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Academic research trends involving public health education may reflect a certain degree of talent construction status. This study systematically reviews the data for published literature on graduate public health education, aiming to provide evidence for the optimization of public health postgraduate training mechanisms in China. Keyword cooccurrence analysis was performed based on high-frequency keywords. From 1992 to 2008, the annual number of publications in this field was relatively low in China, averaging fewer than 5 articles. The number of publications showed a steep increase after 2009. The publications were mostly from single research institutions, including comprehensive universities and military medical universities, concentrated in Beijing and Shanghai. The high-frequency keywords were public health and preventive medicine, postgraduate training, professional degree, MPH, curriculum, and teaching reform. Hotspots consisted of practical teaching research, training, educational reform and comparative education research. Research on public health postgraduate education has not reached scale and has insufficient support. Moreover, many problems in graduate public health education still cannot be solved by existing studies: authentic and practical learning, a unified approach to cultivate graduate students, organizational change of graduate public health education, and international cooperation and public health education.

Overviews synthesising the results of multiple systematic reviews help inform evidence-based clinical practice. In this first of two companion papers, we evaluate the bibliometrics of overviews, including their prevalence and factors affecting citation rates and journal impact factor (JIF). We searched MEDLINE, Epistemonikos and Cochrane Database of Systematic Reviews (CDSR). We included overviews that: (1) synthesised reviews; (2) conducted a systematic search; (3) had a methods section; and (4) examined a healthcare intervention. Multivariable regression was conducted to determine the association between citation density, JIF and six predictor variables. We found 1218 overviews published from 2000 to 2020; the majority (73%) were published in the most recent 5-year period. We extracted a selection of these overviews (n = 541; 44%) dated from 2000 to 2018. The 541 overviews were published in 307 journals; "CDSR" (8%), "PLOS ONE" (3%) and "Sao Paulo Medical Journal" (2%) were the most prevalent. The majority (70%) were published in journals with impact factors between 0.05 and 3.97. We found a mean citation count of 10 overviews per year, published in journals with a mean JIF of 4.4. In multivariable analysis, overviews with a high number of citations and JIFs had more authors, larger sample sizes, were open access and reported the funding source. An eightfold increase in the number of overviews was found between 2009 and 2020. We identified 332 overviews published in 2020, which is equivalent to one overview published per day. Overviews perform above average for the journals in which they publish.

Integrating education practices and measurements of brain activity has the potential to make learning more engaging and productive. Direct recordings of electrical activity in the brain provide important information about the complex dynamics of the cognitive processes and mental states that occur during learning, which can ultimately empower learners. In this article, electroencephalographic (EEG) methodologies, including the time-frequency and event-related potential techniques, are introduced, and the application of these techniques to studies of digital learning studies is discussed. Considerations of how to collect high quality data in both laboratory and real world settings are also presented, along with potential research directions. Finally, a general guideline for publishing results is offered. These issues are critical for producing useful applications of EEG studies to the digital learning research community.

The aim of this study is to evaluate a 3D (Three Dimensional) Traditional Chinese Medicine (TCM) e-learning platform and determine the factors affecting students' intention to continue to use the platform in TCM courses. Students from two classes were invited to participate in the experiment. To compare the effectiveness of both learning methods, one class serves as the control group and used the traditional classroom lecture method while the other serves as the experimental group using the 3D e-learning platform. To determine the factors affecting TCM students' intention to continue to use the platform, we propose an evaluation model modified from the post-acceptance model of information systems. Data collected from the experimental group students are used to test the proposed research model via the PLS-SEM method. We find that TCM students using the 3D e-learning platform outperformed those who used the traditional classroom lecture method. Meanwhile, the integrated evaluation model is found to provide reasonable explanatory power regarding TCM students' intention to continue to use the e-learning platform.

Background: The significant increase in medical disputes and lawsuits in recent years in Taiwan has severely affected behavior and ecology in medical practice. For this reason, we designed integrated courses on ethics and law and conducted a questionnaire-based career plan study to understand whether these issues influence their specialty selection process. Method: We randomly selected sixth-year medical students that rotated to our hospital to take an integrated course on medical ethics, laws and regulations, and problem-based learning. The students completed the same questionnaire before and after the course. We used a five-point Likert scale for agreement. In addition to calculating the proportion of agreement, we used paired t-tests in the question items before and after the course at a 0.05 level of significance. A qualitative analysis was also made. Results: This study included 98 medical students, 65 of whom were male, and 33 were female. In terms of reasons for studying medicine, the question item with the highest agreement proportion was "I chose to study medicine because being a doctor will enable me to lead a stable life"; in terms of career plans, it was "I will choose my specialty based on my personal aspirations and interests". On agreement scale, significant increases were presented in "I will choose my specialty based on my personal aspirations and interests" and "I will choose my specialty based on my sense of accomplishment". However, a significant reduction was found in "I will choose my specialty based on quality-of-life considerations". Qualitative analysis indicated that the students learnt that "acquiring good communication skills and fulfilling the obligation to obtain informed consent are the fundamental means of preventing medical disputes". Conclusion: After completing the course, medical students put greater emphasis on personal aptitude, interests, and sense of accomplishment, and less on quality-of-life in choosing a specialty.

BackgroundChronic pain is associated with poor physical and emotional functioning. Nonpharmacological interventions can help, but improvements are small and not sustained. Previous clinical trials do not follow recommendations to comprehensively target objectively measured and performance-based physical function in addition to self-reported physical function. ObjectiveThis study aimed to establish feasibility benchmarks and explore improvements in physical (self-reported, performance based, and objectively measured) and emotional function, pain outcomes, and coping through a pilot randomized controlled trial of a mind-body physical activity program (GetActive) with and without a digital monitoring device (GetActive-Fitbit), which were iteratively refined through mixed methods. MethodsPatients with chronic pain were randomized to the GetActive (n=41) or GetActive-Fitbit (n=41) programs, which combine relaxation, cognitive behavioral, and physical restoration skills and were delivered in person. They completed in-person assessments before and after the intervention. Performance-based function was assessed with the 6-min walk test, and step count was measured with an ActiGraph. ResultsFeasibility benchmarks (eg, recruitment, acceptability, credibility, therapist adherence, adherence to practice at home, ActiGraph wear, and client satisfaction) were good to excellent and similar in both programs. Within each program, we observed improvement in the 6-min walk test (mean increase=+41 m, SD 41.15; P

Abstract Background Staphylococcal enterotoxin and fungal sensitization can influence asthma severity; however, the effects on the clinical outcomes of asthma remain unclear. This study investigated the clinical outcomes of asthma in patients with or without staphylococcal enterotoxin sensitization and further analyzed the effects of fungal sensitization on the clinical outcomes of patients with staphylococcal enterotoxin sensitization. Methods This retrospective study included patients with asthma who had undergone a staphylococcal enterotoxin-specific immunoglobulin E test at our hospital between January and August 2021. Data on clinical manifestations, medication use, pulmonary function, clinic and emergency room visits and hospitalization were collected from 106 patients. Results The prevalence of staphylococcal enterotoxin sensitization was 27.3%. Among the patients with staphylococcal enterotoxin sensitization, 50% also presented with fungal sensitization. The risk of hospitalization and emergency room visits was higher among patients with staphylococcal enterotoxin sensitization than among those without, as was the need for high-level asthma treatment, including triple inhaler therapy and biologics. After the 12-month Program enrollment, the rates of emergency room visits and hospitalization were similar in the two cohorts. Patients with concomitant staphylococcal enterotoxin and fungal sensitization exhibited a notable post-treatment decline in pulmonary function. Conclusion Adherence to asthma treatment protocols was shown to improve clinical outcomes in patients with or without staphylococcal enterotoxin sensitization. Among patients with staphylococcal enterotoxin sensitization, those with concomitant fungal sensitization were more likely to exhibit a rapid decline in pulmonary function during a 1-year high-level treatment program.

Abstract Prescriptive BW charts can facilitate discrimination between normal and abnormal birthweight. This study aimed to develop a prescriptive BW chart specific to Asian populations and assess its utility in predicting infant mortality. A retrospective cohort study was conducted using data from Taiwan National Health Insurance Research Database and National Birth Reporting Database. This study included 2 956 475 live-born singleton infants born to healthy mothers with uncomplicated pregnancies in Taiwan from January 1, 2004, to December 31, 2019. BW percentiles were estimated from GA 24–42 weeks by ranking the data in ascending order and calculating the percentile values based on the relative position of each observation within the dataset. Infant mortality rates were calculated for different GA groups, and optimal BW percentile cutoffs for predicting mortality were determined. A total of 2,255,989 infants (77.6%) from low-risk pregnancies were included in the development of the BW chart. Sex-specific BW percentiles were calculated. Optimal cutoff for predicting mortality were identified as follows: below the 22nd percentile or above the 96th percentile for extremely preterm infants (GA: 24–27 + 6 weeks), below the 11th percentile or above the 98th percentile for very preterm infants (GA: 28–31 + 6 weeks), below the 9th percentile or above the 99th percentile for moderately preterm infants (GA: 32–33 + 6 weeks), below the 8th percentile or above the 98th percentile for late preterm infants (GA: 34–36 + 6 weeks), and below the 7th percentile or above the 100th percentile for term infants (GA: > 37 weeks). A prescriptive BW chart was developed using data from a large population of Asian infants from low-risk pregnancies. BW percentiles were determined to predict infant mortality. Clinicians can utilize this approach to provide effective consultations to parents and improve decision-making processes.

Abstract This study is to analyse the failure patterns and long-term survival after stereotactic body radiotherapy (SBRT) in patients with T1-3N0M0 inoperable non-small cell lung cancer (NSCLC). Early-stage NSCLC patitents who received SBRT at Zhejiang Cancer Hospital from January 2012 to September 2018 were retrospectively analyzed. The primary endpoint were the patterns of disease progression, which were divided into local recurrence, regional failure, and distant metastasis. Kaplan-Meier method survival analysis was used to calculate overall survival (OS), progression-free survival (PFS). Cox model was used for univariate analysis and multivariate analysis. A total of 215 patients with 224 lesions were enrolled. After the median follow-up time of 50.8 months (1.0-117.9 months), 76 (35.3%) patients progressed, with regional progression occurring in 4 cases (1.8%), local and local-regional progression in 17 cases (7.9%), various distant metastases developing in 55 cases (25.6%). The OS rates at 1, 3, and 5 years were 97.1%, 80.9%, and 63.8%, respectively, with a median OS of 92.2 months (95%CI, 61.5-122.9 months). The PFS rates at 1, 3, and 5 years were 87.5%, 65.9%, and 50.8%, respectively, with a median PFS of 62.2 months (95% CI, 45.0-59.4 months). There was no significant difference in OS (P = 0.832) and PFS (P = 0.672) between the two groups with or without pathology. Multivariate analysis showed that BED and patient age were independent prognostic factors affecting early-stage lung cancer survival (all P

Abstract Background Chronic pain poses a clinical challenge due to its associated costly disability and treatment needs. Determining how pain transitions from acute to chronic is crucial for effective management. Upregulation of the chemokine C-X-C motif ligand 12 (CXCL12) in nociceptive pathway is associated with chronic pain. Our previous study has reported that elevated plasma CXCL12 mediates intracerebral neuroinflammation and the comorbidity of cognitive impairment in neuropathic pain, but whether it is also involved in the pathogenesis of pathologic pain has not been investigated. Methods Intravenous or intrathecal injection (i.v. or i.t.) of recombinant mouse CXCL12, neutralizing antibody (anti-CXCL12) or AMD3100 [an antagonist of its receptor C-X-C chemokine receptor type 4 (CXCR4)] was used to investigate the role of CXCL12 signaling pathway in pain chronicity. Two behavioral tests were used to examine pain changes. ELISA, immunofluorescence staining, Western blot, quantitative Real Time-PCR and Cytokine array were applied to detect the expressions of different molecules. Results We found that increased plasma CXCL12 was positively correlated with pain severity in both chronic pain patients and neuropathic pain model in mice with spared nerve injury (SNI). Neutralizing plasma CXCL12 mitigated SNI-induced hyperalgesia. A single i.v. injection of CXCL12 induced prolonged mechanical hyperalgesia and activation of the nociceptive pathway. Multiple intravenous CXCL12 caused persistent hypersensitivity, enhanced structural plasticity of nociceptors and up-regulation of the CXCL12/CXCR4 axis in the dorsal root ganglion (DRG) and spinal dorsal horn (SDH). However, intrathecal blocking of CXCL12/CXCR4 pathway by CXCL12 antibody or CXCR4 antagonist AMD3100 significantly alleviated CXCL12-induced pain hypersensitivity and pathological changes. Conclusions Our study provides strong evidence that a sustained increase in plasma CXCL12 contributes to neuropathic pain through a positive feedback loop that enhances nociceptor plasticity, and suggests that targeting CXCL12/CXCR4 axis in plasma or nociceptive pathways has potential value in regulating pain chronicity.

Abstract Aerobic glycolysis is a hallmark of cancer and is regulated by growth factors, protein kinases and transcription factors. However, it remains poorly understood how these components interact to regulate aerobic glycolysis coordinately. Here, we show that sine oculis homeobox 1 (SIX1) phosphorylation integrates growth factors (e.g. TGFβ, EGF) to control aerobic glycolysis and determines its tumor-promoting activity. SIX1 is phosphorylated at serine 225 (S225) by growth factors-activated protein kinases ERK1/2 and its phosphorylation is responsible for glycolysis stimulated by some growth factors. SIX1 is dephosphorylated by the atypical protein phosphatase eyes absent 4 (EYA4). Phosphorylation blocks non-canonical ubiquitination and degradation of SIX1 through the E3 ubiquitin ligase FZR1. Unexpectedly, the non-canonical phosphorylation mimic SIX1 (S225K), but not the canonical phosphorylation mimic SIX1 (S225D/E), phenocopies the effects of SIX1 phosphorylation on glycolysis and cancer cell growth and metastasis in vitro and in mice. Compared to normal liver tissues, SIX1 phosphorylation at S225 (pS225) is upregulated in human liver cancer tissues. ERK1/2 expression is positively correlated with pS225 and EYA4 expression is negatively associated with pS225 in liver cancer specimens. Moreover, low expression of pS225 had longer disease-free survival and overall survival in patients with liver cancer. Thus, we identify a common mechanism underlying growth factors-mediated glycolysis, and provide a previously unidentified mode for non-classical phosphorylation mimics of a protein. Targeting growth factors/SIX1 signaling pathway may be beneficial to cancer treatment.

Objectives. Labyrinthitis significantly reduces quality of life due to prolonged vestibular symptoms in patients experiencing sudden sensorineural hearing loss with vertigo (SSNHLV). This study employed a novel coherence analysis in the video head impulse test (vHIT) to explore vertigo outcomes in SSNHLV patients. Methods. A retrospective review was conducted on 48 SSNHLV patients who completed high-dose steroid treatment between December 2016 and April 2023. Additionally, 38 healthy volunteers were prospectively enrolled from November 2022 to April 2023 at our academic tertiary referral center. The magnitude-squared wavelet coherence between eye and head velocities during the vHIT was measured to assess correlations across frequency bands. Recovery from vertigo, determined by a visual analog scale (VAS) score of 0 at both 2 weeks and 2 months, was analyzed using multivariable Cox regression. Results. The mean VAS for patients with SSNHLV was 5.73±2.45. Higher coherent frequencies in the horizontal semicircular canal (SCC), posterior SCC, and the mean and minimal coherent frequencies of all three SCCs combined were significantly associated with early complete remission of vertigo 2 weeks posttreatment. In the multivariate analysis, the minimal coherent frequency among the three SCCs emerged as an independent factor (hazard ratio, 2.040; 95% CI, 1.776–2.304). Two months posttreatment, in addition to the previously significant parameters, abnormalities in the vestibulo-ocular reflex (VOR) in the posterior SCC, gains in the horizontal and posterior SCCs, total and overt saccades in the horizontal SCC, coherent frequency in the anterior SCC, and mean VOR gain of all three SCCs combined were also statistically significantly related to total relief from vertigo. Conclusion. The highest minimal coherent frequency among the three SCCs significantly contributed to earlier vertigo relief in patients with SSNHLV. Coherence analysis in vHIT may offer greater sensitivity than time series analysis for predicting the prognosis of vertigo.

Abstract Background The management of Garden IV femoral neck fractures presents a formidable challenge. This study aimed to assess the safety and efficacy of a novel technological approach for treating Garden IV femoral neck fractures, involving intracapsular decompression and the utilization of supported hollow screws. Methods Between October 2018 and October 2021, a cohort of 46 patients, comprising 25 males and 21 females, was admitted for Garden IV femoral neck fractures. The surgical intervention employed a novel methodology, involving closed reduction of femoral neck fractures on a traction bed and percutaneous implantation of decompression support hollow screw internal fixation in the capsule. Operative parameters such as intraoperative bleeding volume, incision length, and fluoroscopy frequency were recorded. Postoperative angiography was performed to evaluate the blood supply to the femoral neck and femoral head, while long-term follow-up records documented femoral neck fracture healing and patient functional recovery. Results The closed reduction and minimally invasive implantation of decompression support screws in the femoral neck capsule proved effective in successfully fixing Garden IV femoral neck fractures. The screw placement time was 20–45 min, with an average of 25.2 min. The number of fluoroscopy was 6–14, with an average of 7. The postoperative follow-up was 20–25 months, with an average duration of 22 months. All patients exhibited uneventful single-stage wound healing, devoid of complications such as nerve, blood vessel, or important tissue structure injuries. While femoral head necrosis occurred in one case and femoral neck shortening in another, all femoral neck fractures exhibited healing. Post-surgery, patients experienced rapid recovery, enabling early functional exercise with satisfactory functional restoration. Conclusion The innovative technology, employing femoral neck capsule decompression support hollow screws, not only offers structural support, but also facilitates capsule decompression post-femoral neck fracture surgery. This approach promotes the restoration of blood flow to the femoral head and neck, accelerates fracture healing, diminishes the likelihood of femoral head necrosis, and enhances the overall therapeutic outcome for Garden IV femoral neck fractures. The merits of this novel technique warrant its widespread adoption and application.

Abstract Currently, there is limited evidence regarding the association between prenatal exposure to environmental fine particulate matter (PM2.5) and the occurrence of cryptorchidism. The objective of this study was to evaluate the potential correlation between prenatal exposure to PM2.5 and the likelihood of cryptorchidism developing in offspring. We performed a 1:1 case–control study, defining the cases as children diagnosed with cryptorchidism at the Children’s Hospital Affiliated to Chongqing Medical University from 2013 to 2017, while the control group comprised children born in the corresponding years who did not have any birth defects, chromosomal abnormalities, and had only trauma-related treatments. Between 2012 and 2017, monthly averages of PM2.5, other pollutants (O3, PM10) and temperature were gathered based on the geographical coordinates of patients’ residences. The study assessed the correlation between the two using multivariate logistic regression model, and sensitivity analysis was conducted to assess the stability of the model. We included a total of 2137 cases and 2137 matched controls from 2013 to 2017. Our findings revealed that there was a positive association between exposure to PM2.5 during the first 2 months of pregnancy and the occurrence of cryptorchidism. According to this study, the development of cryptorchidism appears to be associated with maternal exposure to PM2.5 during early pregnancy.

Abstract Efficacy and safety analysis of the combination of decitabine priming followed by CHAG chemotherapy in treatment of relapsed/refractory(r/r) acute myeloid leukemia (AML). Between January 2013 and June 2020, 62 r/r AML patients in our center receiving therapy including combination of decitabine and CHAG pre-excitation regimen were enrolled. Primary objectives were overall response (ORR: complete remission + partial remission), adverse events, overall survival (OS) and relapse-free survival (RFS). There were 46 patients (74.2%) with complete remission (CR), 5 patients (8.06%) with partial remission (PR), ORR was 82.2%. Main adverse events were bone marrow suppression, fever and infection, and no chemotherapy-related deaths occurred. The median RFS time was 4.3 months (0.3 ~ 65 months), and median OS time was 7.75 months (1 ~ 66.3 months). Decitabine priming followed by CHAG regimen is effective and tolerated in patients with r/r AML, and can be used as a salvage treatment for patients with r/r AML.

Abstract Heart failure (HF) is the leading cause of death in patients with maintenance hemodialysis (MHD). Biomarkers has an important guiding role in the early diagnosis, risk stratification, and prognostic assessment of HF. Increasing studies have indicated that long non-coding RNAs (lncRNAs) have played an indispensable role in the regulatory network of HF. This study was aiming to explore the expression profiles of lncRNAs in patients treated with MHD developing heart failure. Peripheral blood mononuclear cells were isolated from 4 hemodialysis patients with reduced ejection fraction (HFrEF) and 4 hemodialysis patients with preserved ejection fraction (HFpEF), respectively. The expression profile analysis of lncRNAs was performed by using Illumina Novaseq 6000 sequencer. Quantitative real time polymerase chain reaction (qRT-PCR) was used to verify the expression of representative differentially expressed lncRNAs. Based on lncRNA-miRNA-mRNA-KEGG network analysis, the potential role of candidate lncRNAs and their association with the severity of HF were further evaluated. In total, 1,429 differentially expressed lncRNAs were found between patients with HFrEF and patients with HFpEF, of which 613 were up-regulated and 816 were down-regulated (P

Abstract Background This study aimed to evaluate the performance of GPT-3.5, GPT-4, GPT-4o and Google Bard on the United States Medical Licensing Examination (USMLE), the Professional and Linguistic Assessments Board (PLAB), the Hong Kong Medical Licensing Examination (HKMLE) and the National Medical Licensing Examination (NMLE). Methods This study was conducted in June 2023. Four LLMs (Large Language Models) (GPT-3.5, GPT-4, GPT-4o and Google Bard) were applied to four medical standardized tests (USMLE, PLAB, HKMLE and NMLE). All questions are multiple-choice questions and were sourced from the question banks of these examinations. Results In USMLE step 1, step 2CK and Step 3, there are accuracy rates of 91.5%, 94.2% and 92.7% provided from GPT-4o, 93.2%, 95.0% and 92.0% provided from GPT-4, 65.6%, 71.6% and 68.5% provided from GPT-3.5, and 64.3%, 55.6%, 58.1% from Google Bard, respectively. In PLAB, HKMLE and NMLE, GPT-4o scored 93.3%, 91.7% and 84.9%, GPT-4 scored 86.7%, 89.6% and 69.8%, GPT-3.5 scored 80.0%, 68.1% and 60.4%, and Google Bard scored 54.2%, 71.7% and 61.3%. There was significant difference in the accuracy rates of four LLMs in the four medical licensing examinations. Conclusion GPT-4o performed better in the medical licensing examinations than other three LLMs. The performance of the four models in the NMLE examination needs further improvement. Clinical trial number Not applicable.

Abstract Neurotoxic effects of general anesthetics, particularly sevoflurane, on pediatric neurodevelopment are a global concern. This study investigated the molecular and metabolic impacts of repeated short exposures to sevoflurane in neonatal rats. Metabolomics analysis revealed significant changes in fatty acid and mitochondrial energy metabolism. Transcriptomic analysis identified altered gene expression related to neurodevelopment and mitochondrial function. Various analyses emphasized upregulation in oxidative phosphorylation and DNA repair pathways. Weighted gene co-expression network analysis (WGCNA) identified key gene modules associated with sevoflurane exposure. Despite these acute changes, no significant long-term memory impairments were detected. These findings highlight the impact of sevoflurane on mitochondrial energy metabolism, oxidative stress, and neuroinflammation, emphasizing its relevance to pediatric neurodevelopment. The absence of substantial long-term memory impairments provides insights into the safety and implications of sevoflurane use in pediatric anesthesia, calling for further research.

Abstract Microvascular obstruction (MVO) is linked with adverse clinical outcome in acute coronary syndrome (ACS) patients, therefore, early prediction of MVO with non-invasive peripheral microcirculation is crucial in facilitating optimal treatment. Current study aims to analyze the significance of opisthenar microvessel area (OMA, measured using optical coherence tomography, OCT) in predicting coronary stenosis (Gensini score, GS) and short-term cardiac recovery of ACS patients and the results were compared to those of arterial stiffness parameters (Pulse Wave Velocity, PWV; Ankle-Brachial Index; ABI). Results showed that cardiac functional parameters (e.g. ejection fraction, EF; fractional shortening, FS) and OMA were higher in normal/low risk (GS 0–≤ 20, n = 69) compared to medium/high risk patients (GS > 20, n = 44, P

Abstract Background Cancer survivors face elevated risks of heart failure (HF) and death, with cardiac dysfunction being a significant concern. Current evaluations often emphasize systolic function while insufficiently addressing diastolic function. This study aims to investigate the prevalence of diastolic dysfunction and assess its prognostic implications in long-term cancer survivors. Methods We analyzed participants from the Atherosclerosis Risk in Communities (ARIC) Study with complete echocardiographic assessments and documented cancer histories. Diastolic function was classified by guideline criteria: normal (≤ 1 abnormal parameter), indeterminate (2 abnormal parameters), and dysfunction (≥ 3 abnormal parameters). The primary outcomes were incident HF and all-cause death. Diastolic dysfunction prevalence was compared between cancer survivors and non-cancer participants after propensity score matching. Cox regression, Kaplan–Meier, and restricted cubic spline (RCS) analyses were used to assess associated risks. Results A total of 5322 participants were included, with 18.4% (N = 979) being cancer survivors. The mean age of cancer survivors at echocardiography was 76.3 (5.10) years, with a median of 12.17 years since diagnosis. There were no significant differences in diastolic dysfunction prevalence (12.26% vs 10.73%, P = 0.29) after matching. Cox regression revealed a graded association between diastolic dysfunction and risks of HF and death. Fully adjusted hazard ratios were 2.59 (95% CI: 1.59–4.20, P

Abstract Introduction Hypoxemia is a common complication of sedation. This meta-analysis aimed to evaluate the efficacy and safety of supraglottic jet oxygenation and ventilation (SJOV) in preventing hypoxemia during sedative procedures. Methods Randomized controlled trials (RCTs) that compared SJOV with conventional oxygen therapy in sedated patients were searched in five databases (MEDLINE, EMBASE, Cochrane Library, China National Knowledge Infrastructure [CNKI], and Google Scholar) from their inception to March 2024. The primary outcome was the proportion of patients who developed hypoxia (SpO2

Abstract Adequate nutrition in a hospital setting is essential for achieving optimal health outcomes in oncology patients. This study specifically investigated the interrelationships between nutritional status, daily habits, and hospital length of stay (LOS) in ovarian cancer patients undergoing chemotherapy. A prospective longitudinal study was conducted from August 2019 to January 2022 in a tertiary hospital. Throughout the study, nutritional status, biochemical indicators, diet, and physical activity were meticulously recorded at different stages of chemotherapy: before chemotherapy (T0), the first course (T1), third course (T2), and fifth course (T3). To determine the factors influencing LOS, a generalized estimation equation (GEE) was employed. A total of 460 patients completed the follow-up period. The findings revealed a decline in nutritional risk among patients by 9.90% at T1, 17.62% at T2 and 18.26% at T3 (χ 2 = 79.220, P

Abstract Follicular lymphoma (FL) is an immune-responsive tumor with spontaneous remission. T cells play a pivotal role in the anti-lymphoma immune response. However, the dynamics of T cells during treatment, their impact on FL clinical outcomes, and the risk factors contributing to T-cell cytopenia remain largely unexplored. T-cell and their subsets in the peripheral blood of FL patients at diagnosis, during 2–4 cycles and after 6 cycles of treatment, as well as healthy individuals were detected by flow-cytometry. The predictive effects of T cells for early progression and risks for T-cell cytopenia were analyzed. FL patients exhibited a significant decrease in CD3+, CD4+, and CD8 + T cells compared to healthy individuals, with aging intensifying the decline of CD3+, and CD4 + T cells. Notably, a reduction in CD4 + T cells, predominantly contributing to treatment-related T-cell reduction, was only observed in patients undergoing Bendamustine-based regimens. Moreover, a significantly decreased CD4 + and CD8 + T-cell at diagnosis rather than after induction therapy was observed in patients with treatment failure. Furthermore, lower CD4 + T-cell (

Abstract The aim of this study was to investigate the relationship between red blood cell distribution width and albumin ratio (RAR) levels and mortality in adult patients with sarcopenic obesity in the United States. The study included 1,361 adult patients with sarcopenic obesity from the National Health and Nutrition Examination Survey (1999–2006). The X-tile was used to determine the optimal subgroup thresholds for RAR values, and propensity score matching (PSM) was employed to reduce baseline bias. Cox regression analysis, Kaplan-Meier survival curves, and restricted cubic spline analysis were utilized to assess the relationship between RAR levels and all-cause and cardiovascular mortality. Subgroup analysis and the Subpopulation Treatment Effect Pattern Plot were employed to determine survival advantages across different subgroups. Time-dependent ROC analysis to evaluate the accuracy of RAR level in predicting survival outcomes at different time points. Post-PSM multifactorial Cox regression analyses revealed that RAR was a significant independent predictor of all-cause mortality (HR 1.487, 95% CI: 1.259–1.756) and an independent risk factor for cardiovascular mortality (HR 1.487, 95% CI: 1.260–1.758) in patients with sarcopenic obesity. The survival advantage was consistent across subgroups. Restricted cubic spline analysis indicated an approximate S-shaped association between RAR levels and mortality. Time-dependent ROC curves demonstrate that the areas under the all-cause mortality curves at the RAR level for 1-year, 3-year, 5-year, and 10-year are 0.79, 0.66, 0.64, and 0.63, respectively. The areas under the cardiovascular mortality curve are 0.80, 0.70, 0.66, and 0.61, respectively. Moreover, in comparison to the baseline model lacking covariates, the AUC values of the joint model exhibited heightened levels at various time points. Therefore, We demonstrated that the RAR level is an independent prognostic factor for mortality risk in the American population with sarcopenic obesity, and it is reasonable to consider the RAR level as a simple and effective risk prediction tool.

Abstract The accurate prenatal diagnosis of skeletal anomaly (SKA) using prenatal imaging alone remains challenging. We aimed to investigate the efficacy of whole-exome sequencing (WES) in the prenatal molecular genetic diagnosis of skeletal system abnormalities, with or without additional ultrasound anomalies. All fetuses with SKA were subjected to sequential genetic tests, and after excluding fetal chromosomal abnormalities and clinically significant copy number variations (CNVs) consistent with the observed phenotype, the affected fetuses were further subjected to WES. The clinical features of fetal SKA were collected, and the results of molecular genetic testing and perinatal outcomes were analyzed. Following negative routine genetic test results of the 78 fetuses, trio-WES was conducted for 73 fetuses, and fetus-only WES (single WES) was performed for five fetuses due to parental refusal. Fetal skeletal system abnormalities in our cohort were subdivided into seven groups: 39 (50%) had short long bones, 14 (17.9%) had abnormal limb morphology, 4 (5.1%) had polydactyly, 4 (5.1%) had the absence of the radius tibia or tibiofibula, 5 (6.4%) had spine anomalies, 6 (7.7%) had strephenopodia, and 6 (7.7%) had multiple deformities. In total, we identified the molecular diagnoses for 32/78 fetuses with SKAs, and confirmed 41 pathogenic/likely pathogenic variants in 28 genes, including nine novel variants in our cohort. The overall diagnostic rate was 41% (32/78). Our findings demonstrate that WES can greatly improve the genetic diagnostic rate of fetal SKAs following routine genetic testing, which can comprehensively guide perinatal management and help assess the risk of recurrence in future pregnancies. Our data also provide a basis for the association between the SKA phenotype and related genotypes and expand the spectrum of fetal SKA phenotypes and related genes.

Abstract The relationship between serum uric acid (SUA) and mortality in patients with cardiovascular disease (CVD) remains controversial. We aimed to explore the relationship between SUA and all-cause mortality (ACM) and cardiovascular mortality (CVM) in adult patients with CVD. This cohort study included 3977 patients with CVD from the National Health and Nutrition Examination Survey (2005–2018). Death outcomes were determined by linking National Death Index (NDI) records through December 31, 2019. We explored the association of SUA with mortality using weighted Cox proportional hazards regression models, subgroup analysis, Kaplan-Meier survival curves, weighted restricted cubic spline (RCS) models, and weighted threshold effect analysis among patients with CVD. During a median follow-up of 68 months (interquartile range, 34–110 months), 1,360 (34.2%) of the 3,977 patients with cardiovascular disease died, of which 536 (13.5%) died of cardiovascular deaths and 824 (20.7%) died of non-cardiovascular deaths. In a multivariable-adjusted model (Model 3), the risk of ACM (HR 1.38, 95% CI 1.16–1.64) and the risk of CVM (HR 1.39, 95% CI 1.04–1.86) for participants in the SUA Q4 group were significantly higher. In patients with CVD, RCS regression analysis revealed a nonlinear association (p

Abstract This study aimed to compare the serum lipid profiles between tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) in the long-term treatment of chronic hepatitis B (CHB). We analyzed data from treatment-naïve CHB patients administered with TDF or TAF, collected from electronic medical records between May 2017 and September 2022. Serum lipid indices, including total cholesterol (TC), triglycerides (TG), low-density (LDL) and high-density lipoprotein (HDL), and their ratios (TC/HDL, LDL/HDL), were assessed at baseline, and at 48 and 96 weeks. Propensity score matching (PSM) adjusted for baseline differences between groups. From 2344 patients initially screened, 418 were included for the 48-week analysis (265 on TDF, 153 on TAF) and 292 for the 96-week analysis (238 on TDF, 54 on TAF). At 48 weeks, comparing the serum lipid indicators between the pre- and post-treatment, TDF significantly reduced TC and TC/HDL, whereas TAF induced widespread dyslipidemia, characterized by elevated levels of TC, TG, LDL, LDL/HDL, and TC/HDL, and reduced HDL (P

Abstract Prostate cancer (PC) treatment, particularly androgen deprivation therapy (ADT), remains pivotal, albeit linked to increased fracture risk due to osteoporosis. The advent of novel hormonal agents (NHAs) has spurred inquiries into their influence on bone health. This study aimed to evaluate the impact of NHAs on bone health in patients receiving combination therapy. We conducted a retrospective analysis using Taiwan’s National Health Insurance Research Database, encompassing men aged 45 and above diagnosed with PC without bone metastasis and undergoing ADT between 2000 and 2018. The study involved 25,949 patients, categorized into those receiving standard ADT (n = 25,166) and those on NHA combination therapy (n = 783). Our analysis delved into fracture risk, comorbidities, and osteoporosis treatments. Patients on NHA combination therapy faced significantly higher risks of any osteoporotic fracture and major osteoporotic fracture than those on ADT alone (HR = 1.29, 95% CI 1.04–1.61; HR = 1.37, 95% CI 1.06–1.75, respectively). Notably, age emerged as a critical factor, with the highest risk observed in those aged 90 or above. The 5-year overall survival rates were lower for patients who experienced any osteoporotic fracture, major osteoporotic fracture, and hospitalization due to osteoporotic fracture compared to those who did not experience these fractures (51.5% vs. 56.5%, 47.1% vs. 56.7%, and 48.2% vs. 56.3%, respectively, p

Abstract Background Empathy is an important factor in the doctor-patient relationship, but mental illness is more difficult to understand than other diseases. Besides traditional skills, virtual reality (VR) has been identified as a promising tool in empathy education. This study aimed to investigate the ability of empathy enhancement, the feasibility of depression education, and the changes in thoughts and attitudes in medical students through a single VR experience. Methods We recruited medical students and randomly assigned them to two groups based on their completed Interpersonal Response Index scores. Two sets of VR systems were provided; the intervention group experienced the daily life of the depressed medical student, while the control group experienced the general medical student scenario. The improvement of empathy was assessed using the Jefferson Scale of Empathy-Health Professional Students (JSE-HPS), and the change of attitude was assessed through the Implicit Association Test. In addition, other questionnaires were used to evaluate the user experience of this VR system, and correlation analysis was conducted to examine the association between the use of VR and changes in the JSE and IAT scores. Results A total of 59 medical students were enrolled in this study. The intervention group showed a significant increase in the perspective-taking (pre: mean 5.817, SD 0.536; post: mean 5.947, SD 0.620; P = .03) and compassionate care (pre: mean 5.546, SD 0.581; post: mean 5.721, SD 0.629; P = .01) domains of the JSE score and a significant decrease in the standing in the patient’s shoes (SP) domain (pre: mean 3.583, SD 1.253; post: mean 2.967, SD 1.252; P = .002). The Pearson correlation analysis found a significant positive correlation between the JSE score with immersion aspect (r = .308, P = .049) and presence aspect (r = .415, P = .01), and we also found a significant negative correlation between the IAT score and presence aspect (r=-.333, P = .04). Conclusions This study is the first randomized case-control study to investigate the effect of two different versions of VR on empathy development toward depression for medical students. Although the single VR experience was unable to induce a great improvement in empathy or attitude, the VR system could help medical students enhance their understanding of depressive disorders. Trial registration This trial was retrospectively registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) (21/03/2024, ACTRN12624000297527). https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=386683&isReview=true .

Abstract Pulmonary fibrosis is a chronic interstitial lung disease with no curative therapeutic treatment, leading to significant mortality. The aims of this study were to investigate the regulatory mechanisms of mitophagy in the progression of pulmonary fibrosis. Through bioinformatics analysis, we identified the downregulation of long-chain fatty acyl-CoA synthetase 1 (ACSL1) as being associated with the severity of pulmonary fibrosis. A pulmonary fibrosis model was established through bleomycin (BLM) exposure both in vivo and in vitro. Mitoquinone (MitoQ) pretreatment significantly decreased redox damage, stabilized mitochondrial membrane potential (MMP), improved mitochondrial dynamics, and activated PINK1/Parkin-mediated mitophagy, thereby alleviating pulmonary fibrosis. In vitro, overexpression of ACSL1 mitigated mitochondrial damage and restored PINK1/Parkin-mediated mitophagy under BLM exposure. In contrast, ACSL1 inhibition exacerbated pulmonary fibrosis, and these adverse effects could not be reversed by MitoQ treatment. Taken together, our study reveals a novel mechanism underlying the pathogenesis of pulmonary fibrosis and suggests a potential therapeutic target for its treatment.

Abstract Septic cardiomyopathy (SCM), a complication initiated by sepsis, presents a significant clinical challenge, leading to increased mortality rates. However, the mechanisms of SCM have not been fully uncovered. Our study involved analyzing RNA sequencing (RNA-seq) data from rat heart tissue, along with utilizing molecular docking and molecular dynamics (MD) simulations, to discover key targets and potential pharmacological actions of the calcitonin gene-related peptide (CGRP) against SCM. A lipopolysaccharide-induced SCM model was established in rats (LPS 10 mg/kg, intraperitoneal (i.p.)). Thereafter, the myocardial tissues from the three groups of rats (Ctrl group, LPS group, and CGRP group) (n = 5) were extracted and underwent RNA-seq, followed by bioinformatics analyses. The qPCR-validated hub targets potentially interacting with CGRP were identified. Following this, homology modeling was utilized to obtain the 3D structure of hub targets, and molecular docking was conducted to evaluate the interaction between CGRP and hub targets. MD simulations (300 ns) were performed to confirm the findings further. Our findings demonstrated that CGRP significantly lowered mortality in SCM rats. 633 DEGs were affected by LPS, contrasted with the Ctrl group. 96 DEGs were affected by CGRP compared to the LPS group. In total, ten fully annotated CGRP-triggered hub genes were obtained. The molecular docking and MD simulations indicate that the relationship between CGRP and eight hub genes is extremely strong. This research offers a thorough examination of the possible objectives and fundamental molecular processes of CGRP in combating SCM, laying the groundwork for investigating the potential protective mechanisms of CGRP against SCM.

Fluconazole-resistant clade 4 Candida tropicalis causing candidemia in humans has been detected in tropical/subtropical areas, including those in China, Singapore, and Australia. We analyzed 704 individual yeasts isolated from fruits, soil, water, and farmers at 80 orchards in Taiwan. The most common pathogenic yeast species among 251 isolates recovered from farmers were Candida albicans (14.7%) and C. parapsilosis (11.6%). In contrast, C. tropicalis (13.0%), C. palmioleophila (6.6%), and Pichia kudriavzevii (6.0%) were prevalent among 453 environmental isolates. Approximately 18.6% (11/59) of C. tropicalis from the environment were resistant to fluconazole, and 81.8% (9/11) of those belonged to the clade 4 genotype. C. tropicalis susceptibility to fluconazole correlated with susceptibilities to the agricultural azole fungicides, difenoconazole, tebuconazole, and triadimenol. Tandem gene duplications of mutated ERG11 contributed to azole resistance. Agriculture environments are a reservoir for azole-resistant C. tropicalis; discontinuing agricultural use of azoles might reduce emergence of azole-resistant Candida spp. strains in humans.

Abstract Severe psoriasis has a long course and poor outcome, and it has long been a problem for patients. Understanding the independent risk factors that contribute to patients with severe psoriasis is critical for the development of effective treatment strategies. This large, multicenter study recruited 2,109 plaque psoriasis patients from 12 hospitals across China (October 31, 2019 – May 31, 2022). The logistic regression model underwent internal validation and external validation using two independent cohorts over future time periods (June 1, 2022 – January 31, 2023). The discriminative power of our model was substantiated by a C-index of 0.863 (95% CI: 0.848–0.879) in internal validation, further affirmed through 1,000 bootstrap validation (C-index: 0.860, 95% CI: 0.836–0.885) and external validation cohorts, where the C-index reached up to 0.910 (95% CI: 0.868–0.953) and 0.951 (95% CI: 0.924–0.977) in 2 external validation cohorts. To enhance accessibility for clinicians, the model has been made available as a dynamic nomogram and QR code. Our study identified 10 risk factors (the “DELPHI” consensus dichotomy, the DLQI index, the extent of skin involvement as measured by body surface area, the age of the patient at the time of clinical visit, sex, body weight in kilograms, career, the presence of scalp involvement, facial involvement, and arthropathy) for the overall severity of psoriasis (PASI ≥ 10). “Nomogram-10” provides clinicians with a practical tool to develop personalized intervention strategies based on an individual’s risk profile. Trial registration: Chinese Clinical Trial Registry: ChiCTR1900024852.

Abstract Recently, cellular senescence-induced unstable carotid plaques have gained increasing attention. In this study, we utilized bioinformatics and machine learning methods to investigate the correlation between cellular senescence and the pathological mechanisms of unstable carotid plaques. Our aim was to elucidate the causes of unstable carotid plaque progression and identify new therapeutic strategies. First, differential expression analysis was performed on the test set GSE43292 to identify differentially expressed genes (DEGs) between the unstable plaque group and the control group. These DEGs were intersected with cellular senescence-associated genes to obtain 40 cellular senescence-associated DEGs. Subsequently, key genes were then identified through weighted gene co-expression network analysis, random forest, Recursive Feature Elimination for Support Vector Machines algorithm and cytoHubba plugin. The intersection yielded 3 CSA-signature genes, which were validated in the external validation set GSE163154. Additionally, we assessed the relationship between these CSA-signature genes and the immune landscape of the unstable plaque group. This study suggests that cellular senescence may play an important role in the progression mechanism of unstable plaques and is closely related to the influence of the immune microenvironment. Our research lays the foundation for studying the progression mechanism of unstable carotid plaques and provides some reference for targeted therapy.

Abstract Dual cognitive-walking treadmill training (DTT), designed to replicate real-life walking conditions, has shown promise effect in individuals with Parkinson’s disease (PD). This study aims to compare the effects of DTT versus single treadmill training (STT) on cognitive and walking performance under both single and dual task conditions, as well as on fall, patients’ subjective feeling, and quality of life. Sixteen individuals with PD were randomly assigned to DTT or STT group and underwent 8 weeks of training. The DTT group received treadmill training with cognitive loads, while the STT group received treadmill training without cognitive load. Outcome measures included gait parameters (speed, step length) and cognitive performance (reaction time, accuracy, composite score) under both single and dual task conditions. Unified Parkinson’s Disease Rating Scale-part III (UPDRS-III), Falls Efficacy Scale (FES), Patient Global Impression of Change (PGIC), and Parkinson’s Disease Questionnaire (PDQ-39) were also measured. Both DTT and STT groups showed increased comfortable walking speed and step length. Only the DTT group demonstrated significant improvements in cognitive composite score under both single and dual task conditions, as well as UPDRS-III, FES, and PDQ-39(p

Abstract Acute respiratory infections (ARIs) are the most common issue in pediatric clinical practice. They pose a significant public threat, with high morbidity and mortality rates worldwide. Aiming at understanding the epidemiological characteristics of respiratory pathogens and their risk factors among children in eastern Guangdong, China. Samples obtained from 15,993 children hospitalized with ARIs in eastern Guangdong Province were tested for 14 pathogens via multiplex polymerase chain reaction (PCR) from May 2019 to July 2023. The number of hospitalizations for ARIs was correlated with pathogens, age, meteorological parameters, and the pandemic of COVID-19. The data were analyzed by different statistical methods. Among all the samples, the positive rate with ARIs accounted for 68.94% (11,026/15,993) in hospitalized patients. Cytomegalovirus (CMV) (24.49%), Streptococcus pneumoniae (SP) (20.54%), and Respiratory Syncytial Virus (RSV) (14.16%) were the top three pathogens with the greatest infection rates. Among hospitalized patients, there were more single infections in pediatric patients (40.91%, P

Abstract This study evaluates the clinical significance of nano-carbon suspension in total thyroidectomy with cervical lymph node dissection for papillary thyroid carcinoma (PTC). The objective of this study was to assess the efficacy of nano-carbon suspension in enhancing parathyroid gland preservation, reducing postoperative complications, and improving surgical precision. A retrospective analysis on 219 PTC patients who underwent total thyroidectomy with cervical lymph node dissection between March 2014 and March 2018 was conducted. Patients were divided into two groups: an experimental group (n = 107) that received nano-carbon suspension and a control group (n = 112) that did not. Comparative analyses included demographics, surgical parameters, postoperative calcium and parathyroid hormone (PTH) levels, the number of dissected lymph nodes, and the incidence of complications. Baseline characteristics, including age, sex, and BMI, showed no statistically significant differences between the experimental and control groups. Postoperative calcium levels were significantly more stable in the experimental group, with median levels of 2.22 mmol/L on day 1 versus 2.06 mmol/L in the control group (P

Abstract This cross-sectional survey aims to determine whether cotinine exposure would enhance the relationship between blood manganese (Mn) and non-alcoholic fatty liver disease (NAFLD) in children using the NHANES database. Restricted cubic spline (RCS) and logistic regression analyses were adopted to determine the potential relationship. Besides, we tested the robustness of the results by performing trend tests and subgroup analyses. The study finally enrolled 866 children aged 18 years and below. Blood Mn was linearly linked to NAFLD and the risk of NAFLD was increased with the blood Mn elevation (P

Abstract This research was intended to compare the clinical efficacy of hepatic arterial infusion chemotherapy (HAIC) in conjunction with lenvatinib and PD-1 inhibitors to first-line systemic chemotherapy for advanced intrahepatic cholangiocarcinoma(ICC). The research enrolled advanced ICC patients who underwent HAIC plus lenvatinib and PD-1 inhibitor(n = 51) or first-line systemic chemotherapy(cisplatin + gemcitabine, n = 39) between July 2020 to January 2023 in Zhongshan People’s Hospital.Their clinical outcomes were assessed through measurement of parameters encompassing objective response rate (ORR), disease control rate (DCR), median overall survival (mOS), median progression-free survival (mPFS), median duration of response (mDOR), and treatment-related adverse events (TRAEs). In accordance with the RECIST1.1, the ORR in the HAIC + L + P and SC groups was 43.1% and 20.5%, while the DCR was 90.2% and 69.2%, respectively (P = 0.04 and = 0.02, respectively). The change in the maximum diameter of intrahepatic target lesions in patients before and after treatment and the diameter of intrahepatic tumors in the HAIC + L + P group were sharply smaller versus the SC group ( P

Abstract This study assessed the clinical safety and efficacy of elliptical thin-flap LASIK with a low–pulse energy femtosecond laser in 3 thickness subgroups (85, 90, and 100 μm). A total of 80 patients who underwent bilateral LASIK surgery at Taiwan between April and September 2019 were retrospectively enrolled. Elliptical corneal flaps with wide temporal hinges and inverted-angled side cuts were created. Target flap thickness was calculated on the basis of residual stromal bed thickness and percent tissue altered. Before flap creation, an optical coherence tomography image for visualization of the precut flap position was obtained with the built-in camera. At postoperative month 1, the overall mean logMAR uncorrected distance visual acuity (UDVA) was − 0.04 ± 0.07 (20/18 Snellen), with 96% of eyes achieving UDVA of 20/20 or better. Postoperative mean manifest spherical equivalent was − 0.37 ± 0.42 D at 1 month. The visual and refractive outcomes in each of the 3 subgroups were similar. The achieved flap thicknesses were found to be highly predictable and consistent in the respective thickness subgroups. Optical coherence tomography–guided thin-flap LASIK performed with the low–pulse energy femtosecond laser was found to be safe with no intraoperative or postoperative complications.

Abstract BIVV003 is a gene-edited autologous cell therapy in clinical development for the potential treatment of sickle cell disease (SCD). Hematopoietic stem cells (HSC) are genetically modified with mRNA encoding zinc finger nucleases (ZFN) that target and disrupt a specific regulatory GATAA motif in the BCL11A erythroid enhancer to reactivate fetal hemoglobin (HbF). We characterized ZFN-edited HSC from healthy donors and donors with SCD. Results of preclinical studies show that ZFN-mediated editing is highly efficient, with enriched biallelic editing and high frequency of on-target indels, producing HSC capable of long-term multilineage engraftment in vivo, and express HbF in erythroid progeny. Interim results from the Phase 1/2 PRECIZN-1 study demonstrated that BIVV003 was well-tolerated in seven participants with SCD, of whom five of the six with more than 3 months of follow-up displayed increased total hemoglobin and HbF, and no severe vaso-occlusive crises. Our data suggest BIVV003 represents a compelling and novel cell therapy for the potential treatment of SCD.

Abstract The pathogenesis of doxorubicin-induced cardiomyopathy remains unclear. This study was carried out to test our hypothesis that ADAM17 aggravates cardiomyocyte apoptosis induced by doxorubicin and inhibition of ADAM17 may ameliorate doxorubicin-induced cardiomyopathy. C57BL/6J mice were intraperitoneally injected with a cumulative dose of doxorubicin to induce cardiomyopathy. Cardiomyocyte-specific ADAM17-knockout (A17α-MHCKO) and ADAM17-overexpressing (AAV9-oeA17) mice were generated. In addition, RNA sequencing of the heart tissues in different mouse groups and in vitro experiments in neonatal rat cardiomyocytes (NRCMs) receiving different treatment were performed. Mouse tumor models were constructed in A17fl/fl and A17α-MHCKO mice. In addition, cardiomyocyte-specific TRAF3-knockdown and TRAF3-overexpressing mice were generated. ADAM17 expression and activity were markedly upregulated in doxorubicin-treated mouse hearts and NRCMs. A17α-MHCKO mice showed less cardiomyocyte apoptosis induced by doxorubicin than A17fl/fl mice, and cardiomyocyte ADAM17 deficiency did not affect the anti-tumor effect of doxorubicin. In contrast, AAV9-oeA17 mice exhibited markedly aggravated cardiomyocyte apoptosis relative to AAV9-oeNC mice after doxorubicin treatment. Mechanistically, doxorubicin enhanced the expression of transcription factor C/EBPβ, leading to increased expression and activity of ADAM17 in cardiomyocyte, which enhanced TNF-α shedding and upregulated the expression of TRAF3. Increased TRAF3 promoted TAK1 autophosphorylation, resulting in activated MAPKs pathway and cardiomyocyte apoptosis. ADAM17 acted as a positive regulator of cardiomyocyte apoptosis and cardiac remodeling and dysfunction induced by doxorubicin by upregulating TRAF3/TAK1/MAPKs signaling. Thus, targeting ADAM17/TRAF3/TAK1/MAPKs signaling holds a promising potential for treating doxorubicin-induced cardiotoxicity.

Abstract Few studies have explored the association between residential noise exposure and burnout. In this study, we investigated the association between residential noise exposure and burnout prevalence among 5416 health-care workers in Taiwan from 2012 to 2017. Burnout was evaluated using the Mandarin version of the Copenhagen Burnout Inventory by considering both continuous and binary measures. We applied ordinary Kriging models to calculate the annual average residential noise exposure at an individual level. Multivariable linear regression models and logistic regression models were employed. Restricted cubic splines were used to explore dose–response relationships. The median age of the health-care workers was 31.5 years. In the multivariable linear regression models, exposure to residential noise (per 1 dBA) was associated with increases in personal burnout and work-related burnout scores by 1.59 ± 0.25 and 1.38 ± 0.20, respectively. In the multivariable logistic regression models, the adjusted odds ratios were 1.24 (95% confidence interval [CI]: 1.16, 1.32) for personal burnout and 1.19 (95% CI: 1.13, 1.26) for work-related burnout per 1-dBA increase in residential noise exposure. Linear dose–response associations of burnout with residential noise level were detected. Our findings suggest that exposure to residential noise may increase the risk of burnout among health-care workers.

Abstract Defoliation is a primary agronomic traits, its variation depends on different plant species or cultivars. The present article assess the leaf morphological responses, oxidative metabolites and enzymatic activities at sheath base of sugarcane cultivars during defoliation stage of plant leaves. The mature leaf sheath of GT47 strongly wrapped to the stem, and no stem was exposed. The upper and lower edges of the immature fusing abscission zone were parallel, and slightly lower browning area (+ 3 to + 7 leaf position). The ROC22 cultivar was monitored highest leaf sheath-based cellulose and lignin content, followed by GT60 and GT47. Peroxidase activity was higher in leaf sheath base edge (ROC22) as compare to other cultivars. The malondialdehyde content was found highest in GT60, followed by ROC22, and GT47. The exo-β-1,4-glucanase/ cellobiohydrolase activity was found highest in the margin of GT47 than lateral and medial axis of ROC22 and GT60. The axis activity increased exponentially, and ROC22 gradually decreased from the periphery of the mid-axis and lower than GT47 and GT60 in the lateral and mid-axis of leaf. In conclusion, the mature leaves are easy to defoliate mainly loose leaf sheaths, large leaf sheath inclination angles, more deformation during the growth period of the abscission zone, early with large cracks, and slow browning process. Leaf sheaths with high fibre and lignin content showed significant hardness and thickness. The sugarcane cultivars showed positive correlation between peroxidase and malondialdehyde content with the browning process at the base of mature leaf sheaths.

Abstract Background The aim of this study was to explore the relationships between teaching competence, career development, industrial orientation, and specialty construction in the case of intelligent medicine specialties in universities of traditional Chinese medicine, as well as the influencing factors of specialty construction. Methods Two-stage sampling with unequal probability was conducted to distribute self-administered questionnaires in the fieldwork. A structural equation model was built to investigate the influencing factors of specialty construction. Forty-two teachers were recruited and completed the questionnaire. Results The study found that teaching competence, career development, and industrial orientation positively affect specialty construction at a significant level. Career development and industrial orientation play chain mediating roles in the effect of teaching competence on specialty construction. Conclusions In the construction of intelligent medicine specialties, a professional curriculum system should be built that caters to industrial demand and is combined with industrial development, the traditional mode of teaching should be transformed, and the transformation of theoretical knowledge into practical ability should be promoted. Innovations in teaching modes should be achieved by introducing information technology, and the teacher evaluation system should be optimized.

Abstract Background Collaborative learning is an essential pedagogy in medical education, within which small group learning constitutes an integral component. Online small group teaching has been widely applied and blended with in-person sessions in the aftermath of the Covid-19 pandemic. This study examined whether group metacognition was associated with teamwork satisfaction in an online small group teaching curriculum for medical students. Methods We enrolled medical students of the 2nd and 4th years during the 2021 fall semester after they participated in 3 consecutive sessions of online small group tutorials (SGTs), which have been implemented in our medical school for more than 20 years. The students completed a group metacognitive scale (GMS) and a teamwork satisfaction scale (TSS) after the sessions. We analyzed whether group metacognition in 4 dimensions (knowledge of cognition, planning, evaluating, and monitoring) could be connected with medical students’ teamwork satisfaction using partial least squares-structural equation modeling (PLS-SEM). Results A total of 263 medical students participated in this study. Both GMS and TSS exhibited good reliability and validity. Three of the 4 dimensions of group metacognition (cognition, planning, and evaluating) positively correlated with teamwork satisfaction (path coefficients 0.311, 0.279, and 0.21; p = 0.002, 0.002, and 0.043, respectively) following the online SGT curriculum, whereas the monitoring dimension did not (path coefficient 0.087; p = 0.357). The model achieved an adjusted R square of 0.683. Conclusion We discovered that group metacognition correlated positively with better teamwork satisfaction, supporting the importance of group metacognitive competency for online collaborative learning.

Abstract Plasma epidermal growth factor receptor mutation (EGFRm) circulating tumor DNA (ctDNA) dynamics exhibit promise in predicting outcomes in patients with EGFRm-advanced non-small cell lung cancer (NSCLC). However, there remains limited trial-level data on integrating ctDNA monitoring into clinical practice. We performed a prospective, multicenter trial to investigate the relationship between EGFRm ctDNA dynamic changes and clinical outcomes in NSCLC patients with EGFRm. Ninety-eight treatment-naive EGFRm-advanced NSCLC patients were recruited and administered icotinib until disease progression. Plasma samples were collected at baseline and four weeks after icotinib administration. ctDNA was analyzed using a droplet-digital polymerase chain reaction. At baseline, 71.4% of patients had detectable EGFRm ctDNA. Among them, 45.9% of patients’ ctDNA became undetectable within four weeks of treatment. These patients demonstrated significantly longer progression-free survival (PFS) and overall survival (OS) than those with detectable ctDNA after treatment (P = 0.004 and

Abstract PCOS is one of the most common endocrine disorders among women of reproductive age. While the mechanism involved is not yet fully characterized. Our study aims to examine the pregnancy outcomes of embryo transfers in women with PCOS after pretreatment, and to explore the possible effect of high androgen levels on endometrial receptivity. Retrospective cohort study was conducted to analyze pregnancy outcomes among 2714 infertile women with tubal factor and 452 PCOS women. Endometrium samples were collected from 6 controls and 6 PCOS patients to detect the expression of endometrial receptivity marks. The implantation rate, clinical and ongoing pregnancy rates and live birth rate in women with PCOS followed fresh embryo transfers were obviously decreased even after the pretreatment. Similar pregnancy outcomes were found in frozen-thawed embryo transfer cycles between women with or without PCOS. Strikingly, serum total testosterone (TT) levels on trigger day were significantly higher in PCOS women. Women with high TT levels presented significantly lower clinical and ongoing pregnancy rates, and the expression of insulin-like growth factor binding protein 1 (IGFBP-1), and leukemia inhibitory factor (LIF) in the endometria decreased significantly as well. High doses of testosterone significantly down-regulated the expression of IGFBP-1 and LIF in Ishikawa cells. Although endocrine abnormalities had been improved before the controlled ovarian stimulation (COS) cycle started, higher serum TT levels were detected on the trigger day of the COS cycle in PCOS patients, which may contribute to the decreased fresh embryo implantation by impairing endometrial receptivity.