Development and validation of a nomogram for oral mucosal membrane pressure injuries in ICU patients: A prospective cohort study.

AIMS: Establishing a nomogram to estimate the probability of oral mucosal membrane pressure injury of endotracheal tube-intubated hospitalized patients in intensive care unit. DESIGN: Multicentre prospective cohort study. METHODS: Using Lasso regression and COX regression, variable selection was performed on demographic, clinical and laboratory data of 1037 ICU endotracheal tube-intubated hospitalized patients from West China Hospital, to construct a nomogram. External validation was conducted on 484 ICU endotracheal tube-intubated patients from People's Hospital of Zhongjiang County. RESULTS: Among 38 potential predictors, five variables emerged as independent predictors, integrated into the nomogram: administration of antibiotics, nutritional therapy duration, agitation, hypotension and albumin levels. CONCLUSIONS: We established a nomogram based on the hospital characteristics of ICU endotracheal tube-intubated patients, aiding in the prediction of the occurrence of oral mucosal membrane pressure injury. REPORTING METHOD: The study followed TRIPOD guidelines. RELEVANCE TO CLINICAL PRACTICE: The nomogram we developed can assist clinical worker in better identifying at-risk patients and risk factors. It enables the implementation of evidence-based nursing interventions in care to prevent the development of oral mucosal membrane pressure injury. TRIAL REGISTRATION: The study has been registered with the Chinese Clinical Trial Registry (http://www.chictr.org.cn) under registration number ChiCTR2200056615.

Early mobilisation practice in intensive care units: A large-scale cross-sectional survey in China.

BACKGROUND: The field of early rehabilitation has developed slowly in mainland China and there are limited data on the implementation of early mobilisation (EM) practice in intensive care unit (ICUs) in China. AIMS: To investigate the implementation of EM in ICUs in mainland China and to analyse its influencing factors. STUDY DESIGN: A cross-sectional electronic survey was conducted in 444 ICUs across 11 provinces in China. Head nurses provided data on institutional characteristics and EM practice in ICUs. Logistic regression models were used to identify factors associated with the implementation of EM. RESULTS: In all, 56.98% (253/444) of ICUs implemented EM with comprehensive or complete implementation in 86 ICUs. Of the 191 ICUs that did not use EM, 136 planned to implement EM in the near future. Of the 253 ICUs that used EM, 21.34% of ICUs implemented EM for all eligible patients, while 24.90% would evaluate and carry out EM within 48 h after ICU admission, 39.13% had collaborative EM teams, 34.39% reported the use of EM protocols, 14.63% reported multidisciplinary rounds and 17.39% had medical orders and charging standards for all EM activities. Only 18.18% of ICUs conducted frequent professional training for EM, and abnormal events occurred in 15.41% of ICUs during EM practice. Multivariate logistic regression analysis revealed that an economically strong province, the presence of a dedicated therapist team, more ICU beds and a higher staff-to-bed ratio favoured the implementation of EM. Furthermore, multidisciplinary rounds, well-established medical orders and charging standards, and a high frequency of professional training can lead to the comprehensive promotion and development of EM practice in ICUs. CONCLUSIONS: Both the implementation rate and quality of EM practice for critically ill patients require improvement. EM practice in Chinese ICUs is still nascent and requires development in a variety of domains. RELEVANCE TO CLINICAL PRACTICE: To facilitate the implementation of EM in ICUs, more human resources, especially the involvement of a professional therapist team, should be deployed. In addition, health providers should actively organize multidisciplinary rounds and professional training and formulate appropriate EM medical orders and charging standards.

A novel circular RNA, circ-ATAD1, contributes to gastric cancer cell progression by targeting miR-140-3p/YY1/PCIF1 signaling axis.

Circular RNAs (circRNAs) has been shown to be involved in the progression of various malignancies. Nevertheless, the mechanism of dysregulated circRNAs in gastric cancer (GC) remains to be understood. CircRNA microarray was utilized for identifying circRNA expression profiles in GC tissues. Circ-ATAD1 expression was measured by qRT-PCR. The clinical significance of circ-ATAD1 was analyzed by Fisher's exact test, Kaplan-Meier plots, and Cox regression model. The function of circ-ATAD1 was explored by using CCK-8, clone formation, flow cytometric and transwell experiments. RNA sequencing, bioinformatics, RNA pulldown, chromatin immunoprecipitation followed by sequencing, and dual-luciferase reporter assays were applied to determine the regulatory networks of circ-ATAD1 in GC cells. Circ-ATAD1 expression was increased in cancerous tissues. The prognostic value of circ-ATAD1 was identified in GC patients. For GC cells, circ-ATAD1 increased cell progression by sponging miR-140-3p to upregulate YY1. Additionally, YY1 directly bound to the promoter of PCIF1, thereby activating its transcription. Collectively, circ-ATAD1 plays an important role in GC tumorigenesis and progression and might be an important biomarker/therapeutic target for GC.

Arx is required for normal enteroendocrine cell development in mice and humans.

Enteroendocrine cells of the gastrointestinal (GI) tract play a central role in metabolism, digestion, satiety and lipid absorption, yet their development remains poorly understood. Here we show that Arx, a homeodomain-containing transcription factor, is required for the normal development of mouse and human enteroendocrine cells. Arx expression is detected in a subset of Neurogenin3 (Ngn3)-positive endocrine progenitors and is also found in a subset of hormone-producing cells. In mice, removal of Arx from the developing endoderm results in a decrease of enteroendocrine cell types including gastrin-, glucagon/GLP-1-, CCK-, secretin-producing cell populations and an increase of somatostatin-expressing cells. This phenotype is also observed in mice with endocrine-progenitor-specific Arx ablation suggesting that Arx is required in the progenitor for enteroendocrine cell development. In addition, depletion of human ARX in developing human intestinal tissue results in a profound deficit in expression of the enteroendocrine cell markers CCK, secretin and glucagon while expression of a pan-intestinal epithelial marker, CDX2, and other non-endocrine markers remained unchanged. Taken together, our findings uncover a novel and conserved role of Arx in mammalian endocrine cell development and provide a potential cause for the chronic diarrhea seen in both humans and mice carrying Arx mutations.

The ability of critical care nurses to identify pressure injury and incontinence-associated dermatitis: A multicentre cross-sectional survey.

AIM: To investigate the ability of critical care nurses to identify pressure injury and incontinence-associated dermatitis and analyse the possible influencing factors. DESIGN: Cross-sectional survey. METHODS: This study was conducted at 24 hospitals across 12 provinces in China. A self-made electronic questionnaire was used. Nurses identified and judged injuries according to the information provided. RESULTS: The average identification score for pressure injury and incontinence-associated dermatitis was 9.00 ± 3.51 points, and only 2.16% of nurses scored ≥16 points. The average correct identification rate for pressure injury and incontinence-associated dermatitis was 45%. The correct identification rate for stage 1 pressure injury was the highest, while those for stage 3, stage 4, deep tissue pressure injury and unstageable pressure injury were all lower than 50%; incontinence-associated dermatitis was also easily misjudged. Nurses' educational backgrounds, professional titles, job positions, hospital levels and learning frequency were the factors that affected their ability to identify pressure injury and incontinence-associated dermatitis.

Islet-1 regulates Arx transcription during pancreatic islet alpha-cell development.

Aristaless related homeodomain protein (Arx) specifies the formation of the pancreatic islet α-cell during development. This cell type produces glucagon, a major counteracting hormone to insulin in regulating glucose homeostasis in adults. However, little is known about the factors that regulate Arx transcription in the pancreas. In this study, we showed that the number of Arx(+) cells was significantly reduced in the pancreata of embryos deficient for the Islet-1 (Isl-1) transcription factor, which was also supported by the reduction in Arx mRNA levels. Chromatin immunoprecipitation analysis localized Isl-1 activator binding sites within two highly conserved noncoding regulatory regions (Re) in the Arx locus, termed Re1 (+5.6 to +6.1 kb) and Re2 (+23.6 to +24 kb). Using cell line-based transfection assays, we demonstrated that a Re1- and Re2-driven reporter was selectively activated in islet α-cells, a process mediated by Isl-1 in overexpression, knockdown, and site-directed mutation experiments. Moreover, Arx mRNA levels were up-regulated in islet α-cells upon Isl-1 overexpression in vivo. Isl-1 represents the first known activator of Arx transcription in α-cells, here established to be acting through the conserved Re1 and Re2 control domains.

Myofibrillogenesis in skeletal muscle cells in zebrafish.

The "premyofibril" model of myofibrillogenesis, based on observations in cultured avian muscle cells, proposes that mature myofibrils are preceded by two intermediary structures: premyofibrils and nascent myofibrils. To determine if this model applies to zebrafish skeletal muscle development, we stained developing embryos with antibodies to sarcomeric alpha-actinin and myosin II. In the youngest muscle cells, sarcomeric alpha-actinin and non-muscle myosin II were each localized in linear arrays of small bands that resembled the premyofibrils in avian myocytes. The distribution of muscle-specific myosin II began as scattered short filaments followed in time by overlapping bundles of filaments and organized A-bands in the older somites. Alpha-actinin organization changed from small z-bodies to beaded Z-bands and ordered Z-bands in myofibrils that extended the length of the elongating somites. In older somites with mature myofibrils, premyofibrils were also present at the ends of the mature myofibrils, suggesting that as the cells and somites grew longer, premyofibrils were involved in the elongation of existing mature myofibrils. Fluorescence Recovery After Photobleaching showed that the exchange of proteins (actin, alpha-actinin, FATZ, myotilin and telethonin) between sarcoplasm and the Z-bands of mature myofibrils in zebrafish resembled that seen for the same proteins in cultured avian myotubes, suggesting that myofibril assembly and maintenance in zebrafish share common properties with avian muscle. Cell Motil. Cytoskeleton 2009. (c) 2009 Wiley-Liss, Inc.

Cardiac myofibrillogenesis inside intact embryonic hearts.

How proteins assemble into sarcomeric arrays to form myofibrils is controversial. Immunostaining and transfections of cultures of cardiomyocytes from 10-day avian embryos led us to propose that assembly proceeded in three stages beginning with the formation of premyofibrils followed by nascent myofibrils and culminating in mature myofibrils. However, premyofibril and nascent myofibril arrays have not been detected in early cardiomyocytes examined in situ in the forming avian heart suggesting that the mechanism for myofibrillogenesis differs in cultured and uncultured cells. To address this question of in situ myofibrillogenesis, we applied non-enzymatic procedures and deconvolution imaging techniques to examine early heart forming regions in situ at 2- to 13-somite stages (beating begins at the 9-somite stage), a time span of about 23 h. These approaches enabled us to detect the three myofibril stages in developing hearts supporting a three-step model of myofibrillogenesis in cardiomyocytes, whether they are present in situ, in organ cultures or in tissue culture. We have also discovered that before titin is organized the first muscle myosin filaments are about half the length of the 1.6 mum filaments present in mature A-bands. This supports the proposal that titin may play a role in length determination of myosin filaments.

[Paragonimus skrjabini infection in animal reservoir hosts and questionnairing in residents at a village of Hubei Province].

Freshwater crabs (Sinopotamon denticulatum) were examined for metacercariae. Cats and dogs were also examined for Paragonimus infection. Questionnairing was carried out on health knowledge and behaviors among local residents in a village of Baokang County, Hubei Province. Results showed that the infection rate of Paragonimus skrjabini metacercariae in Sinopotamon denticulatum was 20.5% (46/214), with 15.6% (20/128) in a mining area and 30.2% (26/86) for the non-mining area respectively (chi2 = 6.5, P < 0.05). The prevalence in cats and dogs was 25.0% (6/24) and 17.6% (6/34) respectively (chi2 = 0.46, P > 0.05). Questionnairing showed that dogs and cats were with the habit of foraging and defecating at streams and children had the habits of eating raw or under-cooked crabs. The natural and ecological environments are in favor of the life cycle of P. skrjabini.

Clinicopathological significance of CHFR methylation in non-small cell lung cancer: a systematic review and meta-analysis.

Checkpoint with Forkhead-associated and Ring finger domains (CHFR) is a G2/M checkpoint and tumor-suppressor gene. Recent publications showed the correlation of CHFR promoter methylation with clinicopathological significance of non-small cell lung cancer (NSCLC), however, the results remain inconsistent. The aim of this study is to investigate the Clinicopathological significance of CHFR promoter methylation in NSCLC with a meta-analysis. A total of nine studies were included in the meta-analysis that 816 patients were involved. Our data indicated that the frequency of CHFR promoter methylation was higher in NSCLC than in normal lung tissue, Odd Ratios (OR) was 9.92 with 95% corresponding confidence interval (CI) 2.17-45.23, p = 0.003. Further subgroup analysis revealed that CHFR promoter was more frequently methylated in squamous cell carcinoma (SCC) than in adenocarcinoma (ADC), OR was 4.46 with 95% CI 1.65-12.05, p = 0.003, suggesting the mechanism of SCC pathogenesis is different from ADC. Notably, CHFR promoter methylation was correlated with smoking behavior in NSCLC. In conclusion, CHFR could be a biomarker for diagnosis of NSCLC, and a promising drug target for development of gene therapy in SCC. CHFR promoter methylation is potentially associated with poor overall survival, additional studies need to be carried out for confirmation in future.

TNF-α Promoter Polymorphisms Predict the Response to Etanercept More Powerfully than that to Infliximab/Adalimumab in Spondyloarthritis.

While previous studies have researched in association analyses between TNFα promoter polymorphisms and responses to TNF blockers in spondyloarthritis patients, their results were conflicting. Therefore, we aimed to determine whether TNFα promoter polymorphisms could predict response to TNF blockers and find the source of heterogeneity. Data were extracted and analyzed from published articles and combined with our unpublished data. We found that the greatest potential sources of heterogeneity in the results were gender ratio, disease type, continents, and TNF blockers. Then Stratification analysis showed that the TNFα -308 G allele and the -238 G allele predicted a good response to TNF blockers (OR = 2.64 [1.48-4.73]; 2.52 [1.46-4.37]). However, G alleles of TNFα -308 and -238 could predict the response to etanercept (OR = 4.02 [2.24-7.23]; 5.17 [2.29-11.67]) much more powerfully than the response to infiliximab/adalimumab (OR = 1.68 [1.02-2.78]; 1.28 [0.57-2.86]). TNFα -857 could not predict the response in either subgroup. Cumulative meta-analysis performed in ankylosing spondylitis patients presented the odds ratio decreased with stricter response criteria. In conclusion, TNFα -308 A/G and -238 A/G are more powerful to predict the response to Etanercept and it is dependent on the criteria of response.

Islet-1 Is essential for pancreatic ß-cell function.

Islet-1 (Isl-1) is essential for the survival and ensuing differentiation of pancreatic endocrine progenitors. Isl-1 remains expressed in all adult pancreatic endocrine lineages; however, its specific function in the postnatal pancreas is unclear. Here we determine whether Isl-1 plays a distinct role in the postnatal ß-cell by performing physiological and morphometric analyses of a tamoxifen-inducible, ß-cell-specific Isl-1 loss-of-function mouse: Isl-1(L/L); Pdx1-CreER(Tm). Ablating Isl-1 in postnatal ß-cells reduced glucose tolerance without significantly reducing ß-cell mass or increasing ß-cell apoptosis. Rather, islets from Isl-1(L/L); Pdx1-CreER(Tm) mice showed impaired insulin secretion. To identify direct targets of Isl-1, we integrated high-throughput gene expression and Isl-1 chromatin occupancy using islets from Isl-1(L/L); Pdx1-CreER(Tm) mice and ßTC3 insulinoma cells, respectively. Ablating Isl-1 significantly affected the ß-cell transcriptome, including known targets Insulin and MafA as well as novel targets Pdx1 and Slc2a2. Using chromatin immunoprecipitation sequencing and luciferase reporter assays, we found that Isl-1 directly occupies functional regulatory elements of Pdx1 and Slc2a2. Thus Isl-1 is essential for postnatal ß-cell function, directly regulates Pdx1 and Slc2a2, and has a mature ß-cell cistrome distinct from that of pancreatic endocrine progenitors.

Glucagon deficiency reduces hepatic glucose production and improves glucose tolerance in adult mice.

The major role of glucagon is to promote hepatic gluconeogenesis and glycogenolysis to raise blood glucose levels during hypoglycemic conditions. Several animal models have been established to examine the in vivo function of glucagon in the liver through attenuation of glucagon via glucagon receptor knockout animals and pharmacological interventions. To investigate the consequences of glucagon loss to hepatic glucose production and glucose homeostasis, we derived mice with a pancreas specific ablation of the alpha-cell transcription factor, Arx, resulting in a complete loss of the glucagon-producing pancreatic alpha-cell. Using this model, we found that glucagon is not required for the general health of mice but is essential for total hepatic glucose production. Our data clarifies the importance of glucagon during the regulation of fasting and postprandial glucose homeostasis.

Islet-1 is required for the maturation, proliferation, and survival of the endocrine pancreas.

OBJECTIVE: The generation of mature cell types during pancreatic development depends on the expression of many regulatory and signaling proteins. In this study, we tested the hypothesis that the transcriptional regulator Islet-1 (Isl-1), whose expression is first detected in the mesenchyme and epithelium of the developing pancreas and is later restricted to mature islet cells, is involved in the terminal differentiation of islet cells and maintenance of islet mass. RESEARCH DESIGN AND METHODS: To investigate the role of Isl-1 in the pancreatic epithelium during the secondary transition, Isl-1 was conditionally and specifically deleted from embryonic day 13.5 onward using Cre/LoxP technology. RESULTS: Isl-1-deficient endocrine precursors failed to mature into functional islet cells. The postnatal expansion of endocrine cell mass was impaired, and consequently Isl-1 deficient mice were diabetic. In addition, MafA, a potent regulator of the Insulin gene and beta-cell function, was identified as a direct transcriptional target of Isl-1. CONCLUSIONS: These results demonstrate the requirement for Isl-1 in the maturation, proliferation, and survival of the second wave of hormone-producing islet cells.

How to build a myofibril.

Building a myofibril from its component proteins requires the interactions of many different proteins in a process whose details are not understood. Several models have been proposed to provide a framework for understanding the increasing data on new myofibrillar proteins and their localizations during muscle development. In this article we discuss four current models that seek to explain how the assembly occurs in vertebrate cross-striated muscles. The models hypothesize: (a) stress fiber-like structures as templates for the assembly of myofibrils, (b) assembly in which the actin filaments and Z-bands form subunits independently from A-band subunits, with the two subsequently joined together to form a myofibril, (c) premyofibrils as precursors of myofibrils, or (d) assembly occurring without any intermediary structures. The premyofibril model, proposed by the authors, is discussed in more detail as it could explain myofibrillogenesis under a variety of different conditions: in ovo, in explants, and in tissue culture studies on cardiac and skeletal muscles.

Myofibrillogenesis in the first cardiomyocytes formed from isolated quail precardiac mesoderm.

De novo assembly of myofibrils was investigated in explants of precardiac mesoderm from quail embryos to address a controversy about different models of myofibrillogenesis. The sequential expression of sarcomeric components was visualized in double- and triple-stained explants before, during, and just after the first cardiomyocytes began to beat. In explants from stage 6 embryos, cultured for 10 h, ectoderm, endoderm, and the precardiac mesoderm displayed arrays of stress fibers with alternating bands of the nonmuscle isoforms of alpha-actinin and myosin IIB. With increasing time in culture, mesoderm cells contained fibrils composed of actin, nonmuscle myosin IIB, and sarcomeric alpha-actinin. Several hours later, before beating occurred, both nonmuscle and muscle myosin II localized in some of the fibrils in the cells. Concentrations of muscle myosin began as thin bundles, dispersed in the cytoplasm, often overlapping one another, and progressed to small, aligned A-band-sized aggregates. The amount of nonmuscle myosin decreased dramatically when Z-bands formed, the muscle myosin became organized into A-bands, and the cells began beating. The sequential changes in protein composition of the fibrils in the developing muscle cells supports the model of myofibrillogenesis in which assembly begins with premyofibrils and progresses through nascent myofibrils to mature myofibrils.

A talin fragment as an actin trap visualizing actin flow in chemotaxis, endocytosis, and cytokinesis.

A C-terminal 63-kDa fragment of talin A from Dictyostelium discoideum forms a slowly dissociating complex with F-actin in vitro. This talin fragment (TalC63) has been tagged with GFP and used as a trap for actin filaments in chemotactic cell movement, endocytosis, and mitotic cell division. TalC63 efficiently sequesters actin filaments in vivo. Its translocation reflects the direction and efficiency of an actin flow. Along the body of a migrating Dictyostelium cell, this flow is directed from the front to the tail. If during chemotaxis one or two new fronts are induced, the flow is always directed away from these fronts. The flow thus reflects the re-programming of cell polarity in response to changing gradients of chemoattractant. In endocytosis, the fluorescent complexes are translocated to the base of a phagocytic or macropinocytic cup. During mitosis, the complexes of F-actin with TalC63 accumulate within the midzone of anaphase cells. If TalC63 is strongly expressed, the entire cleavage furrow is filled out by sequestered actin filaments, and cytokinesis is severely impaired. These cells are considered to mimic the phenotype of mutants deficient in the shredding of actin filaments that normally occurs in the mid-zone of a dividing cell.