ObjectiveTo explore the spatial distribution patterns of flavonoid glycosides in Epimedium sagittatum and the influences of environmental factors on the accumulation of these components. MethodsThe spatial statistical analysis and GeoDetector model were used to analyze the distribution patterns of epimedin A，epimedin B，epimedin C，icariin，and total flavonoid glycosides in E. sagittatum samples from 92 different production areas in 36 cities of 13 provinces/municipalities/autonomous regions of China，as well as the effects of 28 environmental factors on the accumulation of each component. ResultsThe average content of flavonoid glycosides 64 （69.56%） producing areas and 30 （83.33%） cities met the quality standard of no less than 1.50% of total flavonoid glycosides in the 2020 edition of Chinese Pharmacopoeia.Epimedin A，epimedin B，epimedin C，icariin，and their sum showed significantly high accumulation.The hot spots regions of epimedin A and epimedin B were similar with each other，mainly located in western Hunan，eastern Hubei，eastern Guizhou，and northern Guangxi.The common hot spot areas of epimedin C and total flavonoid glycosides were in western and southwestern Hunan，southern Henan，northern Anhui，eastern Guizhou，and southern Chongqing.The hot spots areas of icariin were in southern Chongqing，western Hunan，and eastern and northeastern Guizhou.The interactions between environmental factors had stronger explanatory power for the accumulation of components than single factors.The strongest single factor and interactive factor affecting the accumulation of epimedin C were precipitation of wettest quarter （q=0.16） and its interaction with temperature seasonality （q=0.35），respectively.The strongest single factor influencing both the accumulation of icariin and total flavonoid glycosides was the precipitation of coldest quarter （q equals 0.15 and 0.22，respectively）.The strongest interactions were observed between precipitation of coldest quarter and gravel content （q=0.34），as well as between precipitation of coldest quarter and aspect （q=0.35）. ConclusionThirteen cities，including Zhumadian and Nanyang in Henan，Huaihua，Shaoyang，and Zhangjiajie in Hunan，and Zunyi，Qiandongnan，and Tongren in Guizhou，were hot spots of total flavonoid glycosides in E.sagittatum.Precipitation，gravel content，temperature seasonality，and aspect significantly influence the accumulation of flavonoid glycosides in E.sagittatum.This study provides reference for the utilization and production zoning of E.sagittatum.

OBJECTIVE To compare the predictive accuracy and clinical applicability of four vancomycin individualized dosing tools （SmartDose， ClinCalc， Gulou， Pharmado） and provide a basis for rational clinical medication use. METHODS A retrospective cohort study was conducted， enrolling 479 adult patients who received vancomycin therapy and underwent steady-state trough concentration monitoring in Zhongshan Hospital， Fudan University （Xiamen Branch） from January 1， 2022， to June 30， 2024. The predictive accuracy of each tool was evaluated using indicators， such as mean error （ME）, mean absolute error （MAE）， mean percentage error （MPE）， mean absolute percentage error （MAPE）， the proportion of patients with an absolute percentage error （APE） of less than 30%， the 95% limits of agreement， and the overall relative percentage difference between predicted and measured values. Using indicators such as accessibility， patient management， and recommendation of multiple treatment options， the clinical panxso@163.com applicability of the tools for all patients was evaluated； using the discrepancy in accuracy between the predicted and actual measured blood drug concentrations as an indicator， the clinical applicability was assessed for patients in different renal function subgroups （hyperfunction， normal， mild impairment， moderate impairment， and severe impairment）. RESULTS In terms of accuracy， SmartDose demonstrated the best overall performance with an MAPE of 46.40% and a proportion of APE ＜30% （46.56%）. Bland-Altman analysis indicated that SmartDose had the smallest overall relative percentage difference （－7.25%）， although the 95% limits of agreement were broad for all tools， with differences between the upper and lower limits exceeding 200%. In terms of applicability， all four dosing tools were freely accessible and demonstrated good availability； SmartDose and Pharmado provided the most comprehensive solutions， offering features such as patient management， multiple regimen recommendations， and drug concentration-time curve plotting. Stratified analysis based on renal function revealed that Pharmado showed optimal prediction for hyperfiltration patients （mean difference： 0.11 mg/L）. SmartDose and ClinCalc showed relatively better performance in normal and mild renal impaiment （mean difference： 0.37， 0.51 mg/L and －1.13， －1.33 mg/L，respectively）. SmartDose performed best in moderate renal impairment （mean difference： －2.60 mg/L）. Pharmado and Gulou had smaller prediction biases in severe renal impairment （mean differences： 1.52 mg/L and －0.23 mg/L， respectively）. CONCLUSIONS The four individualized dosing tools demonstrated limited accuracy in the initial prediction of vancomycin concentrations. Among them， SmartDose demonstrates the highest overall prediction accuracy and possesses comprehensive clinical management features. It is recommended that Pharmado be preferred for patients with renal hyperfiltration； SmartDose or ClinCalc can be used for patients with normal or mildly impaired renal function； SmartDose is recommended for patients with moderately impaired renal function； Pharmado or Gulou may be considered for patients with severely impaired renal function.

Clinical management of atopic dermatitis (AD) is challenged by its susceptibility to recurrence, side effects, and high costs. We found that Portulaca oleracea L.-derived nanovesicles (PDNV) exert anti-inflammatory effects by modulating macrophage M1/M2 polarization. These effects were achieved through pathways including inhibition of nuclear factor-κB (NF-κB) and stimulator of interferon genes (STING) protein expression in diseased tissues, demonstrating their potential to ameliorate AD symptoms. To increase the transdermal permeation of PDNV, dissolvable microneedles composed primarily of hyaluronic acid (HA) were developed as an adjunctive means of delivery. Meanwhile, polysaccharides of Portulaca oleracea L., which were synergistic with PDNV, were used as microneedle constituent materials to enhance the mechanical properties and physical stability of HA. This new means of delivery significantly improves the treatment of AD and also provides new options for the efficient utilization of plant extracellular vesicles and the treatment of AD. In addition, transcriptomic analysis of PDNV showed that the mRNAs of Portulaca oleracea L. are closest to those of ferns, which may shed light on related evolutionary and plant species identification studies.

OBJECTIVES: To investigate the effect of avitinib for suppressing NLRP3 inflammasome activation and alleviating septic shock and explore the underlying mechanism. METHODS: Mouse bone marrow-derived macrophages (BMDM), human monocytic leukemia cell line THP-1, and peripheral blood mononuclear cells (PBMC) isolated from healthy volunteers were pre-treated with avitinib, followed by activation of the canonical NLRP3 inflammasome using agonists including nigericin, monosodium urate (MSU) crystals, or adenosine triphosphate (ATP). Non-canonical NLRP3 inflammasome activation was induced via intracellular transfection of lipopolysaccharide (LPS). Western blotting was used to detect the secretory protein markers of NLRP3 inflammasome activation and assess pyroptosis, and the levels of inflammatory cytokines in cell culture supernatant were determined with ELISA. In a mouse model of LPS-induced septic shock, the effect of avitinib treatment on the levels of inflammatory cytokines in serum and peritoneal lavage fluid were examined with ELISA, and survival curves of the mice were plotted using the Kaplan-Meier method. RESULTS: Avitinib significantly inhibited NLRP3 inflammasome activation in multiple cell types, and dose-dependently reduced IL-1β secretion and caspase-1 cleavage while suppressing GSDMD-mediated pyroptosis without obviously affecting IL-6 or TNF-α levels. In the mouse models of LPS-induced septic shock, avitinib significantly lowered IL-1β levels in serum and peritoneal fluid and extended survival time of the mice. CONCLUSIONS Avitinib suppresses NLRP3 inflammasome activation and alleviates septic shock in mice.
Animals ; Shock, Septic/metabolism* ; Mice ; NLR Family, Pyrin Domain-Containing 3 Protein ; Inflammasomes/drug effects* ; Humans ; Macrophages/metabolism* ; Interleukin-1beta/metabolism* ; Lipopolysaccharides

Sensorineural hearing loss (SNHL), the most commonly-occurring form of hearing loss, is caused mainly by injury to or the loss of hair cells and spiral ganglion neurons in the cochlea. Numerous environmental and physiological factors have been shown to cause acquired SNHL, such as ototoxic drugs, noise exposure, aging, infections, and diseases. Several programmed cell death (PCD) pathways have been reported to be involved in SNHL, especially some novel PCD pathways that have only recently been reported, such as ferroptosis, necroptosis, and pyroptosis. Here we summarize these PCD pathways and their roles and mechanisms in SNHL, aiming to provide new insights and potential therapeutic strategies for SNHL by targeting these PCD pathways.
Humans ; Hearing Loss, Sensorineural/metabolism* ; Necroptosis/drug effects* ; Pyroptosis/drug effects* ; Ferroptosis/drug effects* ; Animals

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

Abstract Respiratory diseases represent prevalent conditions that pose a significant threat to public health. The pathogenesis of these diseases is complex involving a variety of cells and cytokines. Cell culture technology serves as a fundamental tool for investigating pathological mechanisms and drug efficacy. However, traditional monolayer cell culture fail to mimic the intricate cell-cell interactions, limiting its applicability. In contrast, cell co-culture offers a more physiologically relevant approach by closely mimicking the multicellular microenvironment. This advancement provides a robust model for elucidating pathological pathways and evaluating pharmacological interventions in respiratory diseases. In this review, the applications of cell co-culture technologies in common respiratory diseases, including chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, lung cancer, asthma, and pneumonia are summarized, in order to propose strategies for the prevention and treatment of these diseases.

Threatened abortion is a common disease of obstetrics and gynecology and one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in TCM obstetrics and gynecology， Western medicine obstetrics and gynecology， and pharmacology to deeply discuss the advantages of TCM and integrated Chinese and Western medicine treatment as well as the medication plans for threatened abortion. After discussion， the experts concluded that chromosome， endocrine， and immune abnormalities were the key factors for the occurrence of threatened abortion， and the Qi and blood disorders in thoroughfare and conception vessels were the core pathogenesis. In the treatment of threatened abortion， TCM has advantages in preventing miscarriages， alleviating clinical symptoms and TCM syndromes， relieving anxiety， regulating reproductive endocrine and immune abnormalities， personalized and diversified treatment， enhancing efficiency and reducing toxicity， and preventing the disease before occurrence. The difficulty in diagnosis and treatment of threatened abortion with traditional Chinese and Western medicine lies in identifying the predictors of abortion caused by maternal factors and the treatment of thrombophilia. Recurrent abortion is the breakthrough point of treatment with integrated traditional Chinese and Western medicine. It is urgent to carry out high-quality evidence-based medicine research in the future to improve the modern diagnosis and treatment of threatened abortion with TCM.

Objective:To investigate the effect and mechanism of different doses of luteolin on memory function and apoptosis-related proteins of aging rats induced by D-galactose.Methods:Forty-eight SPF-grade male Wistar rats aged 6-8 weeks were randomly divided into control group, model group, luteolin low-dose group (25 mg/kg), medium-dose group (50 mg/kg), high-dose group (100 mg/kg), and vitamin C group (100 mg/kg), with 8 rats in each group. D-galactose (1 000 mg/kg) was subcutaneously injected to establish the aging rat model, while luteolin was used for preventive treatment. The Morris water maze test was used to evaluate the learning and memory abilities of the rats.Transmission electron microscopy was used to detect the morphology of hippocampal neurons in rats.Spectrophotometry was used to detect the levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD), malondialdehyde (MDA), and the total antioxidant capacity (T-AOC). RT-PCR was used to detect miR-34a mRNA expression.Western blot technique was used to detect the expression levels of silent regulator protein 1 (SIRT1), B-cell lymphoma-2 (Bcl-2), cleaved caspase-3, p53, and p21. Statistical analysis was performed using SPSS 22.0, and one-way ANOVA was used for multi-group comparison, followed by LSD- t test for further pairwise comparisons. Results:(1) The differences in escape latency among the 6 groups of rats were statistically significant ( F=120.93, P<0.001). The latency of first finding the platform location of the model group rats ((54.61±3.60) s) was higher than that of the control group ((10.54±4.27) s) ( P<0.05). The latency of first finding the platform location of rats in the low, medium and high dosage groups of luteolin ((45.50±3.81)s, (37.46±2.94) s, (32.32±3.14) s) was lower than that of the model group ((54.61±3.60) s) (all P<0.05). (2) The differences of SOD, MDA, T-AOC, TNF-α, IL-1β, and IL-6 levels in the cerebral cortex of the 6 groups of rats were all statistically significant ( F=281.636, 75.119, 208.228, 38.999, 28.428, 52.767, all P<0.001). Compared with the control group, the model group showed abnormal levels of inflammatory factors and antioxidant indexes. In the medium and high dosage groups of luteolin, the SOD and T-AOC contents in the cerebral cortex of rats were higher than those in the model group (all P<0.05), while the levels of MDA, TNF-α, IL-1β, and IL-6 were lower than those in the model group (all P<0.05). (3) The differences in relative expression levels of miR-34a mRNA among the 6 groups of rats were statistically significant ( F=81.439, P<0.001). The expression levels of miR-34a mRNA in the hippocampal tissues of rats in the luteolin treatment group were lower than those in the model group ( P<0.05). (4) The differences in protein expression levels of SIRT1, p53, and p21 in the hippocampal tissues of the 6 groups of rats were statistically significant ( F=159.946, 38.342, 123.608, all P<0.001). The expression levels of p53 and p21 in the medium and high dosage groups of luteolin were lower than those in the model group (all P<0.05), while the expression level of SIRT1 protein was higher than that in the model group ( P<0.05). (5) The differences in protein expression levels of Bcl-2 and cleaved caspase-3 in the hippocampal tissues of the 6 groups of rats were statistically significant ( F=112.659, 43.296, both P<0.05). The expression levels of Bcl-2 in the low, medium, and high dosage groups of luteolin ((0.24±0.04), (0.40±0.03), (0.48±0.05) pg/μg) were higher than those in the model group ((0.09±0.06) μg) ( P<0.05), while the expression levels of cleaved caspase-3 in the low, medium, and high dosage groups of luteolin ((0.62±0.04), (0.61±0.09), (0.51±0.10) μg) were lower than those in the model group ((0.75±0.05) μg) ( P<0.05). Conclusions:Luteolin can alleviate cellular oxidative damage through downregulating the miR-34a SIRT1/p53 signaling pathway and reducing cell apoptosis.