Purpose: This study aimed to develop and implement an antimicrobial stewardship education program for physician assistant nurses and to evaluate its effects on their knowledge and clinical performance. Methods: A quasi-experimental, single-group pre-post design was conducted with 50 physician assistant nurses at a university hospital in Seoul, Republic of Korea. The antimicrobial stewardship education program, developed using the ADDIE model, consisted of 12 sessions including lectures and case-based learning (CBL)-based discussions.Knowledge was measured before and immediately after the intervention, while performance was assessed pre-intervention and four weeks post-program. Data were analyzed using paired t-tests, Wilcoxon signed-rank tests, and analysis of covariance (ANCOVA). Results: Knowledge scores significantly improved from 44.65±7.45 to 58.50±10.11 (p<.001), and all subdomains showed significant increases (p<.001). Performance scores increased from 3.68±0.77 to 4.28±0.68 (p<.001). Knowledge gain did not differ significantly between the medical and surgical departments (p=.710). Likewise, after adjusting for pre-test scores, no significant difference in performance improvement was observed between the two departments (ANCOVA, p=.170). These results indicate that the program was effective across both departments regardless of their characteristics. Conclusion The antimicrobial stewardship education program improved both knowledge and performance among physician assistant nurses. This program may contribute to the standardization of antimicrobial stewardship education and to appropriate antimicrobial use and the reduction of antimicrobial resistance.

Objective To understand mosquito density, species composition, and seasonal variations around the Beijing Capital International Airport(BCIA)and provide scientific evidence for mosquito-borne disease prevention and control. Methods Meteorological data were collected from 2016 to 2022, and mosquito density was monitored at seven surveillance sites around the BCIA from May to October each year using CO2-baited mosquito traps to analyze the relationship between mosquito density and meteorological factors. Results In total,68 518 female mosquitoes were captured, with a mosquito density of 10.20 per light · hour. The dominant species was Culex pipiens pallens(73.90%), followed by Aedes albopictus(9.71%)and Ae. vexans(9.29%);the mosquito density was highest in 2016(14.8 per light·hour)and lowest in 2022(4.46 per light·hour). Significant statistical differences were observed in mosquito density among different species(F=18.118, P<0.05). The density of Cx. pipiens pallens and other mosquito species showed a mutually exclusive trend; the peak of mosquito density varied based on years and habitats, with significant statistical differences in mosquito density among different habitats(F=8.504, P<0.05). The highest mosquito density was observed near the Wenyu River(21.50 per light·hour), whereas the lowest was recorded at the BCIA construction site(2.44 per light· hour). The monthly average temperature(r=0.595), monthly average highest temperature(r=0.575), and monthly average lowest temperature(r=0.624)showed moderate positive correlations, whereas the monthly average air pressure(r=-0.484)showed a moderate negative correlation. The monthly average minimum temperature was included in the regression model(F=25.575, P<0.000), and the equation Y=1.029X4-8.181 was used. The monthly average air pressure 2 months prior(b=-2.418, β=-1.619, P<0.05)and the monthly average relative humidity(b=-0.739, β=-1.201, P<0.05)significantly negatively predicted the mosquito density. Notably, the regression equation used was y=2526.170+(-2.418)X9+(-0.739)X13. The exposure-response analysis revealed that the density of mosquitoes was not linearly related to the average monthly air pressure, rainfall, and duration of sunshine. Conclusions The dominant mosquito species around the BCIA was Cx. pipiens pallens, Ae. albopictus, and Ae. vexans. During the control of Cx. pipiens pallens, the impact on other mosquito species must also be considered. Environmental management, breeding sites, and scientific use of pesticides should be prioritized based on the activity periods of mosquitoes. Further studies on mosquitoes and meteorological factors should be conducted to provide references and novel avenues for mosquito control.

The sensitive scalp is a complex syndrome characterised by abnormal nerve sensations, such as stinging, itching, burning, and tightness, and diminished tolerance to physical or chemical stimuli that would not typically cause such unpleasant responses, with its pathology involving physical barrier destruction at the stratum corneum level, neural hyperreactivity and sensory nerve sensitization, and local immunological dysregulation and chronic low‑grade inflammation. The homeostasis of the scalp microenvironment plays a crucial regulatory role in maintaining the hair follicle growth cycle, yet this “soil” factor has long been underappreciated in hair loss research, which has traditionally centered on intrinsic follicular defects, such as genetic predisposition or androgen-driven mechanisms. In this review, we summarized the potential mechanisms underlying the imbalance in the “barrier-neural-immune” network in sensitive scalps. Sensitive scalp is further manifested as impaired skin barrier, including increased transepidermal water loss and abnormal lipid secretion. These alterations are accompanied by increased surface pH, excessive secretion of sebum rich in free fatty acids, reduced microbial diversity, and dysbiosis characterized by a reduction in Cutibacterium and an increase in Staphylococcus colonization. Mechanistically, we also analyzed how neurogenic inflammation, mediated by substances such as substance P (SP) and calcitonin gene-related peptide (CGRP), along with persistent low-grade inflammation, disrupts the microenvironment of the hair follicle stem cell niche through mechanisms involving mechanosensitive ion channels (e.g., Piezo1), oxidative stress, and cytokine cascades. When the barrier is compromised, the weakened stratum corneum may facilitate the penetration of external stimuli, sensitizing cutaneous nerve endings. Those hyperresponsive nerves then fire off neuropeptides like substance P and CGRP. These peptides activate mast cells and other immune cells via the MrgprB2 receptor, prompting degranulation and a wave of pro-inflammatory mediators that kick off neurogenic inflammation. At the same time, oxidative stress and inflammatory cytokines drive a persistent low-grade inflammation that directly damages the hair follicle stem cell niche. Physical compression from shrinking hair shafts activates Piezo1 channels, setting off calcium influx and Caspase‑3‑dependent apoptotic signaling. We primarily considered the interactions between inflammatory signaling and the sensitization of the androgen receptor (AR) pathway, as well as the inhibition of the Wnt/β‑catenin pathway, which may subsequently contribute to hair follicle miniaturization and disruption of the growth cycle. The inflammatory microenvironment appears to boost AR expression in dermal papilla cells, making them more sensitive to dihydrotestosterone (DHT). This heightened sensitivity may promote the expression of transforming growth factor-β1 (TGF-β1), TGF-β2, and Dickkopf-1 (DKK1), which suppress the Wnt/β‑catenin pathway—essential for follicle growth and regeneration—potentially accelerating follicular miniaturization and stalling the growth cycle. Coupled with direct inflammatory apoptosis, oxidative stress, and circadian disruption, these routes may collectively speed up hair follicle stem cell depletion and diffuse hair thinning. These findings point to the need for more mechanistic and translational research to test the proposed pathways and explore therapies that target the microenvironment in sensitive scalp-related hair loss. Ultimately, we hope to provide theoretical support for the intervention of hair loss by restoring the steady state of the scalp microenvironment and combining with new precision delivery technologies such as microneedles.

ObjectiveObesity has been identified as one of the most important risk factors for cognitive dysfunction. Physical exercise can ameliorate learning and memory deficits by reversing synaptic plasticity in the hippocampus and cortex in diseases such as Alzheimer’s disease. In this study, we aimed to determine whether 8 weeks of treadmill exercise could alleviate hippocampus-dependent memory impairment in high-fat diet-induced obese mice and investigate the potential mechanisms involved. MethodsA total of sixty 6-week-old male C57BL/6 mice, weighing between 20-30 g, were randomly assigned to 3 distinct groups, each consisting of 20 mice. The groups were designated as follows: control (CON), high-fat diet (HFD), and high-fat diet with exercise (HFD-Ex). Prior to the initiation of the treadmill exercise protocol, the HFD and HFD-Ex groups were fed a high-fat diet (60% fat by kcal) for 20 weeks. The mice in the HFD-Ex group underwent treadmill exercise at a speed of 8 m/min for the first 10 min, followed by 12 m/min for the subsequent 50 min, totally 60 min of exercise at a 0° slope, 5 d per week, for 8 weeks. We employed Y-maze and novel object recognition tests to assess hippocampus-dependent memory and utilized immunofluorescence, Western blot, Golgi staining, and ELISA to analyze axon length, dendritic complexity, number of spines, the expression of c-fos, doublecortin (DCX), postsynaptic density-95 (PSD95), synaptophysin (Syn), interleukin-1β (IL-1β), and the number of major histocompatibility complex II (MHC-II) positive cells. ResultsMice with HFD-induced obesity exhibit hippocampus-dependent memory impairment, and treadmill exercise can prevent memory decline in these mice. The expression of DCX was significantly decreased in the HFD-induced obese mice compared to the control group (P<0.001). Treadmill exercise increased the expression of c-fos (P<0.001) and DCX (P=0.001) in the hippocampus of the HFD-induced obese mice. The axon length (P<0.001), dendritic complexity (P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P<0.001) in the hippocampus were significantly decreased in the HFD-induced obese mice compared to the control group. Treadmill exercise increased the axon length (P=0.002), dendritic complexity(P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P=0.001) of the hippocampus in the HFD-induced obese mice. Our study found a significant increase in MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of HFD-induced obese mice compared to the control group. Treadmill exercise was found to reduce the number of MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of obese mice induced by a HFD. ConclusionTreadmill exercise led to enhanced neurogenesis and neuroplasticity by increasing the axon length, dendritic complexity, dendritic spine numbers, and the expression of PSD95 and DCX, decreasing the number of MHC-II positive cells and neuroinflammation in HFD-induced obese mice. Therefore, we speculate that exercise may serve as a non-pharmacologic method that protects against HFD-induced hippocampus-dependent memory dysfunction by enhancing neuroplasticity and neurogenesis in the hippocampus of obese mice.

Aim To investigate the changes in hepatic lactylation during liver regeneration and its impact on regeneration.Methods A partial hepatectomy(PHx)mouse model was used to study liver regenera-tion.Sodium oxamate was administered intraperitoneal-ly to inhibit lactate dehydrogenase,and blood and liver tissues were collected at different time points post-sur-gery.The histopathological status was observed using HE staining.Proliferating cell nuclear antigen(PC-NA)levels were detected by immunohistochemistry.Lactylation was assessed using immunofluorescence.Liver LDH enzyme activity,lactate levels and serum alanine aminotransferase(ALT)and aspartate trans-aminase(AST)levels were measured using assay kits.Results After PHx,the liver volume of mice gradual-ly increased,returning to preoperative size on day 7.PCNA levels peaked at 48 hours post-surgery.Liver tissue lactate levels increased to approximately 1.5 times the preoperative level at 12 hours post-surgery and remained elevated until day 7.The lactylation lev-el in hepatocytes peaked at 24 hours post-surgery,gradually declined after 48 hours,and returned to pre-operative levels on day 7.Compared to the PHx group,the sodium oxamate(750 mg·kg-1)+PHx group showed significantly reduced lactylation levels in hepa-tocytes and a smaller liver regeneration volume on day 7.Conclusion Lactylation regulates hepatocyte pro-liferation and promotes liver regeneration after PHx.

Aim To investigate the changes in hepatic lactylation during liver regeneration and its impact on regeneration.Methods A partial hepatectomy(PHx)mouse model was used to study liver regenera-tion.Sodium oxamate was administered intraperitoneal-ly to inhibit lactate dehydrogenase,and blood and liver tissues were collected at different time points post-sur-gery.The histopathological status was observed using HE staining.Proliferating cell nuclear antigen(PC-NA)levels were detected by immunohistochemistry.Lactylation was assessed using immunofluorescence.Liver LDH enzyme activity,lactate levels and serum alanine aminotransferase(ALT)and aspartate trans-aminase(AST)levels were measured using assay kits.Results After PHx,the liver volume of mice gradual-ly increased,returning to preoperative size on day 7.PCNA levels peaked at 48 hours post-surgery.Liver tissue lactate levels increased to approximately 1.5 times the preoperative level at 12 hours post-surgery and remained elevated until day 7.The lactylation lev-el in hepatocytes peaked at 24 hours post-surgery,gradually declined after 48 hours,and returned to pre-operative levels on day 7.Compared to the PHx group,the sodium oxamate(750 mg·kg-1)+PHx group showed significantly reduced lactylation levels in hepa-tocytes and a smaller liver regeneration volume on day 7.Conclusion Lactylation regulates hepatocyte pro-liferation and promotes liver regeneration after PHx.

Objective:To explore the risk factors of delayed extubation after expanded thymectomy in patients with myasthenia gravis.Methods:Patients with myasthenia gravis who underwent expanded thymectomy from May 2021 to January 2024 and were admitted to Intensive Care Unit (ICU) after surgery were retrospectively analyzed. Patients were divided in to the delayed extubation and successful extubation according to the length of mechanical ventilation whether exceeding than 48 hours. Multivariable logistics regression was used to explore the risk factors for delayed extubation after expanded thymectomy in patients with myasthenia gravis.Results:A total of 95 patients were included.15 (15.8%) of whom were delayed extubation. Compared with the successful extubation patients, the length of mechanical ventilation (94.0 h vs. 15.5 h, P<0.001), ICU station (7.1 days vs. 1.7 days, P<0.001), and hospitalization station (16.0 days vs. 9.1 days, P<0.001) were significantly prolonged in the delayed extubation patients. Adjusted for age,gender, BMI, clinical classification, pathological classification of thymoma, dose of pyridostigmine preoperative, perioperative pneumonia, preoperative pulmonary dysfunction, SBT passing for the first time, neck lift time greater than 20 seconds, the multivariable logistic regression shown, the risk of delayed extubation increased by 29% ( OR=1.290, 95% CI 1.090-1.714), 1% ( OR=1.009, 95% CI 1.002-1.034), 3.9-fold ( OR=4.977, 95% CI 1.486-10.939), and 64% ( OR=1.635, 95% CI 1.396-2.682) for every 60 mg/day increase in preoperative dose of pyridostigmine, pathological classification of thymoma, perioperative pneumonia, and preoperative pulmonary dysfunction, respectively. Neck lift time greater than 20 seconds can reduce the risk of delayed extubation 48% ( OR=0.524, 95% CI 0.322-0.794). Conclusion:Preoperative administration of a large dose of pyridostigmine, pulmonary dysfunction, pathological classification of thymoma, and perioperative pneumonia were risk factors for delayed extubation after thymectomy in these patients. And neck lift time greater than 20 seconds decreased the risk of delayed extubation. In the clinical practice,for high risk of MG patients with delayed extubation, the neck lifting test may be used to assess muscle strength and reduce the occurance of tracheal reintubation and its advise effects.

OBJECTIVE: This study aimed to investigate possible serum 25-hydroxyvitamin D [25(OH)D] cutoffs for the associations between 25(OH)D and Bone turnover markers (BTMs), and how GC gene variation influences such cutoffs in Chinese women of childbearing age. METHODS: In total, 1,505 non-pregnant or non-lactating women (18-45 years) were recruited from the 2015 Chinese Adult Chronic Disease and Nutrition Surveillance. Serum 25(OH)D, osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP), β-CrossLaps of type 1 collagen containing cross-linked C-telopeptide (β-CTX), and single nucleotide polymorphisms were determined. Locally weighted regression and smoothing scatterplot and segmented regression were performed to estimate the 25(OH)D thresholds. RESULTS: The median serum 25(OH)D was 16.63 (11.96-22.55) ng/mL and the prevalence of low serum 25(OH)D (< 12 ng/mL) was 25.2%. Women with the lowest 25(OH)D had the highest β-CTX. After adjustment for the confounders, 25(OH)D cutoffs for OC [14.04 (12.84-15.23) ng/mL], β-CTX [13.94 (12.49-15.39) ng/mL], and P1NP [13.87 (12.37-15.37) ng/mL] in the whole population, cutoffs for OC [12.30 (10.68-13.91) ng/mL], β-CTX [12.23 (10.22-14.23) ng/mL], and P1NP [11.85 (10.40-13.31) ng/mL] in women with the GC rs2282679 G allele, and cutoffs for OC [12.75 (11.81-13.68) ng/mL], β-CTX [13.05 (11.78-14.32) ng/mL], and P1NP [12.81 (11.57-14.06) ng/mL] in women with the GC rs2282679 T allele, were observed. Below these cutoffs, BTMs were negatively associated with 25(OH)D, while above these cutoffs, BTMs plateaued. CONCLUSION In Chinese women of childbearing age, there were thresholds effect of serum 25(OH)D concentrations on BTMs. The results indicated that serum 25(OH)D concentrations < 13.87 ng/mL in this population had adverse influences on maintaining bone remodeling. BTMs were suppressed at a relatively lower serum 25(OH)D in women with the GC rs2282679 G allele compared with those with the T allele.
Humans ; Female ; Vitamin D/blood* ; Adult ; Middle Aged ; Polymorphism, Single Nucleotide ; Adolescent ; Young Adult ; China ; Biomarkers/blood* ; Bone Remodeling/genetics* ; Vitamin D-Binding Protein/genetics* ; Procollagen/blood* ; Osteocalcin/blood* ; Peptide Fragments/blood* ; East Asian People

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Objective:To explore the risk factors of delayed extubation after expanded thymectomy in patients with myasthenia gravis.Methods:Patients with myasthenia gravis who underwent expanded thymectomy from May 2021 to January 2024 and were admitted to Intensive Care Unit (ICU) after surgery were retrospectively analyzed. Patients were divided in to the delayed extubation and successful extubation according to the length of mechanical ventilation whether exceeding than 48 hours. Multivariable logistics regression was used to explore the risk factors for delayed extubation after expanded thymectomy in patients with myasthenia gravis.Results:A total of 95 patients were included.15 (15.8%) of whom were delayed extubation. Compared with the successful extubation patients, the length of mechanical ventilation (94.0 h vs. 15.5 h, P<0.001), ICU station (7.1 days vs. 1.7 days, P<0.001), and hospitalization station (16.0 days vs. 9.1 days, P<0.001) were significantly prolonged in the delayed extubation patients. Adjusted for age,gender, BMI, clinical classification, pathological classification of thymoma, dose of pyridostigmine preoperative, perioperative pneumonia, preoperative pulmonary dysfunction, SBT passing for the first time, neck lift time greater than 20 seconds, the multivariable logistic regression shown, the risk of delayed extubation increased by 29% ( OR=1.290, 95% CI 1.090-1.714), 1% ( OR=1.009, 95% CI 1.002-1.034), 3.9-fold ( OR=4.977, 95% CI 1.486-10.939), and 64% ( OR=1.635, 95% CI 1.396-2.682) for every 60 mg/day increase in preoperative dose of pyridostigmine, pathological classification of thymoma, perioperative pneumonia, and preoperative pulmonary dysfunction, respectively. Neck lift time greater than 20 seconds can reduce the risk of delayed extubation 48% ( OR=0.524, 95% CI 0.322-0.794). Conclusion:Preoperative administration of a large dose of pyridostigmine, pulmonary dysfunction, pathological classification of thymoma, and perioperative pneumonia were risk factors for delayed extubation after thymectomy in these patients. And neck lift time greater than 20 seconds decreased the risk of delayed extubation. In the clinical practice,for high risk of MG patients with delayed extubation, the neck lifting test may be used to assess muscle strength and reduce the occurance of tracheal reintubation and its advise effects.