BACKGROUND:Macrophage polarization plays a key role in chronic inflammatory joint diseases such as rheumatoid arthritis.Cerium dioxide(CeO2)nanoparticles have a wide range of biomedical applications such as modulating the local inflammatory microenvironment of tissues.OBJECTIVE:To investigate the role of CeO2 nanoparticles on macrophage polarization and inflammatory factor expression,as well as inflammatory modulation in a co-culture system of macrophages and fibroblasts.METHODS:(1)CeO2 nanoparticles were dispersed and observed morphologically by transmission electron microscopy.(2)Human leukemia monocytes(THP-1)were induced to differentiate and establish the M1 macrophage pro-inflammatory cell model of rheumatoid arthritis.The cells were divided into M0 group(undifferentiated macrophages),M1 group(successful macrophage modeling),CeO2 nanoparticle treatment group(M1 group with CeO2 nanoparticle treatment),and dexamethasone control group(M1 group with dexamethasone treatment)and incubated for 48 hours.The effects of CeO2 nanoparticles on the expression of inflammatory factors(endogenous nitric oxide synthase,CD86,CD80)in M1 macrophages and M1 macrophage phenotype(CD80,CD206)were detected by RT-qPCR,western blot assay,and flow cytometry.(3)A co-culture system of macrophages and fibroblasts was established,and CeO2 nanoparticles acted on the upper macrophages.The regulation of CeO2 nanoparticles on the expression of inflammatory factors(interleukin-6,tumor necrosis factor-α,cyclooxygenase-2,and endogenous nitric oxide synthase)of fibroblasts in the co-culture system was observed at the mRNA and protein levels.RESULTS AND CONCLUSION:(1)Transmission electron microscopy showed that the diameter of CeO2 nanoparticles was(19.5±2.0)nm.(2)Compared with the M0 group,the mRNA of endogenous nitric oxide synthase and CD86,and the protein expression of endogenous nitric oxide synthase and CD80 in the M1 group were upregulated.Compared with the M1 group,the mRNA expression of endogenous nitric oxide synthase and CD86,and the protein expression of endogenous nitric oxide synthase and CD80 in the CeO2 nanoparticle treatment group were downregulated.Flow cytometry showed that 20 nm CeO2 nanoparticles downregulated the number of M1 macrophages.(3)Compared with the M1 group,20 nm CeO2 nanoparticles downregulated the mRNA and protein expression of inflammatory factors(tumor necrosis factor α,interleukin 6,cyclooxygenase 2,and endogenous nitric oxide synthase)in the co-culture system HFL1 cells.(4)The results showed that 20 nm CeO2 nanoparticles can alleviate inflammation in the co-culture system by inhibiting the expression of pro-inflammatory factors in M1 macrophages,providing a new idea for the treatment of inflammatory diseases such as rheumatoid arthritis.

BACKGROUND:In 2019,the modified cortical bone trajectory technique was proposed by our team,significantly improving traditional methods.Previous studies have highlighted its superior biomechanical properties for segment fixation.However,a comprehensive systematic analysis of its specific biomechanical effects on adjacent segment degeneration is lacking,particularly regarding its influence on range of motion and intervertebral disc stress in posterior lumbar interbody fusion and transforaminal lumbar interbody fusion techniques.OBJECTIVE:To investigate the biomechanical effects of modified cortical bone trajectory screw techniques on adjacent segment degeneration in posterior lumbar interbody fusion and transforaminal lumbar interbody fusion.METHODS:CT scans were performed on three human cadaver specimens to establish and validate three-dimensional intact finite element models of the L1-S1 segment.For each of these,the posterior lumbar interbody fusion or transforaminal lumbar interbody fusion with three different fixation techniques was reconstructed at the L4-L5 segment.The L4-L5 segment was fixed using three different internal fixation techniques(modified cortical bone trajectory,cortical bone trajectory,and traditional pedicle screws).The range of motion and von Mises stress of the intervertebral disc of the L3-L4 and L5-S1 segments were recorded with a 400 N compressive load and 7.5 N moments in flexion,extension,left-right bending,and left-right rotation.The impacts of the three internal fixation techniques on adjacent segment degeneration in the two kinds of fusion were compared and analyzed.RESULTS AND CONCLUSION:(1)In the posterior lumbar interbody fusion model,the modified cortical bone trajectory screw group showed a reduced range of motion on adjacent segments(L3-L4,L5-S1)under six loading conditions compared to both the cortical bone trajectory screw group and traditional bone trajectory screw group.Specifically,the modified cortical bone trajectory screw group significantly reduced the maximum stress on the intervertebral disc in the superior adjacent segment(L3-L4)during extension compared to the traditional bone trajectory screw group(P=0.005),while the stress on the intervertebral disc in the inferior adjacent segment(L5-S1)exhibited greater dispersion.Similarly,the cortical bone trajectory screw group also significantly reduced the maximum stress on the intervertebral disc in the superior adjacent segment(L3-L4)during extension compared with the traditional bone trajectory screw group(P=0.03).(2)Compared with transforaminal lumbar interbody fusion,the three internal fixation techniques(modified cortical bone trajectory,cortical bone trajectory,and traditional pedicle screws)showed a trend of reduced range of motion in the inferior adjacent segment(L5-S1)under six loading conditions.In contrast,the maximum stress on the intervertebral discs in both the superior and inferior adjacent segments(L3-L4,L5-S1)exhibited an increasing trend in the posterior lumbar interbody fusion model.(3)It is concluded that in the posterior lumbar interbody fusion model,the modified cortical bone trajectory screw exhibited superior biomechanical properties in reducing the range of motion at adjacent segments,which may have a beneficial effect on reducing the risk of adjacent segment degeneration.

BACKGROUND:Macrophage polarization plays a key role in chronic inflammatory joint diseases such as rheumatoid arthritis.Cerium dioxide(CeO2)nanoparticles have a wide range of biomedical applications such as modulating the local inflammatory microenvironment of tissues.OBJECTIVE:To investigate the role of CeO2 nanoparticles on macrophage polarization and inflammatory factor expression,as well as inflammatory modulation in a co-culture system of macrophages and fibroblasts.METHODS:(1)CeO2 nanoparticles were dispersed and observed morphologically by transmission electron microscopy.(2)Human leukemia monocytes(THP-1)were induced to differentiate and establish the M1 macrophage pro-inflammatory cell model of rheumatoid arthritis.The cells were divided into M0 group(undifferentiated macrophages),M1 group(successful macrophage modeling),CeO2 nanoparticle treatment group(M1 group with CeO2 nanoparticle treatment),and dexamethasone control group(M1 group with dexamethasone treatment)and incubated for 48 hours.The effects of CeO2 nanoparticles on the expression of inflammatory factors(endogenous nitric oxide synthase,CD86,CD80)in M1 macrophages and M1 macrophage phenotype(CD80,CD206)were detected by RT-qPCR,western blot assay,and flow cytometry.(3)A co-culture system of macrophages and fibroblasts was established,and CeO2 nanoparticles acted on the upper macrophages.The regulation of CeO2 nanoparticles on the expression of inflammatory factors(interleukin-6,tumor necrosis factor-α,cyclooxygenase-2,and endogenous nitric oxide synthase)of fibroblasts in the co-culture system was observed at the mRNA and protein levels.RESULTS AND CONCLUSION:(1)Transmission electron microscopy showed that the diameter of CeO2 nanoparticles was(19.5±2.0)nm.(2)Compared with the M0 group,the mRNA of endogenous nitric oxide synthase and CD86,and the protein expression of endogenous nitric oxide synthase and CD80 in the M1 group were upregulated.Compared with the M1 group,the mRNA expression of endogenous nitric oxide synthase and CD86,and the protein expression of endogenous nitric oxide synthase and CD80 in the CeO2 nanoparticle treatment group were downregulated.Flow cytometry showed that 20 nm CeO2 nanoparticles downregulated the number of M1 macrophages.(3)Compared with the M1 group,20 nm CeO2 nanoparticles downregulated the mRNA and protein expression of inflammatory factors(tumor necrosis factor α,interleukin 6,cyclooxygenase 2,and endogenous nitric oxide synthase)in the co-culture system HFL1 cells.(4)The results showed that 20 nm CeO2 nanoparticles can alleviate inflammation in the co-culture system by inhibiting the expression of pro-inflammatory factors in M1 macrophages,providing a new idea for the treatment of inflammatory diseases such as rheumatoid arthritis.

BACKGROUND:In 2019,the modified cortical bone trajectory technique was proposed by our team,significantly improving traditional methods.Previous studies have highlighted its superior biomechanical properties for segment fixation.However,a comprehensive systematic analysis of its specific biomechanical effects on adjacent segment degeneration is lacking,particularly regarding its influence on range of motion and intervertebral disc stress in posterior lumbar interbody fusion and transforaminal lumbar interbody fusion techniques.OBJECTIVE:To investigate the biomechanical effects of modified cortical bone trajectory screw techniques on adjacent segment degeneration in posterior lumbar interbody fusion and transforaminal lumbar interbody fusion.METHODS:CT scans were performed on three human cadaver specimens to establish and validate three-dimensional intact finite element models of the L1-S1 segment.For each of these,the posterior lumbar interbody fusion or transforaminal lumbar interbody fusion with three different fixation techniques was reconstructed at the L4-L5 segment.The L4-L5 segment was fixed using three different internal fixation techniques(modified cortical bone trajectory,cortical bone trajectory,and traditional pedicle screws).The range of motion and von Mises stress of the intervertebral disc of the L3-L4 and L5-S1 segments were recorded with a 400 N compressive load and 7.5 N moments in flexion,extension,left-right bending,and left-right rotation.The impacts of the three internal fixation techniques on adjacent segment degeneration in the two kinds of fusion were compared and analyzed.RESULTS AND CONCLUSION:(1)In the posterior lumbar interbody fusion model,the modified cortical bone trajectory screw group showed a reduced range of motion on adjacent segments(L3-L4,L5-S1)under six loading conditions compared to both the cortical bone trajectory screw group and traditional bone trajectory screw group.Specifically,the modified cortical bone trajectory screw group significantly reduced the maximum stress on the intervertebral disc in the superior adjacent segment(L3-L4)during extension compared to the traditional bone trajectory screw group(P=0.005),while the stress on the intervertebral disc in the inferior adjacent segment(L5-S1)exhibited greater dispersion.Similarly,the cortical bone trajectory screw group also significantly reduced the maximum stress on the intervertebral disc in the superior adjacent segment(L3-L4)during extension compared with the traditional bone trajectory screw group(P=0.03).(2)Compared with transforaminal lumbar interbody fusion,the three internal fixation techniques(modified cortical bone trajectory,cortical bone trajectory,and traditional pedicle screws)showed a trend of reduced range of motion in the inferior adjacent segment(L5-S1)under six loading conditions.In contrast,the maximum stress on the intervertebral discs in both the superior and inferior adjacent segments(L3-L4,L5-S1)exhibited an increasing trend in the posterior lumbar interbody fusion model.(3)It is concluded that in the posterior lumbar interbody fusion model,the modified cortical bone trajectory screw exhibited superior biomechanical properties in reducing the range of motion at adjacent segments,which may have a beneficial effect on reducing the risk of adjacent segment degeneration.

The key to the onset and progression of the functional impairments of orthopedic diseases is imba-lance of deficiency and excess， disharmony of movement and stillness， dislocation of sinews and bones， imbalance of rigidity and flexibility， and disharmony of body and spirit. Based on this， the "five views" treatment principle has been proposed for traditional Chinese medicine （TCM） orthopedic rehabilitation， which include the view of balancing deficiency and excess， combining movement and stillness， focusing on both sinews and bones， integrating rigidity and flexibility， and harmonizing body and spirit. Correspondingly， the "five views" collaborative rehabilitation clinical model is established， providing a reference for enhancing the systematization and targeting of TCM orthopedic rehabilitation.

ObjectiveTo identify the pathogen species responsible for the wilt disease of Tetradium ruticarpum in Chongqing， investigate there biological characteristics， and screen effective fungicides， so as to provide a theoretical basis for disease control in production. MethodsThe pathogen was isolated via the tissue culture method. Pathogenicity was verified according to Koch's postulates. The pathogen was identified based on morphological characteristics and multi-gene phylogenetic analysis. The mycelial growth rate method was used for biological characterization of the pathogen and fungicide screening. ResultsThe pathogen colonies were nearly circular with irregular edges， white， short， velvety aerial hyphae， and pale purple undersides. Macroconidia were colorless， sickle-shaped， with 3-5 septa， while microconidia were transparent， elliptical， aseptate or with 1-2 septa. Multi-gene phylogenetic analysis showed that the pathogen clustered in the same clade as Fusarium fujikuroi with 100% support， which， combined with morphological characteristics， identified the pathogen causing wilt of T. ruticarpum in Chongqing as F. fujikuroi. The optimal conditions for the mycelial growth of F. fujikuroi were mung bean agar （MBA） with glucose as the carbon source， beef extract and yeast powder as nitrogen sources， 28 ℃， pH 7.0， and alternating light/dark conditions. The optimal conditions for sporulation were potato dextrose agar （PDA） with glucose as the carbon source， beef extract as the nitrogen source， 28 ℃， pH 7.0， and complete darkness. Among chemical fungicides， phenazine-1-carboxylic acid exhibited the strongest inhibitory effect on F. fujikuroi. Shenqinmycin and tetramycin were the most effective bio-fungicides. ConclusionThis study is the first to report F. fujikuroi as the causal agent of wilt disease in T. rutaecarpa. The chemical fungicide phenazine-1-carboxylic acid and the bio-fungicides shenqinmycin and tetramycin showed strong inhibitory effects against F. fujikuroi.

ObjectiveTo analyze the pharmacodynamic substance basis of Shangkeling Spray and its potential mechanisms in intervening knee osteoarthritis （KOA） using ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS）， network pharmacology， and molecular docking technology. MethodsUPLC-MS was used to identify the chemical components of Shangkeling Spray. Pharmacokinetic properties were employed to screen potential active ingredients. Network pharmacology methods were utilized to collect potential targets of these ingredients and the pathological gene set of KOA. An "active ingredient-disease" target network was constructed using databases such as STRING. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） functional enrichment analyses were performed using clusterProfiler. Libraries including NumPy were employed to calculate shortest path lengths to identify dominant pharmacodynamic links. Core gene clusters were identified using MCODE， validated through the Gene Expression Omnibus （GEO） database， and molecular docking was performed between key active ingredients and core targets. ResultsA total of 322 and 314 chemical components were identified under positive and negative ion modes， respectively， with 410 components in total after de-duplication， mainly including flavonoids， coumarins， terpenoids， organic acids， and alkaloids. Analysis of the "active ingredient-disease" network identified "development and regeneration"， "cell growth and death"， "immune system"， and "nervous system" as the dominant pharmacodynamic links of Shangkeling Spray in the treatment of KOA. Molecular docking showed that key active ingredients， such as bletillin A， formononetin， morin， oxymatrine， aconitine， gallic acid， curdione， apigenin， naringenin， and oleanolic acid， tightly bound to functional domains of 10 key targets including Jun proteins（JUN）， interleukin-6 （IL-6）， protein kinase B1 （Akt1）， Caspase-3， nuclear transcription factor-κB subunit p65（RELA）， nuclear factor-kappaB1（NF-κB1）， Cyclin D₁， mammalian target of rapamycin（mTOR）， tumor necrosis factor （TNF）， and Fos proto-oncogene protein （FOS）. These interactions synergistically regulated the phosphatidylinositol 3-kinase （PI3K）/Akt/mTOR-related signaling axis and nervous system-related pathways， mediating cartilage repair， reducing inflammation and pain， and improving KOA. ConclusionThis study preliminarily clarifies the pharmacodynamic substance basis of Shangkeling Spray and suggests that its main active ingredients may improve KOA by synergistically regulating the PI3K/Akt/mTOR-related pathways， providing a reference for subsequent exploration of its substance benchmark and mechanism of action.

OBJECTIVE To investigate the clinical characteristics and risk factors for batroxobin-related severe hypofibrinogenemia （HFIB） and construct a risk prediction model. METHODS A retrospective analysis was conducted on inpatients treated with batroxobin in the First Medical Center of a tertiary hospital from January 1， 2020， to December 31， 2024. Patients were categorized into non-severe HFIB group and severe HFIB group based on the severity of HFIB. Univariate and multivariate Logistic regression analyses were performed to identify the independent influencing factors for batroxobin-related severe HFIB. A nomogram was developed using the “rms” package in R 4.5 software. The predictive performance of the model was evaluated using the receiver operating characteristic curve. Calibration was assessed via the Bootstrap resampling method， and goodness-of-fit was evaluated with the Hosmer-Lemeshow test. RESULTS A total of 1 472 patients were included in this study. Of these， 1 445 developed HFIB， yi elding an incidence of 98.17%. Furthermore， 895 were classified as severe HFIB， accounting for 60.80% of the cohort. Multivariate Logistic regression analysis showed that increased age， high initial dose per 10 kg body weight， use of maintenance dose， and concomitant glucocorticoid use were independent risk factors for batroxobin-related severe HFIB， while high baseline fibrinogen （FIB） level was identified as a protective factor. The model demonstrated an area under the curve of 0.760 （95% CI： 0.735-0.785）. The mean absolute error of the calibration curve was 0.006. The P value of the Hosmer-Lemeshow test was 0.609. CONCLUSIONS Batroxobin can rapidly and significantly reduce FIB levels and carries a risk of inducing severe HFIB. Patients with advanced age， high initial dose per 10 kg body weight， use of maintenance dose and concomitant glucocorticoid use had a higher risk of batroxobin-related severe HFIB， while high baseline FIB level had a lower risk of batroxobin-related severe HFIB. The risk prediction model developed based on these factors can be used to predict the likelihood of batroxobin-related severe HFIB.

The onset and progression of chronic heart failure （CHF） are closely associated with myocardial energy metabolism disorders， and this pathological process significantly affects patient prognosis. Traditional Chinese medicine （TCM）， grounded in time-based medical theories such as the correspondence between humans and nature and the theory of circadian flow of meridians （Ziwu Liuzhu）， exhibits intrinsic consistency with modern circadian rhythm theory， providing a unique theoretical framework for understanding and intervening in CHF from a temporal perspective. This article systematically explores the impact of circadian rhythms on energy metabolism and the potential mechanisms by which TCM active ingredients intervene in CHF through a review of relevant literature. It is found that various TCM active ingredients， including flavonoids （such as nobiletin）， alkaloids （such as berberine）， and polyphenols （such as resveratrol）， can improve mitochondrial function， promote fatty acid oxidation， enhance glucose uptake and utilization efficiency， maintain metabolic balance， and alleviate oxidative stress and inflammatory responses in myocardial cells by regulating the expression and rhythms of core circadian clock genes such as CLOCK， BMAL1， PER， and CRY. These actions thereby correct energy metabolism disorders and improve cardiac function. Further exploration of the interaction mechanisms between these components and the circadian rhythms holds promise for providing novel theoretical foundations and potential intervention strategies for the prevention and treatment of CHF.

ObjectiveTo identify potential influencing factors of urate crystal deposition at ankle/foot in patients with hyperuricemia （HUA）， and to analyze the predictive value of inflammatory indicators for urate crystal deposition in patients with different traditional Chinese medicine （TCM） syndromes， so as to provide potential reference for clinical risk assessment and individualized TCM intervention. MethodsA retrospective study was carried out with the enrollment of 231 HUA patients from The Third Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine between January 2021 and December 2024. The enrolled patients were further divided into a crystal deposition-positive group （143 cases） and a crystal deposition-negative group （88 cases） according to the results of dual-energy computed tomography （CT）. Sociodemographic data， living habits， serum uric acid levels， and inflammatory indicators of the enrolled patients were collcted， and TCM syndrome differentiation was performed. Furthermore， univariate analysis was used to compare inter-group differences in clinical characteristics. MMultivariate Logistic regression was applied to identify the influencing factors of urate crystal deposition. In addition， the receiver operating characteristic （ROC） curves were plotted to evaluate the predictive efficacy of inflammatory indicators for crystal deposition across different TCM syndromes. ResultsThere were statistically significant inter-group differences in the proportion of males， age， body mass index， proportion of mental labor， rate of low water intake， and rate of high-sugar beverage consumption （P<0.05），whereas no significant difference in low exercise intensity was found between the two groups. Furthermore， compared with the negative group， the positive group had higher serum uric acid level， neutrophil-to-lymphocyte ratio （NLR）， and platelet-to-lymphocyte ratio （PLR）， but lower systemic immune-inflammation index （SIRI） （P<0.05）. Regarding the distribution of TCM syndromes， the positive group was dominated by the dampness-heat accumulation syndrome （55/143，38.46%）， while the negative group was mainly characterized by the phlegm-turbidity obstruction syndrome （44/88，50.00%）. Multivariate Logistic regression analysis revealed that high-sugar beverage consumption， elevated NLR， and elevated PLR were risk factors for urate crystal deposition ［odd ratio （OR） = 8.002， 5.377， 1.034， respectively； 95% CI 1.572-40.732， 2.179-13.270， 1.013-1.054，all P<0.05］， while SIRI was a protective factor （OR = 0.869， 95% CI 0.778-0.971， P<0.05）. In the positive group， patients with the dampness-heat accumulation syndrome exhibited the highest NLR， while the lowest PLR and SIRI， showing statistically significant differences with those of other syndromes （all P<0.05）. In addition， ROC curve analysis indicated that for the dampness-heat accumulation syndrome， the combined "NLR + PLR" model had an area under the curve （AUC） of 0.901 （95% CI 0.850-0.951， P<0.01）， with a sensitivity of 89.1% and a specificity of 79.5%； for the blood stasis-heat obstruction syndrome， the combined "NLR + PLR" model had an AUC of 0.880 （95% CI 0.825-0.934， P<0.01）， with a sensitivity of 100.0% and a specificity of 67.3%； for the liver-kidney Yin-deficiency syndrome， the single PLR model had an AUC of 0.842 （95% CI 0.731-0.952， P<0.01）， with a sensitivity of 83.3% and a specificity of 84.0%. ConclusionUrate crystal deposition in HUA patients exhibits intimate associations with high-sugar beverage consumption as well as elevated NLR and PLR levels. Meanwhile， TCM syndrome differentiation has potential correlation with inflammatory characteristics. The inflammatory indicator-based prediction model constructed based on TCM syndromes exhibits good predictive value.