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 clinical, imaging and neuropathological characteristics of neuronal intranuclear inclusion disease (NIID) with symptoms of the central nervous system, and to improve the diagnosis and treatments of NIID.Methods:The clinical data of 7 patients with NIID diagnosed by brain biopsy in Xuanwu Hospital, Capital Medical University, Beijing, China from February 2009 to December 2024 were collected. The characteristics of clinical manifestations, imaging, and histology on brain biopsy were retrospectively analyzed.Results:Among the 7 patients, 5 were male and 2 were female. Their ages ranged from 44 to 70 years, median 56 (52, 65) years. Patients were classified into three types of tumor, stroke and encephalitis according to the onset symptoms, imaging manifestations and pathological changes. The chief complaint of the 5 patients was headache, while 4 patients had paroxysmal convulsions, 3 had speech disorders, 2 had abnormal mental behaviors, 2 had memory decline, and 1 had fever accompanied by consciousness disorders. Diffusion-weighted magnetic resonance imaging of the head showed the "ribbon sign" at the junction of the cortex and medulla in 2 cases. Most of the patients had white matter lesions, gyrus swelling and cerebral atrophy. Occasionally gyrus-like enhancement was observed. Brain biopsy reveals the histological changes that matched those on images and initial symptoms. There were proliferation of oligodendrocytes and astrocytes in the white matter, leukoaraiosis and edema, cortical disintegration and lamellar necrosis, as well as infiltration of lymphocytes and microglia, etc. However, the characteristic changes were eosinophilic hyaline inclusions in the nuclei of neurons and astrocytes. Immunohistochemical staining of p62 and ubiquitin showed homogeneous staining in round or ring-shaped nuclei.Conclusions:The clinical manifestations of NIID are highly variable, and a correct diagnosis of NIID requires careful integration of clinical, imaging and histopathologic data. For patients with a high suspicion of NIID, immunohistochemical staining of p62 and ubiquitin is diagnostically valuable.

Objective To investigate the relationships of serum levels of Xenin-25 and activin A with pregnancy outcomes in patients with gestational diabetes mellitus(GDM).Methods A total of 269 pregnant women with GDM admitted to our hospital between December 2020 and February 2023 were enrolled.Serum levels of Xenin-25 and activin A were measured,and pregnancy outcomes were recorded.Based on pregnancy outcomes,patients were divided into poor pregnancy outcome group(91 cases)and good pregnancy outcome group(178 cases).The influencing factors of adverse preg-nancy outcomes of GDM patients and the predictive value of Xenin-25 and activin A for GDM preg-nancy outcomes were analyzed.Results The poor pregnancy outcome group had higher age,pre-pregnancy body mass index(BMI),proportion of adverse obstetric history,as well as levels of fasting plasma glucose(FPG),glycated hemoglobin(HbA1c),and activin A compared to the good preg-nancy outcome group,and serum level of Xenin-25 was lower in the poor pregnancy outcome group(P＜0.05).High HbA1c and high activin A levels were identified as risk factors for pregnancy out-comes in GDM patients,while high Xenin-25 was a protective factor for pregnancy outcomes(P＜0.05).The areas under the curve(AUCs)for predicting adverse pregnancy outcomes in GDM pa-tients using Xenin-25 and activin A were 0.895 and 0.865,respectively,while the AUC for com-bined prediction was 0.981,which was higher than that of Xenin-25 or activin A alone(P＜0.05).Conclusion Xenin-25 and activin A in GDM patients are associated with adverse pregnancy outcomes and can serve as biomarkers for predicting pregnancy outcomes.

Objective To investigate the relationship between serum G protein-coupled estrogen receptor 1(GPER1),complement factor H(CFH)levels and pregnancy outcomes in patients with gestational diabetes mellitus(GDM).Methods A total of 120 patients with GDM(GDM group)and 60 healthy pregnant women(control group)were included in this study.According to the pregnancy outcome,GDM patients were divided into the adverse pregnancy outcome(APO)group(50 cases)and the non-APO group(70 cases).The basic data of GDM patients were collected.Fasting blood glucose,fasting insulin and blood lipids were measured,and homeostasis model assessment of insulin resistance index(HOMA-IR)was calculated.The serum levels of GPER1 and CFH were detected by enzyme-linked immunosorbent assay.Pearson correlation analysis was used to analyze the correlation between serum levels of GPER1,CFH and HOMA-IR in GDM patients.Multivariate unconditional Logistic regression and receiver operating characteristic(ROC)curve were used to analyze the relationship between serum GPER1 and CFH levels and APO in GDM patients and to predict energy efficiency.Results Compared with the control group,serum levels of GPER1 and CFH were increased in the GDM group(P<0.05).Serum GPER1 and CFH levels were positively correlated with HOMA-IR in GDM patients(r=0.722 and 0.714,respectively,P<0.001).Compared with the non-APO group,serum levels of GPER1 and CFH were increased in the APO group(P<0.05).Elevated levels of HOMA-IR,GPER1 and CFH were independent risk factors for APO in GDM patients(P<0.05).The combined prediction of serum GPER1 and CFH[AUC=0.887(95%CI:0.816-0.937)]was superior to serum GPER1[AUC=0.789(95%CI:0.705-0.858)]and CFH[AUC=0.786(95%CI:0.701-0.856)]alone in predicting APO in GDM patients.Conclusion Serum levels of GPER1 and CFH in GDM patients are increased,which are closely related to the enhancement of insulin resistance and APO.The combination of the two has a higher predictive efficiency for APO.

Objective To investigate the relationship between serum G protein-coupled estrogen receptor 1(GPER1),complement factor H(CFH)levels and pregnancy outcomes in patients with gestational diabetes mellitus(GDM).Methods A total of 120 patients with GDM(GDM group)and 60 healthy pregnant women(control group)were included in this study.According to the pregnancy outcome,GDM patients were divided into the adverse pregnancy outcome(APO)group(50 cases)and the non-APO group(70 cases).The basic data of GDM patients were collected.Fasting blood glucose,fasting insulin and blood lipids were measured,and homeostasis model assessment of insulin resistance index(HOMA-IR)was calculated.The serum levels of GPER1 and CFH were detected by enzyme-linked immunosorbent assay.Pearson correlation analysis was used to analyze the correlation between serum levels of GPER1,CFH and HOMA-IR in GDM patients.Multivariate unconditional Logistic regression and receiver operating characteristic(ROC)curve were used to analyze the relationship between serum GPER1 and CFH levels and APO in GDM patients and to predict energy efficiency.Results Compared with the control group,serum levels of GPER1 and CFH were increased in the GDM group(P<0.05).Serum GPER1 and CFH levels were positively correlated with HOMA-IR in GDM patients(r=0.722 and 0.714,respectively,P<0.001).Compared with the non-APO group,serum levels of GPER1 and CFH were increased in the APO group(P<0.05).Elevated levels of HOMA-IR,GPER1 and CFH were independent risk factors for APO in GDM patients(P<0.05).The combined prediction of serum GPER1 and CFH[AUC=0.887(95%CI:0.816-0.937)]was superior to serum GPER1[AUC=0.789(95%CI:0.705-0.858)]and CFH[AUC=0.786(95%CI:0.701-0.856)]alone in predicting APO in GDM patients.Conclusion Serum levels of GPER1 and CFH in GDM patients are increased,which are closely related to the enhancement of insulin resistance and APO.The combination of the two has a higher predictive efficiency for APO.

Objective:To investigate the clinical, imaging and neuropathological characteristics of neuronal intranuclear inclusion disease (NIID) with symptoms of the central nervous system, and to improve the diagnosis and treatments of NIID.Methods:The clinical data of 7 patients with NIID diagnosed by brain biopsy in Xuanwu Hospital, Capital Medical University, Beijing, China from February 2009 to December 2024 were collected. The characteristics of clinical manifestations, imaging, and histology on brain biopsy were retrospectively analyzed.Results:Among the 7 patients, 5 were male and 2 were female. Their ages ranged from 44 to 70 years, median 56 (52, 65) years. Patients were classified into three types of tumor, stroke and encephalitis according to the onset symptoms, imaging manifestations and pathological changes. The chief complaint of the 5 patients was headache, while 4 patients had paroxysmal convulsions, 3 had speech disorders, 2 had abnormal mental behaviors, 2 had memory decline, and 1 had fever accompanied by consciousness disorders. Diffusion-weighted magnetic resonance imaging of the head showed the "ribbon sign" at the junction of the cortex and medulla in 2 cases. Most of the patients had white matter lesions, gyrus swelling and cerebral atrophy. Occasionally gyrus-like enhancement was observed. Brain biopsy reveals the histological changes that matched those on images and initial symptoms. There were proliferation of oligodendrocytes and astrocytes in the white matter, leukoaraiosis and edema, cortical disintegration and lamellar necrosis, as well as infiltration of lymphocytes and microglia, etc. However, the characteristic changes were eosinophilic hyaline inclusions in the nuclei of neurons and astrocytes. Immunohistochemical staining of p62 and ubiquitin showed homogeneous staining in round or ring-shaped nuclei.Conclusions:The clinical manifestations of NIID are highly variable, and a correct diagnosis of NIID requires careful integration of clinical, imaging and histopathologic data. For patients with a high suspicion of NIID, immunohistochemical staining of p62 and ubiquitin is diagnostically valuable.

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) for the prenatal diagnosis of chromosomal mosaicisms. METHODS: A total of 775 pregnant women who had visited the Prenatal Diagnosis Center of Yancheng Maternal and Child Health Care Hospital from January 2018 to December 2020 were selected as study subjects. Chromosome karyotyping analysis and CMA were carried out for all women, and FISH was used to validate the suspected mosaicism cases. RESULTS: Among the 775 amniotic fluid samples, karyotyping has identified 13 mosaicism cases, which yielded a detection rate of 1.55%. Respectively, there were 4, 3, 4 and 2 cases for sex chromosome number mosaicisms, abnormal sex chromosome structure mosaicisms, abnormal autosomal number mosaicisms and abnormal autosomal structure mosaicisms. CMA has only detected only 6 of the 13 cases. Among 3 cases verified by FISH, 2 cases were consistent with the karyotyping and CMA results, and clearly showed low proportion mosaicism, and 1 case was consistent with the result of karyotyping but with a normal result by CMA. Eight pregnant women had chosen to terminate the pregnancy (5 with sex chromosome mosaicisms and 3 with autosomal mosaicisms). CONCLUSION For fetuses suspected for chromosomal mosaicisms, CMA, FISH and G-banding karyotyping should be combined to determine the type and proportion of mosaicisms more precisely in order to provide more information for genetic counseling.
Female ; Pregnancy ; Humans ; Mosaicism ; In Situ Hybridization, Fluorescence ; Chromosome Disorders/genetics* ; Prenatal Diagnosis/methods* ; Chromosome Aberrations ; Sex Chromosome Aberrations ; Microarray Analysis/methods* ; Chromosomes

The chemical complexity of traditional Chinese medicines (TCMs) makes the active and functional annotation of natural compounds challenging. Herein, we developed the TCMs-Compounds Functional Annotation platform (TCMs-CFA) for large-scale predicting active compounds with potential mechanisms from TCM complex system, without isolating and activity testing every single compound one by one. The platform was established based on the integration of TCMs knowledge base, chemome profiling, and high-content imaging. It mainly included: (1) selection of herbal drugs of target based on TCMs knowledge base; (2) chemome profiling of TCMs extract library by LC‒MS; (3) cytological profiling of TCMs extract library by high-content cell-based imaging; (4) active compounds discovery by combining each mass signal and multi-parametric cell phenotypes; (5) construction of functional annotation map for predicting the potential mechanisms of lead compounds. In this stud TCMs with myocardial protection were applied as a case study, and validated for the feasibility and utility of the platform. Seven frequently used herbal drugs (Ginseng, etc.) were screened from 100,000 TCMs formulas for myocardial protection and subsequently prepared as a library of 700 extracts. By using TCMs-CFA platform, 81 lead compounds, including 10 novel bioactive ones, were quickly identified by correlating 8089 mass signals with 170,100 cytological parameters from an extract library. The TCMs-CFA platform described a new evidence-led tool for the rapid discovery process by data mining strategies, which is valuable for novel lead compounds from TCMs. All computations are done through Python and are publicly available on GitHub.

Objective:To investigate the correlation between systemic inflammatory response index (SIRI) and the outcomes at 90 d after intravenous thrombolysis in patients with acute ischemic stroke.Methods:Patients with acute ischemic stroke received intravenous thrombolysis in Nanjing Drum Tower Hospital from January 2016 to December 2019 were retrospectively enrolled. SIRI was calculated according to neutrophil count, lymphocyte count, and monocyte count at admission. The modified Rankin Scale score was used to evaluate the outcomes at 90 d after onset. 0-2 was defined as good outcome, and 3-6 were defined as poor outcome. Multivariate logistic regression analysis was used to evaluate the independent correlation between SIRI and poor outcomes. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of SIRI for poor outcomes. Results:A total of 303 patients with acute ischemic stroke receiving intravenous thrombolysis were enrolled in the study, including 178 (58.7%) males. Their median age was 69 years (interquartile range 60-78 years), and 69 patients (22.8%) had poor outcomes. SIRI in the poor outcome group was significantly higher than that in the good outcome group (1.53±2.45 vs. 3.51±4.73; P<0.05). Multivariate logistic regression analysis showed that the National Institutes of Health Stroke Scale (NIHSS) score at admission (odds ratio [ OR] 1.230, 95% confidence interval [ CI] 1.151-1.315; P<0.001) and SIRI ( OR 1.240, 95% CI 1.074-1.432; P=0.003) were significantly associated with the poor outcomes at 90 d. ROC curve analysis showed that the areas under the curve for SIRI and NIHSS scores alone and in combination to predict poor outcomes were 0.721 (95% CI 0.650-0.792; P<0.001), 0.824 (95% CI 0.771-0.878; P<0.001) and 0.853 (95% CI 0.804-0.902; P<0.001), respectively. The best cut-off values were 1.59, 8.00, and 0.23, respectively, and the sensitivity and specificity were 60.9% and 73.9%, 76.8% and 75.6%, 75.4% and 82.5%, respectively. Conclusions:High SIRI at admission is independently associated with 90-day poor outcomes in patients with acute ischemic stroke treated with intravenous thrombolysis. SIRI may be used as an outcome predictor in patients undergoing intravenous thrombolysis.

Objective:To analyze the diagnostic value of metabolic makers in cerebrospinal fluid in advanced lung adenocarcinoma patients with leptomeningeal metastases (LM) .Methods:A total of 46 cerebrospinal fluid samples (LM group) from lung adenocarcinoma patients with LM admitted to Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School from December 2019 to December 2021 were collected, and 48 cerebrospinal fluid samples (control group) from patients with benign neurological diseases during the same period were collected. Metabolomics analysis of cerebrospinal fluid was carried out by high-performance liquid chromatography-mass spectrometry. Principle component analysis (PCA) and orthogonal to partial least squares discriminant analysis (OPLS-DA) were used for modeling. Multi-criteria assessment was used to identify the different metabolites between the two groups. Receiver operating characteristic (ROC) curve, pathway enrichment analysis and other methods were used to screen metabolites and pathways related to LM from lung adenocarcinoma.Results:There were no statistically significant differences in the proportions of age ( Z=-0.41, P=0.210) , gender ( χ2=1.19, P=0.275) , history of smoking ( χ2=2.86, P=0.091) , Karnofsky performance status score ( χ2=0.65, P=0.419) and increased intracranial pressure ( χ2=0.65, P=0.419) between the LM group and control group. The models of PCA (R2X was 0.608 and 0.583, Q2 was 0.462 and 0.513 in electrospray ion positive and negative modes, respectively) and OPLS-DA (R2Y was 0.967 and 0.889, Q2 was 0.959 and 0.852 in electrospray ion positive and negative modes, respectively) showed that the overall data quality was good. Meanwhile, the model interpretation rate and prediction rate were effective. The permutation tests duplicated for 200 times and showed no over-fitting of the established model. The metabolic profiles of the two groups were significantly different. A total of 30 endogenously differential metabolites were screened by using multi-criteria assessment. Six potential biomarkers with larger area under the curve (AUC) were identified through ROC curve analysis, including tyrosine (AUC=0.967, 95% CI: 0.906-1.000) , phenylalanine (AUC=0.992, 95% CI: 0.973-1.000) , pyruvate (AUC=0.976, 95% CI: 0.935-1.000) , tryptophan (AUC=0.935, 95% CI: 0.880-0.973) , glucose (AUC=0.932, 95% CI: 0.880-0.975) and adenosine monophosphate (AUC=0.993, 95% CI: 0.987-1.000) . The 30 selected differential metabolites were enriched and analyzed for metabolic pathways, and 20 relevant metabolic pathways were matched. Among them, the four metabolic pathways most likely to cause changes in metabolites were glycolysis and glucose metabolic synthesis, pyruvate metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis. Conclusion:Untargeted metabolomics analysis can effectively screen specific cerebrospinal fluid metabolites in lung adenocarcinoma patients with LM. Six potential metabolites such as tyrosine, phenylalanine, pyruvate, tryptophan, adenosine monophosphate, glucose and their metabolic pathways may be involved in the pathogenesis of LM from lung adenocarcinoma.