Autophagy-related risk signature based on CDNK2A to facilitate survival prediction of patients with endometrial cancer.

BACKGROUND: Autophagy plays an important role in immunity and inflammation. The present study aimed to explore the prognostic significance of autophagy-related genes (ARGs) in endometrial cancer (EC) using bioinformatics. METHODS: The list of ARGs was obtained from the Human Autophagy Database. The differentially expressed ARGs (DEARGs) between the EC and normal endometrial tissue samples were screened from The Cancer Genome Atlas database. Cox regression analysis was performed on the DEARGs to screen the prognostic ARGs and construct risk signatures for overall survival (OS) and progression-free survival (PFS). The hub ARGs were identified from a protein-protein interaction network, and CDKN2A was obtained from the intersection of prognostic ARGs and hub ARGs. The association of CDKN2A expression with clinical characteristics and immune infiltration were analyzed. Finally, the role of CDKN2A in autophagy was confirmed in EC cell lines. RESULTS: CDKN2A, PTK6 and DLC1 were used to establish risk signatures for predicting the survival of EC patients. Receiver operating characteristic curve analysis indicated that the risk signatures can accurately predict both OS and PFS. CDKN2A was the only hub prognostic ARG, and showed significant association with the age, survival status, grade, histological type, body mass index and FIGO (i.e. International Federation of Gynecology and Obstetrics) stage (p < 0.05). Furthermore, CDKN2A expression was also correlated with the infiltration of immune cells, indicating that CDKN2A might play a critical role in regulating the immune microenvironment and immune responses in EC. In addition, silencing of CDKN2A gene promoted autophagy in the HEC-1A cell line and upregulated the expression levels of autophagy-related proteins. CONCLUSIONS: CDKN2A is a prognostic factor and therapeutic target in EC, and is likely associated with the tumor immune landscape and autophagy.

Maternal Myometrium Metabolomic Profiles in Labor: Preliminary Results.

INTRODUCTION: Parturition involves multiple complex metabolic processes that supply essential metabolites to facilitate fetal delivery. Little is known about the dynamic metabolic responses during labor. OBJECTIVE: To profile the changes of myometrial metabolites between nonlabor and labor. METHODS: The study involved 30 women in nonlabor and 30 in labor who underwent cesarean section. The characteristics of myometrial metabolite changes during parturition were explored through untargeted metabolomic analysis. Data were analyzed by multivariate and univariate statistical analysis. RESULTS: Partial least squares-discriminant analysis plots significantly differentiated between the groups. In total, 392 metabolites were significantly distinct between the groups, among which lipid molecules were predominant. A 75% increase in fatty acids, 67% increase in fatty acid carnitines, 66% increase in glycerophospholipids, 83% increase in mono- and diacylglycerols, and 67% decrease in triacyclglycerols were observed in the patients during labor. Most glucose, amino acid, and steroid hormone metabolism also slightly increased in labor. CONCLUSIONS: An increase in lipolysis, fatty acid oxidation, amino acid catabolism, and steroid hormone metabolism was observed during parturition. The change of lipolysis and fatty acid oxidation is the most significant.

The effects of epidural analgesia using low-concentration local anesthetic during the entire labor on maternal and neonatal outcomes: a prospective group study.

PURPOSE: The purpose of this study was to study the impact of epidural analgesia using low-concentration local anesthetic during the entire labor on maternal and neonatal outcomes. METHODS: The authors enrolled 2310 parturient mothers who underwent vaginal delivery at their hospital since January 1, 2019. The parturients were allocated either into the analgesia or into the non-analgesia groups based on whether they received analgesia during the delivery process. To investigate the effects of epidural analgesia using low-concentration local anesthetic on maternal and neonatal outcomes, the authors assessed between-group differences in the labor duration, newborn Apgar score, and maternal and neonatal outcomes. RESULTS: Compared to the non-analgesia group, the first and second labor stage durations in the analgesia group were significantly longer. Similarly, the analgesia group had a higher frequency of oxytocin injections, Category II and III fetal heart rate tracing during labor, and intrapartum fever development. Further, the need for episiotomy and assisted vaginal delivery was higher in the analgesia group than that in the non-analgesia group. Regarding neonatal outcomes, the neonatal hospitalization rate and incidence rate of umbilical cord blood pH < 7.2 were higher in the analgesia group than those in the non-analgesia group. However, there were no significant between-group differences in the incidence rates of stained amniotic fluid, mild neonatal asphyxia, and severe perinatal asphyxia. CONCLUSION: Patient-controlled epidural analgesia using low-concentration local anesthetic during the entire labor did not increase the incidence rate of severe adverse outcomes in neonates born through vaginal delivery; however, it increased the delivery duration, and thus, the chance of possible perinatal interventions.

Changes in alpha-7 nicotinic acetylcholine receptor and macrophage polarization state participate in the regulation of cervical remodeling in pregnant rats†.

To test the hypothesis that changes in alpha-7 nicotinic acetylcholine receptor (α7nAChR) expression on macrophages and macrophage polarization participate in cervical remodeling during normal pregnancy, pregnant rats from gestational days (GDs) 14, 16, 18, 20, and 22 were used in the present study. The expression of α7nAChR on macrophages and the numbers of M1 and M2 macrophages were detected by double immunofluorescence staining. The levels of α7nAChR and collagens were detected by western blotting. M1 markers (inducible nitric oxide synthase and inflammatory cytokines) and M2 markers (arginase 1, anti-inflammatory cytokines) were detected to evaluate the macrophage polarization state by immunohistochemistry staining, western blotting, and the enzyme-linked immunosorbent assay. Matrix metalloproteinase 9 (MMP-9) expression was determined by immunohistochemistry staining and western blotting. We found that the α7nAChR expression on macrophages significantly decreased on GD22 compared to GDs 14, 16, 18, and 20. There was an increased number of M1 macrophages and decreased number of M2 macrophages in late pregnancy. The expression of M1 macrophage biomarkers was much higher on GDs 20 and 22 than on GDs 14, 16, and 18, but expression of M2 biomarkers decreased on GDs 20 and 22 compared to GDs 14, 16, and 18. MMP-9 expression was higher on GD22 than on GDs 14, 16, 18, and 20, and collagen expression significantly decreased on GDs 18, 20, and 22 compared to GD14. Our results indicated that the decreased expression of α7nAChR and increased number of M1 macrophages are associated with cervical remodeling.

Neuroendocrine immune-regulatory of a neuropeptide ChGnRH from the Hongkong oyster, Crassostrea Hongkongensis.

It is increasingly appreciated that neuroendocrine-immune interactions hold the key to understand the complex immune system. In this study, we explored the role of a reproductive regulation-related hormone, GnRH, in the regulation of immunity in Hong Kong oysters. We found that vibrio bacterial strains injection increased the expression of ChGnRH. Moreover, ChGnRH neuropeptide promotes the phagocytic ability and bacterial clearance effect of hemocytes which regarded to be the central immune organ. The content of cAMP after incubation with ChGnRH peptide was increased, which could be blocked by adenylyl cyclase inhibitor SQ 22,536. Furthermore, the stimulated effect of ChGnRH peptide on the phagocytosis and bacterial clearance was also blocked by SQ 22,536, H89 and enzastaurin, strongly demonstrating that cAMP dependent PKA and PKC signaling pathway was involved in ChGnRH mediated immune regulation. In conclusion, this study confirms the presence of neuroendocrine-immune regulatory system in marine invertebrates, which contributes to understand the complexity of oyster immune defense system.

The Therapeutic Effect of Dexmedetomidine on Rat Diabetic Neuropathy Pain and the Mechanism.

Diabetic neuropathy pain (DNP) is a common chronic complication of diabetes characterized by spontaneous pain, hyperalgesia and allodynia. Dexmedetomidine is a selective α2 adrenergic agonist that relieves sympathetic nervous tension and reduces the release of glutamate. Thus, it is possible that dexmedetomidine may relieve DNP as well. In this study, we examined the effect of dexmedetomidine on DNP in the presence or absence of the α2 adrenergic antagonist yohimbine in rats utilizing a streptozotocin (STZ)-induced diabetes as a model of DNP. To examine DNP, we examined behavior using the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) tests, and microglia and astrocyte activation was examined by immunofluorescence staining. The levels of pro-inflammatory cytokine tumor necrosis factor (TNF)-α and interleukin (IL)-1ß in the spinal cord were measured by enzyme-linked immunosorbent assay (ELISA). Cell apoptosis in spinal cord was examined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. Glutamate production in caudal lumbar was measured by HPLC. We found that STZ-treated rats had decreased pain threshold, elevated activation of microglia but not astrocytes, increased level of pro-inflammatory cytokines, increased apoptosis and glutamate production compared to control animals, and these effects were ameliorated by dexmedetomidine treatment. Pretreatment of yohimbine abolished almost all of the protective effects of dexmedetomidine except for glutamate production. IN CONCLUSION: our data confirmed that dexmedetomidine can relieve hyperalgesia in diabetic neuropathy pain, and protect spinal cord cells from apoptotic death. The mechanism may be related to dexmedetomidine-mediated inhibition of microglia activation, reduction of inflammatory reaction in the spinal cord, and suppression of glutamate production.

[Effect of Interaction between PLIN Gene Polymorphisms and Open Lifestyle Intervention on Weight-loss in Chinese Han Adults].

OBJECTIVE: To explore the effect of the interaction between PLIN gene polymorphisms and open lifestyle intervention on weight-loss in Chinese Han adults. METHODS: Totally 109 overweight or obese subjects were assigned by random number table to the intervention group (n=56) or control group (n=53),and subjects in the intervention group received 22-week open lifestyle intervention. Anthropometric and metabolic indicators were measured for all subjects before and after intervention,and the PLIN1,PLIN4,and PLIN6 genotypes were amplified by polymerase chain reaction and sequenced through the first-generation sequencing technologies. RESULTS: Among all these subjects,the rare allele C was dominant at PLIN1 (0.619),the common allele G was dominant at PLIN4 (0.606),and the common allele A was dominant at PLIN6 (0.564),in which PLIN1 and PLIN4 as well as PLIN4 and PLIN6 were in strong linkage disequilibrium (D'>0.9). After intervention,the body mass index,waist circumference,and body fat percent of female subjects were significantly decreased in intervention group and were lower than in control group;in male subjects,however,only the waist circumference showed significant difference with the control group (P<0.05). Subjects carrying rare allele homozygote of PLIN6 got less weight/fat loss than those carrying common alleles in intervention group,while subjects carrying rare allele of PLIN1 had more weight/fat increase than those with common allele homozygote in control group (P<0.05). Females in intervention group carrying any one of rare allele homozygotes of PLIN1,PLIN4 and PLIN6 got less weight/fat loss than those with common alleles,and female subjects carrying the rare allele homozygote haplotype of PLIN1/PLIN4 or PLIN4/PLIN6 got less weight/fat loss than those with other haplotypes (P<0.05). CONCLUSION: The interaction between open lifestyle intervention and PLIN gene polymorphisms can directly influence weight-loss in Chinese Han overweight and obese adults.

Defining three ferroptosis-based molecular subtypes and developing a prognostic risk model for high-grade serous ovarian cancer.

BACKGROUND: As a newly defined regulated cell death, ferroptosis is a potential biomarker in ovarian cancer (OV). However, its underlying mechanism in tumor microenvironment (TME) and clinical prediction significance in OV remained to be elucidated. METHODS: The transcriptome data of high-grade serous OV from The Cancer Genome Atlas (TCGA) database were downloaded. Molecular subtypes were classified based on ferroptosis-correlated genes from the FerrDb database by performing consensus clustering analysis. The associations between the subtypes and clinicopathologic characteristics, mutation, regulatory pathways and immune landscape were assessed. A ferroptosis-related prognostic model was constructed and verified using International Cancer Genome Consortium (ICGC) cohort and GSE70769. RESULTS: Three molecular subtypes of OV were defined. Patients in subtype C3 tended to have the most favorable prognosis, while subtype C1 showing more mesenchymal cells, increased immune infiltration of Macrophages_M2, lower tumor purity, and epithelial-to-mesenchymal transition (EMT) features had the poorest prognosis. A ferroptosis-related risk model was constructed using 8 genes (PDP1, FCGBP, EPHA4, GAS1, SLC7A11, BLOC1S1, SPOCK2, and CXCL9) and manifested a strong prediction performance. High-risk patients had enriched EMT pathways, more Macrophages_M2, less plasma cells and CD8 cell infiltration, greater tendency of immune escape and worse prognosis. The risk score has negatively correlated relation with LAG3, TIGIT, CTLA4, IDO1, CD27, ICOS, and IL2RB but positively correlated with PVR, CD276, and CD28. Moreover, low-risk patients were more sensitive to Cisplatin and Gefitinib, Gemcitabine. CONCLUSIONS: Our results could improve the understanding of ferroptosis in OV, providing promising insights for the clinical targeted therapy for the cancer.

Clinical features of renal damage associated with Epstein-Barr virus infection in children.

Objective: To understand the renal damage and clinical features of pediatric patients with acute Epstein-Barr virus (EBV) infection. Methods: In this retrospective observational study, 548 pediatric patients who were admitted to and treated at the Xiamen Women and Children Health Center between January 2017 and December 2021 and who met the criteria of acute EBV infection were selected as participants. The sociodemographic and clinical data of these patients were collected for statistical analysis. The study population was divided into a renal damage group (41 patients) and a non-renal damage group (507 patients), and the characteristics of the two groups were compared. Results: (1) Of the 548 enrolled patients, 340 and 208 were boys and girls, respectively. Among them, 41 patients showed renal damage (renal damage group), including 26 boys and 15 girls, and the incidence rate of renal damage was 7.48%. (2) The major renal involvements in the 41 pediatric patients with acute EBV infection in the renal damage group manifested as hematuria (56.1%), proteinuria (37.71%), hematuria + proteinuria (12.9%), edema (51.22%), hypertension (17.07%), oliguria (4.88%), and acute renal failure (2.44%). (3) The pediatric patients in the renal damage group had statistically significantly longer fever durations, higher blood EBV-DNA loads, and lower blood CD4+/CD8+ T lymphocyte ratios than those in the non-renal damage group. Conclusion: In pediatric patients, the incidence rate of acute EBV-induced renal damage is not low. The clinical manifestations are mostly hematuria or proteinuria, with an overall good prognosis, but occasionally severe renal damage such as acute renal failure. The possibility of secondary renal damage is high when pediatric patients with acute EBV have prolonged fever, high blood EBV-DNA loads, and decreased blood CD4+/CD8+ ratios.

Clinical features and effectiveness of Chinese medicine in patients with COVID-19 from overseas: A retrospective study in Xiamen, China.

COVID-19, referred to as new coronary pneumonia, is an acute infectious disease caused by a new type of coronavirus SARS-CoV-2. To evaluate the effect of integrated Chinese medicine and Western medicine in patients with COVID-19 from overseas. Data were collected from 178 COVID-19 patients overseas at First Affiliated Hospital of Xiamen University from April 1, 2021 to July 31, 2021. These patients received therapy of integrated Chinese medicine and western medicine. Demographic data and clinical characteristics were extracted and analyzed. In addition, the prescription which induced less length of PCR positive days and hospitalization days than the median value was obtained. The top 4 frequently used Chinese medicine and virus-related genes were analyzed by network pharmacology and bioinformatics analysis. According to the chest computed tomography (CT) measurement, abnormal lung findings were observed in 145 subjects. The median length of positive PCR/hospitalization days was 7/7 days for asymptomatic subjects, 14/24 days for mild subjects, 10/15 days for moderate subjects, and 14/20 days for severe subjects. The most frequently used Chinese medicine were Scutellaria baicalensis (Huangqin), Glycyrrhiza uralensis (Gancao), Bupleurum chinense (Chaihu), and Pinellia ternata (Banxia). The putative active ingredients were baicalin, stigmasterol, sigmoidin-B, cubebin, and troxerutin. ACE, SARS-CoV-2 3CL, SARS-CoV-2 Spike, SARS-CoV-2 ORF7a, and caspase-6 showed good binding properties to active ingredients. In conclusion, the clinical results showed that integrated Chinese medicine and Western medicine are effective in treating COVID-19 patients from overseas. Based on the clinical outcomes, the putative ingredients from Chinese medicine and the potential targets of SARS-CoV-2 were provided, which could provide a reference for the clinical application of Chinese medicine in treating COVID-19 worldwide.

Stimulation of α7 Nicotinic Acetylcholine Receptor by Nicotine Suppresses Decidual M1 Macrophage Polarization Against Inflammation in Lipopolysaccharide-Induced Preeclampsia-Like Mouse Model.

Changes in decidual macrophage polarization affect local inflammatory microenvironment and lead to adverse pregnancy outcomes. However, the regulatory mechanism of macrophage polarization in preeclampsia (PE) remains unclear. In this study, we found that α7nAChR expression was significantly down-regulated in decidual macrophages in PE patients compared to normal pregnant women, accompanied by a reduced proportion of M2 phenotype and an increased proportion of M1 phenotype; these results suggested that the reduced α7nAChR activity might contribute to changes in the polarization of decidual macrophages. Then, we further investigated the regulatory role of α7nAChR activation by nicotine on decidual macrophage polarization and placental remodeling in the PE-like mouse model. The PE mice were obtained by i.p. injection of 10 µg/kg lipopolysaccharide (LPS) gestational day (GD) 13, and 40 µg/kg LPS daily until GD16. Subcutaneous injection of 1.0 mg/kg nicotine was administrated from GD14 to GD18. Nicotine treatment increased the decreased M2 phenotype and inhibited the increased M1 phenotype in decidua of pregnant mice induced by LPS. The levels of pro-inflammatory cytokines in decidua were higher but the levels of anti-inflammatory cytokines were lower in PE mice compared to the controls, nicotine reversed these changes. The level of choline acetyltransferase (CHAT) was reduced in the LPS-treated group, it was increased following nicotine treatment. Damage of spiral artery remodeling and down-regulation of markers related to trophoblast invasion in placentas were found in PE mice; nicotine improved these pathological structures of placentas. α-bungarotoxin (α-BGT) which is specific antagonist for α7nAChR could abolish the effects of nicotine on decidual macrophage polarization, trophoblast arrangement and vascular structure in placental tissue in PE mice. These results suggest that α7nAChR plays an important regulatory role in maternal-fetal inflammation and placental remodeling in preeclampsia and may provide a theoretical basis for the discovery of new strategies for preeclampsia.

The effects of ropivacaine 0.0625% and levobupivacaine 0.0625% on uterine and abdominal muscle electromyographic activity during the second stage of labor.

BACKGROUND: This study investigated the effect of ropivacaine on uterine and abdominal muscle electromyographic activity during the second stage of labor. METHODS: A total of 161 patients, including 48 patients receiving 0.0625% ropivacaine for patient-controlled epidural analgesia (PCEA), 64 patients receiving 0.0625% levobupivacaine for PCEA, and 49 patients with no PCEA completed the study. Uterine and abdominal muscle electromyographic activity was continuously recorded from the abdominal surface during the second stage of labor. Maternal demographic and clinical characteristics, maternal and neonatal outcomes, and various electromyographic parameters were recorded. RESULTS: Second stage of labor was significantly prolonged (P=0.007) for levobupivacaine compared to ropivacaine or no PCEA. The root-mean-square and duration of uterine muscle electromyographic activity was significantly lower for levobupivacaine or ropivacaine compared to no PCEA. The root-mean-square and power of abdominal muscle electromyographic activity was significantly lower for levobupivacaine compared to ropivacaine or no PCEA; the peak frequency of abdominal muscle electromyographic activity was significantly higher for ropivacaine. Visual analogue scale pain scores in patients in the levobupivacaine group or ropivacaine group decreased significantly over time compared to patients in the no PCEA group. CONCLUSIONS: In conclusion 0.0625% ropivacaine does not suppress abdominal muscle electromyographic activity during the second stage of labor. Maternal and neonatal outcomes were similar in patients receiving ropivacaine or no PCEA.

[Diurnal change of photosynthetic characteristics of native Vetiveria zizanioides in western Guangdong].

The determinations on the photosynthetic parameters of native Vetiveria zizanioides in Western Guangdong in autumn showed that the net photosynthetic rate (P(n)) of V. zizanioides had a diurnal change with two peaks, transpiration rate (T(r)) and stomatal conductance (G(s)) were similar with P(n), while intercellular CO2 concentration (C(i)) was in adverse. There was a significant positive correlation between P(n) and photosynthetic active radiation (PAR) (P < 0.01) , T(r) and PAR (P < 0.01), air temperature (T(a)) and relative humidity (RH) (P < 0.01), and G(s) and T(a) (P < 0.05). Same environmental factors had different effects on P(n), T(r) and G(s), and PAR had most intensive effect on the photosynthesis of V. zizanioides. Among the test photosynthetic parameters, T(r) was most sensitive to the environmental factors.