Significance of circulating tumor cell monitoring in targeted therapy for gastrointestinal stromal tumors / 中华胃肠外科杂志

Objective: To explore the significance of circulating tumor cell (CTC) monitoring in evaluating the efficacy of targeted therapy for gastrointestinal stromal tumor (GIST). Methods: A prospective cohort study was performed. The data of patients with locally advanced GIST or liver metastasis who were admitted to The Affiliated Hospital of Nantong University from August 2013 to December 2018 were collected. Inclusion criteria: (1) patients aged older than 18 years; (2) patients who were diagnosed with GIST based on pathology; (3) patients without surgery, whose preoperative imaging evaluation of GIST found the violations of the surrounding organs or partial transfer of an estimated difficulty to achieve R0 resection, or the maximum diameter of the tumor > 10 cm, or the liver metastasis, or the expectation of higher risk of surgical complications; (4) patients who were treated with the imatinib 400 mg/d for the first time; (5) Eastern Cooperative Oncology Group (ECOG) score of 0-2. Exclusion criteria: (1) genetic testing revealed a D842V mutation in exon 18 of the PDGFRA gene; (2) alanine aminotransferase and/or aspartate aminotransferase > 2.5 times the normal upper limit; (3) serum total bilirubin >1.5 times of normal upper limit; (4) neutrophil count < 1.5×10(9)/L, or platelet count < 75×10(9)/L, or hemoglobin < 60 g/L; (5) creatinine > normal upper limit; (6) patients had serious cardiovascular and cerebrovascular diseases within 12 months before enrollment; (7) female patients were pregnant or lactating; (8) patients suffered from other serious acute and chronic physical or mental problems, and were not suitable for participating in this study judged by researchers. The patients who could not tolerate treatment regimen, or developed serious adverse reactions and did not follow the medication scheme after enrollment were excluded. Before imatinib treatment and 1-month and 2-month after treatment, quantitative PCR was used to detect the DOG-1 expression of monocytes in peripheral blood, and the ratio of DOG-1/β-actin > 3×10(-5) was used as the CTC positive threshold of GIST. The positive rate of CTC, the efficacy of imatinib treatment (complete response, partial response, stable disease, progressive disease, and occurrence of adverse reactions), and the relationship between CTC positive rate and clinicopathological characteristics of patients were analyzed. Furthermore, the ratio of DOG-1 decrease/baseline DOG-1 after 1-month of treatment was used as an indicator to evaluate whether targeted therapy was effective. The receiver operating characteristic (ROC) curve was rendered, and the area under the curve (AUC) was calculated. Results: A total of 68 GIST patients were enrolled in this study, including 39 cases of locally advanced GIST and 29 cases with liver metastases, 32 males and 36 females with the mean age of (51.2±11.8) (range 31 to 74) years. After 2-month of imatinib treatment, 43 cases were evaluated as partial response, 11 cases as stable disease, and 14 cases as progressive disease, with an effective rate of 79.4% (54/68). During the treatment of imatinib, the incidence of grade 3 or higher adverse reactions was 22.1% (15/68), including 12 cases of grade 3 neutropenia and 3 of grade 4 drug eruption, which were all relieved after conservative treatment. The positive rates of CTC in 68 patients before treatment, 1-month and 2-month after treatment were 66.2% (45/68), 41.2% (28/68) and 23.5% (16/68), respectively. The positive rate of CTC was associated with tumor size, liver metastasis, mitotic count and risk level (all P<0.05). By analyzing the effective group and the ineffective group of targeted therapy, it was found that the positive rate of CTC in the effective group showed a decreasing trend, while the positive rate of CTC in the ineffective group showed an increasing trend. The AUC of predicting the efficacy of targeted therapy for GIST was 0.823 by detecting the change trend of CTC 1-month after treatment (P<0.001). When the DOG-1 content decreased by more than 57.5% 1-month after treatment, it can be used as an indicator to judge the effectiveness of the treatment, whose sensitivity was 72.2% and specificity was 100%. Conclusion: The detection of peripheral blood CTC can evaluate the efficacy of targeted therapy in GIST patients and can provide decision-making basis for further clinical treatment.

Explore Ying and Wei Regulating Therapy on Diabetic Peripheral Neuropathy from Perspective of Neural Microenvironment / 中国实验方剂学杂志

A good neural microenvironment is an important basis for improving the damaged nerves and promoting axonal repair and regeneration. The destruction of neural microenvironment， closely related to the lack of neurotrophic factors， microcirculation disorders and immune abnormalities， is the key pathogenesis leading to diabetic peripheral neuropathy （DPN）. In traditional Chinese medicine， disharmony between Ying and Wei is considered as the key pathology in the development of DPN. It may be manifested as Ying and Wei deficiency， or Ying and Wei impassability， or Ying， Wei， Qi and blood intersection disorders， all of which may cause body fluid condensed into phlegm， blood into blood stasis， further leading to the mutual knot of phlegm and blood stasis， meridian obstruction， numbness and pain of limbs. "Regulating Ying and Wei and tonifying spleen and stomach" is the main therapeutic idea to promote intersection between Ying and Wei and unblock Qi and blood. The method has a significant effect on DPN. However， the current studies on the mechanism of regulating Ying and Wei in the treatment of DPN are still in lack of in-depth discussion， and the studies are mostly limited to the microcirculation disorders. Numerous studies have confirmed that the courses and distribution， physiological characteristics， functions of Ying and Wei are closely related to nerve， immune， metabolic substances and microcirculation. Based on the modern medicine essence of Ying and Wei， the author thinks that the discussion on connotation of the Ying and Wei from the perspective of neural microenvironment has a scientific basis， and regulating Ying and Wei is not only inherited from the traditional Chinese medicine theory， but also conforms to the modern understanding on DPN pathogenesis and treatment. Regulating Ying and Wei and smoothing middle-jiao can improve neural microenvironment and give play to the role of restoring damaged nerve， and its mechanism may be related to regulating neurotrophic factors， immune active substances， metabolites， and microcirculation dysfunction.

Long-Term Retrospective Analysis of Prognostic Factors in Patients with Newly Diagnosed Multiple Myeloma without Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To retrospectively analyze the cases of multiple myeloma treated with chemotherapeatic regimens based on thalidomide, and to investigate the factors affecting MM patients treated using chemotherapeutic regimens with or without bortezomib.@*METHODS@#The clinical, laboratorial and survival data of 200 patients with newly diagnosed MM from October 2007 to December 2015 were collected, and the correlation of clinical and laboratorial indicators with the clinical characteristics and prognosis of MM patients was analyzed by using χ test, COX regression analysis, Kaplan-Meier method and Log-rank test.@*RESULTS@#Multivariable analysis showed that age (≥65 years old), ISS staging (Ⅲ), complex karyotypes and no-complete remission were the independent prognostic factors for OS in bortezomib-treated group, while the β-MG (≥8.95 mg/L), no-complete remission were the independent prognostic factros for OS in traditional therapy group. In addition, the MPI-1 myeloma prognostic index 1, consisted of age, complex karyotypes and complete remission in bortezomib-treated group, and MPI-2 consisted of β-MG (≥8.95 mg/L), complex karyotypes, complete remission in traditional therapy group were suitable for evaluating the pregnosis of MM patients treated with regimens contiaining bortezomib and traditional chemotherapentic regimans.@*CONCLUSION@#The differences of prognostic factors exist in MM patients treated with different chemotherapeutic regimens, moreover, the patients with comples karyotypes and no-complete remisson have poor prognosis. The MPI as more simple and easy clinical parameter, may be come an useful and complemental method for evaluation of prognosis except ISS and R-ISS.

Analysis on Pathogenesis of Diabetes Mellitus Based on Theory of Ascending and Descending of Qi Movement of Gut Microbiota / 中国实验方剂学杂志

The gut microbiota and its metabolites play a critical role on health maintenance, because they are involved in the absorption and metabolism of nutrients in the human bodies. This is also similar to traditional Chinese medicine (TCM) view that the ascending and descending of Qi movement affects Yin-Yang, Qi-blood, pneuma and body fluid, viscera and meridians of our bodies. More and more studies have demonstrated that gut microbiota is closely related to the development and progression of diabetes and its complications. Gut microbiota disorder could affect host metabolic signaling pathways, thereby promoting the formation and development of diabetes. The smooth ascending and descending of Qi movement is the basic form of maintaining host metabolic homeostasis, whose dysfunction however can lead to internal environment disturbance. Based on the theory of ascending and descending of Qi movement, this paper focuses on the pathogenesis of imbalanced intestinal flora in the process of the induction of diabetes mellitus from a dynamic perspective. It is assumed that the imbalance of Qi ascending and descending may act as a trigger for such symptoms as lung Qi impairment, spleen deficiency to dissipating essence, liver Qi stagnation and kidney Yang deficiency. Under this circumstance, gut microbiota will be out of balance, which will further lead to the nutrient substance metabolic disturbance in the body, and thus induce diabetes. Thus, it is significant to explore the regulatory mechanism of gut microbiota and its metabolites on diabetes based on the theory of ascending and descending of Qi movement, so as to reveal the scientific connotation of TCM in regulating substance metabolism homeostasis in the body.

Prognostic Value of Red Blood Cell Distribution Width in Senile Potients with Non-trans planted Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the prognostic value of red blood cell distribution width (RDW) in senile patients with non-transplanted multiple myeloma (MM).@*METHODS@#The RDW and clinical parameters such as β-2 microglobulin, creatiain, LDH and so on at diagnosis of 99 newly diagnosed senile MM patients were analysed retrospectively. The 99 patients were treated with chemotherapeutic regimens with or without bertezomib. The patients were divided into 2 groups: high (≥17.95%) and low (<17.95%) RDW groups according to ROC curve, then the prognosis of patients was compared between high and low RDW groups.@*RESULTS@#The levels of hemoglobin and C-reactive protein in high RDW group were lower than those in low RDW group, while the ratio of myeloma cells in high RDW group was higher than that in low RDW group. The unvariate and multivariate analyses in patients trented with chemotherapeutic regimen without bertezomib showed that the overall survival (OS) and progress free survival (PFS) time were shorter, while the high RDW group demonstrated the showter PFS in patients treated with chemotherapeutic regimen including bortezomib.@*CONCLUSION@#he RDW as a simple and easly available biomarker, suggests unfavorable prognosis for senile patients with non-transplanted MM; however the prognosis shows a certain difference on the basis of different chemotherapeutic regimens.

Meta analysis of the survival and prognosis of patients with sigmoid colon cancer and rectal cancer by ligation of inferior mesenteric artery / 中国现代普通外科进展

Objective:To investigate the effect of ligation of inferior mesenteric artery on the survival outcome and recurrence rate of patients with sigmoid colon cancer and rectal cancer by Meta analysis.Methods:CNKI,Wan Fang,Cochrane library,CBM and other search engines,combined with manual retrieval method,retrieval from January 2010 to January 2016,domestic and foreign literature about the inferior mesenteric artery ligation in sigmoid colon and rectal cancer patients with postoperative survival and tumor recurrence rate,using the Meta analysis method to summarizeand analyze the.Results:the total screened met the inclusion criteria and exclusion criteria of the 11 references,there are two kinds of low ligation and high ligation of inferior mesenteric artery ligation,recurrence and prognosis of different ligation mode,no statistical significance (P＞0.05).Conclusion:the inferior mesenteric artery ligation and high ligation of the sigmoid colon and rectal cancer patients survival did not differ significantly,and the two kinds of ligation of the postoperative recurrence rate is relatively close,there is not much evidence that high ligation has more advantages.

Interference of invasion and metastasis of colorectal cancer cells by EMS1-siRNA encoded by a recombinant lentiviral vector / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the effect of Cortactin on invasion and metastasis of human colorectal cancer cells through silencing the expression of Cortactin by transfecting colorectal cancer cells with EMS1-siRNA encoded by a recombinant lentiviral vector.</p><p><b>METHODS</b>EMS1-siRNA lentiviral vector and negative control lentiviral vector were both transfected into HCT8 cells after virus packing, then the expression of Cortactin of the cells was examined by Western blot to determine the inhibited level of Cortactin. The cells were defined as three groups: EMS1-siRNA transfecting cells, negative control transfecting cells and un-transfection cells. Cell invasion was evaluated with Transwell body. In addition, cells metastasis was observed in animal models. Thirty nude mice were evenly divided into three groups and all the mice were injected through tail vein with 1×10(7) cells/0.2 ml per animal for each group with the three kinds of cells. The mice were sacrificed 6 weeks after injection and examined for lung metastases development.</p><p><b>RESULTS</b>The expression of Cortactin and the ability of invasion of the EMS1-siRNA transfecting cells were all decreased. Lung metastasis rates of EMS1-siRNA transfecting group, negative control group and un-transfection group were 20%, 80% and 80%, respectively.</p><p><b>CONCLUSION</b>siRNA silencing of Cortactin expression can decrease the colorectal cancer cells invasion, and can also decrease the cells' implantation metastasis in animals.</p>

Effect of siRNA-mediated inhibition of nuclear transcription factor-kappa B on apoptosis of hepatocarcinoma cells / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the effect of siRNA-mediated inhibition of NF-κB on apoptosis of hepatocarcinoma cells.</p><p><b>METHODS</b>Specific small interfering RNA Targeting NF-κB gene was synthesized and transfected into HepG2 cells by liposomes. Nested RT-PCR and quantitative RT-PCR were used to detect the mRNA expression of NF-κB. Immunohistochemistry, enzyme-linked immunosorbent assay and Western blot were performed to examine the protein expression of NF-κB. Annexin V-FITC was used to test cell apoptosis.</p><p><b>RESULTS</b>The expression of NF-κB in HepG2 cells (1.13+/-0.03) was significantly higher (t=27.02, P<0.05) than that in normal hepatocytes (0.29+/-0.07). The down-regulation of NF-κB expression was depended on the dosage of siRNA and the time after transfection. 72 h after siRNA transfection, NF-κB expression reduced by 93% and 62% at the mRNA and protein levels, respectively. The apoptosis of HepG2 cells increased by 85% with NF-κB inhibition.</p><p><b>CONCLUSIONS</b>NF-κB is abnormally active in HepG2 cells and NF-κB inhibition mediated by siRNA promotes HepG2 cells apoptosis. It suggested that NF-κB could be a potential target for HCC prevention gene therapy.</p>

Expression and significance of NET-1 protein in hepatocellular carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>This study was designed to investigate the expression and significance of NET-1 in hepatocellular carcinoma (HCC) and analyze the relationship between NET-1 gene expression and clinicopathologic factors in HCC.</p><p><b>METHODS</b>NET-1 gene protein expression was detected by Western blot, fluorescence immunocytochemistry, confocal laser scanning microscopy and immunohistochemistry in 8 cases of HCC tissues, human hepatoma cell line SMMC-7721, and paraffin-embeded sections from 130 cases of HCC.</p><p><b>RESULTS</b>NET-1 gene protein expressed in 8 cases of HCC tissues by Western blot. The NET-1 gene protein positively located in the cytoplasm as irregular granules near Golgi apparatus in SMMC-7721cells, detected by fluorescent immunocytochemistry and observed by confocal laser scanning microscopy. The positive rate of NET-1 protein expression revealed by immunohistochemistry was 96.9% in HCC (126/130). NET-1 Protein expression in HCC was clearly correlative with HCC cytological variants, there were pronounced higher expressions in clear cell type, pleomorphic cell type, and sarcomatous change than that in hepatocytic type (P < 0.05). NET-1 Protein expression in HCC was positively correlative with the histopathologic grading, clinical stages and HCC with hepatitis and cirrhosis (P < 0.05), respectively, and negatively correlated with the presence of patches of necrosis (P < 0.05). But NET-1 protein expression was not associated with AFP level, tumor size and growth patterns, respectively.</p><p><b>CONCLUSION</b>NET-1 protein is expressed in cytoplasm of HCC cells as irregular granules near Golgi apparatus. NET-1 gene expression may promote the uncontrolled proliferation and abnormal differentiation in HCC cells.</p>