Objective According to the analyses of adverse drug reactions (ADR) in clinic, we supply reasonable drug information for clinical usage to reduce recurrence of adverse reactions. Methods Analyze the ADR reports of our hospital from April, 2007 to December, 2008 and make statistical analysis by terms of age of patients, kinds of drugs, route of administration, clinical manifestation, and recovery, etc. Result The incidence rate of ADR in the female is more than the male. ADR mainly involves with the skin, nervous system, respiratory system, and digestive system. Clinical manifestations mainly show as rash, local swelling, erythema, irritations, dizziness, headache, fever, sweating, shiver, chest tightness, short breath, heart palpitation, dyspnea, sickness, vomiting, abdominal pain and distension etc. Conclusion Antibiotics should be reasonably used; Traditional Chinese medicinal injection should be used according to syndrome differentiation and be avoided used with the combination with other medicines. Dosage and injecting speed should also be strictly controlled to reduce and avoid ADR happening again.

Objective To explore the clinical efficiency and safety of radiofrequency ablation combined with Tegafur,Gimeracil and Oteracil Porassium Capsules( S-1 capsules) for hepatocellular carcinoma.Methods Sixty HCC patients included in this study were underwent initial radiofrequency ablation and then they were di-vided into RFA+S-1 group and RFA control group according to the metronomic chemotherapy either with S-1 or not.The local tumor control and disease free survival outcome between the two groups were compared.Results Follow-up observation showed that the total control rate after 9 months′treatment was 93.3%in RFA+S-1 group vs.73.4%in RFA control group(P=0.038).During the 18 months of follow up,the median time for dis-ease free survival was 16.25 months in RFA+S-1 group vs.12.25 months in RFA control group( P<0.001) . One-year progression free survival rate in RFA group was 53.3%,which was significantly lower than the RFA+S-1 group(83.3%)(P=0.012).The major complication rate was 13.3%.No procedu rerelated death or severe complications occurred.Conclusion Metronomic chemotherapy with S-1 following initial radiofrequency ablation delays tumor progression and prolongs overall survival of patients with HCC tumors.

Objective To test the effect of metastasis associated in lung adenocarcinoma transcript 1 ( MALAT1) and／or osimertinib on the proliferation and apoptosis of HCC827 cells, and explore the potential mechanism of MALAT1 induced resistance to osimertinib. Methods We transfected HCC827 cells with LV?vector or LV?over／MALAT1. Stable transfected cells ( HCC827／Vector, HCC827／MALAT1) were selected by adding puromycin. HCC827／MALAT1 cells were further transfected with the shRNA?negative control ( NC) or shRNA?human epidermal growth factor receptor 3 ( ERBB3 ) plasmid. The effects of overexpression of MALAT1, knockdown of ERBB3 and／or osimertinib on the proliferation of HCC827 cells were evaluated by 3?(4,5?dimethyl?2?thiazolyl)?2,5?diphenyl?2H tetrazolium bromide ( MTT) assay. Cell apoptosis induced by MALAT1 overexpression, knockdown of ERBB3 and／or osimertinib treatment were analyzed by flow cytometry analysis. The expressions of EGFR and ERBB3 signal pathway related proteins in HCC827 cells treated with overexpression of MALAT1, knockdown of ERBB3 and／or osimertinib treatment were detected by western blot. Results The MTT assay showed that sensitivity to osimertinib of HCC827／MALAT1 cells were significantly repressed. The 50% inhibitive concentration (IC50 ) of osimertinib ＞4 000 nmol／L in HCC827／MALAT1 cells.However, knockdown of ERBB3 facilitated the anti?proliferation effect of osimertinib, and the IC50 of osimertinib in shRNA?ERBB3 cells was (17.27±3.21) nmol／L. The results of flow cytometry analysis showed that the apoptotic rate of HCC827／MALAT1 cells induced by 10 nmol／L osimertinib was (8.38±0.92)%, significantly lower than ( 27.17± 5.83)% of knockdown of ERBB3 ( P＜0.01). Western blotting showed that the expression of p?ERBB3, p?AKT and p?extracellular regulated protein kinases ( ERK) in HCC827／MALAT1 cells was markedly up?regulated, while the expression of p?epithelial growth factor receptor (EGFR) was inhibited. The expressions of p?ERBB3, p?AKT and p?ERK were marginally affected by osimertinb. However, osimertinib downregulated the expressions of p?EGFR, p?ERBB3, p?AKT and p?ERK in ERBB3 deleted cells. Conclusions MALAT1 confers resistance to osimertinb in HCC827 cells by activating of the ERBB3／PI3K／AKT and ERBB3／MAPK／ERK signaling pathways.

Objective To investigate the relationship of procollagen?lysine 2?oxoglutarate 5?dioxygenase 2 ( PLOD2 ) expression and the clinical characteristics of osteosarcoma, and explore the potential mechanism of tumour metastasis promoted by PLOD2. Methods The expression of PLOD2 in osteosarcoma tissues and paired adjacent tissues were detected by immunohistochemistry and qRT?PCR. Correlation of PLOD2 expression in osteosarcoma with the clinical pathologic features was analyzed by Chi square test and Kaplan?Meier analysis.Fibrillar collagen formation and collagen deposition in the tumor tissues were detected by picrosirius red staining. We transfected U?2OS cells with LV?vector, LV?over／PLOD2, sh?NC and sh?PLOD2. The expression of PLOD2 was detected by qRT?PCR. The impact of POLD2 on U?2OS cell invasion was determined by wound?healing assay and Transwell migration assay. The expressions of PLOD2／FAK／JAK2?STAT3 signal pathway related proteins were detected by western blotting. Results The high expression level of PLOD2 in osteosarcoma tissues was 72.5%, significantly higher than 0% in paired adjacent noncancerous tissues ( P＜0.01), the expression of PLOD2 was positively correlated with lymph node metastasis, pulmonary metastasis and poor outcome (P＜0.01). The same results were also observed in qRT?PCR assay. The median survival time of patients with high expression of PLOD2 protein was 13 months, significantly shorter than 32 months of patients with low expression of PLOD2 ( P＜0.05). The result of picrosirius red staining showed that the percentage of collagen fiber deposition in the osteosarcoma tissue with high level of PLOD2 was (74.43+9.63)%, significantly higher than ( 9.67± 1.28)% in tissue with low expression of PLOD2 (P＜0.001).The result of wound?healing and Transwell migration assay showed that over?expression of PLOD2 markedly promoted the invasion, however, knockdown of PLOD2 suppressed the invasion of U?2OS cells ( both P＜0.01).The result of western blotting showed that over?expression of PLOD2 significantly increased the expression levels of p?FAK, p?JAK2, p?STAT3, but knockdown PLOD2 decreased the levels of p?FAK, p?JAK2, p?STAT3 in U?2OS cells. Conclusions Up?regulation of PLOD2 in osteosarcoma is correlated with lymphatic and distant metastasis. PLOD2 promotes invasion and metastasis of osteosarcoma might through FAK／JAK2?STAT3 signal pathway.

Objective To test the effect of metastasis associated in lung adenocarcinoma transcript 1 ( MALAT1) and／or osimertinib on the proliferation and apoptosis of HCC827 cells, and explore the potential mechanism of MALAT1 induced resistance to osimertinib. Methods We transfected HCC827 cells with LV?vector or LV?over／MALAT1. Stable transfected cells ( HCC827／Vector, HCC827／MALAT1) were selected by adding puromycin. HCC827／MALAT1 cells were further transfected with the shRNA?negative control ( NC) or shRNA?human epidermal growth factor receptor 3 ( ERBB3 ) plasmid. The effects of overexpression of MALAT1, knockdown of ERBB3 and／or osimertinib on the proliferation of HCC827 cells were evaluated by 3?(4,5?dimethyl?2?thiazolyl)?2,5?diphenyl?2H tetrazolium bromide ( MTT) assay. Cell apoptosis induced by MALAT1 overexpression, knockdown of ERBB3 and／or osimertinib treatment were analyzed by flow cytometry analysis. The expressions of EGFR and ERBB3 signal pathway related proteins in HCC827 cells treated with overexpression of MALAT1, knockdown of ERBB3 and／or osimertinib treatment were detected by western blot. Results The MTT assay showed that sensitivity to osimertinib of HCC827／MALAT1 cells were significantly repressed. The 50% inhibitive concentration (IC50 ) of osimertinib ＞4 000 nmol／L in HCC827／MALAT1 cells.However, knockdown of ERBB3 facilitated the anti?proliferation effect of osimertinib, and the IC50 of osimertinib in shRNA?ERBB3 cells was (17.27±3.21) nmol／L. The results of flow cytometry analysis showed that the apoptotic rate of HCC827／MALAT1 cells induced by 10 nmol／L osimertinib was (8.38±0.92)%, significantly lower than ( 27.17± 5.83)% of knockdown of ERBB3 ( P＜0.01). Western blotting showed that the expression of p?ERBB3, p?AKT and p?extracellular regulated protein kinases ( ERK) in HCC827／MALAT1 cells was markedly up?regulated, while the expression of p?epithelial growth factor receptor (EGFR) was inhibited. The expressions of p?ERBB3, p?AKT and p?ERK were marginally affected by osimertinb. However, osimertinib downregulated the expressions of p?EGFR, p?ERBB3, p?AKT and p?ERK in ERBB3 deleted cells. Conclusions MALAT1 confers resistance to osimertinb in HCC827 cells by activating of the ERBB3／PI3K／AKT and ERBB3／MAPK／ERK signaling pathways.

Objective To investigate the relationship of procollagen?lysine 2?oxoglutarate 5?dioxygenase 2 ( PLOD2 ) expression and the clinical characteristics of osteosarcoma, and explore the potential mechanism of tumour metastasis promoted by PLOD2. Methods The expression of PLOD2 in osteosarcoma tissues and paired adjacent tissues were detected by immunohistochemistry and qRT?PCR. Correlation of PLOD2 expression in osteosarcoma with the clinical pathologic features was analyzed by Chi square test and Kaplan?Meier analysis.Fibrillar collagen formation and collagen deposition in the tumor tissues were detected by picrosirius red staining. We transfected U?2OS cells with LV?vector, LV?over／PLOD2, sh?NC and sh?PLOD2. The expression of PLOD2 was detected by qRT?PCR. The impact of POLD2 on U?2OS cell invasion was determined by wound?healing assay and Transwell migration assay. The expressions of PLOD2／FAK／JAK2?STAT3 signal pathway related proteins were detected by western blotting. Results The high expression level of PLOD2 in osteosarcoma tissues was 72.5%, significantly higher than 0% in paired adjacent noncancerous tissues ( P＜0.01), the expression of PLOD2 was positively correlated with lymph node metastasis, pulmonary metastasis and poor outcome (P＜0.01). The same results were also observed in qRT?PCR assay. The median survival time of patients with high expression of PLOD2 protein was 13 months, significantly shorter than 32 months of patients with low expression of PLOD2 ( P＜0.05). The result of picrosirius red staining showed that the percentage of collagen fiber deposition in the osteosarcoma tissue with high level of PLOD2 was (74.43+9.63)%, significantly higher than ( 9.67± 1.28)% in tissue with low expression of PLOD2 (P＜0.001).The result of wound?healing and Transwell migration assay showed that over?expression of PLOD2 markedly promoted the invasion, however, knockdown of PLOD2 suppressed the invasion of U?2OS cells ( both P＜0.01).The result of western blotting showed that over?expression of PLOD2 significantly increased the expression levels of p?FAK, p?JAK2, p?STAT3, but knockdown PLOD2 decreased the levels of p?FAK, p?JAK2, p?STAT3 in U?2OS cells. Conclusions Up?regulation of PLOD2 in osteosarcoma is correlated with lymphatic and distant metastasis. PLOD2 promotes invasion and metastasis of osteosarcoma might through FAK／JAK2?STAT3 signal pathway.

Objective: To investigate the effect and mechanism of long non-coding RNA-metastasis associated lung adenocarcinoma transcript 1, (LncRNA-MALAT1) on invasion and metastasis of esophageal cancer cell EC-109. Methods: EC-109 cells were transfected with lentiviral vector carrying short hairpin RNA of MALAT1( shRNA-MALAT1) or a nonspecific shRNA control (shRNA-control). The expressions of MALAT1, microRNA-200a, ZEB1 and ZEB2 were detected by qRT-PCR. The effect of shRNA-MALAT1 on invasion of EC-109 cells was determined by transwell assay. The expressions of components of epithelial-msenchymal transition pathway in EC-109 cells were determined by immunofluorescence array and western blotting. The expression relationship between MALAT1 and miR-200a in EC-109 cells was detected by dual-luciferase reporter assay. Results: The result of qRT-PCR showed that the expressions levels of MALAT1, ZEB1 and ZEB2 in shRNA-MALAT1 group were 0.43±0.06, 0.64±0.04 and 0.51±0.04, respectively, significantly lower than 0.97±0.08, 1.06±0.07 and 0.98±0.05 in shRNA-control group and 1 in control group, respectively(all P<0.05). Transwell assay showed that the number of invaded cells in shRNA MALAT1 group was (96.81±10.43) per low-power field, markedly lower than that of (278.44±13.28) per low-power field in shRNA-control group (P<0.01). Immunofluorescence staining and Western blotting showed that MALAT1 downregulation significantly reduced the expressions of proteins related to EMT signal pathway in EC-109 cells.Dual luciferase reporter assay showed that compared to negative control, the activities of luciferase reporter in EC-109 cells co-transfected with pmirGLO-MALAT1-wt and miR-200a were significantly down-regulated. While co-transfected pmirGLO-MALAT1-mut with miR-200a mimics had no effect on the luciferase reporter activities of MALAT1. Conclusion LncRNA MALAT1 functions as a competing endogenous RNA to regulate the expressions of ZEB1 and ZEB2 by sponging miR-200a and promotes invasion and migration of esophageal cancer cells through inducing epithelial-mesenchymal transition.

Objective: To investigate PLOD2 expression in esophageal squamous cell carcinoma, and to explore the potential mechanism by which PLOD2 promotes tumor metastasis. Methods: The expression of PLOD2 in 60 cases of esophageal squamous cell carcinoma (the patients were collected at the first Affiliated Hospital of Xinxiang Medical University, from January 2016 to December 2017) was investigated by immunohistochemistry. Fibrillar collagen formation and collagen deposition were detected by picrosirius red staining. Correlation of PLOD2 expression with clinical pathologic features of the patients was performed using χ² test and Kaplan-Meier analysis. After EC-109 cells were transfected with LV-vector and LV-over/PLOD2, the expression of PLOD2 was detected by real time PCR and the impact of POLD2 on invasion in EC-109 cells was determined by transwell migration and invasion assays. The expression of PLOD2/AKT epithelial-to-mesenchymal transition signal pathway related proteins was detected by Western blot. Results: The expression level of PLOD2 in esophageal squamous cell carcinoma was 81.7% (49/60 cases),higher than their paired noncancerous tissues(8.3%, 5/60; P<0.01), and correlated significantly with tumor depth of invasion and nodal metastasis (P<0.01). Picrosirius red staining showed that collagen deposition was increased and the degree of fibrillar organization was enhanced in carcinoma tissues that had higher PLOD2 expression. Transwell migration and invasion assays showed that PLOD2 significantly promoted the migration and invasion ability of EC-109 cells. Western blot showed that PLOD2 significantly increased the expression levels of p-FAK, p-AKT and vimentin in EC-109 cells. Conclusions Esophageal squamous cell carcinoma has a high expression of PLOD2 that correlates with tumor invasion and lymph node metastasis. PLOD2 promotes invasion and metastasis of esophageal squamous cell carcinoma through epithelial-to-mesenchymal transition via FAK/AKT signal pathway.

Objective: To test the effect of metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) and/or osimertinib on the proliferation and apoptosis of HCC827 cells, and explore the potential mechanism of MALAT1 induced resistance to osimertinib. Methods: We transfected HCC827 cells with LV-vector or LV-over/MALAT1. Stable transfected cells (HCC827/Vector, HCC827/MALAT1) were selected by adding puromycin. HCC827/MALAT1 cells were further transfected with the shRNA-negative control (NC) or shRNA-human epidermal growth factor receptor 3 (ERBB3) plasmid. The effects of overexpression of MALAT1, knockdown of ERBB3 and/or osimertinib on the proliferation of HCC827 cells were evaluated by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay. Cell apoptosis induced by MALAT1 overexpression, knockdown of ERBB3 and/or osimertinib treatment were analyzed by flow cytometry analysis. The expressions of EGFR and ERBB3 signal pathway related proteins in HCC827 cells treated with overexpression of MALAT1, knockdown of ERBB3 and/or osimertinib treatment were detected by western blot. Results: The MTT assay showed that sensitivity to osimertinib of HCC827/MALAT1 cells were significantly repressed. The 50% inhibitive concentration (IC₅₀) of osimertinib >4 000 nmol/L in HCC827/MALAT1 cells. However, knockdown of ERBB3 facilitated the anti-proliferation effect of osimertinib, and the IC₅₀ of osimertinib in shRNA-ERBB3 cells was (17.27±3.21) nmol/L. The results of flow cytometry analysis showed that the apoptotic rate of HCC827/MALAT1 cells induced by 10 nmol/L osimertinib was (8.38±0.92)%, significantly lower than (27.17±5.83)% of knockdown of ERBB3 (P<0.01). Western blotting showed that the expression of p-ERBB3, p-AKT and p-extracellular regulated protein kinases (ERK) in HCC827/MALAT1 cells was markedly up-regulated, while the expression of p-epithelial growth factor receptor (EGFR) was inhibited. The expressions of p-ERBB3, p-AKT and p-ERK were marginally affected by osimertinb. However, osimertinib downregulated the expressions of p-EGFR, p-ERBB3, p-AKT and p-ERK in ERBB3 deleted cells. Conclusions MALAT1 confers resistance to osimertinb in HCC827 cells by activating of the ERBB3/PI3K/AKT and ERBB3/MAPK/ERK signaling pathways.

Objective: To investigate the relationship of procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2) expression and the clinical characteristics of osteosarcoma, and explore the potential mechanism of tumour metastasis promoted by PLOD2. Methods: The expression of PLOD2 in osteosarcoma tissues and paired adjacent tissues were detected by immunohistochemistry and qRT-PCR. Correlation of PLOD2 expression in osteosarcoma with the clinical pathologic features was analyzed by Chi square test and Kaplan-Meier analysis.Fibrillar collagen formation and collagen deposition in the tumor tissues were detected by picrosirius red staining. We transfected U-2OS cells with LV-vector, LV-over/PLOD2, sh-NC and sh-PLOD2. The expression of PLOD2 was detected by qRT-PCR. The impact of POLD2 on U-2OS cell invasion was determined by wound-healing assay and Transwell migration assay. The expressions of PLOD2/FAK/JAK2-STAT3 signal pathway related proteins were detected by western blotting. Results: The high expression level of PLOD2 in osteosarcoma tissues was 72.5%, significantly higher than 0% in paired adjacent noncancerous tissues (P<0.01), the expression of PLOD2 was positively correlated with lymph node metastasis, pulmonary metastasis and poor outcome (P<0.01). The same results were also observed in qRT-PCR assay. The median survival time of patients with high expression of PLOD2 protein was 13 months, significantly shorter than 32 months of patients with low expression of PLOD2 (P<0.05). The result of picrosirius red staining showed that the percentage of collagen fiber deposition in the osteosarcoma tissue with high level of PLOD2 was (74.43+ 9.63)%, significantly higher than (9.67±1.28)% in tissue with low expression of PLOD2 (P<0.001). The result of wound-healing and Transwell migration assay showed that over-expression of PLOD2 markedly promoted the invasion, however, knockdown of PLOD2 suppressed the invasion of U-2OS cells (both P<0.01). The result of western blotting showed that over-expression of PLOD2 significantly increased the expression levels of p-FAK, p-JAK2, p-STAT3, but knockdown PLOD2 decreased the levels of p-FAK, p-JAK2, p-STAT3 in U-2OS cells. Conclusions Up-regulation of PLOD2 in osteosarcoma is correlated with lymphatic and distant metastasis. PLOD2 promotes invasion and metastasis of osteosarcoma might through FAK/JAK2-STAT3 signal pathway.