Disease severity-based subgrouping of type 2 diabetes does not parallel differences in quality of life: the Maastricht Study.

AIMS/HYPOTHESIS: Type 2 diabetes is a highly heterogeneous disease for which new subgroups ('clusters') have been proposed based on disease severity: moderate age-related diabetes (MARD), moderate obesity-related diabetes (MOD), severe insulin-deficient diabetes (SIDD) and severe insulin-resistant diabetes (SIRD). It is unknown how disease severity is reflected in terms of quality of life in these clusters. Therefore, we aimed to investigate the cluster characteristics and cluster-wise evolution of quality of life in the previously defined clusters of type 2 diabetes. METHODS: We included individuals with type 2 diabetes from the Maastricht Study, who were allocated to clusters based on a nearest centroid approach. We used logistic regression to evaluate the cluster-wise association with diabetes-related complications. We plotted the evolution of HbA1c levels over time and used Kaplan-Meier curves and Cox regression to evaluate the cluster-wise time to reach adequate glycaemic control. Quality of life based on the Short Form 36 (SF-36) was also plotted over time and adjusted for age and sex using generalised estimating equations. The follow-up time was 7 years. Analyses were performed separately for people with newly diagnosed and already diagnosed type 2 diabetes. RESULTS: We included 127 newly diagnosed and 585 already diagnosed individuals. Already diagnosed people in the SIDD cluster were less likely to reach glycaemic control than people in the other clusters, with an HR compared with MARD of 0.31 (95% CI 0.22, 0.43). There were few differences in the mental component score of the SF-36 in both newly and already diagnosed individuals. In both groups, the MARD cluster had a higher physical component score of the SF-36 than the other clusters, and the MOD cluster scored similarly to the SIDD and SIRD clusters. CONCLUSIONS/INTERPRETATION: Disease severity suggested by the clusters of type 2 diabetes is not entirely reflected in quality of life. In particular, the MOD cluster does not appear to be moderate in terms of quality of life. Use of the suggested cluster names in practice should be carefully considered, as the non-neutral nomenclature may affect disease perception in individuals with type 2 diabetes and their healthcare providers.

Accelerating attribute-focused process and product development through the development and deployment of autonomous process analytical technology platform system.

Enabling real-time monitoring and control of the biomanufacturing processes through product quality insights continues to be an area of focus in the biopharmaceutical industry. The goal is to manufacture products with the desired quality attributes. To realize this rigorous attribute-focused Quality by Design approach, it is critical to support the development of processes that consistently deliver high-quality products and facilitate product commercialization. Time delays associated with offline analytical testing can limit the speed of process development. Thus, developing and deploying analytical technology is necessary to accelerate process development. In this study, we have developed the micro sequential injection process analyzer and the automatic assay preparation platform system. These innovations address the unmet need for an automatic, online, real-time sample acquisition and preparation platform system for in-process monitoring, control, and release of biopharmaceuticals. These systems can also be deployed in laboratory areas as an offline analytical system and on the manufacturing floor to enable rapid testing and release of products manufactured in a good manufacturing practice environment.

Comprehensive transcriptomic profiling and mutational landscape of primary gastric linitis plastica.

BACKGROUND: Primary gastric linitis plastica (GLP) is a distinct phenotype of gastric cancer with poor survival. Comprehensive molecular profiles and putative therapeutic targets of GLP remain undetermined. METHODS: We subjected 10 tumor-normal tissue pairs to whole exome sequencing (WES) and whole transcriptome sequencing (WTS). 10 tumor samples were all GLP which involves 100% of the gastric wall macroscopically. TCGA data were compared to generate the top mutated genes and the overexpressed genes in GLP. RESULTS: Our results reveal that GLP has distinctive genomic and transcriptomic features, dysfunction in the Hippo pathway is likely to be a key step during GLP development. 6 genes were identified as significantly highly mutated genes in GLP, including AOX1, ANKRD36C, CPXM1, PTPN14, RPAP1, and DCDC1). MUC6, as a previously identified gastric cancer driver gene, has a high mutation rate (20%) in GLP. 20% of patients in our GLP cohort had CDH1 mutations, while none had RHOA mutations. GLP exhibits high immunodeficiency and low AMPK pathway activity. Our WTS results showed that 3 PI3K-AKT pathway-related genes (PIK3R2, AKT3, and IGF1) were significantly up-regulated in GLP. Two genes were identified using immunohistochemistry (IHC), IGF2BP3 and MUC16, which specifically expressed in diffuse-type-related gastric cancer cell lines, and its knockdown inhibits PI3K-AKT pathway activity. CONCLUSIONS: We provide the first integrative genomic and transcriptomic profiles of GLP, which may facilitate its diagnosis, prognosis, and treatment.

Bibliometric analysis of post-traumatic growth after childbirth.

AIM: To make a bibliometric analysis on post-traumatic growth (PTG) after childbirth. METHODS: The topic advanced search strategy extracted the information from the Web of Science Core Collection. Descriptive statistics were performed using Excel, and bibliometric analysis was performed using VOSviewer. RESULTS: A total of 362 publications were published in 199 journals were obtained in the WoSCC from 1999 to 2022. Postpartum post-traumatic growth is in a trend of fluctuating growth, and the United States (N = 156) and Bar-Ilan University (N = 22) were the top contributing countries and institutions, respectively. Research hotspots mainly focus on theoretical models of PTG, postpartum post-traumatic stress disorder (PTSD) as a predictor of PTG, facilitators of PTG, and the relationship between mother-infant attachment and PTG. CONCLUSION: This bibliometric study provides a comprehensive overview of the current state of research on PTG after childbirth, an area that has received considerable scholarly attention in recent years. However, research on post-traumatic growth after childbirth is lacking, and further research is needed.

Morphologic Changes of the Temporomandibular Joint in Pruzansky-Kaban Type IIa Hemifacial Microsomia Postmandibular Distraction Osteogenesis.

OBJECTIVE: Mandibular distraction osteogenesis (MDO) is a powerful tool for the correction of hemifacial microsomia (HFM). The temporomandibular joint (TMJ) is the focus of attention in the diagnosis and treatment of HFM. This observational retrospective cross-sectional study aimed to investigate morphologic changes in TMJ post-MDO in type IIa HFM. METHODS: We recruited 48 patients with unilateral type IIa HFM who had completed MDO and mandibular distractor extraction (MDE). Data relating to the length, distance, angle, and volume of the TMJ were measured on 3-dimension models created by the analysis of computed tomography data. Normality analysis was performed by using the Shapiro-Wilk test. Data were compared with the paired t test and Wilcoxon signed-ranks test. RESULTS: The spaces between the affected condyle and the affected glenoid fossa before MDO were all significantly larger than before MDE (P<0.05). The breadth of the affected glenoid fossa before MDO was significantly longer than before MDE (P<0.001). The height of the affected condyle before MDO was significantly longer than before MDE (P<0.001). The volume of the affected condyle before MDO was significantly larger than before MDE (P<0.001). The ratio between the volume of the affected condyle and unaffected condyle before MDO was 0.20±0.13. The ratio between the volume of the affected condyle before MDE and MDO was 0.65±0.32. The resorption rate of the affected condyle post-MDO was 0.35±0.32. CONCLUSION: Herein, we characterized anatomic changes of the TMJ in type- IIa HFM post-MDO. Condylar resorption and the compression of space between the condyle and the glenoid fossa on the affected side were 2 typical manifestations. Our findings enhanced the understanding of the application of MDO on HFM.

Three-Dimensional Measurement of the Temporomandibular Joint in Pruzansky-Kaban Type IIa Hemifacial Microsomia.

OBJECTIVE: This observational retrospective cross-sectional study aimed to investigate the morphological characteristics of the temporomandibular joint (TMJ) in type IIa hemifacial microsomia (HFM). METHODS: We recruited 88 patients with unilateral type IIa HFM. Data relating to the length, distance, and angle of the TMJ, were measured on 3-dimensional models created by the analysis of computed tomography data. Normality analysis was performed by using the Shapiro-Wilk test. Data were compared with the paired t test and Wilcoxon signed-rank test. RESULTS: The height, long axis, and short axis of the affected condyle were significantly shorter than the unaffected side ( P <0.001); the ratios were 0.41±0.15, 0.75±0.20, and 0.95±0.24, respectively. The spaces between the condyle and the glenoid fossa were significantly larger in affected TMJs ( P <0.001). The ratio between the ipsilateral and contralateral anterior space in the sagittal plane was 4.62±2.59; this was significantly different than the ratio of inner space (1.50±1.70), superior space (1.70±0.97), and lateral space (1.28±0.62) in the coronal plane ( P <0.001) and the ratio of superior space (1.43±1.05) and posterior space (1.47±0.98) in the sagittal plane ( P <0.001); there were no statistical differences between the 5 spaces ( P >0.05). The breadth and depth of the glenoid fossa were significantly shorter in affected TMJs ( P <0.001), the ratio of the breadth in the affected and unaffected glenoid fossa was between 0.5 and 1 and the depth of the affected glenoid fossa was almost half of that on the unaffected side. The ratio between the ipsilateral and contralateral height of the condyle was significantly different when compared with the length of the mandibular ramus ( P <0.001). The ratio between the ipsilateral height of the condyle and the length of the mandibular ramus was significantly different when compared with that of the contralateral side ( P <0.001). The height of the affected condyle were significantly different ( P =0.005) among different ages. CONCLUSIONS: We found that hypoplasia was more severe in terms of the height of the condyle than the long axis and short axis of the condyle. The degree of condyle deformity was more severe than the mandible. And the affected condyle still had growth potential in the vertical direction with age.

Understanding innovation of health technology assessment methods: the IHTAM framework.

Adequate methods are urgently needed to guarantee the good practice of health technology assessment (HTA) for technologies with novel properties. The aim of the study was to construct a conceptual framework to help understand the innovation of HTA methods (IHTAM). The construction of the IHTAM framework was based on two scoping reviews, one on the current practice of innovating methods, that is existing HTA frameworks, and one on theoretical foundations for innovating methods outside the HTA discipline. Both aimed to identify and synthesize concepts of innovation (i.e., innovation processes and roles of stakeholders in innovation). Using these concepts, the framework was developed in iterative brainstorming sessions and subsequent discussions with representatives from various stakeholder groups. The framework was constructed based on twenty documents on innovating HTA frameworks and fourteen guidelines from three scientific disciplines. It includes a generic innovation process consisting of three phases ("Identification," "Development," and "Implementation") and nine subphases. In the framework, three roles that HTA stakeholders can play in innovation ("Developers," "Practitioners," and "Beneficiaries") are defined, and a process on how the stakeholders innovate HTA methods is included. The IHTAM framework visualizes systematically which elements and stakeholders are important to the development and implementation of novel HTA methods. The framework could be used by all stakeholders involved in HTA innovation to learn how to engage dynamically and collaborate effectively throughout the innovation process. HTA stakeholders in practice have welcomed the framework, though additional testing of its applicability and acceptance is essential.

Toward a less costly but accurate calculation of the CCSD(T)/CBS noncovalent interaction energy.

The popular method of calculating the noncovalent interaction energies at the coupled-cluster single-, double-, and perturbative triple-excitations [CCSD(T)] theory level in the complete basis set (CBS) limit was to add a CCSD(T) correction term to the CBS second-order Møller-Plesset perturbation theory (MP2). The CCSD(T) correction term is the difference between the CCSD(T) and MP2 interaction energies evaluated in a medium basis set. However, the CCSD(T) calculations with the medium basis sets are still very expensive for systems with more than 30 atoms. Comparatively, the domain-based local pair natural orbital coupled-cluster method [DLPNO-CCSD(T)] can be applied to large systems with over 1,000 atoms. Considering both the computational accuracy and efficiency, in this work, we propose a new scheme to calculate the CCSD(T)/CBS interaction energies. In this scheme, the MP2/CBS term keeps intact and the CCSD(T) correction term is replaced by a DLPNO-CCSD(T) correction term which is the difference between the DLPNO-CCSD(T) and DLPNO-MP2 interaction energies evaluated in a medium basis set. The interaction energies of the noncovalent systems in the S22, HSG, HBC6, NBC10, and S66 databases were recalculated employing this new scheme. The consistent and tight settings of the truncation parameters for DLPNO-CCSD(T) and DLPNO-MP2 in this noncanonical CCSD(T)/CBS calculations lead to the maximum absolute deviation and root-mean-square deviation from the canonical CCSD(T)/CBS interaction energies of less than or equal to 0.28 kcal/mol and 0.09 kcal/mol, respectively. The high accuracy and low cost of this new computational scheme make it an excellent candidate for the study of large noncovalent systems.

Microbial communities inhabiting the fairy ring of Floccularia luteovirens and isolation of potential mycorrhiza helper bacteria.

Floccularia luteovirens, an important edible mushroom widely distributed in the Qinghai-Tibet plateau, is ecologically important as an ectomycorrhizal fungus and can form the fairy ring. To explore the influence of F. luteovirens fairy ring on soil microbial communities, we compared the soil microbial communities in three different fairy ring zones (inside the fairy ring (IN); beneath the fairy ring (ON); and outside the fairy ring (OUT)). A total of 1.77 million bacterial reads and 1.59 million fungal reads were obtained. Moreover, sequence clustering yielded 519,613 (57,735 per sample) bacterial OTUs, and 513,204 (57,023 per sample) fungal OTUs representing. Microbial diversity was lower in samples from the ON zone compared with the other two zones. Mycorrhiza helper bacteria (MHB) such as Bradyrhizobium and Paenibacillus were more common in the ON zone, and we isolated four potential MHB from rhizosphere soil. Canonical correspondence analysis showed that the soil nutritional condition and physical changes caused by F. luteovirens shaped the microbial communities in the ON zone. This is the first report on the study of soil microbial diversity influenced by fairy ring F. luteovirens, and further studies need to be conducted to study the ecological function influenced by this species.

[Huotan Jiedu Tongluo decoction alleviates early atherosclerosis of rabbits by inhibiting eNOS uncoupling pathway].

The aim of this paper was to study the curative effect of Huotan Jiedu Tongluo (HTJDTL) decoction on a rabbit model with early atherosclerosis (AS),and furtherly to explore whether it could inhibit the BH4/eNOS uncoupling ROS or not. Twenty-four Japanese white rabbits were randomly divided into sham operation group, model group, HTJDTL decoction group and atorvastatin group. Rabbit models with early atherosclerosis were established by high fat diet, nitrogen drying and carotid artery balloon injury. The rabbits were sacrificed at 7th days after balloon injury and several parameters were measured. The pathological morphology of the common carotid artery was observed by HE staining. The blood lipids were detected by peroxidase method. The ratio of vascular eNOS dimer and monomer was measured by Western blot. The ELISA and biochemical technology were respectively used for testing BH4 and ROS levels in serum. The results showed that compared with the sham operation group, the model group had mild stenosis of the common carotid artery lumen, uneven intimal hyperplasia, lipid deposition in the intima and media, and obvious hyperplasia of the adventitia with inflammatory cell infiltration. The HTJDTL decoction could significantly inhibit the intimal hyperplasia compared with the model group, meanwhile, reduce the lipid deposition of the media and the infiltration of the adventitial cells. Compared with the sham operation group, the blood lipids and ROS of the model animals significantly increased, but BH4 and the ratio of eNOS dimer/monomer decreased. Compared with the model group, HTJDTL decoction significantly reduced the TC, ox-LDL and ROS levels, and also up-regulated eNOS dimer/monomer ratio, but it increased BH4 trend without statistical difference. According to the results, it was found that HTJDTL decoction couldsignificantly prevent and improve the vascular remodeling of rabbits model with early atherosclerosis. The mechanism of decoction may largely be related to the inhibition of BH4/eNOS uncoupling and the reduction of oxidative stress.

Cell-Free RNA Content in Peripheral Blood as Potential Biomarkers for Detecting Circulating Tumor Cells in Non-Small Cell Lung Carcinoma.

Circulating tumor cells (CTCs) have been implicated in tumor progression and prognosis. Techniques detecting CTCs in the peripheral blood of patients with non-small cell lung carcinoma (NSCLC) may help to identify individuals likely to benefit from early systemic treatment. However, the detection of CTCs with a single marker is challenging, owing to low specificity and sensitivity and due to the heterogeneity and rareness of CTCs. Herein, the probability of cell-free RNA content in the peripheral blood as a potential biomarker for detecting CTCs in cancer patients was investigated. An immunomagnetic enrichment of real-time reverse-transcription PCR (RT-PCR) technology for analysis of CTCs in NSCLC patients was also developed. The mRNA levels of four candidate genes, cytokeratin 7 (CK7), E74-like factor 3 (ELF3), epidermal growth factor receptor (EGFR), and erythropoietin-producing hepatocellular carcinoma receptor B4 (EphB4) that were significantly elevated in tumor tissues and peripheral blood mononuclear cells (PBMCs) were determined. The expression of CK7 and ELF3 in tumor tissues and EGFR in PBMCs was associated with lymph node metastasis (all p < 0.05). The expression of CK7 in PBMCs was correlated with age and EphB4 in PBMCs correlated with histopathological type, respectively (all p < 0.05). The expression of all four genes in tumor tissues and PBMCs was significantly correlated with the clinical stage (all p < 0.01). Survival analysis showed that the patients with enhanced expression of CK7, ELF3, EGFR, and EphB4 mRNA in PBMCs had poorer disease-free survival (DFS) and overall survival (OS) than those without (all p < 0.0001). The present study showed that this alteration of cell-free RNA content in peripheral blood might have clinical ramifications in the diagnosis and treatment of NSCLC patients.

The aldosterone receptor antagonist spironolactone prevents peritoneal inflammation and fibrosis.

Peritoneal fibrosis is a complication of patients with long-term continuous ambulatory peritoneal dialysis (CAPD). Reports have indicated that angiotensin (Ang) II may correlate with the development of peritoneal fibrosis. However, it is unknown whether aldosterone also has a role in the development of peritoneal inflammation and fibrosis. The aim of the present study was to clarify the role of aldosterone in peritoneal inflammation and fibrosis. A rat model of peritoneal inflammation and fibrosis was established by daily intraperitoneal injection of dialysates and lipopolysaccharide in a 4-day interval over a period of 7 days. The animals were randomly assigned to five groups as follows: control (C); peritoneal dialysis (PD); peritoneal dialysis-spironolactone (PD-S); peritoneal dialysis-cilazapril (PD-C); and peritoneal dialysis-spironolactone-cilazapril (PD-SC). After 30 days, the TGF-ß1 concentration in dialysates from all treatment groups was determined by ELISA. The histopathology of the parietal peritoneum was examined, and the expression of MCP-1, c-Jun, fibronectin (FN) and TGF-ß1 in the abdominal membrane was determined by immunohistochemistry. Mineralocorticoid receptor (MR), 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2) and CYP11B2 (aldosterone synthase) were analyzed by real time-PCR. Collagen deposition was significantly higher in PD compared with the other groups. The expression of MR, 11ß-HSD2 and CYP11B2 was significantly higher in PD compared with the other groups. Spironolactone and/or cilazapril treatment partially ablated the increase in monocyte chemoattractant protein (MCP)-1, p-c-Jun, transforming growth factor (TGF)-ß1, FN, MR, 11ß-HSD2 and CYP11B2. Furthermore, treatment with spironolactone and/or cilazapril also reduced the infiltration of CD-4- and ED-1-positive cells in rat peritoneal tissues after peritoneal fibrosis. Exogenous aldosterone may have a key role in the development of peritoneal inflammation and fibrosis. Spironolactone decreased peritoneal inflammation and fibrosis, which was associated with reduced secretion from peritoneal macrophages, inactivation of the c-Jun N-terminal kinase (JNK) pathway and subsequent downregulation of the expression of TGF-ß1.

The effect of Se-deficient diet on gene expression of inflammatory cytokines in chicken brain.

Selenium (Se) plays an important role in the brain development, function, and degeneration, nutritional encephalomalacia is closely related with dietary Se in avian. However, there is little evidence on the relationship between inflammation and encephalomalacia in avian and the mechanism which Se regulates the inflammatory response in brain tissues remains to be unclear. The present paper describes the effects of Se-deficient granulated diet on one transcription factor-nuclear factor kappaB and four pro-inflammatory cytokines-tumor necrosis factor, cyclooxygenase2, inducible nitric oxide synthase and Prostaglandin E synthase mRNA expression in the chicken brain tissues associated encephalomalacia. One hundred male chickens (1 day old; Weiwei Co. Ltd., Harbin, China) were divided into two groups (50 chickens per group). The expression levels in the brain tissues (cerebral gray matter, cerebral white matter, marrowbrain, cerebellum, thalamus and brain stem) were determined by real-time PCR on days 15, 25, 35, 45, and 55, respectively. The results showed the productions of pro-inflammatory mediators were increased following Se-deficiency. These data indicate the correlations between nutritional encephalomalacia and inflammatory response and the activity of inflammatory response in chicken brain may be induced by Se-deficiency.

Tools for assessing quality of studies investigating health interventions using real-world data: a literature review and content analysis.

OBJECTIVES: We aimed to identify existing appraisal tools for non-randomised studies of interventions (NRSIs) and to compare the criteria that the tools provide at the quality-item level. DESIGN: Literature review through three approaches: systematic search of journal articles, snowballing search of reviews on appraisal tools and grey literature search on websites of health technology assessment (HTA) agencies. DATA SOURCES: Systematic search: Medline; Snowballing: starting from three articles (D'Andrea et al, Quigley et al and Faria et al); Grey literature: websites of European HTA agencies listed by the International Network of Agencies for Health Technology Assessment. Appraisal tools were searched through April 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included a tool, if it addressed quality concerns of NRSIs and was published in English (unless from grey literature). A tool was excluded, if it was only for diagnostic, prognostic, qualitative or secondary studies. DATA EXTRACTION AND SYNTHESIS: Two independent researchers searched, screened and reviewed all included studies and tools, summarised quality items and scored whether and to what extent a quality item was described by a tool, for either methodological quality or reporting. RESULTS: Forty-nine tools met inclusion criteria and were included for the content analysis. Concerns regarding the quality of NRSI were categorised into 4 domains and 26 items. The Research Triangle Institute Item Bank (RTI Item Bank) and STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) were the most comprehensive tools for methodological quality and reporting, respectively, as they addressed (n=20; 17) and sufficiently described (n=18; 13) the highest number of items. However, none of the tools covered all items. CONCLUSION: Most of the tools have their own strengths, but none of them could address all quality concerns relevant to NRSIs. Even the most comprehensive tools can be complemented by several items. We suggest decision-makers, researchers and tool developers consider the quality-item level heterogeneity, when selecting a tool or identifying a research gap. OSF REGISTRATION NUMBER: OSF registration DOI (https://doi.org/10.17605/OSF.IO/KCSGX).

A literature review of quality assessment and applicability to HTA of risk prediction models of coronary heart disease in patients with diabetes.

This literature review had two objectives: to identify models for predicting the risk of coronary heart diseases in patients with diabetes (DM); and to assess model quality in terms of risk of bias (RoB) and applicability for the purpose of health technology assessment (HTA). We undertook a targeted review of journal articles published in English, Dutch, Chinese, or Spanish in 5 databases from 1st January 2016 to 18th December 2022, and searched three systematic reviews for the models published after 2012. We used PROBAST (Prediction model Risk Of Bias Assessment Tool) to assess RoB, and used findings from Betts et al. 2019, which summarized recommendations and criticisms of HTA agencies on cardiovascular risk prediction models, to assess model applicability for the purpose of HTA. As a result, 71 % and 67 % models reporting C-index showed good discrimination abilities (C-index >= 0.7). Of the 26 model studies and 30 models identified, only one model study showed low RoB in all domains, and no model was fully applicable for HTA. Since the major cause of high RoB is inappropriate use of analysis method, we advise clinicians to carefully examine the model performance declared by model developers, and to trust a model if all PROBAST domains except analysis show low RoB and at least one validation study conducted in the same setting (e.g. country) is available. Moreover, since general model applicability is not informative for HTA, novel adapted tools may need to be developed.

Mechanism of Qili Qiangxin Capsule for Heart Failure Based on miR133a-Endoplasmic Reticulum Stress.

OBJECTIVE: To investigate the pharmacological mechanism of Qili Qiangxin Capsule (QLQX) improvement of heart failure (HF) based on miR133a-endoplasmic reticulum stress (ERS) pathway. METHODS: A left coronary artery ligation-induced HF after myocardial infarction model was used in this study. Rats were randomly assigned to the sham group, the model group, the QLQX group [0.32 g/(kg·d)], and the captopril group [2.25 mg/(kg·d)], 15 rats per group, followed by 4 weeks of medication. Cardiac function such as left ventricular ejection fraction (EF), fractional shortening (FS), left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), the maximal rate of increase of left ventricular pressure (+dp/dt max), and the maximal rate of decrease of left ventricular pressure (-dp/dt max) were monitored by echocardiography and hemodynamics. Hematoxylin and eosin (HE) and Masson stainings were used to visualize pathological changes in myocardial tissue. The mRNA expression of miR133a, glucose-regulated protein78 (GRP78), inositol-requiring enzyme 1 (IRE1), activating transcription factor 6 (ATF6), X-box binding protein1 (XBP1), C/EBP homologous protein (CHOP) and Caspase 12 were detected by RT-PCR. The protein expression of GRP78, p-IRE1/IRE1 ratio, cleaved-ATF6, XBP1-s (the spliced form of XBP1), CHOP and Caspase 12 were detected by Western blot. TdT-mediated dUTP nick-end labeling (TUNEL) staining was used to detect the rate of apoptosis. RESULTS: QLQX significantly improved cardiac function as evidenced by increased EF, FS, LVSP, +dp/dt max, -dp/dt max, and decreased LVEDP (P<0.05, P<0.01). HE staining showed that QLQX ameliorated cardiac pathologic damage to some extent. Masson staining indicated that QLQX significantly reduced collagen volume fraction in myocardial tissue (P<0.01). Results from RT-PCR and Western blot showed that QLQX significantly increased the expression of miR133a and inhibited the mRNA expressions of GRP78, IRE1, ATF6 and XBP1, as well as decreased the protein expressions of GRP78, cleaved-ATF6 and XBP1-s and decreased p-IRE1/IRE1 ratio (P<0.05, P<0.01). Further studies showed that QLQX significantly reduced the expression of CHOP and Caspase12, resulting in a significant reduction in apoptosis rate (P<0.05, P<0.01). CONCLUSION: The pharmacological mechanism of QLQX in improving HF is partly attributed to its regulatory effect on the miR133a-IRE1/XBP1 pathway.

Gene expression of endoplasmic reticulum resident selenoproteins correlates with apoptosis in various muscles of se-deficient chicks.

Dietary selenium (Se) deficiency causes muscular dystrophy in various species, but the molecular mechanism remains unclear. Our objectives were to investigate: 1) if dietary Se deficiency induced different amounts of oxidative stress, lipid peroxidation, and cell apoptosis in 3 skeletal muscles; and 2) if the distribution and expression of 4 endoplasmic reticulum (ER) resident selenoprotein genes (Sepn1, Selk, Sels, and Selt) were related to oxidative damages in these muscles. Two groups of day-old layer chicks (n = 60/group) were fed a corn-soy basal diet (33 µg Se/kg; produced in the Se-deficient area of Heilongjiang, China) or the diet supplemented with Se (as sodium selenite) at 0.15 mg/kg for 55 d. Dietary Se deficiency resulted in accelerated (P < 0.05) cell apoptosis that was associated with decreased glutathione peroxidase activity and elevated lipid peroxidation in these muscles. All these responses were stronger in the pectoral muscle than in the thigh and wing muscles (P < 0.05). Relative distribution of the 4 ER resident selenoprotein gene mRNA amounts and their responses to dietary Se deficiency were consistent with the resultant oxidative stress and cell apoptosis in the 3 muscles. Expression of Sepn1, Sels, and Selt in these muscles was correlated with (r > 0.72; P < 0.05) that of Sepsecs encoding a key enzyme for biosynthesis of selenocysteine (selenocysteinyl-tRNA synthase). In conclusion, the pectoral muscle demonstrated unique expression patterns of the ER resident selenoprotein genes and GPx activity, along with elevated susceptibility to oxidative cell death, compared with the other skeletal muscles. These features might help explain why it is a primary target of Se deficiency diseases in chicks.

Effect of oxygen free radicals and nitric oxide on apoptosis of immune organ induced by selenium deficiency in chickens.

Selenium is an essential element with antioxidant roles in immune regulation, but there is little understanding of how Se acts in apoptosis in the immune organs of birds. The aim of study was to evaluate the influence of Se deficiency on oxygen free radicals, NO and apoptosis in immune organ of chickens. 160 1-day-old chickens were randomly assigned to two groups of 80 each and were fed on a low-Se diet (0.032 mg/kg Se) or a control diet (0.282 mg/kg Se), respectively. OFR production in blood was determined on days 30, 45, 60 and 75, respectively. The iNOS-NO system activity in immune organ (thymus, spleen, bursa of fabricius) was identified by NO content and NOS activity assay on days 30, 45, 60 and 75, respectively. Apoptosis was measured by DNA ladder analysis, ultrastructural observations, TdT-mediated dUTP nick end labeling TUNEL assay and flow cytometric analysis of apoptotic DNA. The transcription of factor-associated suicide, caspase-3 mRNA was tested by fluorescence quantitative PCR. The results showed that OFR production, NO and inducible NO synthases (iNOS) activity in the low-Se group were significantly increased (p < 0.05) than in the control group. In addition, apoptosis was observed in chicken immune organ in the low-Se group. The degree and the number of apoptotic cells rose in a time-dependent manner. The expression of Fas and caspase-3 mRNA increased (p < 0.05) than in the control group. It indicated that the oxidative stress and NO played a causative role in the apoptosis of immune tissues induced by selenium deficiency.

The satisfaction of the undergraduate nursing classroom teaching quality based on the Kano model in China.

Objectives: To investigate the satisfaction of the undergraduate nursing classroom teaching quality based on the Kano model and provide a reference for improving the overall quality of educational services. Methods: A total of 621 sophomores and juniors of nursing at Hubei University of Medicine were selected to conduct questionnaires based on the Kano model using convenient sampling. Results: The 16 items are all a one-dimensional factor. The satisfaction and importance are 0.77 to 0.86 and -0.58 to -0.80, respectively. In the quadrant analysis chart, there are four items in the dominant area, three items for improvement, three in the observation area, and six in the retention area. Conclusion: Analyzing the satisfaction of nursing undergraduates' classroom teaching quality can help us effectively understand the intrinsic needs of students and improve the overall quality of nursing undergraduates' curriculum teaching services.