Objective To investigate the effects of low, mid, and high flux smoothness modes on plan quality, treatment efficiency, equipment loss, and clinical economic benefits in fixed-field intensity-modulated radiotherapy for cervical cancer, and establish a decision-making model for parameter optimization and economic benefits. Methods Fifteen patients with cervical cancer undergoing radiotherapy were selected. Using the Monaco system and adjusting only the flux smoothness parameter, low, mid, and high plans were designed for each patient. Dosimetric differences were compared for the target volume (D₂, D₉₈, D_mean, homogeneity index, conformity index) and organs at risk (small intestine, rectum, colon, bladder, femoral head). The number of segments, monitor units, and their correlations with treatment efficiency and equipment loss were analyzed, as well as the potential impact on clinical costs. Results There were statistically significant differences in the three groups' planned target areas D₂, D₉₈, D_mean, CI, HI, and the dose parameters of organs at risk (P<0.001), but the absolute differences were all lower than the clinical tolerance limits in the ICRU 83 report (±3% – ±5%), with an effect size d<0.5 (except for the small intestine with d = 0.51). There was no clinical significance. Compared with the mid mode, the high mode had a 13.3% reduction in the number of subfields (effect size d = 0.85), a 11.6% reduction in machine jumps (d = 1.0), and a 13.0% reduction in treatment time. Based on the mid mode, the relative loss rate of the accelerating tube in the high mode was 11.6%, the theoretical risk change rate of equipment failure was 12.7%, and the accelerating tube lifespan was extended by approximately 1.2 years. Comprehensive economic benefits: Calculated based on 1,200 treatments per year, the annual cost savings are approximately 920,000 yuan. Conclusion Adoption of the high flux smoothness mode in fixed-field intensity-modulated radiotherapy for cervical cancer using the Monaco system can significantly enhance treatment efficiency and reduce operating costs while ensuring dosimetric quality. It is recommended for routine clinical use.

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 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 clinical, radiological, and pathological features of anaplastic gangliogliomas (AGGs) and to determine whether these tumors represent a distinct entity.Methods:Consecutive 667 cases of ganglioglioma (GG) diagnosed at the Xuanwu Hospital, Capital Medical University, Beijing, China between January 2015 and July 2023 were screened. Among these cases, 9 pathologically confirmed AGG cases were identified. Their clinical, radiological, treatment, and outcome data were analyzed retrospectively. Most of the tumor samples were subject to next-generation sequencing, while a subset of them were subject to DNA methylation profiling.Results:Among the 9 patients, there were five males and four females, with a median age of 8 years. Epileptic seizures (5/9) were the most frequently presented symptom. Radiological examinations showed three types of radiological manifestations: four cases showed abnormal MRI signals with no significant mass effects and mild enhancement; two cases demonstrated a mixed solid-cystic density lesion with peritumoral edema, which showed significant heterogeneous enhancement and obvious mass effects, and one case displayed cystic cavity formation with nodules on MRI, which showed evident enhancements. All cases exhibited mutations that were predicted to activate the MAP kinase signaling pathway, including seven with BRAF p.V600E mutation and two with NF1 mutation. Five AGGs with mutations involving the MAP kinase signaling pathway also had concurrent mutations, including three with CDKN2A homozygous deletion, one with a TERT promoter mutation, one with a H3F3A mutation, and one with a PTEN mutation.Conclusions:AGG exhibits a distinct spectrum of pathology, genetic mutations and clinical behaviors, differing from GG. Given these characteristics suggest that AGG may be a distinct tumor type, further expansion of the case series is needed. Therefore, a comprehensive integration of clinical, histological, and molecular analyses is required to correctly diagnose AGG. It will also help guide treatments and prognostication.

Objective To evaluate the clinical efficacy of clear aligner for crowded dentition in early permanent teeth by moving the upper and lower molars far.Methods A total of 36 adolescent patients with Class Ⅰ Angle malocclusion admitted in our department from March 2017 to August 2023 were enrolled,and they were 17 males and 19 females,and at a mean age of 13.20±0.53 years.Clear aligner was applied to push the upper and lower molars backward to obtain a neat dentition.Lateral cephalometric X-ray film before and after treatment was measured,and paired t-test was used to compare the cephalometric measurements before and after treatment.Results The average course of treatment was 21.2 months.Overbite,overjet and molar relationship were turned to normal after treatment,and the soft tissue profile was maintained.Analysis of relevant cephalometric items showed that the Ptm-U6 distance was decreased by 2.89±1.22 mm,and the Go-L6 distance was decreased by 2.61±1.07 mm after treatment,with significant differences(P＜0.01).While,there were no statistically differences in UL-EP,LL-EP,NLA and FCA before and after treatment.Conclusion With reasonable treatment target and good tooth movement design,clear aligner can effectively move the upper and lower molar distally to correct moderate dentition congestion in early permanent teeth,and meanwhile the patients'profile is maintained.

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 evaluate the effects of intrathecal infusion chemotherapy on intracranial pressure (ICP) in non-small cell lung cancer (NSCLC) patients with leptomeningeal metastases (LM) by ultrasound measurement of the optic nerve beside the bed of optic nerve sheath diameter (ONSD) .Methods:A total of 31 NSCLC-LM patients who underwent intrathecal infusion chemotherapy at Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School from June 10, 2021 to December 25, 2022 were collected. The ONSD values were measured before and after the first lumbar puncture by bedside optic nerve ultrasound, and measured dynamically 30 min before intrathecal infusion chemotherapy (T0) , 30 min (T1) , 1 h (T2) , 2 h (T3) , 4 h (T4) , 6 h (T5) , and 24 h (T6) after intrathecal infusion chemotherapy. ICP ONSD was calculated, with differences between ICP LP and ICP ONSD, and differences between ONSD and ICP ONSD series at different time being compared separately. Mean arterial pressure (MAP) , heart rate, and headache score were assessed and compared respectively at T0, T1, T2, T3, T4, T5 and T6. Spearman analysis was used to evaluate the correlation between the response assessment in neuro-oncology (RANO) score and ICP. Results:Before the first lumbar puncture for cerebrospinal fluid drainage, ICP LP was (218.55±63.83) mmH 2O, left eye, right eye, and binocular eyes ICP ONSD were (217.28±57.17) mmH 2O, (223.64±51.13) mmH 2O, and (220.46±52.50) mmH 2O respectively, in NSCLC-LM patients, with no statistically significant difference ( F=0.77, P=0.463) . After first lumbar puncture for cerebrospinal fluid drainage, ICP LP was (214.68±58.01) mmH 2O, left eye, right eye, and binocular eyes ICP ONSD were (216.71±48.96) mmH 2O, (216.62±47.18) mmH 2O, and (216.67±47.86) mmH 2O respectively, with no statistically significant difference ( F=0.12, P=0.757) . At T0, T1, T2, T3, T4, T5, and T6, the MAP during intrathecal infusion chemotherapy was 89.80 (83.40, 93.67) mmHg, 95.00 (80.83, 99.37) mmHg, 91.86 (79.88, 100.14) mmHg, 90.15 (79.04, 100.55) mmHg, 105.14 (88.55, 114.74) mmHg, 98.96 (81.72, 111.81) mmHg, and 89.29 (85.45, 100.38) mmHg, with a statistically significant difference ( χ2=16.11, P=0.013) ; heart rates were 80.00 (75.00, 84.50) times/min, 80.00 (72.50, 87.50) times/min, 74.00 (66.00, 87.50) times/min, 82.00 (72.00, 90.00) times/min, 80.00 (70.50, 90.00) times/min, 77.00 (68.00, 91.00) times/min, 77.00 (71.50, 88.50) times/min, with no statistically significant difference ( χ2=2.18, P=0.902) ; headache scores were 2.00 (0.50, 3.00) score, 2.00 (1.00, 3.00) score, 2.00 (2.00, 3.00) score, 2.00 (1.00, 3.00) score, 2.00 (1.00, 2.00) score, 2.00 (1.00, 2.00) score, and 2.00 (0.00, 2.00) score, with no statistically significant difference ( χ2=11.64, P=0.071) . At T0, T1, T2, T3, T4, T5, and T6, left eye, right eye, and binocular ONSD were (5.85±0.64) mm, (5.72±0.68) mm, (7.11±1.11) mm, (6.42±0.78) mm, (5.69±0.63) mm, (5.61±0.64) mm, (5.65±0.88) mm, (5.85±0.12) mm, (5.89±0.12) mm, (6.93±0.20) mm, (6.40±0.14) mm, (5.71±0.12) mm, (5.66±0.12) mm, (5.33±0.14) mm, (5.85±0.64) mm, (5.81±0.64) mm, (7.02±1.03) mm, (6.41±0.75) mm, (5.70±0.63) mm, (5.64±0.63) mm, (5.49±0.76) mm, with statistically significant differences ( F=58.48, P<0.001; F=49.34, P<0.001; F=78.05, P<0.001) ; ICP ONSD were (222.81±56.81) mmH 2O, (211.89±60.29) mmH 2O, (335.12±98.32) mmH 2O, (274.17±68.87) mmH 2O, (208.77±56.12) mmH 2O, (201.75±56.79) mmH 2O, (205.59±78.36) mmH 2O, (223.26±58.33) mmH 2O, (227.08±61.68) mmH 2O, (319.36±101.10) mmH 2O, (272.33±69.61) mmH 2O, (211.21±57.73) mmH 2O, (206.51±57.22) mmH 2O, (177.22±68.98) mmH 2O, (223.03±57.24) mmH 2O, (219.49±57.24) mmH 2O, (327.24±91.56) mmH 2O, (273.25±67.04) mmH 2O, (209.99±56.26) mmH 2O, (204.13±56.29) mmH 2O, (191.40±67.95) mmH 2O, with statistically significant differences ( F=58.48, P<0.001; F=49.34, P<0.001; F=78.13, P<0.001) . The ONSD of the left eye, right eye, and binocular eyes and the corresponding ICP ONSD increased significantly at T2 compared with T0, T1, T3, T4, T5, and T6, with statistically significant differences (all P<0.05) . Pre- and post-treatment RANO scores were 4.00 (3.00, 7.00) score and 3.00 (2.00, 6.00) score respectively. Pre- and post-treatment RANO scores were positively correlated with ICP ONSD in the left eye ( r=0.55, P=0.001; r=0.60, P<0.001) , right eye ( r=0.54, P=0.001; r=0.46, P=0.009) and binocular eyes ICP ONSD ( r=0.45, P=0.010; r=0.37, P=0.043) . Conclusion:Intrathecal infusion chemotherapy for NSCLC-LM patients can cause a transient increase in ONSD and ICP, with the greatest effect at 1 hour after intrathecal infusion chemotherapy. RANO score is positively correlated with ICP ONSD before and after treatment, which can provide an important reference for evaluating the efficacy of intrathecal infusion chemotherapy.

Objective:To investigate the pharmacokinetics of cerebrospinal fluid pemetrexed following intrathecal injection chemotherapy in patients with leptomeningeal metastasis (LM) from lung adenocarcinoma and provide a basis for clinical intrathecal injection chemotherapy.Methods:A total of 21 patients with lung adenocarcinoma LM who underwent pemetrexed intrathecal injection chemotherapy via Ommaya capsule at Nanjing Drum Tower Hospital, Aiffilitated Hospital of Nanjing University Medical School from November 2019 to November 2022 were collected, and divided into 30, 40 and 50 mg groups ( n=10, n=4, n=7) according to pemetrexed dose. Cerebrospinal fluid was collected at 0, 0.5, 1, 2, 4, 6, 12, 24 and 48 h after the first intrathecal injection chemotherapy, and day 8 of each cycle for three groups. Reversed phase high performance liquid chromatography was used to determine the drug concentration in cerebrospinal fluid, to clarify the drug-related pharmacokinetic parameters, and to compare the differences in pemetrexed concentration among groups. Finally, cerebrospinal fluid pemetrexed concentration changes were observed and compared after different intrathecal injection chemotherapy cycles. Results:There were statistically significant differences in cerebrospinal fluid drug concentrations of patients in three groups at 0, 0.5, 1, 2, 4, 6, 12, 24 and 48 h after the first intrathecal injection chemotherapy (30 mg group: F=20.56, P<0.001; 40 mg group: F=27.06, P<0.001; 50 mg group: F=28.63, P<0.001), and there were statistically significant differences in the concentration of cerebrospinal fluid drugs in each dose group at 0.5, 1, 2, 4, 6 and 12 h compared to 0 h after intrathecal injection chemotherapy (all P<0.05). Compared to the 30 mg group, cerebrospinal fluid drug concentrations in the 50 mg group increased at 1, 2, 4, 6, 12 and 24 h after intrathecal injection chemotherapy, with statistically significant differences (all P<0.05). Pharmacokinetic analysis of cerebrospinal fluid pemetrexed showed that area under the concentration-time curve (AUC) 0-∞ of the 30, 40 and 50 mg groups were (5 696.12±283.32), (7 886.29±396.57), and (14 202.70±440.19) h·mg/L, respectively, with a statistically significant difference ( F=1 159.00, P<0.001) ; AUC 0-∞ increased in the 50 mg group compared to the 30 and 40 mg groups (both P<0.05) ; AUC 0-∞ increased in the 40 mg group compared to the 30 mg group ( P<0.05). The half-lives of three groups were (8.75±0.23), (11.29±0.59) and (16.42±1.23) h, respectively, with a statistically significant difference ( F=206.80, P<0.001) ; half-life was longer in the 50 mg group compared to the 30 and 40 mg groups (both P<0.05) ; half-life was longer in the 40 mg group compared to the 30 mg group ( P<0.05). The peak time of three groups were (1.55±0.10), (1.00±0.01), (1.43±0.11) h, respectively, with a statistically significant difference ( F=48.11, P<0.001) ; the peak time was shorter in the 40 and 50 mg groups compared to the 30 mg group (both P<0.05). Clearance of three groups were (7.02±2.46), (5.80±1.25) and (3.66±1.32) L/h, respectively, with a statistically significant difference ( F=6.02, P=0.009) ; clearance was decreased in the 50 mg group compared to the 30 mg group ( P<0.05). The peak concentration of three groups were (540.45±32.25), (820.75±46.47) and (1 014.78±64.96) mg/L, respectively, with a statistically significant difference ( F=207.70, P<0.001) ; peak concentration increased in the 50 mg group compared to the 30 and 40 mg groups (both P<0.05) ; peak concentration increased in the 40 mg group compared to the 30 mg group ( P<0.05). Cerebrospinal fluid drug concentrations were dynamically monitored after 4 cycles of intrathecal injection chemotherapy, in which cerebrospinal fluid pemetrexed concentrations in 30 mg group were (13.76±4.79), (11.41±7.08), (9.41±2.59) and (7.86±4.02) mg/L, respectively; 40 mg group were (14.45±6.59), (12.87±15.73), (11.24±2.48) and (9.09±3.38) mg/L, respectively; 50 mg group were (12.94±10.34), (9.72±7.62), (8.15±8.17) and (4.34±4.21) mg/L, respectively. There was a statistically significant difference in cerebrospinal fluid drug concentrations among different intrathecal injection chemotherapy cycles in 30 mg group ( F=4.04, P=0.016), and the cerebrospinal fluid drug concentration decreased in cycles 3 and 4 compared to cycle 1 (both P<0.05). There were no statistically significant differences in cerebrospinal fluid drug concentrations among different treatment cycles in 40 and 50 mg groups ( F=0.28, P=0.837; F=3.57, P=0.066) . Conclusion:Reversed phase high performance liquid chromatography method can effectively detect the pemetrexed concentration in cerebrospinal fluid; dynamic monitoring of cerebrospinal fluid pemetrexed concentration can provide a basis for the dosage and the treatment cycle of intrathecal injection chemotherapy in LM patients with lung adenocarcinoma.

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.

BACKGROUND: Tumor markers (TM) in cerebrospinal fluid (CSF) are useful for diagnosing leptomeningeal metastasis (LM). It has not been fully exploited the diagnostic possibilities of the CSF levels since the basic fact that the TM concentration of CSF depends strongly upon the serum levels as well as upon the condition of the blood brain barrier (BBB). To analyze the intrathecal TM synthesis and evaluate the integrity of BBB can be helpful for the definitive diagnosis of LM. Therefore, the aim of this study was to further explore the clinical value of intrathecal TM synthesis and BBB in the diagnosis for the lung cancer patients with LM. METHODS: Twenty-five lung cancer patients with LM and 57 patients with nonmalignant neurological diseases (NMNDs) admitted to Nanjing Drum Tower Hospital from December 2016 to March 2020 were included. We compared the integrity of BBB and intrathecal TM synthesis between two groups, analyzed the correlation of CSF TM between the detection and intrathecal synthesis, and evaluated serial CSF cytology, the integrity of BBB and intrathecal TM synthesis when intrathecal chemotherapy for one patient. RESULTS: Ninety-four percent LM patients showed the dysfunction of BBB, and all LM patients showed at least one intrathecal synthesized TM in CSF. In one patient, the CSF cytology was negative for the first time, but LM was eventually diagnosed based on the the intrathecal TM synthesis and positive CSF cytology of repeated lumbar puncture. In LM group, no correlation was observed between the detection and intrathecal synthesized TM in CSF. In the control group, only 3.5% (2/57) NMNDs patients had the dysfunction of BBB and no patients had intrathecal TM synthesis, both the differences of which were statistically significant (P<0.05). Finally, evaluating the CSF cytology, integrity of BBB and intrathecal TM synthesis can be used to assess the intracranial treatment effect. Moreover, intrathecal TM synthesis changes earlier than cytology. CONCLUSIONS The evaluation of intrathecal TM synthesis and integrity of BBB are novel clinical diagnostic tools. In addition, serial measurement of intrathecal synthesized TM may play an important role in monitoring efficacy of lung cancer patients with LM, which is worthy of further promotion and clinical application.