N⁶-methyladenosine (m⁶A) modification plays a critical role in cell cycle regulation, while the mechanism of m⁶A in regulating mitosis remains underexplored. Here, we found that the total m⁶A modification level in cells increased during mitosis by the liquid chromatography-mass spectrometry/mass spectrometry and m⁶A dot blot assays. Silencing methyltransferase-like 3 (METTL3) or METTL14 results in delayed mitosis, abnormal spindle assembly, and chromosome segregation defects by the immunofluorescence. By analyzing transcriptome-wide m⁶A targets in HeLa cells, we identified polo-like kinase 1 (PLK1) as a key gene modified by m⁶A in regulating mitosis. Specifically, through immunoblotting and RNA pulldown, m⁶A modification inhibits PLK1 translation via YTH N⁶-methyladenosine RNA binding protein 1, thus mediating cell cycle homeostasis. Demethylation of PLK1 mRNA leads to significant mitotic abnormalities. These findings highlight the critical role of m⁶A in regulating mitosis and the potential of m⁶A as a therapeutic target in proliferative diseases such as cancer.
Humans ; Polo-Like Kinase 1 ; Cell Cycle Proteins/metabolism* ; Proto-Oncogene Proteins/metabolism* ; Protein Serine-Threonine Kinases/metabolism* ; Mitosis/physiology* ; HeLa Cells ; Adenosine/genetics* ; Methyltransferases/metabolism* ; RNA, Messenger/metabolism* ; RNA-Binding Proteins/metabolism*

Objective:To investigate the alterations in brain functional activity before and after chemotherapy in breast cancer patients with chemotherapy-related cognitive impairment (CRCI) using resting-state functional magnetic resonance imaging (rs-fMRI) and their relations with cognitive impairment.Methods:A prospective observational study was performed; female breast cancer patients with CRCI admitted to Department of Oncology, Affiliated Hospital 6 of Nantong University were recruited, and age- and education level-matched female healthy controls were chosen. Before and one month after chemotherapy, statuses of cognitive function, depression and anxiety in breast cancer patients with CRCI were evaluated by Montreal cognitive assessment (MoCA), functional assessment of cancer therapy-cognitive function (FACT-cog), self-rating depression scale (SDS), and self-rating anxiety scale (SAS); subsequently, conventional MRI and resting-state functional magnetic resonance imaging (rs-fMRI) were conducted. The healthy controls accepted MoCA, SDS, and SAS, followed by conventional MRI and rs-fMRI. Differences in clinical data and amplitude of low-frequency fluctuation (ALFF, rs-fMRI brain spontaneous neural activity index) were compared between breast cancer patients with CRCI before chemotherapy and healthy controls, and in the breast cancer patients with CRCI between before and after chemotherapy. Taking the brain regions with significant differences in ALFF before and after chemotherapy in breast cancer patients with CRCI as seed points, the difference in whole-brain functional connectivity (FC) before and after chemotherapy was compared in breast cancer patients with CRCI. Pearson or Spearman correlation tests were used to analyze the correlations of ALFF and FC in brain regions with significant differences in ALFF with cognitive function scores in breast cancer patients with CRCI.Results:(1) A total of 22 breast cancer patients with CRCI and 22 healthy controls were enrolled. Compared with the healthy controls, the breast cancer patients with CRCI before chemotherapy had significantly higher SDS and SAS scores ( P<0.05). Compared with breast cancer patients with CRCI before chemotherapy, the breast cancer patients with CRCI after chemotherapy had significantly lower MoCA, FACT-cog-perceived cognitive impairment, FACT-cog-comment from others on cognitive function, and FACT-cog-perceived cognitive ability ( P<0.05). (2) Compared with those before chemotherapy, breast cancer patients with CRCI after chemotherapy exhibited significantly increased ALFF in the right precuneus, right middle occipital gyrus, and left superior frontal gyrus, while statistically decreased FC in the right middle occipital gyrus-left middle temporal gyrus, right precentral gyrus-right middle temporal gyrus, and left superior frontal gyrus-left fusiform gyrus ( P<0.05). (3) ALFF in the right precentral gyrus in breast cancer patients with CRCI after chemotherapy was negatively correlated with difference value of FACT-cog before and after chemotherapy ( r=-0.497, P=0.018) and difference value of PCA before and after chemotherapy ( r s=-0.436, P=0.042); FC in the left superior frontal gyrus-left fusiform gyrus was positively correlated with score of FACT-cog-perceived cognitive impairment ( r=0.621, P=0.002). Conclusion:Chemotherapy induces compensatory enhancement of spontaneous neural activity in multiple brain regions in breast cancer patients with CRCI, accompanied by FC disruption at specific brain areas, which are associated with cognitive impairment.

Objective: To analyze the consumption frequency of major foods among Chinese children aged 6-17 years old, and to provide a basis for optimizing the dietary structure of children in China. Methods: Using data from the China Nutrition and Health System Survey and Application Program for Children 0-18 years old, 56 734 children aged 6-17 years old from North, Norththeast East, Central, South, Southwest and Northwest seven regions in China were selected for the study using stratified cluster random sampling from 2019 to 2021. A food frequency questionnaire was used to investigate the intake frequency of eight food groups in a month, including fresh vegetables, fresh fruits, livestock and poultry meats, aquatic products, eggs, dairy products, legumes, and cereals and potatoes. The foods were grouped according to whether they met the recommended intake criteria outlined in the Dietary Guidelines for Chinese Residents 2022. The〖KG*2〗χ2 test was used to compare the differences in the proportion of childrens intake frequency of each food group meeting the standard in different regions and age groups. Results: The proportions of Chinese children aged 6-17 years who consumed fresh vegetables and cereals and potatoes ≥3 times/d were 12.1% and 67.2%, respectively. The proportions of children who consumed fresh fruits, livestock and poultry meats, eggs and dairy products ≥1 time/d were 50.8%, 58.8%, 36.0% and 54.3%, respectively. The proportion of legumes consumed ≥4 times/week was 37.4%, and the proportion of aquatic products consumed ≥2 times/week was 39.7%. Fresh vegetables (5.5%), fresh fruits (33.1%), and dairy products (36.4%) had the lowest frequency of meeting the recommended standards in South China, and aquatic products (27.4%) and eggs (21.1%) had the lowest frequency of meeting the recommended standards in Northwest (P<0.008 3). Conclusion The overall intake frequency of fresh vegetables, fresh fruits, legumes, and dairy products are insufficient among Chinese children, with significant regional variations.

Objective: To analyze the association of eating dining locations and their association with nutritional status among Chinese children aged 6-17 years,so as to provide reference for guiding children s reasonable diet. Methods: Stratified random cluster sampling was used to select children aged 6 to 17 years from 28 cities and rural areas of 14 provinces in East, North, Central, South, Southwest, Northwest, Northeast of China, and a total of 52 535 children were included in the study from 2019 to 2021. Information including dining locations, demographic characteristics, dietary intakes and physical activity were collected through a questionnaire survey. Fasting body height and weight were measured in the morning. Unordered multiclass Logistic regression analysis was conducted to assess the relationship between dining locations and nutritional status in children. Results: Regarding children s dining locations, 66.3% ate breakfast at home,25.8% ate breakfast at school,7.9% ate breakfast outside (small dining tables, restaurants, stalls, etc.); 67.7% ate dinner at home,29.0% ate dinner at school,3.3% ate dinner outside; and 63.6% ate lunch at school,30.8% ate lunch at home,5.7% ate lunch outside. The prevalence rates of overweight/obesity and undernutrition were 28.6% and 9.3%, respectively. The adjusted multiclass Logistic regression analysis (controlling for age, region, parental education, household income, total energy intake, and moderate-to-vigorous physical activity) demonstrated that, compared to eating at home, school based breakfast and dinner consumption was associated with significantly lower overweight/obesity risks for both genders (boys: breakfast OR =0.70, 95% CI =0.65-0.75; dinner OR =0.80, 95% CI = 0.74- 0.86; girls: breakfast OR = 0.89 , 95% CI = 0.82-0.96; dinner OR =0.88, 95% CI =0.81-0.95), whereas eating lunch away from home significantly increased overweight/obesity risks (boys: OR =1.32, 95% CI =1.17-1.48; girls: OR =1.43, 95% CI =1.26- 1.62 ), with all associations being statistically significant ( P <0.05). After adjusting for confounding factors, boys who ate breakfast away from home showed a significantly reduced risk of undernutrition ( OR =0.80,95% CI =0.66-0.97), while those consuming lunch away from home had an increased risk ( OR =1.26, 95% CI =1.01-1.57) ( P <0.05). Conclusions The choice of dining locations for children is becoming more diverse, and a relatively high proportion of children eat meals outside the home and at school. Eating out have a higher risk of malnutrition for children. School feeding may be beneficial to children s physical health.

Background and purpose:Intrathecal chemotherapy is one of the mainstay treatment options for leptomeningeal metastases(LM)from solid tumors.A previous phase Ⅰ study demonstrated the safety and potential efficacy of intrathecal anti-programmed death receptor 1(anti-PD-1)for LM from melanoma.The synergistic efficacy of systemic chemotherapy combined with anti-PD-1 has been widely known.This study aimed to evaluate the safety and feasibility of intrathecal chemotherapy(pemetrexed)and anti-PD-1(toripalimab)for LM patients from solid tumors.Methods:The subjects were patients with LM from solid tumors who were treated at Affiliated Huizhou Hospital of Guangzhou Medical University/Third People's Hospital of Huizhou City.A 3+3 dose de-escalation strategy was implemented to determine the recommended dose with an initial dose of PD-1 inhibitor(toripalimab)40 mg and pemetrexed 15 mg.Pemetrexed was administered twice weekly for the initial 2 weeks of induction therapy,once weekly for the subsequent 4 weeks of consolidation therapy,and once monthly during maintenance therapy.PD-1 inhibitor was initiated at the 4th administration of pemetrexed,administered every 2 weeks for 6 weeks;subsequently,responders continued monthly maintenance therapy alongside pemetrexed.The primary objective was to assess safety based on adverse events and the recommended dose.All participants were observed to investigate the clinical response rate(CRR),disease control rate(DCR)and overall survival(OS).This study was approved by the ethics committee of Affiliated Huizhou Hospital of Guangzhou Medical University/Third People's Hospital of Huizhou City(ethics number:2024-KY-029-01).Results:Seven patients(male:3,female:4,median age:57 years)were enrolled between June and September 2024,including non-small cell lung cancer(6)and breast cancer(1).All patients presented with positive cerebrospinal fluid(CSF)cytology.Six patients presented LM-related neurological dysfunction.Five patients showed LM-related neuroimaging findings.Six patients completed the induction and consolidation therapy,and subsequently received maintenance therapy.One patient,due to bacterial meningitis,did not complete the final administration of toripalimab during consolidation therapy,and maintenance therapy was administered after infection control.Adverse events rate was 100%(7/7),including myelosuppression(100.00%,n=7),elevation of hepatic aminotransferases(42.86%,n=3),fatigue(28.57%,n=2)and hypothyroidism(14.29%,n=1).Three(42.86%)patients had grade 3 adverse events(myelosuppression).The immune-related adverse event(irAE)rate was 14.29%,manifested as hypothyroidism(Grade 2).No dose-limiting toxicity(DLT)was observed.Thus,no de-escalation was applied.The recommended dose was determined to be PD-1 inhibitor 40 mg in combination with pemetrexed 15 mg.Three patients showed improved neurological dysfunction,1 with CSF cytological response,and 2 with neuroimaging improvement.CRR was 57.14%(4/7)by response assessment in neuro-oncology(RANO)proposal criteria.DCR was 100%(7/7).Three patients exhibited abscopal effects with regression of brain metastasis lesions,primary lung lesion and mediastinal lymph nodes,respectively.As of April 10,2025,1 patient died.The median follow-up time was 7.7(5.9-9.3)months.The median OS was not reached with a 6-month OS rate of 85.71%.Conclusion:The combination therapy of intrathecal pemetrexed and a PD-1 inhibitor was well-tolerated and feasible,while also exhibiting potential clinical efficacy in treating LM from solid tumors including non-small cell lung cancer.

Objective: To understand the prevalence of elevated blood pressure and its association with dietary patterns in children and adolescents in China, providing evidence for developing dietary intervention of hypertension in children and adolescents. Methods: Data were derived from the China Children s Nutrition and Health System Survey and Application Project(2019-2021). A stratified cluster random sampling method was used to include 7 933 participants from 28 survey sites in seven major regions of Northeast, North, Northwest, East, Central, South and Southwest China. Multivariate Logistic regression models were used to analyze associations between demographic characteristics, nutritional status and elevated blood pressure. Exploratory factor analysis identified dietary patterns, which were divided into three quartile groups (T3, T2, T1) based on factor scores (compliance for dietary pattern) from high to low, and multivariate Logistic regression model assessed the correlation between elevated blood pressure and dietary patterns. Results: The prevalence of elevated blood pressure was 15.4% among Chinese children aged 7-17 years. Significant differences were observed across nutritional status (reference: underweight; normal weight: OR =1.57; overweight: OR = 2.61 ; obesity: OR =3.85), urban/rural residence (reference: rural; urban: OR =0.86), and paternal education (reference: junior high school and below; bachelor degree or above: OR =0.68) ( P <0.05). The detection rates of high blood pressure in T3 group children and adolescents with four dietary patterns (staple food, animal based food, snacks, vegetables and fruits) were 15.7%, 14.6%, 16.8%, and 15.8%, respectively. After adjusting for residence, paternal education, and nutritional status, the "snack dietary pattern" (mainly candy, sugar sweetened beverages, and processed snacks) showed positive associations with elevated blood pressure in T2 ( OR =1.21) and T3 ( OR =1.19) tertiles ( P <0.05). Conclusions The snack dietary pattern is a related factor for elevated blood pressure in children and adolescents. Restricting unhealthy snack intake may promote cardiovascular health.

Objective To systematically review the quality of pediatric off-label medication guidelines and consensus,compare the differences among guidelines and consensus,and to provide recommendations for clinical application.Method Searching the guidelines and literature databases and websites such as TRIP,GIN,NICE,PubMed,CNKI,WanFang Data,MedLink,to collect off-label drug use guidelines or consensus.The AGREE Ⅱ was used to evaluate the methodological quality of the included guidelines or consensus,and the differences among the recommendations of guidelines and consensus were analyzed and compared.The differences in scores between guidelines and consensus and international and domestic guidelines and consensus were compared in each domain.Results A total of 7 papers were included,comprising 3 guidelines and 4 consensuses,1 from Austria and 6 from China.The AGREE Ⅱ results showed that the scores of 2 domains,"Scope and Purpose"and"Stakeholder Involvement",were above 60％.There were significant differences in scores in the remaining four domains(Rigour of Development,Clarity of Presentation,Applicability,and Editorial Independence).There were differences in the insufficient items of the guidelines and consensus.The"Scope and Purpose"of the guidelines scored significantly higher than the consensus.In addition,the grading of evidence and grading of recommendations of the guidelines and consensus were different,including GRADE,Micromedex,Oxford Centre for Evidence-based Medicine standards,and custom methods.According to the AGREE Ⅱ,among the 7 guidelines and consensus,3 were recommended,3 were recommended after modification,and 1 was not recommended.Conclusion There are relatively few existing pediatric guidelines and consensus on off-label medication.At present,there are differences in the quality of guidelines and consensus,with inconsistent standards for evidence quality and recommendation strength.

Objective:To investigate the alterations in brain functional activity before and after chemotherapy in breast cancer patients with chemotherapy-related cognitive impairment (CRCI) using resting-state functional magnetic resonance imaging (rs-fMRI) and their relations with cognitive impairment.Methods:A prospective observational study was performed; female breast cancer patients with CRCI admitted to Department of Oncology, Affiliated Hospital 6 of Nantong University were recruited, and age- and education level-matched female healthy controls were chosen. Before and one month after chemotherapy, statuses of cognitive function, depression and anxiety in breast cancer patients with CRCI were evaluated by Montreal cognitive assessment (MoCA), functional assessment of cancer therapy-cognitive function (FACT-cog), self-rating depression scale (SDS), and self-rating anxiety scale (SAS); subsequently, conventional MRI and resting-state functional magnetic resonance imaging (rs-fMRI) were conducted. The healthy controls accepted MoCA, SDS, and SAS, followed by conventional MRI and rs-fMRI. Differences in clinical data and amplitude of low-frequency fluctuation (ALFF, rs-fMRI brain spontaneous neural activity index) were compared between breast cancer patients with CRCI before chemotherapy and healthy controls, and in the breast cancer patients with CRCI between before and after chemotherapy. Taking the brain regions with significant differences in ALFF before and after chemotherapy in breast cancer patients with CRCI as seed points, the difference in whole-brain functional connectivity (FC) before and after chemotherapy was compared in breast cancer patients with CRCI. Pearson or Spearman correlation tests were used to analyze the correlations of ALFF and FC in brain regions with significant differences in ALFF with cognitive function scores in breast cancer patients with CRCI.Results:(1) A total of 22 breast cancer patients with CRCI and 22 healthy controls were enrolled. Compared with the healthy controls, the breast cancer patients with CRCI before chemotherapy had significantly higher SDS and SAS scores ( P<0.05). Compared with breast cancer patients with CRCI before chemotherapy, the breast cancer patients with CRCI after chemotherapy had significantly lower MoCA, FACT-cog-perceived cognitive impairment, FACT-cog-comment from others on cognitive function, and FACT-cog-perceived cognitive ability ( P<0.05). (2) Compared with those before chemotherapy, breast cancer patients with CRCI after chemotherapy exhibited significantly increased ALFF in the right precuneus, right middle occipital gyrus, and left superior frontal gyrus, while statistically decreased FC in the right middle occipital gyrus-left middle temporal gyrus, right precentral gyrus-right middle temporal gyrus, and left superior frontal gyrus-left fusiform gyrus ( P<0.05). (3) ALFF in the right precentral gyrus in breast cancer patients with CRCI after chemotherapy was negatively correlated with difference value of FACT-cog before and after chemotherapy ( r=-0.497, P=0.018) and difference value of PCA before and after chemotherapy ( r s=-0.436, P=0.042); FC in the left superior frontal gyrus-left fusiform gyrus was positively correlated with score of FACT-cog-perceived cognitive impairment ( r=0.621, P=0.002). Conclusion:Chemotherapy induces compensatory enhancement of spontaneous neural activity in multiple brain regions in breast cancer patients with CRCI, accompanied by FC disruption at specific brain areas, which are associated with cognitive impairment.

Objective:To investigate the influencing factors for safe abdominal wall recons-truction in giant ventral hernia based on imaging and clinical features.Methods:The retrospective case-control study was conducted. The imaging and clinical data of 369 patients with giant ventral hernia who were admitted to Beijing Chaoyang Hospital of Capital Medical University from January 2017 to December 2023 were collected. There were 182 males and 187 females, aged (63±14)years. Among 369 patients, 311 cases underwent safe abdominal wall reconstruction and 58 underwent high-risk abdominal wall reconstruction. Observation indicators: (1) clinical and imaging characteris-tics; (2) analysis of influencing factors for safe abdominal wall reconstruction in giant ventral hernia. Comparison of measurement data with normal distribution between groups was conducted using the t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the nonparametic rank sum test. Logistic regression, Lasso regression, and random forest analyses were used for influencing factors analysis. Results:(1) Clinical and imaging characteristics. There were significant differences between patients with safe and high-risk abdominal wall reconstruction in presence of a definite secondary abdominal cavity, maximum axial diameter of the defect, maximum transverse diameter of the defect, abdominal wall defect area, component separation index (CSI), abdominal wall opening angle, ratio of CSI, muscle grayscale at the defect, hernia sac volume, hernia sac-abdominal cavity volume ratio, and defect long-axis-to-abdominal cavity ratio ( P<0.05). (2) Analysis of influencing factors for safe abdominal wall reconstruction in giant ventral hernia. Results of Logistic regression analysis showed that presence of a definite secondary abdominal cavity, maximum axial diameter of the defect, maximum transverse diameter of the defect, abdominal wall defect area, CSI, abdominal wall opening angle, ratio of CSI, muscle grayscale at the defect (inner-superior or right), hernia sac volume, hernia sac-abdominal cavity volume ratio, and defect long-axis-to-abdominal cavity ratio were factors associated with safe abdominal wall reconstruction in giant ventral hernia [ odds ratio ( OR)=3.955, 1.189, 1.395, 1.127, 2.006, 1.042, 1.095, 0.881, 1.102, 1.109, 1.601, 95% confidence interval ( CI) as 2.179-7.178, 1.113-1.271, 1.267-1.537, 1.090-1.166, 1.651-2.437, 1.014-1.071, 1.066-1.125, 0.798-0.972, 1.057-1.148, 1.067-1.153, 1.343-1.909]. The top 3 factors for discriminative performance were abdominal wall CSI, ratio of CSI, maximum transverse diameter of the defect and the abdominal wall defect area, with area under the curve of 0.794, 0.777, 0.772, and 0.772, respectively. Results of Lasso regression analysis showed that body mass index, smoking, chronic obstructive pulmonary disease, American Society of Anesthesiologists classification, presence of a definite secondary abdominal cavity, abdominal wall defect area, abdominal wall opening angle, abdominal wall CSI, muscle grayscale at the defect (inner-superior or right), and hernia sac-to-abdominal cavity volume ratio were associated factors with safe abdominal wall reconstruction in giant ventral hernia (coefficients as -0.002, 0.003, 0.007, 0.014, 0.021, 0.077, 0.023, 0.059, -0.010, 0.037). Results of random forest analysis showed the abdominal wall CSI, maximum transverse diameter of the defect, abdominal wall defect area, ratio of defectr opening angle, maximum axial long diameter of the defect, hernia sac-to-abdominal cavity volume ratio, abdominal wall opening angle, defect long-axis-to-abdominal cavity ratio, muscle grayscale at the defect (inner-superior or right), and body mass index as associated factors with safe abdominal wall reconstruction in giant ventral hernia (importance score=0.092, 0.089, 0.079, 0.056, 0.051, 0.047, 0.045, 0.039, 0.038, 0.035). Conclusion:Abdominal wall CSI, abdominal wall defect area, abdominal wall opening angle, muscle grayscale at the defect (inner-superior or right), and hernia sac-to-abdominal cavity volume ratio are factors associated with safe abdominal wall reconstruction in giant ventral hernia.

Background and purpose:Intrathecal chemotherapy is one of the mainstay treatment options for leptomeningeal metastases(LM)from solid tumors.A previous phase Ⅰ study demonstrated the safety and potential efficacy of intrathecal anti-programmed death receptor 1(anti-PD-1)for LM from melanoma.The synergistic efficacy of systemic chemotherapy combined with anti-PD-1 has been widely known.This study aimed to evaluate the safety and feasibility of intrathecal chemotherapy(pemetrexed)and anti-PD-1(toripalimab)for LM patients from solid tumors.Methods:The subjects were patients with LM from solid tumors who were treated at Affiliated Huizhou Hospital of Guangzhou Medical University/Third People's Hospital of Huizhou City.A 3+3 dose de-escalation strategy was implemented to determine the recommended dose with an initial dose of PD-1 inhibitor(toripalimab)40 mg and pemetrexed 15 mg.Pemetrexed was administered twice weekly for the initial 2 weeks of induction therapy,once weekly for the subsequent 4 weeks of consolidation therapy,and once monthly during maintenance therapy.PD-1 inhibitor was initiated at the 4th administration of pemetrexed,administered every 2 weeks for 6 weeks;subsequently,responders continued monthly maintenance therapy alongside pemetrexed.The primary objective was to assess safety based on adverse events and the recommended dose.All participants were observed to investigate the clinical response rate(CRR),disease control rate(DCR)and overall survival(OS).This study was approved by the ethics committee of Affiliated Huizhou Hospital of Guangzhou Medical University/Third People's Hospital of Huizhou City(ethics number:2024-KY-029-01).Results:Seven patients(male:3,female:4,median age:57 years)were enrolled between June and September 2024,including non-small cell lung cancer(6)and breast cancer(1).All patients presented with positive cerebrospinal fluid(CSF)cytology.Six patients presented LM-related neurological dysfunction.Five patients showed LM-related neuroimaging findings.Six patients completed the induction and consolidation therapy,and subsequently received maintenance therapy.One patient,due to bacterial meningitis,did not complete the final administration of toripalimab during consolidation therapy,and maintenance therapy was administered after infection control.Adverse events rate was 100%(7/7),including myelosuppression(100.00%,n=7),elevation of hepatic aminotransferases(42.86%,n=3),fatigue(28.57%,n=2)and hypothyroidism(14.29%,n=1).Three(42.86%)patients had grade 3 adverse events(myelosuppression).The immune-related adverse event(irAE)rate was 14.29%,manifested as hypothyroidism(Grade 2).No dose-limiting toxicity(DLT)was observed.Thus,no de-escalation was applied.The recommended dose was determined to be PD-1 inhibitor 40 mg in combination with pemetrexed 15 mg.Three patients showed improved neurological dysfunction,1 with CSF cytological response,and 2 with neuroimaging improvement.CRR was 57.14%(4/7)by response assessment in neuro-oncology(RANO)proposal criteria.DCR was 100%(7/7).Three patients exhibited abscopal effects with regression of brain metastasis lesions,primary lung lesion and mediastinal lymph nodes,respectively.As of April 10,2025,1 patient died.The median follow-up time was 7.7(5.9-9.3)months.The median OS was not reached with a 6-month OS rate of 85.71%.Conclusion:The combination therapy of intrathecal pemetrexed and a PD-1 inhibitor was well-tolerated and feasible,while also exhibiting potential clinical efficacy in treating LM from solid tumors including non-small cell lung cancer.