[Significance of expression of Myc-induced nuclear antigen 53 in hepatocellular carcinoma and its relationship with patient prognosis].

Objective: To detect the expression of Myc-induced nuclear antigen 53 (Mina53) and liver tissue >5 cm from the edge of the tumor (LTM5), and analyze its relationship with tumorigenesis, clinicopathological characteristics, and patient survival and prognosis in hepatocellular carcinoma (HCC). Methods: The expression levels of Mina53 mRNA and protein in 18 pairs of fresh HCC and LTM5 were assessed by qRT-PCR and Western blot, respectively. The expression of Mina53 in 284 pairs of HCC and LTM5 sample was determined by immunohistochemistry. Paired-sample t-test was used for the comparison of measurement data among groups, and heterogeneity of variance was tested using Wilcoxon rank-sum test. χ (2) test was used for the comparison of measurement data among groups. Kaplan-Meier method and log-rank test were used for survival analysis. Cox regression model was used for single factor and multi factor analysis. Results: The relative expression levels of Mina53 mRNA and protein in 18 fresh HCC tissues were significantly higher than those in LTM5 tissues (mRNA: -4.41 ± 1.48 and -5.93 ± 1.65, t = 3.100, P = 0.007; protein: 1.12 ± 0.29 and 0.46 ± 0.21, t = 10.616, P < 0.001). The relative expression level of Mina53 in 284 HCC tissues was higher than that of LTM5 (z = -18.739, P < 0.001). The expression level of Mina53 was associated with tumor size (χ (2) = 5.474, P = 0.019), vascular invasion (χ (2) = 8.965, P = 0.003), pathological grade (χ (2) = 12.006, P = 0.002), and TNM stage (χ (2) = 16.686, P < 0.001). The overall postoperative survival time and disease-free survival time of patients with high expression of Mina53 (28.5 months and 22.7 months, respectively) were shorter than those with low expression (33.0 months and 31.8 months, respectively) (P < 0.05) in HCC. Cox multivariate regression analysis showed that Mina53 and multiple tumors were independent prognostic factors affecting the overall postoperative survival time and disease-free survival time of HCC patients (P < 0.05). Conclusion: Mina53 may play an important role in the occurrence of HCC and participate in the process of tumor growth as well as invasion and metastasis. The high expression of Mina53 signifies that the patient has a poor prognosis and thus can be used as a potential marker for judging the prognosis of HCC patients.

[Rectum-preserving surgery after consolidation neoadjuvant therapy or totally neoadjuvant therapy for low rectal cancer: a preliminary report].

Objective: To investigate the feasibility and safety of sphincter-preserving surgery after neoadjuvant chemoradiotherapy (nCRT) with consolidation chemotherapy in the interval period or total neoadjuvant therapy (TNT) for low rectal cancer. Methods: A descriptive case series study was carried out. Clinical data of patients with locally advanced low rectal cancer (LALRC) who achieved complete clinical response (cCR) or nearly cCR (near-cCR) after nCRT at the Department of Colorectal Surgery of Fujian Medical University Union Hospital from May 2015 to February 2019 were retrospectively analyzed. Case inclusion criteria: (1) Low rectal adenocarcinoma within 6 cm from the anal verge. (2) After nCRT, tumor presented markedly regression as mucosal nodule or abnormalities, superficial ulcer, scar or a mucosal erythema (< 2 cm); no regional lymph node metastasis or distant metastasis was found in rectal ultrasonography, pelvic MRI and PET-CT; MRI showed obvious fibrosis in the original tumor site; and post-treatment CEA was normal. (3) The patient and the family members adhered to receive the transanal full-thickness local excision with informed consent. (4) When the residual lesions were difficult to detect after nCRT, patients received the watch and wait (W&W) strategy. Exclusion criteria: (1) Before nCRT, pathological results showed poorly differentiated or signet-ring cell carcinoma; lateral lymph node metastasis was suspected. (2) When the residual lesion size was more than 3 cm after nCRT, it was difficult to perform local excision. The consolidation nCRT group received 3-4 cycles of CAPOX regimen (oxaliplatin and capecitabine) or six cycles of mFOLFOX6 (oxaliplatin, leucovorin, and 5-fluorouracil) combined with the long-course radiotherapy (intensity-modulated radiation therapy with a total dose of 50.4Gy). Patients with concurrent chemotherapy more than or equal to five cycles of CAPOX or eight cycles of mFOLFOX6 were defined as total neoadjuvant therapy (TNT) group. Local resection was recommended for patients who were near-cCR according to modified MSKCC criteria 8-33 weeks after the end of radiotherapy. Patients with a near-cCR, who were judged as ycN0 according to PET-CT and MRI and were ypT0 after local excision, could enter the W&W strategy. Patients with pathologic stage more advanced than ypT1, and those with positive resection margin, or lymphovascular invasion were recommended for salvage radical surgery after local excision. The ypT1 patients with a negative resection margin and without lymphovascular invasion might receive the W&W management carefully if they refused radicalsurgery to sacrifice the sphincter for low rectal cancer. Results: Of 32 patients, 14 were males and 18 were females with the average age of 59 years old. Twenty-three patients underwent consolidation nCRT, and 9 received TNT. The first evaluation after treatments showed 19 cases with cCR and 13 with near-cCR. Twenty-nine patients received local excision while 3 patients with undetectable lesions received W&W policy. Four cases (12.5%) underwent salvage radical surgery with abdominoperineal resection. After local excision, 3 cases underwent salvage radical surgery immediately, and the final pathologic result was ypT3N0, ypT2N0, and ypT2N0 respectively, of whom 2 cases were in the group of consolidation CRT and 1 was in the TNT group. Of these 3 cases, 1 case with an initial cT3 stage showed a pathologic stage of ypT1 and a negative circumferential resection margin after consolidation nCRT and local excision, however, the final pathologic stage was ypT3 with fragmented tumor deposits in the mesorectum after the salvage radical surgery. Meanwhile 1 patient in the TNT group receiving W&W suffered from intraluminal regrowth after 7.4 months follow-up and underwent salvage abdominoperineal resection. One patient in the consolidation nCRT group died of stroke 42.5 months after local resection. Another patient in the TNT group had cerebral metastasis 10 months after the W&W policy, but no local recurrence was found in the pelvic cavity, then received resection of the metastatic tumors. The average follow-up for all the patients was 23 (5-51) months. The cumulative local regrowth rate was 5.0%. The overall survival rate was 85.7%, and the sphincter-preservation rate was increased from 25.0% (28/32) in the original plan to 87.5% (28/32) actually. The 3-year disease-free survival rate was 89.7%. The 3-year organ-preserving survival rate was 85.7%, and the 3-year stoma-free survival rate was 82.5%. At present, 31 patients still survived. Conclusions: After nCRT with consolidation chemotherapy or TNT for low rectal cancer, patients with cCR, ycN0 according to PET-CT and MRI, and ypT0 after local excision, can consider the W&W strategy. Strict patient selection with a near-cCR for local resection and sphincter-preserving strategy can reduce the local regrowth of cancer, and the short-term outcomes are satisfactory.

[Identification of gene biomarkers to predict responses to neoadjuvant chemoradiotherapy in patients with rectal cancer and pathways enrichment analysis].

Objective: To screen out the potential gene biomarkers to predict responses to neoadjuvant chemoradiotherapy (CRT) in patients with rectal cancer and to explore the main downstream pathways of resistance. Methods: The gene expression profiles (GSE35452) of locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy from 46 specimens (24 responders, TRG 0/1, and 22 non-responders, TRG 2/3) were downloaded from the GEO database. The differentially expressed genes were identified to screen out the potential biomarkers by use of the GCBI platform. GO and KEGG pathways enrichment analysis were performed to integrate enrichment results of differentially expressed genes. Signal-signal interaction network was constructed and analyzed to screen out potential main downstream pathways. Results: A total of 1079 differentially expressed genes were screened, including 657 up-regulated and 422 down-regulated ones. Among these genes, REG4 had the maximum fold change value of -6.029 491. In GO term, these differentially expressed genes were mainly enriched in molecule metabolic process, cell cycle, DNA-dependent transcription, signal transduction and apoptotic process. The KEGG pathways enrichment analysis showed that the differentially expressed genes were enriched in 65 KEGG pathways, including metabolic pathways, cell cycle and metabolism pathways. Signal-signal interaction network analysis showed that MAPK signaling pathway and cell cycle pathway might play a determinant role in the development of neoadjuvant chemoradiotherapy resistance. Further analysis showed that CDKN1B, CDKN2A, RBL1, TFDP1, CCND2, CCNE2, CDC6 and CDK6 in cell cycle might induce chemoradiotherapy resistance by blocking G1/S phase cell cycle arrest, decreasing the apoptosis of tumor cells and increasing S phase ratio of chemoradiotherapy resistance. Conclusion: G1/S phase cell cycle arrest blocking plays an important role in the development of chemoradiotherapy resistance in patients with rectal cancer. Moreover, the key genes, such as REG4, may be useful in predicting responses to neoadjuvant chemoradiotherapy.

[Effects of neoadjuvant chemoradiotherapy on the rates of sphincter preserving surgery in lower rectal cancer and analysis of their prognostic factors].

Objectives: To identify independent factors of sphincter preserving surgery, and to evaluated whether preoperative chemoradiotherapy (CRT) improves the sphincter preservation rate for lower rectal cancers. Methods: A total of 541 consecutive patients who underwent curative surgery for locally advanced rectal cancer (cT3-4Nx or cTxN+ ) within 6 cm of the anal verge with or without neoadjuvant CRT in Department of Colorectal Surgery, Union Hospital, Fujian Medical University between September 2000 and September 2013 were reviewed. Of these, 333 patients underwent surgery alone (Non-CRT group) and 208 patients also received preoperative chemoradiotherapy (CRT group). Clinical data were retrospectively reviewed to determine the factors influencing sphincter preservation, and to evaluate sphincter preservation rate according to tumor height over 1-cm intervals. The categorical variables were compared using χ2 test and Fisher exact test. Continuous variables were compared using t test. Logistic regression was used to identify factors influencing sphincter preservation. A receiver operating characteristic (ROC) curve was constructed, and Youden's index was calculated to evaluate the predictive abilities of factors. Results: Multivariate analysis indicated that the independent factors influencing sphincter preservation were tumor height (OR=5.867, 95% CI: 4.155 to 8.285, P=0.000), pathological T stage (OR=0.688, 95% CI: 0.462 to 1.025, P=0.066), CRT (OR=2.088, 95% CI: 0.971 to 4.492, P=0.060) and histopathological type (OR=0.288, 95% CI: 0.136 to 0.611, P=0.001). The results of ROC analysis showed that the cut-off points for factors affecting sphincter preservation were as follows: (1) tumor height prior to CRT higher than 4.5 cm, (2) not mucinous or signet ring adenocarcinoma, (3) pathological T stage higher than T3, (4) had received preoperative CRT. In an analysis according to tumor height, the sphincter preservation rate was higher in CRT group only when tumor was located in 3.0 to 3.9 cm and 4.0 to 4.9 cm from the annal verge (3.0 to 3.9 cm, 59.4% vs. 2.8%, χ2=26.138, P=0.000; 4.0 to 4.9 cm, 76.9% vs. 37.9%, χ2=10.563, P=0.001). Conclusions: There is a large increased rate of sphincter preservation when patients meet the following conditions: (1) tumor height prior to CRT higher than 4.5 cm, (2) not mucinous or signet ring adenocarcinoma, (3)pathological T stage higher than T3, (4) had received preoperative CRT. Only when tumors are between 3 and 5 cm from the anal verge, CRT could increase the rate of anal sphincter preservation.

[Prognostic factors of postoperative incisional surgical site infections for colorectal cancer].

Objective: To explore the prognostic factors of postoperative incisional surgical site infections (I-SSI) for colorectal cancer. Methods: Clinical data of 2 385 colorectal cancer patients undergoing resection by the same surgical team in Department of Colon and Rectum Surgery, Fujian Medical University Union Hospital from January 2000 to February 2014 was analyzed retrospectively. There were 1 421 male and 964 female patients, with a mean age of (59±13) years. Univariate analysis and multivariate Logistic regression analysis were performed for independent prognostic factors of I-SSI. Results: The I-SSI occurred in 77 patients (3.23%). The results of univariate analysis showed that there were statistical differences in body mass index (t=-3.356), operation time (t=-3.609), length of incision (t=-5.492), radical operation (χ2=8.963), laparoscopic surgery (χ2=25.884), combined evisceration (χ2=6.349) and intraoperative blood infusion (χ2=4.176) between two groups (all P<0.05) . The results of multivariate Logistic regression analysis showed that independent prognostic factors of I-SSI were identified to be body mass index (OR=1.087, 95%CI: 1.023 to 1.155, P=0.007), operation time (OR=1.007, 95%CI: 1.002 to 1.012, P=0.006), preoperative chemoradiotherapy (OR=2.434, 95%CI: 1.099 to 5.393, P=0.028) and combined evisceration (OR=2.596, 95%CI: 1.060 to 6.357, P=0.037). The independent protective prognostic factor of I-SSI was identified to be the laparoscopic surgery (OR=0.386, 95%CI: 0.170 to 0.877, P=0.023). Conclusions: Body mass index, operation time, preoperative chemoradiotherapy and combined evisceration are identified to be independent prognostic factors for I-SSI. High-risk patients should receive individualized perioperative intervention. Nevertheless, the laparoscopic surgery can decrease the incidence of I-SSI.

Selecting stage ypT0-1N0 for locally advanced rectal cancer following preoperative chemoradiotherapy: implications for potential candidates of organ-sparing management.

AIM: Local excision or a wait-and-see policy may offer the possibility of organ preservation for locally advanced rectal cancer (LARC) after preoperative chemoradiotherapy (CRT). Identifying associated factors of good responders (GR) with stage ypT0-1N0 would probably influence the selection of potential candidates who were theoretically eligible for organ-sparing management. This study was to establish a scoring system to select stage ypT0-1N0 for LARC following preoperative CRT. METHOD: Between 2009 and 2014, 262 patients with middle and low LARC were treated with CRT and radical surgery. Clinicopathological data which were found to be significantly associated with GR were incorporated into a scoring system. RESULTS: Fifty-seven (21.8%) patients were GR with stage ypT0-1N0 in the operative specimen. Multivariate analyses indicated that a low level of pretreatment carcinoembryonic antigen (CEA) and post-treatment CEA <2.55 ng/ml (P = 0.008 and P = 0.009 respectively) and long-axis diameter of residual tumours (P = 0.006) were independently associated with stage ypT0-1N0. The three factors were incorporated into a scoring system. Using receiver operating characteristic curve analysis, we determined a cutoff value of -0.3 for scores, at which the system's sensitivity was 71.9% and specificity 73.1%. When applied to testing samples, the sensitivity was 74.1% and specificity 76.2%. CONCLUSION: We demonstrated that low levels of pretreatment and post-treatment CEA and the long-axis diameter of residual tumours were associated with stage ypT0-1N0 for LARC after CRT. Therefore, the three-factor scoring system may be used to select potential candidates for organ-sparing management.

Association of ERCC1 polymorphisms (rs3212986 and rs11615) with the risk of head and neck carcinomas based on case-control studies.

PURPOSE: Current data regarding association between ERCC1 polymorphisms and the risk of head and neck squamous cell carcinomas (HNSCC) have shown controversial results. The current study aims to achieve a more accurate estimation of the association between two well-characterized ERCC1 polymorphisms (rs3212986 and rs11615) and HNSCC risk by a meta-analysis of all eligible studies. METHODS: The meta-analysis was performed by reviewing seven studies on the ERCC1 C8092A (rs3212986) polymorphism including 2055 cases and 2635 controls and four studies on the T19007C (rs11615) polymorphism including 910 cases and 1337 controls. RESULTS: For ERCC1 rs3212986 polymorphism, no significant association with HNSCC was found in overall analysis, but subgroup analysis revealed that a significant association of the rs3212986 polymorphism was found among Asians (A vs. C: OR 0.83; 95% CI 0.70-0.99) but not Caucasians. For ERCC1 rs11615 polymorphism, a significant association with HNSCC (TC + CC vs. TT: OR 1.23; 95% CI 1.03-1.47) was found in overall analysis. Consistently, subgroup analysis revealed that significant associations of the rs3212986 polymorphism were found among Asians (C vs. T: OR 1.32; 95% CI 1.04-1.69) and in laryngeal carcinoma (CC vs. TC + TT: OR 1.32; 95% CI 1.02-1.72). CONCLUSION: The findings of the meta-analysis indicated that a decreased risk for the ERCC1 rs3212986 polymorphism was found among Asians, and an increased risk for the ERCC1 rs11615 polymorphism was found in overall HNSCC, especially in Asian subgroup and laryngeal site, suggesting that ERCC1 rs3212986 polymorphism in Asians may act as a protective factor and rs11615 polymorphism may be a risk factor for HNSCC.

The inhibition of eugenol on glucan is essential for the biofilm eradication effect on caries-related biofilm in an artificial mouth model.

This study aimed to evaluate the inhibitory effects of herbal extracts on caries-related bacteria, glucan and biofilm in vitro. Sensitive tests of bacteria were carried out by broth dilution method on a 96-microwell plate. Glucan inhibition tests were carried out using the phenol sulphate method. A minimum biofilm inhibitory concentration (MBIC) test was performed in an artificial mouth model. The results of the MBIC of agents were 8, 16 and 32 mg mL(-1) for eugenol, tannic acid and magnolol, respectively. For the results of glucan inhibition tests, over 63%, 28% and 27% inhibition occurred on insoluble glucan syntheses of Streptococcus sobrinus for eugenol, magnolol and tannic acid, respectively. Over 46%, 16% and 13% inhibition on soluble glucan syntheses for eugenol, magnolol and tannic acid, respectively, were also observed. In conclusion, the inhibition of eugenol on glucan is essential for the biofilm inhibition effect on caries-related biofilm in an artificial mouth model in vitro.

Influence of nanotips on the hydrophilicity of metallic nanorod surfaces.

The hydrophilicity of vertically aligned metal nanorods with sharp nanotips were investigated experimentally. Ruthenium and platinum nanorod arrays were deposited on flat silicon substrates using oblique angle sputter deposition. We show that the effects of nanotips on nanorods should be considered in the "hemiwicking" model for hydrophilic metallic samples. With the influence of nanotips, we successfully explained the experimental contact angles of water sessile drops on metallic nanorod surfaces. Our experiments confirm that the shape of the nanorods is an important parameter in determining the hydrophilicity of the nanostructured surfaces.

Mechanical testing of isolated amorphous silicon slanted nanorods.

Mechanical testing was performed on a new class of nanostructures-amorphous Si slanted nanorods of rectangular cross section, fixed at one end to the substrate. These nanorods were grown spatially well separated on nano-pillars under the oblique angle physical vapor deposition technique. Various samples with different dimensions and inclination angles were tested in bending using an atomic force microscope. The material response was elastic up to large stresses/deflections. The Young's modulus was calculated from the slope of the experimentally observed stiffness versus the geometrical factor common to all the samples and was found to be (94.14 +/- 10.21) GPa. No size effect of this parameter was observed within the accuracy of the present measurement.

Mechanics of patterned helical Si springs on Si substrate.

The elastic response, including the spring constant, of individual Si helical-shape submicron springs, was measured using a tip-cantilever assembly attached to a conventional atomic force microscope. The isolated, four-turn Si springs were fabricated using oblique angle deposition with substrate rotation, also known as the glancing angle deposition, on a templated Si substrate. The response of the structures was modeled using finite elements, and it was shown that the conventional formulae for the spring constant required modifications before they could be used for the loading scheme used in the present experiment.