Sepsis is a systemic inflammatory response caused by severe infection or trauma, and is one of the common causes of acute lung injury(ALI) and acute respiratory distress syndrome(ARDS). Sepsis-acute lung injury(SALI) is a critical clinical condition with high morbidity and mortality. Its pathogenesis is complex and not yet fully understood, and there is currently a lack of targeted and effective treatment options. Pyroptosis, a novel form of programmed cell death, plays a key role in the pathological process of SALI by activating inflammasomes and releasing inflammatory factors, making it a potential therapeutic target. In recent years, the role of traditional Chinese medicine(TCM) in regulating signaling pathways related to pyroptosis through multi-components and multi-targets has attracted increasing attention. TCM may intervene in pyroptosis by inhibiting the activation of NLRP3 inflammasomes and regulating the expression of Caspase family proteins, thus alleviating inflammatory damage in lung tissues. This paper systematically reviews the molecular regulatory network of pyroptosis in SALI and explores the potential mechanisms and research progress on TCM intervention in cellular pyroptosis. The aim is to provide new ideas and theoretical support for basic research and clinical treatment strategies of TCM in SALI.
Pyroptosis/drug effects* ; Humans ; Sepsis/genetics* ; Acute Lung Injury/physiopathology* ; Animals ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Inflammasomes/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics*

OBJECTIVES: To evaluate the efficacy of molecular targeted agents in children with progressive pediatric low-grade gliomas (pLGG). METHODS: A retrospective analysis was conducted on pLGG patients treated with oral targeted therapies at the Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University, from July 2021. Treatment responses and safety profiles were assessed. RESULTS: Among the 20 enrolled patients, the trametinib group (n=12, including 11 cases with BRAF fusions and 1 case with BRAF V600E mutation) demonstrated 4 partial responses (33%) and 2 minor responses (17%), with a median time to response of 3.0 months. In the vemurafenib group (n=6, all with BRAF V600E mutation), 5 patients achieved partial responses (83%), showing a median time to response of 1.0 month. Comparative analysis revealed no statistically significant difference in progression-free survival rates between the two treatment groups (P>0.05). The median duration of clinical benefit (defined as partial response + minor response + stable disease) was 11.0 months for vemurafenib and 18.0 months for trametinib. Two additional cases, one with ATM mutation treated with olaparib for 24 months and one with NF1 mutation receiving everolimus for 21 months, discontinued treatment due to sustained disease stability. No severe adverse events were observed in any treatment group. CONCLUSIONS Molecular targeted therapy demonstrates clinical efficacy with favorable tolerability in pLGG. Vemurafenib achieves high response rates and induces early tumor shrinkage in patients with BRAF V600E mutations, supporting its utility as a first-line therapy.
Humans ; Glioma/genetics* ; Male ; Female ; Child ; Child, Preschool ; Retrospective Studies ; Brain Neoplasms/genetics* ; Molecular Targeted Therapy/adverse effects* ; Adolescent ; Infant ; Proto-Oncogene Proteins B-raf/genetics* ; Pyrimidinones/therapeutic use* ; Mutation

OBJECTIVES: To identify potential plasma lipidomic biomarkers that distinguish non-metastatic medulloblastoma (nmMB) from metastatic medulloblastoma (mMB) in children. METHODS: In this prospective study, 17 children with mMB and 20 matched children with nmMB were enrolled. Plasma samples were analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Lipid metabolites were evaluated for their associations and diagnostic performance. RESULTS: Orthogonal partial least squares discriminant analysis based on lipid profiles clearly separated nmMB from mMB, and 14 differential lipids were identified, including DG(18:2/20:4/0:0) and SM(d18:1/20:0). Receiver operating characteristic analysis showed nine metabolites with area under the curve greater than 0.7. Differential lipids were enriched in sphingolipid, glycerophospholipid, and arachidonic acid metabolism, suggesting an association with the metastatic phenotype. CONCLUSIONS Plasma lipidomics provides a new approach to identify mMB, and the identified lipid metabolites may support early diagnosis and treatment, prognostic assessment, and selection of therapeutic targets for metastatic medulloblastoma.
Humans ; Medulloblastoma/diagnosis* ; Lipidomics ; Child ; Male ; Female ; Child, Preschool ; Cerebellar Neoplasms/blood* ; Biomarkers, Tumor/blood* ; Neoplasm Metastasis ; Prospective Studies ; Adolescent ; Lipids/blood*

Objective:To explore the relationship between anxiety status and progestogen level in perimenopausal women and their effects on the pathogenesis of uterine fibroid.Methods:A total of 376 perimenopausal women who visited the Department of Gynecology and Neurology of Nanjing Tongren Hospital affiliated School of Medicine of Southeast University from August 2019 to July 2023 were selected as the study subjects.Based on the and divided into two groups according to the Self-Rating Anxiety Scale(SAS),they were divided into a non-anxiety group(n=202,SAS score<50)and an anxiety group(n=174,SAS score≥50).Additionally,according to the presence or absence of uterine fibroids,they were categorized into a non-uterine fibroid group(n=225)and a uterine fibroid group(n=151).The t test or x2 test was used to compare general demographic and clinical data between the non-uterine fibroid group and the uterine fibroid group.Multivariate logistic regression analysis was used to analyze the correlation between anxiety status,progesterone level,and uterine fibroid risk in perimenopausal women.The bootstrap method was used to analyze whether progesterone level mediate the relationship between anxiety status and uterine fibroid risk.Results:Comparison of baseline data between the non-uterine fibroid group and the uterine fibroid group showed that previous caesarean section,number of abortions,hemoglobin level,neutrophil count,lymphocyte count,and neutrophil-to-lymphocyte ratio(NLR)were not associated with the incidence of uterine fibroid(all P>0.05).In contrast,menstrual period,menstrual cycle,progesterone level,and SAS score were significantly associated with the incidence of uterine fibroid(all P<0.05).Analysis of the effects of different clinical features on the risk of uterine fibroid showed that age,chronic diseases history,and dysmenorrhea history were all significantly associated with the incidence of uterine fibroid in perimenopausal women(all P<0.05).Further,univariate logistic regression analysis showed that age≥55 years,chronic diseases,and dysmenorrhea were significant risk factors for uterine fibroid in perimenopausal women(all P<0.05).These seven significant risk factors(menstrual period,menstrual cycle,progesterone level,SAS score,age,chronic disease history,and dysmenorrhea history)were included in a multivariate logistic regression analysis,which identified SAS score and progesterone level as independent risk factors for uterine fibroid in perimenopausal women.Specifically,SAS score was positively correlated with uterine fibroid risk,while progesterone level was negatively correlated with the risk.Restriction cubic spline analysis showed a nonlinear quantitative response relationship between continuously changing progesterone level and the risk of uterine fibroid(x2=12.315,P<0.001),when progesterone level was≤2.00 ng/mL,the risk of uterine fibroid decreased with the increase of progesterone level(HR=1.014,95%CI:1.006-1.012,P<0.001),and when progesterone level was>2.00 ng/mL,the risk of uterine fibroid stabilized with further increases in progesterone level(HR=1.003,95%CI:0.998-1.002,P=0.001).After further adjusting for a variety of related confounding factors affecting the incidence of uterine fibroid in perimenopausal women,it was found that SAS score was an independent risk factor for predicting the incidence of uterine fibroid in perimenopausal women.Mediation effect analysis revealed that SAS score had a direct effect on the incidence of uterine fibroid(β1=0.202,95%CI:0.124-0.216),and progesterone level partially mediated the effect of SAS score on uterine fibroid risk(β2=0.196,95%CI:0.152-0.207).The total effect value was βtotal=0.398,and the mediating effect accounted for 49.25%of the total effect.Conclusion:There was an independent correlation between anxiety status and progestogen level in perimenopausal women,anxiety status was a risk factor for the development of uterine fibroids,while progestogen levelwas a protective factor.

Hypoxemia is a common pathological state characterized by low oxygen saturation in the blood. This condition compromises mucosal barrier integrity particularly in the gut and oral cavity. However, the mechanisms underlying this association remain unclear. This study used periodontitis as a model to investigate the role of platelet activation in oral mucosal immunopathology under hypoxic conditions. Hypoxia upregulated methyltransferase-like protein 4 (METTL4) expression in platelets, resulting in N⁶-methyladenine modification of mitochondrial DNA (mtDNA). This modification impaired mitochondrial transcriptional factor A-dependent cytosolic mtDNA degradation, leading to cytosolic mtDNA accumulation. Excess cytosolic mt-DNA aberrantly activated the cGAS-STING pathway in platelets. This resulted in excessive platelet activation and neutrophil extracellular trap formation that ultimately exacerbated periodontitis. Targeting platelet METTL4 and its downstream pathways offers a potential strategy for managing oral mucosa immunopathology. Further research is needed to examine its broader implications for mucosal inflammation under hypoxic conditions.
DNA, Mitochondrial/metabolism* ; Mouth Mucosa/pathology* ; Hypoxia/immunology* ; Methyltransferases/metabolism* ; Blood Platelets/metabolism* ; Animals ; Periodontitis/immunology* ; Humans ; Platelet Activation ; Mice

Objective To investigate the profile of common oral diseases in the Inner Mongolia region and the im-pact on local residents,and to obtain a clear picture of technology availability for local oral physicians and their needs for oral medical training.This will provide an important basis for optimizing the content of continuing educa-tion program and the direction of counterpart assistance in order to improve the technical level of local oral physi-cians and the practicality of oral medical teaching.Methods The study selected oral physicians from the Inner Mongolia region as subjects and designed a questionnaire to explore the current status of oral diseases and the training needs of oral physicians in this area.The chi-square test or Fisher's exact probability method was used for statistical testing.Results Data collected from the survey questionnaires of 181 oral physicians in the Inner Mongolia region indicated that 56.83%of physicians were engaged in routine oral medicine,reaching 56.83%.Dental caries and peri-odontitis were the most common oral diseases in the region(70.37%and 65.74%respec-tively).The most common impacts of these diseases on patients were pain and discomfort.In terms of clinical skills,diagnostic imaging skills,oral examination skills and root canal therapy were the most important as the ob-jective of training there were 70.17%of respondents expressed expectation to get the learning and training opportu-nity for new technologies and methods.Conclusions Continuing education programs and specific targeted assistance projects should focus on strengthening basic professional training for dental practitioners in Inner Mongolia and the promotion of capacity building in the field of healthcare and promotion of oral health in the region.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

Objective:To translate Amyotrophic Lateral Sclerosis Impairment Multidomain Scale(AIMS)into Chinese,and to investi-gate its reliability and validity among Amyotrophic Lateral Sclerosis(ALS)patients.Methods:A total of 161 ALS patients who were registered in the registry system of Integrated Traditional Chinese and Western Medicine Treatment Center for Motor Neuron Disease in Hubei Provincial Hospital of Traditional Chinese Medicine from August 2023 to July 2024 were enrolled as subjects,and the Chinese version of AIMS was used for investigation after translation and revision.The Rasch model was used to assess the unidimensionality,in-ternal consistency,content validity,construct validity,and criterion-related validity of the questionnaire,and the classical test theory was used for item analysis,test-retest reliability analysis,and criterion-related validity analysis.Results:Unidimensionality testing showed that all three dimensions of AIMS have good unidimensionality.For all items except item 18,information-weighted fit statis-tic mean square(Infit MNSQ)and outlier-sensitive fit statistic mean square(Outfit MNSQ)ranged from 0.5 to 1.5,and point-measure correlation(PT-Measure)ranged from 0.63 to 0.87.The threshold between adjacent options of each item was>1.4 logit.Wright maps showed that item difficulties ranged from-2.24 to 2.08 logit,and the differential item functioning analysis showed that the absolute values of differences between patients across different char-acteristic subgroups were<1 logit.The overall scale and each di-mension had a reliability of>0.9,with an individual reliability of>0.7.The dimension of respiration had a separation index of 1.56,while the overall scale and the other dimensions had a separation in-dex of>2.The item analysis showed that the correlation coefficient between the items in each dimension and their respective dimen-sions ranged from 0.622 to 0.865(P<0.01).The overall scale and the dimensions of medulla oblongata,motor,and respiration had a test-retest reliability of 0.994,0.970,0.990,and 0.972,respectively(P<0.01).The criterion-related validity analysis showed that the correlation coefficients of total score and the score of each dimension between the Chinese version of AIMS and the revised version of AIMS were 0.863,0.829,0.876,and 0.755,respectively(P<0.01).Conclusion:The Chinese version of AIMS has a good degree of fit-ting and relatively high levels of reliability and validity,with moderate item difficulty,reasonable option settings,and high overall qual-ity,and it is suitable for the functional assessment of ALS patients in China.

Objective:To construct an evaluation index system for the operational management capability in tertiary public hospitals and validate its feasibility,providing a reference for accurately assessing the operational management capability of public hospitals.Methods:A literature review and Delphi method were employed to construct the index system.The Analytic Hierarchy Process was used to calculate weights,and a weighted comprehensive index method was applied to evaluate the operational management capability of sample hospitals.Results:A hierarchical indicator system was established,comprising 6 first-level indicators,16 second-level indicators,and 40 third-level indicators,covering the dimensions of resource allocation,service efficiency,economic operation,risk prevention and control,development capacity,and social benefits.Empirical results indicated that the composite score of the sample hospital decreased from 71.5 in 2019 to 53.8 in 2020 and rebounded to 57.9 by 2023.Conclusions:The empirical outcomes align well with the operational capacity as understood by the operational management personnel of the sample hospital,demonstrating that the indicator system is scientifically sound and rational,possessing a high evaluative capability.