BACKGROUND: The incidence of leptomeningeal metastasis (LM) in patients with advanced non-small cell lung cancer (NSCLC) is increasing gradually. However, it poses therapeutic challenges due to limited effective interventions. Intrathecal Pemetrexed (IP) holds broad application prospects in the therapeutic domain of LM. This study aims to evaluate the efficacy, safety, and optimal combination strategies of IP in NSCLC-LM patients with epidermal growth factor receptor (EGFR) mutation-positive status, with the aim of providing real-world data support for exploring more precise personalized treatment strategies for these patients. METHODS: 104 EGFR-mutated NSCLC-LM patients who received IP treatment at Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School from January 2018 to June 2024 were analyzed retrospectively. Clinical parameters, treatment regimens, and survival outcomes were collected. The overall survival (OS), progression-free survival (PFS), clinical response rate and adverse events (AEs) were evaluated. RESULTS: The cohort demonstrated a median PFS of 9.6 months and OS of 13.0 months with 6-month and 1-year OS rates of 80.8% and 56.5%, respectively. Clinical response was observed in 77.9% of patients. The common AEs were myelosuppression (58.7%) and elevation of hepatic aminotransferases (25.0%). Nine (8.7%) patients experienced grade 4 myelosuppression and recovered to normal after receiving symptomatic treatment. Subgroup analyses revealed prolonged OS in patients with Karnofsky performance status (KPS) ≥60 versus <60 (14.4 vs 9.0 months, P=0.0022) and those receiving Bevacizumab therapy versus not (19.2 vs 10.5 months, P=0.0011). CONCLUSIONS IP exhibits promising efficacy and manageable toxicity in EGFR-mutated NSCLC-LM patients. When combined with Bevacizumab, it exerts synergistic antitumor effects with the potential to further improve clinical outcomes.
Humans ; Pemetrexed/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Male ; Female ; Middle Aged ; Lung Neoplasms/pathology* ; ErbB Receptors/genetics* ; Aged ; Mutation ; Adult ; Retrospective Studies ; Injections, Spinal ; Meningeal Neoplasms/genetics* ; Treatment Outcome ; Aged, 80 and over

Objective: To investigate the attention cognitive function and symptom correlations of school aged children with attention deficit hyperactivity disorder (ADHD)using event related potential (ERP) technology, so as to provide references for the early diagnosis of children with ADHD. Methods: A total of 52 school aged children diagnosed with ADHD at the outpatient department of the Third Affiliated Hospital of Zhengzhou University from September 2022 to September 2024 and 50 age /sex matched healthy controls were selected. The ERP experiment adopted the auditory Oddball task to conduct comparative analyses of the amplitude and latency of the mismatch negative(MMN) at the Fz, Cz, and Pz points of the scalp electrode and the P3a component respectively. The symptom assessment scales adopted the Swanson,Nolan,and Pelham-Ⅳ Rating Scale (SNAP-Ⅳ) and the Parent Symptom Questionnaire (PSQ), which were filled out by the parents. Spearman correlation analysis was used to analyze the correlation between ERP components and symptoms in schoolaged children with ADHD. Results: The latency of MMN components in the healthy control group on the Fz lead was (188.30±2.06)ms, and the amplitude was (-15.54±1.35)μV; the latency of the P3a component on the Pz lead was (312.82±7.80)ms, and the amplitude was (3.80±0.18)μV. The latency of MMN components in the ADHD group on the Fz lead was (188.94±1.39)ms, and the amplitude was (-14.78±1.40)μV; the latency of the P3a component on the Pz lead was (317.21±5.65)ms, and the amplitude was (3.70±0.13)μV. Compared with normal children, the MMN of children with ADHD had smaller amplitudes in the Fz and Cz leads, and the P3a had greater latency and smaller amplitudes in the Cz and Pz leads ( t =2.79,2.20；-2.04，-3.25；2.35,3.21， P <0.05). Correlation analysis showed that the latency of MMN in children with ADHD was positively correlated with the inattention score in the SNAP-Ⅳ( r =0.22), and the amplitude of MMN was negatively correlated with the inattention score in the SNAP-Ⅳ and the learning problem score in PSQ ( r = -0.26 , -0.34)( P <0.05). The latency of P3a was positively correlated with the scores of inattention in the SNAP-Ⅳ and the score of learning problems in the PSQ ( r =0.26 ,0.24); the amplitude of P3a was negatively correlated with the scores of attention deficit and hyperactivity/impulsivity in the SNAP-Ⅳ and the scores of learning problems and impulsivity/hyperactivity in the PSQ( r = -0.26 , -0.22, -0.25,-0.32)( P <0.05). Conclusions School aged ADHD children exhibit abnormal MMN/P3a components, indicating attention related cognitive dysfunction. Symptoms such as inattention, learning problems and hyperactivity/impulsivity in children with ADHD are related to abnormal components of MMN and P3a.

Objective: To explore the association between CDKAL1 rs35261542, FAIM2 rs 3205718, and VGLL4 rs 2574704 polymorphisms with childhood obesity and related metabolic phenotypes to provide evidence for personalized prevention and management strategies. Methods: Based on the 2023 Long term Nutritional Health Effects of Early Childhood Nutrition Package Intervention project, the study enrolled 1 078 children aged 5-7 years from four counties in Henan (Songxian and Ruyang countries) and Guizhou (Guiding and Fuquan countries) provinces. Using BMI Z scores, 87 overweight and obese(OVOB) children were selected and matched by sex, age, and BMI Z score with 117 normal weight controls. Participants were further stratified into four metabolic phenotype groups: metabolically healthy normal weight (MHNW, n =51), metabolically unhealthy normal weight (MUNW, n =66), metabolically healthy obesity (MHO, n =31) and metabolically unhealthy obesity (MUO, n =56) based on four conventional cardiometabolic risk factor (CR) criteria. Data were collected through questionnaires, anthropometric measurements, serum biochemical tests, and KASP genotyping. The distribution of three genetic polymorphisms ( CDKAL1 rs35261542, FAIM2 rs3205718, VGLL4 rs 2574704) across metabolic subgroups was analyzed. Multivariate Logistic regression models assessed associations between these polymorphisms and obesity/metabolic phenotypes. Results: Multivariate Logistic regression analysis showed that Homozygous mutant AA genotype of CDKAL1 rs 35261542 was positively associated with OVOB( OR =3.63), MHO ( OR =11.04), MUO ( OR = 4.88 ) ( P <0.05). Homozygous TT genotype of FAIM2 rs 3205718 increased OVOB risk ( OR =4.44, P <0.05) but showed no association with metabolic phenotypes ( P >0.05). Homozygous mutant TT of VGLL4 rs 2574704 reduced the risks of MHO and MUO ( OR = 0.30, 0.24， P <0.05). Cumulative genetic effects analysis demonstrated carriers of 1 or 2 risk genotypes of rs 35261542 and rs 3205718 had progressively higher OVOB risk ( OR =2.53, 20.79), and the combination of rs 35261542 and rs 2574704 increased risks for both MHO ( OR =8.50) and MUO ( OR =5.00) ( P <0.05). Conclusions The AA genotype of rs 35261542 ( CDKAL1 ) positively correlates with childhood obesity and metabolic abnormalities. The TT genotype of rs 3205718 ( FAIM 2) increases obesity risk but not metabolic phenotypes. The TT genotype of rs 2574704 ( VGLL 4) shows protective effects against metabolic dysfunction. Risk genotypes exhibit dosedependent cumulative effects on obesity and metabolic outcomes.

Background Occupational disease diagnosis appraisal is an appeal procedure initiated when a party disagrees with the occupational disease diagnosis conclusion. It is a legal procedure to safeguard the health rights of employees and the legitimate rights and interests of employers. Objective To analyze the data of occupational disease diagnosis appraisal in Shanghai, identify existing problems, and provide suggestions for improving. Methods Statistical analysis was conducted on basic situation, characteristics of workers and employers, disease classification, and consistency between diagnosis and appraisal conclusions of all occupational disease diagnosis appraisal cases from 2012 to 2024. All diagnosis conclusions were named in accordance with the Classified Catalogue of Occupational Diseases included employers were classified according to the Measures for the Statistical Classification of Large, Medium, Small and Micro Enterprises" and the Notice on Adjusting the Provisions for Classifying Enterprise Registration Types; industry classification followed the Industrial Classification for National Economic Activities (GB/T 4754-2017). Results From 2012 to 2024, a total of 260 cases of occupational diseases diagnosis appraisal were closed. The main diagnosis were 138 cases of ear, nose, throat, and oral diseases (53.1%), chemical poisoning (18.8%), and pneumoconiosis and other respiratory diseases (16.2%). The proportion of ear, nose, throat, and oral diseases gradually increased (2022 excluded). The incidence of annual municipal and provincial cases decreased by 76.3% and 85.0% respectively (2024 vs 2012). The consistency rate of conclusions between appraisal and diagnosis gradually increased. The total consistency rates between final appraisals and diagnostic conclusions were 81.5%, and 79.7%, 87.8%, 100.0%, 85.0% for ear, nose, throat, and oral diseases, chemical poisoning, and pneumoconiosis and other respiratory system diseases, respectively. Specifically, the consistency rates were 80.1% and 80.0% for noise-induced deafness and chronic benzene poisoning. In terms of inconsistency reasons, "inconsistent interpretation of standards and excessive discretion in standard application" accounted for 43.8%, followed by "failure to correctly apply standards" (31.3%) and and "discrepancies in occupational exposure history recognition" (15.6%). Conclusion The revisions and improvements of the legal system for occupational disease diagnosis appraisal have played a positive role in improving the consistency of conclusions between appraisal and diagnosis of occupational diseases in Shanghai. It is suggested to further strengthening the publicity and training of occupational disease diagnosis standards to improve the quality of occupational disease diagnosis.

Objective To evaluate the overall implementation of the WS 76-2020 standard in Anhui Province, China and identify and analyze the factors affecting the implementation of the standard, and to provide a basis for the effective implementation and revision of WS 76-2020. Methods According to the requirements of the Notice of the Department of Regulations in National Health Commission on the 2024 assessment of implementation of mandatory standards, an evaluation of radiological health standards was organized and conducted in Anhui Province. The evaluation involved the three dimensions of standard implementation status, technical content of the standards, and effectiveness of standard implementation, with subsequent data analysis. Results The total evaluation score for WS 76-2020 was 87.83 points, indicating that the standard effectively guided the quality control testing of medical X-ray diagnostic equipment. However, stability testing was either underutilized or not performed in practice. The qualified rate of X-ray diagnostic equipment in the province was 94.26%, with equipment performance issues identified as the leading contributor to non-qualified instances. Expert discussions highlighted recommendations particularly concerning the operability, applicability, and scientific rigor of the standard. Conclusion It is recommended to strengthen the dissemination and training for the standard, promote medical institutions to voluntarily conduct stability testing, provide supplementary clarifications or revisions for problematic clauses, and standardize quality control testing techniques for radiological diagnostic equipment.

Objective:To explore and compare the clinical application value of 8-channel head phased-array coil, an 8-channel temporomandibular joint (TMJ)-specific surface coil, and a single-channel surface coil in TMJ MRI examinations.Methods:A total of 600 temporomandibular disorders (TMD) patients (1 200 joints) who underwent TMJ MRI examination in the First People′s Hospital of Jinzhong from June 2020 to January 2025 were retrospectively screened. Based on inclusion/exclusion criteria, 120 TMD patients (240 joints) with closed-mouth oblique sagittal proton density weighted imaging (OSag PDWI), coronal T2 fat-suppression weighted imaging (OCor fs T2WI) and open-mouth oblique sagittal proton density weighted imaging (OSag PDWI) were included. Patients were divided into groups A, B, and C, with 40 cases in each group. Group A (31female, 9male, median age 24 years old), underwent 8-channel head phased-array coil imaging. Group B (29 female, 11male, median age 23.5 years old) underwent TMJ imaging with an 8-channel surface coil. Group C (29 female, 11male, median age 22.5 years old) underwent single-channel surface coil imaging. There were no significant differences in age, gender, type or disease types among groups ( P>0.05). Six healthy volunteers without TMD (4 female, 2 male, range 19 to 45 years old) underwent imaging with all three coils as self-control. The signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and image quality were compared for five regions of interest (ROI) in both patients and volunteers. Results:Under the same sequence and the same parameters, SNR and CNR in group B were higher than those in group A, and SNR and CNR in group C were also higher than those in group A, the differences were statistically significant ( P<0.05). However, there were significant differences in SNR and CNR between group B and group C in the closed and open positions of ROI1, the open positions of ROI3 and the open positions of ROI5 ( P<0.05), and there were no significant differences in other positions ( P>0.05). Group B had the best image quality, followed by group C and group A had the worst image quality. There were significant differences in the visualization of OSag PDWI in the closed mouth position, OCor T2WI in the coronal position, and OSag PDWI in the open mouth position, such as condyle, anterior attachment, joint disc, double lamina area, joint cavity and lateral pterygoid muscle ( P<0.05). There were significant differences between group B and group C in showing the joint cavity in the closed mouth position and showing the structure of the bilaminar area in the open mouth position ( P<0.05). There was no significant difference in other regions of interest ( P>0.05). The subjective scores of condyle, anterior attachment, articular disc, bilaminar area, articular cavity, lateral pterygos muscle and other structures were medium to high in group A, high in group B, and high or high in group C by two radiologists independently. In the five rois, the 8-channel TMJ surface coil showed more details, especially in the articular disc, condyle and lateral pterygoid muscle regions, and had more advantages in both volunteers and patients. Conclusions:The 8-channel TMJ-specific surface coil provides significantly clearer visualization of critical anatomical details within the ROIs, demonstrating the highest clinical application value and is recommended as the preferred choice.

Objective To analyze the predictive value of CT cerebral perfusion(CTP)combined with CT angiography(CTA)for the prognosis of patients with large atherosclerotic cerebral infarction.Methods A retrospective study was performed in 98 patients with large atherosclerotic cerebral infarction who were admitted to Haian People's Hospital from January 2021 to November 2024.There were 63 males and 56 females with a mean age of(57.26±5.03)years.The mean time from onset to admission was(4.89±0.69)h.There were 20 patients with a history of smoking.After admission,CTP and CTA were performed to evaluate relative cerebral blood volume(rCBV),relative cerebral blood flow(rCBF),relative mean transit time(rMTT),relative time to peak(rTTP),and CTA score.The prognosis was evaluated according to the modified Rankin scale(mRS)3 months after intravenous thrombolysis.Then the patients were assigned to good prognosis group(0-2 points)or poor prognosis group(3-6 points).The basic data and the parameters of CTP and CTA were compared between the two groups.The receiver operating characteristic(ROC)curve was used to analyze the CTP-and CTA-related influencing factors of poor prognosis in patients with large atherosclerotic cerebral infarction.Results During 3-month follow-up,poor prognosis was found in 30 patients(25.21%).The rCBV,rCBF and CTA scores of the poor prognosis group were significantly lower than those of the good prognosis group,while the National Institutes of Health stroke scale(NIHSS)score,rMTT and rTTP at admission in the good prognosis group were significantly higher than those in the good prognosis group(P<0.05).Logistic regression equation analysis(introduction level 0.05,exclusion level 0.10)showed that NIHSS score(OR=1.622,95%CI:1.258 to 2.093),rMTT level(OR=10.757,95%CI:2.847 to 40.640)and rTTP level(OR=14.774,95%CI:3.280 to 66.558)at admission were risk factors for poor prognosis in patients with large atherosclerotic cerebral infarction(P<0.05),while CTA score(OR=0.315,95%CI:0.163 to 0.608),rCBF level(OR=0.008,95%CI:0.001 to 0.109),and rCBV level(OR=0.016,95%CI:0.002 to 0.155)were protective factors for poor prognosis in these patients(P<0.05).ROC curve analysis showed that the sensitivities of CTA score,rCBF,rCBV,rMTT,and rTTP in predicting poor prognosis in patients with large atherosclerotic cerebral infarction were 79.2%,75.0%,70.8%,58.3%,and 83.3%,respectively;the specificities were 62.2%,64.9%,70.3%,72.0%,and 70.3%,respectively;their combination had a relatively high predictive value for poor prognosis(area under the curve was 0.863).Conclusion The combination of CTP and CTA has a relatively high value in predicting the prognosis of patients with large atherosclerotic cerebral infarction.

Atherosclerosis is a chronic inflammatory disease that occurs in walls of blood vessels and is common pathological basis of cardiovascular diseases.A variety of immune cells and inflammatory factors are involved in occurrence and development of atherosclerosis.Neutrophils and granular proteins are closely related to occurrence and development of atherosclerosis and formation of thrombus.Neutrophils play an important role in occurrence and development of atherosclerosis by releasing granular protein and neutrophil extracellular trapping net.Neutrophils and their released active molecules can be used as new targets for treatment of athero-sclerosis and other cardiovascular diseases.

The mechanism of action of traditional Chinese medicine (TCM) remains unclear. Historically, research on TCM has mainly focused on exploring the mechanisms of active components acting on single targets. However, it is insufficient to explain the complex mechanisms by which these active components in TCM treat diseases. In recent years, the emergence of molecular glues (MGs) theory has provided new strategies to address this issue. MGs are small molecules that can promote interactions between proteins at their interface. The characteristic of MGs is to establish connections between diverse protein structures, thereby enabling a chemically-mediated proximity effect that triggers a wide spectrum of biological functions. Natural products are the result of billions of years of evolutionary processes in the natural environment. Thus, the extensive structural diversity of natural products renders them a rich source of MGs, including polyketides, terpenoids, steroids, lignans, organic acids, alkaloids and other classes. Currently, several well-known natural MGs, including the immunosuppressants cyclosporin A (CsA) and tacrolimus (FK506), as well as the anticancer agent taxol, have been incorporated into clinical practice. Meanwhile, the advancement of new technologies is propelling the discovery of novel MGs from natural products. Thus, we primarily summarize a growing variety of MGs from natural origins reported in recent years and categorize them based on the chemical structural types. Moreover, the main sources of TCM are natural products. The discovery of natural MGs promises to provide a new perspective for the elucidation of the molecular mechanism behind the efficiency of TCM. In summary, this review aims to provide insights from the perspective of natural products that could potentially influence TCM and modern drug development.

Image 1.