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    08 December 2015, Volume 42 Issue 12 Previous Issue    Next Issue
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    Smac playing vital role in enhancing the sensitivity of cyclophosphamide and doxorubicin in breast cancer MCF-7 cell line
    Cheng Liying, Sun Tao, Chen Wenqiang, Meng Qingsong
    2015, 42 (12):  881-885.  doi: 10.3760/cma.j.issn.1673-422X.2015.12.001
    Abstract ( 305 )   PDF (1130KB) ( 1447 )   Save
    ObjectiveTo investigate the influence of Smac to the chemosensitivity of cyclophosphamide (CTX) and doxorubicin (DOX) in MCF-7 cells. MethodsMCF-7 cells were exposed to CTX, DOX and the combination of both. 3(4,5dimethyl2thiazoly)2,5diphenyl2Htetrazolium bromide (MTT) assay was used to estimate the cell viability. Apoptosis was measured by acridine orange staining and Ho.33342/PI double staining. The mRNA and protein expressions of Smac were determined by RTPCR and Western blotting. The study also analyzed the changes of proapoptotic proteins active caspase3 and active caspase9. ResultsCTX, DOX and the combination of both drugs reduced the cell survival rates in a concentrationdependent manner. The cell viability after being treated with 4.0 μg/ml CTX or 0.2 μg/ml DOX or 2.0 μg/ml CTX and 0.1 μg/ml DOX for 48 hours was (52.90±8.78)%, (53.35±6.29)% and (34.19±5.43)%, respectively. The drug combination developed a stronger inhibitory effect compared to the single drugs (t=9.051, P=0.014; t=9.074, P=0.014). The Smac mRNA and protein levels in 2.0 μg/ml CTX and 0.1 μg/ml DOX group were 7.47±0.82 and 4.13±0.36, which were higher than those in 4.0 μg/ml CTX group (3.27±0.40 and 2.28±0.27; t=-50.120, P=0.000; t=-42.588,P=0.000) and 0.2 μg/ml DOX group (3.34±0.62 and 2.45±0.40; t=-46.233, P=0.000; t=-39.541, P=0.000). Furthermore, proapoptotic proteins active caspase3 and active caspase9 increased activity was confirmed by Western blotting. ConclusionSmac plays a vital role in enhancing the sensitivity of chemotherapeutic drugs CTX and DOX in MCF-7 cell line.
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    Effect and mechanism of CRISPR/Cas system on proliferation and apoptosis of human cervical cancer cells
    Wang Ruiling, Hu Zheng, Xia Wei, Wei Bo, Ye Wanglian, Zhu Hongfang
    2015, 42 (12):  886-890.  doi: 10.3760/cma.j.issn.1673-422X.2015.12.002
    Abstract ( 418 )   PDF (1534KB) ( 1484 )   Save
    ObjectiveTo investigate the effect and mechanism of HPV16E7 gene specific CRISPR/Cas (clustered regularly interspaced short palindromic repeat/CRISPR associated system) on the cell apoptosis and proliferation of human cervical cancer SiHa cell line. MethodsHPV16 positive cervical cancer SiHa cells and HPV16 negative human embryonic kidney HEK293 cells were cultured and each of the cells were divided into 3 groups respectively in the experiment: the control group was untreated, the C9 group was transfected only with Cas9 plasmid, and the Cri group was cotransfected with guide RNA (gRNA) plasmid and Cas9 plasmid (1∶3). T7 endonuclease Ⅰ assay was used to detect double strand break (DSB) formation in SiHa cells. The apoptosis rates of SiHa and HEK293 cells were detected by flow cytometry (FCM). CCK8 was used to evaluate the proliferation of SiHa and HEK293 cells. Western blotting was applied to detect E7 and pRb protein expression. ResultsThe SiHa cells in Cri group showed DSB formation at 48 h after transfection. The apoptosis rate of Cri group at 48 h was 26.6%, higher than 2.6% in control group (χ2=5.455, P=0.020) and 3.1% in C9 group (χ2=6.279, P=0.012). The apoptosis rates of control, C9 and Cri group were 7.4%, 7.6%, 7.9% for HEK293 cells respectively. Compared with the control and C9 group, the apoptosis rate of the Cri group showed no statistical significance (χ2=0.032, P=0.858; χ2=0.034, P=0.853). After 72 h transfection, the inhibition rate of SiHa cells in Cri group was 29.4%, higher than 15.0% in control group (χ2=22.481, P=0.000) and 18.0% in C9 group (χ2=24.879, P=0.000). The inhibition rate of the HEK293 cells in Cri group was 3.2%, and it showed no significant difference compared with the inhibition rate of C9 group (2.2%, χ2=2.857, P=0.091) and control group (2.3%, χ2=3.438, P=0.064) respectively. Downregulated expression of E7 protein and upregulated expression of pRb protein were detected of the SiHa cells in Cri group compared with the control group, while the E7 protein and pRb protein level did not show difference in the C9 group. ConclusionCRISPR specifically targeting HPV16E7 oncogene can promote apoptosis of SiHa cells, and inhibit the cell proliferation. It is speculated that CRISPR system may induce DSB event of E7 gene, and result into increased expression of tumor suppressor protein pRb.
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    Correlation study of the different expression changes of Ki67 after neoadjuvant chemotherapy and chemotherapy curative effect for the different molecular classification breast cancers
    Wu Xiuping, Liu Fei, Wu Saihong, Ran Wangjun, Zeng Dexue, Zheng Xiaoyan, Hu Liandi, Xie Yuanfu, Zhuo Yanhong
    2015, 42 (12):  891-895.  doi: 10.3760/cma.j.issn.1673-422X.2015.12.003
    Abstract ( 812 )   PDF (895KB) ( 1179 )   Save
    ObjectiveTo explore the correlation of the different expression changes of Ki67 after neoadjuvant chemotherapy and chemotherapy curative effect for the different molecular classification breast cancers. MethodsOne hundred and sixty cases with breast surgery in Zhengxing Hospital of Zhangzhou of Fujian Province from March 2008 to March 2010 were selected using simple random sampling method (40 cases of Luminal A, 61 cases of Luminal B, 21 cases of HER2 over expression type, 38 cases of three negative breast cancer). All included patients were treated with neoadjuvant chemotherapy, every 21 days for a cycle, a total of 4 cycles. The expressions of Ki67 before and after neoadjuvant chemotherapy were detected, and the correlations of Ki67 expression changes and chemotherapy curative effect for the different molecular classification breast cancers were analyzed. ResultsAfter neoadjuvant chemotherapy, the pathological complete response rates of the four types of breast cancer were 12.5%, 14.8%, 19.0%, 28.9%, with statistical significant (χ2=8.992, P=0.030). For Luminal A type and triple negative breast cancer, there were statistical significant differences for 5year disease free survival rates of patients with Ki67 decreased and those patients with Ki67 increased or to usual (81.3% vs. 61.3%, χ2=9.021, P=0.031; 54.3% vs. 41.2%, χ2=7.583, P=0.043). Multifactor analysis revealed that neoadjuvant chemotherapy curative effect (RR=3.12, 95%CI: 1.373.54, χ2=12.183, P=0.001) and clinical stage (RR=2.16, 95%CI: 1.222.79, χ2=8.057, P=0.005) were independent factors for patients with Luminal A type breast cancer. Neoadjuvant chemotherapy curative effect (RR=2.57, 95%CI: 1.873.15, χ2=4.832, P=0.027), clinical stage (RR=2.70, 95%CI: 1.723.79, χ2=5.218, P=0.015) and expression change of Ki67 (RR=2.15, 95%CI: 2.132.38, χ2=4.276, P=0.044) were independent factors for patients with triple negative breast cancer. ConclusionThe expression change of Ki67 after neoadjuvant chemotherapy is the independent factor of the disease free survival rates for patients with triple negative breast cancer. Ki67 has some reference value for the prognosis of triple negative breast cancer.
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    Clinicopathological significance and expression of Numb and α-catenin in gastric carcinoma
    Liu Xuefei, Li Wenhui, Xin Yan
    2015, 42 (12):  896-899.  doi: 10.3760/cma.j.issn.1673-422X.2015.12.004
    Abstract ( 351 )   PDF (1229KB) ( 1091 )   Save
    ObjectiveTo detect the expressions of Numb and αcatenin in the gastric cancer and matched normal gastric mucosa, and to analyze their relationship with clinicopathological factors of gastric cancer and explore their roles in gastric carcinogenesis and progression. MethodsImmunohistochemical method was used to detect the expressions of Numb and αcatenin in 109 cases of tumor specimens and 97 cases of matched normal gastric mucosa. The correlations between Numb, αcatenin and clinicopathological factors were analyzed. ResultsThe positive rates of Numb and αcatenin in gastric cancer were significantly lower than those in normal gastric mucosa (60.6%∶100.0%, χ2=48.361, P=0.000; 76.1%∶100.0%, χ2= 26.480, P=0.000). The expression of Numb protein was correlated with Lauren type (χ2=17.018, P=0.000) and tubular adenocarcinoma differentiation (χ2=17.586, P=0.000). The expression of αcatenin protein was correlated with Borrmann type (χ2=6.700, P=0.035), Lauren type (χ2=11.098, P=0.001), tubular adenocarcinoma differentiation (χ2=8.203, P=0.017) and lymph node metastasis (χ2=6.402, P=0.011). The expressions of Numb and αcatenin were statistically correlated in 109 cases of gastric cancer (rk=0.184, P=0.028). ConclusionCompared with normal gastric mucosa, both Numb and αcatenin expressions are downregulated and the two expressions are correlated in gastric cancer. Numb and αcatenin may be involved in the regulation of histological differentiation of gastric cancer by certain passages, Numb protein may be adjusted by αcatenin pathway which is involved in Wntβcatenin pathway, and thus plays an important role in promoting cell proliferation, invasion and metastasis in human gastric cancer.
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    Expressions and clinical significances of microRNA-126 and vascular endothelial growth factor in gastric carcinoma
    Li Zhihan, Zhang Xiliang, Wang Wei
    2015, 42 (12):  900-902.  doi: 10.3760/cma.j.issn.1673-422X.2015.12.005
    Abstract ( 387 )   PDF (712KB) ( 993 )   Save
    ObjectiveTo observe the expressions of microRNA-126 (miR-126) and vascular endothelial growth factor (VEGF) in gastric carcinoma tissues, and their associations with clinicopathologic features in gastric carcinoma. MethodsFifty cases of gastric carcinoma and matched tumor adjacent tissue specimens were collected from January 2012 to March 2014 in Shangqiu First People′s Hospital of He′nan Province. Expression levels of miR-126 and VEGF were examined using reverse transcriptasepolymerase chain reaction. Their correlations and the relationships between them and the clinicopathologic features in gastric carcinoma were analyzed. ResultsThe expression levels of miR126 in the tumor tissues and in the adjacent tissues were 0.652±0.102 and 0.379±0.069, and the expression levels of VEGF in the two kinds of tissues were 1.523±0.142 and 0.604±0.152, with statistical differences (t=8.374, P=0.001; t=29.508, P=0.000). The expressions of miR-126 and VEGF were significantly positively correlated (r=0.735, P=0.001). The expressions of miR-126 and VEGF were associated with TNM stage (t=22.981, P=0.001; t=18.053, P=0.001), depth of tumor invasion (t=26.792, P=0.001; t=20.234, P=0.001) and tumor node metastasis (t=26.668, P=0.001; t=14.857, P=0.001). ConclusionmiR126 is high expressed in the gastric carcinoma tissue, which may upregulate the expression of VEGF, and lead to the formation of new blood vessels, then to promote gastric carcinogenesis and the development process.
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    Expression and clinical value of Pokemon in hepatocellular carcinoma
    Zhang Quanle, Xing Xizhi, Li Fengyan, Qin Yanhong, Zhang Liying
    2015, 42 (12):  903-906.  doi: 10.3760/cma.j.issn.1673-422X.2015.12.006
    Abstract ( 508 )   PDF (1019KB) ( 1189 )   Save
    ObjectiveTo detect the serum expression level of Pokemon and explore its clinical value combines with AFP, AFPL3 or DCP in hepatocellular carcinoma (HCC). MethodsIn this study, the serum levels of Pokemon, AFP, AFPL3 and DCP in 30 patients with HCC, 34 patients with benign liver diseases and 30 healthy controls were examined by enzymelinked immunosorbent assay. Then, the clinical significance of Pokemon expression level was analyzed. In the end, the diagnostic evaluation of four serum biomarker alone detection was used to analyze the sensitivity, specificity, the area under the curve and Youden index in the diagnosis of HCC. ResultsThe serum expression level of Pokemon in patients with HCC was (22.63±6.82)ng/ml, which was significantly higher than that in the group with benign liver diseases and healthy controls [(3.54±1.26)ng/ml, t=8.594, P<0.001; (1.95±0.57)ng/ml, t=10.021, P<0.001]. The expression level of Pokemon in HCC patients was correlated to tumor size (t=2.678, P=0.021) and TNM stag (t=2.578, P=0.034). The serum expression levels of AFP, AFPL3 and DCP in patients with HCC were (774.56±96.52)ng/ml, (26.37±2.54)ng/ml and (93.49±30.45)mAU/ml, which were significantly higher than those in the group with benign liver diseases [(22.21±3.57)ng/ml, (7.05±2.71)ng/ml, (34.68±10.13)mAU/ml] and healthy controls [(14.65±4.45)ng/ml, (3.84±1.09)ng/ml, (25.87±9.01)mAU/ml, F=58.46, P=0.000; F=12.47, P=0.000; F=23.41, P=0.000]. The sensitivity and specificity of Pokemon, AFP, AFPL3, DCP in the diagnosis of HCC were 84.6% and 87.5%, 52.5% and 78.9%, 95.0% and 80.0%, 77.1% and 87.5%, respectively. ConclusionThe enhanced Pokemon serum level, with its sensitivity and specificity higher than AFP, points out Pokemon may be a potentially useful biomarker to diagnose HCC.
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    Panitumumab compared with cetuximabirinotecan therapy in patients with KRAS wildtype metastatic colorectal cancer
    Hu Haifeng, Nian Liang, Sun Xiaodong, Qiao Jian, Duan Wei, Gao Na, Zhang Lu, Liu Ningning, Liu Yiting
    2015, 42 (12):  907-910.  doi: 10.3760/cma.j.issn.1673-422X.2015.12.007
    Abstract ( 479 )   PDF (809KB) ( 1513 )   Save
    ObjectiveTo compare the curative effect of KRAS wildtype metastatic colorectal cancer patients treated with either single agent panitumumab or combination therapy with cetuximab and irinotecan. MethodsUsing the random number table method (concealment of allocation), the study enrolled 35 patients with KRAS wildtype metastatic colorectal cancer, who had received epidermal growth factor receptor inhibitor, either panitumumab (20 cases) or combination cetuximabirinotecan (15 cases). The differences of curative effect between groups were assessed by statistical analysis. ResultsFive (25.0%) panitumumab and four (26.7%) cetuximabirinotecantreated patients had partial response, and the difference was not statistically significant (P=0.64). Median overall survival was 8.3 months for the panitumumab group and 8.5 months for the cetuximabirinotecan group (χ2=1.161, P=0.13). Multivariate analysis demonstrated that survival outcomes were similar regardless of the therapy selected and the difference was not statistically significant (HR=1.17, 95%CI: 0.682.04, χ2=1.01, P=0.47). 95% patients who received panitumumab and all cetuximabirinotecantreated patients (100%) experienced treatmentrelated adverse events (P=0.72). ConclusionThe drug therapy of panitumumab and cetuximabirinotecan treatment were similar to KRAS wildtype metastatic colorectal cancer patients and can be reasonable used as thirdline treatment options for patients with chemoresistant metastatic colorectal neoplasms.
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    Roles of cell signaling pathways in thyroid carcinoma
    Xu Yingkai, Hu Jie, Liu Wei
    2015, 42 (12):  911-915.  doi: 10.3760/cma.j.issn.1673-422X.2015.12.008
    Abstract ( 420 )   PDF (731KB) ( 1720 )   Save
    The intracellular signal transduction pathways play an important role in the occurrence and development of thyroid cancer. Mitogen activated protein kinase (MAPK) signal transduction pathway, phosphatidylinositol 3kinase (PI3K)AKT pathway, NFκB pathway and RASSF1MST1FOXO3 pathway affect the occurrence and development of thyroid cancer by modulating the activity and expression of specifical proteins, and determine the growth and apoptosis of thyroid cancer cells.
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    Neoadjuvant chemotherapy for locally advanced cancer
    Liu Hui, Rui Jing
    2015, 42 (12):  916-919.  doi: 10.3760/cma.j.issn.1673-422X.2015.12.009
    Abstract ( 341 )   PDF (721KB) ( 1619 )   Save
    Neoadjuvant chemotherapy is one of the common means in multidisciplinary treatment of locally advanced breast cancer, with anthracyclines and taxanes as main chemotherapeutic drugs. In recent years, molecular target agents have significantly improved the efficacy of chemotherapy, as well as have provided more choices and ideas for clinical treatment. Currently, the widely studied molecular targeted drugs include trastuzumab, lapatinib, pertuzumab, TDM1 and bevacizumab.
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    |Medical therapy of bone metastases of breast cancer
    Xie Xiaojuan, Tong Zhongsheng
    2015, 42 (12):  920-923.  doi: 10.3760/cma.j.issn.1673-422X.2015.12.010
    Abstract ( 541 )   PDF (719KB) ( 1382 )   Save
    Approximately 70% advanced breast cancer will develop bone metastases. Bone metastases can cause a series of complications such as skeletalrelated events, seriously affecting the quality of life of the patients. Therefore, it is very important to choose the reasonable and effective treatments. Bisphosphonates are the standard treatments of bone metastatic breast cancer, denosumab may also be a reasonable alternative to bisphosphonates in the near future, while chemotherapy, endocrinotherapy and targeted therapy are the basic treatments of advanced breast cancer, combined use of various treatments will get the best efficacy.
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    Applications of the biomakerdetection technology guiding neoadjuvant therapy for advanced esophageal cancer
    Li Chen, Cheng Yufeng
    2015, 42 (12):  924-927.  doi: 10.3760/cma.j.issn.1673-422X.2015.12.011
    Abstract ( 258 )   PDF (720KB) ( 1484 )   Save
    At present, the technology to predict the response to neoadjuvant therapy with biomakers has been widely used in clinical practice. The approaches of biomarkers detection are various, including immunohistochemistry, detection of serum biomarkers conventional blood tests, gene expression profile analysis, single nucleotide polymorphisms, miRNAs, proteomics analysis. With the development of biotechnology, the technology of biomarkers detection is expected to become effective means in assessment of adjuvant therapy, risk, prognosis and individualization in esophageal cancer treatment.
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    Applications of 18FFDG PETCT for accurate radiotherapy of esophageal cancer
    Wei Li, Li Duojie
    2015, 42 (12):  928-931.  doi: 10.3760/cma.j.issn.1673-422X.2015.12.012
    Abstract ( 303 )   PDF (720KB) ( 1194 )   Save
    Precise target delineation, target amendment and treatment plan regulation before radiotherapy and effect evaluation after radiotherapy are critical for the treatment of esophageal cancer. 18Ffluorodeoxyglucose (FDG) positron emission tomography (PET)/CT, a unique combination of the functionally metabolic PET imaging and the anatomical CT imaging, can provide more anatomical details for PET, and it can reflect differences in tumor and normal tissue metabolic states and biochemical changes at the molecular level, and provide more valuable assistance for the treatment of esophageal cancer.
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    Clinical study on the radiosensitizer of esophageal carcinoma
    Kang Mei, Quan Xunfeng
    2015, 42 (12):  932-935.  doi: 10.3760/cma.j.issn.1673-422X.2015.12.013
    Abstract ( 476 )   PDF (719KB) ( 1644 )   Save
    Radiosensitizer as a promising novel antitumor medicine has synergetic effects with radiotherapy, and can enhance the kill rate of tumor cells and radiotherapy effect. In recent years, due to the new theory and technology, the researches of radiosensitizer extend to different fields, from the traditional DNA target sensitizer to new radiosensitizer including nanoparticles. Consequently, radiosensitizer combined with radiotherapy will become a new and effective treatment strategy for esophageal carcinoma to enhance the therapeutic effect of esophageal carcinoma.
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    Digestive tract reconstruction after proximal gastrectomy
    Huang Ling, Wang Xinbao
    2015, 42 (12):  936-938.  doi: 10.3760/cma.j.issn.1673-422X.2015.12.014
    Abstract ( 625 )   PDF (711KB) ( 1623 )   Save
    In numerous digestive reconstruction techniques after proximal gastrectomy for tumor of the gastroesophageal junction, widely used methods are esophagogastrostomy, esophagogastric tube reconstruction and jejunalinterposition reconstruction. More studies have been focused on jejunalinterposition reconstruction in recent years, from which a variety of modified reconstructions derive. In clinical practice, a flexible choice is needed according to the actual situation of patients.
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    Effect of IL-2 on primary hepatic carcinoma and its potential clinical value
    Pang Jing, Deng Zhihua
    2015, 42 (12):  939-941.  doi: 10.3760/cma.j.issn.1673-422X.2015.12.015
    Abstract ( 417 )   PDF (712KB) ( 1170 )   Save
    As a T cell subsets growth factor, interleukin-2 (IL-2) can inhibit cancer cell proliferation, reduce tumorigenicity and transitivity, improve local tumor microenvironment, enhance the immunogenicity of hepatocellular carcinoma cells, reduce the load of hepatitis virus and greatly enhance the ability of antitumor. On the other hand, it can enhance tumor hypercoagulable state. The effect of IL-2 on primary hepatic carcinoma and its potential clinical value have a bright future.
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    Diagnosis and treatment of carcinoma of unknown primary
    Li Zhenzhen, Xie Conghua
    2015, 42 (12):  942-945.  doi: 10.3760/cma.j.issn.1673-422X.2015.12.016
    Abstract ( 681 )   PDF (720KB) ( 2354 )   Save
    The primary focal area of carcinoma of unknown primary (CUP) can not be determined by clinical examination. It is difficult to find the primary site and its prognosis is poor. The traditional diagnostic approaches mainly include pathological examination, endoscopy, imaging technology and so on. However, positron emission tomography is the preferred approach. In recent years, gene expression profiling has become a new diagnostic approach to find the source of CUP. The detection rate by gene expression profiling is high, and the approach can accurately identify the primary site. The recommended therapies include classic platinum or paclitaxelbased chemotherapy, radiotherapy or surgery, and sitedirected therapy by gene expression profiling for patients with CUP improves their survival rate.
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    Pathogenesis, clinical evaluation and treatment of neuropathic cancer pain
    Liu Weishuai, Shao Yuejuan, Wang Kun
    2015, 42 (12):  946-949.  doi: 10.3760/cma.j.issn.1673-422X.2015.12.017
    Abstract ( 480 )   PDF (718KB) ( 2129 )   Save
    Neuropathic cancer pain (NCP) arises from physical or chemical damage to peripheral or central neurons or in the neural conduction system. The mechanisms of NCP include pain directly related to tumor involvement, pain associated with chemotherapy, radiotherapy and surgery, neuropathic syndromes associated with paraneoplastic syndromes, inflammation and other factors. A detailed history and careful physical examination are important means of diagnosis of NCP. The clinical evaluation of NCP should use standardized pain assessment scale. Till now, the treatments of NCP include opioid combined with auxiliary analgesic drugs, interventional treatment and gene treatment. Deciding treatment strategies according to the pathogenesis of NCP, multidisciplinary collaboration, combined therapy with different analgesic drugs and technologies are the therapeutic directions for NCP.
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