NEDD4L mediates ITGB4 ubiquitination and degradation to suppress esophageal carcinoma progression.

The ubiquitination-mediated protein degradation exerts a vital role in the progression of multiple tumors. NEDD4L, which belongs to the E3 ubiquitin ligase NEDD4 family, is related to tumor genesis, metastasis and drug resistance. However, the anti-tumor role of NEDD4L in esophageal carcinoma, and the potential specific recognition substrate remain unclear. Based on public esophageal carcinoma database and clinical sample data, it was discovered in this study that the expression of NEDD4L in esophageal carcinoma was apparently lower than that in atypical hyperplastic esophageal tissue and esophageal squamous epithelium. Besides, patients with high expression of NEDD4L in esophageal carcinoma tissue had longer progression-free survival than those with low expression. Experiments in vivo and in vitro also verified that NEDD4L suppressed the growth and metastasis of esophageal carcinoma. Based on co-immunoprecipitation and proteome analysis, the NEDD4L ubiquitination-degraded protein ITGB4 was obtained. In terms of the mechanism, the HECT domain of NEDD4L specifically bound to the Galx-ß domain of ITGB4, which modified the K915 site of ITGB4 in an ubiquitination manner, and promoted the ubiquitination degradation of ITGB4, thus suppressing the malignant phenotype of esophageal carcinoma.

The potential health effects associated with electronic-cigarette.

A good old gateway theory that electronic-cigarettes (e-cigarettes) are widely recognized as safer tobacco substitutes. In actuality, demographics also show that vaping cannibalizes smoking, the best explanation of the data is the "common liability". However, the utilization of e-cigarette products remains a controversial topic at present. Currently, there has been a widespread and substantial growth in e-cigarette use worldwide owing to their endless new flavors and customizable characteristics. Furthermore, e-cigarette has grown widespread among smokers as well as non-smokers, including adolescents and young adults. And some studies have shown that e-cigarette users are at greater risk to start using combustible cigarettes while e-cigarettes use was also observed the potential benefits to people who want to quit smoking or not. Although it is true that e-cigarettes generally contain fewer toxic substances than combustible cigarettes, this does not mean that the chemical composition in e-cigarettes aerosols poses absolutely no risks. While concerns about toxic substances in e-cigarettes and their widespread use in the population are reasonable, it is also crucial to consider that e-cigarettes have been associated with the potential for promoting smoking cessation and the clinically relevant improvements in users with smoking-related pathologies. Meanwhile, there is still short of understanding of the health impacts associated with e-cigarette use. Therefore, in this review, we discussed the health impacts of e-cigarette exposure on oral, nasal, pulmonary, cardiovascular systems and brain. We aspire for this review to change people's previous perceptions of e-cigarettes and provide them with a more balanced perspective. Additionally, we suggest appropriate adjustments on regulation and policy for e-cigarette to gain greater public health benefits.

Multi-omics and multi-stages integration identified a novel variant associated with silicosis risk.

Assessing the association between candidate single-nucleotide polymorphisms (SNPs) identified by multi-omics approaches and susceptibility to silicosis. RNA-seq analysis was performed to screen the differentially expressed mRNAs in the fibrotic lung tissues of mice exposed to silica particles. Following this, we integrated the SNPs located in the above human homologenes with the silicosis-related genome-wide association study (GWAS) data to select the candidate SNPs. Then, expression quantitative trait locus (eQTL)-SNPs were identified by the GTEx database. Next, we validated the associations between the functional eQTL-SNPs and silicosis susceptibility by additional case-control study. And the contribution of the identified SNP and its host gene in the fibrosis process was further validated by functional experiments. A total of 12 eQTL-SNPs were identified in the screening stage. The results of the validation stage suggested that the variant T allele of rs419540 located in IL12RB1 significantly increased the risk of developing silicosis [additive model: odds ratio (OR) = 1.78, 95% confidence interval (CI) 1.11-2.85, P = 0.017]. Furthermore, the combination of GWAS and the results of validation stage also indicated that the variant T allele of rs419540 in IL12RB1 was associated with increased silicosis risk (additive model: OR = 2.07, 95% CI 1.38-3.12, P < 0.001). Additionally, after knockdown or overexpression of IL12RB1, the levels of pro-inflammatory factors, such as IL-12, IFN-γ, and other pro-inflammatory factors, were correspondingly decreased or increased. The novel eQTL-SNP, rs419540, might increase the risk of silicosis by modulating the expression levels of IL12RB1.

Integration of apaQTL and eQTL analysis reveals novel SNPs associated with occupational pulmonary fibrosis risk.

To explore the association between apaQTL/eQTL-SNPs and the susceptibility to silicosis. A silicosis-related GWAS was initially conducted to screen for single nucleotide polymorphisms (SNPs) associated with the risk of silicosis. Candidate SNPs with apaQTL and eQTL functions were then obtained from the 3'aQTL-atlas and GTEx databases. Subsequently, additional case-control studies were performed to validate the relationship between the candidate apaQTL/eQTL-SNPs and the risk of silicosis. Finally, experiments were conducted to illustrate APA events occurring at different alleles of the identified apaQTL/eQTL-SNPs. The combined results of the GWAS and iMLDR validations indicate that the variant T allele of the rs2974341 located on SMIM19 (additive model: OR = 0.66, the 95% CI = 0.53-0.84, P = 0.001) and the variant T allele of the rs2390488 located on TMTC4 (additive model: OR = 0.72, 95% CI = 0.57-0.90, P = 0.005) were significantly associated with decreased risk of developing silicosis susceptibility. Furthermore, 3'RACE experiments verified the presence of two poly (A) sites (proximal and distal) in SMIM19, rs2974341 may remotely regulate the binding between miRNA-3646 and SMIM19 with its high LD locus rs2974353 to affect the expression level of SMIM19. The rs2974341 variant T allele may contribute to the generation of the shorter 3'UTR transcript of SMIM19 and affect the binding of miRNA-3646 to the target gene SMIM19. The apaQTL/eQTL-SNPs may provide new perspectives for evaluating the regulatory function of SNPs in the development of silicosis.

Fluctuations in Detection Indicators and Their Significance for the Diagnosis of Early Pressure Injury in Rat Models.

PURPOSE: The aim of this study was to identify the most meaningful diagnostic indicator for distinguishing blanchable erythema (BE) and stage 1 pressure injury (early PI) in an in vivo (rat) model. DESIGN: A prospective case-control design was used to complete a horizontal and vertical comparison of detection indicators during the process of fading of BE or the deterioration of early PI into ulcer in rat models. MATERIALS AND SETTING: The sample comprised 5 hairless rats with 20 injuries, of which 10 were BE and the other 10 were early PI. Data were collected at Nagano College of Nursing in 2020 in Nagano, Japan. METHODS: The BE and PI rat models were established by subjecting the dorsal skin of a hairless rat to compression between 2 neodymium magnets for 45 minutes and 3.45 hours, respectively. The affected skin was observed based on the following: (1) photography, (2) hardness, (3) temperature, (4) moisture, and (5) spectrophotometric (a* value and ultraviolet [UV] reflectance) measurements. All measurements of BE were performed at the beginning to 60 minutes after decompression, and those for early PI were performed until 48 hours after decompression. RESULTS: Multiple BE factors, such as the degree of erythema (macroscopy and a* value), hardness, temperature, and moisture, were found to have unstable fluctuations. Only UV reflectance gradually decreased from 6 hours and decreased significantly at 48 hours after decompression (P = .001 vs 1 hour). In contrast to early PI, erythema in BE obviously faded within 10 minutes. CONCLUSIONS: Study findings indicate that a continuous decrease in UV reflectance can reflect the worsening of hemorrhage in early (stage 1) PI. In contrast, other indicators including photography, skin hardness, temperature, and moisture fluctuated and did not prove predictive for PI progression. The obvious fading of erythema in BE a short time after decompression can be used for clinical observations.

HKDC1 upregulation promotes glycolysis and disease progression, and confers chemoresistance onto gastric cancer.

There is increasing evidence that hexokinase is involved in cell proliferation and migration. However, the function of the hexokinase domain containing protein-1 (HKDC1) in gastric cancer (GC) remains unclear. Immunohistochemistry analysis and big data mining were used to evaluate the correlation between HKDC1 expression and clinical features in GC. In addition, the biological function and molecular mechanism of HKDC1 in GC were studied by in vitro and in vivo assays. Our study indicated that HKDC1 expression was upregulated in GC tissues compared with adjacent nontumor tissues. High expression of HKDC1 was associated with worse prognosis. Functional experiments demonstrated that HKDC1 upregulation promoted glycolysis, cell proliferation, and tumorigenesis. In addition, HKDC1 could enhance GC invasion and metastasis by inducing epithelial-mesenchymal transition (EMT). Abrogation of HKDC1 could effectively attenuate its oncogenic and metastatic function. Moreover, HKDC1 promoted GC proliferation and migration in vivo. HKDC1 overexpression conferred chemoresistance to cisplatin, oxaliplatin, and 5-fluorouracil (5-Fu) onto GC cells. Furthermore, nuclear factor kappa-B (NF-κB) inhibitor PS-341 could attenuate tumorigenesis, metastasis, and drug resistance ability induced by HKDC1 overexpression in GC cells. Our results highlight a critical role of HKDC1 in promoting glycolysis, tumorigenesis, and EMT of GC cells via activating the NF-κB pathway. In addition, HKDC1-mediated drug resistance was associated with DNA damage repair, which further activated NF-κB signaling. HKDC1 upregulation may be used as a potential indicator for choosing an effective chemotherapy regimen for GC patients undergoing chemotherapy.

Developing a Machine Learning Risk-adjustment Method for Hospitalizations and Emergency Department Visits of Nursing Home Residents With Dementia.

BACKGROUND: Long-stay nursing home (NH) residents with Alzheimer disease and related dementias (ADRD) are at high risk of hospital transfers. Machine learning might improve risk-adjustment methods for NHs. OBJECTIVES: The objective of this study was to develop and compare NH risk-adjusted rates of hospitalizations and emergency department (ED) visits among long-stay residents with ADRD using Extreme Gradient Boosting (XGBoost) and logistic regression. RESEARCH DESIGN: Secondary analysis of national Medicare claims and NH assessment data in 2012 Q3. Data were equally split into the training and test sets. Both XGBoost and logistic regression predicted any hospitalization and ED visit using 58 predictors. NH-level risk-adjusted rates from XGBoost and logistic regression were constructed and compared. Multivariate regressions examined NH and market factors associated with rates of hospitalization and ED visits. SUBJECTS: Long-stay Medicare residents with ADRD (N=413,557) from 14,057 NHs. RESULTS: A total of 8.1% and 8.9% residents experienced any hospitalization and ED visit in a quarter, respectively. XGBoost slightly outperformed logistic regression in area under the curve (0.88 vs. 0.86 for hospitalization; 0.85 vs. 0.83 for ED visit). NH-level risk-adjusted rates from XGBoost were slightly lower than logistic regression (hospitalization=8.3% and 8.4%; ED=8.9% and 9.0%, respectively), but were highly correlated. Facility and market factors associated with the XGBoost and logistic regression-adjusted hospitalization and ED rates were similar. NHs serving more residents with ADRD and having a higher registered nurse-to-total nursing staff ratio had lower rates. CONCLUSIONS: XGBoost and logistic regression provide comparable estimates of risk-adjusted hospitalization and ED rates.

The relative abundance of fecal bacterial species belonging to the Firmicutes and Bacteroidetes phyla is related to plasma levels of bile acids in young adults.

BACKGROUND: Gut bacteria play a crucial role in the metabolism of bile acids (BA). Whether an association exists between the fecal microbiota composition and circulating BA levels in humans is poorly understood. Here, we investigated the relationship between fecal microbiota diversity and composition with plasma levels of BA in young adults. METHODS: Fecal microbiota diversity/composition was analyzed with 16S rRNA sequencing in 80 young adults (74% women; 21.9 ± 2.2 years old). Plasma levels of BA were measured using liquid chromatography-tandem mass spectrometry. PERMANOVA and Spearman correlation analyses were used to investigate the association between fecal microbiota parameters and plasma levels of BA. RESULTS: Fecal microbiota beta (P = 0.025) and alpha diversity indexes of evenness (rho = 0.237, P = 0.033), Shannon (rho = 0.313, P = 0.004), and inverse Simpson (rho = 0.283, P = 0.010) were positively associated with plasma levels of the secondary BA glycolithocholic acid (GLCA). The relative abundance of genera belonging to the Firmicutes and Bacteroidetes phyla was positively correlated with plasma levels of GLCA (all rho ≥ 0.225, P ≤ 0.049). However, the relative abundance of species from Firmicutes and Bacteroidetes phyla were negatively correlated with plasma levels of primary and secondary BA (all rho ≤ - 0.220, P ≤ 0.045), except for the relative abundance of Bacteroides vulgatus, Alistipes onderdonkii, and Bacteroides xylanisolvens species (Bacteroidetes phylum) that were positively correlated with the plasma levels of GLCA. CONCLUSIONS: The relative abundance of specific fecal bacteria species is associated with plasma levels of BA in young adults. However, further investigations are required to validate whether the composition of the gut microbiota can regulate the plasma concentrations of BA in humans.

Comparative proteomics study of exosomes in Vibrio harveyi and Vibrio anguillarum.

Exosomes are a class of extracellular vesicles released by bacteria and contain diverse biomolecules. In this study, we isolated exosomes from Vibrio harveyi and Vibrio anguillarum, which are both serious pathogens in mariculture, using a supercentrifugation method, and the proteins in the exosomes of these two vibrios were analyzed by LC-MS/MS proteomics. Exosome proteins released by V. harveyi and V. anguillarum were different; they not only contained virulence factors (such as lipase and phospholipase in V. harveyi, metalloprotease and hemolysin in V. anguillarum), but also participated in the important life activities of bacteria (such as fatty acid biosynthesis, biosynthesis of antibiotics, carbon metabolism). Subsequently, to verify whether the exosomes participated in bacterial toxicity, after Ruditapes philippinarum was challenged with V. harveyi and V. anguillarum, the corresponding genes of virulence factors from exosomes screened by proteomics were tested by quantitative real-time PCR. All the genes detected were upregulated which suggested that exosomes were involved in vibrio toxicity. The results could provide an effective proteome database for decoding the pathogenic mechanism of vibrios from the exosome perspective.

A prospective cohort study of methotrexate plus idarubicin in newly diagnosed primary CNS lymphoma.

PURPOSE: High-dose methotrexate (HD-MTX)-based chemotherapy regimen is the first-line option for primary central nervous system lymphoma (PCNSL). This prospective cohort study aimed to evaluate the efficacy and adverse effects of HD-MTX plus idarubicin (IDA) in patients with newly diagnosed immunocompetent PCNSL. METHODS: We recruited newly diagnosed PCNSL patients from January 2017 to August 2020. Patients were assigned into two groups: HD-MTX monotherapy and HD-MTX plus IDA (HD-MTX/IDA). In the HD-MTX monotherapy group, patients were treated with MTX 8 g/m2 alone on day 1, while the HD-MTX/IDA group received MTX 8 g/m2 on day 1 and IDA 10 mg/m2 on day 2. Treatments were repeated every 3 weeks for 8 cycles except for progression and/or unacceptable toxicity. RESULTS: We recruited 61 PCNSL patients, including 36 in the HD-MTX and 25 in the HD-MTX/IDA group. The CR rate was 68% in the HD-MTX/IDA group and 72.22% of patients in the HD-MTX monotherapy group (p = 0.7221), while the overall response rate was 72% vs. 77.78% (p = 0.6063). Median PFS in HD-MTX/IDA group and HD-MTX monotherapy group were 15.6 months and 18.5 months, respectively (p = 0.6374). Median OS was not reached in both groups. There were no significant differences in adverse effects between the two groups. CONCLUSIONS: The combination of IDA with HD-MTX showed no obvious therapeutic advantage over HD-MTX monotherapy in newly diagnosed patients with PCNSL. HD-MTX dose of 8 g/m2 monotherapy can still provide better therapeutic benefits in patients with acceptable adverse effects. Future studies could explore HD-MTX in combination with other chemotherapeutic agents in the first-line treatment of PCNSL.

[Analysis and Reflection on Drafting Units of Medical Device Industry Standards in China].

Standard drafting is an important part in the process of standard formulation and revision. By analyzing the status of the medical device industry standards drafting, thoughts and suggestions were proposed to further promote all relevant parties to actively participate in the standard drafting, effectively improve the quality of the standards, strengthen the technical support and promote the high-quality development of the industry. The statistical data of the participation of social organizations in the drafting and as the first unit drafting medical devices standards from 2017 to 2021 was researched, and the problems in the drafting of standards at this stage were analyzed. Based on the research and analyses, some thoughts and suggestions were proposed to strengthen the management of standard drafting units and promote the participation of all relevant parties in standard drafting. It is necessary to expand and enhance social participation in standard drafting further by innovating incentives, refining and strengthening normative requirements, and creating a positive social atmosphere.

Evaluating the association of frailty with communication about aging-related concerns between older patients with advanced cancer and their oncologists.

BACKGROUND: A geriatric assessment (GA) intervention improves communication about aging-related concerns, but its effect on communication in patients with various levels of frailty is unknown. METHODS: This was a secondary analysis of a nationwide trial of patients aged ≥70 years with incurable cancer and impairment on 1 or more GA domains (ClinicalTrials.gov Identifier NCT02107443; principal investigator Supriya G. Mohile). Practice sites were randomized to either the GA-intervention or usual care. Frailty was assessed with a deficit accumulation index (range, 0-1), and patients were stratified as robust (0 to <0.2), prefrail (0.2 to <0.35), or frail (≥0.35). The clinic visit after the GA-intervention was audio-recorded, transcribed, and coded to evaluate the number and quality of conversations about aging-related concerns. Linear mixed models examined differences in the number and quality of conversations within and between arms. All P values were 2-sided. RESULTS: Patients (n = 541) were classified as robust (27%), prefrail (42%), or frail (31%). In the usual care arm, frail patients (vs robust ones) engaged in more aging-related conversations (adjusted mean difference, 1.73; 95% confidence interval [CI], 0.59-2.87), conversations of higher quality (difference, 1.12; 95% CI, 0.24-2.0), and more discussions about evidence-based recommendations (difference, 0.71; 95% CI, 0.04-1.38; all P values ≤ .01). Similarly, in the GA intervention arm, frail patients (vs robust ones) engaged in more aging-related conversations (difference, 2.49; 95% CI, 1.51-3.47), conversations of higher quality (difference, 1.31; 95% CI, 0.56-2.06), and more discussions about evidence-based recommendations (difference, 0.87; 95% CI, 0.32-1.42; all P values ≤ .01). Furthermore, the GA-intervention significantly improved the number and quality of conversations in all patients: robust, prefrail, and frail (all P values ≤ .01). CONCLUSIONS: Patients with higher degrees of frailty and those exposed to the GA-intervention had more and higher quality conversations about aging-related concerns with oncologists. LAY SUMMARY: A geriatric assessment (GA) intervention improves communication about aging-related concerns, but its effect on communication in patients with various levels of frailty is unknown. This study conducted a secondary analysis of a nationwide trial of patients aged ≥70 years with incurable cancer and 1 or more GA domain impairments. Patients were stratified as robust, prefrail, or frail. The number and quality of conversations about aging-related concerns that occurred during the clinic visit after the GA-intervention were determined. Patients with higher degrees of frailty and those in the GA intervention arm had more and higher quality conversations about aging-related concerns with oncologists.

Evaluation of geriatric assessment and management on the toxic effects of cancer treatment (GAP70+): a cluster-randomised study.

BACKGROUND: Older adults with advanced cancer are at a high risk for treatment toxic effects. Geriatric assessment evaluates ageing-related domains and guides management. We examined whether a geriatric assessment intervention can reduce serious toxic effects in older patients with advanced cancer who are receiving high risk treatment (eg, chemotherapy). METHODS: In this cluster-randomised trial, we enrolled patients aged 70 years and older with incurable solid tumours or lymphoma and at least one impaired geriatric assessment domain who were starting a new treatment regimen. 40 community oncology practice clusters across the USA were randomly assigned (1:1) to the intervention (oncologists received a tailored geriatric assessment summary and management recommendations) or usual care (no geriatric assessment summary or management recommendations were provided to oncologists) by means of a computer-generated randomisation table. The primary outcome was the proportion of patients who had any grade 3-5 toxic effect (based on National Cancer Institute Common Terminology Criteria for Adverse Events version 4) over 3 months. Practice staff prospectively captured toxic effects. Masked oncology clinicians reviewed medical records to verify. The study was registered with ClinicalTrials.gov, NCT02054741. FINDINGS: Between July 29, 2014, and March 13, 2019, we enrolled 718 patients. Patients had a mean age of 77·2 years (SD 5·4) and 311 (43%) of 718 participants were female. The mean number of geriatric assessment domain impairments was 4·5 (SD 1·6) and was not significantly different between the study groups. More patients in intervention group compared with the usual care group were Black versus other races (40 [11%] of 349 patients vs 12 [3%] of 369 patients; p<0·0001) and had previous chemotherapy (104 [30%] of 349 patients vs 81 [22%] of 369 patients; p=0·016). A lower proportion of patients in the intervention group had grade 3-5 toxic effects (177 [51%] of 349 patients) compared with the usual care group (263 [71%] of 369 patients; relative risk [RR] 0·74 (95% CI 0·64-0·86; p=0·0001). Patients in the intervention group had fewer falls over 3 months (35 [12%] of 298 patients vs 68 [21%] of 329 patients; adjusted RR 0·58, 95% CI 0·40-0·84; p=0·0035) and had more medications discontinued (mean adjusted difference 0·14, 95% CI 0·03-0·25; p=0·015). INTERPRETATION: A geriatric assessment intervention for older patients with advanced cancer reduced serious toxic effects from cancer treatment. Geriatric assessment with management should be integrated into the clinical care of older patients with advanced cancer and ageing-related conditions. FUNDING: National Cancer Institute.

Cancer disparities in the context of rurality: risk factors and screening across various U.S. rural classification codes.

PURPOSE: Prior cancer research is limited by inconsistencies in defining rurality. The purpose of this study was to describe the prevalence of cancer risk factors and cancer screening behaviors across various county-based rural classification codes, including measures reflecting a continuum, to inform our understanding of cancer disparities according to the extent of rurality. METHODS: Using an ecological cross-sectional design, we examined differences in cancer risk factors and cancer screening behaviors from the Behavioral Risk Factor Surveillance System and National Health Interview Survey (2008-2013) across rural counties and between rural and urban counties using four rural-urban classification codes for counties and county-equivalents in 2013: U.S. Office of Management and Budget, National Center for Health Statistics, USDA Economic Research Service's rural-urban continuum codes, and Urban Influence Codes. RESULTS: Although a rural-to-urban gradient was not consistently evident across all classification codes, the prevalence of smoking, obesity, physical inactivity, and binge alcohol use increased (all ptrend < 0.03), while colorectal, cervical and breast cancer screening decreased (all ptrend < 0.001) with increasing rurality. Differences in the prevalence of risk factors and screening behaviors across rural areas were greater than differences between rural and urban counties for obesity (2.4% vs. 1.5%), physical activity (2.9% vs. 2.5%), binge alcohol use (3.4% vs. 0.4%), cervical cancer screening (6.8% vs. 4.0%), and colorectal cancer screening (4.4% vs. 3.8%). CONCLUSIONS: Rural cancer disparities persist across multiple rural-urban classification codes, with marked variation in cancer risk factors and screening evident within rural regions. Focusing only on a rural-urban dichotomy may not sufficiently capture subpopulations of rural residents at greater risk for cancer and cancer-related mortality.

Sodium Butyrate Attenuates Diabetic Kidney Disease Partially via Histone Butyrylation Modification.

Inflammation and fibrosis are the important pathophysiologic processes in diabetic kidney disease (DKD), which is induced by epigenetics, especially histone posttranslational modification (HPTMs). Recent reports highlighted that butyrate, one of the short-chain fatty acids (SCFAs) primarily originated from the fermentation of dietary fiber in the gut, attenuates inflammation and fibrosis in the prevention and treatment of DKD; however, the molecular mechanisms are still unclear. Histone lysine butyrylation (Kbu), a novel histone modification marker induced by butyrate, has been found to be involved in the regulation of pathophysiological processes. To reveal the mechanisms of butyrate-induced histone (Kbu), in the prevention and treatment of DKD, both DKD models in vivo and in vitro were treated with sodium butyrate (NaB). Our results confirmed that exogenous NaB improved the disorder of glucose and lipid metabolism, prevented proteinuria and renal failure, and inhibited renal inflammation and fibrosis. Meanwhile, NaB also induced histone Kbu and H3K9 butyrylation (H3K9bu) in vivo and in vitro; however, inhibition of histone Kbu with the histone modification enzyme p300 inhibitor A485 reversed the anti-inflammatory and anti-fibrosis effects of NaB. In conclusion, our data reveal that NaB antagonizes renal inflammatory and fibrosis injury and attenuates DKD possibly via histone Kbu, suggesting that butyrate-induced histone Kbu or H3K9bu may be an important molecular mechanism in the pathogenesis and treatment of DKD.

A novel circRNA-SNP may increase susceptibility to silicosis.

In this study, we aimed to reveal the association between circRNA-related single nucleotide polymorphisms (SNPs) with the susceptibility of silicosis. To achieve this goal, a silicosis-related GWAS was constructed to select the candidate SNPs, and circBase database was utilized to select the promising SNPs which may locate on circRNAs. In addition, the eQTL analysis between the SNPs and located genes was performed to select the candidate SNPs. Finally, the association between candidate SNPs with the susceptibility of silicosis was validated. As a result, we firstly selected 10,922 SNPs with P < 1 × 10-3 through the silicosis-related GWAS. Among which, 1,752 SNPs were identified that may locate on 2,660 circRNAs. After the MAF evaluation and the sequences checking, we obtained 94 SNPs and related 105 circRNAs. EQTL analysis indicated that 7 circRNA-SNPs might regulate the expression of located genes. Subsequently, a strong association was found between variant A of rs17115143 and silicosis risk in the validation stage (OR= 1.68, P = 0.032). Combination of the GWAS data and Taqman genotyping data also revealed a strong association between rs17115143 and silicosis risk in both dominant and additive models (dom: OR= 1.96, P = 3.98 × 10-4; add: OR= 1.40, P = 3.06 × 10-4). In conclusion, the variant A allele of circRNA-SNP rs17115143 could be a risk factor in the progression of silicosis. And related 6 circRNAs may function as novel biomarkers for the diagnostic of silicosis. Further researches to explore the biological mechanisms of rs17115143 related 6 circRNAs in the regulation of silicosis are warranted.

Peripheral blood circular RNA hsa_circ_0058493 as a potential novel biomarker for silicosis and idiopathic pulmonary fibrosis.

Existing studies reported that some circular RNAs (circRNAs) play vital roles in the development of pulmonary fibrosis. However, few studies explored the biomarker potential of circRNAs for pulmonary fibrosis based on population data. Therefore, we aimed to identify peripheral blood circRNAs as potential biomarkers for diagnosing silicosis and idiopathic pulmonary fibrosis (IPF). In brief, an RNA-seq screening based on 4 silicosis cases and 4 controls was initially performed. Differentially expressed circRNAs were combined with the human serum circRNA dataset to identify overlapping serum-detectable circRNAs, followed by validation using the GEO dataset (3 IPF cases and 3 controls) and subsequent qRT-PCR, including 84 additional individuals. Following the above steps, 243 differentially expressed circRNAs were identified during the screening stage, with fold changes ≥ 1.5 and P < 0.05. Of note, the human serum circRNA dataset encompassed 28 of 243 circRNAs. GEO (GSE102660) validation revealed two highly expressed circRNAs (P < 0.05) in the IPF case group. Furthermore, at the enlarged sample validation stage, hsa_circ_0058493 was highly expressed in both silicosis and IPF cases (silicosis: P = 1.16 × 10-6; IPF: P = 7.46 × 10-5). Additionally, hsa_circ_0058493 expression was significantly increased in MRC-5 cells upon TGF-ß1 treatment, while hsa_circ_0058493 knockdown inhibited the expression of fibrotic molecules by affecting the epithelial-mesenchymal transition process. These shreds of evidence indicated that hsa_circ_0058493 might serve as a novel biomarker for diagnosing silicosis and IPF.

Related factors associated with fear of hypoglycemia in parents of children and adolescents with type 1 diabetes - A systematic review.

PROBLEM: Fear of hypoglycemia is a significant concern for parents of children/ adolescents with type 1 diabetes. Although some studies have explained the parental fear of hypoglycemia, the related factors were yet to be determined. This systematic review aims to identify the related factors of fear of hypoglycemia in the parents of children and adolescents with type 1 diabetes and provide a theoretical basis for further intervention. ELIGIBILITY CRITERIA: PubMed, MEDLINE, EMBASE, Scopus, CINAHL, EBSCO, Web of Science, and Cochrane Library were systematically searched from 2010 to 2021. Studies evaluating the fear of hypoglycemia of parents and its associated factors were included. SAMPLE: Twenty-three observational articles met the criteria. RESULTS: Significant associations were found between fear of hypoglycemia and specific factors, including motherhood, nocturnal hypoglycemia, and the number of blood glucose monitoring. Psychological factors, including anxiety, depression, pediatric parenting stress, mindfulness, self-efficacy, quality of life, and sleep disorders, were conclusive and associations with parental fear of hypoglycemia. CONCLUSIONS: Understanding parental fear of hypoglycemia can help parents prevent potential problems in diabetes management, thus promoting children's growth. According to current evidence, effective targeted interventions based on modifiable relevant factors can be developed to reduce the fear of hypoglycemia in parents while maintaining optimal blood glucose control in children/ adolescents. IMPLICATIONS: Health professionals should pay more attention to the mental health of parents, and parents should be involved in the care plan and have the opportunity to discuss their fear of hypoglycemia in the most appropriate way to manage type 1 diabetes.

Effect of Heat Shock Preconditioning on Pressure Injury Prevention via Hsp27 Upregulation in Rat Models.

Pressure injury (PI) prevention is a huge industry and involves various interventions. Temperature and moisture are important factors for wound healing; however, the active mechanism by which "moist heat" affects PI prevention has not yet been clarified. Thus, we explored the protective and therapeutic effects of hydrotherapy on PI based on the preconditioning (PC) principle, which might be useful for clinical practice. This study aimed to investigate the preventive mechanisms of heat shock preconditioning on PIs in rat models. The experiment was performed in the basic medical laboratory of Nagano College of Nursing in Japan. Ten rats were divided into two groups, with five rats in each group. Rats in the control group were not bathed. Rats in the preconditioning group (PC group) were bathed with hot tap-water. Bathing was conducted thrice a week. After bathing for 4 weeks, the PI model was constructed on the rats' dorsal skin. The skin temperature, skin moisture, and area of ulcers were compared between the two groups. In vitro, we investigated the expression of heat shock protein 27 (Hsp27) in 6, 12, and 24 h after the PI model was constructed through Western blot analysis. Ulcers occurred in the control group 24 h after the PI model constructed, wheras the PC group exhibited ulcers after 36 h. The ulcer area was larger in the control group than that in the PC group after 24 h (all p < 0.05). The temperatures of PI wounds in the control group decreased and were lower than those in the PC group after 1, 6, 12, 36, and 48 h (all p < 0.05). However, the skin moisture levels of PI wounds increased in the control group and were higher than those in the PC group at the same time (all p < 0.05). Using Western blot analysis, hydrotherapy preconditioning showed the potential to increase Hsp27 expression after pressure was released (p < 0.05). We determine that heat shock preconditioning had a preventive effect on PIs in rat models, a result that may be associated with their actions in the upregulation of Hsp27.

Anxiety and sleep quality among front-line nurses treating first wave COVID-19 in China: The mediating role of mindfulness.

AIM: To explore anxiety, sleep quality, and mindfulness of frontline nurses at the initial epicenter of the pandemic, to examine the mediating effects of mindfulness. BACKGROUND: COVID-19 was first identified in Wuhan, China in January 2020. Nurses were at the forefront of care and treatment across hospitals in response to the pandemic. METHODS: Single site cross-sectional survey conducted in Wuhan province (China) between March and April in 2020. Quantitative analysis of survey data from N118 nurses working in the frontline COVID response. Questionnaires included: The general information questionnaire, the Self-Anxiety Scale, the Short Inventory of Mindfulness, and the Pittsburgh Sleep Quality Index. RESULTS: Front-line nurses' anxiety was positively associated with sleep quality and mindfulness was negatively associated with anxiety and sleep quality. Mindfulness had a mediating role on anxiety and sleep quality, with intermediary adjustment effects (ES = 0.136, 95 % CI 0.02 to 0.26), accounting for 21.9 % of the total effect ratio. CONCLUSIONS: Anxiety causes a reduction in sleep quality and mindfulness can help with anxiety. Mindfulness strategies may help during periods of higher anxiety in the workplace; however, other factors must be considered. Further research is required on strategies for assisting nurses during periods of extreme anxiety.