ObjectiveTo analyze the pharmacodynamic substance basis of Shangkeling Spray and its potential mechanisms in intervening knee osteoarthritis （KOA） using ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS）， network pharmacology， and molecular docking technology. MethodsUPLC-MS was used to identify the chemical components of Shangkeling Spray. Pharmacokinetic properties were employed to screen potential active ingredients. Network pharmacology methods were utilized to collect potential targets of these ingredients and the pathological gene set of KOA. An "active ingredient-disease" target network was constructed using databases such as STRING. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） functional enrichment analyses were performed using clusterProfiler. Libraries including NumPy were employed to calculate shortest path lengths to identify dominant pharmacodynamic links. Core gene clusters were identified using MCODE， validated through the Gene Expression Omnibus （GEO） database， and molecular docking was performed between key active ingredients and core targets. ResultsA total of 322 and 314 chemical components were identified under positive and negative ion modes， respectively， with 410 components in total after de-duplication， mainly including flavonoids， coumarins， terpenoids， organic acids， and alkaloids. Analysis of the "active ingredient-disease" network identified "development and regeneration"， "cell growth and death"， "immune system"， and "nervous system" as the dominant pharmacodynamic links of Shangkeling Spray in the treatment of KOA. Molecular docking showed that key active ingredients， such as bletillin A， formononetin， morin， oxymatrine， aconitine， gallic acid， curdione， apigenin， naringenin， and oleanolic acid， tightly bound to functional domains of 10 key targets including Jun proteins（JUN）， interleukin-6 （IL-6）， protein kinase B1 （Akt1）， Caspase-3， nuclear transcription factor-κB subunit p65（RELA）， nuclear factor-kappaB1（NF-κB1）， Cyclin D₁， mammalian target of rapamycin（mTOR）， tumor necrosis factor （TNF）， and Fos proto-oncogene protein （FOS）. These interactions synergistically regulated the phosphatidylinositol 3-kinase （PI3K）/Akt/mTOR-related signaling axis and nervous system-related pathways， mediating cartilage repair， reducing inflammation and pain， and improving KOA. ConclusionThis study preliminarily clarifies the pharmacodynamic substance basis of Shangkeling Spray and suggests that its main active ingredients may improve KOA by synergistically regulating the PI3K/Akt/mTOR-related pathways， providing a reference for subsequent exploration of its substance benchmark and mechanism of action.

Methods: Cervical radiographs were analyzed. EOP hyperplasia was classified into three subtypes with standardized length measurements. Variables encompassed demographics, ONL-related indices, and sagittal parameters. Subtype comparisons and multivariate regression analyses (with EOP length as dependent variable) were conducted. Results: Analysis of 187 CSM patients (64.2% male) identified gender-specific patterns: males exhibited greater EOP length (9.4±6.8 mm vs. 4.6±3.4 mm, p<0.001). Type III EOP demonstrated male predominance (82.4% vs. type I 31.8%, type II 51.4%; p<0.001), with associated longer hyperplasia length (11.6±6.6 mm vs. type II 5.1±1.9 mm, p<0.001). Type III EOP was associated with higher ONL prevalence (type III 64.8% vs. type I 45.5%, type II 41.9%; p=0.010) and longer ONL osteophyte length (type III 18.8±9.8 mm vs. type I 14.2±8.1 mm, type II 14.2±9.4 mm; p=0.046). Multivariate regression confirmed male sex (β=–3.82, p=0.009), ONL osteophyte length (β=0.16, p=0.017), T1 slope (β=0.27, p=0.041), and spino-cranial angle (β=–0.19, p=0.009) as factors independently associated with EOP length (adjusted R²=0.382). Conclusions Severe EOP hyperplasia exhibits a male-predominant distribution pattern and demonstrates significant radiological associations with ONL and cervical sagittal imbalance in CSM patients. These findings advocate for EOP evaluation in clinical evaluations to identify high-risk biomechanical profiles.

Although global brain science research has progressed rapidly in recent decades, several fundamental questions in neuroscience remain unresolved. In particular, the physical mechanism underlying neural signal transmission remains controversial, and the carriers responsible for neural information storage and retrieval have not yet been fully clarified. These unresolved issues motivate us to re-examine the processes of neural information generation, transmission, integration, storage, and retrieval from multiple perspectives. A key observation is that neural electromagnetic activities are closely associated with time. Their duration, temporal structure, and dynamic evolution play crucial roles in neural information processing. In this work, we analyze neural electromagnetic activities from the perspective of temporal scales (referred to here as the “time course”). By reviewing and integrating findings from previous studies, we examine the characteristic time requirements and dynamic features of neural processes occurring at different stages of information processing. These stages include neural signal generation, signal transmission along axons, synaptic integration, synaptic plasticity, and memory formation and retrieval. Based on this temporal analysis, we outline a framework describing neural electromagnetic activities across a wide range of time scales, spanning from microseconds to minutes, hours, or even longer periods associated with long-term memory, which suggests that neural information processing involves multiple physical processes operating at different time levels. Rapid electromagnetic events may occur on microsecond scales, whereas electrophysiological phenomena such as action potentials typically last on the order of milliseconds. Longer time scales are associated with synaptic plasticity and memory-related processes. From this perspective, we propose that the physical carrier of neural information may be transient electromagnetic pulses with durations on the microsecond scale. In this framework, action potentials can be interpreted as the macroscopic electrophysiological manifestation of underlying electromagnetic processes triggered by ionic currents across neuronal membranes. Rather than being the fundamental neural signal itself, the action potential may represent a measurable membrane-level response associated with the successful activation of these electromagnetic events. Moreover, we discuss a possible mechanism for long-term memory storage. Considering the apparent temporal contradiction between the millisecond-scale excitation of neurons and the long-term persistence of memories, we believe that long-term memory information may be stored within neural network topologies formed by electrical synapse coupling. Such structures, referred to as electrically coupled memory networks (ECMNs), may enable neurons within the same network to respond rapidly and synchronously to stimuli, thereby facilitating efficient memory retrieval. Overall, this study emphasizes the importance of considering the temporal organization of neural electromagnetic activities when interpreting neural signaling mechanisms. It may provide new insights into the physical nature of neural information carriers and the mechanisms of memory storage and retrieval. Furthermore, highlighting the potential role of electromagnetic interactions in neural activity may contribute to the development of new theoretical frameworks and experimental approaches in neuroscience. Such perspectives may also offer valuable references for future research on neural coding, brain function mechanisms, and neuromodulation technologies.

Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

Xanthine oxidase (XO) is an important therapeutic target for the treatment of hyperuricemia and gout. Based on the previously identified potent XO inhibitor 1, seventeen oxadiazoles and their ring-opening analogues were designed and synthesized via the bioisostere replacement strategy. Among them, compounds 2l, 2n, and 3b showed obvious XO inhibitory activity at the concentration of 10 μmol·L^-1, and compound 3b exhibited an IC₅₀ value of 1.45 μmol·L^-1.

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

OBJECTIVES: The detection rate of scoliosis among school-aged children has been rising annually, varying by region, and has become a major public health concern affecting both physical and mental health. Its onset is multifactorial, and early screening combined with targeted interventions can alter disease progression. This study aims to investigate the prevalence and influencing factors of scoliosis among primary and secondary school students in Hunan Province, providing scientific evidence for targeted prevention strategies. METHODS: A stratified, randomized cluster sampling method was used to select 281 401 students from 14 prefecture-level cities in Hunan Province for scoliosis screening, physical examination, and questionnaire survey. The chi-square test was used for group comparisons, and trend chi-square test analyzed differences in screening positive rate by age. A multilevel regression model was applied to identify influencing factors, and ArcGIS was used to visualize spatial distribution patterns of scoliosis. RESULTS: The overall screening positive rate for scoliosis among Hunan students was 1.61%. Urban areas had a significantly higher rate than rural counties (2.81% vs 0.98%; P<0.01). The rate was equal between boys and girls (1.61% each). Underweight students had a higher rate than those with normal weight, overweight, or obesity (P<0.01). Stratified by age, urban students aged 6-18 years consistently showed higher positive rates than rural peers (P<0.001). No significant gender differences were observed at most ages (all P>0.05), except at age 11, where the females had a higher rate (1.28% vs 1.02%; P=0.048). After age 11, underweight students exhibited significantly higher positive rates than those with normal or higher BMI(all P<0.05). Across all groups, urban/rural, male/female, underweight/normal/overweight/obese, the scoliosis rate increased with age. By region, the screening positive rate ranged from 0.38% to 3.36%, with the top three being Chenzhou (3.36%), Xiangtan (2.78%), and Hengyang (2.71%), while the lowest was Xiangxi Tujia and Miao Autonomous Prefecture (0.38%). Multilevel regression analysis revealed that age (OR=1.160, 95% CI 1.135 to 1.186) and urban residence (OR=2.497, 95% CI 1.946 to 3.205) were positively associated with scoliosis risk (both P<0.01). Conversely, female gender (OR=0.931, 95% CI 0.874 to 0.993), normal nutritional status (OR=0.751, 95% CI 0.671 to 0.840), overweight (OR=0.513, 95% CI 0.447 to 0.590), obesity (OR=0.418, 95% CI 0.358 to 0.489), and engaging in ≥ 60 minutes of moderate-to-vigorous physical activity 2 to 4 days (OR=0.928, 95% CI 0.865 to 0.996) or 5 to 7 days per week (OR=0.912, 95% CI 0.833 to 0.998) were negatively associated with scoliosis risk (all P<0.05). CONCLUSIONS The prevalence of scoliosis among primary and secondary school students in Hunan Province is relatively high and is significantly associated with age, gender, urban-rural status, nutritional condition, and physical activity frequency. Targeted interventions and enhanced monitoring in high-risk regions and populations are essential to prevent and control scoliosis.
Humans ; Scoliosis/epidemiology* ; Male ; Female ; Adolescent ; China/epidemiology* ; Prevalence ; Child ; Students/statistics & numerical data* ; Rural Population/statistics & numerical data* ; Urban Population/statistics & numerical data* ; Surveys and Questionnaires ; Risk Factors ; Thinness/epidemiology*

Objective To compare the effects of different exercise acclimatization(EA)durations on liver injury and inflammatory response in mice with exertional heatstroke(EHS).Methods A total of 168 male C57BL/6 mice were randomly assigned to four groups using a random number table:no exercise acclimation group(EA0W,n=54),1-week exercise acclimation group(EA1W,n=54),2-week exercise acclimation group(EA2W,n=54),and blank control group(n=6).The blank control group did not undergo acclimatization training or EHS modeling.The EA1W and EA2W groups underwent daily 2-hour exercise training at a speed of 10 m/min in an environment maintained at(26.0±0.5)℃for 1 and 2 weeks,respectively,followed by a 2-day rest after training completion.EHS modeling was performed in mice of EA0W,EA1W,and EA2W groups through running at 10 m/min under controlled environmental conditions(39.5℃ambient temperature,65%relative humidity).The modeling endpoint was defined as loss of consciousness accompanied by a core body temperature≥42.7℃.All modeling procedures were systematically documented.Following modeling,18 mice from EA0W,EA1W,and EA2W groups underwent 24-hour survival analysis.Blood samples from the abdominal aorta and liver tissues were collected at 6,12 and 24 hours post-modeling(6 mice per time point for each group).Plasma levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and creatine kinase(CK)were quantified.Interleukin(IL)-1β and IL-6 concentrations were determined using enzyme-linked immunosorbent assay(ELISA).Liver tissue specimens underwent hematoxylin-eosin(HE)staining and pathological scoring.Results The EHS model was successfully established in all EA groups.When all mice in EA0W group developed EHS(65 min after the modeling initiation),the incidence rates in EA1W and EA2W groups were 50.0%and 22.2%,respectively,with a statistically significant difference between EA0W group and the latter two groups(P<0.05).When all mice in the three groups developed EHS,the time to EHS onset was significantly longer in both EA1W and EA2W groups compared to EA0W group,with EA2W group showing a longer onset time than EA1W group(P<0.05).Survival analysis revealed a significantly higher 24-hour survival rate in EA2W group(61.1%)compared to EA0W group(33.3%)(P<0.05),while no significant difference was observed between EA1W group and the other two groups(P>0.05).The levels of IL-1β,IL-6,and CK were highest at 6 h post-modeling in all EA groups(P<0.05),and liver injury was most severe at 12 h post-modeling(P<0.05).Compared to EA0W group,the levels of ALT,AST,and IL-1β,as well as liver pathology scores,were significantly lower at 12 h post-modeling in both EA1W and EA2W groups(P<0.05),with EA2W group showing significantly lower ALT and AST levels,as well as liver pathology scores than EA1W group(P<0.05).At 6 h post-modeling,CK levels were significantly higher in EA1W and EA2W groups compared to EA0W group(P<0.05),with EA2W group exhibiting higher CK levels than in EA1W group(P<0.05).Conclusions Exercise acclimation helps reduce the incidence of EHS.Following EHS onset,the survival rate of exercise-acclimated mice is higher than that non-acclimated mice,with a significantly higher survival rate in mice acclimated for 2 weeks compared to non-acclimated mice.However,no significant difference in survival rate is observed between mice acclimated for 1 week and non-acclimated mice.Additionally,exercise acclimation for 2 weeks is more effective in reducing liver injury and inflammatory responses compared to 1-week acclimation.

Objective To investigate the epidemiological characteristics of Mycoplasma pneumoniae(MP)infection among pediatric inpatients with respiratory tract infections(RTIs)at Children's Hospital of Hebei Province,providing evidence for clinical diagnosis and treatment.Methods A retrospective analysis was conducted on 79 546 children hospitalized for RTIs between January 2016 and February 2024.Nasopharyngeal aspirates or deep sputum samples were collected,and polymerase chain reaction(PCR)was used to detect nucleic acids of 13 respiratory pathogens,including MP and adenovirus.The epidemiological trends across different years,seasons,genders,and age groups were analyzed.Results Among the 79 546 enrolled cases(male:47 437,59.6%;female:32 109,40.4%),the MP-positive rate was 17.7%(14 106/79 546),peaking in 2023(28.8%)and reaching the lowest in 2021(7.0%).Except for the period from July 2020 to March 2021 with exceptionally low MP positivity,epidemic peaks consistently occurred between August and February or March of the following year.Seasonal analysis revealed significantly higher MP positivity in autumn and winter compared to spring(P<0.001).Female children exhibited a higher MP-positive rate(20.1%,6444/32 109)than males(16.2%,7662/47 437)(P<0.001).The MP-positive rate increased with age:infancy(3.2%,849/26 741),toddlerhood(9.3%,1935/20 763),preschool(21.2%,3918/18 448),and school-age(54.5%,7404/13 594)(P<0.001).Co-infections with other respiratory pathogens were observed in 37.3%(5264/14 106)of MP-positive cases,with human rhinovirus(HRV)being the most frequent co-pathogen(43.3%,2279/5264 of mixed infections).Conclusion MP is a major pathogen of RTIs in hospitalized children at Children's Hospital of Hebei Province.Infections occur year-round but predominantly in autumn,with higher susceptibility in females and school-age children.Targeted preventive measures should be implemented during peak seasons to mitigate transmission risks.

Drug-induced liver injury(DILI)is a common adverse drug reaction in clinical practice,which can lead to acute liver failure and even death in severe cases.In recent years,with the continuous introduction of new drugs and the expansion of their usage,the incidence and mortality rates of DILI have shown an upward trend,posing significant challenges to public health and clinical treatment.Macrophages,as a crucial component of the innate immune system,exhibit high plasticity and heterogeneity.They can polarize into pro-inflammatory M1 type or anti-inflammatory M2 type in response to microenvironmental signals.Research has demonstrated that macrophage polarization plays a central regulatory role in the occurrence and progression of DILI by influencing various processes such as inflammatory responses,cell apoptosis,and tissue repair.This review focuses on elucidating the regulatory mechanisms and roles of macrophage polarization in DILI,providing a theoretical framework for developing precise immunotherapeutic strategies.