Recent advances of multifunctional zwitterionic polymers for biomedical application.

Zwitterionic polymers possess equal total positive and negative charges in the repeating units, making them electrically neutral overall. This unique property results in superhydrophilicity, which makes the zwitterionic polymers highly effective in resisting protein adsorption, thus endowing the drug carriers with long blood circulation time, inhibiting thrombus formation on biomedical devices in contact with blood, and ensuring the good sensitivity of sensors in biomedical application. Moreover, zwitterionic polymers have tumor-targeting ability and pH-responsiveness, rendering them ideal candidates for antitumor drug delivery. Additionally, the high ionic conductivity of zwitterionic polymers makes them an important raw material for ionic skin. Zwitterionic polymers exhibit remarkable resistance to bacterial adsorption and growth, proving their suitability in a wide range of biomedical applications such as ophthalmic applications, and wound dressings. In this paper, we provide an in-depth analysis of the different structures and characteristics of zwitterionic polymers and highlight their unique qualities and suitability for biomedical applications. Furthermore, we discuss the limitations and challenges that must be overcome to realize the full potential of zwitterionic polymers and present an optimistic perspective for zwitterionic polymers in the biomedical fields. STATEMENT OF SIGNIFICANCE: Zwitterionic polymers have a series of excellent properties such as super hydrophilicity, anti-protein adsorption, antibacterial ability and good ionic conductivity. However, biomedical applications of multifunctional zwitterionic polymers are still a major field to be explored. This review focuses on the design and application of zwitterionic polymers-based nanosystems for targeted and responsive delivery of antitumor drugs and cancer diagnostic agents. Moreover, the use of zwitterionic polymers in various biomedical applications such as biomedical devices in contact with blood, biosensors, ionic skin, ophthalmic applications and wound dressings is comprehensively described. We discuss current results and future challenges for a better understanding of multifunctional zwitterionic polymers for biomedical applications.

"Let them be": Family members' perspectives on the participation of advanced cancer patients in nursing research: A qualitative descriptive study.

BACKGROUND: Recruiting advanced cancer patients is crucial for nursing research in cancer care. However, nurse researchers often face various socio-cultural challenges, particularly in mainland China, where cultural taboos around death pose significant obstacles. An unexplored constraint in this context is the pivotal role Chinese family members play in patients' healthcare decision-making. This research gap underscores the need for a deeper understanding of Chinese family members' perspectives on the engagement of advanced cancer patients in nursing research. OBJECTIVE: To explore the perceptions and concerns of family members regarding the recruitment and participation of advanced cancer patients in nursing research. DESIGN: A qualitative descriptive study was conducted. SETTINGS: Three cancer hospitals in mainland China. PARTICIPANTS: A purposive sample of 18 family members, consisting of children or spouses of advanced cancer patients, was recruited as participants. METHODS: Semi-structured interviews were conducted to collect data between September 2022 and January 2023. The thematic analysis method was used to analyze the data. RESULTS: Three themes were identified: The absence of prior participation, Family members' reluctance to facilitate patient involvement, and Strategies to encourage patients' future participation. Family members were hesitant to allow their relatives with advanced cancer to engage in nursing research, primarily due to concerns about distressing patients, the use of potential sensitive language, stigma, and the risks involved in participation. To address these concerns, they emphasized the importance of gaining family approval prior to patient enrolment. They highlighted the need of family involvement on behalf of sick relatives in research, advocating for the inclusion of a wide range of patients rather than targeting specific subgroups. They also reiterated the significance of choosing the right time for participation and avoiding using sensitive terms such as 'cancer', 'dying', and 'death' when engaging with patients. Moreover, they proposed the recruitment of patients by trusted professionals, shortening the duration of research activities and simplifying research procedures. CONCLUSIONS: This study provides fresh insights into the perspectives of family members concerning the recruitment and engagement of advanced cancer patients in nursing research. It emphasizes the importance of addressing their concerns and recommendations, aiding nurse researchers in developing culturally sensitive recruitment strategies and fostering the inclusive participation of advanced cancer patients in nursing research within the context of family-centered care and cultural taboos surrounding death.

Experimental study to compare the strength of concrete with different amounts of polypropylene fibers at high temperatures.

It is widely known that adding fibers to concrete improves the properties of concrete, which has a brittle behavior. Although concrete has high compressive strength but poor tensile strength, this has led researchers to offer a variety of ways to deal with this weakness. The use of fibers is one of the methods used to enhance concrete behavior. Fire is one of the most important cases in structures; if the temperature is high or its duration is long, it will cause serious damage to the structure. The present study is an experimental study in which different concrete samples with different amounts of polypropylene fibers and different cement content are exposed once at a normal temperature of 25 °C and again at high temperatures, including 250 °C and 500 °C. The effect of temperature on the compressive and tensile strengths of concrete containing 0.5%, 1.5%, and 2% polypropylene fibres and with cement contents of 200 kg/m3, 260 kg/m3, and 320 kg/m3. The compressive and tensile strength was evaluated at curing 28 days of strength. The results showed a severe strength loss for all concretes after exposure to 500 °C. The relative compressive strengths of concretes containing PP fibers were higher than those of concretes without PP fibers. The tensile strength of concrete was more sensitive to high temperatures than the compressive strength. Based on the test results, it can be concluded that adding 2% PP fibers can significantly promote the residual mechanical properties of concrete during heating. The compressive strength at 25 °C with 2% PP fibres decreases by 43% with cement contents of 200 kg/m3 and 64% with cement contents of 260 kg/m3, and 37% with cement contents of 320 kg/m3, respectively. Also, the compressive strength at 500 °C with 2% PP fibres decreases by 61% with 200 kg/m3, 59% with 260 kg/m3, and 42% with cement contents of 320 kg/m3, respectively.

Retinal giant cyst treated by the scleral buckling procedure: A case report.

INTRODUCTION: Retinal cysts are rare lesions of the fundus that are essentially fluid-filled cavities located or originating in the retina, with a diameter larger than the normal retinal thickness. To date, there have been few case reports of giant retinal cyst hemorrhage with retinoschisis. CASE PRESENTATION: A 32-year-old woman with no other medical history complained of decreased vision for 3 days after a severe cough. The best-corrected visual acuity in the right eye was 0.5. A comprehensive ophthalmological examination including slit-lamp fundoscopy, ultrasound scan of the eye, optical coherence tomography scan, and orbital magnetic resonance imaging was performed. Ophthalmological examination revealed grade III anterior chamber blood cells and grade III vitreous hemorrhage in the right eye and a large herpetic cyst on the nasal side of the retina. The cyst projected into the vitreous, with a large amount of hemorrhage vaguely visible within it. The cyst was clearly visible, and a superficial retinal limiting detachment was observed around it. Ultrasound showed a retinal cyst with retinal detachment in the right eye. Laboratory test results were unremarkable. After 3 months of conservative treatment, the patient's intracystic hemorrhage was significantly absorbed, but the size of the cyst cavity did not show any significant change. Scleral buckling with external compression combined with external drainage of the intracystic fluid was performed, the patient's visual acuity was gradually restored to a normal 1.0 after the operation, and the retina appeared flattened. The patient was finally diagnosed with a giant retinal cyst with retinoschisis in the right eye. The presumed cause was heavy coughing leading to rupture and hemorrhage of the retinal cyst, similar to the mechanism of rupture of an arterial dissection. To the best of our knowledge, this case of retinal cyst rupture and hemorrhage caused by heavy coughing with good recovery after external surgical treatment has never been reported before. CONCLUSIONS: Giant cystic retinal hemorrhage with retinoschisis is very rare. Orbital magnetic resonance imaging and ocular B-scan ultrasound are essential for its diagnosis, and the selection of an appropriate surgical procedure is necessary to maximize the benefit for affected patients.

Structural insights into the Clp protein degradation machinery.

The Clp protease system is important for maintaining proteostasis in bacteria. It consists of ClpP serine proteases and an AAA+ Clp-ATPase such as ClpC1. The hexameric ATPase ClpC1 utilizes the energy of ATP binding and hydrolysis to engage, unfold, and translocate substrates into the proteolytic chamber of homo- or hetero-tetradecameric ClpP for degradation. The assembly between the hetero-tetradecameric ClpP1P2 chamber and the Clp-ATPases containing tandem ATPase domains from the same species has not been studied in depth. Here, we present cryo-EM structures of the substrate-bound ClpC1:shClpP1P2 from Streptomyces hawaiiensis, and shClpP1P2 in complex with ADEP1, a natural compound produced by S. hawaiiensis and known to cause over-activation and dysregulation of the ClpP proteolytic core chamber. Our structures provide detailed information on the shClpP1-shClpP2, shClpP2-ClpC1, and ADEP1-shClpP1/P2 interactions, reveal conformational transition of ClpC1 during the substrate translocation, and capture a rotational ATP hydrolysis mechanism likely dominated by the D1 ATPase activity of chaperones.IMPORTANCEThe Clp-dependent proteolysis plays an important role in bacterial homeostasis and pathogenesis. The ClpP protease system is an effective drug target for antibacterial therapy. Streptomyces hawaiiensis can produce a class of potent acyldepsipeptide antibiotics such as ADEP1, which could affect the ClpP protease activity. Although S. hawaiiensis hosts one of the most intricate ClpP systems in nature, very little was known about its Clp protease mechanism and the impact of ADEP molecules on ClpP. The significance of our research is in dissecting the functional mechanism of the assembled Clp degradation machinery, as well as the interaction between ADEP1 and the ClpP proteolytic chamber, by solving high-resolution structures of the substrate-bound Clp system in S. hawaiiensis. The findings shed light on our understanding of the Clp-dependent proteolysis in bacteria, which will enhance the development of antimicrobial drugs targeting the Clp protease system, and help fighting against bacterial multidrug resistance.

Study of clinical traits and systemic immune inflammation index assessments in patients with endogenous endophthalmitis over the last ten years.

PURPOSE: The clinical aspects and prognosis of eyes with endogenous endophthalmitis were compared over the last ten years. The occurrence and progression of endophthalmitis are linked to the systemic immune inflammation index (SII) and clinical features. METHODS: The study comprised patients with endogenous endophthalmitis and 64 patients without endophthalmitis who were treated at Hebei Province Eye Hospital in the last ten years. According to the prognostic visual acuity, patients with endophthalmitis were split into two groups: Group A and Group B. Underlying disease (hypertension, diabetes, tuberculosis), infection risk (liver abscess, urinary tract infection, and recent abdominal surgery), signs and symptoms, and complete blood count were among the evaluation parameters (neutrophil count, lymphocyte count, monocyte count, platelet count, red blood cell distribution width). The NLR, PLR, MLR, and SII values were calculated. A nonparametric test was used to examine the clinical features and complete blood count results of patients in each group. To determine the parameters linked to endophthalmitis progression, researchers used principal component and ordinal logistic regression analyses. RESULTS: The study comprised a total of 25 eyes and 22 individuals with endogenous endophthalmitis. Infectious bacteria included Staphylococcus aureus, Micrococcus luteus, Staphylococcus hemolyticus, and so on. The visual acuity of the affected eye ranged from 2.7 (1.55, 2.7) LogMAR to 1.22 (0.6, 2.7) LogMAR during the 6-month to 8-year follow-up period. The neutrophil, monocyte, and PLT counts, NLR, PLR, and SII values and other markers were considerably higher in Groups A and B than in the control group. The likelihood model of the SII and sex, age, onset time, diabetes, hypertension, monocyte count, and red blood cell distribution was the best, and its increase was strongly connected with the occurrence and progression of endophthalmitis, according to ordinal regression analysis. CONCLUSION: Patients with endophthalmitis had significantly higher blood neutrophil, monocyte, and PLT counts and SII, NLR, PLR, and MLR values. The SII can be employed as a biomarker for predicting endophthalmitis severity and prognosis.

Construction Strategy of Functionalized Liposomes and Multidimensional Application.

Liposomes are widely used in the biological field due to their good biocompatibility and surface modification properties. With the development of biochemistry and material science, many liposome structures and their surface functional components have been modified and optimized one by one, pushing the liposome platform from traditional to functionalized and intelligent, which will better satisfy and expand the needs of scientific research. However, a main limiting factor effecting the efficiency of liposomes is the complicated environmental conditions in the living body. Currently, in order to overcome the above problem, functionalized liposomes have become a very promising strategy. In this paper, binding strategies of liposomes with four main functional elements, namely nucleic acids, antibodies, peptides, and stimuli-responsive motif have been summarized for the first time. In addition, based on the construction characteristics of functionalized liposomes, such as drug-carrying, targeting, long-circulating, and stimulus-responsive properties, a comprehensive overview of their features and respective research progress are presented. Finally, the paper critically presents the limitations of these functionalized liposomes in the current applications and also prospectively suggests the future development directions, aiming to accelerate realization of their industrialization.

Long Non-Coding RNA ANRIL Regulates Inflammatory Factor Expression in Ulcerative Colitis Via the miR-191-5p/SATB1 Axis.

Ulcerative colitis, an inflammatory bowel disease, manifests with symptoms such as abdominal pain, diarrhea, and mucopurulent feces. The long non-coding RNA (lncRNA) ANRIL exhibits significantly reduced expression in UC, yet its specific mechanism is unknown. This study revealed that ANRIL is involved in the progression of UC by inhibiting IL-6 and TNF-α via miR-191-5P/SATB1 axis. We found that in patients with UC, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were significantly overexpressed in inflamed colon sites, whereas ANRIL was significantly under-expressed and associated with disease severity. The downregulation of ANRIL resulted in the increased expression of IL-6 and TNF-α in LPS-treated FHCs. ANRIL directly targeted miR-191-5p, thereby inhibiting its expression and augmenting SATB1 expression. Moreover, overexpression of miR-191-5p abolished ANRIL-mediated inhibition of IL-6 and TNF-α production. Dual luciferase reporter assays revealed the specific binding of miR-191-5p to ANRIL and SATB1. Furthermore, the downregulation of ANRIL promoted DSS-induced colitis in mice. Together, we provide evidence that ANRIL plays a critical role in regulating IL-6 and TNF-α expression in UC by modulating the miR-191-5p/SATB1 axis. Our study provides novel insights into progression and molecular therapeutic strategies in UC.

Ultraviolet light C in promoting rapid healing of delayed wound union: A case report.

INTRODUCTION AND IMPORTANCE: The purpose of this case is to present a useful phototherapy for rapid healing of recalcitrant postoperative wound disunion due to implantation of allogeneic bone and metal. CASE PRESENTATION: In this case, a middle-aged man was diagnosed as complex fracture of the left tibial plateau which caused movement loss, swelling and pain of the left knee. The patient's wound disunion was still present after been surgery for 26 days, with yellowish liquid persistently oozing out of the wound after several wound dressing. We treated the postoperative wound with ultraviolet light C (UVC) to promote wound healing. CLINICAL DISCUSSION: Incision disunion is a common complication of surgery, which increases patients' hospital days. Prevention and treatment of wound disunion is one of the key considerations for perioperative management. CONCLUSION: During 3-day consecutive UVC treatment, the yellowish wound exudate gradually reduced and disappeared. Subsequently, the non-healing postoperative wound scared over and healed rapidly. As a convenient, non-invasive, non-polluting and effectively physical therapy, UVC can promote rapid healing of recalcitrant wound disunion caused by implants in complex tibial plateau fracture.

Stellate nonheritable idiopathic foveomacular retinoschisis in juveniles: case report.

BACKGROUND: Stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR) is a rare type of retinoschisis with a spoke-like splitting that occurs in the outer plexus layer. We present a case of stellate nonhereditary idiopathic foveomacular retinoschisis in a juvenile, in which two eyes show different development trends and macular retinoschisis could be associated with mechanical force in the Henle fibre layer. The removal of mechanical force can partially restore vision. CASE PRESENTATION: A 14-year-old girl with bilateral SNIFR was diagnosed and followed up with spectral-domain optical coherence tomography (SD-OCT). During the two follow-up visits, vitreous adhesion was released in the left eye, and visual acuity improved. Neuroepithelial detachment was aggravated in the right eye, and visual acuity decreased. Therefore, vitrectomy was performed on the right eye. After surgery, the patient's retina was reattached, and her vision was partially restored. CONCLUSIONS: We reported a juvenile with bilateral SNIFR. Each of her eyes showed different development trends, so we adopted different treatment methods for each eye. Vitrectomy was performed on the patient to address progressive vision loss, which improved the patient's vision. It was further confirmed that the Henle layer of SNIFR patients was susceptible to posterior vitreous membrane adhesion.

Does inflammatory bowel disease promote kidney diseases: a mendelian randomization study with populations of European ancestry.

BACKGROUND: This study aimed to investigate a causal relationship between IBD and multiple kidney diseases using two-sample Mendelian randomization (MR) analyses. METHODS: We selected a group of single nucleotide polymorphisms (SNPs) specific to IBD as instrumental variables from a published genome-wide association study (GWAS) with 86,640 individuals of European ancestry. Summary statistics for multiple kidney diseases were obtained from the publicly available GWAS. Genetic data from one GWAS involving 210 extensive T-cell traits was used to estimate the mediating effect on specific kidney disease. Inverse-variance weighted method were used to evaluate the MR estimates for primary analysis. RESULTS: Genetic predisposition to IBD was associated with higher risk of IgA nephropathy (IgAN) (OR, 1.78; 95% CI, 1.45-2.19), but not membranous nephropathy, diabetic nephropathy, glomerulonephritis, nephrotic syndrome, chronic kidney disease, and urolithiasis. CD4 expression on CD4 + T cell had a significant genetic association with the risk of IgAN (OR, 2.72; 95% CI, 1.10-6.72). Additionally, consistent results were also observed when IBD was subclassified as ulcerative colitis (OR, 1.38; 95% CI, 1.10-1.71) and Crohn's disease (OR, 1.37; 95% CI, 1.12-1.68). MR-PRESSO and the MR-Egger intercept did not identify pleiotropic SNPs. CONCLUSIONS: This study provides genetic evidence supporting a positive casual association between IBD, including its subclassification as ulcerative colitis and Crohn's disease, and the risk of IgAN. However, no casual association was found between IBD and other types of kidney diseases. Further exploration of IBD interventions as potential preventive measures for IgAN is warranted.

SASH1: A Novel Eph Receptor Partner and Insights into SAM-SAM Interactions.

The Eph (erythropoietin-producing human hepatocellular) receptor family, the largest subclass of receptor tyrosine kinases (RTKs), plays essential roles in embryonic development and neurogenesis. The intracellular Sterile Alpha Motif (SAM) domain presents a critical structural feature that distinguishes Eph receptors from other RTKs and participates in recruiting and binding downstream molecules. This study identified SASH1 (SAM and SH3 domain containing 1) as a novel Eph receptor-binding partner through SAM-SAM domain interactions. Our comprehensive biochemical analyses revealed that SASH1 selectively interacts with Eph receptors via its SAM1 domain, displaying the highest affinity for EphA8. The high-resolution crystal structure of the EphA8-SASH1 complex provided insights into the specific intermolecular interactions between these proteins. Cellular assays confirmed that EphA8 and SASH1 co-localize and co-precipitate in mammalian cells, with cancer mutations (EphA8 R942H or G978D) impairing this interaction. We demonstrated that SAM-SAM interaction is critical for SASH1-mediated regulation of EphA8 kinase activity, shedding new light on the Eph signaling pathway and expanding our understanding of the molecular basis of the tumor suppressor gene SASH1.

Intern nursing students' perceived barriers to providing end-of-life care for dying cancer patients in a death taboo cultural context: A qualitative study.

Objective: Internationally, intern nursing students' experiences with dying patients and death are an area of great concern. However, barriers to providing end-of-life care for dying cancer patients have not been extensively investigated in mainland China, where death remains a taboo issue. Therefore, this study aimed to elucidate intern nursing students' perceived barriers to their performance in providing end-of-life cancer care in the Chinese cultural context. Methods: This was a descriptive, qualitative study. Twenty-one intern nursing students from three cancer centers in mainland China were interviewed between January 2021 and June 2022. A thematic analysis method was used to analyze the data. The theory of planned behavior was adopted to design the study and identify themes. Results: A range of barriers related to attitudes, subjective norms, and perceived behavioral control that hindered intern nursing students from acquiring abilities to deal with patient dying and death were identified in the Chinese cultural context. Conclusions: Chinese intern nursing students encountered many barriers that affected their provision of end-of-life care to dying cancer patients. Strategies to improve their ability to provide appropriate end-of-life care should focus on helping them develop appropriate attitudes toward dying and death and how to overcome subjective norms and behavioral control barriers.

Loss of BCAA catabolism enhances Rab1A-mTORC1 signaling activity and promotes tumor proliferation in NSCLC.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a leading cause of cancer death. Branched-chain amino acid (BCAA) homeostasis is important for normal physiological metabolism. Branched-chain keto acid dehydrogenase kinase (BCKDK) is a rate-limiting enzyme involved in BCAA degradation. BCAA metabolism has been highlighted in human cancers. The aberrant activation of mTORC1 has been implicated in tumor progression. Rab1A is a small GTPase, an activator of mTORC1, and an oncogene. This study aimed to reveal the specific role of BCKDK-BCAA-Rab1A-mTORC1 signaling in NSCLC. METHODS: We analyzed a cohort of 79 patients with NSCLC and 79 healthy controls. Plasma BCAA assays, immunohistochemistry, and network and pathway analyses were performed. The stable cell lines BCKDK-KD, BCKDK-OV A549, and H1299 were constructed. BCKDK, Rab1A, p-S6 and S6 were detected using western blotting to explore their molecular mechanisms of action in NSCLC. The effects of BCAA and BCKDK on the apoptosis and proliferation of H1299 cells were detected by cell function assays. RESULTS: We demonstrated that NSCLC was primarily involved in BCAA degradation. Therefore, combining BCAA, CEA, and Cyfra21-1 is clinically useful for treating NSCLC. We observed a significant increase in BCAA levels, downregulation of BCKDHA expression, and upregulation of BCKDK expression in NSCLC cells. BCKDK promotes proliferation and inhibits apoptosis in NSCLC cells, and we observed that BCKDK affected Rab1A and p-S6 in A549 and H1299 cells via BCAA modulation. Leucine affected Rab1A and p-S6 in A549 and H1299 cells and affected the apoptosis rate of H1299 cells. In conclusion, BCKDK enhances Rab1A-mTORC1 signaling and promotes tumor proliferation by suppressing BCAA catabolism in NSCLC, suggesting a new biomarker for the early diagnosis and identification of metabolism-based targeted approaches for patients with NSCLC.

Dl-3-n-butylphthalide promotes synaptic plasticity by activating the Akt/ERK signaling pathway and reduces the blood-brain barrier leakage by inhibiting the HIF-1α/MMP signaling pathway in vascular dementia model mice.

AIMS: DL-3-n-butylphthalide (NBP) exerts beneficial effects on global cognitive functions, but the underlying molecular mechanisms are still poorly understood. The present study aimed to investigate whether NBP mediates synaptic plasticity and blood-brain barrier (BBB) function, which play a pivotal role in the pathogenesis of vascular dementia (VaD), in a mouse model of bilateral common carotid artery stenosis (BCAS). METHODS: NBP was administered to model mice at a dose of 80 mg/kg by gavage for 28 days after surgery. Cognitive function was evaluated by behavioral tests, and hippocampal synaptic plasticity was evaluated by in vivo electrophysiological recording. Cerebral blood flow (CBF), hippocampal volume, and white matter integrity were measured with laser speckle imaging (LSI) and MRI. In addition, BBB leakage and the expression of proteins related to the Akt/ERK and HIF-1α/MMP signaling pathways were assessed by biochemical assays. RESULTS: NBP treatment alleviated cognitive impairment, hippocampal atrophy, and synaptic plasticity impairment induced by BCAS. In addition, NBP treatment increased CBF, promoted white matter integrity, and decreased BBB leakage. Regarding the molecular mechanisms, in mice  with BCAS, NBP may activate the Akt/ERK signaling pathway, which upregulates the expression of synapse-associated proteins, and it may also inhibit the HIF-1α/MMP signaling pathway, thereby increasing the expression of tight junction (TJ) proteins. CONCLUSION: In conclusion, our results demonstrated the therapeutic effects of NBP in improving cognitive function via a wide range of targets in mice subjected to BCAS.

Factors associated with prolonged duration of ultrasound-guided brachial plexus block for the upper limb fracture surgery: a cross-sectional study.

Background: Previous studies of factors associated with prolonged duration of ultrasound-guided brachial plexus block have included multiple surgical procedures or multiple anesthetic approaches, all of which are important confounders, and there is no study based on a single method of anesthesia exploring the factors affecting the resolution of brachial plexus block during upper limb surgery, especially in Asians. This study aimed to identify the risk factors affecting the prolonged duration of US-guided brachial plexus block in American Society of Anesthesiologists (ASA) I-II grade patients to improve postoperative analgesia. Methods: This study enrolled patients scheduled to undergo surgery for upper limb fracture in Anting Hospital, Shanghai from May 2021 to September 2021. Inclusion criteria: (I) patients aged 18 years and above; (II) ASA I-II grade patients; (III) success of US-guided brachial plexus block. Based on the median duration of brachial plexus block, patients were divided into a <5-hour group and a ≥5-hour group. The factors were selected base on previous studies conclution and clinical demographic characteristics of patients. Multivariable logistic regression was used to estimate relevant influencing factors. Results: A total of 129 patients (51.2% males; 51.01±16.54 years old) were analyzed. The duration of brachial plexus block was 2-12 hours, with a median duration of 5.09 hours. Multivariable analysis suggested that age 40-49 years [odds ratio (OR): 4.841; 95% confidence interval (CI): 1.033 to 22.695; P=0.045], 50-59 years (OR: 4.730, 95% CI: 1.149 to 19.474; P=0.031), 60 years (OR: 8.540; 95% CI: 1.605 to 45.449; P=0.012), gender (OR: 3.314; 95% CI: 1.330 to 8.257; P=0.010), alanine aminotransferase (ALT; OR: 5.817, 95% CI: 1.509 to 22.472; P=0.011), and glomerular filtration rate (GFR) <60 (OR: 22.700; 95% CI: 1.994 to 198.386; P=0.012) were the risk factors for the duration of brachial plexus block. Conclusions: It is advisable to use the lowest effective dose for the shortest possible time when using ropivacaine in upper limb fracture surgery patients with elevated ALT (≥40 U/L) and lower GFR (<60 mL/min) in male patients aged ≥60 years.

The contribution of perceived death competence in determining the professional quality of life of novice oncology nurses: A multicentre study.

PURPOSE: Novice nurses find it challenging to cope with patient dying and death, especially in a death taboo cultural context, such as mainland China. By taking the example of Chinese novice oncology nurses, this study aimed to explore the contribution of their perceived death competence in determining their professional quality of life. METHOD: A multicentre, cross-sectional study was conducted in six tertiary cancer hospitals in mainland China involving 506 novice oncology nurses. Measurements were the Coping with Death Scale-Chinese version, the Professional Quality of Life Questionnaire, and the Coping Style Questionnaire. Hierarchical multiple regression analyses were used to analyse the data. RESULTS: Death competence was significantly associated with compassion satisfaction (r = 0.509, P < 0.001), burnout (r = -0.441, P < 0.001) and secondary traumatic stress (r = -0.154, P < 0.001) which are the three dimensions of professional quality of life. The results of hierarchical multiple regression analyses demonstrated that death competence positively predicted compassion satisfaction and negatively predicted burnout (P < 0.01), but had no significant impact on secondary traumatic stress after coping style was entered into the model (P > 0.05). CONCLUSIONS: Novice oncology nurses who perceive themselves to be incompetent in dealing with patient dying and death are more likely to experience poor professional quality of life in the death taboo cultural context. Cultural-sensitive interventions and a supportive work environment are important to enhance these nurses' death competence, increasing their professional quality of life and ultimately contributing to better end-of-life cancer care management.

Linc279227 contributes to mitochondrial dysfunction in high glucose-treated mouse renal tubular epithelial cells.

BACKGROUND: The aberrant expression of long noncoding RNAs (lncRNAs) has been associated with diabetic nephropathy (DN), a major complication of diabetes mellitus (DM). This study investigated the differential expression of lncRNAs in DM without renal damage and DM with renal damage, known as DN, and elucidated the functions of a pathogenic lncRNA. METHODS: High-throughput sequencing was performed on the kidneys of male db/db mice with kidney injury, db/db mice without kidney involvement and db/m control littermates. Linc279227 expression was confirmed by RT‒qPCR and fluorescence in situ hybridization. The effects of linc279227 on high glucose (HG)-treated renal tubular epithelial cells (RTECs) were evaluated by autophagy flux monitoring, Western blot determination and mitochondrial morphological detection. RESULTS: With high-throughput sequencing, we identified a 1024 nt long intergenic noncoding RNA, TCONS_00279227 (linc279227), whose expression was markedly increased in the kidneys of db/db mice with kidney injury compared to db/db mice without kidney injury and db/m control littermates. Fluorescence in situ hybridization confirmed that linc279227 was mainly located in the renal tubules of mice with DN. In vitro, linc279227 expression was found to be significantly increased in RTECs treated with high glucose (HG) for 48 h. Silencing linc279227 markedly restored the levels of autophagy-/mitophagy-associated proteins in HG-stimulated RTECs. Furthermore, silencing linc279227 reduced phosphorylated Drp1 expression and increased Mfn2 expression in RTECs exposed to HG. CONCLUSION: Our data suggest that linc279227 plays an important role in mitochondrial dysfunction in HG-treated RTECs and that silencing linc279227 rescues RTECs exposed to HG.

The enzyme activity of sortase A is regulated by phosphorylation in Staphylococcus aureus.

In many Gram-positive bacteria, the transpeptidase enzyme sortase A (SrtA) anchors surface proteins to cell wall and plays a critical role in the bacterial pathogenesis. Here, we show that in Staphylococcus aureus, an important human pathogen, the SrtA is phosphorylated by serine/threonine protein kinase Stk1. S. aureus SrtA can also be phosphorylated by small-molecule phosphodonor acetyl phosphate (AcP) in vitro. We determined that various amino acid residues of S. aureus SrtA are subject to phosphorylation, primarily on its catalytic site residue cysteine-184 in the context of a bacterial cell lysate. Both Stk1 and AcP-mediated phosphorylation inhibited the enzyme activity of SrtA in vitro. Consequently, deletion of gene (i.e. stp1) encoding serine/threonine phosphatase Stp1, the corresponding phosphatase of Stk1, caused an increase in the phosphorylation level of SrtA. The stp1 deletion mutant mimicked the phenotypic traits of srtA deletion mutant (i.e. attenuated growth where either haemoglobin or haem as a sole iron source and reduced liver infections in a mouse model of systemic infection). Importantly, the phenotypic defects of the stp1 deletion mutant can be alleviated by overexpressing srtA. Taken together, our finding suggests that phosphorylation plays an important role in modulating the activity of SrtA in S. aureus.

KFWC: A Knowledge-Driven Deep Learning Model for Fine-grained Classification of Wet-AMD.

BACKGROUND AND OBJECTIVES: Automated diagnosis using deep neural networks can help ophthalmologists detect the blinding eye disease wet Age-related Macular Degeneration (AMD). Wet-AMD has two similar subtypes, Neovascular AMD and Polypoidal Choroidal Vasculopathy (PCV). However, due to the difficulty in data collection and the similarity between images, most studies have only achieved the coarse-grained classification of wet-AMD rather than a fine-grained one of wet-AMD subtypes. Therefore, designing and building a deep learning model to diagnose neovascular AMD and PCV is a great challenge. METHODS: To solve this issue, in this paper, we propose a Knowledge-driven Fine-grained Wet-AMD Classification Model (KFWC) to enhance the model's accuracy in the fine-grained disease classification with insufficient data. We innovatively introduced a two-stage method. In the first stage, we present prior knowledge of 10 lesion signs through pre-training; in the second stage, the model implements the classification task with the help of human knowledge. With the pre-training of priori knowledge of 10 lesion signs from input images, KFWC locates the powerful image features in the fine-grained disease classification task and therefore achieves better classification. RESULTS: To demonstrate the effectiveness of KFWC, we conduct a series of experiments on a clinical dataset collected in cooperation with a Grade III Level A ophthalmology hospital in China. The AUC score of KFWC reaches 99.71%, with 6.69% over the best baseline and 4.14% over ophthalmologists. KFWC can also provide good interpretability and effectively alleviate the pressure of data collection and annotation in the field of fine-grained disease classification for wet-AMD. CONCLUSIONS: The model proposed in this paper effectively solves the difficulties of small data volume and high image similarity in the wet-AMD fine-grained classification task through a knowledge-driven approach. Besides, this method effectively relieves the pressure of data collection and annotation in the field of fine-grained classification. In the diagnosis of wet-AMD, KFWC is superior to previous work and human ophthalmologists.