Alzheimer's disease (AD), a progressive dementia, is one of the most common neurodegenerative diseases. Clinical trial results of amyloid-β (Aβ) and tau regulators based on the pretext of straightforward amyloid and tau immunotherapy were disappointing. There are currently no effective strategies for slowing the progression of AD. Herein, we spotlight the dysregulation of lipid metabolism, particularly the elevation of ceramides (Cers), as a critical yet underexplored facet of AD pathogenesis. Our study delineates the role of Cers in promoting microglial pyroptosis, a form of programmed cell death distinct from apoptosis and necroptosis, characterized by cellular swelling, and membrane rupture mediated by the NLRP3 inflammasome pathway. Utilizing both in vivo experiments with amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mice and in vitro assays with BV-2 microglial cells, we investigate the activation of microglial pyroptosis by Cers and its inhibition by icariin (ICA), a flavonoid with known antioxidant and anti-inflammatory properties. Our findings reveal a significant increase in Cers levels and pyroptosis markers (NOD-like receptor family, pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain, caspase-1, gasdermin D (gasdermin D (GSDMD)), and interleukin-18 (IL-18)) in the brains of AD model mice, indicating a direct involvement of Cers in AD pathology through the induction of microglial pyroptosis. Conversely, ICA treatment effectively reduces these pyroptotic markers and Cer levels, thereby attenuating microglial pyroptosis and suggesting a novel therapeutic mechanism of action against AD. This study not only advances our understanding of the pathogenic role of Cers in AD but also introduces ICA as a promising candidate for AD therapy, capable of mitigating neuroinflammation and pyroptosis through the cyclooxygenase-2 (COX-2)-NLRP3 inflammasome-gasdermin D (GSDMD) axis. Our results pave the way for further exploration of Cer metabolism disorders in neurodegenerative diseases and highlight the therapeutic potential of targeting microglial pyroptosis in AD.

OBJECTIVE To explore the changes of serum Toll-like receptor(TLR)2,TLR4 and 25 hydroxyvitamin D[25(OH)D]in the general anesthesia orthopedic surgery patients with postoperative pulmonary infections and analyze the distribution and drug resistance of pathogens.METHODS A total of 59 general anesthesia orthopedic surgery patients with postoperative pulmonary infections who were treated in Tianjin Fifth Central Hospital from Jul.2019 to Jul.2024 were chosen as the infection group,meanwhile,65 patients who underwent the same surger-y but did not have postoperative pulmonary infection or other acute and chronic infections were chosen as the non-infection group.The etiological characteristics of the postoperative pulmonary infections and the drug re-sistance rates were analyzed.The clinical data and the levels of serum TLR2,TLR4 and 25(OH)D were observed and compared between the two groups of patients.The values of the above indicators in diagnosis of the postopera-tive pulmonary infections in the general anesthesia orthopedic surgery were analyzed.RESULTS Totally 63 strains of pathogens were isolated from the 59 general anesthesia orthopedic surgery patients with postoperative pulmona-ry infections,36(57.14％)of which were gram-negative bacteria.3 of 15 Pseudomonas aeruginosa strains were resistant to meropenem;4 of 12 Klebsiella pneumoniae strians were resistant to meropenem;all of the 11 Staph-ylococcus aureus strains were methicilin-resistant S.aureus.The proportions of patients with age,hypoproteine-mia and diabetes mellitus,the serum TLR2 and TLR4 levels were higher in the infection group than in the non-infection group(P＜0.05),while the 25(OH)D level of the infection group was lower than that of the no in-fection group(P＜0.05).The area under the curves(AUCs)of serum TLR2,TLR4,25(OH)D and the joint de-tection of the above indicators were respectively 0.817,0.801,0.787 and 0.917 in diagnosis of postoperative pul-monary infections in the general anesthesia orthopedic surgery patients,and the AUC of the joint detection of the indicators was greater than that of the single detection(P＜0.05).CONCLUSIONS The general anesthesia or-thopedic surgery patients with postoperative pulmonary infections show high expressions of serum TLR2 and TLR4 and the low expression of 25(OH)D.The joint detection of the above indexes has higher diagnostic value.The gram-negative bacteria are dominant among the pathogens causing the infections.The pathogens vary in the drug resistance.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

Objective:To analyze the correlation between mental health status and metabolic syndrome (MetS) in health checkup people.Methods:It was a cross-sectional study, 2 920 participants who received health checkup in the Health Examination Center of Peking University Third Hospital from January 2019 to December 2023 were selected using cluster sampling method. Their general information, physical examination, biochemical indicators, body composition, and self-evaluation scores on the Symptom Checklist-90 (SCL-90) were collected. According to the inclusion and exclusion criteria, a total of 2 813 study subjects were included, and divided into the MetS group and the non-MetS group based on whether they had MetS. The differences in general demographic information, body composition, blood biochemistry, and SCL-90 scores between the two groups were compared. Binary Logistic regression analysis was used to explore the correlation between mental health status and MetS.Results:Of the 2 813 subjects included, 1 576 were males (56.0%) and 1 237 were females (44.0%), with an average age of (41.7±11.0) years, the MetS group had 586 cases (20.8%) and the non-MetS group had 2 227 cases (79.2%). The MetS group had higher levels of age, body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, total cholesterol, triglycerides, low density lipoprotein cholesterol (LDL-C), fasting blood glucose, glycosylated hemoglobin (HbA 1c), free thyroxine(FT4), total triiodothyronine (TT3), free triiodothyronine (FT3), waist-to-hip ratio, visceral fat area, body fat percentage, uric acid/creatinine, homocysteine (Hcy), aspartate aminotransferases (AST), and alanine transaminase (ALT) levels, as well as higher scores for somatization, hostility, paranoia, and other factor compared to the non-MetS group (all P<0.05), while high density lipoprotein cholesterol (HDL-C) and estimated glomerular filtration rate (eGFR) levels were lower than those in the non-MetS group (all P<0.05). The proportion of male, and the positive rates of SCL-90, somatization, interpersonal sensitivity, hostility, paranoia and other factor in the MetS group were higher than those in the non-MetS group (all P<0.05). Multifactorial analysis showed that individuals with a positive SCL-90 assessment had a 1.34 times higher risk of MetS than those with a negative assessment ( OR=1.34, 95% CI: 1.06-1.68; P=0.014). Among them, individuals with positive somatization ( OR=2.02, 95% CI: 1.25-3.28; P=0.004) and hostility ( OR=1.61, 95% CI: 1.02-2.56; P=0.042) had increased risk of MetS. Conclusion:Poor mental health status increases the risk of MetS.

Environmental Microbiology, as a compulsory foundational course for the major of environmental and ecological engineering. Its knowledge system not only lays a profound theoretical foundation but also evinces a close-knit nexus to practical applications in environmental protection and ecological restoration. This course thus serves as an outstanding platform facilitating both teaching reforms and practical innovations of professional courses. With Environmental Microbiology as a paradigmatic illustration, this paper concentrates on addressing issues like archaic course contents and enervating teaching approaches, with the aspiration of augmenting students' professional acuities, practical dexterities, and innovation and entrepreneurial aptitudes. In light of the aforesaid aim, we initiated an all-encompassing probe into the teaching reform and practicable paradigms from the perspective of amalgamating professional education with innovation-steered stratagems. Across multiple fronts, comprehensive reformative undertakings were implemented, subsuming the optimization and reconfiguration of course contents, the exploration of sundry teaching methodologies, and the scientific erection of an evaluation system. Ultimately, a nascent teaching model dubbed "three-dimensional, six-loop and five-collaborative" was formed. This series of comprehensive and innovative reform measures has not only substantially augmented the profundity and extensiveness of professional knowledge, permeating into the core of disciplinary essence, but also remarkably bolstered students' practical operational capabilities and innovative thinking patterns, thereby catalyzing their transformation into well-rounded individuals with a competitive edge. By virtue of these efforts, a solid foundation has been firmly laid for the teaching reform of Environmental Microbiology and the cultivation of high-caliber environmental professionals in the contemporary era, heralding a new chapter in the development of environmental education.
Environmental Microbiology ; Teaching ; Education, Professional/methods* ; Curriculum

Alzheimer's disease(AD),a progressive dementia,is one of the most common neurodegenerative dis-eases.Clinical trial results of amyloid-β(Aβ)and tau regulators based on the pretext of straightforward amyloid and tau immunotherapy were disappointing.There are currently no effective strategies for slowing the progression of AD.Herein,we spotlight the dysregulation of lipid metabolism,particularly the elevation of ceramides(Cers),as a critical yet underexplored facet of AD pathogenesis.Our study delineates the role of Cers in promoting microglial pyroptosis,a form of programmed cell death distinct from apoptosis and necroptosis,characterized by cellular swelling,and membrane rupture mediated by the NLRP3 inflammasome pathway.Utilizing both in vivo experiments with amyloid precursor protein(APP)/presenilin 1(PS1)transgenic mice and in vitro assays with BV-2 microglial cells,we investigate the activation of microglial pyroptosis by Cers and its inhibition by icariin(ICA),a flavonoid with known antioxidant and anti-inflammatory properties.Our findings reveal a significant increase in Cers levels and pyroptosis markers(NOD-like receptor family,pyrin domain containing 3(NLRP3),apoptosis-associated speck-like protein containing a caspase recruitment domain,caspase-1,gasdermin D(GSDMD),and interleukin-18(IL-18))in the brains of AD model mice,indicating a direct involvement of Cers in AD pathology through the induction of microglial pyroptosis.Conversely,ICA treatment effec-tively reduces these pyroptotic markers and Cer levels,thereby attenuating microglial pyroptosis and suggesting a novel therapeutic mechanism of action against AD.This study not only advances our un-derstanding of the pathogenic role of Cers in AD but also introduces ICA as a promising candidate for AD therapy,capable of mitigating neuroinflammation and pyroptosis through the cyclooxygenase-2(COX-2)-NLRP3 inflammasome-gasdermin D(GSDMD)axis.Our results pave the way for further exploration of Cer metabolism disorders in neurodegenerative diseases and highlight the therapeutic potential of tar-geting microglial pyroptosis in AD.

Objective To explore the impact of gender factors in participant selection during bioequivalence studies,and to provide insights for improving the screening success rate in subsequent trials.Methods A retrospective study was con-ducted to summarize the screening information of healthy subjects in the bioequivalence study conducted in the Phase Ⅰ Clinical Trial Laboratory of the Affiliated Hospital of Xiangnan University from July 2021 to July 2023.The number of failed screening ca-ses in different stages of screening for each project was counted,and the influence of gender factors on subject screening was ana-lyzed.Results A total of 32 bioequivalence studies involving 2 794 subjects,including 1 816 males and 978 females,were in-cluded in the study.The proportion of males was higher in vital signs and BMI abnormalities,and the proportion of females was higher in ECG abnormalities and active withdrawal,and the pass rate was lower in males than in females(40.0％ vs.45.8％),and the existence of the two was statistically significant(P＜0.05).The results of PC A showed that the distribution of data in males was more dispersed,and the distribution of data in females was centralized,and the two could be clearly differentiated.Binary lo-gistic regression analysis showed significant differences between males and females in laboratory test screening failures and BMI(P＜0.05).Further analysis showed that the screening failure rates of blood biochemistry,urine routine,coagulation function and blood transfusion were higher in males than in females,but the screening failure rates of blood routine were lower than those of fe-males.Conclusions Gender is an important influencing factor in the screening process of bioequivalence studies.Including subjects with appropriate gender ratios can help improve enrollment speed and reduce clinical trial costs.

Objective:To construct an indicator system for a nursing science and technology innovation curriculum guided by innovation competence, in order to provide a reference for cultivating innovation ability in nursing students.Methods:The overall research period was from March to December 2024. A nursing innovation curriculum indicator framework was initially developed through literature analysis and brainstorming. From October to December 2024, 19 experts from nine hospitals or universities across five provinces and cities were selected via purposive sampling to participate in two rounds of Delphi consultation. Revisions were made based on expert feedback.Results:Both rounds of expert consultation achieved a 100% response rate. The authority coefficient of the experts was 0.92. The final indicator system included four curriculum elements: course content, course objectives, teaching methods, and assessment, encompassing 14 first-level indicators and 40 second-level indicators.Conclusions:The innovation-oriented indicator system for nursing science and technology education demonstrates good scientific validity and reliability. It offers a foundational framework for advancing innovation-focused nursing education and curriculum design.