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BACKGROUND: Interdisciplinary collaboration is known to foster professional innovation and enhance student learning across different domains. However, the research on the effectiveness of integration of interdisciplinary learning in pediatric nursing education is limited. Therefore, this study aimed to examine the effectiveness of integrating game-based learning, an interdisciplinary approach to teaching, into pediatric nursing education's play courses. METHODS: We used a mixed methods study with pre-test/post-test quantitative analyses and a descriptive qualitative analysis of students' reflection journals. Data were collected between August 2019 and July 2020 to gauge course effectiveness. Quantitative data obtained from the questionnaires were analyzed using a t-test, correlation, and regression analysis. Qualitative data using students' reflective journals were collected and analyzed using content analysis. One hundred and three second-year nursing students enrolled in a four-year nursing program. Nursing students attended classes in university classrooms and served learning in a kindergarten or hospital in Northern Taiwan. RESULTS: The subscales of Students' Learning Outcome in knowledge, abilities, and attitudes showed significantly higher mean post-test scores compared to pre-test scores: 26.15 (SD = 3.35) vs. 16.82 (SD = 4.49), p < .001; 18.03 (SD = 2.13) vs. 11.43 (SD = 2.95), p < .001; and 12.90 (SD = 2.12) vs. 8.72 (SD = 2.52), p < .001. Furthermore, scores on the Service-Learning Abilities Scale indicated a significant increase in communication, problem-solving, knowledge application, and cross-cultural competence. Integrating instruction to improve problem-solving skills and knowledge application predicts student learning outcomes. Qualitative findings revealed nursing students' reflections on integrating different learning areas, communication, problem-solving, and practical knowledge skills. CONCLUSIONS: Integration of interdisciplinary learning effectively stimulates learning among nursing students and enhances their knowledge, abilities, and attitudes toward therapeutic play, benefiting children's health. Our findings demonstrate that integration of interdisciplinary learning significantly enhances nursing students' healthcare-giving competence, particularly in communication, problem-solving, knowledge application, and cross-cultural competence as measured by the Service-Learning Scale. Integrating social service with integration of interdisciplinary learning exposes nursing students to diverse challenges and needs, thereby enhancing their communication skills, knowledge application, and problem-solving abilities. Nursing students can blend knowledge and skills through integrated learning, which is crucial for nursing career preparation. TRIAL REGISTRATION: N/A. It was a survey on educational activities.
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BACKGROUND: The rate of distant metastasis in patients with pancreatic neuroendocrine tumors (PNETs) is 20%-50% at the time of initial diagnosis. However, whether tumor size can predict distant metastasis for PNETs remains unknown up to date. METHODS: We used Surveillance, Epidemiology, and End Results (SEER) population-based data to collect 6089 patients with PNETs from 2010 to 2019. The optimal cut-off point of tumor size to predict distant metastasis was calculated by Youden's index. Multivariate logistic regression analysis was used to figure out the association between tumor size and distant metastasis patterns. RESULTS: The most common metastatic site was liver (27.2%), followed by bone (3.0%), lung (2.3%) and brain (0.4%). Based on an optimal cut-off value of tumor size (25.5 mm) for predicting distant metastasis determined by Youden's index, patients were categorized into groups of tumor size < 25.5 mm and ≥ 25.5 mm. Multivariate logistic regression analyses showed that, compared with < 25.5 mm, tumor size ≥ 25.5 mm was an independent risk predictor of overall distant metastasis [odds ratio (OR) = 4.491, 95% confidence interval (CI): 3.724-5.416, P < 0.001] and liver metastasis (OR = 4.686, 95% CI: 3.886-5.651, P < 0.001). CONCLUSIONS: Tumor size ≥ 25.5 mm was significantly associated with more overall distant and liver metastases. Timely identification of distant metastasis for tumor size ≥ 25.5 mm may provide survival benefit for timely and precise treatment.
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Today, cancer treatment is one of the main challenges for researchers. The main cause of tumor cell formation is mutations that lead to uncontrolled proliferation and inhibition of apoptosis in malignant cells. Tumor cells also create a microenvironment that can suppress the immune system cells' responses through various methods, including producing soluble factors and cell-to-cell communication. After being produced from tumor cells, exosomes can also affect the functions of other cells in this microenvironment. Various studies have shown that exosomes from different sources, including tumor cells and immune cells, can be used to treat cancers due to their characteristics. Since tumor cells are rich sources of various types of tumor peptides, they can induce anti-tumor responses. Immune cells also produce exosomes that mimic the functions of their cells of origin, such that exosomes derived from NK cells and CTLs can directly lead to their apoptosis after merging with tumor cells. However, many researchers have pointed out that naïve exosomes have a limited therapeutic function, and their therapeutic potential can be increased by manipulating and engineering them. There are various methods to modify exosomes and improve their therapeutic potential. In general, these methods are divided into two parts, which include changing the cell of origin of the exosome and encapsulating the exosome to carry different drugs. In this review, we will discuss the studies on the therapeutic use of naive and engineered exosomes and provide an update on new studies in this field.
Subject(s)
Exosomes , Immunotherapy , Neoplasms , Tumor Microenvironment , Exosomes/immunology , Exosomes/metabolism , Humans , Neoplasms/therapy , Neoplasms/immunology , Immunotherapy/methods , Animals , Tumor Microenvironment/immunology , Killer Cells, Natural/immunologyABSTRACT
mRNA lipid nanoparticles (LNPs) have emerged as powerful modalities for gene therapies to control cancer and infectious and immune diseases. Despite the escalating interest in mRNA-LNPs over the past few decades, endosomal entrapment of delivered mRNAs vastly impedes therapeutic developments. In addition, the molecular mechanism of LNP-mediated mRNA delivery is poorly understood to guide further improvement through rational design. To tackle these challenges, we characterized LNP-mediated mRNA delivery using a library of small molecules targeting endosomal trafficking. We found that the expression of delivered mRNAs is greatly enhanced via inhibition of endocytic recycling in cells and in live mice. One of the most potent small molecules, endosidine 5 (ES5), interferes with recycling endosomes through Annexin A6, thereby promoting the release and expression of mRNA into the cytoplasm. Together, these findings suggest that targeting endosomal trafficking with small molecules is a viable strategy to potentiate the efficacy of mRNA-LNPs.
Subject(s)
Endosomes , Liposomes , Nanoparticles , RNA, Messenger , Endosomes/metabolism , Animals , RNA, Messenger/genetics , RNA, Messenger/metabolism , Nanoparticles/chemistry , Mice , Humans , Lipids/chemistry , Gene Transfer Techniques , Endocytosis/drug effectsABSTRACT
Lagerstroemiastenophylla, a new species from southeastern Shaanxi Province and northwestern Hubei Province of China is described. Morphologically, L.stenophylla resembles L.subcostata, but it differs in having 4-angular, subalate branchlets, elliptic-lanceolate, or narrowly elliptic leaves, and relatively larger flowers.
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BACKGROUND: Posthepatitic cirrhosis is one of the leading risk factors for hepatocellular carcinoma (HCC) worldwide, among which hepatitis B cirrhosis is the dominant one. This study explored whether laparoscopic splenectomy and azygoportal disconnection (LSD) can reduce the risk of HCC among patients with hepatitis B virus (HBV)-related cirrhotic portal hypertension (CPH). METHODS: A total of 383 patients with HBV-related CPH diagnosed as gastroesophageal variceal bleeding and secondary hypersplenism were identified in our hepatobiliary pancreatic center between April 2012 and April 2022, and conducted an 11-year retrospective follow-up. We used inverse probability of treatment weighting (IPTW) to correct for potential confounders, weighted Kaplan-Meier curves, and logistic regression to estimate survival and risk differences. RESULTS: Patients were divided into two groups based on treatment method: LSD (n = 230) and endoscopic therapy (ET; n = 153) groups. Whether it was processed through IPTW or not, LSD group showed a higher survival benefit than ET group according to Kaplan-Meier analysis (P < 0.001). The incidence density of HCC was higher in the ET group compared to LSD group at the end of follow-up [32.1/1000 vs 8.0/1000 person-years; Rate ratio: 3.998, 95% confidence intervals (CI) 1.928-8.293]. Additionally, in logistic regression analyses weighted by IPTW, LSD was an independent protective predictor of HCC incidence compared to ET (odds ratio 0.516, 95% CI 0.343-0.776; P = 0.002). CONCLUSION: Considering the ability of LSD to improve postoperative survival and prevent HCC in HBV-related CPH patients with gastroesophageal variceal bleeding and secondary hypersplenism, it is worth promoting in the context of the shortage of liver donors.
Subject(s)
Carcinoma, Hepatocellular , Esophageal and Gastric Varices , Hypersplenism , Hypertension, Portal , Laparoscopy , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/surgery , Carcinoma, Hepatocellular/complications , Hepatitis B virus , Esophageal and Gastric Varices/surgery , Esophageal and Gastric Varices/complications , Retrospective Studies , Hypersplenism/surgery , Hypersplenism/complications , Splenectomy/adverse effects , Liver Neoplasms/surgery , Liver Neoplasms/complications , Gastrointestinal Hemorrhage/etiology , Laparoscopy/adverse effects , Hypertension, Portal/surgery , Hypertension, Portal/complications , Liver Cirrhosis/complications , Liver Cirrhosis/surgeryABSTRACT
BACKGROUND Patients with chronic ankle instability (CAI) can present with abnormal gait. The purpose of this study was to evaluate plantar pressure distributions and posture balance during walking in unilateral CAI patients. MATERIAL AND METHODS We recruited 24 unilateral CAI patients and 24 healthy individuals; plantar pressure analysis was conducted using the Footscan® 3D pressure system. The following parameters were assessed and recorded: peak force/weight (PF/W), time to peak force (TPF), time to boundary (TTB), and COP velocity. The differences between the affected and unaffected side of the CAI group and control group were determined. Pearson correlation analysis and univariate analysis was used to investigate the correlation between plantar pressure parameters and related factors. RESULTS The comparison of PF/W showed that the plantar pressure of both sides in the CAI group were laterally distributed. The comparison of TPF, TTB, and COP velocity in different groups showed that the posture balance on the affected side of CAI patient was more impaired than the unaffected side and the control group. Male patients with CAI tend to have better posture balance than females, and a low CAIT score is correlated with poor posture balance. CONCLUSIONS The plantar pressure on both sides in unilateral CAI patients was laterally distributed and their balance function was impaired. It is necessary for CAI patients to receive functional training of both sides during rehabilitation, and plantar pressure analysis is promising for diagnosis and evaluation of CAI.
Subject(s)
Ankle , Joint Instability , Female , Humans , Male , Ankle Joint , Chronic Disease , Walking , Postural BalanceABSTRACT
BACKGROUND: Liver cirrhosis is the highest risk factor for hepatocellular carcinoma (HCC) worldwide. However, etiological therapy is the only option in cirrhosis patients to decrease the HCC risk. The aim of this study was to explore whether laparoscopic splenectomy and azygoportal disconnection (LSD) decreases the risk of HCC for patients with cirrhotic portal hypertension (CPH). METHODS: Between April 2012 and April 2021, we identified 595 CPH patients in our hepatobiliary pancreatic center who were diagnosed with gastroesophageal variceal bleeding and secondary hypersplenism, and performed a 10-year retrospective follow-up. Inverse probability of treatment weighting (IPTW) was used to adjust for potential confounders, weighted Kaplan-Meier curves and logistic regression to estimate survival and risk differences. RESULTS: According to the method of therapy, patients were divided into LSD (n = 345) and endoscopic therapy (ET; n = 250) groups. Kaplan-Meier analysis revealed that patients who underwent LSD had higher survival benefit with those who underwent ET (P < 0.001). At the end of the follow-up, ET group was associated with a higher HCC incidence density compared with LSD group (28.1/1000 vs 9.6/1000 person-years; Rate ratio [RR] 2.922, 95% confidence intervals [CI] 1.599-5.338). In addition, logistic regression analyses weighted by IPTW revealed that, compared with ET, LSD was an independent protective predictor of HCC incidence (odds ratio [OR] 0.440, 95% CI 0.316-0.612; P < 0.001). CONCLUSIONS: Considering the better postoperative survival and the ability to prevent HCC in CPH patients with gastroesophageal variceal bleeding and secondary hypersplenism, LSD is worth popularization in situations where liver donors are scarce.
Subject(s)
Carcinoma, Hepatocellular , Esophageal and Gastric Varices , Hypersplenism , Hypertension, Portal , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/surgery , Follow-Up Studies , Esophageal and Gastric Varices/etiology , Esophageal and Gastric Varices/surgery , Retrospective Studies , Splenectomy/adverse effects , Splenectomy/methods , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/prevention & control , Liver Neoplasms/surgery , Liver Neoplasms/complications , Hypertension, Portal/surgery , Hypertension, Portal/complications , Liver Cirrhosis/complications , Risk Factors , Treatment OutcomeABSTRACT
BACKGROUND: The optimal treatment options for gallstones together with common bile duct stones (CBDS) remain controversial. The aim of this study was to further compare the recurrence rate of stones after synchronous laparoscopic cholecystectomy combined with laparoscopic common bile duct exploration (SLCL) and synchronous laparoscopic cholecystectomy combined with intraoperative endoscopic sphincterotomy (SLCE) and to determine which option is more effective in reducing the rate of repeated recurrence of CBDS and the incidence rate of hepatolithiasis. METHODS: We retrospectively investigated the clinical data of patients who underwent SLCL or SLCE at our hepatobiliary center between August 2012 and August 2020. The primary and secondary endpoints of this study were the recurrence of CBDS and the occurrence of hepatolithiasis, respectively. RESULTS: In total, 1005 patients were enrolled in this study, including 431 patients in the SLCL group and 574 patients in the SLCE group. SLCL was associated with a significantly decreased rate of CBDS recurrence (4.18% vs. 7.84%, P = 0.018), repeated CBDS recurrence (0.70% vs. 3.00%, P = 0.010), and incidence of hepatolithiasis (0.00% vs. 1.05%, P = 0.040). Compared with SLCE, SLCL was an independent protective predictor of the recurrence of CBDS (relative risk, 0.505; 95% confidence interval, 0.286-0.891; P = 0.018) and repeated recurrence of CBDS (relative risk, 0.226; 95% confidence interval, 0.066-0.777; P = 0.018). CONCLUSIONS: SLCL is an optimal treatment option to SLCE for patients with gallstones combined with CBDS.
Subject(s)
Cholecystectomy, Laparoscopic , Choledocholithiasis , Gallstones , Lithiasis , Liver Diseases , Humans , Gallstones/surgery , Gallstones/complications , Sphincterotomy, Endoscopic/adverse effects , Retrospective Studies , Cholecystectomy, Laparoscopic/adverse effects , Lithiasis/complications , Lithiasis/surgery , Cholangiopancreatography, Endoscopic Retrograde , Liver Diseases/surgery , Common Bile Duct/surgery , Choledocholithiasis/surgery , Choledocholithiasis/etiologySubject(s)
Brain Ischemia , Ischemic Stroke , Stroke , Humans , Computed Tomography Angiography , Tomography, X-Ray Computed , Perfusion , Retrospective StudiesABSTRACT
BACKGROUND: How to precisely protect and preserve anterior and posterior vagal trunks and all their branches during the procedure of splenectomy and azygoportal disconnection is studied rarely. We firstly developed a vagus nerve-guided robotic-assisted laparoscopic splenectomy and azygoportal disconnection (VGRSD). The aim of this study was to evaluate whether VGRSD is feasible and safe and to determine whether VGRSD can effectively eliminate postoperative digestive system complications by protecting vagal nerve precisely. METHOD: In this prospective clinical study, 10 cirrhotic patients with oesophagogastric variceal bleeding and hypersplenism who underwent VGRSD between January 2022 and March 2022 were gathered, and compared with a retrospective cohort who received a part of the vagus nerve-preserving robotic-assisted laparoscopic splenectomy and azygoportal disconnection (VPRSD). They were all followed up for 6 months. RESULTS: In VGRSD group, the operation time was 173.5 ± 16.2 min, blood loss was 68.0 ± 39.1 ml, VAS pain score on the first day was 1.9 ± 0.7, and the postoperative hospital stay was 7.7 ± 0.7 days. There was no incisional complications, pneumonia, gastric fistula, pancreatic fistula, and abdominal infection. No patients suffered from diarrhoea, delayed gastric emptying, and epigastric fullness. Compared with VPRSD, operation time was significantly longer for VGRSD (p < 0.05). However, VGRSD was significantly associated with less diarrhoea and shorter postoperative hospital stay (all p < 0.05). CONCLUSION: VGRSD procedure is not only technically feasible and safe, it also effectively eliminate postoperative digestive system complications. TRIAL REGISTRATION: We registered our research at https://www. CLINICALTRIALS: gov/. The name of research registered is 'Vagus Nerve-guided Robotic-assisted Splenectomy and Azygoportal Disconnection'. The trial registration identifier at clinicaltrials.gov is NCT05300516.
Subject(s)
Esophageal and Gastric Varices , Hypertension, Portal , Laparoscopy , Robotic Surgical Procedures , Humans , Esophageal and Gastric Varices/surgery , Esophageal and Gastric Varices/complications , Gastrointestinal Hemorrhage/complications , Gastrointestinal Hemorrhage/surgery , Hypertension, Portal/complications , Hypertension, Portal/surgery , Laparoscopy/methods , Prospective Studies , Retrospective Studies , Robotic Surgical Procedures/adverse effects , Splenectomy/methods , Treatment Outcome , Vagus Nerve/surgeryABSTRACT
Signal transduction at the synapse is mediated by a variety of protein-lipid interactions, which are vital for the spatial and temporal regulation of synaptic vesicle biogenesis, neurotransmitter release, and postsynaptic receptor activation. Therefore, our understanding of synaptic transmission cannot be completed until the elucidation of these critical protein-lipid interactions. On this front, recent advances in nanodiscs have vastly expanded our ability to probe and reprogram membrane biology in synapses. Here, we summarize the progress of the nanodisc toolbox and discuss future directions in this exciting field.
Subject(s)
Lipid Metabolism , Membrane Proteins , Nanostructures , Synapses , Synaptic Transmission , Synapses/physiology , Synaptic Vesicles , Membrane Proteins/metabolismABSTRACT
BACKGROUND: About 10%-20% of all individuals who develop hepatocellular carcinoma (HCC) do not have cirrhosis. Comparisons are rarely reported regarding the effectiveness of radiofrequency ablation (RFA) and liver resection (LR) in survival of HCC without cirrhosis and stratification by tumor size ≤ 5 cm. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database and identified 1505 patients with a solitary HCC tumor ≤ 5 cm who underwent RFA or LR during 2004-2015. Patients were classified into non-cirrhosis and cirrhosis groups and each group was categorized into three subgroups, according to tumor size (≤ 30 mm, 31-40 mm, 41-50 mm). RESULTS: In patients without cirrhosis, LR showed better 5-year HCC cancer-specific survival than RFA in all tumor size subgroups (≤ 30 mm: 82.51% vs. 56.42%; 31-40 mm: 71.31% vs. 46.83%; 41-50 mm: 74.7% vs. 37.5%; all P < 0.05). Compared with RFA, LR was an independent protective factor for HCC cancer-specific survival in multivariate Cox analysis [≤ 30 mm: hazard ratio (HR) = 0.533, 95% confidence interval (CI): 0.313-0.908; 31-40 mm: HR = 0.439, 95% CI: 0.201-0.957; 41-50 mm: HR = 0.382; 95% CI: 0.159-0.916; all P < 0.05]. In patients with cirrhosis, for both tumor size ≤ 30 mm and 31-40 mm groups, there were no significant survival differences between RFA and LR in multivariate analysis (all P > 0.05). However, in those with tumor size 41-50 mm, LR showed significantly better 5-year HCC cancer-specific survival than RFA in both univariate (54.72% vs. 23.06%; P < 0.001) and multivariate analyses (HR = 0.297; 95% CI: 0.136-0.648; P = 0.002). CONCLUSIONS: RFA is an inferior treatment option to LR for patients without cirrhosis who have a solitary HCC tumor ≤ 5 cm.
Subject(s)
Carcinoma, Hepatocellular , Catheter Ablation , Liver Neoplasms , Radiofrequency Ablation , Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Treatment Outcome , Catheter Ablation/adverse effects , Catheter Ablation/methods , Liver Cirrhosis/complications , Liver Cirrhosis/diagnosis , Liver Cirrhosis/surgery , Radiofrequency Ablation/adverse effects , Retrospective StudiesABSTRACT
Purpose: Although laparoscopic splenectomy and azygoportal disconnection (LSD) can significantly decrease portal vein pressure and even the incidence of hepatocellular carcinoma (HCC) in patients with cirrhotic portal hypertension (CPH), postoperative HCC inevitably occurs in certain patients. The purpose of this study was to seek a novel preoperative non-invasive predictive indicator to predict the occurrence of postoperative HCC. Patients and Methods: From April 2012 to April 2022, we collected clinical data of 178 hepatitis B virus (HBV)-related CPH patients. Based on inverse treatment probability weighting, candidate variables for predicting postoperative HCC were determined by means analysis. Then, a novel preoperative non-invasive prediction indicator (ie, type IV collagen-alpha fetoprotein-fibrosis-4 score [IVAF-FIB-4]) was established based on candidate variables, and its predictive ability was explored. Results: Postoperative HCC occurred in 9 (5.1%) patients. Correlation analyses showed that the IVAF-FIB-4 had a significant positive correlation with HCC (r = 0.835, P < 0.001). IVAF-FIB-4 showed a high accuracy (the area under the receiver operating characteristic curve: 0.939, 95% confidence interval [CI]: 0.818-1.000; sensitivity: 88.9%; specificity: 93.5%). At the end of follow-up, the incidence density of HCC in patients with IVAF-FIB-4 (1) was significant higher than that in patients with IVAF-FIB-4 (0) (138.1/1000 vs 1.1/1000 person-years; rate ratio: 130.475, 95% CI: 16.318-1043.227). In logistic regression, IVAF-FIB-4 was an independent risk factor for HCC (odds ratio: 668.000, 95% CI: 53.895-8279.541; P < 0.001). Conclusion: IVAF-FIB-4 is a novel preoperative noninvasive predictive indicator for predicting postoperative HCC in HBV-related CPH patients after LSD, with satisfactory predictive ability.
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OBJECTIVE: To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding. METHODS: A total of 23 Chinese medical centers participated in this trial. Adult patients with a history of ischemic stroke were randomly assigned in a 1:1 ratio using a block design to receive either Naoxintong Capsule (1.2 g orally, twice a day) or placebo in addition to standard care. The primary endpoint was recurrence of ischemic stroke within 2 years. Secondary outcomes included myocardial infarction, death due to recurrent ischemic stroke, and all-cause mortality. The safety of drugs was monitored. Results were analyzed using the intention-to-treat principle. RESULTS: A total of 2,200 patients were enrolled from March 2015 to March 2016, of whom 143 and 158 in the Naoxintong and placebo groups were lost to follow-up, respectively. Compared with the placebo group, the recurrence rate of ischemic stroke within 2 years was significantly lower in the Naoxintong group [6.5% vs. 9.5%, hazard ratio (HR): 0.665, 95% confidence interval (CI): 0.492-0.899, P=0.008]. The two groups showed no significant differences in the secondary outcomes and safety, including rates of severe hemorrhage, cerebral hemorrhage and subarachnoid hemorrhage (P>0.05). CONCLUSION: The combination of Naoxintong Capsule with standard care reduced the 2-year stroke recurrence rate in patients with ischemic stroke without increasing the risk of severe hemorrhage in high-risk patients. (Trial registration No. NCT02334969).
Subject(s)
Ischemic Stroke , Stroke , Adult , Humans , Secondary Prevention/methods , Stroke/drug therapy , Stroke/prevention & control , Cerebral Hemorrhage/drug therapy , Cerebral Hemorrhage/complications , Double-Blind Method , Platelet Aggregation InhibitorsABSTRACT
Fusion of transmitter-containing vesicles with plasma membranes at the synaptic and neuromuscular junctions mediates neurotransmission and muscle contractions, respectively, thereby underlying all thoughts and actions. The fusion process is driven by the coupled folding and assembly of three synaptic SNARE proteins--syntaxin-1 and SNAP-25 on the target plasma membrane (t-SNAREs) and VAMP2 on the vesicular membrane (v-SNARE) into a four-helix bundle. Their assembly is chaperoned by Munc18-1 and many other proteins to achieve the speed and accuracy required for neurotransmission. However, the physiological pathway of SNARE assembly and its coupling to membrane fusion remains unclear. Here, we review recent progress in understanding SNARE assembly and membrane fusion, with a focus on results obtained by single-molecule manipulation approaches and electric recordings of single fusion pores. We describe two pathways of synaptic SNARE assembly, their associated intermediates, energetics, and kinetics. Assembly of the three SNAREs in vitro begins with the formation of a t-SNARE binary complex, on which VAMP2 folds in a stepwise zipper-like fashion. Munc18-1 significantly alters the SNARE assembly pathway: syntaxin-1 and VAMP2 first bind on the surface of Munc18-1 to form a template complex, with which SNAP-25 associates to conclude SNARE assembly and displace Munc18-1. During membrane fusion, multiple trans-SNARE complexes cooperate to open a dynamic fusion pore in a manner dependent upon their copy number and zippering states. Together, these results demonstrate that stepwise and cooperative SNARE assembly drive stagewise membrane fusion.
Subject(s)
Membrane Fusion , SNARE Proteins , Kinetics , Membrane Fusion/physiology , Munc18 Proteins/chemistry , Munc18 Proteins/genetics , Munc18 Proteins/metabolism , Qa-SNARE Proteins , SNARE Proteins/chemistry , SNARE Proteins/metabolism , Vesicle-Associated Membrane Protein 2/genetics , Vesicle-Associated Membrane Protein 2/metabolismABSTRACT
BACKGROUND: Nursing students often lack knowledge, skills, and appropriate attitudes toward chest physiotherapy, which affects the quality of care provided to children with pneumonia in clinical practice. Helping students learn about the effectiveness of simulations can improve their nursing ability. OBJECTIVES: To develop a rubric associated with the simulation of childhood pneumonia and to examine the learning efficacy of students using the rubric to assess the knowledge, skills, and attitudes in the simulation. DESIGN: A mixed methods study using a post-test survey and a descriptive qualitative analysis of students' reflective journals. SETTINGS: A paediatric simulation classroom at the University Clinical Skills Centre in Northern Taiwan. PARTICIPANTS: 214 third-year students enrolled in a four-year nursing programme. METHODS: Quantitative and qualitative data were collected after the course to obtain a comprehensive understanding of its effects. Quantitative data from the questionnaire were analysed using descriptive statistics. Qualitative data were analysed using content analysis. RESULTS: The quantitative results showed that mean knowledge and nursing students' attitudes were moderate. Of the six sub-indices, chest percussion technique and communication with family and children had the highest mean with 3.32 ± 0.67 and 3.01 ± 0.68, respectively. The students discovered that they often focused on performing technical steps without pre-analysing patient information. Most students also indicated difficulty showing emotional caring behaviours toward patients. The qualitative results revealed that students reflected on their learning post-self-evaluation of the rubric, particularly regarding knowledge of systemic assessments, patient-centred nursing skills, and caring attitudes. CONCLUSIONS: The knowledge, skills, and attitude rubric can help students develop their learning process in a more organised manner, promote the development of their caring performances toward children, and assist them in their future clinical care practices.
Subject(s)
Education, Nursing, Baccalaureate , Students, Nursing , Humans , Child , Students, Nursing/psychology , Education, Nursing, Baccalaureate/methods , Learning , Clinical Competence , CommunicationABSTRACT
BACKGROUND: Esophagogastric variceal bleeding is the most common lethal factor for patients with cirrhotic portal hypertension. We firstly developed a laparoscopic splenectomy and azygoportal disconnection (LSD) with intraoperative endoscopic variceal ligation (LSDL) technique. In this study, we aimed to evaluate whether LSDL is feasible and safe and whether LSDL can effectively prevent esophagogastric variceal re-bleeding (EVR), as compared with single LSD. METHODS: In this randomized controlled single-center study, 88 patients with cirrhosis who had esophagogastric variceal bleeding and hypersplenism were randomly assigned to receive either LSD (n = 44) or LSDL (n = 44) between January 2020 and December 2021. The primary outcome was EVR. RESULTS: No patients withdrew from the study. There were no significant differences in estimated blood loss, incidence of blood transfusion, time to first flatus and off-bed activity, or postoperative hospital stay between the two groups. Compared with that in the LSD group, operation time was significantly longer in the LSDL group (138.5 ± 19.4 min vs. 150.3 ± 19.0 min, P < 0.05); however, LSDL was associated with a significantly decreased EVR rate at 1-year follow-up (8/44 vs. 1/44, P < 0.05). Univariate analysis and multivariate logistic regression revealed that LSDL was a significant independent protective factor against EVR in comparison with LSD (relative risk: 0.105, 95% confidence interval 0.012-0.877; P = 0.037). CONCLUSIONS: Our newly developed LSDL procedure is not only technically feasible and safe; it also contributed to lowering the EVR risk more so than single LSD. TRIAL REGISTRATION: We registered our research at https://www. CLINICALTRIALS: gov/ . The name of research registered is "Laparoscopic Splenectomy and Azygoportal Disconnection with Intraoperative Endoscopic Variceal Ligation." The trial registration identifier at clinicaltrials.gov is NCT04244487.
Subject(s)
Esophageal and Gastric Varices , Laparoscopy , Humans , Azygos Vein/surgery , Esophageal and Gastric Varices/complications , Esophageal and Gastric Varices/surgery , Gastrointestinal Hemorrhage/etiology , Laparoscopy/methods , Ligation/adverse effects , Liver Cirrhosis/complications , Splenectomy/methods , Vagus NerveABSTRACT
Protein-lipid interactions are vital for numerous transmembrane signaling pathways. However, simple tools to characterize these interactions remain scarce and are much needed to advance our understanding of signal transduction across lipid bilayers. To tackle this challenge, we herein engineer nanodisc as a robust fluorescent sensor for reporting membrane biochemical reactions. We circularize nanodiscs via split GFP and thereby create an intensity-based fluorescent sensor (isenND) for detecting membrane binding and remodeling events. We show that isenND responds robustly and specifically to the action of a diverse array of membrane-interacting proteins and peptides, ranging from synaptotagmin and synuclein involved in neurotransmission to viral fusion peptides of HIV-1 and SARS-CoV-2. Together, isenND can serve as a versatile biochemical reagent useful for basic and translational research of membrane biology.