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Objective: Appendiceal mucinous neoplasm (AMN) is a rare obstructive dilatation of the appendix caused by an intraluminal accumulation of mucoid material, showing an insidious onset and few specific clinical manifestations. The purpose of the study is to analyze clinicopathological characteristics of primary AMN and recurrence after radical resection. Methods: A total of 50 patients were included in the retrospective cohort study of AMN. Patient data, such as demographics, tumor characteristics, surgical management, preoperative serum carcinoembryonic antigen (CEA), and carcinoembryonic antigen 19-9 (CA19-9) levels, were collected. All patients were followed-up with interval CT scans until the end of December 2021, with overall survival (OS) and progression-free survival (PFS) being calculated. Results: All patients were confirmed as AMN by pathological diagnosis after surgery, including 28 cases (56.00%) of low-grade AMN (LAMN) and 22 cases (44.00%) of non-LAMN. Among 50 patients with AMN, there were 12 cases (24.00%) complicated with pseudomyxoma peritonei (PMP). Higher proportions of patients with pTis, pT3, pT4a, ruptured at presentation, and PMP were found in patients with non-LAMN patients than LAMN (p < 0.05). There was a remarkable difference about preoperative serum CA19-9 levels between patients with LAMN and non-LAMN (p = 0.044). Patients complicated with PMP had a higher proportion of patients with ruptured at presentation than those who were not (p < 0.001). The patients with PMP had increased tumor size compared with those without PMP (p = 0.031). Remarkable differences were observed in terms of preoperative serum CA19-9 (p = 0.009) levels between patients with PMP and without PMP. We performed a multivariate analysis of the presence or absence of PMP and found that ruptured at presentation was found to be a risk factor for PMP in patients with AMN (p = 0.003). The PFS in the patients with PMP and those without was 33.33% (4/12) and 2.63% (1/38), showing a significant difference (P = 0.002). Conclusion: The study demonstrates that ruptured at presentation and PMP may influence the prognosis and survival of patients with AMN.
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Perioperative hyperglycemia is a common metabolic disorder in the clinic. Hyperglycemia, via upregulation of E74-like ETS transcription factor 3 (ELF3), induces cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS) expressions, thus leading to endothelial apoptosis and vascular endothelial injury. Propofol is a widely used anesthetic. In the present study, we explored whether and how propofol protects against high glucose-induced COX2 and iNOS expressions in human umbilical vein endothelial cells (HUVECs). We found that high glucose level decreases cell viability and increases COX2 and iNOS expressions in HUVECs. Our data also indicated that ELF3 overexpression participates in high glucose-mediated cell viability reduction and high glucose-induced COX2 and iNOS expressions. Moreover, propofol treatment improves high glucose-mediated reduction in cell viability and decreases COX2 and iNOS expressions via inhibition of ELF3 expressions. Furthermore, specificity protein 1 (SP1) was found to regulate ELF3 expression, thus mediating endothelial injury. Propofol inhibits high glucose-induced SP1 expression. High glucose increases the abundance of SP1 bound to the ELF3 promoter, which can be reversed by propofol treatment. The protective effect of propofol is reversed by SP1 overexpression. In conclusion, propofol downregulates high glucose-induced SP1 expression, thus attenuating high glucose-induced ELF3 expression, inhibiting high glucose-induced COX2 and iNOS expressions, and improving high glucose-mediated cell viability reduction in HUVECs.
Assuntos
Hiperglicemia , Propofol , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Glucose/metabolismo , Glucose/toxicidade , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Hiperglicemia/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Propofol/farmacologiaRESUMO
Polyether-ether-ketone (PEEK), with its superior mechanical, chemical, and thermal properties, as well as high biocompatibility, has been used in aerospace, electronics, and biomedical applications. In this paper, a large number of experiments of single-pulse laser drilling on PEEK were performed to analyze the hole morphology and keyhole evolution, which were characterized by an optical microscope, charge-coupled device (CCD), and high-speed camera. A novel method is proposed to observe and measure the dimension of the processed hole rapidly right after laser drilling for special polymer materials with wear-resistance and non-conductivity. Morphological characteristics of holes are presented to illustrate the effect of pulse width and peak power on hole depth, hole diameter, and aspect-ratio. The obtained maximum drilling depth was 7.06 mm, and the maximum aspect-ratio was 23. In situ observations of the dynamic process of laser drilling, including the keyhole evolution together with ejection and vaporization behavior, were also carried out. The keyhole evolution process can be divided into three stages: rapid increment stage (0−2 ms) at a rate of 2.1 m/s, slow increment stage (2−4 ms) at a rate of 0.3 m/s, and stable stage (>4 ms). Moreover, the variation of dimensionless laser power density with the increase in pulse width was calculated. The calculated maximum drilling depth based on energy balance was compared with the experimental depth. It is proven that the laser−PEEK interaction is mainly influenced by a photothermal effect. Ejection is the dominant material-removal mechanism and contributes to over 60% of the depth increment during the rapid increment stage, while vaporization is dominant and contributes to about 80% of the depth increment during the slow increment stage. The results reveal the material removal mechanism for single-pulse laser drilling on PEEK, which is helpful to understand the dynamic process of keyhole evolution. This not only provides a processing window for future laser drilling of PEEK but also gives a guide for the manufacturing of other polymers.
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CC chemokine ligand 2 (CCL2) has been implicated in pathological pain, but the mechanism underlying the pronociceptive effect of CCL2 is not fully understood. Voltage-gated sodium (Nav) channels are important determinants of the excitability of sensory neurons. Hence we tested the hypothesis that CCL2 contributes to inflammatory pain via modulating Nav channel activity of primary afferent neurons. Chronic inflammatory pain was induced in rats by intraplantar injection of the complete Freud adjuvant (CFA) to one of the hind paws. Control rats received intraplantar injection of equal volume of saline. A significant increase of CCL2 mRNA and CCL2 receptor (CCR2) protein expression was detected in the ipsilateral dorsal root ganglion (DRG) in CFA-treated rats. Intraplantar injection of CCL2 protein in the control rats had minimal effect on the paw withdrawal threshold (PWT) in response to mechanical stimulation. However, in CFA-treated rats, intraplantar CCL2 led to an increase in pain responses. Patch-clamp recording of acutely dissociated DRG neurons revealed that CCL2 had minimum effect on the excitability of sensory neurons from control rats. However, CCL2 directly depolarized a large proportion of small to medium-sized sensory neurons from CFA-treated rats. In addition, CCL2 was found to enhance whole-cell TTX-sensitive sodium currents without significantly affecting the TTX-resistant sodium currents and the potassium currents. These results are in agreement with previous reports concerning the involvement of CCL2-CCR2 signaling in inflammatory hyperalgesia and further indicate that enhanced TTX-sensitive channel activity may partly underlie the pronociceptive effects of CCL2.
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Quimiocina CCL2/farmacologia , Inflamação/metabolismo , Neurônios Aferentes/efeitos dos fármacos , Dor/metabolismo , Canais de Sódio/metabolismo , Tetrodotoxina/farmacologia , Animais , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Sinergismo Farmacológico , Adjuvante de Freund , Gânglios Espinais/citologia , Gânglios Espinais/metabolismo , Expressão Gênica/efeitos dos fármacos , Inflamação/induzido quimicamente , Masculino , Potenciais da Membrana/efeitos dos fármacos , Neurônios Aferentes/metabolismo , Técnicas de Patch-Clamp , Ratos Sprague-Dawley , Bloqueadores dos Canais de Sódio/farmacologia , Canais de Sódio/genéticaRESUMO
The accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) lumen leads to ER stress, which is related to cellular reactive oxygen species production. Neuropathic pain may result from spinal dorsal horn (SDH) ER stress. In this study, we examined the cause-effect relationship between ER stress and neuropathic pain using the spinal nerve ligation (SNL) rat model. We showed that ER stress was mutually promotive with oxidative stress during the process. We also tested the hypothesis that spinal sensitization arose from reduced activities of GABA-ergic interneurons and that spinal sensitization was mediated by SDH ER stress. Other important findings in this study including the following: (1) nociceptive behavior was alleviated in SNL rat as long as tauroursodeoxycholic acid injections were repeated to inhibit ER stress; (2) inducing SDH ER stress in healthy rat resulted in mechanical hyperalgesia; (3) blocking protein disulfide isomerase pharmacologically reduced ER stress and nociceptive behavior in SNL rat; (4) cells in the dorsal horn with elevated ER stress were mainly neurons; and (5) whole-cell recordings made in slide preparations revealed significant inhibition of GABA-ergic interneuron activity in the dorsal horn with ER stress vs in the healthy dorsal horn. Taken together, results of the current study demonstrate that coregulation of ER stress and oxidative stress played an important role in neuropathic pain process. Inhibiting SDH ER stress could be a potential novel strategy to manage neuropathic pain.