Background: Disorders of the blood-brain barrier (BBB) arising from diabetes mellitus are closely related to diabetic encephalopathy. Previous research has suggested that neuron-glia antigen 2 (NG2)-glia plays a key role in maintaining the integrity of the BBB. However, the mechanism by which NG2-glia regulates the diabetic BBB remains unclear. Methods: Type 2 diabetes mellitus (T2DM) db/db mice and db/m mice were used. Evans-Blue BBB permeability tests and transmission electron microscopy techniques were applied. Tight junction proteins were assessed by immunofluorescence and transmission electron microscopy. NG2-glia number and signaling pathways were evaluated by immunofluorescence. Detection of matrix metalloproteinase-9 (MMP-9) in serum was performed using enzyme-linked immunosorbent assay (ELISA). Results: In T2DM db/db mice, BBB permeability in the hippocampus significantly increased from 16 weeks of age, and the structure of tight junction proteins changed. The number of NG2-glia in the hippocampus of db/db mice increased around microvessels from 12 weeks of age. Concurrently, the expression of MMP-9 increased in the hippocampus with no change in serum. Sixteen- week-old db/db mice showed activation of the Wnt/β-catenin signaling in hippocampal NG2-glia. Treatment with XAV-939 improved structural and functional changes in the hippocampal BBB and reduced MMP-9 secretion by hippocampal NG2-glia in db/db mice. It was also found that the upregulation of β-catenin protein in NG2-glia in the hippocampus of 16-week-old db/db mice was significantly alleviated by treatment with XAV-939. Conclusion The results indicate that NG2-glia can lead to structural and functional disruption of the diabetic BBB by activating Wnt/β-catenin signaling, upregulating MMP-9, and degrading tight junction proteins.

ObjectiveTo explore the clinical safety of Feilike Mixture （FLK） in the real world. MethodsThe safety of all children who received FLK from 29 institutions in 12 provinces between January 21，2021 and December 25，2021 was evaluated through prospective centralized surveillance and a nested case control study. ResultsA total of 3 035 juveniles were included. There were 29 research centers involved，which are distributed across 12 provinces，including one traditional Chinese medicine （TCM） hospital and 28 general hospitals. The average age among the juveniles was （4.77±3.56） years old，and the average weight was （21.81±12.97） kg. Among them，119 cases （3.92%） of juveniles had a history of allergies. Acute bronchitis was the main diagnosis for juveniles，with 1 656 cases （54.46%）. FLK was first used in 2 016 cases （66.43%），and 142 juvenile patients had special dosages，accounting for 4.68%. Among them，92 adverse drug reactions （ADRs） occurred，including 73 cases of gastrointestinal system disorders，10 cases of metabolic and nutritional disorders，eight cases of skin and subcutaneous tissue diseases，two cases of vascular and lymphatic disorders，and one case of systemic diseases and various reactions at the administration site. The manifestations of ADRs were mainly diarrhea，stool discoloration，and vomiting，and no serious ADRs occurred. The results of multi-factor analysis indicated that special dosages （the use of FLK）［odds ratio （OR） of 2.642， 95% confidence interval （CI） of 1.105-6.323］，combined administration： spleen aminopeptide （OR of 4.978， 95%CI of 1.200-20.655），and reason for combined administration： anti-infection （OR of 1.814， 95%CI of 1.071-3.075） were the risk factors for ADRs caused by FLK. Conclusion92 ADRs occurred among 3 035 juveniles using FLK. The incidence of ADRs caused by FLK was 3.03%，and the severity was mainly mild or moderate. Generally，the prognosis was favorable after symptomatic treatment such as drug withdrawal or dosage reduction，suggesting that FLK has good clinical safety.

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 screen and analyze the differentially expressed genes (DEGs) related to oxidative stress in a silicosis mouse model using transcriptome sequencing technology. Methods i) A total of 30 workers without occupational dust-exposed history were selected as the control group and 17 patients with silicosis were selected as the silicosis group using a judgment sampling method. The levels of glutathione and malondialdehyde in the plasma of workers in the two groups were determined by enzyme-linked immunosorbent assay. ii) RAW264.7 cells in the logarithmic growth phase were randomly divided into the control group and the silica group, treated with 0 and 50 mg/L silica suspensions for 24 hours. Protein expression of superoxide dismutase 2 (SOD2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the cells was determined by Western blotting. iii) The specific pathogen free male C57BL/6 mice were randomly divided into the control group and the silicosis model group, with 10 mice in each group. Mice were exposed to 50 μL of 0.9% sodium chloride solution and silica suspension at a mass concentration of 100 g/L, respectively, using a single tracheal exposure method. After 28 days of exposure, the pathological changes of mouse lung tissues were observed. Transcriptome sequencing was used to screen DEGs in the lung tissues of the silicosis mouse model, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. The expression of DEGs was verified using quantitative real-time polymerase chain reaction (qPCR). Results i) The level of malondialdehyde in the patients′ plasma was higher (P<0.01), while the level of glutathione was lower (P<0.01) in the silicosis group than that of the control group. ii) The relative expression of SOD2 protein decreased (P<0.05), while the relative expression of IL-6 and TNF-α proteins increased (all P<0.05) in the silica group of RAW264.7 cells compared with the control group. iii) The pathological results of lung tissues showed that the alveolar structure of mice was destroyed and silicotic nodules were formed in the silicosis model group. Transcriptome sequencing identified 3 703 DEGs, of which 3 199 were significantly down-regulated and 504 were significantly up-regulated. The GO enrichment analysis results showed that the DEGs were significantly enriched in biological processes such as oxidative stress, inflammation, immunity and hypoxia, with cellular components mainly located in membranes, cytoplasm, and nucleus. Molecular functions were enriched in oxidoreductase activity, protein binding, and adenosine triphosphate binding. The KEGG enrichment analysis results showed that the DEGs were mainly involved in the phosphatidylinositol 3-kinase-protein kinase B signaling pathway, cyclic adenosine monophosphate signaling pathway, chemokine signaling pathway, and apoptosis signaling pathway. A total of 28 DEGs involved in the "oxidative stress response" pathway were screened by GO enrichment analysis. The qPCR verification results showed that the relative expression of DEGs carbonic anhydrase 3 (Car3), matrix metalloproteinase 9 (Mmp9), and MutY DNA glycosylase (Mutyh) involved in the "oxidative stress response" of lung tissues in the silicosis model group were lower than those of the control group (all P<0.05). Conclusion Oxidative stress response exists in silicosis patients. The oxidative stress-related genes Car3, Mmp9, and Mutyh are altered in the mouse lung tissues of the silicosis model through the oxidative stress pathway, suggesting that they could be new targets for the treatment of silicosis.

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 investigate the current status of quality of life and its influencing factors in elderly patients with minor amputations of the diabetic foot,providing a basis for medical staff to formulate intervention strategies.Methods A convergent mixed study design was used.A single-centre cross-sectional survey research method was used to select 168 elderly patients with minor amputation of the diabetic foot admitted to the Department of Wound Repair of a tertiary-level hospital in Beijing from May 2022 to May 2024 for questionnaire surveys and multivariate linear regression analyses of factors affecting the quality of life.During the same period,15 patients were selected for semi-structured interviews using purposive sampling based on ternary interaction determinism.Results Quantitative findings:A total of 167 valid questionnaires were retrieved,and the recovery rate of valid questionnaires was 99.4％.the total quality of life score of 167 respondents was(84.22±12.49)scores;the results of multivariate linear regression analyses showed that age and self-care ability were the independent risk factors affecting the quality of life of patients with minor amputation of the diabetic foot(P＜0.05).Qualitative findings:a total of 3 themes were extracted based on the triadic interactive determinism,including subject level,environmental level and behavioural level.Mixed findings:age and amputation affect the physical and mental state of patients and hinders quality of life improvement;limited work and life,and scarce external resources;the level of self-care ability restricts self-management behaviours and makes it difficult to improve quality of life.Conclusion Elderly patients with minor amputations of the diabetic foot have impaired physiological and psychological health to some degree,and healthcare professionals should be concerned about the negative impact of minor amputations on elderly diabetic foot patients,while also focusing on their individual needs and providing support.

Objective To analyze the main epidemiological characteristics of fungal infection in this hospital in the past 7 years,and to provide reference for clinical treatment and prevention and control strategies of fun-gal infection.Methods The fungal data and clinical data of related patients isolated from clinical samples in Peking Union Medical College Hospital from early January 2018 to the end of May 2024 were selected,and the main epidemiological characteristics of fungal infection in this hospital were identified and described through multi-angle statistical analysis.Results A total of 4 479 patients with filamentous fungal infection were en-rolled.The proportion of male patients[57.5％(2 576/4 479)]was higher than that of female patients[42.5％(1 903/4 143)],mainly distributed in internal medicine,Intensive Care Unit(ICU)and emergency de-partment,among which internal medicine accounted for the highest proportion[50.0％(2 241/4 479)].About 90.0％of the specimens were from the lower respiratory tract,in addition to specimens from skin and soft tis-sue,tissue,ear and blood culture.In terms of seasonal distribution,there are more patients in winter.The fun-gi were mainly composed of Aspergillus,Mucor,Cerdosporium,Fusarium and Penicillium,among which As-pergillus was the most abundant,accounting for 74.6％of the total.Aspergillus fumigatus was the most a-bundant Aspergillus,accounting for 42.5％of the total Aspergillus(1 418/3 340).Among the related infec-tions caused by mold,Aspergillus was the most common in the lower respiratory tract,accounting for 76.8％.Among them,Aspergillus fumigatus accounted for the highest proportion(33.6％).98.6％of the molds infected the ear were Aspergillus,of which Aspergillus niger and Aspergillus terreus were the most common.Skin infections are mainly caused by Sporothrix schenckii,Trichophyton rubrum,Microsporum ca-nis.The results of in vitro drug sensitivity test showed that the four common Aspergillus isolated in this hos-pital were sensitive to voriconazole,and amphotericin B had better antifungal activity against Mucorales in vitro.Conclusion Based on the main epidemiological characteristics of fungal infections in this hospital,it is recommended that special attention be paid to the admission of patients in the respiratory department during the peak infection period in autumn and winter.In the treatment of fungal infections in different regions and on different body parts,attention should be paid to the differences in the distribution of bacterial species.

OBJECTIVE To provide a reference for revising the safety content of traditional Chinese medicine（TCM） instructions. METHODS A systematic analysis was conducted on the relevant announcements on the revision of TCM instruction from 2013 to 2024， including the year of publication， drug name， drug formulation， announcement release time， and the average number of revisions made to three safety contents （contraindication， adverse drug reaction， and precaution）. According to the report data of national adverse drug reaction monitoring from 2013 to 2024， analyze the proportion of TCM in all adverse drug reactions， the composition ratio of adverse drug reaction of different dosage forms of drugs [TCM injection， oral TCM， other （topical） TCM]. RESULTS From 2013 to 2024， the National Medical Products Administration issued a total of 101 notices on the revision of TCM instruction， involving 241 types of TCM. Among them， there were 163 types of oral TCM， 25 types of TCM injection， and 53 types of other （topical） TCM. There were 3， 10 and 0 types of TCM injection， oral TCM， and other （topical） TCM with missing safety content， respectively. The main source of adverse drug reaction data for TCM injections was post- marketing monitoring data （accounting for 48.00%）； the main source of adverse drug reaction data for oral TCM was monitoring data （accounting for 71.17%）； 73.58% of other （topical） TCM did not mention the source of adverse drug reaction data. The report on national adverse drug reaction monitoring showed that the proportion of all adverse drug reactions of TCM had decreased from 17.3% in 2013 to 12.1% in 2024. Among them， the proportion of adverse drug reaction of TCM injection in the three dosage forms of TCM had decreased from 61.3% in 2015 to 24.6% in 2024， while the proportion of adverse drug reaction of oral TCM in the three dosage forms of TCM had increased from 34.7% in 2015 to 64.0% in 2024. CONCLUSIONS The risk management of TCM safety content has achieved results in China， but still faces three major challenges： strongdependence on passive monitoring， insufficient data traceability， and missing key content. It is urgent to improve safety content by dosage form， optimize data sources， and fully utilize real-world evidence to supplement safety content.

BACKGROUND:Transcranial magnetic stimulation has been used in the treatment of Alzheimer's disease,but its mechanism has not been fully clarified. OBJECTIVE:To explore the mechanism of repetitive transcranial magnetic stimulation to increase neural excitability in mice with Alzheimer's disease. METHODS:Sixteen C57BL/6 mice were randomized into control group (n=8) and control+magnetic stimulation group (n=8). Another 16 APP/PS1 mice were randomized into dementia group (n=8) and dementia+magnetic stimulation group (n=8). Mice in the two magnetic stimulation groups were given repetitive transcranial magnetic stimulation,2 hours daily,for 14 continuous days. The water maze was then used to detect the cognitive function of mice. Whole-cell membrane-clamp technique was used to collect action potentials and analyze the effect of Alzheimer's disease on action potentials;and the potassium channe currents were collected and analyzed for the role of their kinetic properties on neural excitability. RESULTS AND CONCLUSION:The results of Morris water maze showed that normal mice could find and determine the original platform more accurately after receiving repetitive transcranial magnetic stimulation,while Alzheimer's disease led to a decrease in the learning and memory ability of mice,a decrease in the number of times they found the platform,and a degeneration of neurons in the hippocampal dentate gyrus. Repetitive transcranial magnetic stimulation could improve the learning and memory ability of mice with Alzheimer's disease. Whole-cell membrane clamp technique assay showed that repetitive transcranial magnetic stimulation could trigger neuronal depolarization and enhance neuronal excitability in Alzheimer's disease mice. Analysis of potassium channel currents showed that Alzheimer's disease caused an increase in the transient outward potassium channel half-activation voltage. The inactivation curve was shifted in the direction of depolarization and the resuscitation time constant was prolonged,causing the delayed rectifier potassium channel activation curve to be shifted in the direction of depolarization. Whereas repetitive transcranial magnetic stimulation delayed the opening and closing of the potassium channel and inhibit the efflux of intracellular potassium ions,which resulted in the retention of a higher intracellular potassium concentration and increased neuronal excitability. To conclude,repetitive transcranial magnetic stimulation may alleviate cognitive decline by increasing neuronal excitability in the hippocampal dentate gyrus.

Objective:To investigate the predictive value of serum HOXA6 and HOXA10 levels in assessing endometrial receptivity in patients with diminished ovarian reserve (DOR).Methods:A total of 248 DOR patients treated at Xi'an People's Hospital from January 2021 to October 2023 were enrolled, with 200 healthy female volunteers as controls. Serum HOXA6 and HOXA10 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Endometrial thickness was assessed via transvaginal ultrasound on days 20-24 of the menstrual cycle, and endometrial receptivity was classified into high receptivity (≥8 mm), moderate receptivity (6-8 mm) and low receptivity (<6 mm) group. Follicle-stimulating hormone (FSH) and anti-Müllerian hormone (AMH) levels were detected by chemiluminescence immunoassay on day 3 of the menstrual cycle. Follicle count and size were recorded via transvaginal ultrasound. Normally distributed data were expressed as Mean±SD, comparison between two groups was performed by independent samples t-test, comparison among multiple groups was performed by one-way ANOVA, pairwise comparison was performed by Tukey's HSD post hoc test. Categorical data were presented as rates or percentages and analyzed by χ2 test. Logistic regression identified independent risk factors for DOR, and Pearson correlation analyzed relationships between HOXA6/HOXA10, endometrial receptivity, and ovarian reserve. Receiver operating characteristic (ROC) curves evaluated the diagnostic value of HOXA6 and HOXA10 in predicting endometrial receptivity. Results:Serum levels of both HOXA6 [(120.34±15.16) ng/L] and HOXA10 [(98.46±12.61) ng/L] in the DOR group were significantly higher than those in the control group [(80.27±10.54) ng/L and (60.36±8.80) ng/L, respectively, t=31.70, 36.20, both P<0.001]. Endometrial thickness in the DOR group [(7.4±1.3) mm] was significantly less than that in the control group [(10.0±1.1) mm]. Serum FSH levels [(12.03±2.54) U/L] were significantly higher in the DOR group compared to the control group [(8.08±2.82) U/L], while AMH levels [(1.56±0.45) μg/L] and the number of follicles [(3.52±1.63) μg/L] were significantly lower than those in the control group [(5.07±1.05) μg/L and (10.09±2.06), respectively]. The differences between the two groups for these parameters were statistically significant ( t=22.52, 15.58, 18.10, 33.58, respectively; all P<0.001). Pearson correlation analysis revealed that serum HOXA6 and HOXA10 levels were negatively correlated with endometrial thickness, AMH levels, and the number of follicles in DOR patients (HOXA6: r=-0.773, -0.647, -0.721, respectively, all P<0.001; HOXA10: r=-0.788, -0.682, -0.834, respectively, all P<0.001), and positively correlated with serum FSH levels ( r=0.667 and 0.670, respectively, both P<0.001). Multivariate logistic regression analysis indicated that serum HOXA6 ( OR=1.179, 95% CI: 1.144-1.215, P<0.001), HOXA10 ( OR=1.223, 95% CI: 1.177-1.270, P<0.001), and FSH levels ( OR=1.827, 95% CI: 1.569-2.129, P<0.001) were independent risk factors for DOR in women. Endometrial thickness ( OR=0.264, 95% CI: 0.205-0.340, P<0.001), serum AMH levels ( OR=0.126, 95% CI: 0.078-0.205, P<0.001), and the number of follicles ( OR=0.058, 95% CI: 0.024-0.143, P<0.001) were identified as protective factors against DOR. ROC curve analysis showed that the AUCs for serum HOXA6, HOXA10, and their combination in predicting poor endometrial receptivity in DOR patients were 0.770, 0.820, and 0.864, respectively. The AUC value for HOXA10 was slightly higher than that for HOXA6, and the combined prediction model had the highest AUC value. Conclusion:Serum HOXA6 and HOXA10 levels demonstrate a statistically significant association with ovarian reserve function and endometrial receptivity. These findings suggest their potential as diagnostic biomarkers for assessing endometrial receptivity in patients with diminished ovarian reserve (DOR).