Hypoxia-preconditioned bone marrow-derived mesenchymal stem cells protect neurons from cardiac arrest-induced pyroptosis.

JOURNAL/nrgr/04.03/01300535-202504000-00027/figure1/v/2024-07-06T104127Z/r/image-tiff Cardiac arrest can lead to severe neurological impairment as a result of inflammation, mitochondrial dysfunction, and post-cardiopulmonary resuscitation neurological damage. Hypoxic preconditioning has been shown to improve migration and survival of bone marrow-derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest, but the specific mechanisms by which hypoxia-preconditioned bone marrow-derived mesenchymal stem cells protect against brain injury after cardiac arrest are unknown. To this end, we established an in vitro co-culture model of bone marrow-derived mesenchymal stem cells and oxygen-glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis, possibly through inhibition of the MAPK and nuclear factor κB pathways. Subsequently, we transplanted hypoxia-preconditioned bone marrow-derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by asphyxia. The results showed that hypoxia-preconditioned bone marrow-derived mesenchymal stem cells significantly reduced cardiac arrest-induced neuronal pyroptosis, oxidative stress, and mitochondrial damage, whereas knockdown of the liver isoform of phosphofructokinase in bone marrow-derived mesenchymal stem cells inhibited these effects. To conclude, hypoxia-preconditioned bone marrow-derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest, and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.

The Potential Role of Female Sex Hormones in Patients With Inflammatory Bowel Disease: A 2-Sample Mendelian Randomization Study.

INTRODUCTION: An association between female sex hormones and inflammatory bowel disease (IBD) has been reported in epidemiological studies. However, a solid causal relationship has not been established. Therefore, we performed a 2-sample Mendelian randomization (MR) study to explore the causal association between genetically predicted female sex hormone exposure, especially estrogen, and IBD. METHODS: Genetic variants for female sex hormone exposure (ovulatory function, reproductive function, oral contraceptive pills, and hormone replacement therapy) were obtained from genome-wide association studies. Summary statistics for IBD were derived from the International Inflammatory Bowel Disease Genetics Consortium. We applied inverse variance weighted (IVW), MR-Egger, and weighted median (WM) methods in this MR study. Heterogeneity, horizontal pleiotropy, and sensitivity analyses were conducted to confirm the accuracy and robustness of our results. RESULTS: Our study found that genetically predicted age at menarche was associated with an increased risk of Crohn's disease (odds ratio [OR] IVW 1.235, 95% confidence interval [CI] 1.028-1.484, P = 0.024), genetically predicted age of the last used hormone replacement therapy was associated with an increased risk of ulcerative colitis (OR WM 1.636, 95% CI 1.011-2.648, P = 0.045), and genetically predicted number of live births was related to a decreased risk of Crohn's disease (OR IVW 0.583, 95% CI 0.373-0.912, P = 0.018). DISCUSSION: This study provided evidence for a link between female sex hormone exposure, especially estrogen, and IBD. Further investigations are needed to explore the causal effect of estrogen on IBD activity and the underlying mechanism of estrogen in IBD.

A bibliometric analysis of indocyanine green (ICG) in hepatobiliary surgery from 2008 to 2021.

Hundreds of scientific documents have reported on the application of indocyanine green (ICG) in hepatobiliary surgery in the past 13 years, but few bibliometric studies have been conducted. This study aimed to identify the situations of authors, countries/regions, institutions, journals, and hot topics in this field. The overall status and prospects of the current research in this field can be elucidated by bibliometric analysis. Publications from 2008 to 2021 were retrieved from the Web of Science (WoS) Core Collection. The search terms included "liver," "hepatic," "gallbladder," "bile duct," "surgery," "hepatectomy," "ICG," "indocyanine green," and related synonyms. The full records of the search results were exported in text, and the cooperation network and hot topics were evaluated and visualized using CiteSpace software. The number of publications increased between 2008 and 2021. A total of 1527 publications were included in the results, and the frequency of citations was 30,742. The largest proportion of the publications emanated from Japan, and the majority of the papers were published by Kokudo. Tian Jie contributed the largest number of papers in China. Research was relatively concentrated among one country/region. The latest hotspots, "preservation" and "resistance", frequently occurred. Cooperation between authors, countries, and institutions needs to be strengthened for high-quality research. Recent studies have focused on hepatectomy, bile duct resection, liver transplantation, and tumors in this field. Future research may focus on other aspects, such as liver preservation and resistance.

Publication trends of vascular endothelial growth factor (VEGF) and anti-VEGF treatment in neovascular age-related macular degeneration during 2001-2020: a 20-year bibliometric study.

PURPOSE: This study sought to provide an overview of the current research and further analyze publication trends in the field of vascular endothelial growth factor (VEGF) and anti-VEGF treatment for neovascular age-related macular degeneration (NVAMD). METHODS: We downloaded all related publications from 2001 to 2020 from the Web of Science Core Collection and conducted a bibliometric analysis using the bibiometrix package in R programming software. RESULTS: A total of 3717 publications were included in the analysis. The USA contributed the largest number of publications (1443), and achieved the highest number of citations (74,946) and H-index value (28). Johns Hopkins University, USA, was the top institution with the most publications, and Peter A. Campochiaro was the most productive professor at The Wilmer Eye Institute, USA. 9.60% of the total publications were from the Journal of Retinal and Vitreous Diseases. Trend analysis demonstrated that anti-VEGF therapy was introduced in early 2000 after steroids, and the last 2 decades have witnessed the blossom of several anti-VEGF agents. "Treat-and-extend" and "resistance" were two popular trend topics in recent years. CONCLUSIONS: The USA occupies a dominant position in the research field of VEGF and anti-VEGF treatments in NVAMD. Steroid administration, photodynamic therapy, and anti-VEGF therapy have been pivotal advances in the treatment of NVAMD patients over the past 2 decades. Limited acting period and resistance are potential investigation directions in future studies.

Double-dose investigation of aflibercept in neovascular age-related macular degeneration (DIANA): a real-world study.

BACKGROUND: To investigate the clinical effects of double-dose (4 mg) aflibercept treatment in neovascular age-related macular degeneration (nAMD), compared with the standard-dose (2 mg) treatment. METHODS: A total of 108 eyes from 97 patients with nAMD and received intravitreal aflibercept 2 mg and/or 4 mg treatment were retrospectively reviewed. The changes of central macular thickness (CMT)/ pigmental epithelium detachment height and the recurrence rate of exudation during the 12-month follow-up were compared between the 2 mg group and the 4 mg group. Self-control comparisons (2 mg switch to 4 mg) were also made between two regimens. RESULTS: Compared with the 2 mg group, tendencies of lower intraretinal fluid incidence and more CMT reduction were observed in the 4 mg group. The later one was also observed when eyes switching from 2 mg to 4 mg regimen. The median remission interval was 5 months in the 4 mg group, 2 months longer than the 3 months in the 2 mg group (P = 0.452). Injections needed in the 4 mg group were 3.644 ± 1.670, less than the 4.286 ± 2.334 injections in the 2 mg group within 12 months as well (P = 0.151). However, no associated vision benefits were gained from the double-douse regimen. No markedly increased-intraocular pressure events, or other adverse events were found in two groups. CONCLUSIONS: Compared to the aflibercept 2 mg treatment in nAMD, tendencies of anatomic gains and relieving treatment burden were brought by the aflibercept 4 mg treatment. This study may have additional importance, given the further application of high-dose aflibercept in real-world settings.

The Identification and Analysis of the Self-Incompatibility Pollen Determinant Factor SLF in Lycium barbarum.

Self-incompatibility is a widespread genetic mechanism found in flowering plants. It plays a crucial role in preventing inbreeding and promoting outcrossing. The genes that control self-incompatibility in plants are typically determined by the S-locus female determinant factor and the S-locus male determinant factor. In the Solanaceae family, the male determinant factor is often the SLF gene. In this research, we cloned and analyzed 13 S2-LbSLF genes from the L. barbarum genome, which are located on chromosome 2 and close to the physical location of the S-locus female determinant factor S-RNase, covering a region of approximately 90.4 Mb. The amino acid sequence identity of the 13 S2-LbSLFs is 58.46%, and they all possess relatively conserved motifs and typical F-box domains, without introns. A co-linearity analysis revealed that there are no tandemly repeated genes in the S2-LbSLF genes, and that there are two pairs of co-linear genes between S2-LbSLF and the tomato, which also belongs to the Solanaceae family. A phylogenetic analysis indicates that the S2-LbSLF members can be divided into six groups, and it was found that the 13 S2-LbSLFs are clustered with the SLF genes of tobacco and Petunia inflata to varying degrees, potentially serving as pollen determinant factors regulating self-incompatibility in L. barbarum. The results for the gene expression patterns suggest that S2-LbSLF is only expressed in pollen tissue. The results of the yeast two-hybrid assay showed that the C-terminal region of S2-LbSLFs lacking the F-box domain can interact with S-RNase. This study provides theoretical data for further investigation into the functions of S2-LbSLF members, particularly for the identification of pollen determinant factors regulating self-incompatibility in L. barbarum.

A programmable targeted protein-degradation platform for versatile applications in mammalian cells and mice.

Myriad physiological and pathogenic processes are governed by protein levels and modifications. Controlled protein activity perturbation is essential to studying protein function in cells and animals. Based on Trim-Away technology, we screened for truncation variants of E3 ubiquitinase Trim21 with elevated efficiency (ΔTrim21) and developed multiple ΔTrim21-based targeted protein-degradation systems (ΔTrim-TPD) that can be transfected into host cells. Three ΔTrim-TPD variants are developed to enable chemical and light-triggered programmable activation of TPD in cells and animals. Specifically, we used ΔTrim-TPD for (1) red-light-triggered inhibition of HSV-1 virus proliferation by degrading the packaging protein gD, (2) for chemical-triggered control of the activity of Cas9/dCas9 protein for gene editing, and (3) for blue-light-triggered degradation of two tumor-associated proteins for spatiotemporal inhibition of melanoma tumor growth in mice. Our study demonstrates that multiple ΔTrim21-based controllable TPD systems provide powerful tools for basic biology research and highlight their potential biomedical applications.

Diagnostic value of new biliary biopsy cannulae for malignant bile duct strictures via endoscopic retrograde cholangiopancreatography pathway.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) plays a major role in the diagnosis of malignant biliary strictures. ERCP fluoroscopy-guided biliary biopsy is more sensitive than brushing, but it is more difficult to perform and less successful. Therefore, a new technique of biliary biopsy using a new biliary biopsy cannula via the ERCP route was developed in our center with the aim of improving the diagnosis rate of malignant biliary strictures. METHODS: This is a retrospective study that included 42 patients who underwent ERCP-guided biliary brushing and biliary biopsy for biliary strictures using a new biliary biopsy cannula in our department from January 2019 to May 2022. The final diagnosis was determined after brushing, biliary biopsy under the new biliary biopsy cannula or adequate follow-up. Diagnostic rates were calculated and analyzed for relevant factors. RESULTS: The satisfactory rates of pathological specimens of 42 patients who underwent bile duct biopsy with bile duct brush and new bile duct biopsy cannula were 57.14% and 95.24% respectively. Cholangiocarcinoma was diagnosed in 45.23% and 83.30% of the samples by biliary brush examination and biliary biopsy using the new biliary biopsy cannula, respectively (p < 0.001). CONCLUSIONS: The ERCP route using a new biliary biopsy cannula for biliary biopsy technique can improve pathology positivity and benefit ratio. It provides a new approach in the diagnosis of malignant stenosis in the bile duct.

ILF3 safeguards telomeres from aberrant homologous recombination as a telomeric R-loop reader.

Telomeres are specialized structures at the ends of linear chromosomes that protect genome stability. The telomeric repeat-containing RNA (TERRA) that is transcribed from subtelomeric regions can invade into double-stranded DNA regions and form RNA:DNA hybrid-containing structure called R-loop. In tumor cells, R-loop formation is closely linked to gene expression and the alternative lengthening of telomeres (ALT) pathway. Dysregulated R-loops can cause stalled replication forks and telomere instability. However, how R-loops are recognized and regulated, particularly at telomeres, is not well understood. We discovered that ILF3 selectively associates with telomeric R-loops and safeguards telomeres from abnormal homologous recombination. Knocking out ILF3 results in excessive R-loops at telomeres and triggers telomeric DNA damage responses (DDR). In addition, ILF3 deficiency disrupts telomere homeostasis and causes abnormalities in the ALT pathway. Using the proximity-dependent biotin identification (BioID) technology, we mapped the ILF3 interactome and discovered that ILF3 could interact with several DNA/RNA helicases, including DHX9. Importantly, ILF3 may aid in the resolution of telomeric R-loops through its interaction with DHX9. Our findings suggest that ILF3 may function as a reader of telomeric R-loops, helping to prevent abnormal homologous recombination and maintain telomere homeostasis.

Noonan syndrome: rhGH treatment and PTPN11 mutation.

OBJECTIVE: To analyze the clinical data and genetic characteristics of Noonan syndrome, both the effect and side effects of recombinant human growth hormone (rhGH) treatment. METHODS: We collected clinical data from 8 children with Noonan syndrome diagnosed from November 2017 to June 2021. The diagnosis was clarified by exome second-generation sequencing and parental PCR-NGS validation and interpretation of the preceding evidence, and growth hormone therapy was administered. Of the cases, four males and four females were seen for slow height growth and the median age at diagnosis was 8 years 7 months (1 year 7 months to 12 years 6 months). RESULTS: Here, 7 children were treated with rhGH. Compared to the pre-treatment period, the growth rate increased after rhGH treatment [3.7 ± 0.5 cm/year before treatment and 8.0 ± 1.0 cm/year after treatment, p < 0.01], with the maximum growth rate between 3 and 6 months of treatment and decreasing with the duration of treatment thereafter. The growth hormone treatment was discontinued and the orthopedic consultation was ordered with regular follow-up, which was considered to be related to the PTPN11 mutation. CONCLUSION: Noonan syndrome is characterized by slow growth, short stature, mental retardation, peculiar facial features, structural heart abnormalities and abnormal bone metabolism. and osteochondroma was found after case 2 rhGH treatment. Genetic examination is mostly caused by PTPN11 mutation. It is recommended to pay attention to bone metabolism abnormalities before growth hormone treatment, especially in children with PTPN11 mutations.

Advances in the use of ECMO in oncology patient.

BACKGROUND: Over the past decade, ECMO has provided temporary cardiopulmonary support to an increasing number of patients, but the use of extracorporeal membrane oxygenation (ECMO) to provide temporary respiratory and circulatory support to adult patients with malignancy remains controversial. OBJECTIVES: This paper reviews the specific use of extracorporeal membrane oxygenation (ECMO) in oncology patients. METHODS: We searched PubMed, CINAHL, Cochrane Library, and Embase databases for studies on the use of ECMO in cancer patients between 1998 and 2022. Twenty-four retrospective, prospective, and case reports were included. The primary outcome was survival during extracorporeal membrane oxygenation. RESULTS: Most studies suggest that ECMO can be used in oncology patients requiring life support during surgery, solid tumor patients with respiratory failure, and hematological tumor patients requiring ECOM as a supportive means of chemotherapy; however, in patients with hematologic oncology undergoing hematopoietic stem cell transplantation, there was no clear benefit after the use of ECMO. CONCLUSION: Current research suggests that ECMO may be considered as a salvage support in specific cancer patients. Future studies should include larger sample sizes than those already conducted, including studies on efficacy, adverse events, and health.

A comparison of the impact on neuronal transcriptome and cognition of rAAV5 transduction with three different doses in the mouse hippocampus.

Introduction: Recombinant adeno-associated viruses (rAAVs) are widely used in genetic therapeutics. AAV5 has shown superior transduction efficiency, targeting neurons and glial cells in primate brains. Nonetheless, the comprehensive impact of AAV5 transduction on molecular and behavioral alterations remains unexplored. This study focuses on evaluating the effects of AAV5 transduction in the hippocampus, a critical region for memory formation and emotional processes. Methods: In this experiment, fluorescence-activated cell sorting (FACS) was utilized to isolate the mCherry-labeled pyramidal neurons in the hippocampus of CaMkIIα-cre mice following three different doses rAAV5-mCherry infusion after 3 weeks, which were then subjected to RNA sequencing (RNA-seq) to assess gene expression profiles. The cytokines concentration, mRNA expression, and glial response in hippocampi were confirmed by ELASA, digital droplet PCR and immunohistochemistry respectively. Locomotion and anxiety-like behaviors were elevated by Open Field Test and Elevated Plus Maze Test, while the Y-Maze were used to assessed spatial working memory. Recognition memory and fear responses were examined by the Novel Object Recognition Test and Fear Conditioning Test, respectively. Results: We found that 2.88 × 1010 v.g rAAV5 transduction significantly upregulated genes related to the immune response and apoptosis, and downregulated genes associated with mitochondrial function and synaptic plasticity in hippocampal pyramidal neurons, while did not induce neuronal loss and gliosis compared with 2.88 × 109 v.g and 2.88 × 108 v.g. Furthermore, the same doses impaired working memory and contextual fear memory, without effects on locomotion and anxiety-related behaviors. Discussion: Our findings highlight the detrimental impact of high-dose administration compared to median-dose or low-dose, resulting in increased neural vulnerability and impaired memory. Therefore, when considering the expression effectiveness of exogenous genes, it is crucial to also take potential side effects into account in clinical settings. However, the precise molecular mechanisms underlying these drawbacks of high-dose rAAV5-mCherry still require further investigation in future studies.

A new protective gel to facilitate ulcer healing in artificial ulcers following oesophageal endoscopic submucosal dissection: a multicentre, randomized trial.

There are significant risks of adverse events following oesophageal endoscopic submucosal dissection (ESD), such as stricture, delayed bleeding and perforation. Therefore, it is necessary to protect artificial ulcers and promote the healing process. The current study was performed to investigate the protective role of a novel gel against oesophageal ESD-associated wounds. This was a multicentre, randomized, single-blind, controlled trial that recruited participants who underwent oesophageal ESD in four hospitals in China. Participants were randomly assigned to the control or experimental group in a 1:1 ratio and the gel was used after ESD in the latter. Masking of the study group allocations was only attempted for participants. The participants were instructed to report any adverse events on post-ESD days 1, 14, and 30. Moreover, repeat endoscopy was performed at the 2-week follow-up to confirm wound healing. Among the 92 recruited patients, 81 completed the study. In the experimental group, the healing rates were significantly higher than those in the control group (83.89 ± 9.51% vs. 73.28 ± 17.81%, P = 0.0013). Participants reported no severe adverse events during the follow-up period. In conclusion, this novel gel could safely, effectively, and conveniently accelerate wound healing following oesophageal ESD. Therefore, we recommend applying this gel in daily clinical practice.

Predicting postoperative delirium after hip arthroplasty for elderly patients using machine learning.

BACKGROUND: Postoperative delirium (POD) is a common and severe complication in elderly hip-arthroplasty patients. AIM: This study aims to develop and validate a machine learning (ML) model that determines essential features related to POD and predicts POD for elderly hip-arthroplasty patients. METHODS: The electronic record data of elderly patients who received hip-arthroplasty surgery between January 2017 and April 2021 were enrolled as the dataset. The Confusion Assessment Method (CAM) was administered to the patients during their perioperative period. The feature section method was employed as a filter to determine leading features. The classical machine learning algorithms were trained in cross-validation processing, and the model with the best performance was built in predicting the POD. Metrics of the area under the curve (AUC), accuracy (ACC), sensitivity, specificity, and F1-score were calculated to evaluate the predictive performance. RESULTS: 476 Arthroplasty elderly patients with general anesthesia were included in this study, and the final model combined feature selection method mutual information (MI) and linear binary classifier using logistic regression (LR) achieved an encouraging performance (AUC = 0.94, ACC = 0.88, sensitivity = 0.85, specificity = 0.90, F1-score = 0.87) on a balanced test dataset. CONCLUSION: The model could predict POD with satisfying accuracy and reveal important features of suffering POD such as age, Cystatin C, GFR, CHE, CRP, LDH, monocyte count, history of mental illness or psychotropic drug use and intraoperative blood loss. Proper preoperative interventions for these factors could reduce the incidence of POD among elderly patients.

Risk Factors Related to Polyp Miss Rate of Short-Term Repeated Colonoscopy.

BACKGROUND: Colonoscopy is regarded as the gold standard for colorectal cancer screening and surveillance. However, previous studies have reported large numbers of polyps were missed during routine colonoscopy. AIMS: To evaluate polyp miss rate in short-term repeated colonoscopy and explore the related risk factors. METHODS: A total of 3695 patients and 12,412 polyps were included in our studies. We calculated the miss rate for polyps of different sizes, pathologies, morphologies and locations, and patients of different characteristics. Univariate and multivariate logistic regression analyses were performed to evaluate risk factors related to miss rate. RESULTS: The polyp miss rate was 26.3% and the adenoma miss rate was 22.4% in our study. The advanced adenoma miss rate was 11.0% and the proportion of missed advanced adenomas in missed adenomas sized > 5 mm was up to 22.8%. Polyps sized < 5 mm had a significantly higher miss rate. The miss rate of pedunculated polyps was lower than that of flat or sessile polyps. Polyps in the right colon were prone to be missed than that in the left colon. For older men, current smokers, individuals with multiple polyps detected in the first colonoscopy, the risk of missing polyps was significantly higher. CONCLUSION: Nearly a quarter of polyps were missed during routine colonoscopy. Diminutive, flat, sessile, and right-side colon polyps were at higher risk of missing. The risk of missing polyps was higher in older men, current smokers, and individuals with multiple polyps detected in the first colonoscopy than their counterparts.

Serum aspartate aminotransferase is an adverse prognostic indicator for patients with resectable pancreatic ductal adenocarcinoma.

OBJECTIVE: In this study, the association between preoperative levels of serum liver enzymes and overall survival (OS) was evaluated in patients with resectable pancreatic cancer. METHODS: Preoperative serum levels of alanine aminotransferase (ALT), aspartate aminotransferases (AST), γ-glutamyltransferase, alkaline phosphatase, and lactate dehydrogenase of 101 patients with pancreatic ductal adenocarcinoma (PDAC) were collected. Univariate and multivariate Cox hazard models were used to identify independent variables associated with OS in this cohort. RESULTS: Patients with elevated AST levels had significantly worse OS than patients with lower AST levels. A nomogram was created using TNM staging and AST levels and was shown to be more accurate in prediction than the American Joint Committee on Cancer 8th edition standard method. CONCLUSION: Preoperative AST levels could be a novel independent prognostic biomarker for patients with PDAC. The incorporation of AST levels into a nomogram with TNM staging can be an accurate predictive model for OS in patients with resectable PDAC.

The value of lactate dehydrogenase to albumin ratio and immune inflammation biomarkers in colorectal cancer.

Background: Colorectal cancer (CRC) is one of the most prevalent gastrointestinal cancers. Evidence for the importance of inflammation and immunology in the development and progression of CRC is growing steadily. The purpose of this study was to determine the clinical importance of Lactic Dehydrogenase (LDH) to Albumin (ALB) Ratio (LAR) and immune-inflammation biomarkers (IIBs) in patients with CRC. Methods: This study enrolled 382 CRC patients. The LAR was determined as the serum LDH(U/l) to ALB(g/l) ratio. We compared the levels of LAR and IIBs in different TNM stages and tumor differentiation. The relationship between LAR and IIBs and overall survival (OS) of CRC was determined by Cox regression models. A prognostic nomogram was created using the results of the multivariate analysis and the effectiveness of the nomogram was assessed using the ROC, calibration, and decision curves. We evaluated the relationship between LAR and IIBs and clinical features of CRC. Results: The levels of LAR, SII, NLR and PLR in TNM IV stage group (LAR:5.92 (5.23-8.24); SII: 1040.02 (499.51-1683.54); NLR: 2.87 (2.07-5.3); PLR:187.08 (125.31-276.63)) were significantly higher than those in other groups. LAR and NLR showed no significant difference in different tumor differentiation groups, while SII and PLR in undifferentiated groups (SII:543.72 (372.63-1110.20); PLR: 147.06 (106.04-203.92)) were significantly higher than those in well and moderate groups (SII: 474.29 (323.75-716.01); PLR: 126.28 (104.31-167.88)). LAR (HR = 1.317, 95% CI = 1.019-1.454), TNM stage (HR = 2.895, 95% CI = 1.838-4.559), age (HR = 1.766, 95% CI = 1.069-2.922) and lymphocytes (HR = 0.663, 95% CI = 0.456-0.963) were predictors of OS. IIBs, including SII, NLR, and PLR are independent of OS. The LAR-based nomogram AUCs of 1-year, 3-year and 5-year survival probabilities in the training cohort were 0.86, 0.72, and 0.71, respectively, and the AUCs of the validation cohort were 0.85, 0.71, and 0.69 respectively. The LAR-based nomogram's ROC curves and calibration curves demonstrated higher OS discriminative performance. The decision curves demonstrated greater net benefit in the survival prediction. Conclusion: Preoperative LAR is a potential prognostic marker in CRC patients, while SII, NLR, and PLR are independent of OS. LAR was associated with tumor stage in CRC patients, but not with tumor differentiation.

Correlation between B-cell lymphoma 6 with the balance of T helper-1/2 and severity of allergic rhinitis.

OBJECTIVE: Allergic rhinitis (AR) is a prevailing immune disorder affecting the nasal mucosa. B-cell lymphoma 6 (BCL6) imposes essential roles in immunity. This study probed into the serum expression of BCL6 and its effect on AR diagnosis and patients' quality of life (QOL). METHODS: A total of 113 patients with AR including 38 cases with mild AR (MAR) and 75 cases with moderate-severe AR (MSAR) were enrolled, with 101 healthy people enrolled as control. Serum expression of BCL6 was detected by RT-qPCR and the diagnostic efficacy of BCL6 for AR was analyzed using the receiver operating characteristic curve. The proportion of T helper-1/2 (Th1/Th2) cells in CD4+ T cells in peripheral blood mononuclear cells was detected using flow cytometry. The correlation between BCL6 and Th1/Th2 cells and the effects of BCL6 expression on patients' QOL were assessed by Pearson analysis and Mini-RQLQ questionnaire. RESULTS: BCL6 was downregulated in patients with AR, serum BCL6 level < 0.8450 had certain auxiliary diagnostic values for AR, and serum BCL6 level < 0.5400 could assist the diagnosis of AR severity. Th1 cell proportion in CD4+ T cells was decreased, whereas Th2 cell proportion was increased with AR severity. BCL6 was positively-linked with Th1 cells but inversely-correlated with Th2 cells in patients with AR. Patients with AR with low BCL6 expression had a poorer QOL compared with high BCL6 expression. The domains most affected by BCL6 expression were practical problems, nasal symptoms, and lacrimation. CONCLUSION: Serum BCL6 is downregulated and low BCL6 expression greatly deteriorates QOL in patients with AR.