Peptidomics insights: neutrophil extracellular traps (NETs) related to the chronic subdural hemorrhage.

Chronic subdural hemorrhage (CSDH) refers to a hematoma with an envelope between the dura mater and the arachnoid membrane and is more common among the elderly. It was reported that the dura mater, which is highly vascularized with capillary beds, precapillary arterioles and postcapillary venules play an important role in the protection of the central nervous system (CNS). Numerous evidences suggests that peptides play an important role in neuroprotection of CNS. However, whether dura mater derived endogenous peptides participate in the pathogenesis of CSDH remains undetermined. In the current study, the peptidomic profiles were performed in human dura of CSDH (three patients) and the relative control group (three non-CSDH samples) by LC-MS (liquid chromatography-mass spectrometry). The results suggested that a total of 569 peptides were differentially expressed in the dura matter of CSDH compared with relative controls, including 217 up-regulated peptides and 352 down-regulated peptides. Gene Ontology (GO) analysis demonstrated that the precursor proteins of those differentially expressed peptides were involved in the various biological processes. Interestingly, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that NETs participated in the pathogenies of CSDH. Further investigate showed that H3Cit was significantly elevated in the dural and hematoma membranes of patients with CSDH compared to patients without CSDH. Taken together, our results showed the differentially expressed peptides in human dura mater of CSDH and demonstrated that NETs formation in the dural and hematoma membranes might be involved in the pathogenesis of CSDH. It is worth noting that pharmacological inhibition of NETs may have potential therapeutic implications for CSDH.

Identification of potential functional peptides involved in demyelinating injury in the central nervous system.

Multiple sclerosis (MS) is a chronic inflammatory neurologic disease characterized by the demyelinating injury of the central nervous system (CNS). It was reported that the mutant peptide came from myelin proteolipid protein (PLP) and myelin basic protein (MBP) might play a critical role in immunotherapy function of MS. However, endogenous peptides in demyelinating brain tissue of MS and their role in the pathologic process of MS have not been revealed. Here, we performed peptidomic analysis of freshly isolated corpus callosum (CC) from the brains of CPZ-treated mice and normal diet controls of male C57BL/6 mice by LC-MS/MS. Identified a total of 217 peptides were expressed at different levels in MS mice model compared with controls. By performed GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis, we found that the precursor protein of these differently expressed peptides (DEPs) were associated with myelin sheath and oxidative phosphorylation. Our study is the first brain peptidomic of MS mice model, revealing the distinct features of DEPs in demyelination brain tissue. These DPEs may provide further insight into the pathogenesis and complexity of MS, which would facilitate the discovery of the potential novel and effective strategy for the treatment of MS.

Pathophysiological roles of integrins in gliomas from the perspective of glioma stem cells.

Glioblastoma is the most common primary intracranial tumor and is also one of the most malignant central nervous system tumors. Its characteristics, such as high malignancy, abundant tumor vasculature, drug resistance, and recurrence-prone nature, cause great suffering to glioma patients. Furthermore, glioma stem cells are the primordial cells of the glioma and play a central role in the development of glioma. Integrins-heterodimers composed of noncovalently bound a and ß subunits-are highly expressed in glioma stem cells and play an essential role in the self-renewal, differentiation, high drug resistance, and chemo-radiotherapy resistance of glioma stem cells through cell adhesion and signaling. However, there are various types of integrins, and their mechanisms of function on glioma stem cells are complex. Therefore, this article reviews the feasibility of treating gliomas by targeting integrins on glioma stem cells.

Analysis of perioperative negative emotion risk factors in patients with pituitary adenoma and its impact on prognosis: a retrospective study.

Background: Pituitary adenoma (PA) is the third most common tumor in craniocerebral surgery. Most patients will experience varying degrees of negative emotions before and after surgery, which may affect the prognosis of surgery. This study analyzed the perioperative negative emotional risk factors of patients with different characteristics of PA and their impact on prognosis, so as to provide a reference for improving the prognosis of patients with PA. Methods: A total of 234 patients who underwent PA surgery in the Affiliated Hospital of Nantong University from January 2017 to January 2022 were selected as the observation population. The general characteristics of the subjects were collated using a general information questionnaire designed by the researchers. The negative emotions of the patients were evaluated using a Self-rating Anxiety Scale (SAS) and a Self-rating Depression Scale (SDS). The prognosis of patients was determined by assessing the hypophyseal hormone levels. Multiple regression analysis and logistic regression were used to analyze the risk factors of perioperative negative emotions and the effects of negative emotions on patient prognosis. Results: Multiple regression analysis showed that with and without children, education, income, PA type, PA size, and surgical approach were independent factors influencing negative emotions in patients after PA surgery (P<0.05). Logistic regression analysis showed that negative emotion was an independent prognostic factor (P<0.05). Conclusions: There are many factors that affect the anxiety and depression of patients after PA surgery. The family members and medical staff of the patients should take effective measures to relieve the anxiety and depression of the patients so as to improve the prognosis of patients according to the influencing factors.

Psychological resilience is related to postoperative adverse events and quality of life in patients with glioma: a retrospective cohort study.

Background: Psychological resilience has played an increasingly important role in the treatment of different diseases and many glioma patients will experience adverse emotional reactions after being diagnosed. However, it remains unclear whether psychological resilience is related to the adverse events and quality of life of patients with glioma. Methods: Patients with glioma between March 2016 and July 2020 were included in this retrospective cohort study. Psychological resilience was evaluated by the Connor-Davidson resilience scale (CD-RISC) 1 day before surgery. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 and EORTC QLQ-BN20 were used for the quality of life (QoL) assessment of the included patients. The relationships between psychological resilience and postoperative adverse events/QoL were determined using multivariable logistic and linear regression analysis, respectively. Some patients were evaluated again after admission, and the patients were divided into an increased resilience group and decreased resilience group for subgroup analysis according to the changes between the two CD-RISC scores. All included patients were followed up for at least 6 months. Results: Ninety-seven patients were included in the high resilience group and 284 patients were included in the low resilience group. More neurological complications occurred in the low resilience group than in the high resilience group (18.7% vs. 8.2%, P=0.016). Also, a higher Karnofsky performance scale score and higher psychological resilience contributed to less adverse events. Patients in the high resilience group had higher postoperative global health status scores than those in the low resilience group. Higher educational level, Karnofsky performance scale score, and psychological resilience acted as a protective factor for postoperative QoL. Subgroup analysis showed that the incidence of neurological complications was significantly higher in the decreased resilience group compared to the increased resilience group (22.9% vs. 3.8%, P=0.039). Lastly, better global health status, physical functioning, and role functioning were observed in glioma patients with increased resilience. Conclusions: The incidence of postoperative adverse events and QoL of glioma patients are closely related to their level of preoperative psychological resilience. Psychological counseling may also be a part of improving the prognosis of glioma patients.

Ex Vivo Liver Resection and Autotransplantation as Surgical Option for Zone II-III Leiomyosarcoma of IVC: A Case Report and Literature Review.

We report the first documented case of leiomyosarcoma at zone II-III of inferior vena cava with thrombi in three hepatic veins undergoing ex vivo liver resection and autotransplantation (ELRA) and hepatic veins thrombectomy. A 33-year-old female patient presented with abdominal distention and lower extremities edema. Abdominal wall varicosis and shifting dullness were positive on physical examination. Her liver function was classified as Child-Pugh B and a solid tumor at retro-hepatic vena cava extending to right atrium with thrombi in three hepatic veins were confirmed. The diagnosis of leiomyosarcoma with Budd-Chiari syndrome was highly suspected with preoperative ultrasound, echocardiogram, CT scan, and three-dimensional reconstruction. A zone II-III leiomyosarcoma of IVC origin was confirmed at surgery and ex vivo liver resection and autotransplantation, and hepatic vein thrombectomy with atrial reconstruction were performed under cardiopulmonary bypass (CPB). Operative time, anhepatic time, and CPB time were 12 h, 128 min, and 84 min, respectively. The patients experienced post-operative liver dysfunction and was cured with conservative therapy. Hepatic recurrence two years after surgery was managed with radiofrequency. The patient was alive with liver metastasis three years after surgery. Despite being regarded as an extremely aggressive procedure, ELRA could be considered in the treatment of advanced leiomyosarcoma with Budd-Chiari syndrome and hepatic vein thrombi.

Laparoscopic Versus Open Appendectomy for Appendicitis in Pregnancy: Systematic Review and Meta-Analysis.

OBJECTIVES: The clinical safety, efficacy and feasibility of laparoscopic appendectomy (LA) compared with open appendectomy (OA) in pregnancy are still controversial. Herein, we are aiming to compare the clinical outcomes of LA and OA in patients with acute appendicitis during their pregnancy. MATERIALS AND METHODS: This was a systematic review and meta-analysis of studies comparing laparoscopic and OA in pregnancy identifying using PubMed, Web of science, Embase, The Cochrane Library, Ovid and Scopus. Two independent reviewers extracted data on surgical complication, fetal loss, preterm delivery, hospital stay, Apgar score in both groups. RESULTS: Twenty-seven studies with total of 6497 patients (4464 in open and 2031 in laparoscopic group) were included. LA was associated with lower rate of wound infection [odds risk (OR)=3.13, 95% confidence interval (CI): 1.77-5.56, P<0.0001] overall complications (OR=2.15, 95% CI: 1.47-3.14, P<0.0001) and shorter hospitalization (mean difference=0.72, 95% CI: 0.43-1.02, P<0.00001) compared with open group. LA was in a lower risk for 5-minute Apgar score (mean difference=0.09, 95% CI: 0.02-0.17, P=0.01) group than open group. No difference was found regarding preterm delivery between 2 groups. LA was associated with higher fetal loss (OR=0.57, 95% CI: 0.41-0.79, P=0.0007) compared with open surgery. However, laparoscopy was not associated with increased fetal loss after 2010 (OR=0.74, 95% CI: 0.44-1.24, P=0.26) compared with open group. CONCLUSIONS: LA in pregnancy seems to be feasible with acceptable outcome, especially in patients with early and mid-trimester period, with sophisticated hands and experienced centers.

Fusion with mesenchymal stem cells differentially affects tumorigenic and metastatic abilities of lung cancer cells.

Cell fusion plays a crucial role in cancer progression and leads to massive aberrant changes in chromosome and gene expression involved in tumor metastasis. Cancer cells can fuse with many cell types, including stromal cells, epithelial cells, macrophages, and endothelial cells. Mesenchymal stem cells (MSCs) have been reported to migrate and incorporate into tumor sites during cancer progression. However, the underlying mechanism of stem cell fusion in tumor metastasis has not been fully deciphered. In this research, we established a cell fusion model between lung cancer cells and MSCs in vitro. We found that the hybrid cells showed enhanced metastatic capacity with increased expression of MMP-2 and MMP-9, whereas the proliferation ability was inhibited and cell cycle was blocked in the G0 /G1 phase with elevated expression of p21, p27, and p53. Moreover, the hybrid cells lost epithelial morphology and exhibited an epithelial-mesenchymal transition (EMT) change with downregulation of E-cadherin and upregulation of N-cadherin, Vimentin, α-SMA and Fibronectin1. Meanwhile, the expressions of EMT transcription factors, including Snail1, Slug, Twist1, Zeb1, and Zeb2, were also increased in hybrid cells. More important, the fusion hybrids acquired stem cell-like properties, which exhibited increased expression stem cell transcription factors Oct4, Sox2, Nanog, Kif4 as well as Bmi1. Taken together, our results suggested that cell fusion between lung cancer cells and MSCs offered enhanced metastatic capacity and characteristics of cancer stem cell by undergoing EMT. This study will contribute to explaning the origin of lung cancer stem cells and to elucidate the role of cell fusion in cancer metastasis.

Effects of selective cyclooxygenase 2 inhibitor on the hyperplasia of parathyroid glands from uremic rats / 中华肾脏病杂志

Objective To investigate the effects of selective cyclooxygenase 2 inhibitor on the hyperplasia of parathyroid glands from uremic rats. Methods Sixty-five 5/6-nephrectomized (Nx) and fifteen sham operated rats were assigned to 4 groups: (1)Sham group (n=14):shamoperated +normal phosphate diet (P 0.8％,Ca 1.2％)； (2) Nx-HP group (n=17):Nx+high phosphate(HP) diet (P 1.2％,Ca 1.2％)； (3)Prophylactic COX2 inhibition group (Prey group,n=18):Nx+HP+celecoxib 100 mg· kg-1·d-1 for 3 months； (4)Therapeutic group (Ther group,n=18):Nx+HP+celecoxib 100 mg·kg-1·d-1 starting at the second month of the 5/6 nephrectomy.At the end of 3 month,blood,urine and parathyroid samples were collected.The expressions of COX2 and PCNA were determined by immunohistochemistry,Western blotting and real-time PCR. Results All of the Nx rats fed with high phosphate diet for 3 months manifested progressively increasing serum creatinine,serum iPTH as well as augmentation of parathyroid gland volume,suggesting that secondary parathyroid hyperplasia animal model was established successfully.Celecoxib significantly decreased serum iPTH levels [Sham (34.77±0.83),Nx-HP(100.73±4.35),Prey (87.36±2.18),Ther (87.47±1.76) ng/L,P＜0.05],the size of the parathyroid glands in Nx rats [Sham (0.461±0.089),Nx-HP (2.436±0.372),Prey (0.987±0.254),Ther (1.27±0.305) mm2/kg,P＜0.05] and PCNA expression in PG determined by Western blotting (decreased to 52.91％ in Prev group and 34.68％ in Ther group respectively,P＜0.05).No significant difference was observed between the two COX2 inhibition groups.The levels of COX2 expression in parathyroid gland were greatly increased in three Nx groups compared with that in sham group (2.47-fold in Nx-HP,2.34-fold in Prey group,3.04-fold in Ther group,P＜0.05).COX2 inhibitor had no effects on COX2 expression in PGs.Real-time PCR analysis demonstrated the same trends of mRNA expression of COX2 and PCNA in PGs of rats. Conclusion Selective inhibition of COX2 may help to suppress the hyperplasia of parathyroid glands in uremic rats.