Risk Factors of Acute Pain in Elderly Patients After Laparoscopic Radical Resection of Colorectal Cancer.

OBJECTIVE: To investigate the risk factors of acute pain after laparoscopic radical resection of colorectal cancer (CRC) in elderly patients. METHODS: Totally, 143 elderly patients (≥ 60 y old) who received laparoscopic radical resection of CRC in the People's Hospital of Xinjiang Uygur Autonomous Region from March 2021 to August 2022 were retrospectively analyzed. The patients were divided into 2 groups according to visual analog scale (VAS) scores 24 h after surgery: mild pain group (VAS score ≤ 3, n=108) and moderate to severe pain group (VAS score >3, n=35). The data of the patients, including sex, age, height, body mass, intraoperative blood loss, intraoperative urine volume, intraoperative opioid dosage, operation duration, preoperative Hospital Anxiety and Depression Scale (HADS) scores, preoperative Mini-Mental State Examination scores, VAS scores, postoperative nausea and vomiting scores were recorded. Multivariate logistic regression analysis was used to screen the risk factors of postoperative acute pain in elderly patients undergoing laparoscopic radical resection of CRC. RESULTS: The preoperative HADS score of the moderate to severe pain group was significantly increased compared with that of the mild pain group (10.8±2.4 vs. 6.2±1.9), as well as the operation duration (226.4±18.3 vs. 186.1±12.7), the intraoperative dosage of remifentanil (3.7±0.2 vs. 3.2±0.4), the preoperative VAS score [4(2, 7) vs. 2 (0, 4)] and postoperative VAS score [5 (4, 6) vs. 3 (2, 3)] ( P <0.05). Multivariate logistic regression analysis showed that high preoperative HADS score, long operation duration, and high preoperative VAS score ( P <0.05) were independent risk factors for acute pain after laparoscopic radical resection of CRC in elderly patients. CONCLUSION: Preoperative anxiety and depression, preoperative pain, and long operation duration are risk factors for acute pain in elderly patients after laparoscopic radical resection of CRC.

The growth inhibitory effects and non-targeted metabolomic profiling of Microcystis aeruginosa treated by Scenedesmus sp.

The health of the aquatic ecosystem has recently been severely affected by cyanobacterial blooms brought on by eutrophication. Therefore, it is critical to develop efficient and secure methods to control dangerous cyanobacteria, such as Microcystis aeruginosa. In this research, we tested the inhibition of M. aeruginosa growth by a Scenedesmus sp. strain isolated from a culture pond. Scenedesmus sp. culture filtrate that had been lyophilized was added to M. aeruginosa, and cultivation for seven days, the cell density, chlorophyll a (Chl-a) concentration, maximum quantum yield of photosystem II (Fv/Fm), the activities of superoxide dismutase (SOD), catalase (CAT), and the concentration of malondialdehyde (MDA) and glutathione (GSH) were measured. Moreover, non-targeted metabolomics was carried out to provide light on the inhibitory mechanism in order to better understand the metabolic response. According to the results, M. aeruginosa is effectively inhibited by the lyophilized Scenedesmus sp. culture filtrate at a rate of 51.2%. Additionally, the lyophilized Scenedesmus sp. clearly inhibit the photosystem and damages the antioxidant defense system of M. aeruginosa cells, resulting in oxidative damage, which worsens membrane lipid peroxidation, according to changes in Chl-a, Fv/Fm, SOD, CAT enzyme activities and MDA, GSH. Metabolomics analysis revealed that the secondary metabolites of Scenedesmus sp. significantly interfere with the metabolism of M. aeruginosa involved in amino acid synthesis, membrane creation and oxidative stress, which is coherent with the morphology and physiology outcomes. These results demonstrate that the secondary metabolites of Scenedesmus sp. exert algal inhibition effect by breaked the membrane structure, destroyed the photosynthetic system of microalgae, inhibited amino acid synthesis, reduced antioxidant capacity, and eventually caused algal cell lysis and death. Our research provides a reliable basis for the biological control of cyanobacterial blooms on the one hand, and on other hand supply application of non-targeted metabolome on the study of microalgae allelochemicals.

Ghrelin infusion into the basolateral amygdala suppresses CTA memory formation in rats via the PI3K/Akt/mTOR and PLC/PKC signaling pathways.

Ghrelin is a circulating orexigenic hormone that promotes feeding behavior and regulates metabolism in humans and rodents. We previously reported that local infusion of ghrelin into the basolateral amygdala (BLA) blocked memory acquisition for conditioned taste aversion (CTA) by activating growth hormone secretagogue receptor 1a. In this study, we further explored the underlying mechanism and signaling pathways mediating ghrelin modulation of CTA memory in rats. Pharmacological agents targeting distinct signaling pathways were infused into the BLA during conditioning. We showed that preadministration of the PI3K inhibitor LY294002 abolished the repressive effect of ghrelin on CTA memory. Moreover, LY294002 pretreatment prevented ghrelin from inhibiting Arc and zif268 mRNA expression in the BLA triggered by CTA memory retrieval. Preadministration of rapamycin eliminated the repressive effect of ghrelin, while Gsk3 inhibitors failed to mimic ghrelin's effect. In addition, PLC and PKC inhibitors microinfused in the BLA blocked ghrelin's repression of CTA acquisition. These results demonstrate that ghrelin signaling in the BLA shapes CTA memory via the PI3K/Akt/mTOR and PLC/PKC pathways. We conducted in vivo multichannel recordings from mouse BLA neurons and found that microinjection of ghrelin (20 µM) suppressed intrinsic excitability. By means of whole-cell recordings from rat brain slices, we showed that bath application of ghrelin (200 nM) had no effect on basal synaptic transmission or synaptic plasticity of BLA pyramidal neurons. Together, this study reveals the mechanism underlying ghrelin-induced interference with CTA memory acquisition in rats, i.e., suppression of intrinsic excitability of BLA principal neurons via the PI3K/Akt/mTOR and PLC/PKC pathways.

Experimental and clinical evidence suggests that GRPEL2 plays an oncogenic role in HCC development.

Hepatocellular carcinoma (HCC) continues to cause severe burden worldwide. The limited options especially toward HCC with metastasis prompts us to identify novel molecules for either diagnostic/prognostic or therapeutic purposes. GRPEL2 is well defined in maintaining mitochondrial homeostasis, which is critical to multiple biological processes for cancer survival. However, its role in HCC progression was not investigated before. In our analysis using data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA LIHC) dataset and tissue microarray, higher expression levels of GRPEL2 were obseved in HCC tissues compared to in normal liver tissues, and indicated higher tumor grade, higher tumor stage, and shorter overall survival (OS). Consistent with the results of above analyses, the functional experiments validated that GRPEL2 acted as a tumor-promoting factor in HCC progression. GRPEL2 knockdown suppressed cell growth, migration, and invasion in vitro, as well as inhibited tumor growth in vivo. Moreover, GRPEL2 deficiency also accelerated reactive oxygen species (ROS) production and increased mitochondrial membrane potential (MMP), leading to cell apoptosis. In addition, we found that the cell cycle and NF-κB signaling pathways were responsible for GRPEL2-induced HCC progression, based on the results of Gene Set Enrichment Analysis (GSEA) and subsequent experimental validation. Our study, for the first time, identified the role of GRPEL2 in HCC development and provided a compelling biomarker for targted therapy in HCC treatment.

SIP/CacyBP promotes autophagy by regulating levels of BRUCE/Apollon, which stimulates LC3-I degradation.

BRUCE/Apollon is a membrane-associated inhibitor of apoptosis protein that is essential for viability and has ubiquitin-conjugating activity. On initiation of apoptosis, the ubiquitin ligase Nrdp1/RNF41 promotes proteasomal degradation of BRUCE. Here we demonstrate that BRUCE together with the proteasome activator PA28γ causes proteasomal degradation of LC3-I and thus inhibits autophagy. LC3-I on the phagophore membrane is conjugated to phosphatidylethanolamine to form LC3-II, which is required for the formation of autophagosomes and selective recruitment of substrates. SIP/CacyBP is a ubiquitination-related protein that is highly expressed in neurons and various tumors. Under normal conditions, SIP inhibits the ubiquitination and degradation of BRUCE, probably by blocking the binding of Nrdp1 to BRUCE. On DNA damage by topoisomerase inhibitors, Nrdp1 causes monoubiquitination of SIP and thus promotes apoptosis. However, on starvation, SIP together with Rab8 enhances the translocation of BRUCE into the recycling endosome, formation of autophagosomes, and degradation of BRUCE by optineurin-mediated autophagy. Accordingly, deletion of SIP in cultured cells reduces the autophagic degradation of damaged mitochondria and cytosolic protein aggregates. Thus, by stimulating proteasomal degradation of LC3-I, BRUCE also inhibits autophagy. Conversely, SIP promotes autophagy by blocking BRUCE-dependent degradation of LC3-I and by enhancing autophagosome formation and autophagic destruction of BRUCE. These actions of BRUCE and SIP represent mechanisms that link the regulation of autophagy and apoptosis under different conditions.

Prognostic value of Rho GDP dissociation inhibitors in patients with hepatocellular carcinoma following liver transplantation.

Rho GDP dissociation inhibitors (GDIs) are pivotal regulators of Rho GTPases, which are essential for tumor progression, yet their role in hepatocellular carcinoma (HCC) remains poorly understood. The purpose of the present study was to assess the role of RhoGDIs in the invasiveness and migration of liver cancer, and to determine their clinical prognostic significances in HCC following liver transplantation (LT). In the present study, the expression of RhoGDIs was assessed using reverse transcription-quantitative polymerase chain reaction and confirmed by western-blot analysis and immunohistochemistry. Their prognostic values were also analyzed, and determined in patients treated with LT. In addition, the functions of RhoGDIs in liver cancer cell line were studied in vitro. As a result, the downregulation of RhoGDI1 and RhoGDI2 at mRNA and protein levels were detected in HCC when compared with that of adjacent noncancerous tissues (P<0.05). However, the level of RhoGDI3 was identified to be similar in tumor and para-carcinoma tissues. Additionally, Kaplan-Meier curves demonstrated that patients with lower expression of RhoGDI1 or RhoGDI2 exhibited significantly increased risk of tumor recurrence following LT (P=0.007 and P=0.006, respectively). Cox proportional hazards model analysis revealed that the decreased expression level of RhoGDI2 was an unfavorable independent prognostic factor (hazard ratio, 3.306; P=0.001). In vitro studies involving the silencing of RhoGDI1 or RhoGDI2 demonstrated a significant increase in the migratory and invasive ability of tumor cells upon the silencing of these genes. Results from the present study indicate that RhoGDI dysregulation is a frequent event in human HCC, and that it promotes cancer progression by stimulating cell migration and invasion. RhoGDI2 may be a prognostic biomarker for patients with HCC following LT, and act as a potential therapeutic target.

Morphologic findings and management strategy of spontaneous isolated dissection of the celiac artery.

OBJECTIVE: We report the morphologic findings and treatment of spontaneous isolated dissection of the celiac artery (SIDCA). METHODS: Twenty-three patients with SIDCA presenting between January 2009 and December 2014 were enrolled in this retrospective study. The demographic data, clinical features, morphologic findings, treatment modalities, and follow-up results of these patients were reviewed. We proposed a morphologic classification for SIDCA similar to that of spontaneous isolated dissection of the superior mesenteric artery. RESULTS: Initially, 11 patients were treated endovascularly, and 12 were treated medically. Four patients treated medically had an aggravation of the dissection and needed endovascular salvage. All patients recovered successfully. None of the patients developed abdominal pain, required reintervention, or died. In the medically treated group, the false lumen was completely thrombosed and absorbed in 4 patients, partially thrombosed in 2, and patent in 2. All stents were patent with the false lumen completely thrombosed and absorbed in the endovascular group. CONCLUSIONS: SIDCA can be treated medically in stable patients but requires intensive follow-up. Endovascular therapy can be applied in high-risk patients with recurrent symptoms, visceral malperfusion, or aneurysm. Open surgery should be considered if endovascular repair is not suitable or has failed. The short-term results of endovascular management are encouraging but further evaluation with long-term follow-up is necessary.

Endovascular treatment of isolated abdominal aortic dissection and postoperative aortic remodeling.

OBJECTIVE: We report our experience of endovascular management and postoperative aortic remodeling of all types of isolated abdominal aortic dissection (IAAD). METHODS: This was retrospective study of 28 IAAD patients treated by endovascular means in our department between January 2007 and July 2013. We reviewed the risk factors, clinical features, computed tomography images, follow-up results, and aortic remodeling of these IAAD patients and propose a new morphologic classification into three types-supraceliac, paravisceral, and infrarenal-according to the location of the primary entry site. RESULTS: There were four supraceliac IAADs, one paravisceral IAAD, and 23 infrarenal IAADs in our case series. Suprarenal (supraceliac + paravisceral) IAAD patients were relatively younger than infrarenal patients (45.2 ± 8.6 years vs 60.6 ± 15.5 years; P < .05). No difference was observed between suprarenal and infrarenal IAADs with respect to true lumen, false lumen, and dissection length on imaging (P > .05). All patients received endovascular treatment. The primary technical success rate was 100%. During a follow-up of 35.7 ± 19.9 months, only one infrarenal patient needed an endovascular reintervention. All patients with supraceliac or infrarenal IAADs were alive at the time of follow-up; however, a paravisceral patient died of a dissecting abdominal aortic aneurysm rupture 21 months after endovascular treatment. In the suprarenal and infrarenal groups, endovascular treatment was associated with a significant decrease in the false lumen size and increase in the true lumen size (P < .05). The maximum abdominal aorta diameter decreased after endovascular treatment in both groups but was statistically significant only in the infrarenal group (P < .05). CONCLUSIONS: IAAD is a rare vascular disease. We propose it should be categorized as supraceliac, paravisceral, and infrarenal IAAD according to the location of the primary entry site. Endovascular treatment for supraceliac and infrarenal IAADs is a safe method with a high technical success rate and promising aortic remodeling, whereas endovascular treatment for paravisceral IAADs remains difficult.

Long non-coding RNA MALAT-1 overexpression predicts tumor recurrence of hepatocellular carcinoma after liver transplantation.

Metastasis-associated lung adenocarcinoma transcript 1(MALAT1), a long non-coding RNA (lncRNA), is up-regulated in many solid tumors and associated with cancer metastasis and recurrence. However, its role in hepatocellular carcinoma (HCC) remains poorly understood. In the present study, we evaluated the expression of MALAT1 by quantitative real-time PCR in 9 liver cancer cell lines and 112 HCC cases including 60 cases who received liver transplantation (LT) with complete follow-up data. Moreover, small interfering RNA (siRNA) was used to inhibit MALAT1 expression to investigate its biological role in tumor progression. We found that MALAT1 was up-regulated in both cell lines and clinical tissue samples. Patients with high expression level of MALAT1 had a significantly increased risk of tumor recurrence after LT, particularly in patients who exceeded the Milan criteria. On multivariate analysis, MALAT1 was an independent prognostic factor for predicting HCC recurrence (hazard ratio, 3.280, P = 0.003).In addition, inhibition of MALAT1 in HepG2 cells could effectively reduce cell viability, motility, invasiveness, and increase the sensitivity to apoptosis. Our data suggest that lncRNA MALAT1 play an important role in tumor progression and could be a novel biomarker for predicting tumor recurrence after LT and serve as a promising therapeutic target.