Formamide Electrosynthesis from Methanol and Ammonia in Water over Pr-Doped MnO2.

A rare earth element doping strategy is reported to boost the activity and enhance the stability of MnO2 for selective formamide production through electrocatalytic oxidation coupling (EOC) of methanol and ammonia. MnO2 doped with 1% Pr was selected as the best candidate with an optimized formamide yield of 211.32 µmol cm-2 h-1, a Faradaic efficiency of 22.63%, and a stability of more than 50 h. The easier formation of Mn6+ species and the lower dissolution rate of Mn species over Pr-doped MnO2 revealed by in situ Raman spectra were responsible for the boosted formamide production and enhanced stability. In addition, a two-electrode flow electrolyzer was developed to integrate EOC with C2H2 semihydrogenation for simultaneously producing value-added products in both the anode and cathode.

[Ontologies Applied in Clinical Decision Support Systems for Diabetes].

A clinical decision support system (CDSS) integrated with electronic health records helps physicians at the grassroots make patient-appropriate and evidence-based treatment decisions and improves the efficiency of diagnosis and treatment. Furthermore, using ontologies to build up the medical knowledge base and patient data for CDSS enhances the automation and transparency of the reasoning process of CDSS and helps generate interpretable and accurate treatment recommendations. Herein, we reviewed the relevant ontologies in the field of diabetes treatment and the progress and challenges concerning ontology-based CDSSs. Firstly, we elaborated on the current status and challenges of diabetes treatment in China, highlighting the urgent need to improve the efficiency and quality of medical services. Then, we presented background information about ontologies and gave an overview of the framework, methodology, and features of using ontologies to construct CDSS. After that, we reviewed the ontologies and instances of ontology-based CDSS in the field of diabetes treatment in China and abroad and summarized their construction methods and features. Last but not the least, we discussed the future prospects of the field, suggesting that integrating evidence-based medicine with ontologies to build a reliable clinical recommendation system should be the current focus of CDSS development.

SRSF3-mediated regulation of N6-methyladenosine modification-related lncRNA ANRIL splicing promotes resistance of pancreatic cancer to gemcitabine.

Serine/arginine-rich splicing factor 3 (SRSF3) regulates mRNA alternative splicing of more than 90% of protein-coding genes, providing an essential source for biological versatility. This study finds that SRSF3 expression is associated with drug resistance and poor prognosis in pancreatic cancer. We also find that SRSF3 regulates ANRIL splicing and m6A modification of ANRIL in pancreatic cancer cells. More importantly, we demonstrate that m6A methylation on lncRNA ANRIL is essential for the splicing. Moreover, our results show that SRSF3 promotes gemcitabine resistance by regulating ANRIL's splicing and ANRIL-208 (one of the ANRIL spliceosomes) can enhance DNA homologous recombination repair (HR) capacity by forming a complex with Ring1b and EZH2. In conclusion, this study establishes a link between SRSF3, m6A modification, lncRNA splicing, and DNA HR in pancreatic cancer and demonstrates that abnormal alternative splicing and m6A modification are closely related to chemotherapy resistance in pancreatic cancer.

Medium-term Clinical Efficacy and Complications of Plasmakinetic Enucleation of the Prostate Versus Transurethral Resection of the Prostate for Benign Prostatic Hyperplasia.

OBJECTIVE: To compare surgical characteristics, clinical efficacy, and complications of plasmakinetic enucleation of the prostate (PKEP) and transurethral resection of the prostate (TURP) for benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: From January 2015 to May 2018, 370 patients underwent TURP were included into the TURP group. Meanwhile, another 370 patients underwent PKEP (matched by age, prostate volume, and duration of BPH) were included into the PKEP group. Then, the differences of surgical characteristics, clinical efficacy, and complications were compared between the two groups. RESULTS: The operative time, intraoperative irrigation volume, postoperative irrigation time and irrigation volume, drop in hemoglobin, blood transfusion, postoperative catheterization time, and hospital stay of the PKEP group were significantly less than those of the TURP group (P <.05). No significant differences were observed in the resected tissue weight, visual analogue scale score, and total cost of hospitalization (P >.05); The quality of life score of the PKEP group was significantly lower than that of the TURP group (P <.05). No significant differences of maximum flow rate, postvoid residual urine, Serum prostate-specific antigen, international prostate symptom score and International Index of Erectile Function score were observed (P >.05); The incidences of urinary tract irritation, massive hemorrhage, secondary hemorrhage, bladder spasm, clot retention, and retrograde ejaculation of the PKEP group were significantly lower than those of the TURP group (P <.05). CONCLUSION: PKEP and TURP are comparable regarding cost burden and clinical efficacy in medium-term follow-up. However, PKEP should be given a priority for BPH treatment because of less complication rate and better safety profile.

Angiotensin-(1-7) ameliorates high glucose-induced vascular endothelial injury through suppressing chloride channel 3.

Diabetes Mellitus (DM) is a significant risk factor for cardiovascular disease (CVD), which is leading cause of deaths in DM patients. However, there are limited effective medical therapies for diabetic CVD. Vascular endothelial injury caused by DM is a critical risk factor for diabetic CVD. Previous study has indicated that Angiotensin-(1-7) (Ang-(1-7)) may prevent diabetic CVD, whereas it is not clear that Ang-(1-7) whether attenuates diabetic CVD through suppressing vascular endothelial injury. In this study, we found that Ang-(1-7) alleviated high glucose (HG)-induced endothelial injury in bEnd3 cells. Moreover, Ang-(1-7) ameliorated HG-induced endothelial injury through downregulating chloride channel 3 (CIC-3) via Mas receptor. Furthermore, HG-induced CIC-3 enhanced reactive oxygen species (ROS) and cytokine production and reduced the level of nitric oxide (NO), while Ang-(1-7) preserved the impact of HG-induced CIC-3 on productions of ROS, cytokine and NO through inhibiting CIC-3 via Mas receptor. Summarily, the present study revealed that Ang-(1-7) alleviated HG-induced vascular endothelial injury through the inhibition of CIC-3, suggested that Ang-(1-7) may preserve diabetic CVD through suppressing HG-induced vascular endothelial injury.

A multicenter clinical study: personalized medication for advanced gastrointestinal carcinomas with the guidance of patient-derived tumor xenograft (PDTX).

BACKGROUND: Establish patient-derived tumor xenograft (PDTX) from advanced GICs and assess the clinical value and applicability of PDTX for the treatment of advanced gastrointestinal cancers. METHODS: Patients with advanced GICs were enrolled in a registered multi-center clinical study (ChiCTR-OOC-17012731). The performance of PDTX was evaluated by analyzing factors that affect the engraftment rate, comparing the histological consistency between primary tumors and tumorgrafts, examining the concordance between the drug effectiveness in PDTXs and clinical responses, and identifying genetic variants and other factors associated with prognosis. RESULTS: Thirty-three patients were enrolled in the study with the engraftment rate of 75.8% (25/33). The success of engraftment was independent of age, cancer types, pathological stages of tumors, and particularly sampling methods. Tumorgrafts retained the same histopathological characteristics as primary tumors. Forty-nine regimens involving 28 drugs were tested in seventeen tumorgrafts. The median time for drug testing was 134.5 days. Follow-up information was obtained about 10 regimens from 9 patients. The concordance of drug effectiveness between PDTXs and clinical responses was 100%. The tumor mutation burden (TMB) was correlated with the effectiveness of single drug regimens, while the outgrowth time of tumorgrafts was associated with the effectiveness of combined regimens. CONCLUSION: The engraftment rate in advanced GICs was higher than that of other cancers and meets the acceptable standard for applying personalized therapeutic strategies. Tumorgrafts from PDTX kept attributes of the primary tumor. Predictions from PDTX modeling closely agreed with clinical drug responses. PDTX may already be clinically applicable for personalized medication in advanced GICs.

CLK1/SRSF5 pathway induces aberrant exon skipping of METTL14 and Cyclin L2 and promotes growth and metastasis of pancreatic cancer.

BACKGROUND: Both aberrant alternative splicing and m6A methylation play complicated roles in the development of pancreatic cancer (PC), while the relationship between these two RNA modifications remains unclear. METHODS: RNA sequencing (RNA-seq) was performed using 15 pairs of pancreatic ductal adenocarcinoma (PDAC) tissues and corresponding normal tissues, and Cdc2-like kinases 1 (CLK1) was identified as a significantly upregulated alternative splicing related gene. Real-time quantitative PCR (qPCR) and western blotting were applied to determine the CLK1 levels. The prognostic value of CLK1 was elucidated by Immunohistochemistry (IHC) analyses in two independent PDAC cohorts. The functional characterizations and mechanistic insights of CLK1 in PDAC growth and metastasis were evaluated with PDAC cell lines and nude mice. SR-like splicing factors5250-Ser (SRSF5250-Ser) was identified as an important target phosphorylation site by phosphorylation mass spectrometry. Through transcriptome sequencing, Methyltransferase-like 14exon10 (METTL14exon10) and Cyclin L2exon6.3 skipping were identified as key alternative splicing events regulated by the CLK1-SRSF5 axis. RIP assays, RNA-pulldown and CLIP-qPCR were performed to confirm molecular interactions and the precise binding sites. The roles of the shift of METTL14exon 10 and Cyclin L2exon6.3 skipping were surveyed. RESULTS: CLK1 expression was significantly increased in PDAC tissues at both the mRNA and protein levels. High CLK1 expression was associated with poor prognosis. Elevated CLK1 expression promoted growth and metastasis of PC cells in vitro and in vivo. Mechanistically, CLK1 enhanced phosphorylation on SRSF5250-Ser, which inhibited METTL14exon10 skipping while promoted Cyclin L2exon6.3 skipping. In addition, aberrant METTL14exon 10 skipping enhanced the N6-methyladenosine modification level and metastasis, while aberrant Cyclin L2exon6.3 promoted proliferation of PDAC cells. CONCLUSIONS: The CLK1/SRSF5 pathway induces aberrant exon skipping of METTL14 and Cyclin L2, which promotes growth and metastasis and regulates m6A methylation of PDAC cells. This study suggests the potential prognostic value and therapeutic targeting of this pathway in PDAC patients.

SHCBP1 interacting with EOGT enhances O-GlcNAcylation of NOTCH1 and promotes the development of pancreatic cancer.

O-GlcNAcylation is important in the development and progression of pancreatic ductal adenocarcinoma (PDAC). The glycosyltransferase EGF domain-specific O-linked GlcNAc transferase (EOGT) acts as a key participant in glycosylating NOTCH1. High-throughput sequencing of specimens from 30 advanced PDAC patients identified SHCBP1 and EOGT as factors of poor prognosis. We hypothesized that they could mediate PDAC progression by influencing NOTCH1 O-GlcNAcylation. Thus, 186 PDAC tissue specimens were immunostained for EOGT and SHCBP1. Pancreatic cancer cell lines and nude mouse models were used for in vitro and in vivo experiments. Respectively, The protein expression of EOGT and SHCBP1 was significantly elevated and correlated with worse prognosis in PDAC patients. In vitro, SHCBP1 overexpression promoted pancreatic cancer cell proliferation, migration and invasion, while knocking down SHCBP1 and EOGT inhibited these malignant processes. In vivo data showed that SHCBP1 overexpression promoted xenograft growth and lung metastasis and shortened survival in mice, whereas knocking down either EOGT or SHCBP1 expression suppressed xenograft growth and metastasis and prolonged survival. We further clarified the molecular mechanisms by which EOGT and SHCBP1 enhance the O-GlcNAcylation of NOTCH1, Subsequently promoting the nuclear localization of the Notch intracellular domain (NICD) and inhibiting the transcription of E-cadherin and P21 in pancreatic cancer cells.

Disordered Gut Microbiota in Children Who Have Chronic Pancreatitis and Different Functional Gene Mutations.

OBJECTIVES: Chronic pancreatitis (CP) is a serious condition whose pathogenic mechanism is unclear. Interactions of host genetic factors with gut microbiota have a role, but little is known, especially in children with CP (CCP), in which the external factors are less important. Our objective was to identify the main gut microbiota genera in CCP and to characterize the functional mutations of these patients. METHODS: We used 16S rRNA sequencing to compare the gut microbiota of healthy controls with patients who had CCP and different functional gene mutations. RESULTS: CCP is characterized by gut microbiota with remarkably reduced alpha diversity. Receiver operating characteristic curve analyses indicated that the abundances of 6 genera-Faecalibacterium, Subdoligranulum, Phascolarctobacterium, Bifidobacterium, Eubacerium, and Collinsella-were significantly decreased in CCP, with an area under curve (AUC) of 0.92 when considering all 6 genera together. Functional analysis of gut microbiota in CCP indicated reduced ribosomal activity, porphyrin and chlorophyll metabolism, starch and sucrose metabolism, and aminoacyl-tRNA biosynthesis, but an enrichment of phosphotransferase system pathways. The abundance of Butyricicoccus was significantly decreased in CCP in the presence of CFTR mutations when combined with mutations in CASR, CTSB, SPINK1, and/or PRSS1. The abundance of Ruminococcaceae was significantly increased in CCP when there were mutations in CASR, CTSB, SPINK1, and/or PRSS1. Patients with CCP but no gene mutations had greater abundances of Veillonella and reduced abundances of Phascolarctobacterium. DISCUSSION: CCP is associated with a depletion of probiotic gut microbiota, and CCP patients with different functional gene mutations have different gut microbiota.

Robotic pancreatectomy for solid pseudopapillary tumors in the pancreatic head: A propensity score-matched comparison and analysis from a single center.

BACKGROUND: Robotic surgery is the most advanced minimally invasive technique for the treatment of complicated solid pseudopapillary tumors (SPT). The aim of this study is to evaluate feasibility of robotic surgery for the treatment of SPTs in the pancreatic head. METHODS: A retrospective analysis of the clinical data of 83 SPTs in pancreatic head was conducted. Clinical characteristics were extracted and propensity score matching (PSM) was used to compare and evaluate mid-term outcomes of the two techniques. RESULTS: Pancreaticoduodenectomy (PD), duodenum-preserving partial pancreatic head resection (DPPHR-P) and tumor enucleation (En) were performed in 51, 24, and 8 patients, respectively. The robotic approach was associated with a significantly lower volume of blood loss, lower need for transfusion, and faster time to post-surgery recovery. Major complications and costs were comparable for both techniques. CONCLUSION: A robotic approach provides an alternative to open surgery for SPTs in the pancreatic head without increasing the incidence of clinically relevant pancreatic fistula (CRPF) or other major complications and with good patient outcomes.

Higher body mass index deteriorates postoperative outcomes of pancreaticoduodenectomy.

BACKGROUND: Previous studies presented controversies in impact of body mass index (BMI) on perioperative complications in pancreatectomy, and mainly focused on Western population. This study aimed to explore the impact of BMI on perioperative outcomes in Chinese patients undergoing pancreaticoduodenectomy. METHODS: Seven hundred and seven adult patients undergoing open pancreaticoduodenectomy between January 2005 and December 2016 at Ruijin Hospital were studied retrospectively and categorized as obese (BMI ≥25 kg/m2), overweight (BMI ≥23 kg/m2 and <25 kg/m2), or normal weight (BMI ≥18.5 kg/m2 and <23 kg/m2). Associations of these BMI groups with perioperative outcomes were evaluated. RESULTS: The overweight and obese groups experienced higher risk of clinically related postoperative pancreatic fistula (CR-POPF) (7.6% vs. 9.9% vs. 17.6%, P = 0.002) and re-operation (1.1% vs. 2.5%  vs. 5.1%, P = 0.017), and longer systemic inflammation response syndrome (SIRS) duration [2 (1-9) d vs. 2 (1-7) d vs. 3 (1-10) d, P = 0.003] and postoperative hospital stay [19 (2-84) d vs. 19 (7-158) d vs. 23 (8-121) d, P = 0.023] than the normal weight group did. The multiple logistic regression models showed obese as an independent risk factor for CR-POPF (P = 0.013). The multiple linear regression analysis confirmed BMI as a predictor for prolonged postoperative hospital stay (P = 0.005). CONCLUSIONS: Higher BMI results in higher morbidity of Chinese patients undergoing open pancreaticoduodenectomy. Pancreaticoduodenectomy is still a safe surgery procedure for overweight and obese patients, with intensive perioperative management.

An allosteric PGAM1 inhibitor effectively suppresses pancreatic ductal adenocarcinoma.

Glycolytic enzyme phosphoglycerate mutase 1 (PGAM1) plays a critical role in cancer metabolism by coordinating glycolysis and biosynthesis. A well-validated PGAM1 inhibitor, however, has not been reported for treating pancreatic ductal adenocarcinoma (PDAC), which is one of the deadliest malignancies worldwide. By uncovering the elevated PGAM1 expressions were statistically related to worse prognosis of PDAC in a cohort of 50 patients, we developed a series of allosteric PGAM1 inhibitors by structure-guided optimization. The compound KH3 significantly suppressed proliferation of various PDAC cells by down-regulating the levels of glycolysis and mitochondrial respiration in correlation with PGAM1 expression. Similar to PGAM1 depletion, KH3 dramatically hampered the canonic pathways highly involved in cancer metabolism and development. Additionally, we observed the shared expression profiles of several signature pathways at 12 h after treatment in multiple PDAC primary cells of which the matched patient-derived xenograft (PDX) models responded similarly to KH3 in the 2 wk treatment. The better responses to KH3 in PDXs were associated with higher expression of PGAM1 and longer/stronger suppressions of cancer metabolic pathways. Taken together, our findings demonstrate a strategy of targeting cancer metabolism by PGAM1 inhibition in PDAC. Also, this work provided "proof of concept" for the potential application of metabolic treatment in clinical practice.

Outcomes of health-related quality of life after open, laparoscopic, or robot-assisted radical prostatectomy in China.

PURPOSE: To compare the outcomes of health-related quality of life (HRQOL) in patients undergoing open (ORP), laparoscopic (LRP), or robot-assisted (RARP) radical prostatectomy. PATIENTS AND METHODS: We retrospectively analyzed 347 men with clinically localized prostate cancer treated with ORP (n=97), LRP (n=71), or RARP (n=179) by high-volume surgeons in our institution between January 2014 and December 2016. The primary endpoint was HRQOL including urinary incontinence and erectile dysfunction. RESULTS: One year after surgery, 15.9% of men reported moderate to severe urinary incontinence (ORP 16.5%, LRP 15.4%, and RARP 15.7%), with only 4.6% using pads. There were no statistically significant differences in the ratios of no pad usage and urinary incontinence bother after 12 months postoperatively among the three groups. However, 67.7% of the men reported moderate to severe erectile dysfunction (ORP 66%, LRP 66.1%, and RARP 69.3%) 12 months after surgery. There was no statistically significant difference in the international index of erectile function-5 (IIEF-5) postoperatively among the different surgical groups. In the univariate and multivariate analyses, age at surgery, preoperative IIEF-5, and neurovascular bundle preservation were the risk factors for moderate to severe sexual bother. Interestingly, 16.1% of men with an erection hardness score of grade 3-4 were hesitant to become sexually active postoperatively. CONCLUSION: ORP, LRP, and RARP have similar early HRQOL outcomes with respect to urinary incontinence and erectile dysfunction. In contrast to urinary continence, erectile dysfunction is still a serious concern for patients who undergo radical prostatectomy.

Silencing of long noncoding RNA LINC00958 prevents tumor initiation of pancreatic cancer by acting as a sponge of microRNA-330-5p to down-regulate PAX8.

Pancreatic cancer (PC) represents a relatively rare but severe malignancy worldwide. Accumulated studies have emphasized the potential of long noncoding RNA (lncRNA) as therapeutic strategies for several human cancers. Thus, we aimed to investigate whether a novel non-coding RNA regulatory circuitry involved in PC. Aberrantly expressed lncRNAs and mRNAs were screened out of microarray database. Following the determination of RNA expression, PANC-1 and BxPC-3 PC cells were adopted, after which the expression of miR-330-5p, PAX8 and LINC00958 were subsequently altered. RNA crosstalk was validated by dual-luciferase reporter gene assay. In order to detect whether LINC00958 could act as ceRNA to competitively sponge miR-330-5p and regulate PAX8, subcellular location of LINC00958 and interaction between LINC00958 and miR-330-5p were measured by FISH and RNA pull down respectively. The epithelial mesenchymal transition (EMT) process, cell invasion, and tumor growth were determined in vitro and in vivo. LINC00958 and PAX8 were up-regulated, while miR-330-5p was down-regulated during PC. LINC00958 mainly expressed in the cytoplasm and LINC00958 competitively sponged miR-330-5p. Upregulated miR-330-5p or downregulated PAX8 inhibited the EMT process as well as the invasion and metastasis ability of the PC cells. Moreover, the results indicated that miR-330-5p negatively targeted PAX8, and LINC00958 ultimately showcasing its ability to bind to miR-330-5p through its interaction with AGO2. Therefore, silencing of LINC00958 may bind to miR-330-5p to inhibit PAX8 in a competitive fashion, thereby preventing the progression of PC.

Caffeine improves bladder function in streptozotocin-induced diabetic rats.

AIMS: To examine the protective effects of caffeine in rats with diabetes mellitus (DM) by using urodynamics. METHODS: Female Sprague-Dawley rats (n = 24) were divided into four groups: control group, DM group, DM + caffeine (5 mg/kg/day), and DM + caffeine (10 mg/kg/day). DM was induced by streptozotocin (STZ). Cystometric studies were conducted on all rats. After 8 weeks of treatment with caffeine, the urodynamic parameters, including bladder capacity, residual urine volume, voiding time, and peak voiding pressure, were measured. RESULTS: DM rats had a higher bladder capacity and post-void residual urine volume (PVR), an increased voiding time and peak voiding pressure, and a markedly lower voiding efficiency than the control group rats. After treatment with caffeine, bladder capacity, post-void residual urine volume, and peak voiding pressure were significant lower than those in the DM group, but voiding efficiency was markedly higher. CONCLUSION: The results suggested that caffeine (5 or 10 mg/kg/day) may improve the bladder function at 8 weeks after STZ induction. Thus, this may represent a potential strategy to increase voiding efficiency in diabetes.

Curcumin ameliorates cisplatin-induced cystopathy via activating NRF2 pathway.

OBJECTIVES: The present work evaluated preventive effect of curcumin on cisplatin-induced bladder cystopathy. METHODS: Fifteen female rats were divided into (i) Control group administered with physiological saline solution for 5 days; (ii) Cis-P group injected with cisplatin (6 mg/kg); and (iii) Cis-Cur group given cisplatin (6 mg/kg) with curcumin for 5 consecutive days. The function of bladder was measured by means of urodynamic analysis. Furthermore, hematoxylin-eosin staining and Masson trichrome staining were performed for morphological analysis. The cell apoptosis was evaluated through terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay and flow cytometry. The expression of nerve growth factor (NGF), NF-E2-related factor 2, and hemeoxygenase-1 (HO-1) levels were measured through Western blotting. RESULTS: Urodynamic assay and histopathological manifestations revealed that curcumin ameliorated the bladder dysfunction induced by cisplatin. The level of cisplatin-induced apoptosis in the bladder decreased following curcumin treatment. Also, the increased protein expression of NGF indicated that the curcumin could offer neuroprotection for bladder against cisplatin. Curcumin also activated NRF2, and elevated the expression of HO-1, but curcumin could not rescue cisplatin-induced apoptosis in the cell lines with knockdown of NRF2. CONCLUSIONS: Taken together, the results of this paper showed that curcumin could ameliorate cisplatin-induced cystopathy and inhibit the apoptosis of bladder cell in cisplatin-treated rats. This may be attributed to curcumin's broad biological functions, particularly antioxidant effect, and to its ability to activate the NRF2 protein.

Baicalein induces the apoptosis of HCT116 human colon cancer cells via the upregulation of DEPP/Gadd45a and activation of MAPKs.

Baicalein has efficient antitumor properties and has been reported to promote the apoptosis of several human cancer cell lines. Decidual protein induced by progesterone (DEPP), a transcriptional target of Forkhead Box O, was originally identified from the human endometrial stromal cell cDNA library. However, the expression and physiological functions of DEPP in human colon cancer cells remain to be fully elucidated. In the present study, it was reported that baicalein stimulated apoptosis and morphological changes of HCT116, A549 and Panc­1 cells in a dose-dependent manner. It also upregulated the mRNA and protein levels of DEPP and growth arrest and DNA damage-inducible 45α (Gadd45a). In addition, the overexpression of DEPP promoted mitogen-activated protein kinase (MAPK) phosphorylation. To further investigate the role of DEPP and Gadd45a in baicalein-induced apoptosis, HCT116 cells were transfected with small interfering RNA against either DEPP or Gadd45a as in vitro models. Through an Annexin V/PI double staining assay, it was observed that baicalein-induced apoptosis was impaired by the inactivation of either DEPP or Gadd45a, which in turn restricted the baicalein-induced activation of caspase­3 and caspase­9 and phosphorylation of MAPKs. In addition, the inhibition of c­Jun N­terminal kinase (JNK)/p38 activity with SP600125/SB203580 decreased the expression of Gadd45a, whereas the inactivation of extracellular signal-regulated kinase with SCH772984 had no effect on the expression of Gadd45a. Taken together, these results demonstrated that baicalein induced the upregulation of DEPP and Gadd45a, which promoted the activation of MAPKs with a positive feedback loop between Gadd45a and JNK/p38, resulting in a marked apoptotic response in human colon cancer cells. These results indicated that baicalein is a potential antitumor drug for the treatment of colon cancer.

Robot-assisted duodenum-preserving pancreatic head resection with pancreaticogastrostomy for benign or premalignant pancreatic head lesions: a single-centre experience.

BACKGROUND: The purpose of this study was to compare short- and long-term outcomes of modified robot-assisted duodenum-preserving pancreatic head resection (RA-DPPHR) versus robot-assisted pancreaticoduodenectomy (RA-PD). METHODS: Matched for age, sex, ASA classification, tumour size, history of abdominal surgery and pathological type, 34 patients undergoing RA-DPPHR and 34 patients undergoing RA-PD between January 2010 and December 2016 were retrospectively analyzed. RESULTS: The RA-DPPHR group had shorter surgical time (188.2 vs. 386.3 min, p < 0.001) and less blood loss (168.2 vs. 386.3 ml, p = 0.026) but higher complication rate (47.1% vs. 32.4%, p = 0.105) and pancreatic fistula rate (32.4% vs. 17.6%, p = 0.161). Hospital mortality was 2.9%. Exocrine insufficiency was lower in the RA-DPPHR group (3.0% vs. 24.2%, p = 0.027). Endocrine insufficiency was observed in one RA-DPPHR patient and 5 RA-PD patients (p = 0.197). CONCLUSIONS: Modified RA-DPPHR benefits in terms of better conservation of exocrine and endocrine pancreatic functions at the expense of a significant morbidity and non-zero mortality.

MicroRNA-300 promotes apoptosis and inhibits proliferation, migration, invasion and epithelial-mesenchymal transition via the Wnt/ß-catenin signaling pathway by targeting CUL4B in pancreatic cancer cells.

The study aims to verify the hypothesis that up-regulation of microRNA-300 (miR-300) targeting CUL4B promotes apoptosis and suppresses proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of pancreatic cancer cells by regulating the Wnt/ß-catenin signaling pathway. Pancreatic cancer tissues and adjacent tissues were collected from 110 pancreatic cancer patients. Expression of miR-300, CUL4B, Wnt, ß-catenin, E-cadherin, N-cadherin, Snail, GSK-3ß, and CyclinD1 were detected using qRT-PCR and Western blot. CFPAC-1, Capan-1, and PANC-1 were classified into blank, negative control (NC), miR-300 mimics, miR-300 inhibitors, siRNA-CUL4B, and miR-300 inhibitors + siRNA-CUL4B groups. The proliferation, migration, invasion abilities, the cell cycle distribution, and apoptosis rates were measured in CCK-8 and Transwell assays. Pancreatic cancer tissues showed increased CUL4B expression but decreased miR-300 expression. When miR-300 was lowly expressed, CUL4B was upregulated which in-turn activated the Wnt/ß-catenin pathway to protect the ß-catenin expression and thus induce EMT. When miR-300 was highly expressed, CUL4B was downregulated which in-turn inhibited the Wnt/ß-catenin pathway to prevent EMT. Weakened cell migration and invasion abilities and enhanced apoptosis were observed in the CUL4B group. The miR-300 inhibitors group exhibited an evident increase in growth rate accompanied the largest tumor volume. Smaller tumor volume and slower growth rate were observed in the miR-300 mimics and siRNA-CUL4B group. Our study concludes that lowly expressed miR-300 may contribute to highly expressed CUL4B activating the Wnt/ß-catenin signaling pathway and further stimulating EMT, thus promoting proliferation and migration but suppressing apoptosis of pancreatic cancer cells.