[Value of high resolution magnetic resonance imaging for preoperative evaluation of Denonvilliers fascia in patients with rectal cancer].

Objective: Total mesorectal excision (TME) is the gold standard for surgical treatment of mid-low rectal cancer, but the postoperative incidence of urination and sexual dysfunction is relatively high. Preserving the Denonvilliers fascia (DF) during TME can reduce the postoperative incidence of urination and sexual dysfunction. In this study, high resolution magnetic resonance imaging (MRI) was used to observe the imaging performance and display of DF, so as to determine the value of this technique in preoperative evaluation of the preservation of DF. Methods: A descriptive cohort study was carried out. Clinical data of patients with rectal cancer who underwent TME and received preoperative high-resolution MRI at department of Gastrointestinal Surgery, the Third Affiliated Hospital of Sun Yat-sen University from August 2015 to June 2017 were retrospectively analyzed. The characteristics of DF were examined, and the shortest distance (d) between the anterior edge of tumor and DF was measured on high-resolution MRI. The distance d was compared between patients with stage T1-T2 and those with stage T3. Receiver operating characteristic (ROC) analysis was used to determine the predictive value of d for stage T1-T2 disease. Results: Thirty-two patients were enrolled in the study, including 27 males and 5 females with mean age of (62.9±8.9) years. DF was visualized in 96.9% (31/32) of cases on the T2WI sequence. The mean distance d in patients with stage T1-T2 disease (n=23) was (6.73±2.65) mm, and in those with stage T3 disease (n=9) was (1.30±1.15) mm (t=5.893, P<0.001). A cutoff of d >3 mm yielded specificity and positive predictive value for diagnosing stage T1-T2 disease of both 100%, sensitivity of 95.7% and negative predictive value of 90%. The optimum threshold of d was >3.05 mm, and Youden index was 0.957. Conclusions: High-resolution MRI can show the DF and accurately evaluate the relationship of DF with tumor in rectal cancer patients. Analysis on d value can provide an objective basis for the safe preservation of DF.

[Anatomy research on Denonvilliers fascia and its significance in nerve-preservation rectal cancer surgery].

Urinary and sexual dysfunctions due to intraoperative pelvic autonomic nerve injury have become the most common complications of rectal cancer surgery, seriously affecting postoperative quality of life. How to protect the nerve and urogenital function while ensuring radical resection for rectal cancer has become the focus of research. We previously carried out a series of systematic studies on Denonvilliers fascia, an important anatomical structure closely related to protection of pelvic autonomic nerve, and demonstrated the importance of Denonvilliers fascia in preservation of intraoperative pelvic autonomic nerve and protection of postoperative urogenital function from aspects of anatomy, physiology, tissue, operation practice and so on. Meanwhile, based on the interim results of our multicenter randomized controlled study, we confirmed that total mesorectal excision with preservation of Denonvilliers fascia (innovative TME, iTME) could effectively reduce the incidence of postoperative urinary and sexual dysfunctions in male patients with mid-low rectal cancer, without sacrificing oncologic outcome. In this article, combined with our research results, we review the literature on anatomy research progress of Denonvilliers fascia to demonstrate the significance and research prospect of Denonvilliers fascia in the pelvic autonomic nerve preservation surgery for rectal cancer.

[Total mesorectal excision with preservation of Denonvilliers' fascia (iTME) based on membrane anatomy].

Total mesorectal excision (TME) has been advocated as the golden standard of mid-low rectal cancer surgery for nearly 30 years. However, the complication of postoperative urinary and sexual dysfunctions due to intraoperative nerve injury has yet to be improved. Based on the concept of membrane anatomy, we carried out a systematic study on the important membrane anatomical structure anterior to the rectum--Denonvilliers' fascia. From multiple aspects including anatomy, physiology, histochemistry and surgical practice, we verified the importance of Denonvilliers' fascia for TME surgery in prevention of intraoperative nerve injury and postoperative urogenital dysfunction. Moreover, based on anatomical study of the surgical marker line of Denonvilliers' fascia (Wei's line) and surgical plane, we proved that total mesorectal excision with preservation of Denonvilliers' fascia (iTME) was feasible and practical. Therefore, we conducted a large multicentric randomized controlled trial (RCT). The mid-term result demonstrated that compared with traditional TME surgery, iTME was more effective in reducing the incidence of postoperative urinary and sexual dysfunctions in male patients with mid-low rectal cancer, without sacrifice of short-term tumor radical outcome. We believe that the final RCT result of iTME, based on membrane anatomy, will provide solid evidence for the update of concepts of rectal cancer surgery.

[Application of polyetheretherketone and its composite as frameworks in fixed dental prostheses].

Characterized by eminent mechanical properties, chemical stability and biosafety, polyetheretherketone (PEEK), as a brand-new type of biomedical material, has been applied in the field of stomatology. This review elaborates on basic behaviors and fabrication methods of PEEK and its composite, and their application in fixed dental prostheses (FDP) as frameworks as well as their adhesive properties. Meanwhile, this review also looks into the prospect of the integration of additive manufacturing in fabricating frameworks of PEEK and its composite in FDP.

LncRNA DQ786243 expression as a biomarker for assessing prognosis in patients with gastric cancer.

OBJECTIVE: Recent studies have revealed that long noncoding RNA DQ786243 (DQ786243) plays an important role in the development of gastric cancer (GC) and colorectal cancer. However, the expression and function of DQ786243 in GC patients remain largely unknown. The purpose of our study was to investigate the clinical significance of DQ786243 expression in GC. PATIENTS AND METHODS: qRT-PCR was used to examine DQ786243 expression in 172 paired GC samples and matched adjacent normal tissues. Besides, the relationship between DQ786243 expression and clinicopathologic characteristics was analyzed. Overall survival (OS) and progression-free survival (PFS) curves of patients in subgroups were constructed by the Kaplan-Meier method. Multivariate regression analyses were performed to analyze independent factors affecting prognosis. RESULTS: We found a significant up-regulation of DQ786243 in GC tissues compared to normal tissues (p < 0.01). High DQ786243 expression was closely associated with invasion depth (p = 0.006), TNM stage (p = 0.009) and lymphatic metastasis (p = 0.017). Moreover, Kaplan-Meier analysis showed that patients with DQ786243 high expression tumors had worse OS (p = 0.0012) and PFS (p = 0.0002) compared to patients with DQ786243 low expression tumors. Finally, multivariate analysis showed that DQ786243 was a significant and independent prognostic predictor for both OS (p = 0.002) and PFS (p = 0.001) of GC patients. CONCLUSIONS: Our data suggest, for the first time, that the evaluation of the DQ786243 expression in GC tissues is a useful tool for predicting prognosis of GC.

Effect of intra-operative autonomic nerve stimulation on pelvic nerve preservation during radical laparoscopic proctectomy.

AIM: This study assessed the effect of intra-operative electrical nerve stimulation (INS) on pelvic autonomic nerve preservation (PANP) during laparoscopic resection for rectal cancer. METHOD: A total of 189 consecutive cases of radical laparoscopic proctectomy were included. PANP was assessed visually or with INS. Urinary function was evaluated by residual urine volume (RUV), International Prostatic Symptom Score (IPSS) and recatheterization rate. Erectile function was evaluated using the International Index of Erectile Function (IIEF-5) scale. RESULTS: INS successfully confirmed PANP in 65 (91.5%) patients, while direct vision confirmed PANP in only 72 (61.0%) patients. Compared with the successfully confirmed patients, failed patients in the INS group exhibited higher postoperative RUV (100.0 ± 34.6 vs 25.2 ± 13.6 ml, P = 0.003), higher IPSS (7 days, 20.0 ± 8.6 vs 6.5 ± 2.4, P = 0.012; 1 month, 13.5 ± 6.0 vs 5.3 ± 1.9, P = 0.020; 6 months, 11.7 ± 5.1 vs 4.5 ± 1.7, P = 0.018), a greater number of incidences of a micturition disorder (66.7% vs 1.5%, P = 0.000), higher recatheterization rates (33.3% vs 1.5%, P = 0.017) and a lower IIEF score at 3 months (8.25 ± 0.96 vs 10.93 ± 1.99, P = 0.012) and 6 months (12.50 ± 1.29 vs 15.63 ± 1.65, P = 0.001) postoperatively. Compared with the vision group, the INS group had less deterioration in postoperative RUV (31.5 ± 26.4 vs 54.0 ± 46.7 ml, P = 0.000), lower IPSS (7 days, 7.7 ± 5.0 vs 11.0 ± 6.6, P = 0.000; 1 month, 6.0 ± 3.3 vs 7.6 ± 5.4, P = 0.012) and higher IIEF score (3 months, 10.69 ± 2.07 vs 9.42 ± 2.05, P = 0.001; 6 months, 15.36 ± 1.85 vs 13.64 ± 2.00, P = 0.000) as well as a lower incidence of urination disorders (7.0% vs 17.8%, P = 0.038). CONCLUSION: INS is effective for the accurate evaluation of PANP during radical laparoscopic proctectomy. Combined with INS, laparoscopic proctectomy is more effective in urogenital function protection.

Serum vascular endothelial growth factor and angiogenesis are related to the prognosis of patients with gastrointestinal stromal tumors.

AIM: To investigate if serum vascular endothelial growth factor (SVEGF), tissue VEGF and microvessel density (MVD) have any relation to progress and prognosis in gastrointestinal stromal tumors (GIST). METHODS: SVEGF was examined using ELISA. VEGF and MVD were examined using immunohistochemical staining. RESULTS: The median level of SVEGF was higher in GIST than in controls. A higher level of SVEGF and a positive expression rate of VEGF were obtained in diameter >or=5 cm, mitotic count >or=2/10 high power fields (HPF), recurrence and high risk groups. The MVD of experimental was higher than that of controls. A higher MVD was observed in mitotic count >or=2/10HPF and recurrence groups. The median level of SVEGF was higher in the VEGF positive group than in the controls. The SVEGF presented a relationship with MVD. Factors predicating poor prognosis were SVEGF and VEGF. CONCLUSIONS: SVEGF and VEGF show a correlation with poor prognosis of GIST.

Molecular mechanisms of cocaine reward: combined dopamine and serotonin transporter knockouts eliminate cocaine place preference.

Cocaine blocks uptake by neuronal plasma membrane transporters for dopamine (DAT), serotonin (SERT), and norepinephrine (NET). Cocaine reward/reinforcement has been linked to actions at DAT or to blockade of SERT. However, knockouts of neither DAT, SERT, or NET reduce cocaine reward/reinforcement, leaving substantial uncertainty about cocaine's molecular mechanisms for reward. Conceivably, the molecular bases of cocaine reward might display sufficient redundancy that either DAT or SERT might be able to mediate cocaine reward in the other's absence. To test this hypothesis, we examined double knockout mice with deletions of one or both copies of both the DAT and SERT genes. These mice display viability, weight gain, histologic features, neurochemical parameters, and baseline behavioral features that allow tests of cocaine influences. Mice with even a single wild-type DAT gene copy and no SERT copies retain cocaine reward/reinforcement, as measured by conditioned place-preference testing. However, mice with no DAT and either no or one SERT gene copy display no preference for places where they have previously received cocaine. The serotonin dependence of cocaine reward in DAT knockout mice is thus confirmed by the elimination of cocaine place preference in DAT/SERT double knockout mice. These results provide insights into the brain molecular targets necessary for cocaine reward in knockout mice that develop in their absence and suggest novel strategies for anticocaine medication development.

Structural correlates for down-regulation of m1 and m2 muscarinic receptor subtypes.

Three chimeric receptors stably expressed in murine fibroblast (B82) cells were used to examine how different parts of the rat muscarinic m1 and m2 receptors contribute to the down-regulation process. The MCH7 chimeric m2 receptor contained a fragment between VIth TM and C-terminal end derived from the m1 receptor. The MCH3 and MCH5 receptors have exchanged N-terminal and third intracellular loop regions of the MCH7 receptor. Fibroblast cells stably expressing individual muscarinic wild type (m1, m2) or chimeric (MCH3, MCH5, or MCH7) receptors were treated with plain medium (control) or medium containing carbachol for 24 h. Receptor density changes were measured by [3H](-)1-N-methyl-3-quinuclidinyl benzilate ([3H](-)MQNB) saturation binding studies. There was a significant loss of receptor density, different for each receptor studied, following carbachol treatment relative to control cells. We related this loss of [3H](-)MQNB binding to the number of amino acids derived from m1 or m2 receptors for each constructed chimera and to the affinity of carbachol to the receptors studied. We demonstrate that: 1) the region from the VIth TMD to the end of C-terminal controls the extent of m1 and m2 receptor down-regulation; 2) the overall receptor conformation and the interaction between intracellular portions of the receptor influence the extent of receptor down-regulation; and 3) resistance to down-regulation by carbachol correlates with the affinity of carbachol to the muscarinic receptor construct.

Pharmacological characterization of N-methyl-D-aspartate receptors in spinal cord of rats with a chronic peripheral mononeuropathy.

N-Methyl-D-aspartate (NMDA) receptor antagonists, acting in the spinal cord, are analgesic. However, the clinical utility of these antagonists is diminished by their adverse effects on cognition and behavior. To facilitate the development of spinal cord-selective NMDA receptor antagonists, we characterized ligand interactions at NMDA receptors in spinal cord of normal rats and rats with a chronic peripheral neuropathy. NMDA receptors in spinal cord were distinguished from those in cerebral cortex on the basis of differences in the potencies of competitive and noncompetitive antagonists and on the basis of differences in their response to spermidine. D(-)-2-Amino-5-phosphonopentanoic acid (AP-5) and (+)-(1-hydroxy-3-aminopyrrolidine-2-one) (HA-966) were more potent in inhibiting NMDA-dependent [3H]TCP binding in spinal cord while, conversely, MK-801 was more potent in inhibiting [3H]TCP binding to NMDA receptors in cerebral cortex. Spermidine increased [3H]TCP binding to NMDA receptors in cerebral cortex (39+/-8%) but not spinal cord (2+/-1%). Based on these properties, NMDA receptors in spinal cord more closely resembled those in cerebellum than those in cerebral cortex. Generation of a chronic neuropathy had no effect on the density of NMDA receptors in lumbar spinal cord. There were also no major changes in the potencies of competitive antagonists or channel blocking ligands, although there was a trend for kynurenic acid and D-CPP to be more potent in the spinal cords of neuropathic animals. These findings indicate that, in both normal and neuropathic pain states, NMDA receptors in spinal cord can be distinguished pharmacologically from those in cerebral cortex. These findings underscore the feasibility of developing spinal cord-selective NMDA receptor antagonists as novel analgesics.

Down-regulation and desensitization of the muscarinic M1 and M2 receptors in transfected fibroblast B82 cells.

Murine fibroblast cell lines stably transfected with the rat muscarinic m1 or m2 receptor genes were used to study the homologous regulation of the muscarinic M1 or M2 receptors. The cells were pretreated with the muscarinic receptor agonists, (+)-cismethyl-dioxolane, carbachol, 2,8-dimethyl-3-methylene-1-oxa-8-aza-spiro- [4,5]decane ((+) or (-)-YM796) or the muscarinic receptor antagonist atropine for up to 24 h. Our study has demonstrated that the muscarinic receptor nonselective full agonist, (+)-cismethyl-dioxolane, induced the down-regulation of both the muscarinic M1 and the M2 receptors in association with desensitization of the receptor-mediated functions. The muscarinic M1 receptors are down-regulated without significant receptor internalization while the muscarinic M2 receptors are more sensitive to down-regulation than the muscarinic M1 receptors because of significant internalization of the muscarinic M2 receptors in our system. The muscarinic M1 receptor partial agonist, (-)-YM796 induced less down-regulation and no significant desensitization of the muscarinic M1 receptors with no substantial effect on the muscarinic M2 receptor density or function.

Pharmacological characterization of a novel muscarinic partial agonist, YM796, in transfected cells expressing the m1 or m2 muscarinic receptor gene.

To investigate the pharmacological effect of a novel compound YM796, we performed radioligand binding experiments and correlative biochemical experiments using the transfected murine fibroblast B82 cells which expressed the m1 and m2 muscarinic receptor genes (cloned cell lines designated as LK3-3 and M2LKB2-2, respectively). [3H](-)methyl-3-quinuclidinyl benzilate [( 3H](-)MQNB) binding in these transfected cell lines was inhibited by different optical isomers of YM796 and other muscarinic drugs, atropine, pirenzepine, AF-DX 116, as well as selected agonists. (-)YM796, (+)YM796 and (+/-)YM796 inhibited [3H](-)MQNB binding in LK3-3 cells with Ki values of 16.4 microM, 30.1 microM and 21.8 microM and in M2LKB2-2 cells with Ki values of 52.0 microM, 108 microM and 77.1 microM, respectively. From functional assays we found the two isomers, (-)YM796 and (+)YM796 had different intrinsic activities for the M1 and M2 muscarinic receptors. (-)YM796 revealed agonistic activity: stimulation of [3H]IP1 accumulation in LK3-3 cells with an EC50 value of 26.5 microM, which was less efficacious (the Emax value was 5.6 times basal) than carbachol, a full agonist (the Emax value was 17.2 times basal). Interestingly, (-)YM796 did not show significant inhibition of cAMP formation in M2LKB2-2 cells except at extremely high concentrations (greater than 1mM). (+)YM796 exhibited no significant efficacy for the M1 and M2 muscarinic receptors. These results suggest that (-)YM796 represents a muscarinic partial agonist with functional selectivity for the M1 muscarinic receptors whereas (+)YM796 shows no efficacy for either M1 or M2 muscarinic receptors in these transfected cells.

[Comparison of the affinities of amoxapine and loxapine for various receptors in rat brain and the receptor down-regulation after chronic administration].

Using radioligand receptor binding methods, the affinities (Ki) of amoxapine and loxapine for various receptors (adrenergic alpha 1, alpha 2, beta; dopaminergic D1, D2; serotoninergic 5-HT1, 5-HT2; Muscarinic, GABA, BZ) were investigated. The two compounds showed high affinities for 5-HT2, D2 and alpha 1 receptors (Ki less than 10(-7) mol/L), moderate affinity for alpha 2 receptor (Ki less than 10(-6) mol/L), and low affinities for M and 5-HT1 receptor (Ki less than 10(-5) mol/L). In addition, amoxapine appeared to have low affinities for D1 and GABA receptors. For D1 receptor, loxapine was found to have moderate affinity which was nearly 20 fold greater than amoxapine, but amoxapine exhibited more potent inhibitory effects on serotonin receptors and weaker inhibitory affects on dopamine receptors. Neither amoxapine nor loxapine showed significant affinity for BZ and beta-adrenergic receptors. These differences in the affinities may be responsible for their different psychopharmacological effects in the clinical treatment of patients. The regulation of 5-HT2 and beta receptors were examined in chronic experiments on rats given amoxapine 8 mg/kg or loxapine 1 mg/kg orally once daily for one to three weeks. The 5-HT2 receptor density was time-dependently reduced but no effect on beta receptors was observed. The down-regulation of 5-HT2 receptors might be associated with antidepressant action of the two drugs.