The impact of antibiotic use on clinical features and survival outcomes of cancer patients treated with immune checkpoint inhibitors

BackgroundNowadays, immune checkpoint inhibitors (ICIs) have become one of the essential immunotherapies for cancer patients. However, the impact of antibiotic (ATB) use on cancer patients treated with ICIs remains controversial.MethodsOur research included retrospective studies and a randomized clinical trial (RCT) with cancer patients treated with ICIs and ATB, from the public database of PubMed, Web of Science, Embase, Cochrane, clinical trials, and JAMA. The survival outcomes included progression-free survival (PFS) and overall survival (OS). Meanwhile, hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated, and subgroup analyses were performed to determine the concrete association between ATB use and the prognosis of cancer patients treated in ICIs.ResultsOur results revealed that ATB use was associated with poor survival outcomes, including OS (HR: 1.94, 95% CI: 1.68–2.25, p <0.001) and PFS (HR: 1.83, 95% CI: 1.53–2.19, p <0.001). The subgroup analysis learned about the association between ATB use and the prognosis of cancer patients with ICI treatment, including 5 cancer types, 3 kinds of ICI, 5 different ATP windows, broad-spectrum ATB class, and ECOG score. ATB treatment was associated with poor OS of non-small-cell lung cancer (NSCLC), renal cell carcinoma (RCC), esophageal cancer (EC), and melanoma (MEL) in patients treated in ICIs, while non-small-cell lung cancer (NSCLC) and renal cell carcinoma (RCC) were associated with poor PFS. Meanwhile, it was strongly related to the ICI type and ATB window. Furthermore, it is firstly mentioned that the use of broad-spectrum ATB class was strongly associated with poor PFS.ConclusionIn conclusion, our meta-analysis indicated that ATB use was significantly associated with poor OS and PFS of cancer patients treated with ICI immunotherapy, especially for patients with ATB use in the period of (−60 days; +30 days) near the initiation of ICI treatment. Also, different cancer types and the ICI type can also impact the survival outcome. This first reveals the strong relationship between the broad-spectrum ATB class and poor PFS. Still, more studies are needed for further study

Performance Analysis of QoS-Oriented OFDMA Protocol Based on IEEE 802.11ax for Cognitive Radio Network

To improve the quality of service (QoS) on the internet of medical things, a cognitive radio (CR) protocol based on orthogonal frequency division multiple access (OFDMA) is proposed, named CR-OFDMA. In this protocol, we divide a complete channel into multiple orthogonal subchannels and enhance the subchannel assignment scheme, which achieves QoS improvement under consideration of priority and fairness. Furthermore, we improve spectrum resource utilization by fully utilizing the remaining subchannels, feedback slots, and backoff slots. Then, a two-dimensional Markov model is established to describe the dynamic characteristics of the protocol operation, where the backoff stage and the backoff counter value constitute the system state. By establishing the traffic conservation equations for the system operation, the transmission probability and collision probability are calculated, and expressions of system throughput, channel utilization, and fairness index are derived. Finally, numerical results validate the advantages of CR-OFDMA

#192 : Comparison of Cytokine Profiles and Th1/Th2 Ratios in the Peri-Implantation Endometrium in Recurrent Reproductive Failure Women with and Without Chronic Endometritis

Background and Aims: Aberrant local endometrial microenvironment in chronic endometritis (CE) may be involved in reduced endometrial receptivity and recurrent reproductive failure. Previous studies have observed some discrepancies between different types of cytokines, without showing the predominance of a specific immune response between women with miscarriage and normal pregnancy. However, exactly how CE alters the endometrial function and interferes with the process of implantation is still uncertain. Method: It was an observational retrospective study. A total of 39 women with unexplained recurrent miscarriage (RM) participated in this study. Endometrial specimens were obtained precisely 7 days after luteinization hormone surge and chronic endometritis was diagnosed by plasma cell density. In total, 24 different cytokines were examined by the Luminex technique after protein extraction and Th1/Th2 ratios are measured. Results: No significant differences in all the endometrial specimens between 14 women who found to have CE and 25 women who did not have CE. However, in the RM group, we found a significantly increased expression of IFN-[Formula: see text] (2.89 pg/mL vs. 0.75 pg/mL, [Formula: see text] = 0.027) in women with CE. In addition, an elevated Th1/Th2 ratio (IFN-[Formula: see text] /IL-4: 288.83 vs. 75.29, [Formula: see text] = 0.027) and a decreased ratio of TNF-[Formula: see text] /IL-6 (1.25 vs. 3.11, [Formula: see text] = 0.006) were observed in RM women with CE than those without CE. Moreover, the levels of VEGF-D (14.63 pg/mL vs. 9.16 pg/mL, [Formula: see text] = 0.041) and EGF (25.13 pg/mL vs. 11.98 pg/mL, [Formula: see text] = 0.023) were higher in women with live births than those women without live births in RM group and infertility group, respectively. Conclusion: In this study, altered cytokine profiles and Th1/Th2 ratios in peri-implantation endometrium is of predictive value for subsequent pregnancy outcome in women with recurrent miscarriage

Identification of complex and cryptic chromosomal rearrangements by optical genome mapping

Abstract Background Optical genome mapping (OGM) has developed into a highly promising method for detecting structural variants (SVs) in human genomes. Complex chromosomal rearrangements (CCRs) and cryptic translocations are rare events that are considered difficult to detect by routine cytogenetic methods. In this study, OGM was applied to delineate the precise chromosomal rearrangements in three cases with uncertain or unconfirmed CCRs detected by conventional karyotyping and one case with a cryptic translocation suggested by fetal chromosomal microarray analysis (CMA). Results In the three cases with CCRs, OGM not only confirmed or revised the original karyotyping results but also refined the precise chromosomal structures. In the case with a suspected translocation not detected by karyotyping, OGM efficiently identified the cryptic translocation and defined the genomic breakpoints with relatively high accuracy. Conclusions Our study confirmed OGM as a robust alternative approach to karyotyping for the detection of chromosomal structural rearrangements, including CCRs and cryptic translocations

High glucose inhibits neural differentiation by excessive autophagy <em>via</em> peroxisome proliferator-activated receptor gamma

The high prevalence of prediabetes and diabetes globally has led to the widespread occurrence of severe complications, such as diabetic neuropathy, which is a result of chronic hyperglycemia. Studies have demonstrated that maternal diabetes can lead to neural tube defects by suppressing neurogenesis during neuroepithelium development. While aberrant autophagy has been associated with abnormal neuronal differentiation, the mechanism by which high glucose suppresses neural differentiation in stem cells remains unclear. Therefore, we developed a neuronal cell differentiation model of retinoic acid induced P19 cells to investigate the impact of high glucose on neuronal differentiation in vitro. Our findings indicate that high glucose (HG) hinders neuronal differentiation and triggers excessive. Furthermore, HG treatment significantly reduces the expression of markers for neurons (Tuj1) and glia (GFAP), while enhancing autophagic activity mediated by peroxisome proliferator-activated receptor gamma (PPARγ). By manipulating PPARγ activity through pharmacological approaches and genetically knocking it down using shRNA, we discovered that altering PPARγ activity affects the differentiation of neural stem cells exposed to HG. Our study reveals that PPARγ acts as a downstream mediator in high glucose-suppressed neural stem cell differentiation and that refining autophagic activity via PPARγ at an appropriate level could improve neuronal differentiation efficiency. Our data provide novel insights and potential therapeutic targets for the clinical management of gestational diabetes mellitus

The association between serum ferritin and blood pressure in adult women: a large cross-sectional study

Background Studies on the relationships between ferritin and blood pressure remain limited, especially in adult women. The aim of the present study was to investigate the associations between serum ferritin and blood pressure among adult women. Methods Using the National Health and Nutrition Examination Survey, a cross-sectional study, including 5521 adult women, was performed. Weighted multivariate regressions, subgroup analyses, threshold effect analyses, and sensitivity analysis were used. Results The authors found that serum ferritin was independently and positively correlated to diastolic blood pressure (DBP), and this positive correlation kept present among women who are 26–30 years old, non-pregnant women, Mexican American women, and women of other races in the subgroup analyses. Additionally, no significant association was found between serum ferritin and systolic blood pressure (SBP), except in women aged 26–30, Mexican American women, and women of other races. In pregnant women, the association between serum ferritin and SBP was an inverted U-shaped curve with an inflection point at 39.5 ng/mL. Conclusions The authors demonstrated that serum ferritin was positively correlated to DBP in adult women, which may provide a novel reference for clinical management

Diagnostic signature and immune characteristic of aging-related genes from placentas in Preeclampsia

Introduction Preeclampsia (PE) is a serious pregnancy syndrome. Advanced maternal age (≥ 35 years old) is one of the major risk factors of PE and placental aging is considered to be related to this disease. However, the mechanisms underlying these phenomena remain obscured. Methods Gene expression profiles of PE and non-PE placental samples were curated from the GSE75010 dataset. A diagnostic model was constructed and immune characteristics of PE subtypes were estimated. Results A total of 58 aging-related genes, which may be associated with PE, were identified. Among them, LEP and FLT1 may be key aging-related genes. Based on 5 top genes (PIK3CB, FLT1, LEP, PIK3R1, CSNK1E), a diagnostic nomogram for PE was built (AUC = 0.872 in the GSE75010 dataset). Three molecular subtypes were clustered, which had different immune and angiogenesis characteristics. Conclusion The present study suggests the potential implications of aging-related genes in diagnosing PE. Diverse immune characteristics may be involved in the placental aging of PE

Association between serum iron and liver transaminases based on a large adult women population

Abstract Background Studies are being focused on the potential roles of iron in various diseases, but remain unclear for the association between serum iron and liver injury, especially in adult women. Methods Based on the National Health and Nutrition Examination Survey, we investigated the relationship between serum iron and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) among 19,185 adult women. Results Using weighted multivariate regression analyses, subgroup analyses, and threshold effect analyses, we found that serum iron was independently and positively correlated with ALT and AST. These associations differed in various age or race. Additionally, we found turning points in the curves of the relationship between serum iron and ALT in all women and the non-pregnant women. Using sensitivity analyses, we further found that the associations between serum iron and the liver transaminases remained positive in the non-pregnant women after adjusting for various covariates, but not in pregnant women. Besides, the positive associations between them kept present after excluding the women with high blood pressure, diabetes, and chronic kidney disease. Conclusion The present study indicated a positive association between serum iron and liver transaminases, indicating that serum iron may be a potential biomarker of liver function

Ferroptosis-Related Proteins Are Potential Diagnostic Molecular Markers for Patients with Preeclampsia

Preeclampsia (PE) is the leading cause of maternal and fetal mortality and morbidity. Early and accurate diagnosis is critical to reduce mortality. Placental oxidative stress has been identified as a major pathway to the development of PE. Ferroptosis, a new form of regulated cell death, is associated with iron metabolism and oxidative stress, and has been suspected to play a role in the pathophysiology of PE, although the mechanism is yet to be elucidated. The identification of potential ferroptosis-related biomarkers is of great significance for the early diagnosis and treatment of PE. A gene expression dataset of peripheral blood samples was downloaded from the Gene Expression Omnibus (GEO) dataset. Differentially expressed genes (DEGs) were filtrated with the R package &ldquo;limma&rdquo;. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the DEGs were then conducted. Ferroptosis-related DEGs were screened by overlapping the ferroptosis-related genes with DEGs. The protein&ndash;protein interaction (PPI) network was used to identify the key ferroptosis-related DEGs. Enzyme-linked immunosorbent assay (ELISA) was used to validate changes in the selected key ferroptosis-related DEGs. The correlations between the key genes and clinical and pathological characteristics were analyzed. Finally, the diagnostic value of these key genes for PE was confirmed by a receiver operating characteristic (ROC) curve. A total of 5913 DEGs were identified and 45 ferroptosis-related DEGs were obtained. Besides, ferroptosis-related pathways were enriched by KEGG using DEGs. The PPI network showed that p53 and c-Jun were the critical hub genes. ELISA showed that p53 in the serum of PE patients was higher than that of the control group, while c-Jun was lower than that of the control group. Analysis of the clinicopathological features showed that p53 and c-Jun were correlated with the PE characteristics. Finally, based on the area under curve (AUC) values, c-Jun had the superior diagnostic power (AUC = 0.87, p &lt; 0.001), followed by p53 (AUC = 0.75, p &lt; 0.001). Our study identified that two key genes, p53 and c-Jun, might be potential diagnostic biomarkers of PE