME model was established by injection of 42 μm microspheres 0. 1 ml (3×10~4/ml, 3000 ) into left ventricle while occluding the ascending aorta. At 30 minutes pre-operation, rats of PD98059 group were injected with PD98059 IV, a specific ERK1/2 inhibitor. Western blot and immunochemical analysis were used to determine the activation and distribution of ERK1/2. Echocardiography was employed to evaluate cardiac functions. The hematoxyhn-eosin staining was used to assay myocardial inflammation. Expression of TNF-α and MIF mRNA was determined by RT-PCR analysis and activity of NF-κB assessed by electrophoretic mobility shift assay. ResultsIn comparison with sham-operated group, CME increased phosphorylatian of ERK1/2 (0. 92±0. 10 vs 0. 61±0. 04), local myocardial inflammatory cells(455±16 vs47± 7), expression of TNF-α mRNA (0. 94± 0. 04 vs 0. 60 ± 0. 09 ) and MIF mRNA ( 1.30 ± 0. 44 vs0. 63 ± 0. 25 ) and activity of NF-κB ( 541 ± 25 vs 311 ± 65 ) in myocardium ( all P<0. 05 ). All of these dramatically induced cardiac dysfunction[LVEF (73 ± 3 ) % vs (83 ± 4) %, P<0. 05]. To compare with CME group, treatment of specific ERK1/2 inhibitor PD98059 blocked the activation of ERK1/2 (0. 48 ±0. 11 vs 0.92 ±0. 10, P <0.05), decreased inflammatory cells (401 ± 12 vs 455 ± 16, P<0.05),decreased expression of TNF-α mRNA ( 0. 42 ± 0. 06 vs 0. 94 ± 0. 04, P<0. 05 ) and suppressed activity of NF-κB (105 ± 14 vs 541 ± 25, P<0. 05 ). Most importantly, PD98059 treatment ameliorated cardiac functions dramatically[LVEF (76±4)% vs (73 ± 3)%, P <0. 05]. However there was no significant change in the expression of MIF mRNA ( 1.17 ± 0. 37 vs 1.30 ± 0. 44, P>0. 05 ). Conclusion The present study demonstrates a novel role of ERK1/2 signaling pathway in promoting myocardial inflammation in CME. And ERK1/2 may be a novel drug target for CME therapy.

Breast carcinoma in situ has always been a hot spot in the field of tumor pathology. Although there have been many research reports on breast carcinoma in situ, some new advances in recent years are worthy of attention, such as molecular subtypes, cytogenetics, progression pathways, clinical diagnosis and treatment of intraductal breast carcinoma (DCIS); Study on Clonality, Chromosome Changes and Variant Types of Breast Lobular Carcinoma in Situ (LCIS); And the research on the relationship between DCIS and LCIS, etc. are summarized here as follows.

Case 1: A 69-year-old female was admitted to the hospital due to laryngeal pain for 2 days and aggravated for half a day.The laryngeal pain was severe at the time of admission, and there was no feeling of holding.She had a history of diabetes for 10 years, self-administered hypoglycemic drugs, and her blood sugar control was not satisfactory (details unknown); Hepatitis history and contact history were denied.

A 30-year-old female was admitted to the hospital in October 2005 due to recurrent right lumbar pain aggravated for 1 1/2 years and 1 month. The physical examination showed that the vital signs were stable, but there were no obvious positive signs. B-ultrasound showed very hypoechoic mass in the right upper kidney, about 5.6 cm ×4.7 cm in size, and hypoechoic mass in the extrarenal kidney, about 6.1 cm ×4.9 cm in size.

A 38-year-old male was diagnosed with non-Hodgkin's lymphoma (NHL, diffuse large-cell type, mute type of B-cell lymphoma rich in T cells) after consultation between Professor Gao Zifen of the Department of Pathology of Peking University and Professor John Chen of Hong Kong.

A 26-year-old male was admitted to the hospital in January 2009 due to palpitations for 1 year and pale complexion for 5 months. The patient developed palpitations without obvious trigger 1 year ago, occasionally precordial pain and asthma after activity. Five months ago, the patient developed pale complexion, accompanied by dizziness and fatigue.