Volume 87  ·   Issue 02  ·  2007

For a recurrent and metastatic advanced breast cancer patient, it is very difficult to achieve the radical cure effect. Even if the lesion resection or radiotherapy resolves, it cannot inhibit the subclinical lesion that has spread out; Even if complete remission (CR) is achieved through systemic drug therapy, it is likely that the tumor will progress again once the drug is stopped. This is a difficult problem that every breast cancer professional doctor will often encounter.

Objective to observe the clinical efficacy of subcutaneous mastectomy with preserving nipple and areola and immediate prosthetic breast reconstruction with axillary lymph node dissection in early breast cancer. Methods 20 patients with early breast cancer (TNM stage: 6 cases in stage Ⅰ and 14 cases in stage Ⅱ) underwent subcutaneous mastectomy with preserving nipple and areola, and immediate prosthetic breast reconstruction with axillary lymph node dissection. After operation, they were treated with CMF (cyclophosphamide, methotrexate, 5-fluorouracil) regimen or FEC (5-fluorouracil, epirubicin, cyclophosphamide) regimen, chemotherapy, radiotherapy and endocrine therapy. Results The average follow-up period was 52.3 months, of which 18 patients were followed up for more than 36 months. All patients survived without local or regional tumor recurrence. One patient had multiple liver and bone metastases 9 months after operation, and now survived for 5 years with tumor. Conclusion Subcutaneous mastectomy with preserving nipple and areola, Axillary lymph node dissection and immediate prosthetic breast reconstruction did not increase the risk of postoperative complications, local or regional tumor recurrence and distant metastasis, and did not affect the comprehensive treatment and long-term survival of postoperative chemotherapy, radiotherapy and endocrine therapy. This procedure could obtain satisfactory cosmetic effect and further improve the quality of life of patients.

Objective to investigate the feasibility of breast-conserving surgery as a local treatment for breast cancer with nipple discharge. Methods the clinical data of 7 cases of breast cancer with nipple discharge were retrospectively summarized by central quadrant resection + latissimus dorsi muscle flap metastasis with or without axillary lymph node dissection. Results All 7 cases were successful in surgery, none had flap necrosis, and the breast appearance was satisfactory. The average follow-up was 7 months, and no local recurrence and distant metastasis were observed. Conclusion It is safe and feasible to use central quadrant resection + latissimus dorsi muscle flap metastasis with or without axillary lymph node dissection as a local treatment for breast cancer with nipple discharge.

Objective to identify long spleen tyrosine kinase [Syk (L)] as a target gene for down-regulation of transcription suppressor in breast cancer, and to explore the suppressive mechanism of Syk (L) in breast carcinoma. Methods Adeno-XTM expression system of CLONTECH was used to construct adenovirus vector of Syk, infected breast cancer cell line MB231 that did not express Syk, and adenovirus LacZ was used as control to screen the expression of Syk (L), Syk (S) regulated genes ID1, Cyclin D1, Fra1 and B-myb by cDNA microarray method. The results of cDNA microarray were verified by Northern hybridization. Results In breast cancer cells, the transcription suppressor Syk (L) can down-regulate the expression of oncogenes ID1, Cyclin D1, Fra1 and B-myb, and Northrn hybridization confirmed the regulation of Syk (L). Conclusion The tumor suppressor Syk (L) can inhibit the development of breast cancer by specifically down-regulating the expression of oncogenes Cyclin D1, ID1, B-myb and Fra1.

Objective to observe the invasive effect of LKB1 gene on breast cancer cells and its mechanism. Methods MDA-MB-435 breast cancer cells transfected with LKB1 gene were screened, one high expression cell line and one low expression cell line were randomly sampled, and compared with those of untransfected and empty plasmid transfected cells. The expressions of matrix metalloproteinase (MMP) -2, MMP-9, VEGF and bFGF were observed by reverse transcription polymerase chain reaction (RT-PCR) and gelatin-zymography, and their proteins were quantitatively analyzed by Western blot. The membrane penetration ability of LKB1 gene transfected breast cancer cells was detected by Tramswell assay. Results The relative absorbance (A) values of MMP-2, MMP-9, VEGF and bFGF gene expression in LKB1 gene transfected breast cancer cells were lower than those in untransfected and empty plasmid cells.

Objective to observe whether the BRCA1 gene mutation found in familial breast cancer population in Shanghai was repeated in enlarged sample.Methods Sixty independent Han families with familial breast cancer from four domestic breast cancer clinical research centers were detected. At least two first-degree relatives or three second-degree relatives in the families had primary breast cancer. Genomic DNA was extracted from peripheral blood leukocytes, and the previously reported pathogenic mutations of BRCA1 gene (1100delAT, IVS17-1G>T, IVS21+1G>C and 5640delA) were analyzed by polymerase chain reaction (PCR) -denaturing high performance liquid chromatography (DHPLC) -DNA direct sequencing. Four markers linked to BRCA1 gene (D17S855, D17S1322, D17S1326 and D17S1327) were selected for allelic analysis. Results Repeated BRCA1 1100delAT mutations were found in two families from northern China, A new pathogenic mutation-BRCA1 5589del8 was also found in the tested fragment.Allelic analysis with markers linked to BRCA1 gene showed that two BRCA1 1100delAT mutant carrying cases from northern China had the same allele.The allelic type of BRCA1 1100delAT mutation in all tested families was 3.16% (3/95). Conclusion The BRCA1 1100delAT mutation may be the mutation hotspot of BRCA1 gene in familial breast cancer population in China. In northern China, this mutation may have "ancestral effect", which needs further studies to confirm in large-scale populations.

Objective to investigate the correlation between the variation of melanocortin 4 receptor (MC4R) gene, an important protein related to feeding behavior and energy metabolism, and obesity in Chinese.Methods 563 Chinese in Shanghai were selected, including 258 cases with BMI ≥30 kg/m2 and 305 cases with BMI<23 kg/m2. The variation of MC4R gene nt-216C/T, nt-178A/C and Val103Ile was detected by DNA sequencing.The height, weight, waist circumference, hip circumference, femoral circumference, diastolic and systolic blood pressure of the selected population were measured. Oral glucose tolerance test was performed in the selected population, and the blood glucose level was measured at fasting and 120 min after glucose loading, and the fasting blood lipid profile was measured. The body fat content was measured by bioelectric impedance assay. Results (1) The variation frequency of nt-216C/T, nt-178A/C and Val103Ile in Chinese was less than 5%; (2) Logistic regression analysis showed that MC4R gene Val103Ile variation was an independent associated factor with obesity (OR =0.414, P =0.040), and the frequency of Ile allele was lower in obese patients. (3) Body fat parameters, blood glucose, blood lipid and blood pressure of Val/Val homozygous and Ile carriers were compared in normal weight group and obese group, respectively, and there was no significant difference. Conclusion MC4R gene Val103Ile variation was associated with obesity in Chinese.

Objective to investigate the correlation between the expression levels of B cell activator (BAFF) receptor family genes and primary biliary cirrhosis (PBC). Methods 18S rRNA was used as the internal reference gene, and the relative quantitative levels of B cell maturation antigen (BCMA), perforating membrane protein activator (TACI) and B cell activator receptor (BAFF-R) genes in peripheral blood mononuclear cells of 30 normal subjects and 30 PBC patients were detected by real-time fluorescence reverse transcription polymerase chain reaction (FQ-RT-PCR). The correlations between the expression levels of BCMA and immunoglobulin IgM, alkaline phosphatase (ALP) and γ-glutamyl transpeptidase (GGT) were analyzed. Results the BCMA mRNA of peripheral blood mononuclear cells of PBC patients was 8.6 times that of normal controls, and the difference was statistically significant (P<0.05). The TACI mRNA was significantly lower than that in the normal control group, and the difference was statistically significant (P<0.05); However, BAFF-R mRNA was slightly lower than that of the normal control group, but the difference was not statistically significant (P>0.05). △ Ct values were correlated with IgM, GGT and ALP (P<0.01); TACI's △ There was a correlation between Ct value and IgM (P<0.05), but no correlation with GGT and ALP (both P>0.05); There was no correlation between BAFF-R and IgM, GGT and ALP (all P>0.05). Conclusion the expression of BCMA mRNA and TACI gene in peripheral blood mononuclear cells of PBC patients was significantly increased and decreased, suggesting that the pathogenesis of PBC was related to the enhancement of humoral immunity and the disruption of immune tolerance, and BCMA may be related to the disease progression of PBC.

Objective to analyze the etiology and composition of delayed hemorrhagic cystitis (LOHC) after allogeneic hematopoietic stem cell transplantation. Methods the LOHC occurred in 200 allogeneic hematopoietic stem cell transplantation patients from 2004 to 2005 in Peking University was retrospectively analyzed. Results A total of 57 of 200 transplanted patients developed hemorrhagic cystitis (HC), all of which were delayed. In 12 cases of clinical complicated viremia, the viremia disappeared after antiviral treatment, but the symptoms of cystitis did not improve. The etiology was attributed to infectious complicated with non-infectious factors, accounting for 21.53%; Another 14 cases had no clinical evidence of infectious agents, of which 5 cases were completely relieved by alkalizing diuretic cystitis alone, and 9 cases were ineffective against infection therapy, and the etiology was attributed to non-infectious, accounting for 24.56%. 13 cases of HC with non-infectious factors were given short-course hormone shock therapy, and 9 cases achieved remission, 2 cases achieved partial remission, and 2 cases were ineffective. A total of 4 cases were ineffective against various treatments, and HC did not resolve at the time of death, and the cause of death was other transplantation-related complications. Conclusion Hemorrhagic HC is a common complication after allogeneic hematopoietic stem cell transplantation, and clinical attention should be paid to the differentiation of infectious and non-infectious causes, and the treatment according to the etiology can improve the curative effect.

Objective to investigate the effective treatment of radioosteonecrosis of temporal bone after radiotherapy for nasopharyngeal carcinoma. Methods 8 cases of radioosteonecrosis of temporal bone complicated by radiotherapy for nasopharyngeal carcinoma were treated by surgery: 2 ears underwent radical mastoidectomy, 1 ear underwent enlarged radical mastoidectomy, and 5 cases underwent radical mastoidectomy + periauricular pedicled tissue flap cavity tamponade. Results A total of 5 ears (62.5%) obtained dry ears without dead bone reformation, and 2 ears (25%) obviously improved their symptoms. After radical mastoidectomy, one ear obtained dry ear, and the other ear formed free dead bone half a year after operation, which was resected by surgery, but the ear was not completely epithelialized and dry, so it was necessary to change the dressing regularly; Conclusion It is difficult to treat temporal bone radioosteonecrosis after radiation in nasopharyngeal carcinoma. The main purpose of surgical treatment is local drainage and prevention of complications. Radical mastoidectomy plus pedicled tissue flap around the ear is an effective therapeutic method.

Objective to investigate the effects of pre-infarction angina pectoris (ischemic preconditioning) and post-ischemic adaptation on the coronary blood flow velocity and prognosis of patients with acute myocardial infarction after interventional therapy. Methods 96 patients with myocardial infarction who underwent emergency coronary intervention within 12 h were divided into 3 groups: pre-conditioning group (35 cases), post-adaptation group (32 cases) and simple reperfusion group (29 cases). The corrected thrombolytic frame number of myocardial infarction (CTFC), blood creatine phosphokinase (CK), creatine phosphokinase isoenzyme (CK-MB) and malondialdehyde were measured, and the wall motion score was measured 8 weeks after operation. Results the CTFC (27±6,27±6) in ischemic preconditioning group and post-adaptation group was significantly faster than that in simple reperfusion group (31±7, both P<0.05), and the peak values of CK and CK-MB were significantly lower than that in simple reperfusion group (1242 U/L ±801 U/L, 1237 U/L ±813 U/L vs 1697 U/L ±966 U/L, both P<0.05); 122 U/L ± 78 U/L, 117 U/L ± 76 U/L vs 172 U/L ± 93 U/L, P<0.05); The MDA in all groups was higher than that in the control group at the time of admission, and it was lower in the ischemic preconditioning group and the post-conditioning group than that in the simple reperfusion group at all postoperative points. The wall motion recovery in the ischemic preconditioning group and the post-conditioning group was better than that in the simple reperfusion group at 8 weeks postoperatively (1.2±0.2, 1.2±0.2 vs 1.4±0.3, P<0.05).

Objective to study the value and mechanism of 18F-FDG dual-probe coincidence line imaging (DHTC) and simultaneous CT fusion technique in the diagnosis and treatment of head and neck tumors. Methods 25 cases of head and neck tumors were examined by 18F-FDG dual-probe coincidence line imaging (DHTC) and simultaneous CT fusion technique, and the results were compared with CT/MRI. Fresh tissue samples of 38 cases of head and neck cancer admitted to the department of otolaryngology and oral surgery were collected and detected by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. Results The sensitivity, specificity and accuracy of SPECT/CT were 100.0%, 87.5% and 96.0%, respectively; The sensitivity, specificity and accuracy of CT/MRI were 64.7%, 50.0% and 60.0%, respectively. In the comparison of SPECT/CT and CT/MRI anatomical imaging at the same site, the anatomical imaging could not make a correct diagnosis in 4 cases of cervical metastatic lymph node carcinoma and the benign and malignant head and neck masses in 4 cases, but coincidence line imaging and image fusion could make a correct judgment. The results of RTPCR and immunohistochemistry showed that the expression of glucose transporter-1 (Glut-1) and Glut-3 genes in head and neck carcinoma was significantly higher than that in normal and adjacent tissues (all P<0.05); The expression of Glut-1 protein in head and neck carcinoma was 78.9%, but Glut-3 protein was not expressed in normal tissues, adjacent tissues and head and neck carcinoma. Conclusion Coincidence line imaging and image fusion can be used as a prospective examination tool for differentiating benign and malignant head and neck tumors, clinical stage and grade of tumors, differentiating the recurrence after surgery or radiotherapy and the detection of unknown primary tumors; The abnormal expression of Glut-1 and Glut-3 is related to the increase of glucose absorption in head and neck cancer.

Objective to study the correlation between thrombotic hazard factors and platelet phospholipid membrane fatty acids in middle-aged and elderly patients with hyperlipidemia in Hangzhou.Methods the contents of various methyl esterified platelet phospholipid membrane fatty acids in the hyperlipidemia group (81 cases) and the normal blood lipid control group (65 cases) were analyzed by gas chromatography, and the thrombotic hazard factors serum homocysteine (Hcy) and thromboxane B2 (TXB2) were determined by standard method, and the correlation between them was analyzed by multiple linear regression. Results There was no significant difference between platelet phospholipid membrane fatty acids in hyperlipidemia patients and healthy controls (P>0.05). Hcy was negatively correlated with the ratio of platelet phospholipid membrane docosahexaenoic acid (DHA), n-3 polyunsaturated fatty acids to n-6 polyunsaturated fatty acids (n-3 PUFA/n-6 PUFA) (r = -0.277, -0.231, all P<0.01). TXB2 was positively correlated with arachidonic acid (r =0.176, P<0.05), and with DHA, cosapentaenoic acid (EPA) and n-3PUFA

Objective to investigate the relationship between C1019T polymorphism of gap junction protein 37 (CX37) gene and coronary artery disease in Han population of northern China. Methods The genotype and allele distribution of C1019T polymorphism of CX37 gene were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) combined with polyacrylamide gel electrophoresis (PAGE) in 514 patients with coronary artery disease diagnosed by coronary angiography and 400 healthy controls with normal angiography. Results The distribution frequencies of C1019T genotypes (CC, TC and TT) were 22.37%, 53.31% and 24.32% in the coronary artery disease group and 17.75%, 46.50% and 35.75% in the control group, respectively (P =0.0007). The frequency of C allele was significantly higher in the coronary artery disease group than in the normal control group (49.03% vs 41.00%,OR =1.38,95% confidence interval was 1.15~1.66,P =0.0006). The number of C allele carriers (CC + TC) was 75.66% in the coronary artery disease group and the control group, respectively The risk of coronary heart disease in C allele carriers (CC + TC) was 1.96 times higher than that of TT type (95% confidence interval 1.38-2.78), but there was no significant difference in the frequency of gene distribution between the two groups in female population (P =0.24). Conclusion C allele of CX37 gene may be associated with the occurrence of coronary heart disease in Han population in northern China.

Objective to investigate the role of apoptotic protein Bax in the regulation of apoptotic resistance of malignant lymphoma cells to tumor necrosis factor apoptosis-inducing ligand (TRAIL), so as to provide a therapeutic target for clinical overcoming tumor drug resistance.Methods Malignant lymphoma cells (CRL) and normal control cells (HRC) were treated with 500 μ g/L TRAIL and/or 10 nmol/L proteasome inhibitor PS-341, respectively.The apoptosis of cells was detected by flow cytometry.The activity of cysteine proteolytic enzyme-8 in cells was detected by fluorescence chromogenic.The expression level of Bax protein in cells was detected by Western blot, and the activity and conformational changes of Bax protein were detected by immunoprecipitation (IP). Results Compared with HRC cells, CRL cells had significant resistance to TRAIL, and the 24h apoptosis index was only 21%, while the former was 32%, and the difference between the two cells was statistically significant (P<0.01); At the same time, the expression of Bax in CRL cells decreased during TRAIL, and the expression level was only 5/17 of the normal amount at 24 h. When PS-341 was used in combination, the degradation of Bax protein was effectively inhibited, and the expression level was 1.2 times of the normal amount at 6 h, which significantly increased the activity; At the same time, the activity of cysteine protease-8 was increased, which was 26.5 μ mol·L-1·h-1·mg-1 protein at 6 h, thus increasing apoptosis. The apoptosis index at 6 h reached 54%, and the differences were statistically significant compared with the control group (all P<0.01). Conclusion The down-regulated expression of pro-apoptotic protein Bax is involved in the drug resistance of malignant lymphoma cells to TRAIL.

Objective to quantitatively observe the sensory neurons innervating levator ani muscle and investigate the etiology of defecation dysfunction after congenital anorectal malformation.Methods The sensory neurons innervating levator ani muscle in Wistar fetal rats at 20 days gestation were labeled with fluorescent gold by fetal surgery, microinjection and neural tracer.The number of labeled neurons was counted and the morphology of neurons was observed by serial transverse section of the spinal cord. The animal model of congenital anorectal malformation was made by teratogenesis of ethylene thiourea. Results The sensory neurons innervating levator ani muscle were mainly distributed in the spinal dorsal root ganglion of the spinal cord in the L5-S1 spinal cord segment. The number of labeled neurons in the normal control group (24 fetal rats) was (11 804 2362), the number of labeled neurons in the congenital anorectal malformation group was significantly reduced, the number of labeled neurons in the low malformation group (18 fetal rats) was (2886 705), and the number of labeled neurons in the high malformation group (41 fetal rats) was (1026 425). The difference between the two malformation groups and the normal control group was statistically significant (all P<0.05). Conclusion There were obvious abnormalities in the development of sensory neurons in the lumbosacral cord of the innervating levator anus muscle in fetal rats with congenital anorectal malformation.

Pancreaticoduodenectomy is the most complicated operation in digestive surgery. With the increasing popularization of this operation and the emergence of many improved procedures, such as pyloric-preserving pancreaticoduodenectomy (PPPD) and extended pancreaticoduodenectomy, there have been many controversies around this operation, such as the effectiveness and indications of PPPD, and whether extended pancreaticoduodenectomy can improve survival, etc. Since the concept of "evidence-based medicine" was introduced in JAMA in 1992, randomized controlled studies (RCT) based on it have greatly promoted the progress of clinical research and also deeply influenced the field of pancreatic surgery. Kaido analyzed the reports of randomized controlled studies on pancreaticoduodenectomy published in English in the past 10 years, which were published in October 2006<Pancreas, 2006, 33: 228-232.

Infectious keratitis is a very common ophthalmic disease. Its common pathological process is that after the pathogen infects the cornea or relapses, cellular infiltration first occurs, and then corneal opacity and edema occurs. Under the joint action of pathogen and host, corneal ulcer, neovascular invasion and even perforation occur. The prognosis is corneal cloud and pannus in mild cases, and adhesive corneal leukoplakia in severe cases. Like other inflammation sites, the core link of infectious keratitis is the migration and infiltration of inflammatory cells to the lesion and its surroundings. The regulation of this process determines the outcome and prognosis of inflammation. Chemokines and their receptors play an important role in the process of cell migration. The following is a review of the role of chemokines and their receptors in the main infectious keratitis.

Cognitive control refers to a series of processes that adaptively integrate the changes of information to make flexible response to changing or novel task requirements [1]. The research on cognitive control has always been an important content of cognitive science.The most commonly used classical paradigms are Stroop task and flanker task.Stroop task has been applied more widely and longer time.The study of cognitive control by Stroop effect can be carried out through many modes, such as event-related evoked potentials,positron emission tomography and functional magnetic resonance imaging (fMRI). Because fMRI technique can accurately locate neuronal activity without invasion, has high spatial and temporal resolution and good repeatability, it has become a brand-new research method in the field of neuroscience.In recent years, a lot of research has been carried out using this technique, among which fMRI using the classical Stroop task has become a major experimental paradigm to study the conflict resolution and error detection of human brain in cognitive control, and the understanding of cognitive science has been proposed and continuously revised [2-4]. This paper reviews the main tasks and neural mechanisms of cognitive control research, the general principles of fMRI and related clinical applications.