Effect of a self-developed fixation device on preventing endotracheal intubation-related pressure injury: a randomised controlled trial.

OBJECTIVE: To evaluate the effects of our self-developed endotracheal tube fixation device in mechanically ventilated patients. METHODS: In a dual-centre randomised controlled trial, patients who were expected to require mechanical ventilation for over 48 h were assigned to the observation group (using self-developed device) or the control group (using the traditional device). The primary endpoint was the incidence of endotracheal intubation-related pressure injury (EIRPI). RESULTS: Fifty-one patients in the observation group and 54 patients in the control group were analysed. The incidence of EIRPI was 7.8% in the observation group and 33.3% in the control group (p = 0.001). Lip pressure injury (PI) occurred in 0 versus 14 (25.9%) patients in the observation versus control groups (p < 0.001). Both oral-mucosal and facial PIs were similar between the two groups. CONCLUSIONS: The use of the novel device reduced the incidence of EIRPI, especially lip PI. Trial registration Chinese Clinical Trial Registry ChiCTR2300078132. Registered on 29 November 2023.

Hypermethylation of PPARG-encoding gene promoter mediates fine particulate matter-induced pulmonary fibrosis by regulating the HMGB1/NLRP3 axis.

The inflammatory response induced by fine particulate matter (PM2.5), a common class of air pollutants, is an important trigger for the development of pulmonary fibrosis. However, the specific mechanisms responsible for this phenomenon are yet to be fully understood. To investigate the mechanisms behind the onset and progression of lung fibrosis owing to PM2.5 exposure, both rats and human bronchial epithelial cells were subjected to varying concentrations of PM2.5. The involvement of the PPARG/HMGB1/NLRP3 signaling pathway in developing lung fibrosis caused by PM2.5 was validated through the utilization of a PPARG agonist (rosiglitazone), a PPARG inhibitor (GW9662), and an HMGB1 inhibitor (glycyrrhizin). These outcomes highlighted the downregulation of PPARG expression and activation of the HMGB1/NLRP3 signaling pathway triggered by PM2.5, thereby eliciting inflammatory responses and promoting pulmonary fibrosis. Additionally, PM2.5 exposure-induced DNA hypermethylation of PPARG-encoding gene promoter downregulated PPARG expression. Moreover, the DNA methyltransferase inhibitor 5-azacytidine mitigated the hypermethylation of the PPARG-encoding gene promoter triggered by PM2.5. In conclusion, the HMGB1/NLRP3 signaling pathway was activated in pulmonary fibrosis triggered by PM2.5 through the hypermethylation of the PPARG-encoding gene promoter.

Genetic predisposition of six well-defined polymorphisms in HMGB1/RAGE pathway to breast cancer in a large Han Chinese population.

Breast cancer constitutes an enormous burden in China. A strong familial clustering of breast cancer suggests a genetic component in its carcinogenesis. To examine the genetic predisposition of high mobility group box-1/receptor for advanced glycation end products (HMGB1/RAGE) pathway to breast cancer, we genotyped six well-defined polymorphisms in this pathway among 524 breast cancer patients and 518 cancer-free controls from Heilongjiang province, China. There were no deviations from Hardy-Weinberg equilibrium for all polymorphisms. In single-locus analysis, the frequency of rs1800624 polymorphism mutant A allele in RAGE gene was significantly higher in patients than in controls (24.52% versus 19.50%, P = 0.006), with the carriers of rs1800624-A allele being 1.51 times more likely to develop breast cancer relative to those with rs1800624-GG genotype after adjustment (95% confidence interval or CI: 1.17-1.94, P = 0.001). In HMGB1 gene, haplotype analysis did not reveal any significance, while in RAGE gene, haplotypes C-T-A and C-A-G (alleles in order of rs1800625, rs18006024, rs2070600) were significantly associated with an increased risk of breast cancer (adjusted OR = 2.72 and 10.35; 95% CI: 1.20-6.18 and 1.58-67.80; P = 0.017 and 0.015 respectively). In further genetic score analysis, per unit and quartile increments of unfavourable alleles were significantly associated with an increased risk of breast cancer after adjustment (odds ratio or OR = 1.20 and 1.26; 95% CI: 1.09-1.32 and 1.12-1.42; P < 0.001 and <0.001 respectively). Our findings altogether demonstrate a significant association between RAGE gene rs1800624 polymorphism and breast cancer risk, and more importantly a cumulative impact of multiple risk associated polymorphisms in HMGB1/RAGE pathway on breast carcinogenesis.

[Characterization of thermal denaturation process of proteinase K by spectrometry].

The effect of different temperatures on the activity and conformational changes of proteinase K was studied. Methods Proteinase K was treated with different temperatures, then denatured natural substrate casein was used to assay enzyme activity, steady-state and time-resolved fluorescence spectroscopy was used to study tertiary structure, and circular dichroism was used to study secondary structure. Results show with the temperature rising from 25 to 65 degrees C, the enzyme activity and half-life of proteinase K dropped, maximum emission wavelength red shifted from 335 to 354 nm with fluorescence intensity decreasing. Synchronous fluorescence intensity of tryptophan residues decreased and that of tyrosine residues increased. Fluorescence lifetime of tryptophan residues reduced from 4. 427 1 to 4. 032 4 ns and the fraction of alpha-helix dropped. It was concluded that it is simple and accurate to use steady-state/time-resolved fluorescence spectroscopy and circular dichroism to investigate thermal stability of proteinase K. Thermal denaturation of proteinase K followed a three-state process. Fluorescence intensity of proteinase K was affected by fluorescence resonance energy transfer from tyrosine to tryptophan residues. The alpha-helix was the main structure to maintain conformational stability of enzyme active site of proteinase K.

Association between inflammatory bowel disease and risk of stroke: a systematic review and meta-analysis of cohort studies.

Background/objectives: Recently, four meta-analyses have explored the association between inflammatory bowel disease (IBD) and the risk of stroke. These studies have demonstrated that people with IBD may be at an increased risk of stroke. However, some limitations such as high heterogeneity and the lack of uniformity in the types of research, especially the reuse of some sample sizes, cannot be neglected. These factors reduce the credibility of their research conclusions. Therefore, we conducted a meta-analysis to explore this possible association. Methods: PubMed, Embase, and Web of Science were searched from inception to 30 June 2023. A random effects model with the generic inverse variance method was used in this meta-analysis. The Review Manager software was used to obtain all relative risks (RRs) and their 95% confidence intervals (CIs). Publication bias was tested, and sensitivity and subgroup analyses were conducted to explore possible heterogeneities. Results: This meta-analysis included 12 cohort studies (involving 4,495,055 individuals). Meta-analysis of these data has shown that IBD was associated with an increased risk of stroke (RR = 1.19, 95%CI:1.14-1.24, p < 0.00001). Our results were stable and robust in subgroup and sensitivity analyses. Conclusions: Our results suggest that IBD is associated with an increased risk of stroke. To reduce the incidence of stroke, patients with IBD are encouraged to undergo stroke risk assessments, especially for young female patients; assessing the risk of ischemic stroke is of particular importance. Prospective studies considering stroke subtypes, IBD severity and treatments, regions, and other confounding factors are needed to further explore the nature of each association. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022373656.

Novel lncRNA PSMG3­AS1 functions as a miR­143­3p sponge to increase the proliferation and migration of breast cancer cells.

Long non­coding RNAs (lncRNAs) are considered to be important regulators in breast cancer. In the present study, the potential mechanisms and functional roles of lncRNA PSMG3­antisense (AS)1 were investigated in vivo and in vitro. The relative expression levels of lncRNA PSMG3­AS1 and microRNA (miR)­143­3p were determined using reverse­transcription quantitative PCR. The protein expression levels of collagen type 1 alpha 1 (COL1A1) and proliferating cell nuclear antigen (PCNA) were obtained using western blot analysis. Bioinformatics analysis was used to identify the relationship between PSMG3­AS1, miR­143­3p and COL1A1. Colony forming and Cell Counting Kit­8 assays were used to detect cell proliferation. Transwell and wound­healing assays were used to determine cell migration. The results of the present study demonstrated that PSMG3­AS1 expression was increased in breast cancer tumor tissues and cell lines, and that of miR­143­3p was decreased. Knockdown of PSMG3­AS1 increased the level of miR­143­3p expression, which led to the mitigation of proliferation and migration capacity in breast carcinoma cells. Additionally, PSMG3­AS1 knockdown was demonstrated to reduce the mRNA and protein expression levels of COL1A1. miR­143­3p mimic transfection reduced proliferation and migration in MDA­MB­231 and MCF­7 cell lines. Furthermore, miR­143­3p inhibition significantly increased the proliferation and migration of breast cancer cells compared with the negative control group. The mRNA and protein expression levels of PCNA were reduced in the MCF­7 cell line when transfected with miR­143­3p mimics and si­PSMG3­AS1. However, PCNA expression was increased in cells transfected with a miR­143­3p inhibitor. In conclusion, the results of the present study identified a novel lncRNA PSMG3­AS1, which serves as a sponge for miR­143­3p in the pathogenesis of breast cancer. PSMG3­AS1 may be used as a potential therapeutic target gene in breast cancer treatment.

Correlations of breast cancer FHIT gene with the incidence and prognosis of breast cancer.

PURPOSE: The study aimed to investigate the expression level of fragile histidine triad (FHIT) in breast cancer and analyze its prognostic value. METHODS: 148 patients admitted and definitely diagnosed with breast cancer in Daqing Long Nan Hospital from January 2011 to January 2013 were collected. Breast cancer, cancer-adjacent and normal tissues of the patients were taken and immunohistochemically stained, and the relationship between FHIT and p16 expressions were analyzed at the gene and protein levels. In addition, clinical data of patients were collected, and analyzed if there was a correlation between FHIT and p16 expressions. RESULTS: FHIT and p16 were strongly positive in cancer-adjacent tissues and normal tissues but weakly positive in breast cancer tissues, with statistically significant differences in FHIT and p16 expressions (p<0.05). FHIT expression was positively correlated with p16 expression in breast cancer tissues (Spearman's correlation coefficient r=0.352, p=0.026). There were correlations of FHIT with TNM staging of breast cancer, grade of differentiation, lymph node metastasis and formation of portal vein tumor thrombi (p<0.05 in all comparisons). P16 was correlated with tumor size and grade of differentiation (p<0.05 in all comparisons). Expressions of both FHIT and p16 genes and proteins in breast cancer tissues were remarkably lower than those in cancer-adjacent and normal tissues (p<0.05 in all comparisons). Log-rank analysis showed that the 5-year overall survival of patients with FHIT+p16+expressions was significantly longer than that of patients with other phenotypes of expressions (p<0.0001). CONCLUSION: The tumor suppressor gene FHIT is lowly expressed in breast cancer tissues and positively associated with the expression of the multi-tumor suppressor gene p16. The 5-year overall prognosis of patients with FHIT+p16+ expressions was better and can be used as one of the prognostic indicators for breast cancer patients.

Long non-coding RNA SNHG1 promotes Cyclin D1-mediated proliferation in pancreatic cancer by acting as a ceRNA of miR-195.

Pancreatic cancer (PCa) is one of the most fatal cancers worldwide. Recently, many studies have confirmed that long non-coding RNAs (lncRNAs) play crucial roles in the development of many human cancers, including PCa. The purpose of the present study was to investigate the biological role and underlying mechanisms of lncRNA small nucleolar RNA host gene 1 (SNHG1) in PCa progression. The results demonstrated that the expression levels of SNHG1 were increased in PCa cell lines and human tissue samples. High SNHG1 expression was notably correlated with adverse characteristics and poor survival of PCa patients. Knockdown of SNHG1 suppressed PCa cell proliferation in vitro and PCa tumor growth in vivo, and these effects might be associated with the induction of cell cycle arrest. We further confirmed that, in PCa cells, SNHG1 can negatively regulate miR-195 expression by acting as a ceRNA, and Cyclin D1 is a direct target of miR-195. Overexpression of miR-195 abrogated the oncogenic role of SNHG1 in PCa cells. Collectively, our results identified SNHG1 as a novel oncogenic lncRNA in PCa, and indicated that SNHG1/miR-195/Cyclin D1 axis might be a potential therapeutic target for PCa patients.

Release test of alliin/alliinase double-layer tablet by HPLC-Allicin determination.

A simple, precise and accurate method was developed and validated for the determination of allicin release from alliin/alliinase double-layer tablets. According to Appendix XC II of Chinese Pharmacopoeia 2010 edition Volume II, a small glass-method was adopted at the rotational speed of 100 r/min using 100 mL phosphate buffer (pH 6.8) as release medium. The release amount was determined by HPLC with a C18 column (250 mm×4.6 mm, 5 µm) using the mobile phase consisting of methanol -0.4% carboxylic acid (65:35) at a flow rate of 1 mL/min and UV detection at 242 nm. The current method demonstrates good linearity over the range 4.052-405.2 µg/mL (r2=0.9999) with an average recovery of 105.5%(RSD=1.25%). The accumulative release of alliin/alliinase double-layer tablets had good homogeneity for within- and between-batches. The method established is simple, accurate and repeatable for the determination of allicin release from alliin/alliinase double-layer tablets.