2007年·第120卷第20期

Pancreatic cancer often starts silently without symptoms at its early stage but progresses quite rapidly and has a poor prognosis. In recent years the incidence of pancreatic cancer has been rising year by year.1

Breast cancer is one of the neoplasms that have greatest negative psychological impact on the sufferers. Although China is among the low morbidity country of breast cancer, its yearly increasing rate in China is 1%-2% higher than the average rate of the word.1 Due to its largest population in the word, China tops the world in its breast cancer cases but general medical care for the patients still lags behind the developed countries. These issues are related to the diagnosis and treatment of breast cancer in China。

Abstract：Background Chemotherapy is the most frequently adopted adjuvant therapy of pancreatic ductal adenocarcinoma (PDAC), but the development of drug resistance reduces its effectiveness. Clarification of the mechanism of multidrug resistance (MDR) development in PDAC is needed to improve the therapeutic effect of chemotherapy. This study was aimed to investigate the molecular mechanism of MDR of PDAC and to identify genes associated with MDR development.Methods The gene expression profiles of cell line SW1990 and three drug-selected pancreatic chemoresistant sub-lines, SW1990/5-Fu, SW1990/ADM and SW1990/GEM, were obtained using an oligonucleotide microarray (Affymetrix HG U133 2.0 plus) that contained approximately 38 000 human genes. The microarray results were validated by real-time quantitative polymerase chain reaction and Western blot analysis.Results There were 165 genes and expressed sequence tags, some of which have never been linked to drug resistance, that were up- or down-regulated at least 2-fold in all resistant sub-lines when compared with SW1990.According to Gene Ontology annotation, differentially expressed genes related to MDR in pancreatic cancer belong to many functional families and with diverse biological processes. Genes related to antioxidant activity, apoptosis, the cell cycle, signal transduction and intracellular adhesion may undergo epigenetic changes preceding MDR development. A hierarchical clustering was conducted and several interesting clusters were discovered that may be primarily related to cell cycle and developmental regulation. A prediction rule was built from the expression profiles of 117 genes after support vector machine (SVM) analysis, and the prediction result was examined by cytotoxic testing. As a result, a differential gene expression pattern was constructed in multidrug resistant pancreatic cancer cells.Conclusions The findings of this study prove that construction of a chemoresistance prediction rule, based on gene expression patterns, is practical. These data provide new insights into the molecular mechanism of pancreatic cancer MDR development and may be useful for the detection and treatment of MDR in pancreatic cancer patients。

Abstract：Background Tissue factor (TF) is overexpressed in many malignant tumours and is linked to the pathogenesis and prognosis of such malignancies. In vitro studies have proved that reduced expression of TF has inhibitory effect on the angiogenesis and cell proliferation of the malignant tumour. Therefore, TF suppression has been raised as a possible treatment for malignant tumours. Here we investigated the effect of celecoxib on TF expression induced by tumour necrosis factor α (TNFα) in PANC-1 cells and a possible molecular mechanism underlying the celecoxib effect.Methods Various doses of celecoxib solution were added to standard cell numbers of PANC-1 cells mixed with equal dose of TNFα for 6 hours. The expression of tissue factor was detected quantitatively by Western blot, whilst the activation of nuclear factor κB was tested by electromobility shift assay.Results As the doses of celecoxib increased, the tissue factor expression was decreased in PANC-1 cells and so was the activation of nuclear factor κB.Conclusions Celecoxib can downregulate the expression of tissue factor induced by TNFα in PANC-1 cells. This antitumour effect of celecoxib can be explained indirectly via its suppressive role in activation of nuclear factor KB。

Abstract：Background Little is known of the effects of hydrocortisone on cell adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and its counterreceptors (LFA-1, Mac-1) in acute pancreatitis (AP). We investigated the effects of prior treatment with hydrocortisone on the production of ICAM-1 and its counterreceptors (LFA-1 and Mac-1) in AP of rats to clarify the effect of hydrocortisone on induced acute pancreatitis.Methods Acute pancreatitis was induced by infusion of 5% chenodeoxycholic acid into the pancreatic duct, followed by ligation of pancreatic duct. Before induction of acute pancreatitis, rats were treated with hydrocortisone (n=20) or 0.9%saline (n=20). Blood and specimens from pancreas and lung were obtained from 5 rats from each treatment euthanized at 1 hour or 3 hours, 6 hours, 12 hours. Expression of ICAM-1 was assessed by immunohistochemistry and Western blot analysis of pancreas and lungs. The expression of LFA-1 and Mac-1 on neutrophils was detected by flow cytometer.The therapeutic effect of hydrocortisone was assessed from injuries to pancreas and lung.Results ICAM-1 expression in the pancreas of hydrocortisone group was significantly less than in control group at 3 hours and 6 hours. In the lungs of hydrocortisone group, ICAM-1 expression was significantly less than in control group at 3 hours, 6 hours and 12 hours. The expression of LFA-1 and Mac-1 on neutrophils in blood increased significantly in control group over hydrocortisone group. Increased expression of ICAM-1, LFA-1 and Mac-1 preceded leukocyte infiltration. Compared to untreated animals with acute pancreatitis, rats pretreated with hydrocortisone had significantly reduced histological lung injury and output of ascitic fluid.Conclusions Prior treatment with hydrocortisone before the induction of acute pancreatitis ameliorates pulmonary injury and the output of ascitic fluid and reduces the expression of ICAM-1 and its counterreceptors (LFA-1, Mac-1) in acute pancreatitis。

Abstract：Background Axillary lymph node metastasis is a very important metastatic pathway in breast cancer and its accurate detection is important for staging tumour and guiding therapy. However, neither the accuracy of routine detection of lymph node in surgical specimens nor the significance of minute lymph node with metastases in breast cancer is clear. A modified method for conveniently detecting minute lymph node in specimens of axillary dissections in patients with breast cancer was used to analyze their influence on staging breast cancer.Methods Lymph nodes in fresh, unfixed, specimens of axillary dissections from 127 cases of breast cancer were detected routinely. Then the axillary fatty tissues were cut into 1 cm thick pieces, soaked in Carnoy's solution for 6 to 12 hours, taken out and put on a glass plate. Minute lymph nodes were detected by light of bottom lamp and examined by routine pathology.Results Lymph nodes (n= 2483, 19.6±8.0 per case) were found by routine method. A further 879 lymph nodes up to 6 mm (781 ＜ 3 mm, 6.9±5.3 per case, increasing mean to 26.5±9.7) were found from the axillary tissues after soaking in Carnoy's solution. By detection of minute lymph nodes, the stages of lymph node metastasis in 7 cases were changed from pathological node (pN) stage pN0 to pN1 in 4 cases, from pN1 to pN2 in 2 and from pN2 to pN3 in 1.Conclusions The accurate staging of axillary lymph node metastasis can be obtained routinely with number of axillary lymph nodes in most cases of breast cancer. To avoid neglecting minute lymph nodes with metastases, small axillary nodes should be searched carefully in the cases of earlier breast cancer with no swollen axillary nodes. Treatment with Carnoy's solution can expediently detect minute axillary nodes and improve the accurate staging of lymph nodes in breast cancer。

Abstract：Background Estrogen receptor (ER) is a very important biomarker of breast cancer. ER deletion has been consistently associated with tumor progression, recurrence, metastasis and poor prognosis, but the biological mechanism is still unclear. ER negative breast cancer expresses high levels of interieukin-8 (IL-8). ER expression can downregulate IL-8 promotor activity. As a multifunctional cytokine, IL-8 has many important biological activities in tumor genesis and development. With the goal of investigating the role of IL-8 in ER-negative breast cancer progression, we applied RNA interference technology to specifically knockdown the IL-8 expression in ER-negative breast cancer cell line MDA-MB-231.Methods Interfering pRNA-IL-8 and the control was transfected into ER(-) MDA-MB-231. The proliferation, cell apotosis,and invasive ability were recorded in transfected, untransfected and negative transfected cells. These cells were injected into nude mice to assess tumorigenicity, proliferation, metastasis and microvessel density (MVD).Results In vitro, decreased expression of IL-8 was associated with reduced cell invasion (P＜0.001), but had no effect on cell proliferation (P＞0.05). In vivo, neutrophils infiltration was significantly inhibited in pRNA-IL-8 transfected cells compared with untransfected and negatively transfected cells (P=0.001, P＜0.001). Less metastasis was found in transfected cells compared with negatively transfected cells (0% vs 80%, P=0.048). Nevertheless, we observed less MVD in transfected cells compared with control in nude mice (P＜0.001).Conclusions IL-8 inhibits ER-negative breast cancer cell growth and promotes its metastasis in vivo, which may be correlated with neutrophils infiltration induced by IL-8。

Abstract：Background Laparoscopic surgery is advantageous for minimal invasiveness and rapid postoperative recovery. Since the use of laparoscopic hepatectomy in liver resection in the 1990s, it has been performed in a few institutions worldwide.Lack of efficient and safe techniques for liver transaction is the major obstacle preventing from its further development.We developed a new technique for laparoscopic hepatectomy by curettage and aspiration in 1998. In this paper we analyze the clinical outcomes of this technique after 7 years of practice.Methods Altogether 59 consecutive patients underwent laparoscopic hepatectomy by curettage and aspiration from August 1998 to January 2005 at our institution. These patients included 33 males and 26 females, with a mean age of 47 years. For liver transecsion laparoscopic Peng's multifunctional operative dissector (LPMOD) was used. Lesions included malignant liver tumors in 19 patients, benign liver tumors in 17, intrahepatic calculus in 18, and other liver lesions in 5.Procedures included local resections in 30 patients, left lateral segmentectomy in 28, and right hemihepatectomy in 1.Results Laparoscopic operation was completed in 57 patients. Two patients (3.4%) had the operation converted to laparotomy. The mean operating time was 143 minutes and the mean intraoperative blood loss was 456 mi. The mean length of postoperative hospital stay was 7 days. Complications occurred in 2 patients (3.4%), and there was no perioperative death.Conclusion Laparoscopic hepatectomy by curettage and aspiration is efficient and safe for liver resection。

Abstract：Background Drug treatment for secondary hyperparathyroidism caused by chronic renal failure may be available at the early stage of the disease, but it is not as effective for serious patients. The aim of the study was to evaluate the effect of total parathyroidectomy combined with forearm autotransplantation in the uremic patients with secondary hyperparathyroidism.Methods From September 1999 through September 2006, parathroidectomy and autotransplantation was performed in 20 patients. The coherence between the results of preoperative parathyroid ultrasonography and surgical exploration were compared. The serum calcium concentration and intact parathyroid hormone (iPTH) were monitored preoperatively,intraoperatively, and postoperatively.Results A total of 71 hyperplastic parathyroid glands were resected in the 20 patients. The accordance rate of parathyroid localization between B-ultrasonography and intraoperative exploration was 94.4%. The average iPTH value was (110.90±67.42) ng/L, (433.80±243.72) ng/L, (48.80±42.69) ng/L, (229.04±172.68) ng/L and (232.39±224.05) ng/L at day 1, 2, 3, 7, 30 after operation respectively. The clinical symptoms were ameliorated and the levels of serum calcium concentration were controlled within the normal range after operation. Recurrent secondary hyperparathyroidism had happened in 1 case, 4 years postoperatively because of the development of autograft hyperplasia, and in another case 2years postoperatively due to remnant of neck parathyroid glands. The clinical symptoms were all alleviated after re-operation. No surgical complication had occurred in any of the patients.Conclusions The total parathyroidectomy with forearm autotransplantation is feasible, safe, and effective for patients with secondary hyperparathyroidism in the short term. The long-term effects should be further investigated。

Abstract：Background Severe burn-blast combined injury is a great challenge to medical teams for its high mortality. The aim of this study was to elucidate the clinical characteristics of the injury and to present our clinical experiences on the treatment of such cases.Methods Five patients with severe burn-blast combined injuries were admitted to our hospital 77 hours post-injury on June 7, 2005. The burn extent ranged from 80% to 97% (89.6%±7.2%) of TBSA (full-thickness burns 75%-92%(83.4%±7.3%)). All the patients were diagnosed as having blast injury and moderate or severe inhalation injury. Functions of the heart, liver, kidney, lung, pancreas and coagulation were observed. Autopsy samples of the heart, liver, and lungs were taken from the deceased. Comprehensive measures were taken during the treatment, including protection of organ dys function, use of antibiotics, early anticoagulant treatment, early closure of burn wounds, etc. All the data were analyzed statistically with t test.Results One patient died of septic shock 23 hours after admission (four days after injury), the others survived.Dysfunction of the heart, liver, lungs, pancreas, and coagulation were found in all the patients on admission, and the functions were ameliorated after appropriate treatments.Conclusions Burn-blast combined injury may cause multiple organ dysfunctions, especially coagulopathy. Proper judgment of patients' condition, energetic anticoagulant treatment, early closure of burn wounds, rational use of antibiotics, nutritional support, intensive insulin treatment, timely and effective support and protection of organ function are the most important contributory factors in successful treatment of burn-blast combined injuries。

Abstract：Background Wound dressings are divided into traditional and new types. The new dressings are thought to accelerate wound healing. The purpose of this study was to supplement the scanty data on the absorbency of the new dressings and their effects on evaporation from the burn surface.Methods The water absorption rate of four dressings (carbon fiber dressing, hydrogel dressing, silver nanoparticle dressing, and vaseline gauze) were measured by the immersion-weight gain method. A total of 120 inpatients with 10%superficial partial-thickness burn wounds were randomly assigned to four groups, each with 30 participants. Carbon fiber dressing, hydrogel dressing, and silver nanoparticle dressing were used in groups A, B, and C as the primary dressing,and traditional vaseline gauze was used in group D as the control. Multi-spot evaporation from normal skin and naked wound, and from wounds covered with each of the four dressings was measured post-burn on days 1, 3, 5, and 7 by an EP-I evaporimeter under conditions of 21 ℃ -22 ℃ ambient temperature and 74%-78% humidity.Results The absorption rates of the four dressings were 988% with carbon fiber dressing, 96% with silver nanoparticle,41% with vaseline gauze, and 6% with hydrogel. Evaporation from the naked burn wounds was about 1/3 higher than from normal skin (P＜0.01). Compared with wounds without applied dressing, evaporation from dressed wounds decreased and was time-dependent (P＜0.01). The evaporation of wounds with carbon fiber dressing was the lowest ((13.40±2.82)ml·h-1·m-2,P＜0.01) on day 1 post-burn,compared with the other groups.Conclusion All four dressings have water retention capacity while carbon fiber dressing has the highest absorption rate and shows the best containment and evaporation from the burn wound。

Abstract：Background Xiaobuxin-Tang, a traditional Chinese herbal prescription recorded in a silk scroll unearthed from Mogao Caves of Dunhuang has been indicated that it can remit depressive disorder. The present study was designed to investigate its antidepressant effects in various animal depression models.Methods Xiaobuxin-Tang was extracted by 70% alcohol, and then three behavioral despair models and 5-Hydroxytryptophan (HTP)-induced head twitch response model were adopted to assess the antidepressant effects of the ethanolic extract of Xiaobuxin-Tang with the study on spontaneous motor activity. Groups of mice and rats received oral treatment with Xiaobuxin-Tang (150-1200 mg/kg) only once acutely in all tests. The duration of immobility was measured during the last 4 minutes of the 6-minutes test period in mice forced swimming test, rats forced swimming test and mice tail suspension test. In 5-HTP-induced head twitch response, the mice were intraperitoneally administered with 120 mg/kg of L-5-HTP, and then the cumulative number of head twitches was counted in 20 minutes. Spontaneous motor activities of mice were recorded automatically in 10 minutes by VIDEOMEX-V image analyticsystem.Results The extract at doses of 300 mg/kg (p.o.) and 600 mg/kg (p.o.) significantly decreased the duration of immobility time in a dose dependent manner in mice forced swimming test; also, the extract at dose of 1200 mg/kg (p.o.)significantly decreased the duration of immobility time in rat forced swimming test. Furthermore, the extract at a dose of 600 mg/kg had the same effect in mice tail suspension test. Meanwhile, the extract at the effective doses for behavioral despair models, had no effect on spontaneous motor activity in mice. The extract (300-1200 mg/kg, p.o.) also increased the accumulative number of the 5-HTP-induced head twitch response in mice in 20 minutes.Conclusion Our results suggested that the ethanolic extract of Xiaobuxin-Tang exerts antidepressant-like effect。

Abstract：Background The induction of immune tolerance and suppression of allograft rejection has become the focus in the study of liver transplantation. The effect of immune therapy with anti-CD40L mAb alone or in combination with cyclosporine A (CsA) on the recipient survival and Th1/Th2 cytokine profile was studied to elucidate its immunological mechanism and role in rat orthotopic liver transplantation.Methods The model of rat orthotopic liver transplantation was established by modified Kamada's technique.Recipients were divided into group A (control group): SD→SD; group B (group of rejection): SD→Wistar without any treatment; group C: SD→Wistar with CsA monotherapy from day 1 to day 5; and group D: SD→Wistar with CsA from day 1 to day 5 and anti-CD40L mAb on day 0 and day 2. The survival of the recipients in all groups was observed and ELISA technique was used to detect the level of cytokines in peripheral blood on post-transplant day 7.Results The survival period of recipients in groups A (＞60 days) and D (＞60 days) was significantly longer than that in group B (13.8±2.4 days). The serum levels of interleukin 2 (IL-2) and interferon y in group B were significantly higher than those in other groups; the level of tumor necrosis factor α was higher but not statistically significant. In contrast, the serum levels of IL-4 and IL-10 in group D were elevated more significantly than those in group B (P＜0.05).Conclusions Combined immune therapy can prolong the survival of allografts. Increased expression of Th2 cytokines, which is closely related to the induction of tolerance and suppression of rejection, is beneficial to the long-term survival of recipients and allografts。

The acute respiratory distress syndrome (ARDS) is defined by noncardiogenic pulmonary edema and acute respiratory failure in the seriously ill patients。

The antigenicity of inartificial dermis can be minimized by removing cell components while keeping the intrinsic structures.1,2 To minimize the antigenicity, the cell fragments must be wiped off as clearly as possible.Thus, the test of cell fragments is very important for the evaluation of dermal matrix production。

Chylous ascites, an uncommon disease usually caused by obstruction or rupture of the peritoneal or retroperitoneal lymphatic glands, is defined as the accumulation of chyle in the peritoneal cavity。

Microadenocarcinoma (MA) is a rare variant of ductal carcinoma of the pancreas.1 Although it is generally accepted that the MA is a pattern of growth,some researchers regard it as a distinctive entity.2 Here we report a case of MA in China。

Obturator hernia is a relatively rare pelvic hernia and usually occurs in elderly, thin, multiparous women.Because symptoms are nonspecific in most cases,diagnosis is often delayed until laparotomy is performed for treatment of bowel obstruction or peritonitis。

In 1970, a gastric adenocarcinoma patient with increased alpha fetoprotein (AFP) in his serum and liver metastatic tumor was reported by Bourreilile et al.1At that time, it was realized that a gastric adenocarcinoma could produce AFP。