The relationship between organizational support, professional quality of life, decent work, and professional well-being among nurses: a cross-sectional study.

BACKGROUND: Nurses often face challenges such as inadequate welfare protection, injustice, and workplace adversity including violence, bullying, and sexual harassment. In this context, providing sufficient support to nurses is crucial for the promotion of their professional well-being. This study examines the direct and indirect effects of perceived organizational support on nurses' well-being, particularly highlighting the mediating roles of professional quality of life and the perception of decent work. METHODS: A cross-sectional survey design was employed in this study. Convenience sampling was used to survey 792 nurses from five tertiary A-grade hospitals in Shanxi Province in January 2024. Data collection tools included a custom demographic survey, the Perceived Organizational Support Scale, Professional Quality of Life Scale, Decent Work Perception Scale, and Nurse Occupational Well-being Questionnaire. Descriptive statistics, correlation analysis, and mediation effect analyses were performed. RESULTS: The findings demonstrate that perceived organizational support has a direct impact on nurses' occupational well-being (ß = 0.323, p < 0.001). Additionally, professional quality of life and the perception of decent work play chain mediating roles between perceived organizational support and nurses' well-being (ß = 0.019, BootLLCI = 0.010, BootULCI = 0.030). CONCLUSIONS: This study highlighted the importance of organizational support in enhancing nurses' well-being. Professional quality of life and decent work were key mediators. Healthcare institutions should prioritize support measures to improve nurses' well-being. Future research should explore additional mediators and mechanisms to develop effective strategies for nursing policymakers and administrators.

Impact of knowledge, attitudes and self-reported practices of nurses on early mobilization of mechanically ventilated patients in the ICU.

BACKGROUND: Many ICUs worldwide are striving to integrate early mobilization as part of critical care rehabilitation. However, ICU nurses, who are essential contributors to the early mobilization of critically ill patients, still lack comprehensive surveys assessing their knowledge, beliefs, and practices regarding the early mobilization of mechanically ventilated patients. AIM: To analyse the knowledge, attitudes, and practices of intensive care unit (ICU) nurses regarding the early mobilization of mechanically ventilated patients and to explore the effects of these practices. STUDY DESIGN: A multicentre cross-sectional study. ICU nurses in five tertiary hospitals in Zhejiang Province, China, were selected by convenience sampling and invited to complete an online questionnaire between 1 June 2021 and 15 June 2021. Sociodemographic data and the knowledge, attitudes, and practices of ICU nurses regarding early mobilization. RESULTS: A total of 296 valid questionnaires were collected, for a response rate of approximately 77.5%. The average scores for knowledge, attitudes, and practices of ICU nurses regarding the early mobilization of mechanically ventilated patients were 42.7 ± 7.4, 34.3 ± 6.5, and 47.1 ± 6.5, respectively, which were good scores. Quantile regressions showed that at the 25% and 50% quartiles, increases in knowledge and attitude scores resulted in increases in practice scores (p < .001); however, at the 75% quartile, increases in knowledge scores did not result in practice score increases (t = 0.000, p = .999); moreover, there was still a 0.5-point increase in practice scores per 1-point increase in attitude scores (t = 0.500, p < .001). CONCLUSIONS: The knowledge, attitudes, and self-reported practices of ICU nurses were good, although there is room for improvement. Considering that the influence of attitudes on practice improvement is more important than knowledge, ICU managers should promote knowledge transformation, strengthen attitudes, and adopt comprehensive measures to promote the early mobilization of mechanically ventilated patients in the ICU. RELEVANCE TO CLINICAL PRACTICE: To optimize the early mobilization of mechanically ventilated patients in the ICU, introducing multipronged support strategies based on the knowledge and attitudes of ICU nurses is recommended to promote the implementation of such practices.

Effects of the Implementation of Intelligent Technology for Hand Hygiene in Hospitals: Systematic Review and Meta-analysis.

BACKGROUND: The World Health Organization recommends regular hand hygiene monitoring and feedback to improve hand hygiene behaviors and health care-associated infection rates. Intelligent technologies for hand hygiene are increasingly being developed as alternative or supplemental monitoring approaches. However, there is insufficient evidence regarding the effect of this type of intervention, with conflicting results in the literature. OBJECTIVE: We conduct a systematic review and meta-analysis to evaluate the effects of using intelligent technology for hand hygiene in hospitals. METHODS: We searched 7 databases from inception to December 31, 2022. Two reviewers independently and blindly selected studies, extracted data, and assessed the risk of bias. A meta-analysis was performed using the RevMan 5.3 and STATA 15.1 software. Sensitivity and subgroup analyses were also conducted. Overall certainty of evidence was appraised using the Grading of Recommendations Assessment, Development, and Evaluation approach. The systematic review protocol was registered. RESULTS: The 36 studies comprised 2 randomized controlled trials and 34 quasi-experimental studies. The included intelligent technologies involved 5 functions: performance reminders，electronic counting and remote monitoring，data processing，feedback，and education. Compared with usual care, the intelligent technology intervention for hand hygiene improved health care workers' hand hygiene compliance (risk ratio 1.56, 95% CI 1.47-1.66; P<.001), reduced health care-associated infection rates (risk ratio 0.25, 95% CI 0.19-0.33; P<.001), and was not associated with multidrug-resistant organism detection rates (risk ratio 0.53, 95% CI 0.27-1.04; P=.07). Three covariates, including publication year, study design, and intervention, were not factors of hand hygiene compliance or hospital-acquired infection rates analyzed by meta-regression. Sensitivity analysis showed stable results except for the pooled outcome of multidrug-resistant organism detection rates. The caliber of 3 pieces of evidence suggested a dearth of high-caliber research. CONCLUSIONS: Intelligent technologies for hand hygiene play an integral role in hospital. However, low quality of evidence and important heterogeneity were observed. Larger clinical trials are required to evaluate the impact of intelligent technology on multidrug-resistant organism detection rates and other clinical outcomes.

Effect of nutritional status on outcomes in children receiving umbilical cord blood stem cell transplantation.

BACKGROUND AND OBJECTIVES: The impacts of nutritional status on clinical outcomes in children receiving umbilical cord blood stem cell transplantation (UCBT) are not fully described. We evaluated the risk for malnutrition before transplantation admission and influence of weight loss during hospitalization on short-term clinical outcomes in children with UCBT. METHODS AND STUDY DESIGN: We conducted a retrospective study of pediatric patients up to age 18 years who received UCBT and were treated at the Children's Hospital of Fudan University between January 2019 and December 2020. RESULTS: The mean age of the 91 patients was 1.3 years, with 78 (85.7%) men and 13 (14.3%) women (p<0.001). UCBT was performed mostly for primary immunodeficiency disease (PID) (83, 91.2%). The weight loss differences among children with different primary diseases were statistically significant (p=0.003). Children with a large amount of weight loss during hospitalization (n = 24) had higher risks of skin graft-versus-host disease (GVHD) (multivariate OR=5.01, 95% CI: 1.35-18.65), intestinal GVHD (multivariate OR=7.27, 95% CI: 1.74-30.45), a longer median hospital stay (p=0.004), higher antibiotic costs (p=0.008) and higher total hospitalization costs (p=0.004). Malnutrition on admission was significantly positively correlated with longer parenteral nutrition (PN) time (p=0.008). Early nutritional intervention effects on clinical outcomes need further assessment. CONCLUSIONS: Underweight recipient child and excessive weight loss during transplantation increases the length and cost of hospital stay, and is associated with a high incidence of GVHD, which affects the prognosis of transplantation and medical resources consumption.

Critical care nurses' experiences of physical restraint in intensive care units: A qualitative systematic review and meta-synthesis.

INTRODUCTION: Physical restraint is widely used in intensive care units. Critical care nurses are the primary decision makers and practitioners of physical restraint. However, little is known about the qualitative evidence of their experience of physical restraint. AIMS: To aggregate, synthesise and interpret the qualitative evidence of studies that explored critical care nurses' experiences of physical restraint in intensive care units. METHODS: A qualitative systematic review and meta-synthesis was conducted following Joanna Briggs Institute methodology and reported following the ENTREQ statement. Qualitative studies published in the English and Chinese were systematically searched in eight databases. PubMed, Web of Science, CINAHL, EMBASE, PsycINFO, China National Knowledge Infrastructure, Wan Fang, and Chinese Biomedical Literature Database from inception to November 2021. Two reviewers independently assessed the study eligibility and performed the data extraction and the quality appraisal. A meta-aggregative approach was used to synthesise findings. The review protocol was registered prospectively with PROSPERO (CRD42021278671). RESULTS: Thirteen studies were included. A total of 48 intact and definite codes were extracted and classified into ten sub-categories. Four themes were finally identified: intention, alternatives, determinants, and reflection. CONCLUSION: The intention of critical care nurses to use physical restraint is primarily driven by patient safety. Nurses will consider alternatives; however, many determinants urge nurses to implement physical restraint. Nurses prefer to sacrifice patients' comfort to ensure their safety. When nurses reflect on what they have done, some experience moral distress, but most rationalise their decision making. Further studies should explore the safety of alternatives, reduce the use of physical restraint, and pay more attention to nurses' moral distress through these insights. RELEVANCE TO CLINICAL PRACTICE: Developing alternatives, providing relevant training for nurses, physicians, patients, and families to facilitate a restraint-free culture, and developing high-quality guidelines and regulations are essential strategies to reduce the use of physical restraint in ICUs.

Instruments for assessing the spiritual needs of cancer patients: A systematic review of psychometric properties.

AIMS AND OBJECTIVES: To identify available instruments for assessing cancer patients' spiritual needs and to examine their psychometric properties using the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) methodology. BACKGROUND: Cancer patients frequently have significant spiritual needs. The nurse plays an integral role in assessing the patient's spiritual needs as part of providing holistic care. It is crucial to assess these needs using appropriate and reliable instruments. DESIGN: A systematic review based on COSMIN methodology. METHODS: Seven electronic databases (PubMed, EMBASE, CINAHL, Web of Science, ProQuest, CNKI and WANFANG) were systematically searched from inception until 14 February 2023. Two authors independently screened eligible literature, extracted data and evaluated methodological and psychometric quality. This systematic review was conducted following the PRISMA checklist. RESULTS: Sixteen studies have reported 16 different versions of the instruments. None of the instruments were properly assessed for all psychometric properties, nor were measurement error, responsiveness and cross-cultural validity/measurement invariance reported. All of the instruments failed to meet the COSMIN quality criteria for content validity. The quality of evidence for structural validity and/or internal consistency in five instruments did not meet the COSMIN criteria. Eventually, five instruments were not recommended, and 11 were only weakly recommended. CONCLUSION: Instruments to assess spiritual needs exhibited limited reliability and validity. The Spiritual Care Needs Scale is provisionally recommended for research and clinical settings, but its limitations regarding content validity and cross-cultural application must be considered in practice. Future research should further revise the content of available instruments and comprehensively and correctly test their psychometric properties. RELEVANCE TO CLINICAL PRACTICE: The review findings will provide evidence for healthcare professionals to select instruments for recognising spiritual needs in cancer patients. NO PATIENT OR PUBLIC CONTRIBUTION: This study is a systematic review with no patient or public participation.

Evaluation of the Antioxidant Activities and Phenolic Profile of Shennongjia Apis cerana Honey through a Comparison with Apis mellifera Honey in China.

This study evaluates the phenolic profile as well as the antioxidant properties of Shennongjia Apis cerana honey through a comparison with Apis mellifera honey in China. The total phenolic content (TPC) ranges from 263 ± 2 to 681 ± 36 mg gallic acid/kg. The total flavonoids content (TFC) ranges from 35.9 ± 0.4 to 102.2 ± 0.8 mg epicatechin/kg. The correlations between TPC or TFC and the antioxidant results (FRAP, DPPH, and ABTS) were found to be statistically significant (p < 0.01). Furthermore, the phenolic compounds are quantified and qualified by high performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS), and a total of 83 phenolic compounds were tentatively identified in this study. A metabolomics analysis based on the 83 polyphenols was carried out and subjected to principal component analysis and orthogonal partial least squares-discriminant analysis. The results showed that it was possible to distinguish Apis cerana honey from Apis mellifera honey based on the phenolic profile.

The effect of psychological contract on turnover intention among nurses: a meta-analytic review.

BACKGROUND: The turnover intention (TI) of nurses is common, posing a threat to modern healthcare organizations. Psychological contract (PC) is a predictor of TI, affecting significantly nurse's TI. However, the extent of the association between PC and nurse's TI is unknown. We performed a meta-analysis to quantitatively analyze the relationship between PC and nurse's TI. METHODS: We searched nine electronic databases from inception to July 2023. Observational studies were included using a retrieval strategy related to PC and TI. Meta-analyses of common effect and random effect models were performed using R software with Spearman or Pearson correlation coefficients. Meta-regression, subgroup analysis, publication bias, and sensitivity analysis were also carried out . RESULTS: Eighteen studies including 8,908 nurses were identified. Based on various PC-related perspectives, 16 studies explored nurses' TI in terms of the content and three-dimensional structure of PC. Of these, 9 studies reported the negative direction of the correlation between PC and TI (r ranged from - 0.20 to -0.45), whereas 7 studies reported the positive direction of the correlation between PC and TI (r ranged from 0.32 to 0.50). The PC total and its dimensions were found to have moderately significant associations with TI, with the exception of the PCE and PCE-I. Additional, 2 studies reported the relationship between the outcome of PC and TI, the PCF, PCB, and PCV were powerful predictors of nurses' TI. Meta-regression and subgroup analysis found that only nurses working in specialized departments might be the source of heterogeneity. CONCLUSIONS: To our knowledge, this was the first meta-analysis to quantitatively examine the relationship between PC and TI among nurses. The findings reaffirmed the necessity for healthcare administrators and the medical profession to valued nurse' good interpersonal, social support, humanistic environment, and meet nurses' psychological and spiritual needs in addition to their material demands. Moderators of the connection between PC and TI, based on meta-regression and subgroup analyses, should be carefully explored as they may aid in identifying nurses' TI. Additional, longitudinal research, as well as mixed research, should be conducted to more comprehensively explore the relationship between PC and TI.

The prevalence and interventions of xerosis cutis among older adults: A systematic review and meta-analysis.

BACKGROUND: Xerosis cutis in older adults is a geriatric public health issue that severely affects healthy aging, associated with adverse outcomes and increased nursing burden. Skin care plays a significant role in the management of xerosis cutis. AIM: To assess the pooled prevalence and interventions of xerosis cutis among older adults. METHODS: We searched ten databases systematically from inception to August 29, 2023. We estimated pooled prevalence of xerosis cutis using Stata 15.0. RESULTS: 28 articles were included in this review. The pooled prevalence of xerosis cutis was 53 %(95 %CI:36-69 %). We found the prevalence of xerosis cutis was highest in nursing homes and developed countries. The prevalence of xerosis cutis was similar in males and females. The prevalence of mild xerosis cutis and xerosis cutis at lower limbs was relatively high. Regular use of humectant-containing leave-on skin care products and structured skin care regimens were helpful in alleviating xerosis cutis. CONCLUSION: Older adults are at high risk for xerosis cutis. The research provides health professionals with a basic framework for the prevention and management of xerosis cutis.

Targeting Amyloids with [18F]AV-45 for Medullary Thyroid Carcinoma Positron Emission Tomography/Computed Tomography Imaging: A Pilot Clinical Study.

Medullary thyroid carcinoma (MTC) is a malignant neuroendocrine tumor with a high recurrence rate. Amyloid plaques formed from the misfolding of calcitonin are the key characteristics of MTC. Herein, we conducted a first-in-human pilot clinical study by applying a ß-amyloid-specific radiotracer, [18F]AV-45, to positron emission tomography (PET)/computed tomography (CT) imaging of MTC. The presence of amyloid plaques in the tumor tissue sections from five MTC patients was confirmed by hematoxylin and eosin (H&E) and Congo Red staining. [18F]AV-45 selectively accumulated in the amyloid plaques in the continued tumor tissue sections with similar distribution patterns to the H&E and Congo Red staining. In addition, the [18F]AV-45 uptake can be largely blocked by its nonradioactive reference compound. The [18F]AV-45 accumulation in the thyroid, neck lymph nodes, and muscles in healthy human subjects is close to the background indicated by PET/CT imaging. In the comparison PET/CT imaging study of a recurrent MTC patient, 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) showed an elevated uptake by multiple neck lymph nodes. In contrast, only one of these neck lymph nodes had increased [18F]AV-45 uptake. Postoperative histopathological analysis confirmed the [18F]AV-45 PET-positive lymph node as MTC with amyloid deposition, while other [18F]FDG positive lymph nodes were free from MTC and amyloid plaques. Thus, [18F]AV-45 showed the promise for the clinical PET/CT imaging of MTC.

Nutrition status survey of type 2 and 3 spinal muscular atrophy in Chinese population.

OBJECTIVE: To evaluate the nutritional status of children with SMA types II and III in a Chinese population. METHODS: We performed a retrospective medical record review of prospectively collected data from children with SMA types II and III in a single centre. We analysed data including clinical parameters, anthropometrics, and 24-hour dietary intake records in our clinic. RESULTS: We analysed the anthropometric data from 86 children with 69 (80%) SMAII and 17 (20%) SMAIII; 47 (55%) were female, mean age was 5.22 ± 3.73 years. The WAZ of the SMAII (n = 69) and SMAIII (n = 17) were -0.48 (IQR -1.69, 0.57) vs -0.53 (IQR -1.60, 0.55), P = 0.926; the HAZ were -0.62 (IQR -1.4, 0.3) vs -0.6 (IQR -1.61, 0.4), P=0.72; the BMIZ were -0.51 (IQR -1.53, 0.99) vs -0.08 (IQR -1.625, 1.125), P = 0.537.The dietary intake of 51 children was compared to the Chinese Dietary Reference Intakes (DRIs). The actual energy intake in SMAII was similar to the DRIs, but which in SMAIII was less than the DRIs (1312.4 ± 329.5 kcal vs. 1655 ± 640.1 kcal, P = 0.028). The protein intake in SMAII and SMAIII was higher than the DRIs (55 ± 16.3 g/d vs 30.2 ± 4.6 g/d, P < 0.05; 56.8 ± 18.1 g/d vs 41.5 ± 17.5 g/d, p = 0.22), and calcium intake was lower than the recommendation (507.7 ± 177.8 mg/d vs 731.7 ± 123.4 mg/d, P < 0.05; 478.4 ± 207.4 mg/d vs 478.4 ± 207.4 mg/d, P = 0.01). Swallowing on the Neuromuscular Disease Status Scale was 7.41 ± 0.5. CONCLUSIONS: Children with SMAII and SMAIII were at risk for malnutrition and low calcium intake.

[Anti-asthma components and mechanism of Kechuanting acupoint application therapy: based on serum metabolomics and network pharmacology].

This study aims to explore the anti-asthma components and mechanism of Kechuanting acupoint application therapy(KAAT) based on serum metabolomics and network pharmacology. A total of 60 asthma patients who had used low-dose inhaled corticosteroids-formoterol(ICS-formoterol) for a long time were randomized into the western medicine group(low-dose ICS-formoterol) and western medicine+Kechuanting group(KAAT+low-dose ICS-Formoterol), 30 in either group. In addition, 30 healthy people were included as the control(no intervention). The asthma control test(ACT) score, forced expiratory volume in 1 second(FEV1), and peak expiratory flow(PEF) were measured in the western medicine group and western medicine+Kechuanting group before and after treatment. The potential biomarkers of KAAT in the treatment of asthma were screened by gas chromatography-mass spectrometry combined with multivariate analysis, and the related metabolic pathways were further analyzed. UPLC/LTQ-Orbitrap-MS, together with network pharmacology, was employed to construct the component-target-pathway network. Thereby, the effective components and me-chanism of KAAT in the treatment of asthma were clarified. According to the ACT score, FEV1, and PEF, KAAT was effective in the treatment of asthma. A total of 10 endogenous biomarkers of KAAT in the treatment of asthma were screened by serum metabolomics, and the pathways of the metabolism of glycine, serine and threonine, and the metabolism of glyoxylic acid and dicarboxylic acid were obtained. UPLC/LTQ-Orbitrap-MS identified 51 chemical components of KAAT: 24 flavonoids, 11 alkaloids, 8 phenols, 2 diterpenoids, 2 triterpenoids, 2 glycosides, and 2 aldehydes. Network pharmacology analysis suggested that KAAT mainly acted on serum crea-tinine(SRC), matrix metalloproteinase 9(MMP-9), and other target proteins. The treatment was closely related to metabolic pathway, phosphatidylinositol 3-kinase-protein kinase B(PI3 K-Akt), mitogen-activated protein kinase(MAPK), and calcium signaling pathway. Sinapine thiocyanate, corydaline, dihydroberberine, stylopine, leonticine, N-methyl tetrahydroberberine, kaempferide, erio-dictyol, quercetin, catechin, 6-gingerol, 6-shogaol, ingenol, and luteolin may be potential effective compounds of KAAT in the treatment of asthma. This study preliminarily revealed that the effective components and mechanism of KAAT in treatment of asthma based on serum metabolomics and network pharmacology. It lays a theoretical foundation for in-depth study of the mechanism and clinical development and application.

Assessment of the toxicity and toxicokinetics of the novel potent tropomyosin receptor kinase (Trk) inhibitor LPM4870108 in rhesus monkeys.

LPM4870108 is a tropomyosin receptor kinase (Trk) inhibitor that is currently under consideration for human clinical trials. We characterized the toxicity and toxicokinetic properties of LPM4870108 following its oral administration to rhesus monkeys (5, 10, or 20 mg/kg/day for 4 weeks with a 4-week recovery period). No evidence of LPM4870108 toxicity was observed over this study as reflected by an absence of difference in body weight, ophthalmoscopy, urinalysis, gross, or histopathology findings. No significant differences in toxicity-related outcomes were detected when comparing LPM4870108 and control groups, and no significant treatment-related changes in food consumption, electrocardiogram results, blood pressure, hematological parameters, biochemical values, organ weight, or bone marrow parameters were observed. Treatment caused dose-dependent effects of gait disturbance, impaired balance, poor coordination, and decreased grip strength in all LPM4870108-treated animals, with these effects being attributable to excessive on-target Trk receptor inhibition. After the 4-week recovery period, all these abnormal treatment-related findings had fully or partially resolved. The toxicokinetic study of monkeys revealed that the LPM4870108 exposure increased with dose. Overall, LPM4870108 exhibited a safety profile in treated monkeys, indicating that the Highest Non-Severely Toxic Dose (HNSTD) for LPM4870108 in monkeys was 20 mg/kg/day.

A novel splicing mutation of PTCH1 in a Chinese family with nevoid basal cell carcinoma syndrome.

Nevoid basal cell carcinoma syndrome (NBCCS) is a rare autosomal dominant disease characterized by the development of multiple jaw keratocysts and basal cell carcinomas (BCC) and accompanied by diverse phenotypes. The establishment of diagnosis lies on the identification of a heterozygous germline pathogenic variant in the patched homolog 1 gene (PTCH1). PTCH1 has alternative splicing and selective initial coding exon, leading to three types of encoding proteins (PTCHL, PTCHM and PTCHS). The expression of each protein in NBCCS remains ambiguous, especially the importance of the first two exons in translation. Here, we report a Chinese NBCCS family of a novel PTCH1 heterozygous mutation (IVS 2, c.394+1G>T, g.10652G>T) identified by genomic sequencing and reverse-transcription-PCR as aberrant splicing. To the best of our knowledge, this is the first report of NBCCS with a splicing site mutation in intron 2 resulting in exon 2 skipping. Our finding suggests that exon 2 plays an important role in the development of NBCCS and further speculates that the role of longer isoforms PTCHL and PTCHM is crucial in NBCCS, while that of short isoform PTCHS might be dispensable.

[Clinical effect of carvedilol in treatment of children with severe hand-foot-mouth disease caused by enterovirus 71 infection].

OBJECTIVE: To study the clinical effect of carvedilol in the treatment of children with severe hand-foot-mouth disease (HFMD) caused by enterovirus 71 (EV71) infection. METHODS: A retrospective analysis was performed for the clinical data of 86 children with severe HFMD caused by EV71 infection who were admitted to the hospital from April 2016 to August 2017. According to whether carvedilol was used, the children were divided into conventional treatment group with 51 children and carvedilol treatment group with 35 children. A total of 56 healthy children who underwent physical examination at the outpatient service during the same period were enrolled as the control group. The two treatment groups were compared in terms of clinical features and levels of catecholamines (norepinephrine, adrenaline and dopamine), and the levels of catecholamines were compared between these two treatment groups and the control group. RESULTS: Before treatment, the conventional treatment group and the carvedilol treatment group had significantly higher levels of norepinephrine and adrenaline than the control group (P<0.05). After treatment, both the conventional treatment group and the carvedilol treatment group had significant reductions in norepinephrine, adrenaline, blood glucose, systolic pressure, diastolic pressure, heart rate, body temperature and leukocyte count (P<0.05). Compared with the conventional treatment group, the carvedilol treatment group had significantly lower dopamine level, blood glucose, heart rate and respiratory rate after treatment (P<0.05). CONCLUSIONS: Changes in norepinephrine and adrenaline might be involved in the pathogenesis of severe HFMD caused by EV71 infection. Carvedilol, in addition to the conventional treatment, can improve respiration, heart rate and blood glucose in children with severe HFMD caused by EV71 infection.

Non-native Conformers of Cystic Fibrosis Transmembrane Conductance Regulator NBD1 Are Recognized by Hsp27 and Conjugated to SUMO-2 for Degradation.

A newly identified pathway for selective degradation of the common mutant of the cystic fibrosis transmembrane conductance regulator (CFTR), F508del, is initiated by binding of the small heat shock protein, Hsp27. Hsp27 collaborates with Ubc9, the E2 enzyme for protein SUMOylation, to selectively degrade F508del CFTR via the SUMO-targeted ubiquitin E3 ligase, RNF4 (RING finger protein 4) (1). Here, we ask what properties of CFTR are sensed by the Hsp27-Ubc9 pathway by examining the ability of NBD1 (locus of the F508del mutation) to mimic the disposal of full-length (FL) CFTR. Similar to FL CFTR, F508del NBD1 expression was reduced 50-60% by Hsp27; it interacted preferentially with the mutant and was modified primarily by SUMO-2. Mutation of the consensus SUMOylation site, Lys(447), obviated Hsp27-mediated F508del NBD1 SUMOylation and degradation. As for FL CFTR and NBD1 in vivo, SUMO modification using purified components in vitro was greater for F508del NBD1 versus WT and for the SUMO-2 paralog. Several findings indicated that Hsp27-Ubc9 targets the SUMOylation of a transitional, non-native conformation of F508del NBD1: (a) its modification decreased as [ATP] increased, reflecting stabilization of the nucleotide-binding domain by ligand binding; (b) a temperature-induced increase in intrinsic fluorescence, which reflects formation of a transitional NBD1 conformation, was followed by its SUMO modification; and (c) introduction of solubilizing or revertant mutations to stabilize F508del NBD1 reduced its SUMO modification. These findings indicate that the Hsp27-Ubc9 pathway recognizes a non-native conformation of mutant NBD1, which leads to its SUMO-2 conjugation and degradation by the ubiquitin-proteasome system.

VAMP-associated Proteins (VAP) as Receptors That Couple Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Proteostasis with Lipid Homeostasis.

Unesterified cholesterol accumulates in late endosomes in cells expressing the misfolded cystic fibrosis transmembrane conductance regulator (CFTR). CFTR misfolding in the endoplasmic reticulum (ER) or general activation of ER stress led to dynein-mediated clustering of cholesterol-loaded late endosomes at the Golgi region, a process regulated by ER-localized VAMP-associated proteins (VAPs). We hypothesized that VAPs serve as intracellular receptors that couple lipid homeostasis through interactions with two phenylalanines in an acidic track (FFAT) binding signals (found in lipid sorting and sensing proteins, LSS) with proteostasis regulation. VAPB inhibited the degradation of ΔF508-CFTR. The activity was mapped to the ligand-binding major sperm protein (MSP) domain, which was sufficient in regulating CFTR biogenesis. We identified mutations in an unstructured loop within the MSP that uncoupled VAPB-regulated CFTR biogenesis from basic interactions with FFAT. Using this information, we defined functional and physical interactions between VAPB and proteostasis regulators (ligands), including the unfolded protein response sensor ATF6 and the ER degradation cluster that included FAF1, VCP, BAP31, and Derlin-1. VAPB inhibited the degradation of ΔF508-CFTR in the ER through interactions with the RMA1-Derlin-BAP31-VCP pathway. Analysis of pseudoligands containing tandem FFAT signals supports a competitive model for VAP interactions that direct CFTR biogenesis. The results suggest a model in which VAP-ligand binding couples proteostasis and lipid homeostasis leading to observed phenotypes of lipid abnormalities in protein folding diseases.

[Multi-view Stereo 3D Reconstruction of Medical Implants].

In order to facilitate the doctor to obtain information more comprehensively and operate accurately from a three-dimensional perspective in interventional therapy, the paper uses a multi-view stereo reconstruction algorithm for three-dimensional reconstruction of medical implants in vitro. The effects of shooting and environmental conditions on reconstruction time and effect were analyzed. We use the convenient shooting device to collect multi-view images of the stent and open source software to acquire the point cloud data. By using reverse engineering software, the point cloud is processed interactively and the surface is generated. Eventually, the 3D model of the implant is reconstructed, which can be used for industrial production.

Divergent signaling via SUMO modification: potential for CFTR modulation.

The cystic fibrosis transmembrane conductance regulator (CFTR) is generally responsible for the cAMP/PKA regulated anion conductance at the apical membranes of secretory epithelial cells. Mutations in CFTR underlie cystic fibrosis (CF), in which the most common variant, F508del, causes protein misfolding and its proteasome-mediated degradation. A new pathway that contributes to mutant CFTR degradation is mediated by the small heat shock protein, Hsp27, which cooperates with Ubc9, the E2 enzyme for SUMOylation, to selectively conjugate mutant CFTR with SUMO-2/3. This SUMO paralog can form polychains, which are recognized by the ubiquitin E3 enzyme, RNF4, leading to CFTR ubiquitylation and recognition by the proteasome. We found also that F508del CFTR could be modified by SUMO-1, a paralog that does not support SUMO polychain formation. The use of different SUMO paralogs to modify and target a single substrate for divergent purposes is not uncommon. In this short review we discuss the possibility that conjugation with SUMO-1 could protect mutant CFTR from disposal by RNF4 and similar ubiquitin ligases. We hypothesize that such a pathway could contribute to therapeutic efforts to stabilize immature mutant CFTR and thereby enhance the action of therapeutics that correct CFTR trafficking to the apical membranes.

pFPL Vectors for High-Throughput Protein Localization in Fungi: Detecting Cytoplasmic Accumulation of Putative Effector Proteins.

As part of a large-scale project whose goal was to identify candidate effector proteins in Magnaporthe oryzae, we developed a suite of vectors that facilitate high-throughput protein localization experiments in fungi. These vectors utilize Gateway recombinational cloning to place a gene's promoter and coding sequences upstream and in frame with enhanced cyan fluorescent protein, green fluorescent protein (GFP), monomeric red fluorescence protein (mRFP), and yellow fluorescent protein or a nucleus-targeted mCHERRY variant. The respective Gateway cassettes were incorporated into Agrobacterium-based plasmids to allow efficient fungal transformation using hygromycin or geneticin resistance selection. mRFP proved to be more sensitive than the GFP spectral variants for monitoring proteins secreted in planta; and extensive testing showed that Gateway-derived fusion proteins produced localization patterns identical to their "directly fused" counterparts. Use of plasmid for fungal protein localization (pFPL) vectors with two different selectable markers provided a convenient way to label fungal cells with different fluorescent proteins. We demonstrate the utility of the pFPL vectors for identifying candidate effector proteins and we highlight a number of important factors that must be taken into consideration when screening for proteins that are translocated across the host plasma membrane.