BACKGROUND:Scholars at home and abroad consider New Zealand rabbits to be an ideal model animal because of the similar anatomical morphology of the lumbar spine to that of the human lumbar spine.There is a lack of systematic comparison of different ways to establish rabbit intervertebral disc degeneration models under X-ray guidance. OBJECTIVE:To establish a rabbit model of lumbar disc degeneration using X-ray guided acupuncture,end-plate injection and combined method,and to compare the modeling effects of these three methods. METHODS:Eighteen 6-month-old New Zealand white rabbits were randomly selected and divided into four groups:acupuncture group,endplate injection group,combined group and blank control group.In the acupuncture group,three consecutive segments of the intervertebral discs(L2/3,L3/4,L4/5)were needled and modeled;in the endplate injection group,50 μL of anhydrous ethanol was injected at a single point on the endplates of the three consecutive segmental discs;in the combined group,three consecutive segmental intervertebral discs were needled and injected with 50 μL of anhydrous ethanol at four azimuthal points on the endplates of the corresponding segmental discs;and the blank control group received no interventions.X-ray examination was performed to measure the disc height index at 2,4,and 8 weeks after surgery.The intervertebral disc tissues were then taken for anatomical observation and pathological examination. RESULTS AND CONCLUSION:(1)Anatomical examination showed that fibrous annulus rupture,nucleus pulposus degeneration,and total disc structure disorder were the main manifestation in the acupuncture group,endplate injection group,and combined group,respectively.(2)X-ray examination showed that the disc height index showed the most obvious reduction in the acupuncture group at 2 weeks after operation,significant reductions in the endplate injection group at 2 and 4 weeks after operation,and significant reductions in the combined group at 2,4,and 8 weeks after operation.(3)Pathological examination showed that the fibrous ring structure was damaged and the inner annulus fibrosus protruded inward in the acupuncture group;endplate fissure,disordered arrangement and nucleus loss were observed in the endplate injection group;total disc structure disorder with the nucleus pulposus losing water and shrinking and no obvious border with the broken annulus fibrosus was found in the combined group.To conclude,acupuncture,endplate injection and the modified endplate injection method can establish the rabbit intervertebral disc degeneration model.Compared with the single method,the modified endplate injection method can greatly accelerate and aggravate the degeneration of the intervertebral disc,and can effectively shorten the experiment period.

BACKGROUND:Osteosarcoma has a complex pathogenesis and a poor prognosis.While advancements in medical technology have led to some improvements in the 5-year survival rate,substantial progress in its treatment has not yet been achieved. OBJECTIVE:To screen key molecular markers in osteosarcoma,analyze their relationship with osteosarcoma treatment drugs,and explore the potential disease mechanisms of osteosarcoma at the molecular level. METHODS:GSE99671 and GSE284259(miRNA)datasets were obtained from the Gene Expression Omnibus database.Differential gene expression analysis and Weighted Gene Co-expression Network Analysis(WGCNA)on GSE99671 were performed.Functional enrichment analysis was conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes separately for the differentially expressed genes and the module genes with the highest positive correlation to the disease.The intersection of these module genes and differentially expressed genes was taken as key genes.A Protein-Protein Interaction network was constructed,and correlation analysis on the key genes was performed using CytoScape software,and hub genes were identified.Hub genes were externally validated using the GSE28425 dataset and text validation was conducted.The drug sensitivity of hub genes was analyzed using the CellMiner database,with a threshold of absolute value of correlation coefficient|R|>0.3 and P<0.05. RESULTS AND CONCLUSION:(1)Differential gene expression analysis identified 529 differentially expressed genes,comprising 177 upregulated and 352 downregulated genes.WGCNA analysis yielded a total of 592 genes with the highest correlation to osteosarcoma.(2)Gene Ontology enrichment results indicated that the development of osteosarcoma may be associated with extracellular matrix,bone cell differentiation and development,human immune regulation,and collagen synthesis and degradation.Kyoto Encyclopedia of Genes and Genomes enrichment results showed the involvement of pathways such as PI3K-Akt signaling pathway,focal adhesion signaling pathway,and immune response in the onset of osteosarcoma.(3)The intersection analysis revealed a total of 59 key genes.Through Protein-Protein Interaction network analysis,8 hub genes were selected,which were LUM,PLOD1,PLOD2,MMP14,COL11A1,THBS2,LEPRE1,and TGFB1,all of which were upregulated.(4)External validation revealed significantly downregulated miRNAs that regulate the hub genes,with hsa-miR-144-3p and hsa-miR-150-5p showing the most significant downregulation.Text validation results demonstrated that the expression of hub genes was consistent with previous research.(5)Drug sensitivity analysis indicated a negative correlation between the activity of methotrexate,6-mercaptopurine,and pazopanib with the mRNA expression of PLOD1,PLOD2,and MMP14.Moreover,zoledronic acid and lapatinib showed a positive correlation with the mRNA expression of PLOD1,LUM,MMP14,PLOD2,and TGFB1.This suggests that zoledronic acid and lapatinib may be potential therapeutic drugs for osteosarcoma,but further validation is required through additional basic experiments and clinical studies.

BACKGROUND:Many recent studies have shown a close relationship between inflammatory cytokines and osteoporosis and bone mineral density(BMD).However,the causal relationship between inflammatory cytokines and BMD has not been fully revealed. OBJECTIVE:To explore the potential causal relationship between inflammatory cytokines and BMD using a two-sample Mendelian randomization analysis. METHODS:The single nucleotide polymorphisms associated with 41 circulating inflammatory cytokines were selected from the open database of genome-wide association studies(GWAS)as instrumental variables.The GWAS data about BMD were from the Genetic Factors for Osteoporosis Consortium,involving a total of 32 735 individuals of European ancestry.Inverse variance weighting was used as the primary analysis to evaluate the causal effect.Weighted median,MR Egger regression,simple mode,and weighted mode methods were used to supplement the explanation.We used the MR-Egger intercept and MR-PRESSO method to conduct a pleiotropy test,the Cochran's Q test was used to determine whether there was heterogeneity in the results,and the leave-one-out method was used to evaluate the stability of the results.In addition,to more accurately assess the causality,the Bonferroni-corrected test was used to identify inflammatory cytokines that have a strong causal relationship with BMD. RESULTS AND CONCLUSION:(1)According to the results of the inverse variance weighting method,we found a positive causal relationship between interleukin-8 and lumbar spine BMD[β=0.075,95%confidence interval(CI):0.033-0.117,P=0.000 5),while a negative causal relationship between interleukin-17 and lumbar spine BMD(β=-0.083,95%CI:-0.152 to-0.014,P=0.018).There might be a negative causal relationship between tumor necrosis factor b and femoral neck BMD(β=-0.053,95%CI:-0.088 to-0.018,P=0.003),while a positive causal relationship between basic fibroblast growth factor and femoral neck BMD(β=0.085,95%CI:0.016-0.154,P=0.015).There might be a negative causal relationship between macrophage inflammatory protein-1a and total body BMD(β=-0.056,95%CI:-0.105 to-0.007,P=0.025).There was a negative causal relationship between interleukin-5(β=-0.019,95%CI:-0.031 to-0.006,P=0.004),stromal cell-derived factor-1a(β=-0.022,95%CI:-0.038 to-0.005,P=0.010),hepatocyte growth factor(β=-0.021,95%CI:-0.041 to-0.002,P=0.030),interleukin-4(β=-0.016,95%CI:-0.032 to-0.001,P=0.034)and heel BMD,while a positive causal relationship between nerve growth factor(β=0.019,95%CI:0.002-0.036,P=0.033),granulocyte colony-stimulating factor(β=0.011,95%CI:0.000-0.022,P=0.050),and heel BMD.Meanwhile,after the Bonferroni-corrected test,there was a strong positive causal effect between interleukin-8 and lumbar spine BMD(P=0.000 5).And consistent directional effects for all analyses were observed in MR Egger,weighted median,simple mode,and weighted mode methods.(2)Sensitivity analyses revealed no heterogeneity,pleiotropy,or outliers for the causal effect of circulating inflammatory cytokines on BMD.

AIM:To investigate the relationship between the level of monocyte chemoattractant protein-1(MCP-1)in the aqueous humor and macular microcirculation in patients with macular edema secondary to retinal vein occlusion(RVO-ME).METHODS:A total of 327 patients(327 eyes)with RVO-ME treated in our hospital from July 2022 to July 2024 were selected as the research objects. According to the recurrence or not, they were divided into non-recurrence group(291 cases, 291 eyes)and recurrence group(36 cases, 36 eyes). The clinical data, macular microcirculation index and MCP-1 level were collected. Unordered multinomial Logistic regression was used to analyze the effect of MCP-1 on RVO-ME recurrence after excluding the influence of other factors. Cubic spline was used to analyze the dose-response relationship between macular microcirculation indexes and MCP-1 expression level and RVO-ME recurrence. Multiple linear regression was used to analyze the relationship between macular microcirculation parameters and MCP-1 expression level, and the difference of MCP-1 expression level in recurrence under different macular microcirculation parameters was analyzed. Bootstrap method was used to test the mediating effect of macular microcirculation indexes on MCP-1 expression level and RVO-ME recurrence.RESULTS: The course of ME, the incidence of vitreomacular traction(VMT), the incidence of fibrous membrane epiretinal membrane(ERM), best corrected visual acuity(BCVA), hyperreflective foci in the inner and outer retinal layers(HRF), the frequency and dose of anti-vascular endothelial growth factor(VEGF)injection in the recurrence group were significantly higher than those in the non-recurrence group(all P<0.05). The external limiting membrane(ELM)integrity and ellipsoid zone(EZ)integrity in the recurrence group were significantly worse than those in the non-recurrence group(all P<0.05). The central foveal thickness(CFT), central macular thickness(CMT), superficial capillary plexus(SCP)vascular density, deep capillary plexus(DCP)vascular density and MCP-1 in the recurrence group were higher than those in the non-recurrence group(all P<0.05), and the foveal avascular zone(FAZ)area was lower than that in the non-recurrence group(P<0.05). Logistic analysis showed that MCP-1 was a risk factor for RVO-ME recurrence before and after adjusting for confounding factors. There was a significant non-linear dose-response relationship between macular microcirculation indexes and MCP-1 expression and the risk of RVO-ME recurrence(non-linear test, all P<0.001). The vascular density of CFT, CMT, SCP and DCP was positively correlated with the expression level of MCP-1(all P<0.05), while the FAZ was negatively correlated with MCP-1 expression level(P<0.05). With the increase of vessel density in CFT, CMT, SCP and DCP, and the decrease of FAZ, the expression level of MCP-1 increased, and the risk of RVO-ME recurrence showed an upward trend. The proportion of MCP-1 in Q3(>28.47 pg/mL)group was the highest(P<0.05). Macular microcirculation parameters play a mediating effect between MCP-1 expression level and RVO-ME recurrence.CONCLUSION: The level of MCP-1 in aqueous humor is positively correlated with RVO-ME recurrence, and it is closely related to macular microcirculation. Macular microcirculation has a mediating effect between MCP-1 level and RVO-ME recurrence.

ObjectiveTo investigate the association between variant degree of sarcopenia and all-cause mortality in Chinese elderly residents, and to provide insights into the prevention and control of sarcopenia in the elderly population. MethodsData from the China Health and Retirement Longitudinal Study (CHARLS) from 2011 and 2020 were analyzed, and a total of 2 792 subjects aged 65 years or older were selected according to the inclusion and exclusion criteria. Univariate and multivariate Cox proportional hazards regression analysis were performed to explore the potential factors influencing all-cause mortality among the elderly in China, and Kaplan-Meier curves were used to visualize the survival of elderly people with variant degree of sarcopenia. Finally, a multiple-adjusted Cox proportional hazards regression model was used to control the confounding factors and explore the association between sarcopenia and all-cause mortality. ResultsBefore adjusting potential covariates, univariate and multivariate Cox proportional hazards regression models showed that 10-year all-cause mortality was significantly associated with variant degree of sarcopenia, namely possible sarcopenia (HR=1.40, 95%CI: 1.1‒1.68, P<0.001), mild-to-moderate sarcopenia (HR=1.49, 95%CI:1.20‒1.86, P<0.001), and severe sarcopenia (HR=1.68, 95%CI: 1.29‒2.19, P<0.001); after adjusting all confounders, 10-year all-cause mortality remained to be significantly associated with variant degree of sarcopenia, including probable sarcopenia (HR=1.38, 95%CI: 1.15‒1.66, P<0.001), mild-to-moderate sarcopenia (HR=1.48, 95%CI: 1.19‒1.84, P<0.001) and severe sarcopenia (HR=1.71, 95%CI: 1.31‒2.23, P<0.001). ConclusionIn Chinese elderly residents, sarcopenia is positively associated with an increased risk of 10-year all-cause mortality, and the progression of sarcopenia is positively associated with an increased risk of death.

BackgroundSocial support can help alleviate depressive symptoms in patients with major depressive disorder （MDD） and improve individual levels of empathy. The higher the level of empathy， the lower the probability of depressive symptoms. At present， the relationship between social support， empathy and depressive symptoms in MDD patients is unclear. ObjectiveTo explore the pathway of empathy in the relationship between social support and depressive symptoms in patients with MDD， so as to provide references for clinical treatment of MDD patients. MethodsA total of 126 patients who visited the outpatient clinic of Tianjin Anding hospital from July 2020 to September 2022 and met the diagnostic criteria for Major Depressive Disorder （MDD） according to the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） were selected as the study subjects. Hamilton Depression Scale-17 item （HAMD-17）， Interpersonal Reactivity Index （IRI） and Social Support Rating Scale （SSRS） were used for assessment. Pearson correlation analysis was conducted to examine the correlations among the scale scores. Path analysis was performed using Model 4 of the Process 3.4.1. Bootstrap method was used to test the path effects. ResultsAmong MDD patients， HAMD-17 total score was positively correlated with IRI total score and its subscales of fantasy and personal distress （r=0.225， 0.213， 0.220， P<0.05）. HAMD-17 total score was negatively correlated with SSRS total score and its subscales of subjective support and support utilization （r=-0.211， -0.181， -0.208， P<0.05）. The score of support utilization subscale of SSRS was positively correlated with IRI total score and its subscale of perspective taking and empathic concern （r=0.257， 0.261， 0.331， P<0.01）. Empathy served as a pathway between support utilization and depressive symptoms， with an indirect effect of 0.217 （95% CI： 0.060~0.426）， and the effect size was 36.90%. ConclusionEmpathy may serve as a pathway between support utilization and depressive symptoms in patients with MDD.

Biomolecular condensates are formed through phase separation of biomacromolecules such as proteins and RNAs. These condensates exhibit liquid-like properties that can futher transition into more stable material states. They form complex internal structures via multivalent weak interactions, enabling precise spatiotemporal regulations. However, the use of inconsistent and non-standardized terminology has become increasingly problematic, hindering academic exchange and the dissemination of scientific knowledge. Therefore, it is necessary to discuss the terminology related to biomolecular condensates in order to clarify concepts, promote interdisciplinary cooperation, enhance research efficiency, and support the healthy development of this field.

Paclitaxel， a highly effective natural antitumor drug， has been demonstrated to be efficacious in the treatment of a variety of cancers， including breast cancer， ovarian cancer， and lung cancer. The traditional paclitaxel injections have been observed to present certain issues， including overt adverse reactions and a decline in the quality of life of patients following treatment. This ultimately leads to an inability to meet the comprehensive needs of patients， thereby limiting the clinical applications of the drugs. Compared with injectable administration， the oral administration can avoid the risk of infection present in the invasive route， is conducive to improving patient compliance and quality of life， and reduces healthcare costs， and has a good application prospect. However， paclitaxel has low solubility， poor permeability， and is susceptible to the exocytosis of P-glycoprotein， which presents a significant challenge in the development of its oral preparations. Novel drug delivery technologies can enhance the solubility of paclitaxel and facilitate its controlled release， which is beneficial for the oral absorption and efficacy. The paper reviews the development history of oral preparations of paclitaxel， and summarizes the delivery technologies such as polymer micelles， nanoparticles， nanoemulsions and nanocrystals， and discusses the application mechanisms， advantages and limitations of these technologies and their adaptability in different cancer treatments. Finally， the challenges faced in the development of oral preparations of paclitaxel are summarized， and future research directions are proposed in order to provide new ideas for the development of oral delivery of paclitaxel.

The traditional Chinese medicine （TCM） myocardial infarction （MI） unit is a standardized， regulated， and continuous integrated care unit guided by TCM theory and built upon existing chest pain centers or emergency care units. This unit emphasizes multidisciplinary collaboration and forms a restructured clinical entity without altering current departmental settings， offering comprehensive diagnostic and therapeutic services with full participation of TCM in the treatment of MI. Its core medical model is patient-centered and disease-focused， providing horizontally integrated TCM-based care across multiple specialties and vertically constructing a full-cycle treatment unit for MI， delivering prevention， treatment， and rehabilitation during the acute， stable， and recovery phases. Additionally， the unit establishes a TCM-featured education and prevention mechanism for MI to guide patients in proactive health management， reduce the incidence of myocardial infarction， and improve quality of life.

Paclitaxel， a highly effective natural antitumor drug， has been demonstrated to be efficacious in the treatment of a variety of cancers， including breast cancer， ovarian cancer， and lung cancer. The traditional paclitaxel injections have been observed to present certain issues， including overt adverse reactions and a decline in the quality of life of patients following treatment. This ultimately leads to an inability to meet the comprehensive needs of patients， thereby limiting the clinical applications of the drugs. Compared with injectable administration， the oral administration can avoid the risk of infection present in the invasive route， is conducive to improving patient compliance and quality of life， and reduces healthcare costs， and has a good application prospect. However， paclitaxel has low solubility， poor permeability， and is susceptible to the exocytosis of P-glycoprotein， which presents a significant challenge in the development of its oral preparations. Novel drug delivery technologies can enhance the solubility of paclitaxel and facilitate its controlled release， which is beneficial for the oral absorption and efficacy. The paper reviews the development history of oral preparations of paclitaxel， and summarizes the delivery technologies such as polymer micelles， nanoparticles， nanoemulsions and nanocrystals， and discusses the application mechanisms， advantages and limitations of these technologies and their adaptability in different cancer treatments. Finally， the challenges faced in the development of oral preparations of paclitaxel are summarized， and future research directions are proposed in order to provide new ideas for the development of oral delivery of paclitaxel.