The spine is the most common site of skeletal metastasis in lung cancer, which frequently leads to severe complications such as pathological fracture and neurological compromise and is associated with poor prognosis. The development and progression of spinal metastasis from lung cancer are linked to the unique local microenvironment and tumor microenvironment (TME) of the vertebral column. During metastatic evolution, the dense vascular network of the spine and a plethora of signaling molecules, together with the complex cellular constituents and their intricate interactions within the TME, all cooperate to facilitate the tumor invasion and colonization of the vertebral compartment. Mechanistic studies delineating the role of the TME in spinal metastasis from lung cancer have markedly expanded, fostering the emergence of innovative therapeutic strategies—including nanomedicines, sono-photodynamic therapy, gene therapy, and combination regimens. These strategies demonstrate remarkably potential for clinical translation and offer new directions for the precision management of spinal metastasis from lung cancer.

Background Ozone (O₃) is a major air pollutant. The existing monitoring system has uneven distribution of sites, insufficient coverage in underdeveloped areas, and low temporal resolution, making it difficult to obtain hourly data. This limits the dynamic identification of pollution and the formulation of prevention and control strategies. Objective To construct an hourly O₃ concentration estimation model based on ensemble machine learning, aiming to improve the accuracy of pollution exposure assessment and explore O₃ health impacts. Methods This study integrated land use regression modeling with modern machine learning techniques, employing random forest and XGBoost algorithms to construct base models, and stacking integration using non-negative least squares. The ensemble model was trained and validated across China using high-resolution, multi-source geographic data (e.g., meteorologicaldata, population density, land cover types, and aerosol optical thickness). It was tested in Taiyuan City, combined with a distributed lag non-linear model to analyze the association between O₃ and emergency admissions. Results The constructed ensemble model performed well in predicting O₃ concentration, with a higher coefficient of determination (R²) and a lower root-mean-square deviation (RMSE) compared to the single models. The R² improved from 0.90 to 0.92, and the RMSE decreased from 11.41 to 10.62, enhancing both prediction accuracy and generalization ability. In the application to Taiyuan City, the model successfully imputed the hourly-level data for the entire year. The distributed lag non-linear model analysis revealed that the relative risk (RR) values for the 6th to 8th days following O₃ exposure were 1.14 (95%CI: 1.01, 1.29), 1.16 (95%CI: 1.02, 1.31), and 1.14 (95%CI: 1.01, 1.29), respectively, which were significantly higher than 1, indicating a significant lagged association (lagged 6-8 d) between O₃ and the number of emergency room visits. Conclusion A high-precision, hourly-level O₃ concentration estimation model is successfully constructed by combining the land use regression model with an ensemble machine learning approach to provide a scientific basis for environmental policy formulation and public health intervention. The application of the model verifies its generalization ability and practical application value, which can provide a new technical framework for subsequent environmental health research.

OBJECTIVE To establish a method for simultaneous determination of ceftazidime， avibactam and aztreonam concentrations in human plasma.METHODS Stable-isotope-labeled compounds ceftazidime-D 5 ， avibactam- 13 C 5 and aztreonam- 2 H 6 were used as internal standards. Plasma samples were pretreated by protein precipitation with methanol， followed by nitrogen blowing. A ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） technique was applied to develop a quantitative analytical method for simultaneous measurement of ceftazidime， avibactam and aztreonam in human plasma. An ACQUITY UPLC BEH C 18 column was used as the chromatographic column. Gradient elution was performed with 0.01% formic acid-acetonitrile solution as the mobile phase at a flow rate of 0.3 mL/min. The column temperature was set at 40 ℃， and the injection volume was 5 μL. An electrospray ionization source was operated in both positive and negative ion modes for multiple reaction monitoring. Method validation was carried out according to the Guidelines for Bioanalytical Method Validation contained in volume Ⅳ of the 2020 edition of Chinese Pharmacopoeia .RESULTS The linear ranges of ceftazidime， avibactam and aztreonam were 0.04-200， 0.05-50，0.01-50 μg/mL， respectively， with all correlation coefficients no less than 0.996. The relative error （RE） for accuracy was no more than 12.25% （ n ＝5）， and the RSD for precision was no more than 13.49% （ n ＝5）. The RSD of internal-standard-normalized matrix factors was less than 15.00% （ n ＝6）. The RE in stability tests was lower than 15.00% （ n ＝3）.CONCLUSIONS This study successfully established an UPLC-MS/MS method for simultaneous determination of ceftazidime， avibactam and aztreonam concentrations in human plasma. The method possesses favorable accuracy， precision and stability， and can provide methodological support for therapeutic drug monitoring and individualized medication in patients treated with these three combined drugs.

OBJECTIVES: To investigate the regulatory role of the NLRP3 signaling pathway in hepatocyte pyroptosis in nonalcoholic steatohepatitis (NASH) under hypoxia. METHODS: Twenty-four male C57BL/6 mice were randomized equally into hypoxic control (A), hypoxic NASH model (B), hypoxic NASH+NLRP3 inhibitor (C), and hypoxic NASH+caspase-1 inhibitor (D) groups. In groups B-D, the mice were fed a methionine choline-deficient (MCD) diet under hypoxic conditions (to simulate a 5000 m altitude) for 6 weeks; the mice in groups C and D received intraperitoneal injections of the respective inhibitors every other day. RESULTS: Compared with those in group A, the mice in group B showed significantly elevated serum levels of FBG, TC, TG, ALT and AST, increased liver lipid content, inflammatory cell infiltration and collagen fiber deposition, and enhanced hepatic expressions of NLRP3, caspase-1, IL-1β and GSDMD proteins, with obvious swelling, cristae breakage, vacuolization, and outer membrane disruption of the mitochondria, ribosome loss in the cytoplasm, destruction of the nuclear membrane, and pathological changes of the rough endoplasmic reticulum. Treatment with NLRP3 inhibitor and caspase-1 inhibitor both significantly lowered serum levels of TC, TG, ALT and AST (but without significantly affecting FBG) in the mouse models, and reduced liver lipid content, inflammatory cell infiltration, collagen deposition, and expression levels of NLRP3, caspase-1, GSDMD and IL-1β. The treatments also significantly improved pathological changes in the mitochondria, ribosomes and endoplasmic reticulum in liver tissues of the mice. CONCLUSIONS NLRP3 signaling pathway plays a key role in promoting hepatocyte pyroptosis in NASH mice under hypoxic condition, and inhibiting this pathway can effectively reduce liver inflammation, suggesting its potential as a therapeutic target for NASH treatment.
Animals ; Non-alcoholic Fatty Liver Disease/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Pyroptosis ; Mice, Inbred C57BL ; Male ; Hepatocytes/pathology* ; Signal Transduction ; Mice ; Hypoxia/metabolism* ; Caspase 1/metabolism* ; Interleukin-1beta/metabolism* ; Liver/metabolism*

BACKGROUND:Lumbar disc degeneration is a common disease that causes lower back pain and lower limb neurological symptoms.The balance of collagen metabolism plays an important role in maintaining the stability of the intervertebral discs.OBJECTIVE:To review the research progress in the imbalance of collagen metabolism in intervertebral disc degeneration.METHODS:The first author searched for relevant literature published before May 2024 in CNKI,PubMed and Web of Science databases.Search terms were"degenerative disc disease,""collagen metabolism,""collagenase family,""collagen synthesis related factors,"and"collagen breakdown related factors"in Chinese and English.Seventy-six articles were finally included for review.RESULTS AND CONCLUSION:In the process of intervertebral disc degeneration,the balance of collagen metabolism plays a crucial role in maintaining the stability of the normal intervertebral disc.When intervertebral disc degeneration occurs,a large amount of pro-inflammatory factors,collagenase,and oxidative stress reactions occur in the intervertebral disc,which increases the breakdown of collagen in the intervertebral disc.At the same time,it inhibits the generation of growth factors,collagen synthase,and collagen synthesis-related factors,resulting in a decrease in collagen synthesis in the intervertebral disc.The combined effect of the above two conditions disrupts the balance of collagen metabolism in the intervertebral disc,further exacerbating the process of intervertebral disc degeneration.

Objective:To investigate the improvement in nutritional indicators, clinical complications, and respiratory infections among children with cerebral palsy (CP) and malnutrition who meet the indications for tube feeding under oral feeding and tube feeding interventions.Methods:In this retrospective cohort study, 82 children with CP and malnutrition that met the indications for tube feeding from the Children′s Rehabilitation Hospital of the Third Affiliated Hospital of Zhengzhou University from January 2022 to April 2024 were included.These patients were divided into an oral feeding group and a tube feeding group.The t-test, Mann-Whitney U test, or Kruskal-Wallis test was used to analyze nutritional indices such as weight-for-age Z-score (WAZ), height/length-for-age Z-score (HAZ), and weight-for-height/length Z-score (WHZ) before and after intervention in both groups.The improvement in clinical complications and respiratory infections was also analyzed. Results:After 3-month nutritional intervention, there were 60 cases in the oral feeding group and 22 cases in the tube feeding group.The tube feeding group showed better improvement in WHZ [-0.23(-1.79, 0.88) vs.-1.62(-2.02, -0.91) ] than the oral feeding group ( P<0.05).After 6-month nutritional intervention, there were 50 cases in the oral feeding group and 16 cases in the tube feeding group.The tube feeding group showed better improvement in WAZ [-0.80(-1.92, -0.42) vs. -2.26(-2.88, -1.84)], HAZ (-1.31±1.23 vs. -2.32±1.19), and WHZ (-0.74±1.39 vs. -1.58±1.03) than the oral feeding group (all P<0.05).After 12-month nutritional intervention, there were 30 cases in the oral feeding group and 10 cases in the tube feeding group.The tube feeding group showed better improvement in WAZ [-1.06(-1.77, -0.88) vs.-2.25(-3.06, -1.47) ] and HAZ (-1.22±1.63 vs. -2.54±1.50) than the oral feeding group (all P<0.05).Clinical complications improved better in the tube feeding group than those in the oral feeding group.In the tube feeding group, significant differences in choking ( χ2=16.29, P=0.001) and vomiting ( χ2=6.81, P=0.013) were observed before and after nutritional intervention.There was a statistically significant difference in frequency of lower respiratory infections 3 and 6 months after nutritional intervention between the 2 groups (all P<0.05). Conclusions:Compared with oral feeding, tube feeding can effectively improve the clinical nutritional indicators and reduce the clinical complications and the risk of respiratory infections in CP children that meet the indications for tube feeding.

BACKGROUND:Lumbar disc degeneration is a common disease that causes lower back pain and lower limb neurological symptoms.The balance of collagen metabolism plays an important role in maintaining the stability of the intervertebral discs.OBJECTIVE:To review the research progress in the imbalance of collagen metabolism in intervertebral disc degeneration.METHODS:The first author searched for relevant literature published before May 2024 in CNKI,PubMed and Web of Science databases.Search terms were"degenerative disc disease,""collagen metabolism,""collagenase family,""collagen synthesis related factors,"and"collagen breakdown related factors"in Chinese and English.Seventy-six articles were finally included for review.RESULTS AND CONCLUSION:In the process of intervertebral disc degeneration,the balance of collagen metabolism plays a crucial role in maintaining the stability of the normal intervertebral disc.When intervertebral disc degeneration occurs,a large amount of pro-inflammatory factors,collagenase,and oxidative stress reactions occur in the intervertebral disc,which increases the breakdown of collagen in the intervertebral disc.At the same time,it inhibits the generation of growth factors,collagen synthase,and collagen synthesis-related factors,resulting in a decrease in collagen synthesis in the intervertebral disc.The combined effect of the above two conditions disrupts the balance of collagen metabolism in the intervertebral disc,further exacerbating the process of intervertebral disc degeneration.

Objective:To investigate the improvement in nutritional indicators, clinical complications, and respiratory infections among children with cerebral palsy (CP) and malnutrition who meet the indications for tube feeding under oral feeding and tube feeding interventions.Methods:In this retrospective cohort study, 82 children with CP and malnutrition that met the indications for tube feeding from the Children′s Rehabilitation Hospital of the Third Affiliated Hospital of Zhengzhou University from January 2022 to April 2024 were included.These patients were divided into an oral feeding group and a tube feeding group.The t-test, Mann-Whitney U test, or Kruskal-Wallis test was used to analyze nutritional indices such as weight-for-age Z-score (WAZ), height/length-for-age Z-score (HAZ), and weight-for-height/length Z-score (WHZ) before and after intervention in both groups.The improvement in clinical complications and respiratory infections was also analyzed. Results:After 3-month nutritional intervention, there were 60 cases in the oral feeding group and 22 cases in the tube feeding group.The tube feeding group showed better improvement in WHZ [-0.23(-1.79, 0.88) vs.-1.62(-2.02, -0.91) ] than the oral feeding group ( P<0.05).After 6-month nutritional intervention, there were 50 cases in the oral feeding group and 16 cases in the tube feeding group.The tube feeding group showed better improvement in WAZ [-0.80(-1.92, -0.42) vs. -2.26(-2.88, -1.84)], HAZ (-1.31±1.23 vs. -2.32±1.19), and WHZ (-0.74±1.39 vs. -1.58±1.03) than the oral feeding group (all P<0.05).After 12-month nutritional intervention, there were 30 cases in the oral feeding group and 10 cases in the tube feeding group.The tube feeding group showed better improvement in WAZ [-1.06(-1.77, -0.88) vs.-2.25(-3.06, -1.47) ] and HAZ (-1.22±1.63 vs. -2.54±1.50) than the oral feeding group (all P<0.05).Clinical complications improved better in the tube feeding group than those in the oral feeding group.In the tube feeding group, significant differences in choking ( χ2=16.29, P=0.001) and vomiting ( χ2=6.81, P=0.013) were observed before and after nutritional intervention.There was a statistically significant difference in frequency of lower respiratory infections 3 and 6 months after nutritional intervention between the 2 groups (all P<0.05). Conclusions:Compared with oral feeding, tube feeding can effectively improve the clinical nutritional indicators and reduce the clinical complications and the risk of respiratory infections in CP children that meet the indications for tube feeding.

BACKGROUND:Premature birth is a major global health problem associated with high mortality and morbidity.White matter injury is the most common brain injury in preterm infants.Salvia miltiorrhiza is a traditional herbal plant that is commonly used to treat cardiovascular and cerebrovascular diseases in Asian countries. OBJECTIVE:To investigate the therapeutic effect of Salvia miltiorrhiza on white matter injury in preterm infants. METHODS:Eighteen neonatal male Sprague-Dawley rats at 3-day gestational age were selected and randomized into normal group,white matter injury group,and Salvia miltiorrhiza group.Animal models of preterm white matter injury were established by permanent ligation of the right common carotid artery in the latter two groups.Rats in the Salvia miltiorrhiza group were given intraperitoneal injection of Salvia miltiorrhiza(5 mg/kg·d)for 7 consecutive days.Normal group and white matter injury group were given the same volume of PBS for intervention.On the 14th day after modeling,the rats were sacrificed.Brains were pathologically observed by hematoxylin-eosin staining under microscope,and the expression levels of myelin basic protein and CC1 in brain tissue were visualized using immunofluorescence.Furthermore,liquid chromatography-tandem mass spectrometry was used to analyze possible pathways for the action of Salvia miltiorrhiza. RESULTS AND CONCLUSION:In the white matter injury group,the structure of the corpus callosum was irregular and the cells appeared swollen and necrotic.In addition,induction of white matter injury resulted in significantly reduced myelin formation,with irregular and loosely arranged nerve fibers and significantly decreased myelin sheaths.Interestingly,white matter injury rats treated with Salvia miltiorrhiza had reduced cellular swelling,reduced lesions,and increased myelin sheaths.The expression of myelin basic protein was closely related to myelin formation,and CC1 was a marker of myelin oligodendrocytes.Salvia miltiorrhiza significantly up-regulated the expressions of myelin basic protein and CC1 in white matter injury rats(P＜0.000 1),indicating that Salvia miltiorrhiza alleviated white matter injury.Liquid chromatography-tandem mass spectrometry analysis showed that the therapeutic effect of Salvia miltiorrhiza in the rat model of white matter injury was closely related to the regulation of complement and coagulation cascades.To conclude,Salvia miltiorrhiza may be a potential therapeutic agent for treating preterm white matter injury.

ObjectiveThis study aims to explore risk factors for the development of major adverse cardiovascular and cerebrovascular events （MACCEs） in middle-aged and elderly patients with type 2 diabetes mellitus complicated with stable angina pectoris （T2DM-SAP） based on real-world clinical data in traditional Chinese medicine （TCM）， so as to develop a COX proportional risk prediction model and visualize the predicted results using a nomogram. MethodBased on the clinical scientific research information sharing system， the medical records of 586 T2DM-SAP patients （45-94 years old） were collected from January 2012 to December 2019， including age， gender， course of disease， major medical history， laboratory examination， tongue image， pulse image， TCM syndrome， and major treatment drugs. MACCE outcome indicators of patients were obtained by telephone follow-up and re-hospitalization records. The data was divided into a training set and a validation set according to 7∶3. In the training set， COX univariate analysis was used to determine the risk factors for MACCE in T2DM-SAP patients， and then variables were screened by forward-backward stepwise regression method， so as to establish a MACCE risk prediction model and construct a nomogram. The predictive efficacy of the model was reflected by the C-index， receiver operating characteristic （ROC） curve， calibration map， and clinical decision curve. ResultThe history of cerebrovascular disease ［Hazard ratio （HR）=1.983， 95% confidence interval （CI，1.314-2.993）］， low-density lipoprotein （LDL-C/mmol·L^-1）≥4.1［HR=2.683， 95%CI（1.461-4.925）］， dull red tongue ［HR=1.955， 95%CI（1.273-3.002）］， dull purple tongue ［HR=4.214， 95%CI（2.017-8.803）］， white thick coating ［HR=3.030， 95%CI（1.634-9.293）］， thin and weak pulse ［HR=2.233， 95%CI（1.283-3.888）］， and syndrome of wind-phlegm blocking collaterals ［HR=2.007， 95%CI（1.179-3.418）］ were found to be risk factors in middle-aged and elderly T2DM-SAP patients. Insulin ［HR=0.604， 95%CI（0.399-0.914）］， glycosidase inhibitor ［HR=0.627， 95%CI（0.409-0.962）］， and TCM treatment ［HR=0.328， 95%CI（0.214-0.503）］ were protective factors in middle-aged and elderly T2DM-SAP patients. The prediction model was constructed based on the above risk factors. The C-index of the model was 0.818 （95% CI 0.777 -0.859） in the training set and 0.814 （95% CI 0.773-0.855） in the validation set， and the change of C-index over time was plotted. The AUC of patients for 5， 10， 15 years in the training set was 0.71， 0.67， and 0.61. The AUC of patients for 5， 10， and 15 years in the validation set was 0.60， 0.68， and 0.63， respectively. The calibration map and clinical decision curves of 5， 10， 15 years were drawn in the training set and the validation set， respectively. The model was well calibrated and clinically effective. ConclusionThe history of cerebrovascular disease， LDL， dull red tongue， dull purple tongue， white thick coating， thin and weak pulse， and syndrome of wind-phlegm blocking collaterals are risk factors for MACCE in middle-aged and elderly T2DM-SAP patients， and insulin， glycosidase inhibitors， TCM treatment are protective factors for MACCE in middle-aged and elderly T2DM-SAP patients. A clinical prediction model is established accordingly. This model has good discrimination， calibration degree， and clinical effectiveness and provides a scientific basis for the prevention and treatment of MACCE in middle-aged and elderly T2DM-SAP patients.