Factors affecting the safety and efficacy of peroral endoscopic myotomy for achalasia / 南方医科大学学报

<p><b>OBJECTIVE</b>To identify the factors that affect the safety and efficacy of peroral endoscopic myotomy (POEM) for treatment of achalasia.</p><p><b>METHODS</b>Data of consecutive patients undergoing POEM for confirmed achalasia between December, 2010 and December, 2015 were collected, including the procedure time, approach of tunnel entry incision, approach of myotomy, complications and follow-up data.</p><p><b>RESULTS</b>Among the total of 439 patients enrolled, the overall complication rate was 28.7% (126/439). Treatment success (Eckardt score≤3) was achieved in 94.5% of 364 patients followed up for a median of 6 months (1-48 months), and the mean score was reduced significantly from 6.7∓1.5 before treatment to 1.2∓1.1 after the treatment (P<0.05). Logistic regression revealed that the year when POEM was performed and the approach of entry incision were two significant factors contributing to complications: with the year 2015 as the reference, the odds ratio (OR) was 9.454 (95% CI: 2.499-35.76) for the years before 2011, 2.177 (95% CI: 0.794-5.974) for 2012, 3.975 (95% CI: 1.904-8.298) for 2013, and 1.079 (95% CI: 0.601-1.940) for 2014; with the longitudinal entry incision as the reference, the OR was 0.369 (95% CI: 0.165-0.824) for inverted T entry incision and 0.456 (95% CI: 0.242-0.859) for transverse entry incision. The approach of myotomy was the significantly associated with symptomatic relapse: with full-thickness myotomy combined with indwelling an anti-reflux belt as the reference, the OR was 0.363 (95% CI: 0.059-2.250) for gradual full-thickness myotomy, 2.137 (95% CI: 0.440-10.378) for circular muscle myotomy, and 4.385 (95% CI: 0.820-23.438) for circular muscle myotomy in combination with balloon shaping; the recurrence rate was 0 with a full-thickness myotomy.</p><p><b>CONCLUSION</b>The complication rates of POEM appears to decrease over time, and an inverted T entry incision is the best choice for controlling the complications. Gradual full-thickness myotomy is an excellent approach for treatment of achalasia in terms of the relapse rate, procedure time and the incidence of reflux esophagitis.</p>

Aquaporin 8 expression is reduced and regulated by microRNAs in patients with ulcerative colitis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Ulcerative colitis (UC) is associated with differential expression of genes involved in inflammation and tissue remodeling. MicroRNA (miRNA) plays an important role in the pathogenesis of UC by regulating the gene expression at the post-transcriptional level and control crucial physiological processes. This study aimed to identify aquaporin 8 (AQP8) expression and its relationship with miRNA in UC patients.</p><p><b>METHODS</b>Human colon samples, in this study, were obtained from 20 patients with UC and 16 healthy subjects undergoing diagnostic colonoscopy at the Chinese People's Liberation Army General Hospital between December 2009 and June 2010. We screened different genes from UC tissues and healthy subjects using genome-wide microarray, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting. Regulation of gene expression by miRNAs was assessed by luciferase reporter construct assays and transfection of specific miRNA mimics and inhibitor.</p><p><b>RESULTS</b>We identified that 1596 genes were increased and 1301 genes were decreased in UC patients compared to healthy subjects. Among them, we focused on the analysis of AQP8 which was decreased three folds in UC tissues (P < 0.01). The expression of AQP8 mRNA and protein were decreased in UC tissue and tumor necrosis factor (TNF)-α treated HT29 cells compared with controls (P < 0.05). We searched candidate target miRNAs of AQP8 through bioformatics and the luciferase report assay analysis indicated that miR-424, miR-195, miR-330, miR-612, and miR-16 which has complementary site in the 3-untranslated region (3'UTR) of AQP8 could decrease the relative luciferase activities by 10% - 45%.</p><p><b>CONCLUSION</b>AQP8 and its relationship with miRNAs may be involved in the pathogenesis of UC.</p>

Epigenetic regulation of Wnt signaling pathway gene SRY-related HMG-box 17 in papillary thyroid carcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>SRY-related HMG-box 17 (SOX17) encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and in the determination of the cell fate. Recently, it was considered as a tumor suppressor gene to inhibit canonical Wnt/β-catenin signaling pathway in several malignancies. However, the function of SOX17 in thyroid cancer was unknown. Therefore, we investigated the epigenetic changes and the function of SOX17 in thyroid cancer.</p><p><b>METHODS</b>The methylation status of the promoter region of SOX17 was detected using methylation-specific PCR in 63 papillary thyroid carcinoma (PTC) tissue, 10 normal thyroid tissue, and two thyroid cancer cell lines. Semi-quantitative RT-PCR was used to assess mRNA expression of SOX17 before and after 5-aza-2'-deoxycytidine treatment in thyroid cancer cell lines. Expression of SOX17 and β-catenin were detected by immunohistochemistry in PTC and adjacent tissue. Luciferase reporter assay, colony formation, transfection, and Western blotting were employed to analyze the effect of SOX17 on thyroid cancer cell proliferation and the function of SOX17 in the Wnt signal pathway.</p><p><b>RESULTS</b>Loss of SOX17 expression was correlated to the promoter region hypermethylation in thyroid cancer cell lines. Re-expression of SOX17 was found in TPC-1 cell line after 5-aza-2'-deoxycytidine treatment. In primary thyroid cancer, 60.3% (38/63) were methylated and 39.7% (25/63) unmethylated. But no methylation was found in noncancerous thyroid tissues. Methylation of SOX17 was associated reversely with β-catenin expression in the cytoplasm or nucleus significantly in the PTC (P < 0.05). Colony formation was inhibited by re-expression of SOX17 in TPC-1 cells. SOX17 suppressed the Wnt signaling pathway and the HMG domain was essential for this effect.</p><p><b>CONCLUSIONS</b>SOX17 was frequently methylated in human PTC. Loss of SOX17 expression was induced by promoter region hypermethylation. SOX17 inhibited thyroid cancer proliferation. Methylation of SOX17 activated the Wnt signaling pathway in human thyroid cancer.</p>

FHL2 inhibits the Id3-promoted proliferation and invasive growth of human MCF-7 breast cancer cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Id3 plays a key role in the progression of breast cancer. Previously, four and a half LIM protein (FHL2) was identified as a repressor of Id family proteins by interacting with them. This study aimed to investigate the effects of FHL2 on the transcriptional regulation and oncogenic activities of Id3 in human breast cancer cells.</p><p><b>METHODS</b>Cell transfection was performed with SuperFect reagent. Stable transfectants that overexpressed Id3 were obtained by selection on G418. The level of Id3 protein was determined by Western blotting analysis. Dual luciferase assays were used to measure the effect of Id3 and FHL2 on E47-mediated transcriptional activity in MCF-7 human breast cancer cells. The MTT assay was used to measure cell proliferation. The transwell assay was used to measure the invasive capacity of MCF-7 cancer cells.</p><p><b>RESULTS</b>Id3 markedly repressed transcription mediated by the basic helix-loop-helix (bHLH) factor E47 in MCF-7 cells. This Id3-mediated repression was effectively antagonized by FHL2. Overexpression of Id3 markedly promoted the proliferation and invasive capacity of MCF-7 cells; however, these effects were significantly suppressed by the overexpression of FHL2.</p><p><b>CONCLUSIONS</b>FHL2 can inhibit the proliferation and invasive growth of human breast cancer cells by repressing the functional activity of Id3. The functional roles of FHL2-Id3 signaling in the development of human breast cancer need further research.</p>

Inhibitory effect of S-adenosylmethionine on the growth of human gastric cancer cells in vivo and in vitro / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>S-adenosylmethionine (SAM), the most important methyl donor in human body, is generally used to treat cholestasis in clinic. In recent years, SAM has been found to have inhibitory effects on breast cancer, liver cancer and colon carcinoma. This study was to investigate the inhibitory effects of SAM on human gastric cancer cells in vivo and in vitro, and the antitumor mechanisms.</p><p><b>METHODS</b>The effects of SAM on the proliferation of gastric cancer SGC-7901 and MKN-45 cells were determined by MTT assay. After SGC-7901 and MKN-45 cells were treated with 0, 2, and 4 mmol/L SAM for 72 h, the expression and methylation of c-myc and urokinase type plasminogen activator (uPA) were detected by reverse transcription-polymerase chain reaction (RT-PCR) and methylation-specific PCR (MSP). Tumor xenografts were established by injecting SGC-7901 cells subcutaneously in BALB/c nude mice. The mice were randomized into low concentration group [192 µmol/(kg · day)], high concentration group [768 µmol/(kg · day)], and control group [normal saline (NS)], and received peritoneal injection of relative reagents for 15 days. The tumor size was measured, the protein and mRNA expression of c-myc and uPA were detected by immunohistochemistry and RT-PCR, and the methylation of c-myc and uPA genes was detected by MSP.</p><p><b>RESULTS</b>SAM inhibited the growth of SGC-7901 and MKN-45 cells obviously and the effects were enhanced with the increase of SAM concentration and treatment time. The mRNA expression of c-myc and uPA in SGC-7901 cells and that of uPA in MKN-45 cells significantly decreased. The c-myc and uPA genes in SGC-7901 cells and uPA gene in MKN-45 cells were partly or completely methylated after SAM treatment. The tumor volume was significantly lower in low concentration group [(618.51 ± 149.27) mm³] and high concentration group [(444.32 ± 118.51) mm³] than in control group [(1018.22 ± 223.07) mm³] (both P < 0.01). The inhibitory rates of tumor growth were 39.26% in low concentration group and 56.36% in high concentration group. The protein and mRNA expressions of c-myc and uPA were remarkably reduced (all P < 0.01), and the hypomethylation of c-myc and uPA genes were reversed after SAM treatment.</p><p><b>CONCLUSIONS</b>SAM can inhibit the growth of human gastric cancer cells both in vivo and in vitro. The mechanism may be that SAM can reverse the hypomethylation of c-myc and uPA genes, reduce their expression, and then inhibit tumor growth.</p>

Natural orifice translumenal endoscopic surgery (NOTES): current status and challenges / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To give a conceptual description of natural orifice translumenal endoscopic surgery (NOTES), review the early efforts in the NOTES field, and discuss its challenges and limitations.</p><p><b>DATA SOURCES</b>The data were retrieved mainly from publications listed in MEDLINE, PubMed and China Wanfang Database from 2005 to 2009. The search term was "NOTES".</p><p><b>STUDY SELECTION</b>The articles involved in the "NOTES" study were selected and the review articles were excluded from the comparison.</p><p><b>RESULTS</b>A marked increase in quantity in articles was shown each year for NOTES studies from 2006 to 2009. Animal experiments with "NOTES" have been carried out in China from 2007, and two independent "NOTES" procedures on humans were reported in 2009.</p><p><b>CONCLUSION</b>Although still in its infancy, the "NOTES" procedure is promising as another type of minimally invasive surgery and favorable alternative to current interventions.</p>