Neurexins control the strength and precise timing of glycinergic inhibition in the auditory brainstem.

Neurexins play diverse functions as presynaptic organizers in various glutamatergic and GABAergic synapses. However, it remains unknown whether and how neurexins are involved in shaping functional properties of the glycinergic synapses, which mediate prominent inhibition in the brainstem and spinal cord. To address these issues, we examined the role of neurexins in a model glycinergic synapse between the principal neuron in the medial nucleus of the trapezoid body (MNTB) and the principal neuron in the lateral superior olive (LSO) in the auditory brainstem. Combining RNAscope with stereotactic injection of AAV-Cre in the MNTB of neurexin1/2/3 conditional triple knockout mice, we showed that MNTB neurons highly express all isoforms of neurexins although their expression levels vary remarkably. Selective ablation of all neurexins in MNTB neurons not only reduced the amplitude but also altered the kinetics of the glycinergic synaptic transmission at LSO neurons. The synaptic dysfunctions primarily resulted from an impaired Ca2+ sensitivity of release and a loosened coupling between voltage-gated Ca2+ channels and synaptic vesicles. Together, our current findings demonstrate that neurexins are essential in controlling the strength and temporal precision of the glycinergic synapse, which therefore corroborates the role of neurexins as key presynaptic organizers in all major types of fast chemical synapses.

A method for studying escape behavior to terrestrial threats in rodents.

BACKGROUND: Escape is one of the most essential behaviors for an animal's survival because it could be a matter of life and death. Much of our current understanding of the neural mechanisms underlying escape is derived from the looming paradigm, which mimics a diving aerial predator. Yet, the idea of the looming paradigm does not account for all types of threats like lions hunting antelopes or cats stalking mice. Escape responses to such terrestrial threats may require different strategies and neural mechanisms. NEW METHODS: Here, we developed a real-time interactive platform to study escape behavior to terrestrial threats in mice. A closed-loop controlled robot was magnetically pulled to mimic a terrestrial threat that chases a mouse. By using strong magnets and high-precision servo motors, the robot is capable of moving precisely with a high spatial-temporal resolution. Different algorithms can be used to achieve single approach or persistent approach. RESULTS: Animal experiments showed that mice exhibited consistent escape behavior when exposed to an approaching robotic predator. When presented with a persistently approaching predator, the mice were able to rapidly adapt their behavior, as evidenced by a decrease in startle responses and changes in movement patterns. COMPARISON WITH EXISTING METHODS: In comparison to existing methods for studying escape behavior, such as the looming paradigm, this approach is more suitable for investigating animal behavior in response to sustained threats. CONCLUSION: In conclusion, we have developed a flexible platform to study escape behavior to terrestrial threats in mice.

Correlation of contrast sensitivity with ganglion cell/inner plexiform layer thickness and damage location in glaucoma with varying severity.

OBJECTIVES: To investigate the correlation of contrast sensitivity with macular region ganglion cell/inner plexiform layer (GC/IPL) thickness and damage location in open-angle glaucoma (OAG) of varying severity. METHODS: Cross-sectional study with 106 patients (203 eyes) who had OAG. Contrast sensitivity of each eye evaluated by quick contrast sensitivity function test based on intelligent algorithm. The GC/IPL thickness measured with optical coherence tomography; six sectors were delineated for localization of damage area. All eyes were grouped by the healthy macular sector and divided into pre-perimetric, early, moderate, and advanced stages, according to severity of visual field impairment. RESULTS: Mean GC/IPL thickness in the entire macular region and each sector were correlated with parameters that reflected contrast sensitivity (p < 0.01). The structure-function correlations were stronger nasally compared with temporally, and superiorly compared with inferiorly. Eyes with normal structure in inferior temporal sector had less visual field (p' = 0.024) and macular damage (p' = 0.034) compared with eyes that had healthy superior nasal sector; there was no difference in contrast sensitivity (p = 0.898). The structure-function correlations were significant in early, moderate, and advanced glaucoma (p < 0.05) but not in pre-perimetric glaucoma (p = 0.116). CONCLUSIONS: GC/IPL thinning in all sectors of the macular region in OAG was correlated with contrast sensitivity impairment, whereas the inferior temporal sector was least affected. Contrast sensitivity was supported as a severity evaluation indicator of early, moderate, and advanced glaucoma, but not of pre-perimetric glaucoma.

Association between contrast sensitivity function and structural damage in primary open-angle glaucoma.

AIMS: To evaluate the association between contrast sensitivity function (CSF) and glaucomatous structural damage in primary open-angle glaucoma (POAG). METHODS: A cross-sectional study was performed with 103 patients (103 eyes) aged 25-50 years who had POAG without any other ocular disease. CSF measurements were obtained by the quick CSF method, a novel active learning algorithm that covers 19 spatial frequencies and 128 contrast levels. The peripapillary retinal nerve fibre layer (pRNFL), macular ganglion cell complex (mGCC), radial peripapillary capillary (RPC) and macular vasculature were measured by optical coherence tomography and angiography. Correlation and regression analyses were used to assess the association of area under log CSF (AULCSF), CSF acuity and contrast sensitivities at multiple spatial frequencies with structural parameters. RESULTS: AULCSF and CSF acuity were positively associated with pRNFL thickness, RPC density, mGCC thickness and superficial macular vessel density (p<0.05). Those parameters were also significantly associated with contrast sensitivity at 1, 1.5, 3, 6, 12, 18 cycles per degree spatial frequencies (p<0.05) and, the lower the spatial frequency, the higher the correlation coefficient. RPC density (p=0.035, p=0.023) and mGCC thickness (p=0.002, p=0.011) had significant predictive value for contrast sensitivity at 1 and 1.5 cycles per degree, with adjusted R 2 of 0.346 and 0.343, respectively. CONCLUSIONS: Full spatial frequency contrast sensitivity impairment, most notably at low spatial frequencies, is a characteristic change in POAG. Contrast sensitivity is a potential functional endpoint for the measurement of glaucoma severity.

Comparison of the retinal microvasculature between compressive and glaucomatous optic neuropathy.

PURPOSE: To compare the patterns of retinal microvasculature change in the peripapillary and macular region between compressive optic neuropathy (CON) and glaucomatous optic neuropathy (GON), and to assess the ability of optical coherence tomography angiography (OCTA) in differentiating the two conditions. METHODS: This cross-sectional study included 108 participants (108 eyes), 36 with CON, 36 with GON, and 36 healthy controls. The CON and GON eyes were matched by the average peripapillary retinal nerve fiber layer (pRNFL) thickness (1:1). Optical coherence tomography (OCT) and OCTA were performed to compare the structural and vascular change of the peripapillary and macular region between groups. RESULTS: Both CON and GON eyes showed more severe structural and vascular damage than the control eyes. The CON eyes had lower pRNFL thickness than the GON eyes in the temporal and nasal quadrants, and thicker pRNFL thickness in the inferior quadrant. The average GCC thickness did not differ between the two groups. The peripapillary vessel density of the CON group was significantly higher in the inferior sectors than that of the GON group. In the macular region, the CON group had significantly higher vessel density in the whole image, the temporal sector in parafovea region, and the temporal, superior, and inferior sectors in perifovea region. CONCLUSION: To a similar degree of structural damage, CON had less retinal vascular impairment than GON, especially in the macular region, and the significance of the finding needs further evaluation.

Reference values for trans-laminar cribrosa pressure difference and its association with systemic biometric factors.

OBJECTIVES: To provide reference values of trans-laminar cribrosa pressure difference (TLCPD) and reveal the association of TLCPD with systemic biometric factors. METHODS: In this cross-sectional study, 526 quasi-healthy subjects (including 776 eyes) who required lumbar puncture for medical reasons were selected from 4915 neurology inpatients from 2019 to 2022. Patients with any diseases affecting intraocular pressure (IOP) or intracranial pressure (ICP) were excluded. The ICPs of all subjects were obtained by lumbar puncture in the left lateral decubitus position. IOP was measured in the seated position by a handheld iCare tonometer prior to lumbar puncture. TLCPD was calculated by subtracting ICP from IOP. Systemic biometric factors were assessed within 1 h prior to TLCPD measurement. RESULTS: The TLCPD (mean ± standard deviation) was 4.4 ± 3.6 mmHg, and the 95% reference interval (defined as the 2.5th-97.5th percentiles) of TLCPD was -2.27 to 11.94 mmHg. The 95% reference intervals for IOP and ICP were 10-21 and 6.25-15.44 mmHg, respectively. IOP was correlated with ICP (r = 0.126, p < 0.001). TLCPD was significantly negatively correlated with body mass index (r = -0.086, p = 0.049), whereas it was not associated with age, gender, height, weight, blood pressure, pulse, or waist and hip circumference. CONCLUSIONS: This study provides reference values of TLCPD and establishes clinically applicable reference intervals for normal TLCPD. Based on association analysis, TLCPD is higher in people with lower BMI.

Non-invasive intracranial pressure estimation using ultrasonographic measurement of area of optic nerve subarachnoid space.

OBJECTIVE: To verify whether the area of the ONSAS (ONSASA) obtained by transorbital ultrasonography can be used to accurately evaluate the intracranial pressure (ICP). METHODS: The recorded indexes included the optic nerve diameter, the optic nerve sheath diameter (ONSD), the width of both sides of the ONSAS (ONSASW) at 3 mm from the optic nerve head and the entire ONSASA outlined between 3 and 7 mm. After exploring and comparing five models to describe the relationship between body mass index (BMI), mean arterial blood pressure (MABP), ONSASA and ICP, the best model was determined. RESULTS: In all, 90 patients with neurological diseases undergoing continuous invasive ICP monitoring were included in the study. In the training group, the correlation coefficient for the association between the ICP and ONSASA (Pearson's correlation r=0.953) was higher than that for the association of the ICP with the ONSD (r=0.672; p<0.0001) and ONSASW at 3 mm behind the globe (r=0.691; p<0.0001). In the training group, the weighting function for prediction of the ICP was as follows: non-invasive ICP=2.050×ONSASA-0.051×BMI +0.036*MABP-5.837. With 20 mm Hg as the cut-off point for a high or low ICP, the sensitivity and specificity of ONSASA predicting ICP was 1.00 and 0.92. Receiver operator curve analysis revealed that the calculated cut-off value for predicting elevated ICP was 19.96 (area under curve= 0.960, 95% CI 0.865 to 1.00). CONCLUSION: Measurement of the ONSASA using ultrasonography can serve as a practical method for rapid and non-invasive quantification for evaluating ICP through an accurate mathematical formula with the BMI and MABP considered as contributing parameters. TRIAL REGISTRATION NUMBER: The study was registered in the Chinese Clinical Trial Registry (Study no ChiCTR2100045274).

Pigment dispersion syndrome and pigmentary glaucoma: overview and racial disparities.

Pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG) are two stages within the same ophthalmic disease spectrum, which are known to be affected by race. The prevalence of PDS is underestimated, largely due to its minor clinical symptoms. Although the prevalence of PG is low, the visual impairment associated with PG is extremely severe. The prevalence of PDS-PG is four or more times higher in Caucasians than in Blacks or Asians, and the "classic" PDS in Caucasians has long been used as a benchmark diagnostic criterion. Following extensive research focused on African Americans and Asians, the standard for diagnosing PDS-PG was refined. At the same time, the pathogenesis of PDS is not the same in different races. Hence, the effectiveness of preventive treatment and the need for treatment may not be equivalent in different races. The rate of conversion of PDS to PG is nearly 1/3 in Caucasians and higher in blacks and Asians, requiring more aggressive treatment and monitoring. We systematically searched a PubMed database from inception to March 2022 to provide an overview of research progress in various aspects of PDS-PG. Specifically, this paper considers the effects of race on disease prevalence, clinical manifestation, diagnostic criteria, disease mechanism, hereditary traits, treatment, and prevention to provide an accurate and comprehensive guide for the diagnosis and treatment of PDS-PG in various races.

Transient hearing abnormalities precede social deficits in a mouse model of autism.

Hearing abnormalities are important symptoms of autism spectrum disorders (ASDs), a neurological and developmental disorder. However, the characteristics of hearing abnormalities associated with ASD during development have not been fully investigated. We found that in Shank3B knockout mice (a high-confidence mouse model of ASD), transient hearing abnormalities can be found in auditory brainstem response, auditory cortical activity, as well as acoustic startle response. More importantly, all hearing abnormalities at 4 weeks were most prominent and preceded the onset of social deficits at 6 weeks. These hearing abnormalities gradually recovered with age. In addition, analysis of ABR data at 4 weeks using Support Vector Machine (SVM) can faithfully predict the genotype of mice with an accuracy of 85.71%. These findings not only revealed hearing changes in Shank3B knockout autistic-like mice during development, but also suggested that hearing abnormalities could potentially be used as an early and effective indicator of ASD risk.

A temperature-regulated circuit for feeding behavior.

Both rodents and primates have evolved to orchestrate food intake to maintain thermal homeostasis in coping with ambient temperature challenges. However, the mechanisms underlying temperature-coordinated feeding behavior are rarely reported. Here we find that a non-canonical feeding center, the anteroventral and periventricular portions of medial preoptic area (apMPOA) respond to altered dietary states in mice. Two neighboring but distinct neuronal populations in apMPOA mediate feeding behavior by receiving anatomical inputs from external and dorsal subnuclei of lateral parabrachial nucleus. While both populations are glutamatergic, the arcuate nucleus-projecting neurons in apMPOA can sense low temperature and promote food intake. The other type, the paraventricular hypothalamic nucleus (PVH)-projecting neurons in apMPOA are primarily sensitive to high temperature and suppress food intake. Caspase ablation or chemogenetic inhibition of the apMPOA→PVH pathway can eliminate the temperature dependence of feeding. Further projection-specific RNA sequencing and fluorescence in situ hybridization identify that the two neuronal populations are molecularly marked by galanin receptor and apelin receptor. These findings reveal unrecognized cell populations and circuits of apMPOA that orchestrates feeding behavior against thermal challenges.

Association of serum retinol concentration with normal-tension glaucoma.

OBJECTIVES: To evaluate the association between serum retinol concentration and normal-tension glaucoma (NTG). METHODS: A total of 345 study subjects were recruited in a prospective cross-sectional study: 101 patients with NTG, 106 patients with high-pressure primary open-angle glaucoma (POAG) and 138 healthy control subjects. Serum retinol concentration in fasting blood samples was determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). All study subjects were given complete ophthalmic examinations and diagnosed by two glaucoma sub-specialists. RESULTS: Serum retinol concentrations in NTG, POAG, and controls were 338.90 ± 103.23 ng/mL, 405.22 ± 114.12 ng/mL, and 408.84 ± 122.36 ng/mL respectively. NTG patients had lower serum retinol concentrations than POAG (p < 0.001) or healthy controls (p < 0.001). There was no statistical difference between the POAG and healthy controls (p = 0.780). Higher proportion of NTG patients (37.6%) than POAG (17.9%) or controls (21.7%) had serum retinol concentrations lower than 300 ng/mL. Serum retinol was positively correlated with optic nerve sheath diameter (ONSD) (r = 0.349, p = 0.001) in glaucoma patients and not associated with any other demographic features or ophthalmic biometric parameters in the NTG patients. Multivariate logistic regression showed that serum retinol (OR = 0.898, 95CI%: 0.851-0.947) was associated with incident NTG. CONCLUSIONS: NTG patients had lower serum retinol concentrations. Serum retinol uniquely associated with NTG makes it a new potential option for the diagnosis and treatment of the disease.

Relationship between corneal stiffness parameters and lamina cribrosa curvature in normal tension glaucoma.

PURPOSE: To evaluate the relationship between corneal biomechanical parameters and lamina cribrosa (LC) curvature in normal tension glaucoma (NTG). METHODS: 95 eyes of 56 NTG patients were enrolled in this prospective, observational study. Corneal biomechanical parameters, including stiffness parameters at applanation 1 (SP-A1), deformation amplitude ratio (DA ratio), inverse concave radius and biomechanically corrected intraocular pressure estimate (bIOP), were captured using the Corneal Visualization Scheimpflug Technology instrument (Corvis-ST). LC curvature was evaluated by mean adjusted LC curvature index (maLCCI) averaged by the measurements on 12 radial B-scan images obtained using swept-source optical coherence tomography (SS-OCT). Linear mixed models were constructed to assess the relationship between corneal biomechanical parameters and LC curvature. RESULTS: The mean age of participants was 51.04 ± 13.74 years (range, 24-82 years). The SP-A1 and maLCCI were 93.50 ± 13.82 mm Hg/mm and 7.57 ± 1.58, respectively. In univariate and multivariate analysis, SP-A1 (p < 0.001 and p = 0.001) and age (p = 0.010 and p = 0.024) were both significantly associated with maLCCI. The LC curvature increased with softer cornea demonstrated by lower SP-A1 and younger eyes. There was no statistical significance interaction between SP-A1 and age (p = 0.194). CONCLUSIONS: The greater posterior LC curvature was associated with lower corneal stiffness parameters and younger eyes in NTG patients. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900021465.

Pillar[5]arene-Based Switched Supramolecular Photosensitizer for Self-Amplified and pH-Activated Photodynamic Therapy.

Photodynamic therapy (PDT) has emerged as a promising and spatiotemporally controllable cancer treatment modality. However, serious skin photosensitization during the PDT process limits the clinical application of PDT. Thus, the construction of "smart" and multifunctional photosensitizers has attracted substantial interest. Herein, we develop a mitochondria-targeting and pH-switched hybrid supramolecular photosensitizer by the host-guest interaction. The PDT efficacy of supramolecular photosensitizers can be quenched by the Förster resonance energy transfer (FRET) effect during long circulation and activated by the dissociation of supramolecular photosensitizers in an acidic tumor microenvironment, benefitting from the dynamic feature of the host-guest interaction and pH responsiveness of the water-soluble pillar[5]arene on gold nanoparticles. The rational integration of mitochondria-targeting and reductive glutathione (GSH) elimination in the hybrid switchable supramolecular photosensitizer prolongs the lifetime of reactive oxygen species generated in the PDT near mitochondria and further amplifies the PDT efficacy. Thus, the facile and versatile construction of switchable supramolecular photosensitizer offers not only the targeted and precise phototherapy but also high therapeutic efficacy, which would provide a new path for the clinic application of PDT.

The distribution and density of monocarboxylate transporter 2 in cerebral cortex, hippocampus and cerebellum of wild-type mice.

Monocarboxylates cannot cross the blood-brain barrier freely to participate in brain energy metabolism. Specific monocarboxylate transporters (MCTs) are needed to cross cellular membranes. Monocarboxylate transporter 2 (MCT2) is a major monocarboxylate transporter encoded by the SLC16A7 gene. Recent studies reported that neurodegenerative diseases of the CNS, such as Alzheimer's disease (AD) and Parkinson's disease (PD), were related to energy metabolic impairment. MCT2 also plays an important role in energy metabolism in the CNS. To provide experimental evidence for future research on the role of MCT2 in the pathological process of CNS degenerative diseases, the distribution and density of MCT2 in different subregions of wild-type mouse brain was examined using immunohistochemistry, western blot and immunogold post-embedding electron microscopic techniques. The amount of MCT2 was higher in cerebellum than in cortex and hippocampus on western blots, and there was no statistical difference between cortex and hippocampus. Immunohistochemistry assay revealed the highest density of MCT2 in the CA3 of the hippocampus. The granular cell layer of the cerebellum contained more MCT2 than the molecular layer. The MCT2 density on the end feet of astrocytes of molecular layer was lower than in hippocampus, but the postsynaptic densities (PSDs) of asymmetric synapses in the molecular layer exhibited a high density using immunogold post-embedding electron microscopic techniques.

Regular Exercise Enhances Cognitive Function and Intracephalic GLUT Expression in Alzheimer's Disease Model Mice.

Brain energy metabolic impairment is one of the main features of Alzheimer's disease (AD) and is considered an underlying factor involved in cognitive impairment. Therefore, brain energy metabolism may represent a new therapeutic target for AD medical interventions. Among nutrients providing energy, glucose, the primary energy source, cannot cross the blood-brain barrier freely without specific glucose transporters (GLUTs), which are essential for the maintenance of cerebral energy metabolism homeostasis. Several converging lines of evidence suggest that GLUT1 deficiency in mice leads to synapse reduction and dysregulation coupled with mitochondrial morphological changes. In this study, the results revealed that regular exercise (RE) decreased the expression of amyloid-ß and phosphorylated tau by western blot, and enhanced the spatial learning and exploration ability of AD model mice as assessed by Morris water maze test. Mitochondrial cristae and edges were clear and intact, ATP production in the brain raised, the number of synapses increased, and GLUT1 and GLUT3 expression levels improved in the central nervous system (CNS) in AD model mice after RE. Changes in GLUT1 and GLUT3 expression at the protein level after RE are an important part of energy metabolic adaptation in AD model mice. Learning and memory improvement are highly associated with mitochondrial integrity and sufficient synapses in the CNS. This research suggests that increased brain energy metabolism attributed to RE exhibits promising therapeutic potential for AD.

Development and Validation of a Deep Learning System to Detect Glaucomatous Optic Neuropathy Using Fundus Photographs.

Importance: A deep learning system (DLS) that could automatically detect glaucomatous optic neuropathy (GON) with high sensitivity and specificity could expedite screening for GON. Objective: To establish a DLS for detection of GON using retinal fundus images and glaucoma diagnosis with convoluted neural networks (GD-CNN) that has the ability to be generalized across populations. Design, Setting, and Participants: In this cross-sectional study, a DLS for the classification of GON was developed for automated classification of GON using retinal fundus images obtained from the Chinese Glaucoma Study Alliance, the Handan Eye Study, and online databases. The researchers selected 241 032 images were selected as the training data set. The images were entered into the databases on June 9, 2009, obtained on July 11, 2018, and analyses were performed on December 15, 2018. The generalization of the DLS was tested in several validation data sets, which allowed assessment of the DLS in a clinical setting without exclusions, testing against variable image quality based on fundus photographs obtained from websites, evaluation in a population-based study that reflects a natural distribution of patients with glaucoma within the cohort and an additive data set that has a diverse ethnic distribution. An online learning system was established to transfer the trained and validated DLS to generalize the results with fundus images from new sources. To better understand the DLS decision-making process, a prediction visualization test was performed that identified regions of the fundus images utilized by the DLS for diagnosis. Exposures: Use of a deep learning system. Main Outcomes and Measures: Area under the receiver operating characteristics curve (AUC), sensitivity and specificity for DLS with reference to professional graders. Results: From a total of 274 413 fundus images initially obtained from CGSA, 269 601 images passed initial image quality review and were graded for GON. A total of 241 032 images (definite GON 29 865 [12.4%], probable GON 11 046 [4.6%], unlikely GON 200 121 [83%]) from 68 013 patients were selected using random sampling to train the GD-CNN model. Validation and evaluation of the GD-CNN model was assessed using the remaining 28 569 images from CGSA. The AUC of the GD-CNN model in primary local validation data sets was 0.996 (95% CI, 0.995-0.998), with sensitivity of 96.2% and specificity of 97.7%. The most common reason for both false-negative and false-positive grading by GD-CNN (51 of 119 [46.3%] and 191 of 588 [32.3%]) and manual grading (50 of 113 [44.2%] and 183 of 538 [34.0%]) was pathologic or high myopia. Conclusions and Relevance: Application of GD-CNN to fundus images from different settings and varying image quality demonstrated a high sensitivity, specificity, and generalizability for detecting GON. These findings suggest that automated DLS could enhance current screening programs in a cost-effective and time-efficient manner.

[Long-term Efficacy of Radiofrequency Ablation Combined with Chemotherapy 
in the Treatment of Patients with Advanced Non-small Cell Lung Cancer
--A Retrospective Study].

BACKGROUND: Radiofrequency ablation (RFA) combined with chemotherapy has a certain short-term therapeutic effect for the treatment of advanced non-small cell lung cancer (NSCLC), but whether it can improve the long-term survival rate of patients is still controversy. This study retrospectively analyzed the difference of long-term efficacy between RFA combined with chemotherapy and chemotherapy alone in the treatment of patients with advanced NSCLC. METHODS: A total of 77 patients with stage IIIb and stage IV NSCLC who underwent radiofrequency ablation and chemotherapy in the Department of Thoracic Surgery, Xuanwu Hospital, Capital University of Medical Sciences from September 2009 to December 2015 were enrolled as the treatment group. Chemotherapy with no radiofrequency ablation was performed in 56 patients with stage IIIb and stage IV NSCLC as the control group. Two groups of patients were followed up by telephone about their living conditions. "Survival" package of R software version 3.4.1 was used for statistical analysis. Two sets of data baseline levels were tested by chi-square test. The bias was processed by Cox regression model and the survival curve was plotted using covariate mean substitution method. RESULTS: The first-year survival rate of the treatment group was 70.74%, the two-year survival rate was 39.31% and the median survival time was 22.1 months. The one-year survival rate was 54.54% in the control group, the two-year survival rate was 19.49%, the median survival for 18.1 months. The long-term survival rate of the treatment group was better than that of the control group (P<0.05, OR=0.571). CONCLUSIONS: Radiofrequency ablation of lung cancer combined with chemotherapy can significantly improve the 2-year survival rate of patients with stage IIIb and stage IV NSCLC.