Showing papers in "Chinese Medical Journal in 2011"

Coexistence of Th1/Th2 and Th17/Treg imbalances in patients with allergic asthma.

Abstract: Background Recent recognition is that Th2 response is insufficient to fully explain the aetiology of asthma. Other CD4(+) T cells subsets might play a role in asthma. We investigated the relative abundance and activities of Th1, Th2, Th17 and CD4(+)CD25(+) Treg cells in patients with allergic asthma. Methods Twenty-two patients with mild asthma, 17 patients with moderate to severe asthma and 20 healthy donors were enrolled. All patients were allergic to house dust mites. Plasma total IgE, pulmonary function and Asthma Control Questionnaire were assessed. The proportions of peripheral blood Th1, Th2, Th17 and CD4(+)CD25(+) Treg cells were determined by flow cytometry. The expression of cytokines in plasma and in the culture supernatant of peripheral blood mononuclear cells was determined by enzyme linked, immunosorbent assay. Results The frequency of blood Th2 cells and IL-4 levels in plasma and culture supernatant of peripheral blood mononuclear cells were increased in all patients with allergic asthma. The frequency of Th17 cells and the plasma and culture supernatant levels of IL-17 were increased, whereas the frequency of CD4(+)CD25(+) Treg cells and plasma IL-10 levels were decreased in patients with moderate to severe asthma. Dermatophagoides pteronyssinus specific IgE levels were positively correlated with the percentage of blood Th2 cells and plasma IL-4 levels. Forced expiratory volume in the first second was negatively correlated with the frequency of Th17 cells and plasma IL-17 levels, and positively correlated with the frequency of Treg cells. However, mean Asthma Control Questionnaire scores were positively correlated with the frequency of Th17 cells and plasma IL-17 levels, and negatively correlated with the frequency of Treg cells. Conclusions Imbalances in Th1/Th2 and Th17/Treg were found in patients with allergic asthma. Furthermore, elevated Th17 cell responses, the absence of Tregs and an imbalance in Th17/Treg levels were associated with moderate to severe asthma.

Bispectral index monitoring prevent awareness during total intravenous anesthesia: a prospective, randomized, double-blinded, multi-center controlled trial.

Abstract: BACKGROUND Awareness is a serious complication of general anesthesia. In China, the incidence of intraoperative awareness was 1% in patients undergoing total intravenous anesthesia (TIVA). In this study, we compared the incidence of awareness between Bispectral index (BIS)-guided and routine TIVA protocol and evaluated the effect of BIS on preventing awareness. METHODS A prospective, randomized, double-blinded, multicenter controlled trial was performed. Patients (≥ 18 years of age) undergoing TIVA were randomly divided into BIS-guided group (Group A, BIS was monitored and recommended to maintain between 40 - 60) and control group (Group B, BIS was monitored but the screen was covered). The intraoperative BIS values were downloaded and the BIS trends of confirmed awareness cases were analyzed to determine whether light anesthesia existed. RESULTS Of the total 5228 patients, 2919 patients were assigned to Group A and 2309 to Group B. Four cases of confirmed awareness (0.14%) were reported in the BIS-guided group and 15 (0.65%) in the control group (P = 0.002, OR = 0.21, 95% confidence intervals: 0.07 - 0.63). The incidence of possible awareness (0.14% vs. 0.26%, P = 0.485) and dreaming (3.1% vs. 3.1%, P = 0.986) was comparable between BIS-guided group and the control group. Among the 19 confirmed awareness cases, intraoperative BIS trends of six cases were downloaded and identified. Five of them showed signs of light anesthesia as BIS > 60 and lasted 19 - 106 minutes, whereas one case had a stable BIS trend and the values were within 60 during the operation. Another five awareness cases were reviewed for anesthesia procedures, of which improper light anesthesia were confirmed. CONCLUSIONS BIS-guided TIVA (BIS was recommended to maintain between 40 - 60) decreased the risk of awareness compared with routine TIVA. The main reason for awareness was light anesthesia.

MicroRNA-7 regulates glioblastoma cell invasion via targeting focal adhesion kinase expression.

Abstract: Background Invasion growth is the most characteristic biological phenotype of glioblastoma, but the molecular mechanism in glioma cell invasion is poorly understood. Recent data have showed that microRNA plays an essential role in tumor invasion. Our study aimed to explore the mechanism of miR-7 involved in the control of glioblastoma cell invasion. Methods Glioma cell invasion was evaluated by transwell and scratch assays after up-regulation of miR-7 using miR-7 mimics in U87 and U251 cells. Luciferase reporter assay was used to determine focal adhesion kinase (FAK) as a target of miR-7. The levels of miR-7, matrix metalloproteinases (MMP)-2 and MMP-9 mRNA were detected by PCR assay, and the levels of FAK, MMP-2, MMP-9, total and phosphorylation serine/threonine kinase (AKT), and extracellular signal-regulated kinase (ERK) 1/2 were measured by Western blotting analysis. Results Over-expression of miR-7 inhibited the invasion and migration activity of U87 and U251 cells. And up-regulation of miR-7 reduced FAK protein expression, Further, luciferase reporter assay showed that miR-7 modulated FAK expression directly by binding 3'UTR of FAK mRNA. In addition, miR-7 repressed p-ERK1/2 and p-AKT level, MMP-2 and MMP-9 expression. Finally, the inverse relationship between FAK and miR-7 expression was certificated in human glioma tissues. Conclusion To our knowledge, these data indicate for the first time that miR-7 directly regulates cell invasion by targeting FAK in glioblastoma and that miR-7 could be a potential therapeutic target for glioblastoma intervention.

Does erroneous differentiation of tendon-derived stem cells contribute to the pathogenesis of calcifying tendinopathy?

Abstract: Calcifying tendinopathy is a tendon disorder with calcium deposits in the mid-substance presented with chronic activity-related pain, tenderness, local edema and various degrees of incapacitation. Most of current treatments are neither effective nor evidence-based because its underlying pathogenesis is poorly understood and treatment is usually symptomatic. Understanding the pathogenesis of calcifying tendinopathy is essential for its effective evidence-based management. One of the key histopathological features of calcifying tendinopathy is the presence of chondrocyte phenotype which surrounds the calcific deposits, suggesting that the formation of calcific deposits was cell-mediated. Although the origin of cells participating in the formation of chondrocyte phenotype and ossification is still unknown, many evidences have suggested that erroneous tendon cell differentiation is involved in the process. Recent studies have shown the presence of stem cells with self-renewal and multi-differentiation potential in human, horse, mouse and rat tendon tissues. We hypothesized that the erroneous differentiation of tendon-derived stem cells (TDSCs) to chondrocytes or osteoblasts leads to chondrometaplasia and ossification and hence weaker tendon, failed healing and pain, in calcifying tendinopathy. We present a hypothetical model on the pathogenesis and evidences to support this hypothesis. Understanding the key role of TDSCs in the pathogenesis of calcifying tendinopathy and the mechanisms contributing to their erroneous differentiation would provide new opportunities for the management of calcifying tendinopathy. The re-direction of the differentiation of resident TDSCs to tenogenic or supplementation of MSCs programmed for tenogenic differentiation may be enticing targets for the management of calcifying tendinopathy in the future.

Minimally invasive lumbar interbody fusion via MAST Quadrant retractor versus open surgery: a prospective randomized clinical trial.

Abstract: BACKGROUND In recent years, a variety of minimally invasive lumbar surgery techniques have achieved desirable efficacy, but some dispute remains regarding the advantages over open surgery This study aimed to compare minimally invasive lumbar interbody fusion via MAST Quadrant retractor with open surgery in terms of perioperative factors, postoperative back muscle function, and 24-month postoperative follow-up results METHODS From September 2006 to June 2008, patients with single-level degenerative lumbar spine disease who were not responsive to conservative treatment were enrolled in this study Patients were randomized to undergo either minimally invasive surgery (MIS, transforaminal lumbar interbody fusion via MAST Quadrant retractor, 41 cases) or open surgery (improved transforaminal lumbar interbody fusion, 38 cases) RESULTS The MIS group had longer intraoperative fluoroscopy time than the open surgery group, and the open surgery group had significantly increased postoperative drainage volume and significantly prolonged postoperative recovery time compared with the MIS group (P < 005 for all) MRI scanning showed that the T2 relaxation time in the multifidus muscle was significantly shorter in the MIS group than in the open surgery group at 3 months after surgery (P < 001) Surface electromyography of the sacrospinalis muscle showed that the average discharge amplitude and frequency were significantly higher in the MIS group than in the open surgery group (P < 001) The Oswestry disability index and visual analog scale scores were better at 3, 6, 12 and 24 months postoperatively than preoperatively in both groups Both groups of patients met the imaging convergence criteria at the last follow-up CONCLUSIONS MIS can effectively reduce sacrospinalis muscle injury compared with open surgery, which is conducive to early functional recovery In the short term, MIS is superior to open surgery, but in the long term there is no significant difference between the two procedures

Natural herbal medicine Lianhuaqingwen capsule anti-influenza A (H1N1) trial: a randomized, double blind, positive controlled clinical trial.

Abstract: BackgroundThe 2009 influenza A (H1N1) virus infection is associated with the high risk of severe complications and is spreading more rapidly throughout the world than other reported seasonal influenzas. This study aimed to evaluate the efficacy and safety of the nature herbal medicine Lianhuaqingwen

Decreased regional homogeneity in major depression as revealed by resting-state functional magnetic resonance imaging.

Abstract: Backgroud Functional imaging studies indicate abnormal activities in cortico-limbic network in depression during either task or resting state. The present work was to explore the abnormal spontaneous activity shown with regional homogeneity (ReHo) in depression by resting-state functional magnetic resonance imaging (fMRI).Methods Using fMRI, the differences of regional brain activity were measured in resting state in depressed vs. healthy participants. Sixteen participants firstly diagnosed with major depressive disorder and 16 controls were scanned during resting state. A novel method based on ReHo was used to detect spontaneous hemodynamic responses across the whole brain.Results ReHo in the left thalamus, left temporal lobe, left cerebellar posterior lobe, and the bilateral occipital lobe was found to be significantly decreased in depression compared to healthy controls in resting state of depression.Conclusions Abnormal spontaneous activity exists in the left thalamus, left temporal lobe, left cerebellar posterior lobe,and the bilateral occipital lobe. And the ReHo may be a potential reference in understanding the distinct brain activity in resting state of depression.

Evaluation of an extracellular matrix-derived acellular biphasic scaffold/cell construct in the repair of a large articular high-load-bearing osteochondral defect in a canine model.

Abstract: Background Osteochondral lesion repair is a challenging area of orthopedic surgery. Here we aimed to develop an extracellular matrix-derived, integrated, biphasic scaffold and to investigate the regeneration potential of the scaffold loaded with chondrogenically-induced bone marrow-derived mesenchymal stem cells (BMSCs) in the repair of a large, high-load-bearing, osteochondral defect in a canine model. Methods The biphasic scaffolds were fabricated by combining a decellularization procedure with a freeze-drying technique and characterized by scanning electron microscopy (SEM) and micro-computed tomography (micro-CT). Osteochondral constructs were fabricated in vitro using chondrogenically-induced BMSCs and a biphasic scaffold, then assessed by SEM for cell attachment. Osteochondral defects (4.2 mm (diameter) × 6 mm (depth)) were created in canine femoral condyles and treated with a construct of the biphasic scaffold/chondrogenically-induced BMSCs or with a cell-free scaffold (control group). The repaired defects were evaluated for gross morphology and by histological, biochemical, biomechanical and micro-CT analyses at 3 and 6 months post-implantation. Results The osteochondral defects of the experimental group showed better repair than those of the control group. Statistical analysis demonstrated that the macroscopic and histologic grading scores of the experimental group were always higher than those of the control group, and that the scores for the experimental group at 6 months were significantly higher than those at 3 months. The cartilage stiffness in the experimental group (6 months) was (6.95 ± 0.79) N/mm, 70.77% of normal cartilage; osteochondral bone stiffness in the experimental group was (158.16± 24.30) N/mm, 74.95% of normal tissue; glycosaminoglycan content of tissue-engineered neocartilage was (218 ± 21.6) µg/mg (dry weight), 84.82% of native cartilage. Micro-CT analysis of the subchondral bone showed mature trabecular bone regularly formed at 3 and 6 months, with no significant difference between the experimental and control groups. Conclusion The extracellular matrix-derived, integrated, biphasic scaffold shows potential for the repair of large, high-load-bearing osteochondral defects.

Association between non-alcoholic fatty liver disease and coronary artery disease severity.

Abstract: BACKGROUND Both non-alcoholic fatty liver disease (NAFLD) and coronary artery disease (CAD) are closely associated with many metabolic disorders. Invasive coronary angiography (CAG) is a common approach as an intervention for CAD. However, the association between angiographic severity of coronary artery and NAFLD remains controversial. This study aimed to evaluate the relationship between NAFLD and CAD. METHODS Totally 542 consecutive patients who planned to undergo CAG due to a suspected CAD were enrolled. Abdominal computed tomography (CT) was performed before angiography to detect NAFLD. CAD was defined as stenosis of at least 50% in at least one major coronary artery. The severity of CAD was assessed by the number of vessels affected and the vessel score multiplied by the severity score (Gensini score). Significant stenosis was defined as 70% or greater reduction in lumen diameter. A probability value of P < 0.05 was considered statistically significant. RESULTS Of 542 patients studied, 248 (45.8%) were found to have NAFLD by abdominal CT, and 382 patients (88%) were found to have significant CAD by CAG. Age, diabetes mellitus, waist circumference, body mass index, and obesity were associated with NAFLD. According to the results of Logistic regression analysis, the presence of NAFLD independently increased the risk for CAD, as seen in CAG (odds ratio (OR), 95% confidence interval (CI): 7.585 (4.617-12.461); P < 0.001). NAFLD was significantly more common in patients as CAD severity increased (P < 0.001). CONCLUSIONS The presence of NAFLD is associated with high severity of CAD, requiring that patients with abdominal obesity be also investigated for NAFLD. Patients with NAFLD should be closely followed up for the presence and severity of CAD.

Relationship between urinary cadmium and mortality in habitants of a cadmium-polluted area: a 22-year follow-up study in Japan.

Abstract: BACKGROUND Several studies have suggested that the exposure to cadmium (Cd) increased mortalities from renal diseases, cardiovascular diseases and malignant neoplasm, including lung cancer and prostate cancer among inhabitants living in Cd-polluted areas and factory workers. This study aimed to assess the influence of environmental exposure to Cd on long term outcome of inhabitants living in an area polluted by Cd. METHODS A 22-year follow-up study was conducted with 3119 inhabitants (1403 men and 1716 women) living in the Cd polluted Kakehashi River basin in Japan. The subjects were divided into 4 groups according to the amount of urinary Cd level (< 3.0 µg/g creatinine (Cr), 3.0 - 4.9 µg/g Cr, 5.0 - 9.9 µg/g Cr, and ≥ 10.0 µg/g Cr). Mortality was calculated by the person-years method. Hazards ratios (HR) and 95% confidence intervals (CI) were assessed by the Cox's proportional hazard model. RESULTS Compared with urinary Cd < 3.0 µg/g Cr group, the HR of 5.0 - 9.9 µg/g Cr and ≥ 10.0 µg/g Cr groups were significantly increased after adjustment for age in both sexes: 1.24 (95%CI 1.01 - 1.51) and 1.48 (95%CI 1.17 - 1.90) for men; 1.64 (95%CI 1.17 - 2.28) and 1.78 (95%CI 1.27 - 2.50) for women. The most frequent cause of death was malignant neoplasm in men and cardiovascular diseases in women. The significant increase in mortality risk for cardiovascular diseases was observed in the subjects with ≥ 10 µg/g Cr in both sexes: 1.79 for men (95%CI 1.02 - 3.12) and 2.38 for women (95%CI 1.11 - 5.07). When the subjects were divided into 2 categories (< 20 µg/g Cr and ≥ 20 µg/g Cr), the HR of the urinary Cd ≥ 20 µg/g Cr group for nephritis and nephrosis were 4.82 (95%CI 1.07 - 21.61) in men and 7.92 (95%CI 1.77 - 35.33) in women, respectively. The significant increase was not observed for malignant neoplasm. CONCLUSION These results suggest a dose-response relationship between Cd body burden and mortality for cardiovascular diseases, cerebrovascular diseases and nephritis and nephrosis.

Correlations of hypoxia-inducible factor-1α/hypoxia-inducible factor-2α expression with angiogenesis factors expression and prognosis in non-small cell lung cancer.

Abstract: Background Hypoxia-inducible factor (HIF) may play an important role in the process of tumorigenesis as well as tumor progression. The aim of this study was to compare the expression between HIF-1α and HIF-2α in tumor angiogenesis and the overall impact on patient prognosis in human non-small cell lung cancer (NSCLC). Methods In the current work we compared the immunohistochemical expression of HIF-1α and HIF-2α in surgical specimens of 140 patients with NSCLC in a tissue microarray study. Relationships between HIF-α expression and clinicopathological or angiogenic factors, including prognosis, were analyzed. Results High HIF-1α and HIF-2α expression was noted in 49/140 (35.0%) and in 64/140 (45.7%) of the cases, respectively. There was no direct correlation between HIF-1α and HIF-2α expression. Patients with advanced stage tumors had frequent high expression of HIF-2α (P = 0.007), and we also found a significant correlation between HIF-2α and T or N stage (P = 0.030 and 0.043, respectively). HIF-1α showed a marginal association with T stage (P = 0.084), which showed a higher expression in early stage tumors. A significant correlation (P = 0.045) was noticed between HIF-1α and vascular endothelial growth factor (VEGF) expression while the expression levels of thymidine phosphorylase (TP), cyclooxygenase (COX)-2 and microvessel density (MVD) were significantly higher in high HIF-2α tumors (P = 0.020, 0.004, and 0.046, respectively). In addition, univariate analysis of overall survival demonstrated that HIF-2α expression, but not HIF-1α, was related to poor outcome (P = 0.001) and it retained significant in multivariate analysis (P = 0.036). Conclusions Taken together, we conclude that HIF-1α and HIF-2α may differentially regulate the major angiogenic factors in different stages of the tumor process in NSCLC. HIF-2α may play a dominant role in tumor angiogenesis and appears to be of obvious value as a significant prognostic factor in NSCLC.

Autologous bone marrow stem cell transplantation for the treatment of type 2 diabetes mellitus.

Abstract: BACKGROUND Autologous peripheral stem cell transplantation was first reported in 2007 to treat type 1 diabetes mellitus (DM) and achieved encouraging effect, but whether similar outcome can be achieved in type 2 DM is not well demonstrated. The objective of this study was to determine the effect of combination of autologous bone marrow stem cell transplantation (BMT) and hyperbaric oxygen treatment on type 2 DM. METHODS The study involved 31 patients with type 2 DM (aged 33 to 62 years) from January 2009 to January 2011 in the Central Hospital of Wuhan, China. Clinical variables (body mass index, duration of DM, insulin requirement, oral hypoglycemic drugs, time free from insulin, time free from oral drugs) and laboratory variables (hemoglobin A1c (HbA1c)), mononuclear cells infused, and C-peptide in four time points) were assessed. Purified bone marrow stem cells were infused into major pancreatic arteries. Follow-up was performed at the 30, 90, 180, 360, 540 and 720 days (mean 321 days) after BMT. RESULTS Mean HbA1c values showed a significant reduction during follow-up in all patients after BMT. It decreased by more than 1.5% (from 8.7% to 7.1%) as quickly as at 30 days after BMT. Afterwards mean HbA1c fluctuated between plus or minus 0.5% until 24 months rather than declined continuously. At 90 days after the combined therapy C-peptide increased significantly compared with baseline (P 0.3). All patients had insulin and/or oral hypoglycemic drugs reduced to different levels. The dose of insulin of 7 patients (7/26, 27%) reduced for a period of time after BMT. CONCLUSIONS Combined therapy of intrapancreatic BMT and hyperbaric oxygen treatment can improve glucose control and reduce the dose of insulin and/or oral hypoglycemic drugs in type 2 DM patients, but it only improve pancreatic β-cell function transiently. Further randomized controlled clinical trials involved more patients will be required to confirm these findings and the mechanism needs to be illustrated deeply.

Effects of music therapy on depression and duration of hospital stay of breast cancer patients after radical mastectomy

Abstract: Background Breast cancer remains the most important cancer among women worldwide. The disease itself and treatment may have a profound impact on the patients' psychological well being and quality of life. Depression is common in breast cancer patients and affects the therapeutic effects as well as prolongs the duration of hospital stay. However, few studies reported the effectiveness of music therapy on depression and duration of hospital stay of female patients with breast cancer after radical mastectomy. Methods One hundred and twenty subjects were recruited to this clinical trial and randomly allocated to two groups. The experimental group (n=60) received music therapy on the basis of routine nursing care, whereas the control group (n=60) only received the routine nursing care. The whole intervention time was from the first day after radical mastectomy to the third time of admission to hospital for chemotherapy. Data of demographic characteristics and depression were collected by using the General Questionnaire and Chinese version of Zung Self-rating Depression Scale (ZSDS) respectively. One pre-test (the day before radical mastectomy) and three post-tests (the day before discharge from hospital, the second and third admission to hospital for chemotherapy) were utilized. Duration of hospital stay was calculated from the first day after radical mastectomy to the day of discharged from hospital. Results The mean depression score of all subjects was 37.19 +/- 6.30. Thirty-six cases (30%) suffered from depression symptoms, with 26 (72.2%) mild depression cases, 9 (25.0%) moderate depression cases, and 1 (2.8%) severe depression case. After music therapy, depression scores of the experimental group were lower than that of the control group in the three post-tests, with significant differences (F=39.13, P <0.001; F=82.09, P <0.001). Duration of hospital stay after radical mastectomy of the experimental group ((13.62 +/- 2.04) days) was shorter than that of the control group ((15.53 +/- 2.75) days) with significant difference (t=-4.34, P <0.001). Conclusions Music therapy has positive effects on improving depression of female patients with breast cancer, and duration of hospital stay after radical mastectomy can be reduced. It is worthy of applying music therapy as an alternative way of nursing intervention in clinical nursing process of caring female patients with breast cancer. Chin Med J2011;124(15):2321-2327

Bone marrow-derived mesenchymal stem cells protect rats from endotoxin-induced acute lung injury.

Abstract: BACKGROUND Acute lung injury (ALI) is a serious and common condition for which there are currently no specific strategies for treatment. Recent studies have suggested that bone marrow-derived multipotent mesenchymal stem cells (MSCs) may have therapeutic applications in multiple clinical disorders. We explored the biological effects of MSCs during endotoxin-induced ALI and the mechanisms involved. METHODS MSCs were isolated from male rat bone marrow and the ALI model was induced by intravenous endotoxin injection. Female rats were sacrificed at 6 hours, 24 hours, 4 days, 1 week and 3 weeks post-injection of MSCs or saline and the lung tissue, bronchoalveolar lavage fluid, and serum were harvested for analysis. We further evaluated the survival of the rats and examined the effects of endotoxin-induced injury on the interaction between alveolar macrophages (AMs) and MSCs in ex vivo. RESULTS There was a significant decrease in numbers of neutrophils in bronchoalveolar lavage fluid (P < 0.05), and myeloperoxidase activity in the lung (P < 0.01), and of TNF-α and IL-1β in serum (P < 0.05) in the MSC treated rats at 4 days. Furthermore, MSC treated rats exhibited improved survival, lower lung injury score, higher concentration of IL-10 in the serum and a reduced hydroxyproline content, but these differences were not statistically significant. Moreover, co-cultures of MSCs and AMs had significantly reduced levels of TNF-α, IL-1β and macrophage inflammatory protein (MIP)-1α and significantly increased levels of IL-10 (P < 0.05) in the culture supernatants. CONCLUSIONS Treatment with intravenous injection of bone marrow-derived MSCs have beneficial effects on endotoxin-induced ALI in rats. The beneficial effect might be achieved through the engraftment of differentiated MSCs in the lungs and appears derive more from their capacity to secrete soluble factors that modulate immune responses.

A serum metabonomic study on the difference between alcohol- and HBV-induced liver cirrhosis by ultraperformance liquid chromatography coupled to mass spectrometry plus quadrupole time-of-flight mass spectrometry

Abstract: Background Liver cirrhosis is the fatal consequence of chronic hepatitis, making early diagnosis of liver cirrhosis critical. Liver biopsy is still the standard diagnostic method for liver cirrhosis, although its use in a broad population with alcoholism or hepatitis B virus (HBV) infection remains difficult. In this study, we used a metabonomic approach to detect potential biomarkers for early diagnosis of liver cirrhosis. Methods Serum specimens were collected prospectively from normal control subjects (n = 22) and patients with alcoholic cirrhosis (n = 18) or HBV-induced cirrhosis (n = 19). The serum metabonome was analyzed using ultraperformance liquid chromatography (LC)/time-of-flight mass spectrometry (MS) integrated with chemometrics. The acquired LC-MS data were normalized and processed using principal component analysis (PCA) and partial least squares discrimination analysis (PLS-DA). Results Significant differences in the metabonomics among the three groups were observed. Lysophosphatidyl cholines (LPCs) (LPC C16:0, LPC C18:0, LPC C18:2, LPC C18:3, LPC C20:3, LPC C20:5) were decreased in the serum of patients with hepatic cirrhosis, whereas bile acids (glycocholic acid, glycochenodeoxycholic acid), hypoxanthine, and stearamide were increased in the serum of patients with hepatic cirrhosis. These metabolites are considered "common" biomarkers for hepatic cirrhosis. Oleamide and myristamide were increased in the serum of patients with alcoholic cirrhosis but decreased in those with HBV-induced cirrhosis. These could be specific biomarkers for differential diagnosis between alcohol- and HBV-induced hepatic cirrhosis. Conclusions There are significant metabonomic differences between alcohol- and HBV-induced liver cirrhosis. Metabonomics is a top-down systems biology tool for conducting research on clinical problems.

Polymorphisms of GSTP1 is associated with differences of chemotherapy response and toxicity in breast cancer.

Abstract: BACKGROUND Although chemotherapy is one of the most important treatments of breast cancer, it is limited by significant inter-individual variations in response and toxicity. The metabolism of epirubicin (EPI) and cyclophosphamide (CTX) is mainly mediated by cytochrome P450s (CYPs) and glutathione S-transferases (GSTs). It has been well-known that the activities of these enzymes are polymorphic in population due to their genetic polymorphisms. The aim of this research was to examine the effects of genetic polymorphisms in CYP3A, GSTP1 and MDR1 genes on treatment response and side-effects of breast cancer patients receiving EPI/CTX chemotherapy. METHODS One hundred and twenty patients with stage II or III invasive breast cancer were recruited and treated with three to four cycles of EPI 80 mg/m(2) and CTX 600 mg/m(2) every two weeks. The AJCC TNM staging system (sixth edition) was used to evaluate the pathological response of primary tumor and axillary lymph nodes. The genotypes of gene polymorphisms were determined by using PCR-restriction fragment length polymorphism methods. RESULTS Patients carrying GSTP1 (105)Ile/Val or (105)Ile/Ile genotype were more likely to have good response (OR, 0.40; 95%CI, 0.16 - 0.96; P = 0.024) and light toxicity (OR, 0.35; 95%CI, 0.13 - 0.78; P = 0.006) than those carrying (105)Val/Val genotypes. The response to the treatment was not correlated with estrogen receptor, progesterone receptor and Her2/neu status of tumors. No correlation was found between toxicity effect and patient's age, tumor staging, menopause status, and dose intensity of the drugs. CONCLUSION GSTP1 polymorphism was associated with the chemotherapy response or adverse effects of EPI and CTX regimens.

Prevalence estimates for primary brain tumors in China: a multi-center cross-sectional study.

Abstract: BACKGROUND Although the first leading cause of death in China was malignant neoplasms (mortality, 374.1 per 100,000 person-years), the full impact of primary brain tumors (PBT) on the healthcare system is not completely described because there are a few well documented reports about the epidemiologic features of brain tumors. This study aimed to report a comprehensive assessment on the prevalence of PBT. METHODS A multicenter cross-sectional study on brain tumor (MCSBT) in China was initiated in five regional centers: Daqing (northeast), Puyang (north of China), Shiyan (center of China), Ma'anshan (center of China) and Shanghai (southeast). Prevalence rate was calculated by counting the number of people living with a PBT between October 1, 2005 and September 30, 2006 and dividing by the total population of the five communities at January 1, 2006. Estimates of prevalence were expressed as percentages and grouped according to gender and to age in fifteen-year categories. Within these strata, the rates were estimated with 95% confidence intervals (CI) using the accurate calculation of CI for Poisson distribution. A chi-square test was used to compare the various frequencies with α < 0.05. Age-standardized prevalence with the direct method was calculated with the ten-year age-specific prevalence and the age distribution of the Chinese population in 2010, obtained from World population prospects: the 2008 revision. RESULTS We estimated that the overall prevalence of PBT was 24.56 per 100,000 (95%CI, 14.85 to 34.27), and the overall prevalence of PBT in female population (30.57 per 100,000 and its 95%CI ranged from 19.73 to 41.41) was higher than that in male population (18.84 per 100,000 and its 95%CI ranged from 10.33 to 27.35). However, the discrepancy between genders was not statistically significant because the 95%CI overlapped. Of 272 cases of newly diagnosed PBT, the proportion of histological subtypes by age groups, gender was statistically different (χ(2) = 52.6510, P < 0.0001). More than half of all reported tumors (52.57%) were either gliomas or meningiomas. For the youngest (aged from 0 - 19) strata of the population, glioma appeared to occur more than other subtypes, accounting for 55.56% of all of cases. The majority of brain tumors presented in those aged from 20 to 59 years was pituitary adenomas (45.12%) and gliomas (31.10%). Opposed to brain tumors in adults and teenage, gliomas only accounted for 22.22%. Meanwhile, the median ages at diagnosis of the patients with PBT were similar between males and females except for pituitary adenomas (male: 59 years old; female: 45 years old). CONCLUSIONS Age standardized prevalence of PBT is 22.52 per 100,000 (95%CI, 13.22 to 31.82) for all populations, 17.64 per 100,000 (95%CI, 9.41 to 25.87) for men, and 27.94 per 100,000 (95%CI, 17.58 to 38.30) for women. Age standardization to China's 2010 population yielded an estimated population of 304 954 cases with PBT. Our prevalence estimates provide a conservative basis on which to plan health care services and to develop programmatic strategies for surviving. In the future, it would be helpful to have long-term observed survival rates that would make the assumptions and the resulting imprecision in the current estimates unnecessary.

Resveratrol-induced augmentation of telomerase activity delays senescence of endothelial progenitor cells.

Abstract: Background Previous studies have shown that resveratrol increases endothelial progenitor cell (EPC) numbers and functional activity. Increased EPC numbers and activity are associated with the inhibition of EPC senescence. In this study, we investigated the effect of resveratrol on the senescence of EPCs, leading to potentiation of cellular function. Methods EPCs were isolated from human peripheral blood and identified immunocytochemically. EPCs were incubated with resveratrol (1, 10, and 50 μmol/L) or control for specified times. After in vitro cultivation, acidic β-galactosidase staining revealed the extent of senescence in the cells. To gain further insight into the underlying mechanism of the effect of resveratrol, we measured telomerase activity using a polymerase chain reaction (PCR)-enzyme-linked immunosorbent assay (ELISA) technique. Furthermore, we measured the expression of human telomerase reverse transcriptase (hTERT) and the phosphorylation of Akt by immunoblotting. Results Resveratrol dose-dependently inhibited the onset of EPC senescence in culture. Resveratrol also significantly increased telomerase activity. Interestingly, quantitative real-time PCR analysis demonstrated that resveratrol dose-dependently increased the expression of the catalytic subunit, hTERT, an effect that was significantly inhibited by pharmacological phosphatidylinositol 3-kinase (PI3-K) blockers (wortmannin). The expression of hTERT is regulated by the PI3-K/Akt pathway; therefore, we examined the effect of resveratrol on Akt activity in EPCs. Immunoblotting analysis revealed that resveratrol led to dose-dependent phosphorylation and activation of Akt in EPCs. Conclusion Resveratrol delayed EPCs senescence in vitro, which may be dependent on telomerase activation. Chin Med J 2011;124(24):4310-4315

Resveratrol induces apoptosis in pancreatic cancer cells.

Abstract: Background Pancreatic cancer is one of the most lethal human cancers with a very low survival rate of 5 years. Conventional cancer treatments including surgery, radiation, chemotherapy or combinations of these show little effect on this disease. Several proteins have been proved critical to the development and the progression of pancreatic cancer. The aim of this study was to investigate the effect of resveratrol on apoptosis in pancreatic cancer cells. Methods Several pancreatic cancer cell lines were screened by resveratrol, and its toxicity was tested by normal pancreatic cells. Western blotting was then performed to analyze the molecular mechanism of resveratrol induced apoptosis of pancreatic cancer cell lines. Results In the screened pancreatic cancer cell lines, capan-2 and colo357 showed high sensitivity to resveratrol induced apoptosis. Resveratrol exhibited insignificant toxicity to normal pancreatic cells. In resveratrol sensitive cells, capan-2 and colo357, the activation of caspase-3 was detected and showed significant caspase-3 activation upon resveratrol treatment; p53 and p21 were also detected up-regulated upon resveratrol treatment. Conclusion Resveratrol provides a promising anti-tumor strategy to fight against pancreatic cancer.

HIWI expression profile in cancer cells and its prognostic value for patients with colorectal cancer

Abstract: Background HIWI is a member of PIWI gene family and its expression is found in various tumors, indicating that it may play a pivotal role in tumor development. This study was designated to examine HIWI protein expression profile in several cancer cell lines and its prognostic value for patients with colorectal cancer. Methods Totally 270 patients who underwent surgical resection of primary colorectal cancer between January 1999 and December 2002 with a median follow-up time of 33 months were registered in the study. Formalin-fixed and paraffin-embedded specimens from these patients and 236 matched adjacent non-cancerous normal colorectal tissues were collected. Anti-HIWI monoclonal antibodies were generated and used for evaluating HIWI protein expression. χ(2) tests were conducted to determine the association between HIWI expression and the other variables. Survival curves were estimated using the Kaplan-Meier method and compared by the log-rank test. Multivariate analysis was performed by using the Cox regression model. Results By generating antibodies specific for HIWI, we examined HIWI protein expression in several cancer cell lines and demonstrated positive expression of HIWI in 69 out of 270 (25.6%) colorectal cancer tissues; 15 of 236 (6.4%) matched adjacent non-cancerous tissues were also positive for HIWI. Patients with positive HIWI expression in adjacent non-cancerous tissue had statistically lower overall survival (OS) and disease free survival (DFS) compared with negative patients (OS: 10.4% vs. 55.5%, P = 0.009; DFS: 10.4% vs. 55.1%, P = 0.015). For early stage group (stages I and II), patients with positive HIWI expression had significantly lower OS and DFS (OS: 57.4% vs. 79.5%, P = 0.014; DFS: 56.7% vs. 80.5%, P = 0.010). In lymph node negative group, patients with positive HIWI expression had statistically lower OS and DFS (OS: 53.0% vs. 73.5%, P = 0.037; DFS: 52.2% vs. 74.6%, P = 0.025). Multivariate analysis revealed that HIWI over-expression was a significant prognostic factor for OS (95%CI: 1.132 - 2.479, P = 0.010). Conclusion HIWI could be a potential prognostic biomarker for the patients with colorectal cancer, especially for those at early stages or without lymph node metastasis.

Chemoresistance of CD133+ cancer stem cells in laryngeal carcinoma.

Abstract: Background Mounting evidence suggests that tumors are histologically heterogeneous and are maintained by a small population of tumor cells termed cancer stem cells. CD133 has been identified as a candidate marker of cancer stem cells in laryngeal carcinoma. This study aimed to analyze the chemoresistance of CD133(+) cancer stem cells. Methods The response of Hep-2 cells to different chemotherapeutic agents was investigated and the expression of CD133 was studied. Fluorescence-activated cell sorting analysis was used to identify CD133, and the CD133(+) subset of cells was separated and analyzed in colony formation assays, cell invasion assays, chemotherapy resistance studies, and analyzed for the expression of the drug resistance gene ABCG2. Results About 1% - 2% of Hep-2 cells were CD133(+) cells, and the CD133(+) proportion was enriched by chemotherapy. CD133(+) cancer stem cells exhibited higher potential for clonogenicity and invasion, and were more resistant to chemotherapy. This resistance was correlated with higher expression of ABCG2. Conclusions This study suggested that CD133(+) cancer stem cells are more resistant to chemotherapy. The expression of ABCG2 could be partially responsible for this. Targeting this small population of CD133(+) cancer stem cells could be a strategy to develop more effective treatments for laryngeal carcinoma.

A molecular survey on cystic echinococcosis in Sinnar area, Blue Nile state (Sudan).

Abstract: Background Cystic echinococcosis (CE) is a zoonosis caused by the cestodes of the Echinococcus species. Its life cycle involves dogs and other canids as definitive hosts for the intestinal tapeworm, as well as domestic and wild ungulates as intermediate hosts for the tissue-invading metacestode (larval) stage. The disease has a special impact on disadvantaged pastoralist communities and is listed now among the three top priority neglected tropical disease (NTD). Therefore, CE is a neglected disease even in high endemicity regions. This study aimed at investigation of the prevalence of CE in different animals slaughtered for food consumption in Sinnar area, Blue Nile states in Sudan. Methods A survey of CE in livestock was conducted from April 2009 to March 2011 in Sinnar area, Blue Nile state in Sudan. Location, parasitological status and fertility conditions were determined. In addition, 120 hydatid cysts (30 from camels, 62 from cattle and 28 from sheep) were examined by polymerase chain reaction (PCR) and mitochondrial gene sequencing for the genetic allocation of Echinococcus strains or species Results The prevalence of CE was 29.7% (30/101) in camels, 2.7% (62/2310) in cattle and 0.6% (26/4378) in sheep. It was shown that infection rates increased with age in camels, cattle and sheep. In camels, 67% (20/30) of the infected animals were aged between 2–5 years whereas 58% (36/62) of the infected cattle were >5 years. In sheep, the prevalence rate was distributed equally between animals ranging 2–5 years and >5 years. Even though multiple cysts were found in some animals, the average number of cysts per animal was close to 1 in all examined species. Lungs were found to be the predilection sites for the parasite in both camels and cattle, while most of the cysts found in sheep were located in the liver. About 63.4% of cysts encountered in camels were considered as large (5–7 cm), whereas those in cattle and sheep were medium (2–4 cm) and small (<2 cm) respectively. The highest fertility rate was found in camel cysts with 85.4% (35/41) followed by cattle (50.0%, 32/64) and sheep (39.0%, 11/28). All examined cysts belonged to Echinococcus canadensis G6, which was confirmed to be the overwhelmingly predominant species in that area. Conclusion The epidemiological situation in Sinnar area, Blue Nile state is characterized by intense transmission of Echinococcus canadensis G6, thereby closely resembling the situation in most other regions of Sudan. Chin Med J 2011;124(18):2829-2833 chinococcosis is a cosmopolitan zoonosis caused by the adult or larval stages of cestodes belonging to the genus Echinococcus (family Taeniidae). Larval infection (hydatid disease, hydatidosis) is characterized by long-term growth of metacestode (hydatid) cysts in the intermediate host. Hydatid cysts develop in internal organs (mainly liver and lung) of humans and

A historical view of alveolar echinococcosis, 160 years after the discovery of the first case in humans: part 1. What have we learnt on the distribution of the disease and on its parasitic agent?

Abstract: Since the first 2 cases observed in southern Germany and the correct identification of a parasite at the origin of the disease by the famous scientist Rudolf Virchow in 1855, the borders of the endemic area of alveolar echinococcosis (AE) have never stopped to expand. The parasite was successively recognized in Switzerland, then in Russia, Austria and France which were long considered as the only endemic areas for the disease. Cases were disclosed in Turkey in 1939; then much attention was paid to Alaska and to Hokkaido, in Japan. The situation totally changed in 1991 after the recognition of the Chinese endemic areas by the international community of scientists. The world map was completed in the beginning of the 21st century by the identification of AE in most of the countries of central/eastern Europe and Baltic States, and by the recognition of cases in central Asia. Up to now, the disease has however never been reported in the South hemisphere and in the United Kingdom. In the mid-1950s, demonstration by Rausch and Schiller in Alaska, and by Vogel in Germany, of the distinction between 2 parasite species responsible respectively for cystic echinococcosis (“hydatid disease”) and AE put an end to the long-lasting debate between the "dualists", who believed in that theory which eventually proved to be true, and the "unicists", who believed in a single species responsible for both diseases. At the end of the 20th century, molecular biology fully confirmed the "dualist" theory while adding several new species to the initially described E. granulosus; within the past decade, it also confirmed that little variation existed within Echinococcus (E.) multilocularis species, and that AE-looking infection in some intermediate animal hosts on the Tibetan plateau was indeed due to a new species, distinct from E. multilocularis, named E. shiquicus. Since the 1970s, the unique ecological interactions between the landscape, the hosts, and E. multilocularis have progressively been delineated. The important role of the rodent/lagomorph reservoir size for the maintenance of the parasite cycle has been recognized within the last 2 decades of the 20th century. And the discovery of a close relationship between high densities of small mammals and particularities in land use by agriculture/forestry has stressed the responsibility of political/economic decisions on the contamination pressure. Urbanization of foxes in Europe and Japan and the major role of dogs in China represent the new deals at the beginning of the 21st century regarding definitive hosts and prevention measures.

Ex vivo liver resection followed by autotransplantation for end-stage hepatic alveolar echinococcosis.

Abstract: Background For patients with end-stage hepatic alveolar echinococcosis (AE), in vivo resection of the involved parts of the liver is usually very difficult, therefore, allogenic liver transplantation is indicated. However, we hypothesize that for selected patents, ex vivo liver resection for thorough elimination of the involved tissues and liver autotransplantation may offer a chance for clinical cure. Methods We presented a 24-year-old women with a giant hepatic AE lesion who was treated with hepatectomy, ex vivo resection of the involved tissue and hepatic autotransplantation. The patient had moderate jaundice and advanced hepatic AE lesion which involved segments I, IV, V, VI, VII, VIII and retrohepatic inferior vena cava. The lateral segments (II and III) of the left liver remained normal with over 1000 ml in its volume. No extrahepatic metastases (such as to the lung or brain) could be found. As the first step of treatment, X-ray guided percutaneous transhepatic cholangiodrainage (PTCD) was performed twice for bile drainage in segment III and II separately until her serum total bilirubin decreased gradually from 236 to 88 µmol/L. Total liver resection was then performed, followed by extended right hepatic trisegmentectomy and the entire retrohepatic vena cava was surgically removed en bloc while her hemodynamics parameters were stable. Neither veino-veinous bypass nor temporary intracorporeal cavo-caval or porto-caval shunt was used during the 5.7-hour anhepatic phase. The remained AE-free lateral segments of the left liver were re-implanted in situ. The left hepatic vein was directly anastomosed end-to-end to the suprahepatic inferior vena cava due to the lack of the retrohepatic inferior vena cava with AE total infiltration. Because compensatory retroperitoneal porto-caval collateral circulation developed, we enclosed remained infrahepatic inferior vena cava at renal vein level without any haemodynamics problems. Results During a 60-day following-up after operation, the patient had a good recovery except for a mildly elevated serum total bilirubin. Conclusions As a radical approach, ex vivo liver resection and liver autotransplantation in a case has shown a optimal potential for treatment of the end-stage hepatic AE. Strict compliance with its indications, evaluation of vessels of patients pre-operatively, and precise surgical techniques are the keys to improve the prognosis of patients.

Fasudil inhibits platelet-derived growth factor-induced human pulmonary artery smooth muscle cell proliferation by up-regulation of p27kip¹ via the ERK signal pathway.

Abstract: BACKGROUND RhoA/Rho kinase (ROCK) pathway is involved in pulmonary arterial hypertension (PAH) and pulmonary artery smooth muscle cell (PASMC) proliferation. Inhibition of ROCK has been proposed as a treatment for PAH. But the mechanism of RhoA/ROCK pathway and its downstream signaling in proliferation of human PASMCs is unclear. We investigated the effect of fasudil, a selective ROCK inhibitor, on platelet-derived growth factor (PDGF) induced human PASMC proliferation, and the possible association between RhoA/ROCK and extracellular signal-regulated kinase (ERK), p27(Kip1). METHODS Human PASMCs were cultured with the stimulation of 10 ng/ml PDGF, and different concentrations of fasudil were added before the addition of mitogen. Cell viability and cell cycle were determined with MTT and flow cytometry respectively. ROCK activity, ERK activity and protein expression of proliferating cell nuclear angigen (PCNA) and p27(Kip1) were measured by immunoblotting. RESULTS By MTT assay, PDGF significantly increased the OD value that represented human PASMC proliferation, and pretreatment with fasudil significantly reversed this effect in a dose-dependent manner. After PDGF stimulation, the percentage of cells in S phase increased dramatically from 15.6% to 24.3%, while the percentage in G(0)/G(1) phase was reduced from 80.6% to 59%. And pretreatment with fasudil reversed the cell cycle effect of PDGF significantly in a dose-dependent manner. PDGF markedly induced ROCK activity and ERK activity with a peak at 15 minutes, which were significantly inhibited by fasudil. In addition, fasudil significantly inhibited PDGF-induced PCNA expression and fasudil also upregulated p27(Kip1) expression in human PASMCs, which decreased after PDGF stimulation. CONCLUSION RhoA/ROCK is vital for PDFG-induced human PASMC proliferation, and fasudil effectively inhibited PDGF-induced human PASMC proliferation by up-regulation of p27(Kip1), which may be associated with inhibition of ERK activity.

Endovascular treatment of iliac vein compression syndrome.

Abstract: Background Iliac vein compression syndrome (IVCS), the symptomatic compression of the left common iliac vein between the right common iliac artery and the vertebrae, is not an uncommon condition. The aim of this research was to retrospectively evaluate long-term outcome and the significance of endovascular treatment in patients with left IVCS. Methods Between January 1997 and September 2008, 296 patients received interventional therapy in the left common iliac vein. In the second stage, 170 cases underwent saphenous vein high ligation and stripping. Two hundred and thirty-one cases were followed up over a period of 6 to 120 months (average 46 months) and evaluated for symptom improvement with color ultrasound and ascending venography. Results The stenotic or occlusive segments of the left iliac vein were successfully dilated in 285 cases, of whom 272 received stent implantation therapy. Most of the patients achieved satisfactory results on discharge. During the follow-up period, varicose veins were alleviated in 98.7% of the patients, and leg swelling disappeared or was obviously relieved in 84% of cases. About 85% of leg ulcers completely healed. The total patency rate was 91.7% as evaluated with color ultrasound and 91.5% with ascending venography. Conclusions Endovascular treatment of IVCS provides effective symptomatic improvement and good long-term patency in most patients.

Cosmetic outcome and surgical site infection rates of antibacterial absorbable (Polyglactin 910) suture compared to Chinese silk suture in breast cancer surgery: a randomized pilot research.

Abstract: BACKGROUND The primary objective of this multicenter post-market study was to compare the cosmetic outcome of triclosan-coated VICRYL Plus sutures with Chinese silk sutures for skin closure of modified radical mastectomy. A secondary objective was to assess the incidence of surgical site infection (SSI). METHODS Patients undergoing modified radical mastectomy were randomly assigned to coated VICRYL Plus antibacterial (Polyglactin 910) suture or Chinese silk suture. Cosmetic outcomes were evaluated postoperatively at days 12 (± 2) and 30 (± 5), and the evidence of SSI was assessed at days 3, 5, 7, 12 (± 2), 30 (± 5), and 90 (± 7). Cosmetic outcomes were independently assessed via visual analogue scale (VAS) score evaluations of blinded incision photographs (primary endpoint) and surgeon-assessed modified Hollander Scale (mHCS) scores (secondary endpoint). SSI assessments used both CDC criteria and ASEPSIS scores. RESULTS Six Chinese hospitals randomized 101 women undergoing modified radical mastectomy to closure with coated VICRYL Plus suture (n = 51) or Chinese silk suture (n = 50). Mean VAS cosmetic outcome scores for antibacterial suture (67.2) were better than for Chinese silk (45.4) at day 30 (P < 0.0001)). Mean mHCS cosmetic outcome total scores, were also higher for antibacterial suture (5.7) than for Chinese silk (5.0) at day 30 (P = 0.002). CONCLUSIONS Patients using coated VICRYL Plus suture had significantly better cosmetic outcomes than those with Chinese silk sutures. Patients using coated VICRYL Plus suture had a lower SSI incidence compared to the Chinese silk sutures, although the difference did not reach statistical significance.

Human dental pulp stem cell is a promising autologous seed cell for bone tissue engineering.

Abstract: Background The seed cell is a core problem in bone tissue engineering research. Recent research indicates that human dental pulp stem cells (hDPSCs) can differentiate into osteoblasts in vitro, which suggests that they may become a new kind of seed cells for bone tissue engineering. The aim of this study was to evaluate the osteogenic differentiation of hDPSCs in vitro and bone-like tissue formation when transplanted with three-dimensional gelatin scaffolds in vivo, and hDPSCs may become appropriate seed cells for bone tissue engineering. Methods We have utilized enzymatic digestion to obtain hDPSCs from dental pulp tissue extracted during orthodontic treatment. After culturing and expansion to three passages, the cells were seeded in 6-well plates or on three-dimensional gelatin scaffolds and cultured in osteogenic medium. After 14 days in culture, the three-dimensional gelatin scaffolds were implanted subcutaneously in nude mice for 4 weeks. In 6-well plate culture, osteogenesis was assessed by alkaline phosphatase staining, Von Kossa staining, and reverse transcription-polymerase chain reaction (RT-PCR) analysis of the osteogenesis-specific genes type I collagen (COL I), bone sialoprotein (BSP), osteocalcin (OCN), RUNX2, and osterix (OSX). In three-dimensional gelatin scaffold culture, X-rays, hematoxylin/eosin staining, and immunohistochemical staining were used to examine bone formation. Results In vitro studies revealed that hDPSCs do possess osteogenic differentiation potential. In vivo studies revealed that hDPSCs seeded on gelatin scaffolds can form bone structures in heterotopic sites of nude mice. Conclusions These findings suggested that hDPSCs may be valuable as seed cells for bone tissue engineering. As a special stem cell source, hDPSCs may blaze a new path for bone tissue engineering.

Phase I trial of icotinib, a novel epidermal growth factor receptor tyrosine kinase inhibitor, in Chinese patients with non-small cell lung cancer.

Abstract: Background The preclinical experiments and studies of congener drugs show icotinib, a new epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, can specifically bind to the tyrosine kinase domain of the EGFR, block the EGFR related signal, thereby inhibit the growth of tumor cell. The objective of this study was to investigate the safety, tolerability and dose-related biologic effects of icotinib in patients with non-small cell lung cancer (NSCLC) in a Chinese patient population. Methods This was an open-label, phase I, dose escalation, safety/tolerability trial of oral icotinib (100 to 400 mg), administered twice per day for 28-continuous-day cycles until disease progression or undue toxicity. Results Forty patients with stage IIIB (15%) or IV (85%) NSCLC were included in the study. They had mainly adenocarcinoma (85%), with a performance status (PS) of 0 (45%) or 1 (55%) and less than half the patients (45%) had histories of smoking and all were pretreated by at least one regimen of chemotherapy. Patients were assigned to three dose levels of 150 mg b.i.d, 200 mg b.i.d, or 125 mg t.i.d. The follow-up periods ranged from 5 to 80 weeks. Adverse events were found in 35% patients, most of which were mild and reversible. The adverse events mainly occurred in the first 4 weeks and included rash (25%), diarrhea, nausea and abdominal distention. One definite interstitial lung disease (ILD) was found in a patient in the dose of 200 mg b.i.d. According to an 8-week assessment, one (2.5%) patient receiving 150 mg gained complete response (CR) that persisted for 44 weeks, seven (17.50%) patients had partial remission (PR), and 18 (45%) patients had stable disease (SD). The objective response including CR + PR was 20%. The median time of progression-free survival for the 40 patients was 20 weeks (range: 12 to 32 weeks). The response was not affected by pathological type, history of smoking, or numbers of previous therapeutic regimens. No relationship between dose, response, adverse effect, or duration of the study was observed. Conclusions Icotinib, given as oral twice daily, showed favorable safety and tolerability. Mild and reversible rash, diarrhea, and nausea were the main adverse events. Antitumor activity was obvious at each dose in heavily pretreated patients. Pharmacodynamic evaluations and further phase II/III trials are in progress.