Prognostic significance of systemic immune inflammatory index in NSCLC: a meta-analysis.

Aim: The aim of this meta-analysis was to investigate the relationship between the baseline systemic immune inflammatory index (SII) and prognosis in patients with NSCLC. Materials & methods: The relation between pretreatment SII and overall survival, disease-free survival, cancer-specific survival, progression-free survival and recurrence-free survival in NSCLC patients was analyzed combined with hazard ratio and 95% CI. Results: The results showed that high SII was significantly correlated with overall survival and progression-free survival of NSCLC patients, but not with disease-free survival, cancer-specific survival and recurrence-free survival. Conclusion: The study suggests that a higher SII has association with worse prognosis in NSCLC patients. PROSPERO registration number: CRD42022336270.

Conditional knockdown of OsMLH1 to improve plant prime editing systems without disturbing fertility in rice.

BACKGROUND: High-efficiency prime editing (PE) is desirable for precise genome manipulation. The activity of mammalian PE systems can be largely improved by inhibiting DNA mismatch repair by coexpressing a dominant-negative variant of MLH1. However, this strategy has not been widely used for PE optimization in plants, possibly because of its less conspicuous effects and inconsistent performance at different sites. RESULTS: We show that direct RNAi knockdown of OsMLH1 in an ePE5c system increases the efficiency of our most recently updated PE tool by 1.30- to 2.11-fold in stably transformed rice cells, resulting in as many as 85.42% homozygous mutants in the T0 generation. The high specificity of ePE5c is revealed by whole-genome sequencing. To overcome the partial sterility induced by OsMLH1 knockdown of ePE5c, a conditional excision system is introduced to remove the RNAi module by Cre-mediated site-specific recombination. Using a simple approach of enriching excision events, we generate 100% RNAi module-free plants in the T0 generation. The increase in efficiency due to OsMLH1 knockdown is maintained in the excised plants, whose fertility is not impaired. CONCLUSIONS: This study provides a safe and reliable plant PE optimization strategy for improving editing efficiency without disturbing plant development via transient MMR inhibition with an excisable RNAi module of MLH1.

Eliciting Older Cancer Patients' Preferences for Follow-Up Care to Inform a Primary Healthcare Follow-Up Model in China: A Discrete Choice Experiment.

BACKGROUND AND OBJECTIVES: Increasing longevity and advances in treatment have increased the cancer burden in the elderly, resulting in complex follow-up care needs; however, in China, little is known about the follow-up care preferences of these patients. This study quantified older cancer patients' preferences for follow-up care and examined the trade-offs they are willing to make to accept an alternative follow-up model. METHODS: A discrete choice experiment was conducted among inpatients aged over 60 years with breast, prostate, or colorectal cancer, at two large tertiary hospitals in Nantong, China. Preference weights for follow-up care were estimated using mixed logit analysis. Subgroup analysis and latent class analysis were used to explore preference heterogeneity. RESULTS: Complete results were obtained from 422 patients (144 with breast cancer, 133 with prostate cancer, 145 with colorectal cancer), with a mean age of 70.81 years. Older cancer patients stated a preference for follow-up by specialists over primary healthcare (PHC) providers ( ß = -1.18, 95% confidence interval -1.40 to -0.97). The provider of follow-up care services was the most valued attribute among patients with breast cancer (relative importance [RI] 37.17%), while remote contact services were prioritized by patients with prostate (RI 43.50%) and colorectal cancer (RI 33.01%). The uptake rate of an alternative care model integrating PHC increased compared with the baseline setting when patients were provided with preferred services (continuity of care, individualized care plans, and remote contact services). CONCLUSION: To encourage older cancer patients to use PHC-integrated follow-up care, alternative follow-up care models need to be based on patients' preferences before introducing them as a routine option.

Application Value of Early Warning Nursing Model with "Evidence-based Concept" as the Core in Peri-anesthesia Period for Gastric Cancer.

Objective: To assess the effectiveness of an evidence-based early warning nursing model in reducing postoperative complications and enhancing care satisfaction for gastric cancer (GC) patients undergoing elective surgery. Methods: A retrospective analysis was performed on patients who received laparoscopic assisted radical gastrectomy in Tumor Hospital Affiliated To Nantong University from January 2020 to January 2022 as the research subjects. According to the anesthesia plan, the patients were divided into a comprehensive (intervention plans that received an early warning care model centered on evidence-based concepts) and a conventional group (routine evidence-based nursing plan). The postoperative anesthesia recovery, complications, pain level at 24 hours after surgery, anxiety at different times after surgery, and nursing satisfaction were compared between the two groups. Results: The postoperative spontaneous breathing time, consciousness recovery time, tracheal removal time, and defecation recovery time in the patients who received the early warning nursing based on the evidence-based concept were lower than those receiving only evidence-based care (P < .05). The total incidence of postoperative complications in the patients who received the early warning nursing based on the evidence-based concept were lower than those receiving only evidence-based care (P < .05). The postoperative pain levels of patients receiving the early warning nursing model were significantly lower than those receiving only evidence-based care (Z = -2.199, P = .028). After the intervention of different peri-anesthesia nursing modes, the anxiety scores of the two groups showed a downward trend with time (Ftime = 8.552, Ptime < .05), and the decrease in the comprehensive were greater than that in the routine group (F groups = 135.100, Ptime < .05), and there were no interaction (Finteraction = 2.424, Pinteraction < .05). Patients in the group that received the comprehensive early warning nursing model had significantly higher satisfaction with peri-anesthesia care compared to those receiving only evidence-based care (Z = -1.965, P < .05). Conclusion: Under the evidence-based early warning nursing model, nurses accurately assess patients' conditions during the peri-anesthesia period, leading to improved care plans that reduce complications and postoperative pain while enhancing patient satisfaction.

Transcriptomics Based Network Analyses and Molecular Docking Highlighted Potentially Therapeutic Biomarkers for Colon Cancer.

In this study, machine learning-based multiple bioinformatics analysis was carried out for the purpose of the deep and efficient mining of high-throughput transcriptomics data from the TCGA database. Compared with normal colon tissue, 2469 genes were significantly differentially expressed in colon cancer tissue. Gene functional annotation and pathway analysis suggested that most DEGs were functionally related to the cell cycle and metabolism. Weighted gene co-expression network analysis revealed a significant module and the enriched genes that were closely related to fatty acid degradation and metabolism. Based on colon cancer progression, the trend analysis highlighted that several gene sets were significantly correlated with disease development. At the same time, the most specific genes were functionally related to cancer cell features such as the high performance of DNA replication and cell division. Moreover, survival analysis and target drug prediction were performed to prioritize reliable biomarkers and potential drugs. In consideration of a combination of different evidence, four genes (ACOX1, CPT2, CDC25C and PKMYT1) were suggested as novel biomarkers in colon cancer. The potential biomarkers and target drugs identified in our study may provide new ideas for colonic-related prevention, diagnosis, and treatment; therefore, our results have high clinical value for colon cancer.

Genome editing with type II-C CRISPR-Cas9 systems from Neisseria meningitidis in rice.

Two type II-C Cas9 orthologs (Nm1Cas9 and Nm2Cas9) were recently identified from Neisseria meningitidis and have been extensively used in mammalian cells, but whether these NmCas9 orthologs or other type II-C Cas9 proteins can mediate genome editing in plants remains unclear. In this study, we developed and optimized targeted mutagenesis systems from NmCas9s for plants. Efficient genome editing at the target with N4 GATT and N4 CC protospacer adjacent motifs (PAMs) was achieved with Nm1Cas9 and Nm2Cas9 respectively. These results indicated that a highly active editing system could be developed from type II-C Cas9s with distinct PAM preferences, thus providing a reliable strategy to extend the scope of genome editing in plants. Base editors (BEs) were further developed from the NmCas9s. The editing efficiency of adenine BEs (ABEs) of TadA*-7.10 and cytosine BEs (CBEs) of rat APOBEC1 (rAPO1) or human APOBEC3a (hA3A) were extremely limited, whereas ABEs of TadA-8e and CBEs of Petromyzon marinus cytidine deaminase 1 (PmCDA1) exhibited markedly improved performance on the same targets. In addition, we found that fusion of a single-stranded DNA-binding domain from the human Rad51 protein enhanced the base editing capability of rAPO1-CBEs of NmCas9s. Together, our results suggest that the engineering of NmCas9s or other type II-C Cas9s can provide useful alternatives for crop genome editing.

Phosphoproteomics Identifies Significant Biomarkers Associated with the Proliferation and Metastasis of Prostate Cancer.

The spider peptide toxins HNTX-III and JZTX-I are a specific inhibitor and activator of TTX-S VGSCs, respectively. They play important roles in regulating MAT-LyLu cell metastasis in prostate cancer. In order to identify key biomarkers involved in the regulation of MAT-LyLu cell metastasis, iTRAQ-based quantitative phosphoproteomics analysis was performed on cells treated with HNTX-III, JZTX-I and blank. A total of 554 unique phosphorylated proteins and 1779 distinct phosphorylated proteins were identified, while 55 and 36 phosphorylated proteins were identified as differentially expressed proteins in HNTX-III and JZTX-I treated groups compared with control groups. Multiple bioinformatics analysis based on quantitative phosphoproteomics data suggested that the differentially expressed phosphorylated proteins and peptides were significantly associated with the migration and invasion of prostate tumors. Specifically, the toxins HNTX-III and JZTX-I have opposite effects on tumor formation and metastasis by regulating the expression and phosphorylation level of causal proteins. Herein, we highlighted three key proteins EEF2, U2AF2 and FLNC which were down-regulated in HNTX-III treated cells and up-regulated in JZTX-I treated cells. They played significant roles in cancer related physiological and pathological processes. The differentially expressed phosphorylated proteins identified in this study may serve as potential biomarkers for precision medicine for prostate cancer in the near future.

Origin and Characterization of Extracellular Vesicles Present in the Spider Venom of Ornithoctonus hainana.

Extracellular vesicles (EVs), including exosomes and microvesicles, are membranous vesicles released from nearly all cellular types. They contain various bioactive molecules, and their molecular composition varies depending on their cellular origin. As research into venomous animals has progressed, EVs have been discovered in the venom of snakes and parasitic wasps. Although vesicle secretion in spider venom glands has been observed, these secretory vesicles' origin and biological properties are unknown. In this study, the origin of the EVs from Ornithoctonus hainana venom was observed using transmission electron microscopy (TEM). The Ornithoctonus hainana venom extracellular vesicles (HN-EVs) were isolated and purified by density gradient centrifugation. HN-EVs possess classic membranous vesicles with a size distribution ranging from 50 to 150 nm and express the arthropod EV marker Tsp29Fb. The LC-MS/MS analysis identified a total of 150 proteins, which were divided into three groups according to their potential function: conservative vesicle transport-related proteins, virulence-related proteins, and other proteins of unknown function. Functionally, HN-EVs have hyaluronidase activity and inhibit the proliferation of human umbilical vein endothelial cells (HUVECs) by affecting the cytoskeleton and cell cycle. Overall, this study investigates the biological characteristics of HN-EVs for the first time and sheds new light on the envenomation process of spider venom.

Effect of multimedia-based nursing visit on perioperative anxiety in esophageal squamous cell carcinoma patients undergoing video-assisted thoracoscopic surgery.

Little is known about the multimedia-based preoperative nursing visit for squamous cell carcinoma (ESCC) patients undergoing video-assisted thoracoscopic surgery (VAST). The aim of this study was to evaluate the effects of preoperative multimedia-based nursing visit on perioperative anxiety in ESCC patients undergoing VAST. A total of 128 ESCC patients undergoing VAST were randomly divided into intervention group (n = 63) or control group (n = 65). The anxiety level was measured by state-trait anxiety inventory (STAI) and visual analog scale (VAS). The vital signs were also recorded. The data were collected at three different time points: before the intervention, 1 h before surgery and 24 h after surgery. There was no statistically significant difference in baseline STAI score, VAS scores and vital signs (P > 0.05). The intervention group reported significantly lower anxiety and improved vital signs in terms of systolic blood pressure, diastolic blood pressure and heart rate at 1 h before surgery and 24 h after surgery (P < 0.05). However, no significant difference in respiratory rate was observed between two groups at 1 h before surgery and 24 h after surgery (P > 0.05). Preoperative nursing visit with multimedia could reduce perioperative anxiety levels as well as help to stabilize vital sign for ESCC patients undergoing VAST.

Isolation and characterization of three cadmium-inducible promoters from Oryza sativa.

Cadmium (Cd) is an important soil pollutant. Developing genetically engineered crops might be a feasible strategy for Cd decontamination and damage prevention. Both genes and promoters are critical for the effective construction of genetically modified plants. Although many functional genes for Cd tolerance and accumulation have been identified, few reports have focused on plant Cd-inducible promoters. Here, we identified three Cd-inducible genes in the rice genome: two tau class glutathione S-transferase (GSTU) genes, OsGSTU5 and OsGSTU37, and an HSP20/alpha crystallin family protein gene, OsHSP18.6. The promoter sequences were isolated and tested in transgenic rice lines using a GUSplus reporter gene. All of the promoters exhibited low background expression under normal conditions and could be strongly induced by Cd stress. Although their strength was comparable to that of the constitutive OsACTIN promoter under Cd stress, their time-dependent expression patterns under both short- and long-term Cd exposure were markedly different. The responses of the three promoters to other heavy metals were also examined. Furthermore, heavy metal-responsive cis elements in the promoters were computationally analyzed, and regions determining the Cd stress response were analyzed using a series of truncations. Our results indicate that the three Cd-inducible rice promoters described herein could potentially be used in applications aimed at improving heavy metal tolerance in crops or for the bio-monitoring of environmental contamination.

Identification and analysis of the mechanism underlying heat-inducible expression of rice aconitase 1.

Respiratory metabolism is an important though poorly understood facet of plant adaptation to stress. Posttranslational modification of aconitase, a component of the tricarboxylic acid cycle (TCA), may be involved in stress tolerance. However, such stress-related transcriptional regulation and its mechanism remain unknown. In this study, we found that expression of the rice Aconitase gene OsACO1 is induced in a time-dependent manner by heat but not other typical abiotic stresses. To analyze the transcriptional regulation mechanism underlying the response to heat, the OsACO1 promoter (POsACO1) was isolated and characterized in transgenic rice. Using qualitative and quantitative analyses, we found that the expression of the GUS reporter gene responded to heat in different tissues and at different stages of development when driven by POsACO1. A series of 5' distal deletions of POsACO1 was generated to delineate the region responsible for heat-induced gene expression. Transient expression analyses in tobacco leaves identified a 322-bp minimal region between -1386 and -1065 as being essential and sufficient for heat-induced expression by POsACO1. We screened for known heat response-related cis-elements in this 322-bp region; however, sequences correlating with heat-induced gene expression were not identified in POsACO1. Therefore, truncations and successive mutagenesis analyses were performed in this 322-bp region. By comparing the activities of promoter fragments and their derivatives, our results indicated that the heat response element resided in a 9-bp region between -1132 and -1124, a sequence that contains a W-box motif. Additional site-directed mutagenesis analyses eliminated the heat response activity of POsACO1 via the W-box element, and an electrophoretic mobility shift assay (EMSA) indicated the binding of POsACO1 by factors in the nuclear extracts of heat-stressed rice seedlings in a W-box-dependent manner. Our results illustrate the expression pattern of a key component of the TCA response to abiotic stress and establish a putative regulatory pathway in the transcriptional modulation of rice respiratory metabolism genes in response to heat.