Shuchen Chen

Ischemia postconditioning and mesenchymal stem cells engraftment synergistically attenuate ischemia reperfusion-induced lung injury in rats

BACKGROUND It has been reported that ischemic postconditioning (IPO) or mesenchymal stem cell (MSC) engraftment could protect organs from ischemia/reperfusion (I/R) injury. We investigated the synergetic effects of combined treatment on lung injury induced by I/R. METHODS Adult Sprague-Dawley rats were randomly assigned to one of the following groups: sham-operated control, I/R, IPO, MSC engraftment, and IPO plus MSC engraftment. Lung injury was assessed by arterial blood gas analysis, the wet/dry lung weight ratio, superoxide dismutase level, malondialdehyde content, myeloperoxidase activity, and tissue histologic changes. Cytokine expression was detected using real-time polymerase chain reaction, Western blotting, and enzyme-linked immunosorbent assay. Cell apoptosis was determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end assay and annexin V staining. RESULTS MSC engraftment or IPO alone markedly attenuated the lung wet/dry weight ratio, malondialdehyde and myeloperoxidase production, and lung pathologic injury and enhanced arterial partial oxygen pressure, superoxide dismutase content, inhibited pro-inflammatory cytokine levels, and decreased cell apoptosis in lung tissue, compared with the I/R group. In contrast, IPO pretreatment enhanced the protective effects of MSC on I/R-induced lung injury compared with treatment alone. Moreover, in the combined treatment group, the number of MSC engraftments in the lung tissue was increased, associated with enhanced survival of MSCs compared with MSC treatment alone. Additional investigation showed that IPO treatment increased expression of vascular endothelial growth factor and stromal cell-derived factor-1 in I/R lung tissue. CONCLUSIONS IPO might contribute to the homing and survival of transplanted MSCs and enhance their therapeutic effects through improvement of the microenvironment of I/R injury.

Thoracolaparoscopy oesophagectomy and extensive two-field lymphadenectomy for oesophageal cancer: introduction and teaching of a new technique in a high-volume centre

OBJECTIVES The aim of this study was to assess the experience of a high-volume centre with thoracolaparoscopy radical oesophagectomy and to evaluate the feasibility, tumour clearance, the learning curve and reproducibility of this technique. METHODS Eighty patients with thoracic oesophageal cancer who underwent thoracolaparoscopic oesophagectomy (TLE) were enrolled in this study. Two attending surgeons (Mingqiang Kang and Ruobai Lin) independently performed the procedure as operating surgeons. The 60 patients who had surgery performed on them by the senior attending surgeon, Mingqiang Kang, were divided into three groups of 20 patients: groups A, B and C. The results from the three groups were compared in order to detect any changes in the success of TLE as a way of monitoring the development of the surgeons technical skill. Another 20 patients had surgery performed on them by the new attending surgeon, Ruobai Lin, and were classified into the fourth group, D. The results from Group D were compared with those of the other three groups to evaluate the reproducibility of our technique. RESULTS There was no significant difference between the four groups with respect to age, gender, location of tumour or staging. The duration of both the thoracoscopic and laparoscopic procedures was significantly longer in Group A. The amount of estimated blood loss was significantly more in Group A than in the other groups. The number of lymph nodes dissected was similar in Groups A and D, whereas that of retrieved nodes was larger in Groups B and C. There was no significant difference in the incidence of respiratory complications, recurrent nerve palsy, anastomotic leaks, arrhythmia, chylothorax and delayed gastric emptying among the four groups. CONCLUSIONS When TLE procedures are started in units with a large volume of oesophageal resections, and when there is support from colleagues within the unit, transition from open to TLE can be achieved safely, with a satisfactory oncological outcome. A plateau of TLE skill was reached after 40 cases had been performed. If mini-fellowship training with supervision from senior surgeons is used, it is possible for a new attending surgeon to attain the requisite basic skill to perform TLE in a relatively short period of time.

Programmed death-1 polymorphisms is associated with risk of esophagogastric junction adenocarcinoma in the Chinese Han population: A case-control study involving 2,740 subjects

Single nucleotide polymorphisms (SNPs) in Programmed cell death 1 (PD-1) gene may contribute to the development of cancer. In this study, we selected PD-1 rs10204525 T>C, rs2227982 A>G, rs36084323 T>C and rs7421861 A>G polymorphisms and designed a hospital-based case-control study to determine the potential relationship between these functional SNPs in PD-1 gene and esophagogastric junction adenocarcinoma (EGJA) risk. A total of 1,063 EGJA patients and 1,677 controls were enrolled from Eastern Chinese Han population. SNPscanTMgenotyping assay was used to analyze the genotyping of PD-1 polymorphisms. We found that PD-1 rs7421861 A>G polymorphism was associated with the development of EGJA. However, PD-1 rs2227982 A>G polymorphism was a protective factor for EGJA. In addition, PD-1 rs36084323 CC homozygote genotype might be associated with a borderline decreased risk of EGJA. In a subgroup analysis, a decreased risk of EGJA in never drinking and never smoking groups was identified. Haplotype comparison analysis suggested that PD-1 Trs10204525Grs2227982C36084323Ars7421861 haplotype significantly decreased the risk of EGJA. However, Trs10204525Grs2227982C36084323Grs7421861 haplotype in PD-1 gene may confer risk to EGJA. In conclusion, our study highlights rs2227982 A>G, rs36084323 T>C and rs7421861 A>G polymorphisms and haplotypes in PD-1 gene, especially within the intron region, are significantly associated with the risk of EGJA. Further case-control studies with larger sample size and detailed gene-environmental data to replicate these findings in different populations are needed to validate our conclusion.

TCF7L2 rs290481 T>C polymorphism is associated with an increased risk of type 2 diabetes mellitus and fasting plasma glucose level

Genetic polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene may be key agents in the etiology of type 2 diabetes mellitus (T2DM). In the present case-control study, we aimed to assess the possible relationship of TCF7L2 polymorphisms with T2DM and determine the effect of TCF7L2 polymorphisms on the level of fasting plasma glucose (FPG) in Eastern Chinese Han subjects. The TCF7L2 rs7903146C>T and rs290481 T>C polymorphisms were genotyped by SNPscan genotyping assays in 502 subjects with T2DM and 782 non-diabetic controls. After adjusting for age, gender, drinking, smoking and body mass index (BMI), the association of TCF7L2 rs7903146C>T and rs290481 T>C polymorphisms with T2DM was determined. We found that TCF7L2 rs290481 T>C polymorphism increased the susceptibility of T2DM in the overall comparison. In subgroup analyses by age, sex, BMI, alcohol use and smoking status, a significantly increased risk of T2DM was also found in female, older subject and never drinking and BMI < 24 kg/m2 subgroups. The relationship of TCF7L2 rs290481 T>C polymorphism with the biochemistry characteristics in controls was also assessed. We found that TCF7L2 rs290481 T>C polymorphism significantly increased the level of FPG in controls. Our findings suggest that TCF7L2 rs290481 T>C polymorphism is associated with T2DM in Eastern Chinese Han population and links to variations in FPG level. In addition, these relationships are more pronounced in female, older subject and never drinking and BMI < 24 kg/m2 subgroups. A comprehensive fine-mapping study with functional investigation is needed to confirm or refute these potential correlations.

Feasibility and strategy for left tracheobronchial lymph node dissection in thoracolaparoscopic esophageal cancer surgery

This study evaluates the feasibility and strategy of left tracheobronchial lymph node (LN) dissection in the surgical treatment of esophageal cancer, and its impact on surgical outcomes following thoracoscopic esophagectomy.

Investigation of Cytotoxic T-lymphocyte antigen 4 Polymorphisms in Gastric Cardia Adenocarcinoma.

To assess the potential effects of Cytotoxic T‐lymphocyte antigen 4 (CTLA4) gene polymorphisms on susceptibility to gastric cardia adenocarcinoma (GCA), we genotyped four polymorphisms (rs733618 A>G, rs16840252 C>T, rs231775 G>A and rs3087243 G>A) in CTLA4 and calculated odds ratios (ORs) with the corresponding 95% confidence intervals (95% CIs) for the genotype and allele distributions between GCA cases and controls. The CTLA4 genotypes were determined by the polymerase chain reaction–ligase detection reaction (PCR‐LDR) analysis in 330 GCA patients and 608 unrelated cancer‐free controls. In this case–control study, there was no significant difference in the genotype and allele distributions of four CTLA4 polymorphisms between GCA patients and controls. However, haplotype association analysis indicated that compared with CTLA4 Grs733618Crs16840252Grs231775Crs3087243, CTLA4 Grs733618Crs16840252Ars231775Grs3087243 and Ars733618Crs16840252Grs231775Ars3087243 haplotypes conferred increased risks of GCA (OR = 6.46, 95% CI = 1.33–31.28; P = 0.012; both); however, CTLA4 Ars733618Crs16840252Ars231775Grs3087243 and Ars733618Trs16840252Grs231775Grs3087243 haplotypes conferred decreased risks of GCA (P = 0.001 and P = 0.011, respectively). These results highlight that the rare CTLA4 haplotypes may affect the development of GCA in the Chinese population.

Investigation of cyclin D1 rs9344 G>A polymorphism in colorectal cancer: a meta-analysis involving 13,642 subjects

The relationship between cyclin D1 (CCND1) rs9344 G>A polymorphism and colorectal cancer (CRC) risk is still ambiguous. To obtain a precise estimation of the relationship, we performed an extensive meta-analysis based on the eligible studies. Crude odds ratios with their 95% confidence intervals were harnessed to determine the strength of correlation between CCND1 rs9344 G>A polymorphism and CRC risk under the allele, the homozygote, the dominant, and the recessive genetic models, respectively (28 studies with 5,784 CRC cases and 7,858 controls). Our results indicated evidence of the association between CCND1 rs9344 G>A polymorphism and the increased risk of CRC in four genetic models: A vs G, AA vs GG, AA+GA vs GG, and AA vs GA+GG. In a stratified analysis by cancer type of CRC, there was an increased risk of sporadic CRC found in three genetic models: A vs G, AA vs GG, and AA+GA vs GG. In a stratified analysis by ethnicity, there was an increased CRC risk found among Asians in allele comparison genetic models, as well as Caucasians in two genetic models: AA+GA vs GG and A vs T. In summary, this meta-analysis demonstrates that CCND1 rs9344 G>A polymorphism may be a risk factor for CRC.

Investigation of IGF1, IGF2BP2, and IGFBP3 variants with lymph node status and esophagogastric junction adenocarcinoma risk: TANG et al.

Esophagogastric junction adenocarcinoma (EGJA) may be associated with obesity and overweight. Thus, any variant in energy metabolism–related gene may influence the development of EGJA. In this study, we recruited 720 EGJA cases and 1541 noncancer controls. We selected IGF2BP2 rs4402960 G > T, rs1470579 A > C, IGF1 rs5742612 A > G and IGFBP3 rs3110697 G > A, rs2270628 C > T and rs6953668 G > A loci and assessed the relationship of these polymorphisms with lymph node status and susceptibility of EGJA. We found that IGF2BP2 rs1470579 A > C and IGFBP3 rs6953668 G > A polymorphisms were associated with the decreased risk of EGJA ( IGF2BP2 rs1470579: CC vs AA: adjusted odds ratio [OR] = 0.65, 95% confidence interval [CI] = 0.43‐0.98, P = 0.041 and CC vs AA/AC: adjusted OR = 0.62, 95% CI = 0.41‐0.93, P = 0.021 and IGFBP3 rs6953668: GA vs GG: adjusted OR = 0.66, 95% CI = 0.47‐0.93, P = 0.019 and GA/AA vs GG: adjusted OR = 0.68, 95% CI = 0.48‐0.95, P = 0.026). However, we also found that IGF1 rs5742612 A > G polymorphism increased the risk of LNM among patients with EGJA (GG vs AA: adjusted OR = 1.88, 95% CI = 1.02‐3.46, P = 0.042 and GG vs AA/AG: adjusted OR = 1.92, 95% CI = 1.06‐3.47, P = 0.032). This study suggests that IGF2BP2 rs1470579 A > C and IGFBP3 rs6953668 G > A polymorphisms may decrease genetic susceptibility to EGJA in eastern Chinese Han population. In addition, our findings also indicate that IGF1 rs5742612 A > G polymorphism may increase the susceptibility of LNM among patients with EGJA.

Relationship between IGF2BP2 and IGFBP3 polymorphisms and susceptibility to non-small-cell lung cancer: a case–control study in Eastern Chinese Han population

Background IGF2BP2 and IGFBP3 polymorphisms may be associated with cancer risk. Methods With an aim to determine the association of variations in IGF2BP2 and IGFBP3 genes with risk of non-small-cell lung cancer (NSCLC), IGF2BP2 rs1470579 A>C, rs4402960 G>T and IGFBP3 rs2270628 C>T, rs3110697 G>A, and rs6953668 G>A polymorphisms were selected and genotyped in 521 NSCLC patients and 1,030 controls. Results We found that there was no difference in IGF2BP2 and IGFBP3 genotype distribution among the NSCLC patients and controls. The stratified analyses suggested that IGF2BP2 rs1470579 A>C polymorphism decreased the risk of NSCLC in some subgroups (female subgroup: CC vs AA: adjusted P=0.032 and CC vs AC/AA: adjusted P=0.028; <60 years subgroup: CC vs AA: adjusted P=0.012 and CC vs AC/AA: adjusted P=0.013; and never drinking subgroup: CC vs AA: adjusted P=0.046 and CC vs AC/AA: adjusted P=0.031). The stratified analyses also found that IGF2BP2 rs4402960 G>T polymorphism decreased the risk of NSCLC in some subgroups (female subgroup: TT vs GG: adjusted P=0.031 and TT vs GT/GG: adjusted P=0.026; <60 subgroup: TT vs GG: adjusted P=0.037 and TT vs GT/GG: adjusted P=0.038; and never drinking subgroup: TT vs GT/GG: adjusted P=0.046). Haplotype analysis indicated Ars1470579Crs2270628Grs3110697Grs4402960Ars6953668 haplotype decreased susceptibility of NSCLC (P=0.007). Conclusion Our study suggests that IGF2BP2 rs1470579 A>C, rs4402960 G>T single-nucleotide polymorphisms are candidates for decreased susceptibility to NSCLC among female, <60 years, and never drinking subgroups. In the future, more case–control studies with functional analysis are needed to confirm these preliminary findings.

Investigation of Cytotoxic T-lymphocyte antigen-4 polymorphisms in non-small cell lung cancer: a case-control study

The objective of this case-control study was to extensively explore the relationship of Cytotoxic T-lymphocyte antigen-4 (CTLA-4) tagging polymorphisms with susceptibility to non-small-cell lung cancer (NSCLC). We recruited 521 sporadic NSCLC cases and 1,030 non-cancer controls. The genotypes of CTLA-4 rs16840252 C>T, rs231775 G>A, rs3087243 G>A and rs733618 T>C polymorphisms were evaluated using a custom-by-design 48-Plex SNPscan Kit. Our findings revealed there was no statistically significant difference in CTLA-4 genotypes distribution among NSCLC patients and non-cancer controls. Similar findings were observed in the logistic regression analyses. However, the stratified analyses suggested CTLA-4 rs733618 vatiants were correlated with the development of NSCLC in ≥ 60 years subgroup (TC vs. TT: adjusted OR = 1.45, 95% CI = 1.04–2.02, P = 0.030) and even drinking subgroup (TC vs. TT: adjusted OR = 2.27, 95% CI = 1.11–4.60, P = 0.024 and TC/CC vs. TT: adjusted OR = 2.26, 95% CI = 1.15–4.43, P = 0.018). In conclusion, the present case-control study highlights that the CTLA-4 rs733618 T>C polymorphism was associated with the development of NSCLC in ≥ 60 years and even drinking subgroups. A fine-mapping study with functional assessment is necessary to confirm or refute our findings.