Natural variations in a pectin acetylesterase gene, MdPAE10, contribute to prolonged apple fruit shelf life.

Room-temperature shelf life is a key factor in fresh market apple (Malus domestica Borkh.) quality and commercial value. To investigate the genetic and molecular mechanism underlying apple shelf life, quantitative trait loci (QTL) were identified using bulked segregant analysis via sequencing (BSA-seq). Ethylene emission, flesh firmness, or crispness of apple fruit from 1,273 F1 plants of M. asiatica Nakai 'Zisai Pearl' × M. domestica 'Golden Delicious' were phenotyped prior to and during 6 wk of room-temperature storage. Segregation of ethylene emission and the flesh firmness or crispness traits was detected in the population. Thirteen QTL, including three major ones, were identified on chromosome 03, 08, and 16. A candidate gene encoding pectin acetylesterase, MdPAE10, from the QTL Z16.1 negatively affected fruit shelf life. A 379-bp deletion in the coding sequence of MdPAE10 disrupted its function. A single nucleotide polymorphism (SNP) in the MdPAE10 promoter region reduced its transcription activity. These findings provided insight into the genetic control of fruit shelf life and can be potentially used in apple marker-assisted selection.

Role of MdERF3 and MdERF118 natural variations in apple flesh firmness/crispness retainability and development of QTL-based genomics-assisted prediction.

Retention of flesh texture attributes during cold storage is critical for the long-term maintenance of fruit quality. The genetic variations determining flesh firmness and crispness retainability are not well understood. The objectives of this study are to identify gene markers based on quantitative trait loci (QTLs) and to develop genomics-assisted prediction (GAP) models for apple flesh firmness and crispness retainability. Phenotype data of 2664 hybrids derived from three Malus domestica cultivars and a M. asiatica cultivar were collected in 2016 and 2017. The phenotype segregated considerably with high broad-sense heritability of 83.85% and 83.64% for flesh firmness and crispness retainability, respectively. Fifty-six candidate genes were predicted from the 62 QTLs identified using bulked segregant analysis and RNA-seq. The genotype effects of the markers designed on each candidate gene were estimated. The genomics-predicted values were obtained using pyramiding marker genotype effects and overall mean phenotype values. Fivefold cross-validation revealed that the prediction accuracy was 0.5541 and 0.6018 for retainability of flesh firmness and crispness, respectively. An 8-bp deletion in the MdERF3 promoter disrupted MdDOF5.3 binding, reduced MdERF3 expression, relieved the inhibition on MdPGLR3, MdPME2, and MdACO4 expression, and ultimately decreased flesh firmness and crispness retainability. A 3-bp deletion in the MdERF118 promoter decreased its expression by disrupting the binding of MdRAVL1, which increased MdPGLR3 and MdACO4 expression and reduced flesh firmness and crispness retainability. These results provide insights regarding the genetic variation network regulating flesh firmness and crispness retainability, and the GAP models can assist in apple breeding.

Risk factors and consequences of conversion to open surgery in laparoscopic common bile duct exploration.

BACKGROUND: Although laparoscopic common bile duct exploration (LCBDE) has shown many obvious advantages compared with open surgery in the treatment of common bile duct (CBD) stones, it remains unclear regarding risk factors of conversion from LCBDE to open surgery and whether conversion will counteract the advantages of LCBDE. The purpose of this study was to explore risk factors and consequences of conversion from LCBDE to open surgery. METHODS: A retrospective study was conducted, using a database of 644 patients with LCBDE between 2011 and 2017. Risk factors for conversion to open surgery were determined based on univariable and multivariable analysis. The consequences of conversion to open surgery in LCBDE were analyzed. RESULTS: Conversion was required in 27 (4.2%) of 644 patients undergoing LCBDE. Independent risk factors for conversion were as follows: the max diameter of stones in CBD (odds ratio (OR) 2.234, 95%CI 1.031-4.842; p = 0.042), edema of CBD (OR 12.530, 95%CI 4.633-33.887; p < 0.001), and multiple stones in CBD (OR 3.438, 95%CI: 1.133-10.428; p = 0.029). These risk factors and their combined were good predictors for conversion in LCBDE. More blood loss, longer operative time, longer postoperative hospital stay, and higher incision infection were identified in patients with conversion than those without conversion. However, no significant differences were observed regarding mortality, readmission within 30 days, reoperation, bile leakage, and intra-abdominal fluid collection. CONCLUSION: Conversion to open surgery in LCBDE was associated with acute edematous CBD with large and multiple stones. Conversion can offset the advantages of LCBDE.

Increased water salinity applied to tomato plants accelerates the development of the leaf miner Tuta absoluta through bottom-up effects.

Variation in resource inputs to plants may trigger bottom-up effects on herbivorous insects. We examined the effects of water input: optimal water vs. limited water; water salinity: with vs. without addition of 100 mM NaCl; and their interactions on tomato plants (Solanum lycopersicum), and consequently, the bottom-up effects on the tomato leaf miner, Tuta absoluta (Meytick) (Lepidoptera: Gelechiidae). Plant growth was significantly impeded by limited water input and NaCl addition. In terms of leaf chemical defense, the production of tomatidine significantly increased with limited water and NaCl addition, and a similar but non-significant trend was observed for the other glycoalkaloids. Tuta absoluta survival did not vary with the water and salinity treatments, but the treatment "optimal water-high salinity" increased the development rate without lowering pupal mass. Our results suggest that caution should be used in the IPM program against T. absoluta when irrigating tomato crops with saline water.

Braun Enteroenterostomy Following Pancreaticoduodenectomy: A Systematic Review and Meta-Analysis.

Pancreaticoduodenectomy (PD) holds high postoperative morbidity. How to resolve this issue is challenged. An additional anastomosis (Braun enteroenterostomy) following PD may decrease the postoperative morbidity, but holds conflicting results. The objective of this study is to investigate the advantages and disadvantages of Braun enteroenterostomy in PD.Clinical studies compared perioperative outcomes between the Braun group and the non-Braun group following PD before December 21, 2014 were retrieved and filtered from PubMed, EMBASE, Web of Science, the Cochrane Library, and Chinese electronic databases (VIP database, WanFang database, and CNKI database). Relevant data were extracted according to predesigned sheets. Blood loss, operating time, and postoperative mortality and morbidity were evaluated using odds ratio (OR), weighted mean difference, or standard mean difference (SMD).Ten studies concerning 1614 patients were included. No significant differences between the Braun and the non-Braun group were identified in mortality (OR: 0.65, 95% confidence interval [CI]: 0.26-1.60), intraoperative blood loss (SMD: -0.035, 95% CI: -0.253 to 0.183), postoperative pancreatic fistula (POPF) (OR: 0.67, 95% CI: 0.35-1.67), bile leakage (OR: 0.537, 95% CI: 0.287-1.004), postoperative gastrointestinal hemorrhage (OR: 1.17, 95% CI: 0.578-2.385), intraabdominal abscesses (OR: 0.793, 95% CI: 0.444-1.419), wound complications (OR: 0.806, 95% CI: 0.490-1.325), and hospital stay (SMD: -0.098, 95% CI: -0.23 to 0.033). Braun enteroenterostomy extended operating time (SMD: 0.39, 95% CI: 0.02-0.78), but it was associated with lower reoperation rate (OR: 0.380, 95% CI: 0.149-0.968), lower morbidity rate (OR: 0.66, 95% CI: 0.49-0.91), lower clinically relevant delayed gastric emptying (Grades B and C) (OR: 0.375, 95% CI: 0.164-0.858), lower nasogastric tube reinsertion (OR: 0.436, 95% CI: 0.232-0.818), and less postoperative vomiting (OR: 0.444, 95% CI: 0.262-0.755).Braun enteroenterostomy can be safely performed during PD. It is beneficial for patients and could be recommended in PD from the current published data.PROSPERO registration number: CRD42015016198.

Transvaginal cholecystectomy vs conventional laparoscopic cholecystectomy for gallbladder disease: A meta-analysis.

AIM: To compare the results of transvaginal cholecystectomy (TVC) and conventional laparoscopic cholecystectomy (CLC) for gallbladder disease. METHODS: We performed a literature search of PubMed, EMBASE, Ovid, Web of Science, Cochrane Library, Google Scholar, MetaRegister of Controlled Trials, Chinese Medical Journal database and Wanfang Data for trials comparing outcomes between TVC and CLC. Data were extracted by two authors. Mean difference (MD), standardized mean difference (SMD), odds ratios and risk rate with 95%CIs were calculated using fixed- or random-effects models. Statistical heterogeneity was evaluated with the χ(2) test. The fixed-effects model was used in the absence of statistically significant heterogeneity. The random-effects model was chosen when heterogeneity was found. RESULTS: There were 730 patients in nine controlled clinical trials. No significant difference was found regarding demographic characteristics (P > 0.5), including anesthetic risk score, age, body mass index, and abdominal surgical history between the TVC and CLC groups. Both groups had similar mortality, morbidity, and return to work after surgery. Patients in the TVC group had a lower pain score on postoperative day 1 (SMD: -0.957, 95%CI: -1.488 to -0.426, P < 0.001), needed less postoperative analgesic medication (SMD: -0.574, 95%CI: -0.807 to -0.341, P < 0.001) and stayed for a shorter time in hospital (MD: -1.004 d, 95%CI: -1.779 to 0.228, P = 0.011), but had longer operative time (MD: 17.307 min, 95%CI: 6.789 to 27.826, P = 0.001). TVC had no significant influence on postoperative sexual function and quality of life. Better cosmetic results and satisfaction were achieved in the TVC group. CONCLUSION: TVC is safe and effective for gallbladder disease. However, vaginal injury might occur, and further trials are needed to compare TVC with CLC.

One potential oncolytic adenovirus expressing Lipocalin-2 for colorectal cancer therapy.

Colorectal cancer is an aggressive malignancy with a high mortality rate; however, effective therapies are currently lacking. Cancer-targeting gene-virotherapy (CTGVT) has been proposed to be a promising strategy for cancer therapy. The purpose of this study was to investigate the antitumor activity of the oncolytic adenovirus harboring Lipocalin-2 (ZD55-Lipocalin-2, an example of CTGVT) in colorectal cancer. ZD55-Lipocalin-2 was generated by deleting E1B55-KD and inserting the Lipocalin-2 gene. Its cytopathic effects and cell growth inhibition were detected in vitro, and antitumor effects were examined in a nude mouse model of human colorectal cancer xenografts. Results showed that ZD55-Lipocalin-2 significantly inhibited the colorectal cancer growth by selective cytolysis, inducing apoptosis and decreasing the microvessel density in tumors. The anticancer potential of ZD55-Lipocalin-2 showed stronger than that of the isolated Lipocalin-2 gene therapy or isolated ZD55 oncolytic adenovirus therapy. ZD55-Lipocalin-2 may serve as a potential anticancer agent for colorectal cancer treatment.

Treatment of pancreatic cancer using an oncolytic virus harboring the lipocalin-2 gene.

BACKGROUND: The 5-year survival rate for patients with pancreatic cancer is <5%, and it is always resistant to the current chemoradiotherapy. Therefore, new, effective agents for the treatment of pancreatic cancer are urgently needed. The promising strategy of cancer-targeting gene virotherapy (CTGVT) has demonstrated great anticancer potential. The objective of the current study was to determine whether 1 CTGVT approach, oncolytic virus (OV)-harboring lipocalin-2, is capable of treating pancreatic cancer. METHODS: Tissue microarrays were constructed to detect the expression of lipocalin-2 in 60 specimens of pancreatic adenocarcinoma. The clinical significance of lipocalin-2 was investigated in an analysis of correlations between lipocalin-2 expression and matched clinical characteristics. A lipocalin-2-expressing OV, ZD55-lipocalin-2, was constructed by deleting the adenoviral protein E1B55kD. The antitumor efficacy and mechanisms of the OV were investigated in pancreatic cancer cells with v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in vitro and in vivo. RESULTS: Lipocalin-2 expression was correlated with a good prognosis in patients with pancreatic adenocarcinoma. ZD55-lipocalin-2 dramatically inhibited the growth of pancreatic cancer in vitro and in vivo by inducing cytolysis and caspase-dependent apoptosis. CONCLUSIONS: Higher lipocalin-2 expression predicted a better prognosis in patients with pancreatic cancer. The results indicated that ZD55-lipocalin-2, which specifically expressed higher levels of lipocalin-2 in tumor cells, may serve as a potent anticancer drug for pancreatic cancer therapy, especially for patients who have pancreatic adenocarcinoma with KRAS mutations.

Predictive value of serum carbohydrate antigen 19-9 in malignant intraductal papillary mucinous neoplasms.

BACKGROUND: The goal of the present study was to evaluate the predictive value of serum carbohydrate antigen 19-9 (CA 19-9) in the diagnosis of malignant intraductal papillary mucinous neoplasms of pancreas (IPMNs). METHODS: Eighty-six patients with pathological diagnosis of IPMNs in Zhongshan Hospital between March 1999 and November 2008 were retrospectively reviewed. Data reflecting clinical characteristics, tumor marker level, and prognosis were collected. The potential predictive value of CA 19-9 was analyzed by receiver operating characteristic (ROC) curve. RESULTS: Eighty-six consecutive patients with IPMNs all underwent surgical intervention. A high level of CA 19-9 or carcinoembryonic antigen (CEA) was associated with more advanced stage of malignant IPMNs. Carbohydrate antigen 19-9 was significant for judging malignant IPMNs in the binary logistic regression model (p=0.047). The hazard ratio was 1.014, whose 95.0% confidence interval was 0.91-1.028. Receiver operating characteristic analysis showed that the serum CA 19-9 level had good predictive value for malignant or invasive IPMNs, postoperative survival, and disease-specific recurrence. The area under the curve (AUC) was 0.856, 0.893, 0.815, and 0.857 (p<0.05), respectively. According to the follow-up, mean survival time for groups with CA 19-9>63.60 U/ml was dramatically shorter than that for groups with CA 19-9≤63.60 U/ml (57.38±2.85 versus 29.24±5.82 [months]; p<0.01). CONCLUSIONS: Serum CA 19-9 level has good predictive value for malignant or invasive IPMNs. Patients with CA 19-9 > 63.60 U/ml had poor postoperative prognosis in IPMNs. Preoperative abnormal serum CA 19-9 might be predictive for an aggressive surgical intervention in IPMNs.

Removal of CSF pixels on brain MR perfusion images using first several images and Otsu's thresholding technique.

Brain MR perfusion imaging is used to evaluate local perfusion in patients with cerebral vascular disease. Quantitative measurements on the hemodynamic parameters and volume of brain with abnormal perfusion provide an estimation of the severity of the brain perfusion defect. However, quantitative measurements of these focal cerebral hemodynamic parameters are limited by the presence of cerebrospinal fluid (CSF) pixels. We noticed that the CSF has a higher signal than other tissue types on the first perfusion image, which is usually discarded in routine parametric image calculations. This signal difference, however, can be used to segment CSF pixels on the perfusion images. An image division was used to generate ratio images to compensate for spatially dependent signal variation caused by the inhomogeneity of excitation radiofrequency field. By applying an appropriate signal threshold to the ratio images, CSF pixels can be identified and removed from the parametric images. With the removal of CSF pixels, the volume of delayed-perfusion brain parenchyma can be better visualized and the interference from the CSF can be avoided. The proposed technique is simple, fast, automatic, and effective, and no extra scanning is needed to use this technique.