A multi-center retrospective study of perioperative chemotherapy for gastric cancer based on real-world data / 中华胃肠外科杂志

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.

Effect of allergic rhinitis on disease condition and treatment in patients with juvenile-onset systemic lupus erythematosus / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the effect of allergic rhinitis (AR) and its intervention on disease condition and medications in patients with juvenile-onset systemic lupus erythematosus (JSLE).</p><p><b>METHODS</b>The clinical data of 96 children diagnosed with JSLE were collected, and according to the presence or absence of AR or other allergic diseases, they were divided into AR group (n=44), non-AR group (n=20), and non-allergic group (n=32). The children in the AR group were randomly administered with or without intervention (n=22 each). All the children were given standard JSLE treatment. The systemic lupus erythematosus disease active index (SLEDAI) and application of hormones and immunosuppressants were compared between groups.</p><p><b>RESULTS</b>The AR and non-AR groups had significantly higher SLEDAI scores, daily cumulative doses of glucocorticoids, and number of types of immunosuppressants used than the non-allergic group before treatment (P<0.05), while there were no significant differences between the AR and non-AR groups (P>0.05). After one month of treatment, the AR group with intervention had significantly lower SLEDAI scores and daily cumulative doses of glucocorticoids than the AR group without intervention (P<0.05), while there was no significant difference in the application of immunosuppressants between these two groups (P>0.05). After 3 and 6 months of treatment, the AR group with intervention had significantly lower SLEDAI scores, daily cumulative doses of glucocorticoids, and number of types of immunosuppressants than the AR group without intervention (P<0.05).</p><p><b>CONCLUSIONS</b>JSLE combined with allergic diseases such as AR has an adverse effect on disease condition and treatment, and the intervention for AR helps with the control of JSLE.</p>

Heme oxygenase-1 promotes Caco-2 cell proliferation and migration by targeting CTNND1 / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Heme oxygenase-1 (HO-1) can be induced by inflammatory cytokines, oxidation, ischemia, hypoxia, and endotoxins. As a "graft survival protective gene," HO-1 is a hot spot in organ transplantation research. However, the role of HO-1 gene expression in the function of human colon adenocarcinoma cell line (Caco-2) cells has not been reported previously.</p><p><b>METHODS</b>The role of HO-1 in the proliferation and migration of Caco-2 cells was analyzed using a stable HO-1 expression plasmid. We constructed a recombinant adeno-associated virus plasmid containing the HO-1 gene, heme oxygenase 1 (HMOX1), which was transfected into Caco-2 intestinal cells. We identified a number of target genes by global microarray analysis combined with real-time polymerase chain reaction (PCR) and chromatin immunoprecipitation assay.</p><p><b>RESULTS</b>Our results showed that significant HO-1 upregulation was demonstrated in the Caco-2 cells after HO-1 transfection. Restoration of HO-1 expression promoted proliferation and invasion in vitro. The CTNND1 gene, a member of the armadillo protein family, was identified as a direct HO-1 target gene.</p><p><b>CONCLUSION</b>Overexpression of HO-1 promotes Caco-2 cell proliferation and migration by targeting the CTNND1 gene.</p>

Over-expression of VEGF and MMP-9 in residual tumor cells of hepatocellular carcinoma after embolization with lipidol / 华中科技大学学报（医学）（英德文版）

The expression and implication of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in residual hepatic tumor cells after lipiodol embolization were investigated. Two weeks after transplantation of VX2 tumor cells into the livers of rabbits, a xenograft model of the human hepatic neoplasm was successfully established. Forty rabbits were randomly divided into control group (n=20) and lipiodol group (n=20). For the control group, 1 mL normal saline was injected through the gastroduodenal artery, whereas 0.3 mL/kg lipiodol was applied for the lipiodol group. One week after embolization, the expression level of VEGF in the plasma was measured by using enzyme-linked immunosorbent assay (ELISA). A three-step immunohistochemical technique (ABC) was employed to detect the protein levels of VEGF and MMP-9 and the quantitative PCR for their mRNA levels was performed in the residual tumor cells. The VEGF in the plasma was significantly higher in the lipiodol group (1.42±0.29 ng/mL) than in the control group (1.12±0.21 ng/mL) (P<0.01). Moreover, the positive rate of VEGF protein in the residual tumor cells was significantly higher in the lipiodol group (62.13%±7.69%) than in the control group (53.16%±9.17%) (P<0.05). Similarly, the MMP-9 expression in the residual tumor cells was higher in the lipiodol group. The mRNA levels of VEGF (2.9313±2.4231) and MMP-9 (3.5721±1.6107) in the lipiodol group were significantly higher than those in the control group (1.5728±0.9453 and 1.7573±1.0641, respectively, P<0.05). Therefore, it was reasonable to speculate that the increased expression of VEGF and MMP-9 in residual hepatic tumor cells and tumor angiogenesis post-embolization would be responsible for the increased metastatic potentiality and invasiveness of these cells.

Over-expression of VEGF and MMP-9 in residual tumor cells of hepatocellular carcinoma after embolization with lipidol / 华中科技大学学报（医学）（英德文版）

The expression and implication of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in residual hepatic tumor cells after lipiodol embolization were investigated. Two weeks after transplantation of VX2 tumor cells into the livers of rabbits, a xenograft model of the human hepatic neoplasm was successfully established. Forty rabbits were randomly divided into control group (n=20) and lipiodol group (n=20). For the control group, 1 mL normal saline was injected through the gastroduodenal artery, whereas 0.3 mL/kg lipiodol was applied for the lipiodol group. One week after embolization, the expression level of VEGF in the plasma was measured by using enzyme-linked immunosorbent assay (ELISA). A three-step immunohistochemical technique (ABC) was employed to detect the protein levels of VEGF and MMP-9 and the quantitative PCR for their mRNA levels was performed in the residual tumor cells. The VEGF in the plasma was significantly higher in the lipiodol group (1.42±0.29 ng/mL) than in the control group (1.12±0.21 ng/mL) (P<0.01). Moreover, the positive rate of VEGF protein in the residual tumor cells was significantly higher in the lipiodol group (62.13%±7.69%) than in the control group (53.16%±9.17%) (P<0.05). Similarly, the MMP-9 expression in the residual tumor cells was higher in the lipiodol group. The mRNA levels of VEGF (2.9313±2.4231) and MMP-9 (3.5721±1.6107) in the lipiodol group were significantly higher than those in the control group (1.5728±0.9453 and 1.7573±1.0641, respectively, P<0.05). Therefore, it was reasonable to speculate that the increased expression of VEGF and MMP-9 in residual hepatic tumor cells and tumor angiogenesis post-embolization would be responsible for the increased metastatic potentiality and invasiveness of these cells.

Up-regulation of T-lymphoma and metastasis gene 1 in gastric cancer and its involvement in cell invasion and migration / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>T-lymphoma and metastasis gene 1 (Tiam1) produces a guanine nucleotide exchange factor (GNEF) that regulates guanosine triphosphatase, which transforms guanosine diphosphate to guanosine triphosphate. Recently published data indicate that Tiam1 was associated with gastric cancer. The aim of this study was to investigate biological effects and potential mechanisms of Tiam1 in gastric carcinoma.</p><p><b>METHODS</b>We analyzed the expression of Tiam1 in 114 pair-matched gastric neoplastic and adjacent non-neoplastic tissues by quantitative real-time PCR. We investigated Tiam1 expression and its prognostic value for gastric cancer. Furthermore, the functions of Tiam1 over-expression were analyzed with stable-expression Tiam1 plasmid in human gastric cancer cell lines.</p><p><b>RESULTS</b>Tiam1 expression was significantly associated with cell differentiation and lymphatic metastasis; expression of Tiam1 mRNA was up-regulated in gastric cancer compared to pair-matched adjacent non-tumor tissues. Analyses of surgical tissue samples and 5-year survival of gastric cancer patients showed that those with strong Tiam1 expression had significantly shorter overall survival time than those with negative Tiam1 expression. Ectopic expression of Tiam1 promoted cell growth, migration and invasion of gastric cancer cells in vitro.</p><p><b>CONCLUSIONS</b>In gastric cancer cells, Tiam1 affects multiple properties associated with acquisition of the metastatic phenotype, and may be a marker of gastric cancer progression and metastasis in a subset of cancer.</p>

Effects of RNA interference and nolatrexed on thymidylate synthase expression and cell proliferation of human colorectal carcinoma LOVO cells / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of the RNAi and the chemotherapy drugs nolatrxed on the expression of thymidylate synthase(TS) and the growth of the colorectal carcinoma LOVO cells.</p><p><b>METHODS</b>The siRNA was constructed targeting the human TS gene, and then transfected into the human colorectal cancer LOVO cells. RT-PCR and Western blot technique were used to observe the TS gene and protein expression levels, and MTT was used to detect cell proliferation after silencing the TS gene. In addition, siRNA and nolatrxed were applied to the LOVO cells to observe the TS protein expression and cell growth.</p><p><b>RESULTS</b>TS siRNA significantly reduced the expression of TS gene and protein in LOVO cells, and inhibited cell growth. The IC50 value of LOVO cells was (1.46±0.25) μmol/L in TS siRNA combined with nolatrexed group, (6.81±0.31) μmol/L in the negative control group, and (6.47±0.43) μmol/L in the single nolatrexed group. After treatment of TS siRNA combined with nolatrexed on LOVO cells for 36 hours, the apoptosis index was higher than that in single TS siRNA and nolatrexed[(62.12±0.89)% vs.(21.56±0.67)% and(40.51±0.83)%, both P<0.05].</p><p><b>CONCLUSION</b>TS siRNA can partly suppress the expression of TS gene in LOVO cells, inhibit cell proliferation, promote cell apoptosis and enhance cell sensitivity to apoptosis induced by nolatrexd.</p>

Development of bone marrow mesenchymal stem cell culture in vitro / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To review the in vitro development of bone marrow mesenchymal stem cells culture (BM-MSC).</p><p><b>DATA SOURCES</b>The data cited in this review were mainly obtained from articles listed in Medline and PubMed. The search terms were "bone marrow mesenchymal stem cell" and "cell culture".</p><p><b>STUDY SELECTION</b>Articles regarding the in vitro development of BM-MSCs culture, as well as the challenge of optimizing cell culture environment in two-dimensional (2D) vs. 3D.</p><p><b>RESULTS</b>Improving the culture conditions increases the proliferation and reduces the differentiation. Optimal values for many culture parameters remain to be identified. Expansion of BM-MSCs under defined conditions remains challenging, including the development of optimal culture conditions for BMSC and large-volume production systems.</p><p><b>CONCLUSIONS</b>Expansion of BM-MSCs under defined conditions remains challenges, including the development of optimal culture conditions for BMSC and scale-up to large-volume production systems. Optimal values for many culture parameters remain to be identified.</p>

Activity of heme oxygenase-1 affects expression levels of hypoxia inducible factor-1 gene in vitro / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>One effect of solid tumors is severe hypoxia of local tissues. Heme oxygenase-1 (HO-1) is highly expressed in a variety of human tumor tissues; its induction and activity are closely related to growth of solid tumors. Hypoxia inducible factor-1 (HIF-1) is a transcription factor that regulates hypoxia signal transduction and plays a central role in tumor hypoxia regulation. However, whether and how changes in HO-1 activity affect HIF-1 gene expression has not been reported previously.</p><p><b>METHODS</b>Hypoxia-inducible models were established using gastric cancer cell lines (SGC-7901) in a hypoxia incubator. Cells were placed in four groups: Group A, transfected by plasmid harboring HO-1 shRNA; Group B, transfected with scrambled shRNA vector; Group C, treated with hemin; and Group D, exposed to hypoxia only. Expressions of HO-1 and HIF-1 mRNAs were quantified by reverse transcription-polymerase chain reaction. Expressions of HO-1 and HIF-1 proteins were determined by immunohistochemistry and Western blotting.</p><p><b>RESULTS</b>mRNA and protein levels of HO-1 and HIF-1 in the control group were significantly higher than in Group A (P < 0.01), but lower than in Group C (P < 0.01). Chromatin immunoprecipitation analysis showed that HIF-1 was identified as the direct HO-1 target gene.</p><p><b>CONCLUSION</b>While affected by HIF-1, HO-1 up-regulation promotes the expression of HIF-1 and the down-regulation of HO-1 suppresses the expression of HIF-1 gene.</p>

Heme oxygenase-1 is the candidate targeting for organ transplantation / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To review the role of heme oxyenase-1 in organ transplantation and explore the potential applications targeted on overexpression of heme oxyenase-1 gene.</p><p><b>DATA SOURCES</b>The data cited in this review were mainly obtained from the articles listed in Medline and PubMed, published from January 1996 to December 2008. The search terms were "heme oxygenase-1" and "transplantation".</p><p><b>STUDY SELECTION</b>Articles regarding the role of heme oxyenase-1 in organ transplantation and its protective role in transplants were selected. Protective effects of heme oxygenase-1 overexpression using a gene transfer approach against ischaemic reperfusion injury during transplantation were widely explored.</p><p><b>RESULTS</b>Local heme oxygenase-1 overexpression in the graft ameliorates the ischaemic reperfusion injury. This is due to removal of heme, a potent prooxidant and proinflammatory agent, but also because of generation of biologically active products.</p><p><b>CONCLUSIONS</b>Overexpressive heme oxygenase-1 activity is associated with tissue protection in the setting of graft, ischaemic reperfusion injury. Gene therapy is attractive to us; but a long way from general application. In terms of heme oxygenase-1, the gene promoters are polymorphic. Although individualization is an important principle during clinical application, it is difficult to put into practice.</p>

The development of a polarized vernier optometer for tonic accommodation measurement / 中国医疗器械杂志

A vernier optometer, based on the Scheiner principle, that makes use of polarized light, is designed and developed. It is specialized in measurement of tonic accommodation, accommodation and accommodation response. The vernier optometer has been proved by chinical testing results, to be a reliable and effective instrument with fine stabilily, good repeatability and sensitivity for short sight study relating to oculogyral parameters.