Regulating donor configuration to develop AIE-active type I photosensitizers for lipid droplet imaging and high-performance photodynamic therapy under hypoxia.

Type I photodynamic therapy is considered to be a more promising cancer treatment than type II photodynamic therapy due to its non-oxygen-dependent characteristics. In this work, three D-A structure N,N'-dihydrophenazine (DHP)-based photosensitizers DP-CNPY, SMP-CNPY and DMP-CNPY were designed and synthesized by introducing different numbers of methyl groups in the backbone neighbor of DHP as the donor and combined with the typical strong electron acceptor 2-(pyridin-4-yl)acetonitrile. Among the three photosensitizers, SMP-CNPY with one methyl modification showed the best type I ROS (O2-˙, ˙OH) generation capacity and AIE performance. By encapsulation, SMP-CNPY was fabricated into nanoparticles, and SMP-CNPY NPs exhibited lipid droplet targeting ability with near-infrared (NIR) emission. Cell experiments have proved that SMP-CNPY NPs can effectively kill different kinds of cancer cells under normal oxygen conditions. Even under hypoxic and extreme hypoxic conditions, SMP-CNPY NPs can still produce ROS and kill cancer cells. This work holds significant potential in the field of type I AIE-active photosensitizers and provides a new strategy for overcoming the hypoxic dilemma in the malignant tumor microenvironment.

Corrigendum: Assessing causal associations between neurodegenerative diseases and neurological tumors with biological aging: a bidirectional Mendelian randomization study.

[This corrects the article DOI: 10.3389/fnins.2023.1321246.].

Proteus appendicitidis sp. nov., isolated from the appendiceal pus of an appendicitis patient in Yongzhou, China.

A Gram-negative, facultatively anaerobic, short rod-shaped bacterium, designated as strain HZ0627T, was isolated from the appendiceal pus of a patient with appendicitis in Yongzhou, Hunan, China. This strain was subjected to comprehensive phenotypic, phylogenetic, and genomic analyses using polyphasic taxonomic methods. Phylogenetic analysis of the 16S rRNA gene sequence revealed that this strain belonged to the genus Proteus and the family Morganellaceae, whereas that based on the rpoB gene sequence and phylogenomic analysis demonstrated that this strain was distinctly separated from other type strains of Proteus species. Moreover, whole-genome-based analyses, including in silico DNA-DNA hybridization (isDDH) and average nucleotide identity (ANI), revealed that strain HZ0627T had much lower isDDH rates (24.5-55.6%) and ANI (82.04-93.90%) than those of the thresholds (i.e., 70% and 95%, respectively) for species delineation, when compared to the type strains of other Proteus species. The cellular fatty acid profile of strain HZ0627T was dominated by C16:0 (34.5%), cyclo C17:0 (25.8%), C14:0 (12.6%), C16:1 iso I/14:0 3-OH (7.7%), C18:1ω7c/18:1ω6c (6.5%), and C16:1ω7c/16:1ω6c (4.9%), which clearly differentiated it from the documented type strains of Proteus species. In addition, several specific physiological traits, including optimal growth temperature, tolerance to sodium chloride, and carbon source utilization, differed from those of other Proteus species. Therefore, we propose the name Proteus appendicitidis sp. nov. for strain HZ0627T (= CCTCC AB 2022380T = KCTC 92986T), which represents the type strain of this novel Proteus species.

Association between viral infections and glioma risk: a two-sample bidirectional Mendelian randomization analysis.

BACKGROUND: Glioma is one of the leading types of brain tumor, but few etiologic factors of primary glioma have been identified. Previous observational research has shown an association between viral infection and glioma risk. In this study, we used Mendelian randomization (MR) analysis to explore the direction and magnitude of the causal relationship between viral infection and glioma. METHODS: We conducted a two-sample bidirectional MR analysis using genome-wide association study (GWAS) data. Summary statistics data of glioma were collected from the largest meta-analysis GWAS, involving 12,488 cases and 18,169 controls. Single-nucleotide polymorphisms (SNPs) associated with exposures were used as instrumental variables to estimate the causal relationship between glioma and twelve types of viral infections from corresponding GWAS data. In addition, sensitivity analyses were performed. RESULTS: After correcting for multiple tests and sensitivity analysis, we detected that genetically predicted herpes zoster (caused by Varicella zoster virus (VZV) infection) significantly decreased risk of low-grade glioma (LGG) development (OR = 0.85, 95% CI: 0.76-0.96, P = 0.01, FDR = 0.04). No causal effects of the other eleven viral infections on glioma and reverse causality were detected. CONCLUSIONS: This is one of the first and largest studies in this field. We show robust evidence supporting that genetically predicted herpes zoster caused by VZV infection reduces risk of LGG. The findings of our research advance understanding of the etiology of glioma.

[Research on the mechanism of mechanical ventilation induced endoplasmic reticulum stress promoting mechanical ventilation-induced pulmonary fibrosis].

OBJECTIVE: To demonstrate the mechanism of mechanical ventilation (MV) induced endoplasmic reticulum stress (ERS) promoting mechanical ventilation-induced pulmonary fibrosis (MVPF), and to clarify the role of angiotensin receptor 1 (AT1R) during the process. METHODS: The C57BL/6 mice were randomly divided into four groups: Sham group, MV group, AT1R-shRNA group and MV+AT1R-shRNA group, with 6 mice in each group. The MV group and MV+AT1R-shRNA group mechanically ventilated for 2 hours after endotracheal intubation to establish MVPF animal model (parameter settings: respiratory rate 70 times/minutes, tidal volume 20 mL/kg, inhated oxygen concentration 0.21). The Sham group and AT1R-shRNA group only underwent intubation after anesthesia and maintained spontaneous breathing. AT1R-shRNA group and MV+AT1R-shRNA group were airway injected with the adeno-associated virus one month before modeling to inhibit AT1R gene expression in lung tissue. The expressions of AT1R, ERS signature proteins [immunoglobulin heavy chain-binding protein (BIP), protein disulfide isomerase (PDI)], fibrosis signature proteins [collagen I (COL1A1), α-smooth muscle actin (α-SMA)] in lung tissues were detected by immunofluorescence and Western blotting. Hematoxylin-eosin (HE) staining was used to evaluate lung injury and Masson staining was used to evaluate pulmonary fibrosis. RESULTS: Compared with the Sham group, the degree of pulmonary fibrosis and lung injury were more significant in the MV group. In the MV group, the protein expressions of AT1R, BIP, PDI, COL1A1 and α-SMA were increased (AT1R/ß-actin: 1.40±0.02 vs. 1, BIP/ß-actin: 2.79±0.07 vs. 1, PDI/ß-actin: 2.07±0.02 vs. 1, COL1A1/α-Tubulin: 2.60±0.15 vs. 1, α-SMA/α-Tubulin: 2.80±0.25 vs. 1, all P < 0.01). The number of E-cad+/AT1R+ and E-cad+/BIP+ cells in lung tissue increased, and the fluorescence intensity of COL1A1 and α-SMA increased. Compared with the MV group, the degree of pulmonary fibrosis and lung injury were significantly relieved in the MV+AT1R-shRNA group. In the MV+AT1R-shRNA group, the protein expressions of AT1R, BIP, PDI, COL1A1 and α-SMA were decreased (AT1R/ß-actin: 0.53±0.03 vs. 1.40±0.02, BIP/ß-actin: 1.73±0.15 vs. 2.79±0.07, PDI/ß-actin: 1.04±0.07 vs. 2.07±0.02, COL1A1/α-Tubulin: 1.29±0.11 vs. 2.60±0.15, α-SMA/α-Tubulin: 1.27±0.10 vs. 2.80±0.25, all P < 0.01). The number of E-cad+/AT1R+ and E-cad+/BIP+ cells in lung tissue decreased, and the fluorescence intensity of COL1A1 and α-SMA decreased. There was no statistically significant difference in the indicators between AT1R-shRNA group and Sham group. CONCLUSIONS: MV up-regulate the expression of AT1R in alveolar epithelial cells, activate the AT1R pathway, induce ERS and promote the progression of MVPF.

Plasma hepatocyte growth factor as a noninvasive biomarker in small cell lung cancer.

BACKGROUND: Hepatocyte growth factor (HGF) is a peptide-containing multifunctional cytokine, which is overexpressed and/or activated in multiple malignancies and is reported to be associated with tumor development and inferior survival. At present, the role of HGF in small cell lung cancer (SCLC) has not been fully explored yet. MATERIALS AND METHODS: The expression of HGF and its value in predicting survival in SCLC were explored from GEO database and in pan-cancer analysis. Furthermore, we detected the expression of HGF using tumor tissue and paired plasma samples from a validation cohort of 71 SCLC patients at our institute. Correlation between tumor and plasma HGF expression and the prognostic values were analyzed. RESULTS: GEO database analysis revealed that tumor tissue had lower HGF expression than paired normal tissue in SCLC. At our institute, immunohistochemical staining showed negative expression of HGF in tumor tissue of SCLC at our institute (47/47, 100%). The average baseline plasma HGF was 1.28 (range,0.42-4.35) ng/ml. However, plasma HGF was higher in SCLC patients with patients with N3, M1, liver metastasis (LM) and bone metastasis (BM) disease compared with those N0 - 2 (1.25 vs. 1.75 ng/mL, P = 0.000), M0 (1.26 vs. 1.63 ng/mL, P = 0.003), non-LM (1.32 vs. 2.06 ng/mL, P = 0.009), and non-BM (1.35 vs. 1.77 ng/mL, P = 0.047), respectively. Multivariate analysis revealed plasma HGF was an independent predictor for LM and prognostic factor of OS. CONCLUSION: Our results revealed that plasma HGF rather than tumor HGF exhibited a potential role in predicting metastasis and survival in SCLC. Plasma HGF might be used as a non-invasive detecting and monitoring tool for SCLC.

Development of an MCL-1-related prognostic signature and inhibitors screening for glioblastoma.

Introduction: The effect of the conventional treatment methods of glioblastoma (GBM) is poor and the prognosis of patients is poor. The expression of MCL-1 in GBM is significantly increased, which shows a high application value in targeted therapy. In this study, we predicted the prognosis of glioblastoma patients, and therefore constructed MCL-1 related prognostic signature (MPS) and the development of MCL-1 small molecule inhibitors. Methods: In this study, RNA-seq and clinical data of 168 GBM samples were obtained from the TCGA website, and immunological analysis, differential gene expression analysis and functional enrichment analysis were performed. Subsequently, MCL-1-associated prognostic signature (MPS) was constructed and validated by LASSO Cox analysis, and a nomogram was constructed to predict the prognosis of patients. Finally, the 17931 small molecules downloaded from the ZINC15 database were screened by LibDock, ADME, TOPKAT and CDOCKER modules and molecular dynamics simulation in Discovery Studio2019 software, and two safer and more effective small molecule inhibitors were finally selected. Results: Immunological analysis showed immunosuppression in the MCL1_H group, and treatment with immune checkpoint inhibitors had a positive effect. Differential expression gene analysis identified 449 differentially expressed genes. Build and validate MPS using LASSO Cox analysis. Use the TSHR HIST3H2A, ARGE OSMR, ARHGEF25 build risk score, proved that low risk group of patients prognosis is better. Univariate and multivariate analysis proved that risk could be used as an independent predictor of patient prognosis. Construct a nomogram to predict the survival probability of patients at 1,2,3 years. Using a series of computer-aided techniques, two more reasonable lead compounds ZINC000013374322 and ZINC000001090002 were virtually selected. These compounds have potential inhibitory effects on MCL-1 and provide a basis for the design and further development of MCL-1 specific small molecule inhibitors. Discussion: This study analyzed the effect of MCL-1 on the prognosis of glioblastoma patients from the perspective of immunology, constructed a new prognostic model to evaluate the survival rate of patients, and further screened 2 MCL-1 small molecule inhibitors, which provides new ideas for the treatment and prognosis of glioblastoma.

Longitudinal detection of subcategorized CD44v6+ CTCs and circulating tumor endothelial cells (CTECs) enables novel clinical stratification and improves prognostic prediction of small cell lung cancer: A prospective, multi-center study.

Current management of small cell lung cancer (SCLC) remains challenging. Effective biomarkers are needed to subdivide patients presenting distinct treatment response and clinical outcomes. An understanding of heterogeneous phenotypes of aneuploid CD31- circulating tumor cells (CTCs) and CD31+ circulating tumor endothelial cells (CTECs) may provide novel insights in the clinical management of SCLC. In the present translational and prospective study, increased cancer metastasis-related cell proliferation and motility, accompanied with up-regulated mesenchymal marker vimentin but down-regulated epithelial marker E-cadherin, were observed in both lentivirus infected SCLC and NSCLC cells overexpressing the stemness marker CD44v6. Aneuploid CTCs and CTECs expressing CD44v6 were longitudinally detected by SE-iFISH in 120 SCLC patients. Positive detection of baseline CD44v6+ CTCs and CD44v6+ CTECs was significantly associated with enhanced hepatic metastasis. Karyotype analysis revealed that chromosome 8 (Chr8) in CD44v6+ CTCs shifted from trisomy 8 towards multiploidy in post-therapeutic patients compared to pre-treatment subjects. Furthermore, the burden of baseline CD44v6+ CTCs (t0) or amid the therapy (t1-2), the ratio of baseline CD31+ CTEC/CD31- CTC (t0), and CTC-WBC clusters (t0) were correlated with treatment response and distant metastases, particularly brain metastasis, in subjects with limited disease (LD-SCLC) but not in those with extensive disease (ED-SCLC). Multivariate survival analysis validated that longitudinally detected CD44v6+/CD31- CTCs was an independent prognostic factor for inferior survival in SCLC patients. Our study provides evidence for the first time that comprehensive analyses of CTCs, CTECs, and their respective CD44v6+ subtypes enable clinical stratification and improve prognostic prediction of SCLC, particularly for potentially curable LD-SCLC.

Inflammatory factors and risk of meningiomas: a bidirectional mendelian-randomization study.

Background: Meningiomas are one of the most common intracranial tumors, and the current understanding of meningioma pathology is still incomplete. Inflammatory factors play an important role in the pathophysiology of meningioma, but the causal relationship between inflammatory factors and meningioma is still unclear. Method: Mendelian randomization (MR) is an effective statistical method for reducing bias based on whole genome sequencing data. It's a simple but powerful framework, that uses genetics to study aspects of human biology. Modern methods of MR make the process more robust by exploiting the many genetic variants that may exist for a given hypothesis. In this paper, MR is applied to understand the causal relationship between exposure and disease outcome. Results: This research presents a comprehensive MR study to study the association of genetic inflammatory cytokines with meningioma. Based on the results of our MR analysis, which examines 41 cytokines in the largest GWAS datasets available, we were able to draw the relatively more reliable conclusion that elevated levels of circulating TNF-ß, CXCL1, and lower levels of IL-9 were suggestive associated with a higher risk of meningioma. Moreover, Meningiomas could cause lower levels of interleukin-16 and higher levels of CXCL10 in the blood. Conclusion: These findings suggest that TNF-ß, CXCL1, and IL-9 play an important role in the development of meningiomas. Meningiomas also affect the expression of cytokines such as IL-16 and CXCL10. Further studies are needed to determine whether these biomarkers can be used to prevent or treat meningiomas.

Post-therapeutic circulating tumor cell-associated white blood cell clusters predict poor survival in patients with advanced driver gene-negative non-small cell lung cancer.

PURPOSE: This study aimed to investigate the clinical utility of diverse aneuploid circulating tumor cell (CTC) subtypes and particularly CTC-associated white blood cell (CTC-WBC) clusters in predicting treatment response, prognosis and real-time monitoring disease progression in advanced driver gene-negative non-small lung cancer (NSCLC) patients. MATERIALS AND METHODS: A total of 74 eligible patients were prospectively enrolled and serial blood samples were collected at pre-treatment(t0), after two cycles of therapy (t1) and at post-four-to-six treatment cycles (t2). Co-detection of diverse subtypes of aneuploid CTCs and CTC-WBC clusters was conducted in advanced NSCLC patients receiving first-line treatment. RESULTS: At baseline, CTCs were detected in 69 (93.24%) patients and CTC-WBC clusters were detected in 23 (31.08%) patients. Patients with CTCs < 5/6ml or with CTC-WBC clusters undetectable exhibited a better treatment response than patients with pre-therapeutic aneuploid CTCs ≥ 5/6ml or harboring CTC-WBC clusters (p = 0.034 and p = 0.012, respectively). Before treatment, patients bearing tetraploid CTCs ≥ 1/6ml showed significantly inferior progression-free survival (PFS) [hazard ratio (HR):2.420, 95% confidence interval (CI): 1.426-4.106; p = 0.001] and overall survival (OS) compared to patients with tetraploid CTCs < 1/6ml (HR:1.907, 95%CI: 1.119-3.251; p = 0.018). A longitudinal study demonstrated that post-therapeutic patients harboring CTC-WBC clusters displayed the reduced PFS and OS compared with those without CTC-WBC clusters, and subgroup analysis showed that the presence of CTC-WBC clusters indicated a worse prognosis in both lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients. After adjusting for multiple significant factors, post-therapeutic CTC-WBC clusters were the only independent predictor of both PFS (HR:2.872, 95% CI: 1.539-5.368; p = 0.001) and OS (HR:2.162, 95% CI: 1.168-4.003; p = 0.014). CONCLUSIONS: In addition to CTCs, longitudinal detection of CTC-WBC clusters provided a feasible tool to indicate initial treatment response, dynamically monitor disease progression and predict survival in driver gene-negative advanced NSCLC patients.

UHRF1/DNMT1-MZF1 axis-modulated intragenic site-specific CpGI methylation confers divergent expression and opposing functions of PRSS3 isoforms in lung cancer.

As confusion mounts over RNA isoforms involved in phenotypic plasticity, aberrant CpG methylation-mediated disruption of alternative splicing is increasingly recognized as a driver of intratumor heterogeneity (ITH). Protease serine 3 (PRSS3), possessing four splice variants (PRSS3-SVs; PRSS3-V1-V4), is an indispensable trypsin that shows paradoxical effects on cancer development. Here, we found that PRSS3 transcripts and their isoforms were divergently expressed in lung cancer, exhibiting opposing functions and clinical outcomes, namely, oncogenic PRSS3-V1 and PRSS3-V2 versus tumor-suppressive PRSS3-V3, by targeting different downstream genes. We identified an intragenic CpG island (iCpGI) in PRSS3. Hypermethylation of iCpGI was mediated by UHRF1/DNMT1 complex interference with the binding of myeloid zinc finger 1 (MZF1) to regulate PRSS3 transcription. The garlic-derived compound diallyl trisulfide cooperated with 5-aza-2'-deoxycytidine to exert antitumor effects in lung adenocarcinoma cells through site-specific iCpGI demethylation specifically allowing MZF1 to upregulate PRSS3-V3 expression. Epigenetic silencing of PRSS3-V3 via iCpGI methylation (iCpGIm) in BALF and tumor tissues was associated with early clinical progression in patients with lung cancer but not in those with squamous cell carcinoma or inflammatory disease. Thus, UHRF1/DNMT1-MZF1 axis-modulated site-specific iCpGIm regulates divergent expression of PRSS3-SVs, conferring nongenetic functional ITH, with implications for early detection of lung cancer and targeted therapies.

Identification of diagnostic biomarks and immune cell infiltration in ulcerative colitis.

We aimed to explore diagnostic biomarks and immune cell infiltration characteristics in ulcerative colitis (UC). We used the dataset GSE38713 as the training set and dataset GSE94648 as the test set. A total of 402 differentially expressed genes (DEGs) were obtained from GSE38713. Annotating, visualizing, and integrating discovery of these differential genes was performed using Gene Ontology (GO), Kyoto Gene and Genome Encyclopedia Pathway (KEGG), and Gene Set Enrichment Analysis (GSEA). Protein-protein interaction networks were constructed from the STRING database, and protein functional modules were identified using the CytoHubba plugin of Cytoscape. Random forest and LASSO regression were used to screen for UC-related diagnostic markers, and ROC curves were generated to validate their diagnostic value. The composition of 22 immune cells was analyzed, and the immune cell infiltration in UC was analyzed using CIBERSORT. Results: Seven diagnostic markers associated with UC were identified: TLCD3A, KLF9, EFNA1, NAAA,WDR4, CKAP4, and CHRNA1. Immune cell infiltration assessment revealed that macrophages M1, activated dendritic cells, and neutrophil cells infiltrated relatively more compared to normal control samples. Our results suggest a new functional feature of UC and suggest potential biomarkers for UC through comprehensive analysis of integrated gene expression data.

Preparation of plant-based meat analogs using emulsion gels: Lipid-filled RuBisCo protein hydrogels.

RuBisCo from duckweed is a sustainable source of plant proteins with a high water-solubility and good gelling properties. In this study, we examined the impact of RuBisCo concentration (9-33 wt %) and oil droplet concentration (0 to 14 wt %) on the properties of emulsion gels designed to simulate the properties of chicken breast. The color (L*a*b*), water holding capacity (WHC), textural profile analysis, shear modulus, and microstructure of the emulsion gels were measured. The gel hardness and WHC increased significantly with increasing protein concentration, reaching values equivalent to chicken breast. The lightness of the emulsion gels was less than that of chicken breast, due to the presence of pigments (such as polyphenols) in the protein. Shear modulus versus temperature measurements showed that gelation began when the protein solutions were heated to around 40 °C and then the gels hardened appreciably when the temperature was further raised to 90 °C. The shear modulus of the gels then increased during cooling, which was attributed to the strengthening of hydrogen bonds at lower temperatures. The hardness of the gels increased slightly but then decreased when the oil droplet concentration was raised from 0 to 14 %. The lightness of the protein gels increased after adding the oil droplets, which was attributed to increased light scattering. Microstructure analysis showed that the RuBisCo proteins formed a particulate gel after heating, with the oil droplets being in the interstices between the particulates. In summary, RuBisCo proteins can be dissolved at high concentrations and can form strong emulsion gels. Consequently, they may be able to mimic the composition and textural attributes of real chicken.

Prognostic markers of ferroptosis-related long non-coding RNA in lung adenocarcinomas.

Ferroptosis is a recently established type of iron-dependent programmed cell death. Growing studies have focused on the function of ferroptosis in cancers, including lung adenocarcinoma (LUAD). However, the factors involved in the regulation of ferroptosis-related genes are not fully understood. In this study, we collected data from lung adenocarcinoma datasets of the Cancer Genome Atlas (TCGA-LUAD). The expression profiles of 60 ferroptosis-related genes were screened, and two differentially expressed ferroptosis subtypes were identified. We found the two ferroptosis subtypes can predict clinical outcomes and therapeutic responses in LUAD patients. Furthermore, key long non-coding RNAs (lncRNAs) were screened by single factor Cox and least absolute shrinkage and selection operator (LASSO) based on which co-expressed with the 60 ferroptosis-related genes. We then established a risk score model which included 13 LUAD ferroptosis-related lncRNAs with a multi-factor Cox regression. The risk score model showed a good performance in evaluating the outcome of LUAD. What's more, we divided TCGA-LUAD tumor samples into two groups with high- and low-risk scores and further explored the differences in clinical characteristics, tumor mutation burden, and tumor immune cell infiltration among different LUAD tumor risk score groups and evaluate the predictive ability of risk score for immunotherapy benefit. Our findings provide good support for immunotherapy in LUAD in the future.

The effect of different concentrations of chlorine-containing disinfectants on high-frequency contact table in intensive care units: A quasi-experimental study.

BACKGROUND: The hospital environment, particularly the intensive care unit (ICU), contributes to the transmission of several nosocomial pathogens, which can survive in this setting for a longer period of time and, in turn, contaminate the surfaces or the medical tools. Thus, appropriate disinfection of these areas and devices are crucial for controlling and preventing further infection. In this study, we examined the effect of different concentrations of chlorine-containing disinfectants (500mg/L, 1000mg/L, and 2000mg/L) on the ICU environment. METHODS: This quasi-experimental study was based on a convenient sampling method. In this study, High-frequency objects were selected as subjects in ICU, with a total sample of 216.A hall including 6 beds was examined,selecting 4 high-frequency surfaces per bed unit:a bed gear, infusion system, bed end table, and monitor were disinfected with 500, 1000, and 2000 mg/L of chlorine (as Cl2), respectively.The surface dissection was performed at 21:00 o'clock daily, after which ATP fluorescence monitoring and bacterial count detection were performed. RESULTS: There was no significant difference in ATP bioluminescence (F = 2.03, P > 0.05) and bacterial counting (χ2 = 2.03, P > 0.05) when using different concentrations of chlorine-containing disinfectant in the ICU. Yet, compared with high concentration (2000mg/L), a low concentration disinfectant reduced the hospital cost. CONCLUSION: By reducing the concentration of ICU high-frequency contact table disinfectants, it is possible to reduce the risk of long-term contamination with chlorine-containing disinfectants and reduce the cost of using ICU chlorine-containing disinfectants.

Assessing causal associations between neurodegenerative diseases and neurological tumors with biological aging: a bidirectional Mendelian randomization study.

Background: Aging is a significant risk factor for many neurodegenerative diseases and neurological tumors. Previous studies indicate that the frailty index, facial aging, telomere length (TL), and epigenetic aging clock acceleration are commonly used biological aging proxy indicators. This study aims to comprehensively explore potential relationships between biological aging and neurodegenerative diseases and neurological tumors by integrating various biological aging proxy indicators, employing Mendelian randomization (MR) analysis. Methods: Two-sample bidirectional MR analyses were conducted using genome-wide association study (GWAS) data. Summary statistics for various neurodegenerative diseases and neurological tumors, along with biological aging proxy indicators, were obtained from extensive meta-analyses of GWAS. Genetic single-nucleotide polymorphisms (SNPs) associated with the exposures were used as instrumental variables, assessing causal relationships between three neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis), two benign neurological tumors (vestibular schwannoma and meningioma), one malignant neurological tumor (glioma), and four biological aging indicators (frailty index, facial aging, TL, and epigenetic aging clock acceleration). Sensitivity analyses were also performed. Results: Our analysis revealed that genetically predicted longer TL reduces the risk of Alzheimer's disease but increases the risk of vestibular schwannoma and glioma (All Glioma, GBM, non-GBM). In addition, there is a suggestive causal relationship between some diseases (PD and GBM) and DNA methylation GrimAge acceleration. Causal relationships between biological aging proxy indicators and other neurodegenerative diseases and neurological tumors were not observed. Conclusion: Building upon prior investigations into the causal relationships between telomeres and neurodegenerative diseases and neurological tumors, our study validates these findings using larger GWAS data and demonstrates, for the first time, that Parkinson's disease and GBM may promote epigenetic age acceleration. Our research provides new insights and evidence into the causal relationships between biological aging and the risk of neurodegenerative diseases and neurological tumors.

Prevalence and influence factors of occupational exposure to blood and body fluids in registered Chinese nurses: a national cross-sectional study.

BACKGROUND: Occupational exposure to blood and body fluids poses a threat to medical providers and to nurses especially. This harm is not only physical, but psychology as well and can ultimately impact patient safety. This study aims to understand the prevalence of occupational exposure to blood and body fluids among Chinese registered nurses and explores the factors that influence this exposure. METHODS: A cross-sectional online survey was conducted for 31 province-level divisions in China, using a self-created questionnaire entitled Status Survey on Occupational Exposure in Nurses. Descriptive statistics were used to describe both the demographic characteristics of the respondents and the characteristics of occupational exposure. Categorical variables were presented as frequencies and percentage, and the relationship between possible influential factors and the occurrence of occupational exposure was determined using binary logistic regression. RESULTS: Out of a total of 20,791 nurses analyzed, over half (52.1%) of them had experienced occupational exposure to blood or body fluids, but over 1/3 (34.6%) of them did not ever report their exposures to a supervisor/official. The top three causes of under-reporting were: the source patient failed to test positive for infectious pathogens (43.6%), perception of a burdensome reporting process (24.6%), and indifferent attitude towards being infected (16.9%). Nurses who worked over 8 hours per day had higher risks of exposure (OR 1.199, 95% CI 1.130 to 1.272, P < 0.001, respectively). The occupational exposure risk from providing 1-2 types of PPE is 1.947 times that of providing 9-10 types of PPE (OR 1.947, 95% CI 1.740 to 2.178, P < 0.001). Likewise, the occupational exposure risk of providing 1-2 types of safety-engineered injection devices is 1.275 times of that of providing 5-6 types (OR 1.275, 95% CI 1.179 to 1.379, P < 0.001). CONCLUSIONS: Occupational exposure to blood and body fluids in registered nurses is common, but the rate of under-reporting such exposure is high. Implementing engineered "sharp" injury prevention devices, following exposure prevention procedures, giving sufficient education and training to healthcare personnel on exposure prevention and control, and developing exposure reporting policies are all steps that can both reduce exposure and increase its reporting.

A single center analysis of first-line treatment in advanced KRAS mutant non-small cell lung cancer: real-world practice.

PURPOSE: For the first-line treatment of KRAS mutant non-small cell lung cancer (NSCLC) patients, immunotherapy or platinum-based chemotherapy are the main treatment method. Here, we investigated the clinical efficacy and prognosis those two regimens as first-line treatment in real-world practice. METHODS: KRAS mutant NSCLC patients received chemotherapy or immunotherapy as first-line treatment from September 2014 to March 2022 were enrolled. Clinical characteristics, treatment scheme, clinical curative effect and follow-up data of enrolled patients were collected for analysis. RESULTS: Fifty patients received immunotherapy and 115 patients received chemotherapy were enrolled. Patients who received immunotherapy (HR = 0.350, 95%CI 0.156-0.781, P = 0.010), or pemetrexed-based regimen (HR = 0.486, 95%CI 0.255-0.928, P = 0.029), or antiangiogenic therapy (HR = 0.355, 95%CI 0.159-0.790, P = 0.011) were at a low risk of disease progression. And patients received antiangiogenic therapy had lower risk of death than those not (HR = 0.333, 95%CI 0.120-0.926, P = 0.035). Subgroup analysis revealed the immunotherapy compared to chemotherapy alone had lower risk of disease progression (HR = 0.377, 95%CI 0.166-0.856, P = 0.020) in PD-L1 expression ≥1% subgroup. And in non-G12C KRAS subgroup, but not in G12C KRAS subgroup, patients who received antiangiogenic therapy had lower risk of disease progression (HR = 0.254, 95%CI 0.098-0.656, P = 0.005) and death than those not (HR = 0.197, 95%CI 0.056-0.692, P = 0.011). In terms of different chemotherapy regimen, platinum-paclitaxel combined with antiangiogenic therapy achieved the highest ORR and DCR (P < 0.05), while the platinum-pemetrexed combined with antiangiogenic therapy had the longest PFS and OS (P < 0.001). CONCLUSION: For the first-line treatment of KRAS mutant NSCLC patients, immunotherapy, antiangiogenic therapy, and pemetrexed-based regimen could obtain more benefits. Subgroup analysis revealed the benefits of immunotherapy compared to chemotherapy were applicable in PD-L1 expression≥1% subgroup, and antiangiogenic therapy could benefit non-G12C KRAS subgroup, but not G12C KRAS subgroup. In terms of different chemotherapy regimen, platinum-pemetrexed combined with antiangiogenic therapy may be the preferred chemotherapy regimen.

Rituximab combined with GDP regimen can effectively improve the efficacy and immune function of non-Hodgkin lymphoma.

OBJECTIVE: To evaluate the efficacy of rituximab combined with GDP regimen (gemcitabine + cisplatin + dexamethasone) in the treatment of non-Hodgkin lymphoma and its impact on the immune function of patients. METHODS: Clinical data of 88 patients with non-Hodgkin lymphoma (NHL) treated in Affiliated Hospital of Yan'an University from February 2017 to February 2019 were analyzed retrospectively. Among them, 40 patients treated with the second-line regimen (gemcitabine + cisplatin + dexamethasone) were served as the control group, and 48 patients received additional rituximab were as the observation group. The therapeutic effect, incidence of adverse reactions, levels of complement (C3, C4) and immunoglobulin [immunoglobulin (Ig) G, IgM, IgA] before and after treatment were compared between the two groups. Cox regression analysis was used to analyze the prognostic factors of patients. RESULTS: The total response rate of patients in observation group was higher than that in the control group (P<0.05). There was no significant difference in the incidence of adverse reactions (hair loss, nausea and vomiting, thrombocytopenia, anemia and bone marrow suppression) between the two groups (P>0.05). After treatment, the levels of C3 and C4 in both groups were lower than those before treatment, and the decrease in observation group were more evident than that in control group (P<0.05). No notable fluctuation was observed in the levels of IgG, IgM and IgA in both groups between before and after treatment (P>0.05). Cox regression analysis found that Ann Arbor stage and pretreatment disease status were the factors affecting the prognosis of patients. CONCLUSION: Rituximab combined with GDP regimen has a significant effect on the treatment of non-Hodgkin lymphoma, and Ann Arbor stage and pretreatment disease state are prognostic factors for patients with NHL.

[Mechanisms of electroacupuncture at "Zusanli"(ST36) in delaying colon "inflammation-cancer transformation"].

OBJECTIVE: To investigate the mechanism of electroacupuncture (EA) "Zusanli" (ST36) in delaying colon "inflammation-cancer transformation" in mice by anti-inflammatory. METHODS: C57BL/6J mice were randomly divided into normal, model and EA groups, with 12 mice in each group. The mouse model of colorectal cancer (CRC) was established by intrape-ritoneal injection of azomethane (AOM) and feeding dextran sodium sulfate (DSS). At the beginning of the 2nd cycle, EA was applied to bilateral ST36 for 30 min once every other day for 12 times. The number of colon tumors in each group was observed, and the weight and length of colon were recorded. The contents of interleukin (IL)-1ß, IL-6, IL-17A, IL-23, tumor necrosis factor (TNF)-α and CXC chemokine ligand 1 (CXCL1) of serum and colon tissue were detected by MSD multifactorial assay.The apoptosis of local cells in colon tumor was observed by TUNEL staining. Cell proliferation in colon tumor was observed by immunohistochemistry. RESULTS: Compared with the normal group, the colon length was significantly shortened (P<0.05) and the colon mass was significantly increased (P<0.001) in the model group, the contents of IL-1ß, IL-6, TNF-α, IL-17A and CXCL1 of serum and colon tissue were significantly increased (P<0.05, P<0.01, P<0.001), and the content of IL-23 was increased in colon tissue (P<0.05) in the model group. Compared with the model group, the colon mass was decreased (P<0.05) and the contents of IL-1ß, IL-6, TNF-α and IL-17A in serum were decreased (P<0.05), while the contents of IL-17A, CXCL1 and IL-23 in colon tissue were decreased (P<0.05) in the EA group, the percentage of local apoptotic cells in the EA group was increased (P<0.001), the percentage of PCNA positive cells was decreased (P<0.001), the number of tumors and the tumor volume were significantly decreased (P<0.01, P<0.05). The contents of IL-6, TNF-α, IL-17A and IL-23 in serum of CRC mice were positively correlated with tumor burden (P<0.05).The contents of IL-1ß, TNF-α, CXCL1 and IL-23 in colon tissue of CRC mice were positively correlated with tumor burden (P<0.05). CONCLUSION: Electroacupuncture at ST36 can inhibit the inflammatory response of AOM/DSS inflammatory associated CRC mice and delay the "inflammation-cancer transformation" of colon.