Age-related macular degeneration(ARMD)is a progressive visual impairment fundus disease that frequently occurs in individuals aged >55 years. The main risk factors are aging, long-term smoking, genetics, and racial differences. Pathogenesis includes abnormal function of the retinal pigment epithelium, damaged blood-retinal barrier, and abnormal immune function. Currently, intravitreal injection(IVI)of anti-vascular endothelial growth factor(VEGF)drugs is the preferred treatment option for ARMD in clinical practice. However, it also faces challenges such as repeated treatments, high medical costs, and poor patient compliance. The predicament in the treatment of ARMD has given rise to several new treatment options. This article aims to review the treatment methods and progress of dry ARMD and wet ARMD, providing new ideas for addressing the limitations of the current clinical anti-VEGF treatment.

OBJECTIVE To investigate the application status of prescription pre-review systems in healthcare institutions of Yunnan province， evaluate their system functions and management capabilities， and provide a practical basis for promoting rational drug use. METHODS A questionnaire survey was conducted among public healthcare institutions at or above the secondary level in Yunnan province to investigate the deployment status of the systems. A capability maturity assessment framework was constructed， encompassing 6 dimensions and 39 indicators， including real-time prescription review， prescription correlation review， rule setting， evidence-based information support， prescription authority management， and system operation management. This framework was then used to evaluate the institutions that had implemented the pre-review systems. RESULTS A total of 100 valid questionnaires were collected， with 37 institutions having adopted prescription pre-review systems， mainly tertiary hospitals. The system predominantly adopted a modular architecture and was embedded into the hospital information system through application programming interfaces and middleware， providing certain capabilities for real-time prescription risk identification. Evaluation results indicated that basic functions such as reviewing indications， contraindications， and drug compatibility performed well， while deficiencies remained in functions related to parenteral nutrition prescription， review of drug dosage for specific diseases， individual patient characteristic recognition， and rule setting. Moreover， the construction of review centers and establishment of management systems were also not well-developed. CONCLUSIONS The overall application rate of prescription pre-review systems in Yunnan province remains low. System functions and management mechanisms require further improvement. It is recommended to enhance information infrastructure in lower-level institutions and explore regionally unified review models to promote standardized and intelligent development of prescription review practices.

Objective: To understand the prevalence of myopia among primary and secondary school students in minority areas of Yunnan Province, and to explore the influence of outdoor activities and short-distance use of eyes, so as to provide a basis for early myopia intervention. Methods: In October 2020, the survey was conducted among 1 782 primary and secondary school students in three cities of Yunnan through a multi stage random cluster sampling method. All subjects underwent a questionnaire survey and the visual acuity examination at baseline. The first follow-up was conducted in October 2021 to obtain 1 691 valid samples, and the second follow-up was conducted in May 2023 to obtain 1 367 valid samples. Factors associated with myopia among primary and secondary school students were explored by using generalized estimating equations. Results: The prevalence rates of myopia in 2020, 2021 and 2023 were 52.64%, 61.62% and 69.35%, respectively, showing an increasing trend ( χ 2 trend =91.77, P <0.05). The results of multivariate regression analysis on the generalized estimation equations showed that age at baseline ( OR =1.31), girls ( OR =1.76), Hani ethnicity ( OR =0.75), Bai ethnicity ( OR =0.69), parental myopia ( OR =1.97-2.29), parents often reducing children s exercise time for homework or tutoring ( OR =1.35), less than 1 time or 2-3 times of ball sports per week ( OR =1.27, 1.20 ), reading and writing in the classroom during the break ( OR =1.27), reading in direct sunlight occasionally ( OR =1.20), using only desk lamp for writing at home ( OR =0.71), more than 1 hours of short-distance eye use for a break once ( OR =1.23) were associated with myopia among primary and secondary school students ( P <0.05). Conclusions Outdoor activities and short-distance use of eye among primary and middle school students in minority areas in Yunnan province are suboptimal. Enhancing the related environmental and behavioral factors can effectively mitigate the occurrence and progression of myopia.

Objective To introduce an innovative technique, the "balance-shaped sternal elevation device" and its application in the subxiphoid uniportal video-assisted thoracoscopic surgery (VATS) for anterior mediastinal masses resection. Methods Patients who underwent single-port thoracoscopic assisted anterior mediastinal tumor resection through the xiphoid process at the Department of Thoracic Surgery, West China Hospital, Sichuan University from May to June 2024 were included, and their clinical data were analyzed. Results A total of 7 patients were included, with 3 males and 4 females, aged 28-72 years. The diameter of the tumor was 1.9-17.0 cm. The operation time was 62-308 min, intraoperative blood loss was 5-100 mL, postoperative chest drainage tube retention time was 0-9 days, pain score on the 7th day after surgery was 0-2 points, and postoperative hospital stay was 3-12 days. All patients underwent successful and complete resection of the masses and thymus, with favorable postoperative recovery. Conclusion The "balance-shaped sternal elevation device" effectively expands the retrosternal space, providing surgeons with satisfactory surgical views and operating space. This technique significantly enhances the efficacy and safety of minimally invasive surgery for anterior mediastinal masses, reduces trauma and postoperative pain, and accelerates patient recovery, demonstrating important clinical significance and application value.

It is believed that the occurrence and development of squamous cell carcinoma （SCC） is closely associated with inflammatory responses. The theory of fire and heat， advocated by LIU Wansu， provides significant clinical guidance for understanding the pathogenesis and treatment of SCC. Based on this theory， the pathological mechanisms and clinical characteristics of SCC at different stages were analyzed. In the precancerous and early stages， the primary pathogenesis is qi stagnation leading to internal generation of constrained heat； in post-surgery， the condition shifts to qi deficiency with latent yin fire； during the treatment phase， the pathogenesis involves accumulation of pathogenic factors， excess toxins， and severe heat toxicity； in the late stage， the main pathology is yin deficiency with toxic heat， and phlegm-stasis obstruction of the internal organs. Corresponding stage-based treatment strategies are proposed. In the early stage， regulating qi movement to dissipate constrained heat； for post-surgery， tonifying qi and raising yang to dispel latent fire； during treatment stage， clearing heat and detoxifying to eliminate cancerous toxins； and in the late stage， nourishing yin and unblocking the bowels to clear deficiency heat.

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.

BACKGROUND:Our previous study found that Modified Erxian Pill could alleviate inflammation in collagen-induced arthritis rats,but its mechanism needs to be further verified. OBJECTIVE:To analyze the components absorbed in the blood of Modified Erxian Pill,and observe the effect of the drug-containing serum of Modified Erxian Pill on pyroptosis of J774A.1 macrophages. METHODS:(1)Analysis of components absorbed in the blood of Modified Erxian Pill:Ultra-high performance liquid chromatography-high resolution mass spectrometry was used to detect and identify Modified Erxian Pill and its components absorbed in the blood.(2)Effect of the drug-containing serum of Modified Erxian Pill on pyroptosis of J774A.1 macrophages:Molecular docking technology was used to initially verify the sesquiterpenoids and NLRP3 in components absorbed in the blood of Modified Erxian Pill.J774A.1 macrophages were randomly divided into blank control group,lipopolysaccharide+adenosine triphosphate group,and lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill with low(2.5%),medium(5%),and high(10%)dose groups.The release of lactate dehydrogenase in the cell supernatant of each group was detected according to the kit instructions.The levels of interleukin-1β and interleukin-18 in cell supernatant were detected in each group by ELISA.The cell membrane damage was detected by Hoechst/PI staining.The expression levels of NLRP3,Caspase-1,GSDMD,and GSDMD-N protein in the cells of each group were detected by western blot assay. RESULTS AND CONCLUSION:(1)A total of 32 active components of Modified Erxian Pill were identified,and 21 components entered the blood.The main components into blood included a variety of sesquiterpenoids.(2)Molecular docking results showed that 3-O-Acetyl-13-deoxyphomenone,Incensol oxide,Atractylenolide III,Rupestonic acid,and 3,7-Dihydroxy-9,11-eremophiladien-8-one had good binding activity with NLRP3.(3)Compared with the blank control group,lactate dehydrogenase activity and the expression levels of interleukin-1β and interleukin-18 were significantly increased in cell supernatant of lipopolysaccharide+adenosine triphosphate group(P<0.001).Hoechst/PI staining showed that the number of PI-positive cells was significantly increased.After the intervention of lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill group,all of them showed different degrees of reduction.(4)Compared with the blank control group,NLRP3,Caspase-1,GSDMD,and GSDMD-N protein expression levels were significantly increased in the lipopolysaccharide+adenosine triphosphate group(P<0.05).Compared with lipopolysaccharide+adenosine triphosphate group,the protein expressions of NLRP3,Caspase-1,GSDMD,and GSDMD-N were significantly decreased in the lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill group(P<0.05),and had a certain dose dependence.These findings verify that the drug-containing serum of Modified Erxian Pill may inhibit the pyroptosis of J774A.1 macrophages by regulating the NLRP3/Caspase-1/GSDMD pathway.

OBJECTIVE To investigate the effects and mechanism of asperuloside （Asp） on the pyroptosis of intestinal epithelial cells in rats with ulcerative colitis （UC）. METHODS The male SD rats were randomly divided into Control group， model group （UC group）， ASP low-dose and high-dose groups [Asp-L， Asp-H groups， Asp 35， 70 mg/（kg·d）]， ASP high-dose group+AMPK inhibitor Compound C group [Asp-H+Compound C group， Asp 70 mg/（kg·d）+Compound C 0.2 mg/（kg·d）]， with 12 rats in each group. Except for Control group， the other groups were injected with 50% ethanol （0.25 mL）+5% 2，4， 6- trinitrobenzene sulfonic acid solution （2 mL/kg） into the intestinal cavity to construct UC model. After modeling， the rats in each drug group were given corresponding drug solution by gavage or （and） tail vein injection， once a day， for 14 consecutive days. After the last administration， the weight of rats in each group was measured， and the length of their colons was measured； disease activity index （DAI） score and colonic mucosal damage index （CMDI） score were performed， and the serum levels of inflammatory factors （interleukin-18， -1β， -6） were detected. The pathological changes of the colon tissue were observed. The expressions of pyroptosis-related proteins [caspase-1， gasdermin D （GSDMD）] in colon tissue， and pathway-related proteins such as adenosine monophosphate-activated protein kinase （AMPK）， thioredoxin-interacting protein （TXNIP）， NOD-like receptor protein 3 （NLRP3） and apoptosis-associated speck-like protein containing a CARD （ASC） were all detected. RESULTS Compared with Control group， the colon tissue structure of rats in UC group was damaged， with obvious infiltration of inflammatory cells and edema. Their body weight， colon length and phosphorylation level of AMPK protein were significantly reduced or shortened； DAI and CMDI scores， serum levels of inflammatory factors， and the protein expressions of caspase-1， GSDMD， TXNIP， NLRP3 and ASC in colon tissue were increased or upregulated significantly （P＜0.05）. Compared with UC group， the pathological damage of colon tissue in rats was relieved in Asp-L and Asp-H groups， and all quantitative indicators were significantly improved （P＜0.05）； the improvement effect of Asp-H group was more significant （P＜0.05）. Compound C could significantly reverse the improvement effect of high-dose of Asp on the above indicators in UC rats （P＜0.05）. CONCLUSIONS Asp can improve inflammatory damage in colon tissue and inhibit pyroptosis of intestinal epithelial cells in UC rats， which is associated with the activation of AMPK and inhibition of TXNIP/NLRP3 signaling pathway.