Palmitoyltransferase ZDHHC3 is essential for the oncogenic activity of PML/RARα in acute promyelocytic leukemia.

The oncogenic fusion protein promyelocytic leukemia/retinoic acid receptor alpha (PML/RARα) is critical for acute promyelocytic leukemia (APL). PML/RARα initiates APL by blocking the differentiation and increasing the self-renewal of leukemic cells. The standard clinical therapies all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), which induce PML/RARα proteolysis, have dramatically improved the prognosis of APL patients. However, the emergence of mutations conferring resistance to ATRA and ATO has created challenges in the treatment of APL patients. Exploring pathways that modulate the oncogenic activity of PML/RARα could help develop novel therapeutic strategies for APL, particularly for drug-resistant APL. Herein, we demonstrated for the first time that palmitoylation of PML/RARα was a critical determinant of its oncogenic activity. PML/RARα palmitoylation was found to be catalyzed mainly by the palmitoyltransferase ZDHHC3. Mechanistically, ZDHHC3-mediated palmitoylation regulated the oncogenic transcriptional activity of PML/RARα and APL pathogenesis. The knockdown or overexpression of ZDHHC3 had respective effects on the expression of proliferation- and differentiation-related genes. Consistently, the depletion or inhibition of ZDHHC3 could significantly arrest the malignant progression of APL, particularly drug-resistant APL, whereas ZDHHC3 overexpression appeared to have a promoting effect on the malignant progression of APL. Thus, our study not only reveals palmitoylation as a novel regulatory mechanism that modulates PML/RARα oncogenic activity but also identifies ZDHHC3 as a potential therapeutic target for APL, including drug-resistant APL.

The lived experience of mothers caring for school-age children with Pompe disease: A qualitative study.

PURPOSE: To explore the lived experiences of mothers caring for school-age children with Pompe disease. DESIGN AND METHODS: A qualitative study using a descriptive phenomenology approach. Semi-structured interviews were conducted from October to December 2022 with 10 mothers of school-age children diagnosed with Pompe disease, which were identified through the Taiwan Pompe Disease Association. Colaizzi's phenomenological method was employed for data analysis. RESULTS: The study identified five themes in the caregiving experiences of mothers: 1. unwavering parenting beliefs; 2. child-centric approach; 3. focus on peer relationships and coping strategies; 4. integration of learning, treatment, and rehabilitation; and 5. embracing and navigating life's challenges. Mothers balanced education, treatment, and rehabilitation for their children with Pompe disease, offering perspectives into the caregiving experience. CONCLUSIONS: This study highlights the complex experiences of mothers caring for children with Pompe disease, emphasizing the importance of comprehensive support. PRACTICE IMPLICATIONS: Insights into the perspectives of mothers can aid health-care professionals in understanding the challenges faced by families with children diagnosed with Pompe disease and can enable the development of strategies for providing comprehensive psychological support to improve mental health outcomes for these children and their families. Increased awareness among health-care professionals and in the society leads to an informed and empathetic approach to addressing the unique challenges faced by children with Pompe disease and their families.

"Warrior who transcends adversity": A qualitative examination of resilience among mothers caring for adolescents with congenital heart disease.

PURPOSE: Parenting resilience is essential for the well-being and development of children with chronic illnesses. Given the importance of parenting resilience in this context, this study explored the nature of parenting resilience among mothers caring for adolescents with congenital heart disease (CHD). DESIGN AND METHODS: We adopted Husserl's phenomenological approach and conducted semistructured in-depth interviews. In addition, we conducted purposive sampling at the pediatric cardiology outpatient departments of 2 medical centers in Taiwan to recruit 11 mothers of adolescents with CHD; all of these adolescents had received open-heart surgery. Furthermore, we analyzed data by using Colaizzi's approach, and we adhered to the COnsolidated criteria for REporting Qualitative research checklist. RESULTS: Mothers caring for adolescents with CHD was a dynamic process involving problem solving. The 11 mothers in this study employed resilience to remain strong, provided a sense of normalcy for their children, and approached challenges calmly and bravely. We uncovered three major themes among these mothers: "providing support for the child, "facing challenges with equanimity," and "overcoming adversity through positivity and gratitude." CONCLUSIONS: The present results provide a deeper understanding of how mothers caring for adolescents with CHD can cultivate resilience. PRACTICE IMPLICATIONS: The study's findings can inform transitional programs for adolescents with CHD and their families, with nursing professionals supporting mothers' resilience.

Systematic Evaluation of Guidelines for the Diagnosis and Treatment of Hepatitis E Virus Infection.

Background and Aims: The hepatitis E virus (HEV) is a zoonotic disease, and infection with HEV in humans primarily causes acute infections and can progress to chronic manifestation in immunocompromised individuals. Over the past decade, guidelines for diagnosing and treating HEV infection have been developed. This study aimed to systematically assess the quality of current guidelines for diagnosing and treating HEV infection, and we analyzed the differences in guideline quality and primary recommendations and explored possible reasons for these differences. Methods: Guidelines published between 2013 and 2022 were searched, and studies were identified using selection criteria. The study assessed the quality of the included guidelines using the Appraisal of Guidelines for Research and Evaluation tool, extracted the primary recommendations in the guidelines, determined the highest level of evidence supporting the recommendations, and reclassified the evidence using the Oxford Centre for Evidence-Based Medicine grading system. Results: Seven guidelines were included in the final analysis. The quality of the guidelines varied widely. The discrepancies may have been caused by the lack of external experts, the failure to consider influencing factors in guideline application, and the lack of consideration of the public's opinion. Analysis of the heterogeneity in primary recommendations revealed differences in algorithms for managing chronic HEV infection, the dosage of ribavirin, and a low level of evidence supporting the primary recommendations. Conclusions: Guideline quality and primary recommendations vary considerably. Refinement by guideline developers and researchers would facilitate updating and applying guidelines for diagnosing and treating HEV infection.

Asiatic acid ameliorates doxorubicin-induced cardiotoxicity by promoting FPN-mediated iron export and inhibiting ferroptosis.

Doxorubicin (DOX), a common chemotherapeutic agent in cancer therapy, is accompanied by pronounced cardiotoxicity. Ferroptosis has been implicated in the pathogenesis and therapeutics of DOX-induced cardiotoxicity (DIC). Asiatic acid (AA), a pentacyclic triterpene from the Chinese medicinal herb Centella asiatica, displays antioxidant, anti-inflammatory, and antiapoptotic activities. In this study, we investigated the beneficial effects of AA against DOX-induced ferroptosis and cardiotoxicity and the underlying mechanisms. A chronic DIC model was established by challenging mice with DOX (5 mg/kg, i.p.) once per week for 4 weeks. Concurrent with DOX insult, the mice were administered AA (25 mg·kg-1·d-1, i.g.). Cardiac function and mechanical properties of isolated cardiomyocytes were evaluated at the end of treatment. We showed that AA administration preserved cardiac function, significantly reduced cardiac injury, and improved cardiomyocyte contractile function in DIC mice. The beneficial effects of AA were causally linked to the inhibition of DOX-induced ferroptosis both in vivo and in vitro. We revealed that AA attenuated DOX-induced iron accumulation in HL-1 cells by increasing FPN-mediated iron export, in a Nrf2-dependent manner. AA upregulated Nrf2 expression and promoted Nrf2 nuclear translocation in DOX-treated HL-1 cells. Moreover, AA-offered benefits against DOX-induced cardiac dysfunction and ferroptosis were abolished by Nrf2 inhibitor ML385 (30 mg·kg-1·d-1, i.p.) administrated 30 min before AA in DIC mice. Our data favor that AA promotes FPN-mediated iron export to inhibit iron overload and ferroptosis in DIC, suggesting its therapeutic potential in the treatment of DIC.

Hyperglycemia induced cathepsin L maturation linked to diabetic comorbidities and COVID-19 mortality.

Diabetes, a prevalent chronic condition, significantly increases the risk of mortality from COVID-19, yet the underlying mechanisms remain elusive. Emerging evidence implicates Cathepsin L (CTSL) in diabetic complications, including nephropathy and retinopathy. Our previous research identified CTSL as a pivotal protease promoting SARS-CoV-2 infection. Here, we demonstrate elevated blood CTSL levels in individuals with diabetes, facilitating SARS-CoV-2 infection. Chronic hyperglycemia correlates positively with CTSL concentration and activity in diabetic patients, while acute hyperglycemia augments CTSL activity in healthy individuals. In vitro studies reveal high glucose, but not insulin, promotes SARS-CoV-2 infection in wild-type cells, with CTSL knockout cells displaying reduced susceptibility. Utilizing lung tissue samples from diabetic and non-diabetic patients, alongside Leprdb/dbmice and Leprdb/+mice, we illustrate increased CTSL activity in both humans and mice under diabetic conditions. Mechanistically, high glucose levels promote CTSL maturation and translocation from the endoplasmic reticulum (ER) to the lysosome via the ER-Golgi-lysosome axis. Our findings underscore the pivotal role of hyperglycemia-induced CTSL maturation in diabetic comorbidities and complications.

People with diabetes are at greater risk of developing severe COVID-19 and dying from the illness, which is caused by a virus known as SARS-CoV-2. The high blood sugar levels associated with diabetes appear to be a contributing factor to this heightened risk. However, diabetes is a complex condition encompassing a range of metabolic disorders, and it is therefore likely that other factors may contribute. Previous research identified a link between an enzyme called cathepsin L and more severe COVID-19 in people with diabetes. Elevated cathepsin L levels are known to contribute to diabetes complications, such as kidney damage and vision loss. It has also been shown that cathepsin L helps SARS-CoV-2 to enter and infect cells. This raised the question of whether elevated cathepsin L is responsible for the increased COVID-19 vulnerability in patients with diabetes. To investigate, He, Zhao et al. monitored disease severity and cathepsin L levels in patients with COVID-19. This confirmed that people with diabetes had more severe COVID-19 and that higher levels of cathepsin L are linked to more severe disease. Analysis also revealed that cathepsin L activity increases as blood glucose levels increase. In laboratory experiments, cells exposed to glucose or fluid from the blood of people with diabetes were more easily infected with SARS-CoV-2, with cells genetically modified to lack cathepsin L being more resistant to infection. Further experiments revealed this was due to glucose promoting maturation and migration of cathepsin L in the cells. The findings of He, Zhao et al. help to explain why people with diabetes are more likely to develop severe or fatal COVID-19. Therefore, controlling blood glucose levels in people with diabetes may help to prevent or reduce the severity of the disease. Additionally, therapies targeting cathepsin L could also potentially help to treat COVID-19, especially in patients with diabetes, although more research is needed to develop and test these treatments.

Fifty-five cases of hepatic alveolar echinococcosis combined with lymph node metastasis: A retrospective study.

BACKGROUND: Lymph node metastasis is a specific type of metastasis in hepatic alveolar echinococcosis (AE). Currently, there is a scarcity of describing the clinical characteristics and lymph node metastasis rules of patients with hepatic AE combined with lymph node metastasis and its mechanism and management are still controversial. Radical hepatectomy combined with regional lymph node dissection is a better treatment. AIM: To analyse the clinical features of hepatic AE combined with lymph node metastasis to explore its treatment and efficacy. METHODS: A total of 623 patients with hepatic AE admitted to the First Affiliated Hospital of Xinjiang Medical University from 1 January 2012 to 1 January 2022 were retrospectively analysed. Fifty-five patients with combined lymph node metastasis were analysed for their clinical data, diagnosis and treatment methods, follow-up efficacy, and characteristics of lymph node metastasis. Finally, we comparatively analysed the lymph node metastasis rates at different sites. Categorical variables are expressed as frequencies and percentages, and the analysis of difference was performed using the χ 2 test. The Bonferroni method was used for pairwise comparisons when statistical differences existed between multiple categorical variables. RESULTS: A lymph node metastasis rate of 8.8% (55/623) was reported in patients with hepatic AE, with a female predilection (69.1%) and a statistically significant sex difference (χ 2 = 8.018, P = 0.005). Of the 55 patients with lymph node metastasis, 72.7% had a parasite lesion, neighbouring organ invasion, and metastasis stage of P3N1M0 and above, of which 67.3%, 78.2%, and 34.5% of hepatic AE lesions invaded the bile ducts, blood vessels, and distant metastases, respectively. Detection rates of lymph node metastasis of 16.4%, 21.7%, and 34.2% were reported for a preoperative abdominal ultrasound, magnetic resonance imaging, and computed tomography examinations. All patients were intraoperatively suspected with enlarged lymph nodes and underwent radical hepatectomy combined with regional lymph node dissection. After surgery, a routine pathological examination was conducted on the resected lymph nodes. A total of 106 positive lymph nodes were detected in six groups at various sites, including 51 single-group metastasis cases and four multi-group metastasis cases. When the metastasis rates at different sites were statistically analysed, we observed that the metastasis rate in the para-hepatoduodenal ligament lymph nodes was significantly higher than that of the other sites (χ 2 = 128.089, P = 0.000 < 0.05). No statistical difference was observed in the metastasis rate between the five other groups. Clavien-Dindo grade IIIa complication occurred in 14 cases, which improved after administering symptomatic treatment. Additionally, lymph node dissection-related complications were not observed. Recurrence after 2 years was observed in one patient. CONCLUSION: Lymph node metastasis is a rare form of metastasis in hepatic AE, which is more frequent in women. Para-hepatoduodenal ligament lymph nodes are commonly observed. Radical hepatectomy combined with regional lymph node dissection is a safe, effective, and feasible treatment for liver AE combined with lymph node metastasis.

NETs contribute to psoriasiform skin inflammation: A novel therapeutic approach targeting IL-36 cytokines by a small molecule tetrahydroxystilbene glucoside.

BACKGROUND: Psoriasis, a chronic immune-mediated skin disease with pathological features such as aberrant differentiation of keratinocytes, dermal-epidermal inflammation, and angiogenesis. 2,3,5,4'-Tetrahydroxy stilbene 2-Ο-ß-d-glucoside (2354Glu) is a natural small molecule polyhydrostilbenes isolated from Polygonum multiglorum Thunb. The regulation of IL-36 subfamily has led to new pharmacologic strategies to reverse psoriasiform dermatitis. PURPOSE: Here we investigated the therapeutic potential of 2354Glu and elucidated the underlying mechanism in psoriasis. METHODS: The effects of 2354Glu on IL-36 signaling were assessed by psoriasiform in vivo, in vitro and ex vivo model. The in vivo mice model of psoriasis-like skin inflammation was established by applying imiquimod (IMQ), and the in vitro and ex vitro models were established by stimulating mouse primary keratinocyte, human keratinocytes cells (HaCaT) and ex vivo skin tissue isolated from the mice back with Polyinosine-polycytidylic acid (Poly(I:C)), IMQ, IL-36γ and Lipopolysaccharide (LPS) respectively. Moreover, NETs formation was inhibited by Cl-amidine to evaluate the effect of NETs in psoriatic mouse model. The effects of 2354Glu on skin inflammation were assessed by western blot, H&E, immunohistochemistry, immunofluorescence, enzyme-linked immunosorbent assay and real-time quantitative PCR. RESULTS: In Poly(I:C)-stimulated keratinocytes, the secretion of IL-36 was inhibited after treatment with 2354Glu, similar to the effects of TLR3, P2X7R and caspase-1 inhibitors. In aldara (imiquimod)-induced mice, 2354Glu (100 and 25 mg/kg) improved immune cell infiltration and hyperkeratosis in psoriasis by directly targeting IL-36 in keratinocytes through P2X7R-caspase-1. When treatment with 2354Glu (25 mg/kg) was insufficient to inhibit IL-36γ, NETs reduced pathological features and IL-36 signaling by interacting with keratinocytes to combat psoriasis like inflammation. CONCLUSION: These results indicated that NETs had a beneficial effect on psoriasiform dermatitis. 2354Glu alleviates psoriasis by directly targeting IL-36/P2X7R axis and NET formation, providing a potential candidate for the treatment of psoriasis.

Hydraulic properties and drought response of a tropical bamboo (Cephalostachyum pergracile).

Bamboo plants are an essential component of tropical ecosystems, yet their vulnerability to climate extremes, such as drought, is poorly understood due to limited knowledge of their hydraulic properties. Cephalostachyum pergracile, a commonly used tropical bamboo species, exhibited a substantially higher mortality rate than other co-occurring bamboos during a severe drought event in 2019, but the underlying mechanisms remain unclear. This study investigated the leaf and stem hydraulic traits related to drought responses, including leaf-stem embolism resistance (P50leaf; P50stem) estimated using optical and X-ray microtomography methods, leaf pressure-volume and water-releasing curves. Additionally, we investigated the seasonal water potentials, native embolism level (PLC) and xylem water source using stable isotope. We found that C. pergracile exhibited strong resistance to embolism, showing low P50leaf, P50stem, and turgor loss point, despite its rapid leaf water loss. Interestingly, its leaves displayed greater resistance to embolism than its stem, suggesting a lack of effective hydraulic vulnerability segmentation (HVS) to protect the stem from excessive xylem tension. During the dry season, approximately 49% of the water was absorbed from the upper 20-cm-deep soil layer. Consequently, significant diurnal variation in leaf water potentials and an increase in midday PLC from 5.87 ± 2.33% in the wet season to 12.87 ± 4.09% in the dry season were observed. In summary, this study demonstrated that the rapid leaf water loss, high reliance on surface water, and a lack of effective HVS in C. pergracile accelerated water depletion and increased xylem embolism even in the typical dry season, which may explain its high mortality rate during extreme drought events in 2019.

Applying LASSO logistic regression for the prediction of biliary complications after ex vivo liver resection and autotransplantation in patients with end-stage hepatic alveolar echinococcosis.

BACKGROUND: The purpose of this study was to explore the relevant risk factors associated with biliary complications (BCs) in patients with end-stage hepatic alveolar echinococcosis (HAE) following ex vivo liver resection and autotransplantation (ELRA) and to establish and visualize a nomogram model. METHODS: This study retrospectively analysed patients with end-stage HAE who received ELRA treatment at the First Affiliated Hospital of Xinjiang Medical University between August 1, 2010 and May 10, 2023. The least absolute shrinkage and selection operator (LASSO) regression model was applied to optimize the feature variables for predicting the incidence of BCs following ELRA. Multivariate logistic regression analysis was used to develop a prognostic model by incorporating the selected feature variables from the LASSO regression model. The predictive ability, discrimination, consistency with the actual risk, and clinical utility of the candidate prediction model were evaluated using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). Internal validation was performed by the bootstrapping method. RESULTS: The candidate prediction nomogram included predictors such as age, hepatic bile duct dilation, portal hypertension, and regular resection based on hepatic segments. The model demonstrated good discrimination ability and a satisfactory calibration curve, with an area under the ROC curve (AUC) of 0.818 (95% CI 0.7417-0.8958). According to DCA, this prediction model can predict the risk of BCs occurrence within a probability threshold range of 9% to 85% to achieve clinical net benefit. CONCLUSIONS: A prognostic nomogram with good discriminative ability and high accuracy was developed and validated to predict BCs after ELRA in patients with end-stage HAE.

Subjective experience of parent-child relationship in adolescents with congenital heart disease: A qualitative study.

PURPOSE: To explore the parent-child relationship through the subjective experience of adolescents with congenital heart disease (CHD). DESIGN AND METHODS: A descriptive phenomenology approach was adopted. Twelve adolescents aged from 12 to 18 years with CHD were recruited from the pediatric cardiology clinics at two medical centers in Taiwan. Data were collected through in-depth interviews. Data were analyzed using Colaizzi's phenomenological analysis method, and results were reported in accordance with the Consolidated Criteria for Reporting Qualitative Research guidelines. RESULTS: The experiences of the adolescents with CHD revealed five themes: 1. the enhancement of self-worth through parents' love; 2. the importance of parental support in desperate situations; 3. the development of a sense of security through mutual understanding; 4. growth under parental expectations; and 5. parental overcontrol disguised as love. CONCLUSIONS: The parent-child relationship encompasses both positive and negative experiences. Adolescents prioritize their relationship with parents over that with peers. PRACTICE IMPLICATIONS: Nurses caring for adolescents with CHD can improve care by recognizing the influence of parental love, support in challenges, mutual understanding, parental expectations, and potential negative consequences of overcontrol. This insight guides effective guidance for adolescents, enhancing parent-child interactions and overall well-being.

Investigating the influence of the gut microbiome on cholelithiasis: unveiling insights through sequencing and predictive modeling.

BACKGROUND: Cholelithiasis is one of the most common disorders of hepatobiliary system. Gut bacteria may be involved in the process of gallstone formation and are, therefore considered as potential targets for cholelithiasis prediction. OBJECTIVE: To reveal the correlation between cholelithiasis and gut bacteria. METHODS: Stool samples were collected from 100 cholelithiasis and 250 healthy individuals from Huzhou Central Hospital; The 16S rRNA of gut bacteria in the stool samples was sequenced using the third-generation Pacbio sequencing platform; Mothur v.1.21.1 was used to analyze the diversity of gut bacteria; Wilcoxon rank-sum test and linear discriminant analysis of effect sizes (LEfSe) were used to analyze differences in gut bacteria between patients suffering from cholelithiasis and healthy individuals; Chord diagram and Plot-related heat maps were used to analyze the correlation between cholelithiasis and gut bacteria; six machine algorithms were used to construct models to predict cholelithiasis. RESULTS: There were differences in the abundance of gut bacteria between cholelithiasis and healthy individuals, but there were no differences in their community diversity. Increased abundance of Costridia, Escherichia flexneri, and Klebsiella pneumonae were found in cholelithiasis, while Bacteroidia, Phocaeicola, and Phocaeicola vulgatus were more abundant in healthy individuals. The top four bacteria that were most closely associated with cholelithiasis were Escherichia flexneri, Escherichia dysenteriae, Streptococcus salivarius, and Phocaeicola vulgatus. The cholelithiasis model based on CatBoost algorithm had the best prediction effect (sensitivity: 90.48%, specificity: 88.32%, and AUC: 0.962). CONCLUSION: The identification of characteristic gut bacteria may provide new predictive targets for gallstone screening. As being screened by the predictive model, people at high risk of cholelithiasis can determine the need for further testing, thus enabling early warning of cholelithiasis.

Assessing the intention to accept inquiry-based teaching pedagogy among Chinese university students: an extension of technology acceptance model.

Introduction: Due to the limitations of traditional didactic teaching, inquiry-based teaching has attracted increasing attention and has become an important content of curriculum teaching reform in college education. Nevertheless, it is vital to investigate students' subjective acceptance of inquiry-based instruction and its influencing factors before inquiry-based teaching methods are widely implemented. Methods: In light of this, taking into account the psychological factors of students, an acceptance model of inquiry-based teaching pedagogy was established based on the extended technology acceptance model (TAM). Three additional variables, namely self-efficacy, implementation quality, and risk perception, were incorporated into the TAM. Firstly, subjective evaluation data of the influencing factors of inquiry teaching acceptance were obtained through a network questionnaire survey from university students in Guangdong, China, using snowball sampling and convenient sampling. A total of 485 valid questionnaires were retrieved, with an effective response rate of 88.2%. Then, internal consistency and reliability, convergent validity and discriminant validity of the model and its hypothesis were tested with reliability and validity tests. Finally, path analysis was used to examine key determinants of students' acceptance of inquiry teaching and moderators. Results: Results indicated that the constructed model can explain the acceptability of inquiry teaching for college students by 88.6%; Attitude has a positive significant impact on behavioral intention; Perceived ease of use indirectly affects behavioral intention through perceived usefulness, while perceived usefulness indirectly affects behavioral intention through attitude; self-efficacy not only directly affects behavioral intention but also indirectly affects behavioral intention through implementation quality; implementation quality indirectly affects behavioral intention through perceived usefulness and attitude; students' risk perception of inquiry-based teaching has no negative impact on behavioral intention. Conclusion: Overall, this study has implications for policymakers, teachers or learners in terms of the implementation and promotion of inquiry-based teaching in college classroom.

Experience in Professional Resilience for Nurses Caring for Patients with COVID-19: A Qualitative Descriptive Study.

PURPOSE: During the COVID-19 pandemic, nurses have faced many professional and ethical dilemmas and challenges along with bearing physical, mental, and emotional stress resulting from worrying about themselves or their family being infected and stigmatized. This stress can potentially lead to burnout and resignation. Professional resilience is crucial for nurses to cope with these adverse situations. This study aimed to investigate the process by which nurses adapt, change, and overcome challenges during the COVID-19 pandemic and ultimately demonstrate professional resilience. METHODS: Descriptive phenomenology was applied. Semi-structured interviews were conducted with 11 nurses working in COVID-19 wards and intensive care units to collect data. Giorgi's phenomenological analysis method was employed. RESULTS: Based on the interview responses, four major themes were identified: 1) balancing patient care, self-protection, and passing on experience; 2) providing timely pandemic team resources and social support; 3) nurses' perseverance amid social discourse and constrained lives; and 4) selfless dedication shaping nursing's pinnacle experiences. CONCLUSIONS: In the face of a sudden pandemic, frontline nurses play a critical role in maintaining medical capacity. Consequently, they must balance their families, lives, and work while adapting to the impact of the pandemic and changing practices and procedures based on the development of the pandemic and policy demands. The study findings provide insights into the challenges and emotional experiences encountered by nurses during a sudden pandemic outbreak and can serve as a reference for developing strategies to help nurses overcome these challenges and enhance their professional resilience.

Four new species of Puccinia from herbaceous plants in China.

Members of Puccinia (Pucciniaceae, Pucciniales) are known as plant pathogens worldwide, which are characterized by their morphology, host association, and molecular data of various genes. In the present study, 10 specimens of Puccinia were collected from four herbaceous plants (Anaphalis hancockii, Anthriscus sylvestris, Halenia elliptica, and Pilea pumila) in China and identified based on morphology and phylogeny. As a result, 10 samples represent four undescribed species of Puccinia, viz., P. apdensia, P. decidua, P. dermatis, and P. lianchengensis, spp. nov. P. apdensia is characterized by its smooth teliospores with thickened apex. P. decidua represents the first Puccinia species inhabiting the host Anaphalis hancockii and is distinguished from the other Puccinia species by its telia and uredinia surrounded by the epidermis. P. dermatis from Halenia elliptica differs from the other Puccinia species on the host genus Halenia by the telia that have epidermis and teliospores with sparsely irregular granulated protrusions. P. lianchengensis is characterized by its teliospore surface with fishnet ornamentation and urediniospores without prominent caps. All of the new species are described and illustrated in this study.

A CT-based Deep Learning Radiomics Nomogram for the Prediction of EGFR Mutation Status in Head and Neck Squamous Cell Carcinoma.

RATIONALE AND OBJECTIVES: Accurately assessing epidermal growth factor receptor (EGFR) mutation status in head and neck squamous cell carcinoma (HNSCC) patients is crucial for prognosis and treatment selection. This study aimed to construct and validate a contrast-enhanced computed tomography (CECT)-based deep learning radiomics nomogram (DLRN) to predict EGFR mutation status of HNSCC. MATERIALS AND METHODS: A total of 300 HNSCC patients who underwent CECT scans were enrolled in this study. Participants from two hospitals were separated into a training set (n = 200, 56 EGFR-negative and 144 EGFR-positive) from one hospital and an external test set from the other hospital (n = 100, 37 EGFR-negative and 63 EGFR-positive). The least absolute shrinkage and selection operator method was used to select the key features from CECT-based manually extracted radiomics (MER) features and features automatically extracted using a deep learning model (DL, extracted using a GoogLeNet model). The selected independent clinical factors, MER features, and DL features were then combined to construct a DLRN. The DLRN's performance was evaluated using receiver operating characteristics curves. RESULTS: Five MER and six DL features were finally chosen. The DLRN, which includes "gender" and "necrotic areas," along with the selected features, predicted EGFR mutation status of HNSCC (EGFR-negative vs. positive) well in both the training (area under the curve [AUC], 0.901) and test (AUC, 0.875) sets. CONCLUSION: A DLRN using CECT was built to predict EGFR mutation in HNSCC. The model showed high predictive ability and may aid in treatment selection and patient prognosis.

Neuron-derived exosomes mediate sevoflurane-induced neurotoxicity in neonatal mice via transferring lncRNA Gas5 and promoting M1 polarization of microglia.

Sevoflurane exposure during rapid brain development induces neuronal apoptosis and causes memory and cognitive deficits in neonatal mice. Exosomes that transfer genetic materials including long non-coding RNAs (lncRNAs) between cells play a critical role in intercellular communication. However, the lncRNAs found in exosomes derived from neurons treated with sevoflurane and their potential role in promoting neurotoxicity remain unknown. In this study, we investigated the role of cross-talk of newborn mouse neurons with microglial cells in sevoflurane-induced neurotoxicity. Mouse hippocampal neuronal HT22 cells were exposed to sevoflurane, and then co-cultured with BV2 microglial cells. We showed that sevoflurane treatment markedly increased the expression of the lncRNA growth arrest-specific 5 (Gas5) in neuron-derived extracellular vesicles, which inhibited neuronal proliferation and induced neuronal apoptosis by promoting M1 polarization of microglia and the release of inflammatory cytokines. We further revealed that the exosomal lncRNA Gas5 significantly upregulated Foxo3 as a competitive endogenous RNA of miR-212-3p in BV2 cells, and activated the NF-κB pathway to promote M1 microglial polarization and the secretion of inflammatory cytokines, thereby exacerbating neuronal damage. In neonatal mice, intracranial injection of the exosomes derived from sevoflurane-treated neurons into the bilateral hippocampi significantly increased the proportion of M1 microglia, inhibited neuronal proliferation and promoted apoptosis, ultimately leading to neurotoxicity. Similar results were observed in vitro in BV2 cells treated with the CM from HT22 cells after sevoflurane exposure. We conclude that sevoflurane induces the transfer of lncRNA Gas5-containing exosomes from neurons, which in turn regulates the M1 polarization of microglia and contributes to neurotoxicity. Thus, modulating the expression of lncRNA Gas5 or the secretion of exosomes could be a strategy for addressing sevoflurane-induced neurotoxicity.

Research progress of large-scale brain network of Alzheimer's disease based on MRI analysis / 实用医学杂志

With the advent of an aging society,Alzheimer's disease(AD)has gradually become a major ailment affecting the elderly.AD is a neurodegenerative disorder associated with cognitive impairments.In AD patients,brain network connections are disrupted,and their topological properties are also affected,leading to the disintegration of anatomical and functional connections.Anatomical connections can be tracked and evaluated using structural magnetic imaging(MRI)and diffusion tensor imaging(DTI),while functional connections are detected through functional MRI to assess their connectivity status.This review incorporates the findings of previous scholars and summarizes the current research of AD.It mainly discusses the imaging characteristics of large-scale brain network changes in AD patients,so as to provide researchers with scientific and objective imaging markers for AD prediction and early diagnosis,as well as future research.