The Effect of Perioperative Dexamethasone on Postoperative Complications After Pancreaticoduodenectomy: A Multicenter Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect of perioperative dexamethasone on postoperative complications after pancreaticoduodenectomy. BACKGROUND: The glucocorticoid dexamethasone has been shown to improve postoperative outcomes in surgical patients, but its effects on postoperative complications after pancreaticoduodenectomy are unclear. METHODS: This multicenter, double-blind, randomized controlled trial was conducted in four Chinese high-volume pancreatic centers. Adults undergoing elective pancreaticoduodenectomy were randomized to receive either 0.2 mg/kg dexamethasone or a saline placebo as an intravenous bolus within 5 minutes after anesthesia induction. The primary outcome was the Comprehensive Complication Index (CCI) score within 30 days after the operation, analyzed using the modified intention-to-treat principle. RESULTS: Among 428 patients for eligibility, 300 participants were randomized and 265 were included in the modified intention-to-treat analyses. One hundred thirty-four patients received dexamethasone and 131 patients received a placebo. The mean (SD) CCI score was 14.0 (17.5) in the dexamethasone group and 17.9 (20.3) in the placebo group (mean difference: -3.8; 95% CI: -8.4 to 0.7; P = 0.100). The incidence of major complications (Clavien-Dindo grade ≥III; 12.7% vs 16.0%, risk ratio: 0.79; 95% CI: 0.44 to 1.43; P = 0.439) and postoperative pancreatic fistula (25.4% vs 31.3%, risk ratio: 0.81; 95% CI: 0.55 to 1.19; P = 0.286) were not significantly different between the two groups. In the stratum of participants with a main pancreatic duct ≤3 mm (n = 202), the CCI score was significantly lower in the dexamethasone group (mean difference: -6.4; 95% CI: -11.2 to -1.6; P = 0.009). CONCLUSIONS: Perioperative dexamethasone did not significantly reduce postoperative complications within 30 days after pancreaticoduodenectomy.

A retrospective study on application of a classification criterion based on relative intervertebral tension in spinal fusion surgery for lumbar degenerative diseases.

BACKGROUND: As an important part of spinal fusion procedure, the selection of fusion cage size is closely related to the curative effect of the surgery. It mainly depends on the clinical experience of surgeons, and there is still a lack of objective standards. The purpose of this study is to propose the concept of relative intervertebral tension (RIT) for the first time and its grading standards to improve the surgical procedures of lumbar interbody fusion. METHODS: This retrospective study was conducted from January 2018 to July 2019. A total of 83 eligible patients including 45 men and 38 women with lumbar degenerative disease underwent transforaminal lumbar interbody fusion (TLIF) were included in this study. A total of 151 fusion segments were divided into group A, group B and group C according to the grading standards of RIT. In addition, parameters of intervertebral space angle (ISA), intervertebral space height (ISH), intervertebral space foramen (IFH), fusion rates, cage-related complications and cage heights were also compared among the three groups. RESULTS: The ISA in group A was the smallest among three groups in contrast with group C with largest ISA at the final follow-up(P < 0.05). The group A presented the smallest ISH and IFH values(P < 0.05), compared with group B with the largest ISH and IFH values(P < 0.05). These two parameters in the group C were in-between. The fusion rates of group A, group B and group C were 100%, 96.3% and 98.8% at the final follow-up, respectively. No statistical difference in fusion rates and cage-related complications occurred among the three groups(P > 0.05), and a certain correlation between ISH and RIT was also observed. CONCLUSIONS: The concept of RIT and the application of its clinical grading standards could simplify the surgical procedures of spinal fusion and reduce cage-related complications.

A meta-analysis of risk factors for non-superficial surgical site infection following spinal surgery.

BACKGROUND: Surgical site infection (SSI) is the most common complications in spinal surgery. In SSI, non-superficial surgical site infections are more likely to result in poor clinical outcomes. It has been reported that there are multiple factors contributing to postoperative non-superficial SSI, but still remains controversial. Therefore, the aim of this meta-analysis is to investigate the potential risk factors for non-superficial SSI following spinal surgery. METHODS: A systematic database search of PubMed, Embase, Web of Science, Cochrane Library and Clinical Trials was performed for relevant articles published until September 2022. According to the inclusion and exclusion criteria, two evaluators independently conducted literature screening, data extraction and quality evaluation of the obtained literature. The Newcastle-Ottawa Scale (NOS) score was used for quality evaluation, and meta-analysis was performed by STATA 14.0 software. RESULTS: A total of 3660 relevant articles were initially identified and 11 articles were finally included in this study for data extraction and meta-analysis. The results of meta-analysis showed that the diabetes mellitus, obesity, using steroids, drainage time and operative time were related to the non-superficial SSI. The OR values (95%CI) of these five factors were 1.527 (1.196, 1.949); 1.314 (1.128, 1.532); 1.687(1.317, 2.162); 1.531(1.313, 1.786) and 4.255(2.612, 6.932) respectively. CONCLUSIONS: Diabetes mellitus, obesity, using steroids, drainage time and operative time are the current risk factors for non-superficial SSI following spinal surgery. In this study, operative time is the most important risk factor resulting in postoperative SSI.

CircSTX6 promotes pancreatic ductal adenocarcinoma progression by sponging miR-449b-5p and interacting with CUL2.

BACKGROUND: circular RNAs (circRNAs) have been reported to play crucial roles in the biology of different cancers. However, little is known about the function of circSTX6 (hsa_circ_0007905) in pancreatic ductal adenocarcinoma (PDAC). METHODS: circSTX6, a circRNA containing exons 4, 5, 6 and 7 of the STX6 gene, was identified by RNA sequencing and detected by quantitative reverse transcription PCR (qRT-PCR). The biological function of circSTX6 was assessed in vitro and in vivo. The relationship between circSTX6 and miR-449b-5p was confirmed by biotin-coupled circRNA capture, fluorescence in situ hybridization (FISH) and luciferase reporter assays. The interaction of circSTX6 with Cullin 2 (CUL2) was verified by RNA-protein RNA pull-down, RNA immunoprecipitation (RIP) and western blotting assays. RESULTS: circSTX6 was frequently upregulated in PDAC tissues, and circSTX6 overexpression promoted tumor proliferation and metastasis both in vitro and in vivo. Furthermore, circSTX6 expression was associated with tumor differentiation and N stage. Mechanistically, circSTX6 regulated the expression of non-muscle myosin heavy chain 9 (MYH9) by sponging miR-449b-5p. Moreover, circSTX6 was confirmed to participate in the ubiquitin-dependent degradation of hypoxia-inducible factor 1-alpha (HIF1A) by interacting with CUL2 and subsequently accelerating the transcription of MYH9. CONCLUSIONS: Our findings indicate that circSTX6 facilitates proliferation and metastasis of PDAC cells by regulating the expression of MYH9 through the circSTX6/miR-449b-5p axis and circSTX6/CUL2/HIF1A signaling pathway. Therefore, circSTX6 could serve as a potential therapeutic target for the treatment of PDAC.

The short-term outcomes of distal pancreatectomy with portal vein/superior mesenteric vein resection.

BACKGROUND: Portal vein/superior mesenteric vein (PV/SMV) resection during distal pancreatectomy (DP) is often associated with technical difficulties due to the close anatomic relationship between pancreatic head and PV/SMV. In this paper, we present our operative technique and short-term outcomes of DP combined with venous resection (DP-VR) for left-sided pancreatic cancer (PC). METHODS: We reviewed 368 consecutive cases of DP for PC from January 2013 to December 2018 in our institution, and identified 41 patients (11.1%) who had undergone DP-VR. The remaining 327 DP patients (88.9%) were matched to DP-VR using propensity scores in the proportion of 1:2. Demographics, intraoperative details, postoperative complications and the pathological results were compared between the two groups. RESULTS: Out of the 41 DP-VR cases, in 14 (34.1%) venous resection with primary closure was performed, while the remaining 27 (65.9%) underwent end-to-end anastomosis without graft. A propensity-score-matched analysis revealed that DP-VR caused an increased risk of postoperative bleeding (17.1% vs. 3.7%, P = 0.016) and delayed gastric emptying (9.8% vs. 1.2%, P = 0.042) compared to standard DP. Overall morbidity (46.3% vs. 36.6%, P = 0.332), postoperative pancreatic fistula (31.7% vs. 26.8%, P = 0.672), R0 resection (58.5% vs. 67.1%, P = 0.223), 30-day reoperation (2.4% vs. 3.7%, P = 0.719), and 90-day mortality (0% vs. 2.5%, P = 0.550) were comparable between the two groups. In postoperative computed tomographic scans of 34 patients (82.9%) at a 90-day follow-up, PV/SMV stenosis was suggested in two patients (5.9%). CONCLUSION: Despite the higher rates of postoperative bleeding, DP-VR was found to be a feasible and safe surgery with acceptable postoperative morbidity and mortality compared to standard DP for left-sided pancreatic cancer.

The clinical effectiveness and complications of lumbar selective fenestration and concave-side fusion (LSFCF) in degenerative lumbar scoliosis (DLS) combined with lumbar spinal stenosis (LSS).

PURPOSE: This retrospective study was performed to analyze the clinical effects and complications of LSFCF in the surgical treatment of DLS combined with lumbar spinal stenosis (LSS). METHODS: A total of 26 eligible patients (mean age, 64.73 y; 17 men, 9 women) with DLS combined with LSS were included and LSFCF surgery was performed. An independent spine surgeon retrospectively reviewed the medical records and radiographs of all patients to evaluate surgical data and surgery-related complications. Preoperative, postoperative, and follow-up questionnaires were obtained to assess clinical outcomes. RESULTS: The average follow-up period of this study was 20.14 ± 5.21 months. The operation time and blood loss of patients underwent LSFCF were 129.33 ± 15.74 min and 356.13 ± 21.28 ml. The clinical effects of all patients in terms of visual analogue scale (VAS) and Oswestry disability index (ODI) have been significantly improved at the final follow-up postoperatively (P < 0.05). Complications such as infection, cerebrospinal fluid leakage, nerve injury, and internal fixation failure, etc. were not observed during the follow-up period. CONCLUSION: The LSFCF surgery is a safe and effective treatment for DLS patients combined with LSS.

Constructing Cu-C Bonds in a Graphdiyne-Regulated Cu Single-Atom Electrocatalyst for CO2 Reduction to CH4.

Regulating intermediates through elaborate catalyst design to control the reaction direction is crucial for promoting the selectivity of electrocatalytic CO2 -to-CH4 . M-C (M=metal) bonds are particularly important for tuning the multi-electron reaction; however, its construction in nanomaterials is challenging. Here, via rational design of in situ anchoring of Cu SAs (single atoms) on the unique platform graphdiyne, we firstly realize the construction of a chemical bond Cu-C (GDY). In situ Raman spectroelectrochemistry and DFT calculations confirm that due to the fabrication of the Cu-C bond, during CO2 reduction, the formation of *OCHO intermediates is dominant rather than *COOH on Cu atoms, facilitating the formation of CH4 . Therefore, we find that constructing the Cu-C bond in Cu SAs/GDY can supply an efficient charge transfer channel, but most importantly control the reaction intermediates and guide a more facile reaction pathway to CH4 , thereby significantly boosting its catalytic performance. This work provides new insights on enhancing the selectivity for CO2 RR at the atomic level.

Long noncoding RNA AC092155 facilitates osteogenic differentiation of adipose-derived stem cells through the miR-143-3p/STMN1 axis.

BACKGROUND: Numerous studies have demonstrated that long noncoding RNAs (lncRNAs) induce osteogenesis in adipose-derived stem cells (ADSCs). This study aimed to explore the role of lncRNAs AC092155 in promoting osteogenic differentiation of ADSCs. METHODS: MicroRNA (miRNA) and lncRNA sequencing were performed in ADSCs that underwent normal or osteogenic induction. Differentially expressed miRNAs and lncRNAs were identified using R software. The relative expression levels of lncRNA AC092155, miR-143-3p, and STMN1 during the process of osteogenic induction were determined by real-time polymerase chain reaction (RT-PCR). ADSCs were then transfected with agomiR-143-3p and pcDNA3.1-sh-lncRNA AC092155. Alkaline phosphatase (ALP) and alizarin red staining (ARS) were used to confirm the regulatory function of the lncRNA AC092155/miR-143-3p/STMN1 axis in osteogenic differentiation of ADSCs. RESULTS: lncRNA AC092155 was significantly upregulated in ADSCs following induction in the osteogenic medium. lncRNA AC092155 and STMN1 mimics increase the markers of osteogenic differentiation in the early and late phases, which was reflected in increased ALP activity as well as the higher deposition of calcium nodules. An miR-143-3p mimic showed the opposite effect. Luciferase reporter gene analysis demonstrated that lncRNA AC092155 directly targets miR-143-3p. Moreover, the lncRNA AC092155/miR-143-3p/STMN1 regulatory axis was found to activate the Wnt/ß-catenin signaling pathway. CONCLUSIONS: lncRNA AC092155 contributes to the osteogenic differentiation of ADSCs. The lncRNA AC092155/miR-143-3p/STMN1 axis may be a new therapeutic target for bone-related diseases.

Geometrical effect of graded index on the transport of polarized lights.

We investigate the geometrical effect of graded index on the transport of polarized lights in the scope of geometrical optics, and present three effective methods based on the Runge-Kutta ray tracing technique in the Frenet-Serret frame and a fixed global Cartesian frame, respectively, for obtaining the polarization state of a polarized light that propagates in graded-index media. The three methods have their own advantages in accuracy, computational efficiency, and difficulty of implementation, respectively. Simulations on a three-dimensional graded-index model show that the results obtained by the three methods are in perfect agreement with each other.

A novel antisense lncRNA NT5E promotes progression by modulating the expression of SYNCRIP and predicts a poor prognosis in pancreatic cancer.

A novel antisense lncRNA NT5E was identified in a previous microarray that was clearly up-regulated in pancreatic cancer (PC) tissues. However, its biological function remains unclear. Thus, we aimed to explore its function and clinical significance in PC. The lncNT5E expression was determined in PC specimens and cell lines. In vitro and in vivo studies detected the impact of lncNT5E depletion on PC cell proliferation, migration and invasion. Western blotting investigated the epithelial-mesenchymal transition (EMT) markers. The interaction between lncNT5E and the promoter region of SYNCRIP was detected by dual-luciferase reporter assay. The role of lncNT5E in modulating SYNCRIP was investigated in vitro. Our results showed that lncNT5E was significantly up-regulated in PC tissues and cell lines and associated with poor prognosis. LncNT5E depletion inhibited PC cell proliferation, migration, invasion and EMT in vitro and caused tumorigenesis arrest in vivo. Furthermore, SYNCRIP knockdown had effects similar to those of lncNT5E depletion. A significant positive relationship was observed between lncNT5E and SYNCRIP. Moreover, the dual-luciferase reporter assays indicated that lncNT5E depletion significantly inhibited SYNCRIP promoter activity. Importantly, the malignant phenotypes of lncNT5E depletion were rescued by overexpressing SYNCRIP. In conclusion, lncNT5E predicts poor prognosis and promotes PC progression by modulating SYNCRIP expression.

Long noncoding RNA SOX2OT promotes the proliferation of pancreatic cancer by binding to FUS.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors has one of the worst prognoses, and the role of long noncoding RNAs (lncRNAs) in the biological and pathological processes of pancreatic cancer, including tumor cell proliferation, is a popular topic in tumor research. Our previous study revealed the correlation between high levels of the lncRNA-SOX2OT (SOX2OT) with poor survival outcomes. Cell Counting Kit-8, EdU, Flow cytometry and Colony formation assays as well as Xenograft growth of PDAC cells in mice were used for the detection of PDAC cells proliferation progression. Fluorescence in situ hybridization, RNA-binding protein pulldown and RNA immunoprecipitation assays were also used to identify the putative mechanisms of SOX2OT participating in the tumor progression. SOX2OT and its potential downstream targets were verified by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). SOX2OT was confirmed to promote the proliferation of PDAC cells. It was found to directly physically bind to FUS and we also demonstrated that FUS protein stability was affected by binding with SOX2OT and FUS could suppressed PDAC tumor by regulating cell cycle-associated factors CCND1 and p27. Our findings suggest that SOX2OT may act as a tumor promoter in PDAC through physically binding FUS and regulating its downstream cell cycle-associated factors CCND1 and p27. It may serve as an effective target for antitumor treatment for pancreatic cancer.

Prognostic Nomogram for Resected Pancreatic Adenocarcinoma: A TRIPOD-Compliant Retrospective Long-Term Survival Analysis.

BACKGROUND: Prognostic prediction had been widely used in various cancer entities, from early screening to end-stage patient caring. Currently, there is hardly any well-validated nomogram which exists for long-term survival prediction in pancreatic adenocarcinoma (PC) patients in a post-surgery setting. Our objectives are to identify possible prognostic factors in PC patients following radical resection and to develop a prognostic nomogram based on independent survival predictors. METHODS: From 2009 to 2014, a total of 432 PC patients who underwent curative intended surgeries with complete follow-up data were included in this current retrospective long-term survival analysis. Clinicopathological data were extracted from medical records, and all missing values (percentage 0.9-8.3%) were imputed five times with the "PMM" method. Cox proportional hazards models were utilized. A nomogram was formulated based on results from the multivariate regression model so as to predict OS at 1-, 2- and 3-year as well as median OS. Validations, including discrimination and calibration, were carried out with 1000 bootstrap resamples. External validation was conducted in order to verify the accuracy of our nomogram at 1 and 2 years by utilizing the clinicopathological data of 122 PC patients who underwent curative intended surgeries in 2015 in our centre. RESULTS: Age, abdominal pain, back pain, tumour location, preoperative neutrophil-lymphocyte ratio, preoperative CA19-9, tumour differentiation, microscopic nerve invasion, microscopic vascular invasion, T stage, lymph node ratio, M stage and adjuvant chemotherapy were all assembled into nomogram. The concordance index (C-index) of internal and external validation was 0.702 and 0.688, respectively. The C-index of the TNM staging system was 0.572 (P < 0.001 vs. nomogram). CONCLUSION: Our prognostic nomogram based on clinicopathological parameters shows good performance in long-term survival prediction in PC patients following radical surgery and could play a role in further clinical utilization.

Reliability and validity of multi-shot DWI in diagnosis of cervical spondylotic myelopathy: a study based on 3-T MRI.

OBJECTIVE: To investigate whether multi-shot diffusion-weighted imaging (ms-DWI) could be applied in diagnosis and quantitative evaluation of cervical spondylotic myelopathy (CSM). METHODS: Thirty-three normal volunteers and 78 patients with CSM were included in this study. The apparent diffusion coefficient (ADC) values were measured at C2-C7 levels on sagittal section ADC map. The intraclass correlation coefficient (ICC) and Bland and Altman plot and Spearman coefficient were used to quantify the reproducibility of test and retest and inter-rater reliability. Pearson correlations were calculated to compare lADC and rADC versus mJOA and NDI scores. Receiver operating characteristic curve and the area under the curve (AUC) were applied to evaluate the diagnostic reliability. RESULTS: There was no statistically significant difference between ADC values obtained from normal volunteers at C2-C7 levels (P < 0.05). The ICC and spearman coefficient of lADC and rADC indicated excellent test-retest and inter-rater reliability. The mean lADC and rADC were significantly higher from patients than that from volunteers (all P < 0.01). The lADC had moderate to good correlations with mJOA and NDI (all P < 0.0001). Moreover, rADC had good to excellent correlations with mJOA and NDI (all P < 0.0001). Comparing AUCs, rADC was significantly superior in diagnosis which participants were CSM than lADC (P = 0.0118). CONCLUSION: The ms-DWI could be applied in diagnosis and quantitive assessment of CSM according to lADC and rADC. A new parameter, rADC, could be served as a diagnostic indice for CSM, which may quantitively reflect the severity of CSM. These slides can be retrieved under Electronic Supplementary Material.

ACVR1-knockout promotes osteogenic differentiation by activating the Wnt signaling pathway in mice.

Osteogenic differentiation refers to the process of bone formation and remodeling, which is controlled by complex molecular mechanisms. Activin A receptor type I (ACVR1) is reported to be associated with osteogenic differentiation. However, the underlying molecular mechanism remains elusive. Therefore, this study evaluates the function of ACVR1 in osteogenic differentiation through the Wnt signaling pathway. The expression of osteocalcin (Oc) and osterix together with osteogenic differentiation and mineralization was examined in ACVR1-knockout (KO) mouse. Furthermore, the Wnt signaling pathway was inhibited in bone marrow stromal cells (BMSCs) of mice to explore the role of the Wnt signaling pathway in osteogenic differentiation by means of alkaline phosphatase (ALP) activity detection and evaluation of mineralized nodules and calcium content. Subsequently, the effect of ACVR1 on the Wnt signaling pathway was assessed by determining the expression of ACVR1, ß-catenin, glycogen synthase kinase 3 ß (GSK3ß), dickkopf-related protein 1 (DKK1), and frizzled class receptor 1 (FZD1). Both their effects on osteogenic differentiation were further evaluated by determination of Oc, osterix, and Runx2 expression. AVCR1 KO mice exhibited increased Oc and osterix expression and promoted bone resorption and formation. ACVR1-knockout was observed to activate the Wnt signaling pathway with an increase of ß-catenin and reductions in GSK3ß, DKK1, and FZD1. With the inhibited Wnt signaling pathway expression of Oc, osterix, and Runx2 was decreased, and ALP activity, mineralized nodule, and calcium content in cellular matrix were decreased as well, indicating that inactivation of the Wnt signaling pathway reduced the differentiation of BMSCs into osteoclasts. These findings indicate that ACVR1-knockout promotes osteogenic differentiation by activating the Wnt signaling pathway in mice.

A de novo mutation in DHD domain of SKI causing spina bifida with no craniofacial malformation or intellectual disability.

Shprintzen-Goldberg syndrome (SGS) is a rare systemic connective tissue disorder characterized by craniofacial, skeletal, and cardiovascular manifestations. It is associated with a significant risk of intellectual disability, a feature which distinguishes it from Marfan and Loeys-Dietz syndromes. SGS is mainly caused by mutations in the SKI gene, a repressor of TGF-ß activity. Most SKI mutations are found in exon 1 of the gene and are located in the R-SMAD domain, a proposed hotspot for de novo mutations. Here, we report on a de novo SKI mutation located in the DHD domain of SKI. By adding our finding to previously reported de novo SKI mutations, a new mutational hotspot in the DHD domain is proposed. Our patient presented with a lipomeningomyelocele, tethered cord, and spina bifida but with no SGS-related clinical findings apart from a marfanoid habitus and long slender fingers. Specifically, she did not have an intellectual disability, craniofacial, or cardiovascular abnormalities. By comparing the clinical findings on patients with mutations in the R-SMAD and DHD domains of SKI, we propose that mutations in those domains have different effects on TGF-ß activity during embryonic development with resulting phenotypic differences.

Anterior controllable antedisplacement fusion as a choice for 28 patients of cervical ossification of the posterior longitudinal ligament with dura ossification: the risk of cerebrospinal fluid leakage compared with anterior cervical corpectomy and fusion.

PURPOSE: To compare the incidence rate of cerebrospinal fluid (CSF) leakage between anterior controllable antedisplacement fusion (ACAF) and anterior cervical corpectomy and fusion (ACCF) in the treatment of ossification of the posterior longitudinal ligament (OPLL) with dura ossification (DO). METHODS: In the period from June 2015 to June 2017, ACAF and ACCF were performed on patients with OPLL with DO. Double-layer sign was observed on axial bone window of CT images. The operation duration, blood loss, and hospital stay were measured. Radiologic assessment included occupying rate, type and extent of OPLL, decompression width, postoperative area of the spinal canal, and anteroposterior diameter of the spinal cord. The JOA scoring system was used to evaluate the neurological status. Surgery-related complications such as CSF leakage and spinal cord or nerve injury were all recorded. RESULTS: There were 28 patients in ACAF group and 31 in ACCF group. On cross-sectional CT, decompression width and postoperative spinal canal area were both significantly larger in the ACAF group than that in the ACCF group (P < 0.01). The anteroposterior diameter of the spinal cord was significantly larger in the ACAF group (P < 0.05). Mean JOA score was better in the ACAF group (P < 0.05). In the ACCF group, seven (22.6%) patients had CSF leakage. However, only one (3.6%) presented with CSF leakage in the ACAF group. The difference of incidence rate of CSF leakage was significant (P < 0.01). CONCLUSIONS: ACAF, which can significantly reduce CSF leakage and achieve good neurological recovery, is a good option to treat cervical OPLL with DO. These slides can be retrieved under Electronic Supplementary Material.

Long non-coding RNA XLOC_000647 suppresses progression of pancreatic cancer and decreases epithelial-mesenchymal transition-induced cell invasion by down-regulating NLRP3.

BACKGROUND: Long non-coding RNAs (lncRNAs) play an important role in the development and progression of various tumors, including pancreatic cancer (PC). Recent studies have shown that lncRNAs can 'act in cis' to regulate the expression of its neighboring genes. Previously, we used lncRNAs microarray to identify a novel lncRNA termed XLOC_000647 that was down-regulated in PC tissues. However, the expression and function of XLOC_000647 in PC remain unclear. METHODS: The expression of XLOC_000647 and NLRP3 in PC specimens and cell lines were detected by quantitative real-time PCR. Transwell assays were used to determine migration and invasion of PC cells. Western blot was carried out for detection of epithelial-mesenchymal transition (EMT) markers in PC cells. The effect of XLOC_000647 on PC cells was assessed in vitro and in vivo. The function of NOD-like receptor family pyrin domain-containing 3 (NLRP3) in PC was investigated in vitro. In addition, the regulation of NLRP3 by XLOC_000647 in PC was examined in vitro. RESULTS: Here, XLOC_000647 expression was down-regulated in PC tissues and cell lines. The expression level of XLOC_000647 was significantly correlated to tumor stage, lymph node metastasis, and overall survival. Overexpression of XLOC_000647 attenuated cell proliferation, invasion, and EMT in vitro and impaired tumor growth in vivo. Further, a significantly negative correlation was observed between XLOC_000647 levels and its genomic nearby gene NLRP3 in vitro and in vivo. Moreover, XLOC_000647 decreased NLRP3 by inhibiting its promoter activity. Knockdown of NLRP3 decreased proliferation of cancer cells, invasion, and EMT in vitro. Importantly, after XLOC_000647 was overexpressed, the corresponding phenotypes of cells invasion and EMT were reversed by overexpression of NLRP3. CONCLUSIONS: Together, these results indicate that XLOC_000647 functions as a novel tumor suppressor of lncRNA and acts as an important regulator of NLRP3, inhibiting cell proliferation, invasion, and EMT in PC.

YY1 suppresses proliferation and migration of pancreatic ductal adenocarcinoma by regulating the CDKN3/MdM2/P53/P21 signaling pathway.

Pancreatic ductal adenocarcinoma (PDAC) is one of the malignant lethal tumors. It has been reported that the transcriptional regulator Yin Yang-1 (YY1) suppressed the invasion and metastasis of PDAC. However, the function of YY1 on proliferation and migration of pancreatic cancer remains to be clarified. In this study, we found that YY1 overexpression or knockdown can inhibit or promote the proliferation and migration of pancreatic cancer cells. Digital gene expression sequencing indicates that cyclin-dependent kinase inhibitor 3 (CDKN3) may be the candidate target gene of YY1. Then we found that YY1 can downregulate the expression of CDKN3 by directly binding to the promoter region of CDKN3. Silencing CDKN3 expression could inhibit the ability of cell proliferation and migration and overexpression of CDKN3 could restore the effects induced by YY1 overexpression in pancreatic cancer cells. The expression levels of YY1 and CDKN3 were negatively correlated in pancreatic cancer tissues and PDAC patients with higher levels of CDKN3 have poor prognosis. Vitro and vivo study show that CDKN3 can form a complex with MdM2-P53, thus leading to inhibiting the expression of P21, which is the target gene of P53, and finally facilitates the cell cycle to promote the proliferation of pancreatic cancer cells. Hence, YY1 can directly regulate the expression of CDKN3 and participate in the cycle of pancreatic cancer cells, which can inhibit the progression of pancreatic cancer. These results reveal that YY1-CDKN3-MDM2/P53-P21 axis is involved in pancreatic tumorigenesis, which may develop new methods for human pancreatic cancer therapy.

Long non-coding RNA lnc-PCTST predicts prognosis through inhibiting progression of pancreatic cancer by downregulation of TACC-3.

Pancreatic cancer (PC), which is one of the most lethal of malignancies and a major health burden, is associated with a dismal prognosis despite current therapeutic advances. Numerous long noncoding RNAs (lncRNA) have shown to be essential for PC tumorigenesis and progression. Nevertheless, the exact expression pattern of lnc-PCTST and its clinical significance still remain unclear. This study investigates the expression pattern of lnc-PCTST and its associated mRNA in three paired PC tissues and adjacent non-tumor tissues by Microarray-coarray approach. Briefly, our data demonstrated that lnc-PCTST expression is down-regulated in PC tissues. Also, lnc-PCTST has shown to be negatively correlated with transforming acidic coiled-coil 3 (TACC-3) expression. This expression pattern was further confirmed following qRT-PCR validation of 34 out of 48 paired cancer tissues. Furthermore, lnc-PCTST overexpression in PC cell lines inhibited cell proliferation and invasion in vitro, and tumorigenesis in vivo (using nude mice as animal model), but did not altered cell migration. Moreover, lnc-PCTST overexpression increased E-cadherin and repressed vimentin expression in vitro. Additionally, TACC-3 knockdown simulated the inhibiting effect of lnc-PCTST overexpression on PC cell lines, and the impaired proliferation, invasion effect and E-cadherin, vimentin expression on lnc-PCTST over-expressed cell lines can be rescued by overexpressed TACC-3. Significantly, the expression of lnc-PCTST was closely associated with its genomic neighboring gene TACC-3 and inhibited its promoter activity. In conclusion, lnc-PCTST is a potential tumor suppressor in PC, which inhibits cell proliferation, invasion, tumorigenesis and EMT by modulating TACC-3.

miR-32-5p-mediated Dusp5 downregulation contributes to neuropathic pain.

Previous studies have demonstrated that microRNAs (miRNAs) play important roles in the pathogenesis of neuropathic pain. In the present study, we found that miR-32-5p was significantly upregulated in rats after spinal nerve ligation (SNL), specifically in the spinal microglia of rats with SNL. Functional assays showed that knockdown of miR-32-5p greatly suppressed mechanical allodynia and heat hyperalgesia, and decreased inflammatory cytokine (IL-1ß, TNF-α and IL-6) protein expression in rats after SNL. Similarly, miR-32-5p knockdown alleviated cytokine production in lipopolysaccharide (LPS)-treated spinal microglial cells, whereas its overexpression had the opposite effect. Mechanistic investigations revealed Dual-specificity phosphatase 5 (Dusp5) as a direct target of miR-32-5p, which is involved in the miR-32-5p-mediated effects on neuropathic pain and neuroinflammation. We demonstrated for the first time that miR-32-5p promotes neuroinflammation and neuropathic pain development through regulation of Dusp5. Our findings highlight a novel contribution of miR-32-5p to the process of neuropathic pain, and suggest possibilities for the development of novel therapeutic options for neuropathic pain.