目的： 利用网络药理学和分子对接技术分析“茵陈-玉竹”药对治疗糖尿病肾病的机制。方法： 通过中药系统药理学数据库及分析平台(TCMSP)、中医药百科全书(ETCM)、中医药分子机制生物信息学注释数据库(BATMAN-TCM)检索“茵陈-玉竹”药对的主要化学成分，通过药物靶点数据库(TTD)、人类在线孟德尔遗传(OMIM)数据库、DisGeNET、GeneCards等数据库收集糖尿病肾病的疾病靶点，进而筛选茵陈、玉竹与糖尿病肾病的交集核心靶点。利用Cytoscape 3.7.2软件构建“化合物-靶点-疾病网络”，同时基于DAVID数据库对靶点进行GO功能富集和KEGG通路富集分析。结果： 获取“茵陈-玉竹”药对主要活性成分31个，作用靶点351个，糖尿病肾病相关基因2 911个，交集基因185个，其中起关键作用的活性成分为槲皮素、滨蒿内酯、莨菪亭、D-香芹酮和异鼠李素；构建可视化PPI网络得到185个节点，851条边，平均度值9.2，获得前列腺素内过氧化物酶2(PTGS2)、核因子κB1(NFKB1)、丝裂原活化蛋白激酶1(MAPK1)、MAPK3、MAPK14等“茵陈-玉竹”药对治疗糖尿病肾病的关键靶点。GO富集分析获得1 181条相关通路，KEGG通路富集获得180条信号通路。结论： “茵陈-玉竹”药对可能通过调控磷脂酰肌醇3激酶苏氨酸蛋白激酶(PI3K-Akt)、MAPK、糖基化终末产物糖基化终产物受体(AGE-RAGE)等信号通路，抑制各种炎症反应与氧化应激，调节异常代谢，从而对糖尿病肾病产生治疗作用。

Objective: To explore the effect of CXCL14 on pyroptosis of adipocytes and the formation of atherosclerosis in diabetic microenvironment. Methods: ① ApoE^-/- mice were intraperitoneally injected with streptozotocin to construct diabetes mellitus, and diabetic ApoE^-/- mice were fed with high fat diet for 20 weeks, and the diabetic atherosclerosis model (model group) was constructed, and control mice were only fed on a high-fat diet (AS group); ② Anti-CXCL14 short peptide was injected subcutaneously on the medial hind limb of diabetic mice (anti-CXCL14 group), and control diabetic mice were injected subcutaneously with normal saline only; ③ Adeno-associated virus (AAV) was injected in situ into posterior inguinal subcutaneous adipose tissue in diabetic mice to inhibit gastrointestinal dermatin (GSDMD)mediated pyroptosis, divided into: AAV-shscramble group, AAV-shGSDMD group, anti-CXCL14+AAV-shscramble group, anti-CXCL14+AAV-shGSDMDgroup. After 20 weeks of high-fat diet of the mice, the serum of the mice was collected under anesthesia, and the blood lipid levels (total cholesterol, triglycerides, LDL-C, and HDL-C) of the mice were analyzed by biochemical detection kit. The mice were sacrificed, and the epididymal adipose tissue was scanned by electron microscopy to observe the changes of fat cells. qRT-PCR was used to analyze the changes of pyroptosisrelated factors GSDMD, aspartate proteolytic enzyme-1 (Caspase-1), NLR family pyridine domain protein 3 (NLRP3) inflammasome, interleukin-1β (IL-1β) and inflammatory factor interleukin-6 (IL-6). The mouse aorta was isolated and extracted, and the relative area of atherosclerotic plaques was observed by HE staining and oil red O staining. Results: Compared with the AS group, the hypertrophy and number of adipocytes of adipose tissue in the epididymis in the model group decreased (P<0.01), the size of aorticplaque increased, the levels of total cholesterol, triacylglycerol and LDL-C were significantly increased, and HDL-C was significantly reduced. The levels of pyroptosisrelated factors and IL-6 in adipose tissue of epididymis were significantly increased (P<0.05), indicating that diabetes promoted pyroptosis of AS plaque and adipose tissue in mice. Injection of anti-CXCL14 short peptide could reduce the size of aortic plaque, improve blood lipid levels, and inhibit adipose tissue pyroptosis, which increases the number of fat cells. After GSDMD knockdown, the number of adipocytes increased and the area of aortic plaques decreased. However, after the injection of anti-CXCL14 immune peptide, there was no significant change in atherosclerosis in the AAV-shGSDMDgroup. Conclusion: Anti-CXCL14 can attenuate adipose tissue pyroptosis and alleviate the development of diabetic atherosclerosis.
［Key words］CXCL14; pyroptosis; adipose tissue; atherosclerosis; diabetic microenvironment

Objective: To prepare a photothermal drug carrier capable of responding to the tumor environment, enabling controlled drug release within tumor tissues for precise targeting and destruction of tumor cells in vivo. Methods: Chemotherapeutic drug doxorubicin (DOX) was loaded into the surface of graphene oxide (GO) carriers to produce GO-DOX nanoparticles, and the change of DOX fluorescence signal was monitored. First, GO-DOX was respectively incubated with mouse breast cancer 4T1 cells and human gastric epithelial GES-1 cells, and the fluorescence intensity of the two cell types was observed at different time points by confocal microscope. Then, the tumor xenograft model of 4T1 mouse was established and the changes of tumor volume of mice were observed. Last, tumor tissues were collected to prepare pathological sections, and the inhibitory effect of GO-DOX nanoparticles combined with near infrared light on xenografts in mice was evaluated. Results: GO-DOX nanoparticles not only had the environmental responsiveness to control drug release, but also were used to fluorescently image tumor cells. The combination of GO-DOX nanoparticles and near-infrared light effectively inhibited tumor growth and reduced the toxic and side effects of DOX on human body. Conclusion: Environment-responsive GO-DOX nanoparticles were successfully prepared, and can be used to effectively inhibite the growth of tumor and realize real-time imaging of tumor cells.

Objective： To explore the hub genes and potential mechanism of ferroptosis in the development of atherosclerosis (AS) in patients with type 2 diabetes mellitus (T2DM) based on bioinformatics. Methods： The datasets GSE20966 (T2DM) and GSE43292 (AS) were obtained from the GEO database. Differentially expressed genes (DEGs) were identified using the Limma R package. Heatmaps and volcano plots were drawn, and crossanalysis was performed to obtain DEGs associated with the two diseases. GO and KEGG enrichment analysis was performed to explore the biological functions of DEGs. Ferroptosis-related genes (FRGs) obtained from the FerrDb database were crosslinked, and hub genes were screened using LASSO regression and random forest analysis. ROC curves and validation sets GSE76895 (T2DM) and GSE28829 (AS) were used for verification. Finally, the gene-miRNA network was drawn. Results： A total of 606 DEGs were identified related to the T2DM and the AS datasets. Twenty potential genes were obtained by cross-analyzing with FRGs. Cyclin-depedent kinase inhibitors 1A (CDKN1A), poly ADPribose polymerase 8 (PARP8), phosphatidylethanolamine binding protein 1 (PEBP1), and progesterone receptor membrane component 1 (PGRMC1) were hub genes that affected AS in T2DM patients through ferroptosis. The area under the curve (AUC) of the ROC curves in the datasets GSE20966 and GSE43292 of the four genes was all greater than 0.7, which had diagnostic value. PEBP1 and PGRMC1 were significantly down-regulated in the validation sets GSE76895 and GSE28829. In addition, 13 miRNAs were closely associated with 4 hub genes. Conclusion： CDKN1A, PARP8, PEBP1 and PGRMC1 are involved in AS in T2DM patients through ferroptosis and may become new therapeutic targets.
［Key words］ferroptosis; type 2 diabetes mellitus; atherosclerosis; bioinformatics; machine learning

心血管疾病是目前临床上常见和致死致残率较高的疾病之一，而内皮细胞稳态在心血管健康的维持中发挥着不可忽视的作用。作为机体非循环细胞类型中数量最多的一类细胞，内皮细胞能够通过多种方式独立地影响周围组织。本文介绍了内皮细胞的功能、常见损伤机制及其与心血管其他组成细胞之间的相互作用，并进一步探讨内皮细胞在心血管疾病发生发展中的作用及基于内皮细胞的心血管疾病诊疗新进展，以期为通过干预内皮细胞改善心血管疾病预后提供新的视角。

Objective： To establish an albendazole-loaded self-microemulsifying drug delivery system (ABZ-SMEDDS) to improve the solubility and oral bioavailability of the water poorly soluble drug. Methods： The composition of the self-microemulsion prescription was optimized by the establishment of pseudo-triphasic diagrams, then the particle size, drug loading, encapsulation rate, and micromorphology were determined. The in vitro drug release and cytotoxicity and cellular uptake were investigated on a Caco-2 cell model, and finally, the oral bioavailability of ABZ-SMEDDS in rats was investigated. Results： The optimal prescription composition of ABZ-SMEDDS is clove oil, polyoxyethylene hydrogenated castor oil RH40 and polyethylene glycol 400 in a mass ratio of 0.20∶0.64∶0.16. The particle size of ABZ-SMEDDS was (52.14±1.82)nm with a polydispersity index of 0.084±0.006. The drug loading and encapsulation efficiency were (36.60±1.20)mg/g and (98.12±2.2)%, respectively. The results of in vitro release and cell experiments showed that the dissolution rate of ABZ-SMEDDS in different dissolution media were greatly improved compared with ABZ, and it can promote the transmembrane absorption of drugs. Pharmacokinetic results in vivo showed that the relative oral bioavailability of ABZ-SMEDDS in rats was increased to 151.95% compared with the free drug. Conclusion： SMEDDS could be a potential carrier for the enhancement of drug dissolution and oral bioavailability of poorly water soluble drugs.
［Key words］albendazole; selfmicroemulsion; dissolution in vitro; cellular uptake; oral bioavailability

Objective: To investigate the effect of human umbilical cord mesenchymal stem cell derived small extracellular vesicles (hucMSC-sEVs) in attenuating the damage of diabetic kidney disease (DKD) in rats. Methods: HucMSCs were isolated and cultured, and hucMSC-sEVs were extracted from the culture media supernatant. The DKD rat model was established by high fat diet combined with injection of streptozocin, rats were randomly divided into control group, DKD group, and hucMSCsEVs group, with 6 rats in each group. The hucMSC-sEVs group received tail vein injection of hucMSC-sEVs 8 weeks after modeling, and kidney tissues were collected at week 24. Renal tissue pathology and fibrotic changes in rats were assessed using HE staining, PAS staining and Sirius Red staining. The expression of apoptosisrelated proteins Bcl-2 and Bax in kidney tissues was evaluated using Western bloting. Additionally, the expression levels of THBS1 and its receptors CD36 and CD47 in rat renal tissues were determined using histochemical staining, immunofluorescence staining, and Western bloting. Results: Compared with the control group, the DKD group exhibited significant pathological changes in the kidneys, such as thickening of the glomerular basement membrane and mesangial proliferation, dilation of renal tubules accompanied by vacuolar degeneration, and marked interstitial fibrosis with infiltration of inflammatory cells. The expression of the apoptosis marker Bax in kidney tissues showed a significant increase (P<0.05), while the expression of the anti-apoptotic marker Bcl-2 exhibited a significant decrease (P<0.01). The expression levels of THBS1 and its receptors CD36 and CD47 were also significantly elevated (P<0.001). In contrast, compared with the DKD group, the hucMSC-sEVs group demonstrated marked alleviation of renal tissue pathological damage and fibrosis. The expression of Bax significantly decreased (P<0.01), while the expression of Bcl-2 significantly increased (P<0.01). Additionally, the expression levels of THBS1 and its receptors CD36 and CD47 in the kidneys were significantly reduced (P<0.001). Conclusion: HucMSC-sEVs can significantly reduce the renal tissue injury in DKD, which may be related to the targeted inhibition of THBS1 expression.
［Key words］human umbilical cord mesenchymal stem cells; small extracellular vesicles; diabetic kidney disease; THBS1

Objective： To study the optimized formulation of nidanib ethanesulfonate (NE) solution for inhalation and evaluate the formulation in vitro and in vivo. Methods： The prescription of NE solution was studied by optimizing the amount of the antioxidants, osmotic pressure regulators and pH value. The dynamic particle size of NE nebulized inhalation formulations was measured. The in vivo pharmacokinetics of NE nebulized inhalation formulations was determined by high performance liquid chromatography. Lung function, hydroxyproline (HYP), tumor necrosis factor-α(TNF-α), transforming growth factor-β1 (TGF-β1) were used as indicators to evaluate the therapeutic effect in vivo. Results： Optimized prescription was obtained: NE: 10 mg, sodium bisulfite: 4 mg, propylene glycol: 50 mg, water: 2 mL. The pH of the solution was adjusted to 4.0. The average particle size of NE nebulized inhalation was about 3.3 μm. The in vivo pharmacokinetic results in SD rats showed that the elimination half-life of NE inhalation preparation was 5.27 h. The bioavailability was significantly improved, reaching 63.71%. Pulmonary function parameters (tracheal contraction parameters, 50% tidal volume expiratory flow rate, respiratory rate) and lung dry/wet weight ratio, HYP, TNF-α in mice with pulmonary fibrosis model after inhalation administration had been significantly improved. Conclusion： NE inhalation can greatly improve lung function parameters and increase its bioavailability.
［Key words］nidanib ethanesulfonate; inhalation preparations; nebulized inhalation; pharmacokinetics; idiopathic pulmonary fibrosis

目的： 探讨健侧卧奔跑位联合负压吸引技术在逆行输尿管软镜取石术（RIRS）治疗输尿管上段及肾盂结石的临床效果。方法： 回顾性收集2021年7月至2023年4月在清远市人民医院接受常规截石位联合负压吸引（对照组）及健侧卧奔跑位联合负压吸引（观察组）下施行RIRS的76例输尿管上段及肾盂结石患者的临床资料。统计分析患者临床数据，包括患者术后1天的结石清除率、术后1个月结石清除率、平均手术时间及并发症发生情况。结果： 76例患者均顺利完成手术。对照组45例中，术后1天结石清除率57.8%，术后1个月结石清除率86.7%，平均手术时间为（58.53±15.27）min；术后出现较明显的肉眼血尿3例、发热2例。观察组31例中，术后1天结石清除率90.3%，术后1个月结石清除率93.5%，平均手术时间为（63.39±15.67）min；术后出现较明显的肉眼血尿1例、发热1例。两组患者发热经加强抗感染治疗后均恢复良好。结论： 采用健侧卧奔跑位比常规截石位仅在术后短期（1天）结石清除率上有优势，但在术后1个月结石清除率、平均手术时间、住院时间及术后并发症方面无明显优势。

       指南对中医临床开展标准化诊疗具有里程碑的意义，糖尿病肾病作为糖尿病的常见并发症，当前缺少与之相关的全面、规范且标准化的中医诊疗指南。本研究通过对既往发布的糖尿病肾病中医诊疗指南进行梳理，分析指南内容并提出建议，以期今后制定糖尿病肾病的中医诊疗指南能进一步凸显中医特色、提升方法学质量，为临床实践提供更多参考依据。

Objective: Blueberry derived exosome-like nanoparticles (BELNs) were extracted and identified, and the intervention effect of BELNs on the malignant transformation of human normal gastric mucosal epithelial cells induced by (N-methyl-N′-nitro-N-nitrosoguallidine, MNNG) was investigated. Methods: The BELNs were extracted by ultracentrifugation, and the BELNs were identified with particle size, Zeta potential and morphology by nano-particle tracking analyzer and transmission electron microscopy. Laser confocal microscopy was used to observe whether BELNs could be endocytosed by transformed gastric mucosal epithelial cells (TGES-1). TGES-1 cells were treated with 200 and 400 μg/mL BELNs for 72 h, then Western blotting was used to analyze the expression of stemness genes, epithelialmesenchymal transition (EMT) and proliferation related proteins. Results: The results of nano-particle tracking analyzer and transmission electron microscopy showed that BELNs was matched with the characteristics of exosome-like nanoparticles. The results of laser confocal microscopy confirmed that BELNs could be endocytosed by TGES-1 cells. Western blotting showed that 400 μg/mL BELNs inhibited the expression of N-cadherin, E-cadherin, Vimentin, Nanog and proliferating cell nuclear antigen (PCNA) and enhanced expression of E-cadherin in TGES-1 cells. Conclusion: BELNs exert a significant intervention effect on human normal gastric mucosal epithelial cells induced by MNNG.

Objective: To improve the isolation and culture methods of primary cardiomyocytes in neonatal mouse to stably get high activity and purity of primary mouse cardiomyocytes. Methods: Hearts from 1-3day-old neonatal mouse were harvested, and a two-step digestion method combining trypsin and type Ⅱ collagenase was used. Differential adherence was then employed to purify the cardiomyocytes, which were cultured in vitro in modified Dulbecco′s Modified Eagle Medium (DMEM) containing 10% horse serum. The morphological characteristics and beating patterns of the cardiomyocytes were observed under an inverted phase-contrast microscope. Cell viability was assessed by using trypan blue staining, and cardiomyocytes were identified by immunofluorescence staining for cardiac troponin T (cTnT). Results: After 24 hours of culture, the primary neonatal mouse cardiomyocytes adhered to the culture dish and exhibited spontaneous beating. By 96 hours, the cells aggregated into clusters and displayed synchronous beating. The cell survival rate was 90.63%, and the purity of cardiomyocytes reached 93.17%. Conclusion: The modified isolation and culture methods used in this study obtained the primary neonatal mouse cardiomyocytes with high activity and purity.

 Objective： To develop an effective and straightforward tool for assessing the risk of osteoporosis (OP) development in patients with rheumatoid arthritis (RA), thus early intervention can be facilitated to enhance patient prognosis and quality of life. Methods： A retrospective study was conducted, selecting 53 RA patients and 44 RA patients with concurrent OP treated at our institution from January 2018 to June 2023. Twenty-four predictive factors were collected. Key predictors were identified using the Lasso，Boruta and SVM-REF algorithms, and a predictive model was established using multivariate Logistic regression. Further validation of the model was performed using KNN and Lightgbm algorithms. Results： Four critical predictive factors were identified: IL-4, TT4, Anti-CCP, and age. The developed clinical prediction model exhibited a C-index of 0.82 and an area under the ROC curve (AUC) of 0.821. Clinical decision curve analysis indicated the highest net clinical benefit when the threshold probability ranged from 002 to 090, demonstrating the model′s robust predictive capability. Machine learning validation revealed that the KNN and Lightgbm models had AUCs of 0.973 and 0.973, respectively, and areas under the PR curve of 0.974 and 0.969, respectively. Confusion matrix results showed the KNN prediction model had a sensitivity of 0.866, specificity of 0.962, accuracy of 0.928, and F1 score of 0.918; the Lightgbm prediction model had a sensitivity of 0.955, specificity of 0.925, accuracy of 0.938, and F1 score of 0.933. Conclusion： This study successfully constructed a clinical prediction model for RA patients at risk of developing OP, and age, Anti-CCP, and TT4 was identified as high-risk factors, while IL-4 as a protective factor.

Objective： To explore intercellular communication-related signaling molecules in tumor microenvironment (TME) of castration-resistant prostate cancer (CRPC) and analyze their relationship with tumor occurrence and development. Methods： The main components of the TME in CRPC was analyzed using singlecell RNA sequencing (scRNA-seq) data (GSE137829) from CRPC patients found in the Gene Expression Omnibus (GEO) database. CellPhoneDB was used to examine interactions between different cells within the microenvironment, with a focus on revealing the connections between cancer-associated fibroblasts (CAFs) and malignant epithelial cells. CellChat was applied to analyze signaling molecules involved in communication between CAFs and malignant epithelial cells. Data from The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) were integrated to identify signaling molecules closely related to the prognosis of CRPC patients. siRNA was used to knock down the expression of the signaling molecule Delta-like canonical Notch ligand 3 (DLL3) in CRPC cells, and the knockdown efficiency was validated by real-time quantitative PCR and Western blotting. The effects of DLL3 on the biological behaviors of CRPC cells, including proliferation, migration, and invasion, were investigated using CCK8 assays, EdU assays, and Transwell assays with Matrigel, respectively. Singlegene differential analysis, overrepresentation analysis (ORA), and gene set enrichment analysis (GSEA) were also performed to identify pathways enriched with DLL3-related differential expression genes. Results： The results of single-cell transcriptomic sequencing indicated that the main cellular components of the TME in CRPC include malignant epithelial cells, CAFs and immune cells. Close communication between CAFs and malignant epithelial cells was mediated by interaction-related signaling molecules, with 63 signaling molecules identified as closely related to the communication between CAFs and malignant epithelial cells. Univariate Cox regression analysis identified key signaling molecules, including tumor necrosis factorrelated ligand superfamily member 12 (TNFSF12) and DLL3, whose transcriptional expression were significantly associated with the prognosis of CRPC patients. Notably, high expression of DLL3 was significantly associated with poor prognosis in CRPC patients. In vitro experimental results demonstrated that knockdown of DLL3 significantly inhibited the growth, proliferation, migration and invasion capabilities of CRPC cells. KEGG and GSEA enrichment analyses indicated that differentially expressed genes related to DLL3 were significantly enriched in metabolic pathways. Conclusion： In the TME, CAFs and malignant epithelial cells communicate closely through intercellular signaling molecules. Among these signaling molecules, the expression of DLL3 is negatively correlated with cancer prognosis and affects the biological behavior of CRPC cells, suggesting that DLL3 may be a key signaling molecule in the malignant progression of human CRPC.
［Key words］castration-resistant prostate cancer; scRNA-seq; tumor microenvironment; cell communication; DLL3

Objective: To investigate the risk factors of hospital infection in stroke patients and construct a risk prediction model of nosocomial infection. Methods: A total of 300 stroke patients with nosocomial infection during hospitalization in the Department of Neurology and Neurosurgery of Affiliated Hospital of Nantong University from January 2020 to December 2023 were also selected (infection group), and another 300 stroke patients without nosocomial infection during the same period were selected (control group). The distribution of nosocomial infection and pathogenic bacteria were analyzed, and clinical characteristics of the two groups were compared. Multivariate Logistic regression was used to analyze the risk factors of nosocomial infection in stroke patients, and a nomogram model for predicting risk was established by incorporating R language, and the predictive effect of the model was evaluated. Results: The predominant nosocomial infection site of stroke patients was the respiratory system (62.67%, 188/300), the predominant pathogenic bacteria of nosocomial infection were Gram-negative bacteria (59.90%, 121/202), and the multidrug-resistant bacteria infection accouned for 34.16% (69/202). Compared with the control group, the infection group had higher proportion of cerebral hemorrhage, diabetes, hypertension, coronary heart disease, disturbance of consciousness, central venous catheters, ventilators, urinary catheters, and preventive use of antibiotics, body mass index(BMI)≥24 kg/m² and hospitalization time≥14 d (P<0.05). Multivariate Logistic regression analysis showed that stroke type, hypertension, diabetes, BMI≥24 kg/m2, disturbance of consciousness, use of ventilator, indwelling urinary catheter, preventive use of antibiotics, and hospitalization time≥14 d were independent risk factors for nosocomial infection in stroke patients (P<0.05). A nomogram prediction model was constructed based on the regression results, and the area under ROC curve was 0.983 (95%CI: 0.975-0.991). The sensitivity and specificity was 0.940 and 0.937, respetictively. The Hosmer-Lemeshow test (χ2=5.454, P=0.708) indicated that the model had a good fit and predictive performance. Conclusion: The risk factors of nosocomial infection in stroke patients include stroke type, hypertension and diabetes, etc. The prediction model based on the risk factors could accurately predict the risk of nosocomial infection in stroke patients.

Objective: To explore the effect of long noncoding RNA (lncRNA) small nucleolar RNA host gene 11 (SNHG11) on the proliferation and stemness of pancreatic cancer cells and its possible mechanisms. Methods: The expression of lncRNA SNHG11 in pan cancer and corresponding paracancerous tissues, pancreatic cancer and pancreatic tissues were analyzed by TCGA and GTEx databases; the expression of lncRNA SNHG11 in pancreatic cancer PANC1, PaTu8988 and MIApaca-2 cells was detected by qRT-PCR; pcDNA3.1 and pcDNA3.1-SNHG11 plasmids were transfected into PANC1 and PaTu8988 cells, respectively; sh-EGFP and sh-SNHG11 plasmids were transfected into PANC1 and MIApaca-2 cells, respectively. Plasmid transfection efficiency was measured by qRT-PCR, cell proliferation rate was measured by CCK8 assay, clone formation experiment was used to detect the number and size of cell clones, qRT-PCR and Western blotting were used to detect the mRNA and protein levels of stemness indicators, including NANOG homeobox protein (NANOG), sex determining region of Y-chromosome related HMG-box2 (SOX2), octamer binding transcription factor 4 (OCT4), cellular oncogene myc (c-myc) and LIN28 homolog A (LIN28A), respectively. Stem cell spheroidization experiment was used to detect changes in the number and diameter of stem cell spheroidization; RNA immunoprecipitation assay was used to detect the binding of SNHG11 and LIN28A. Co-ransfection of pcDNA3.1-SNHG11+sh-LIN28A or co-transfection of sh-SNHG11+3×FlagLIN28A, qRT-PCR was used to detect the mRNA levels of stemness indicators NANOG, SOX2, OCT4, and c-myc. Stem cell spheroidization experiments were used to detect changes in the number and diameter of stem cell spheroidization. Results: SNHG11 is highly expressed in a variety of malignant tumors, including pancreatic cancer. The relative expression of lncRNA SNHG11 in pancreatic cancer cells from low to high was PaTu8988, PANC1, MIApaca-2 (P<0.05). Up-regulating of SNHG11 expression significantly increased the proliferation and stemness of pancreatic cancer cells, while down-regulating exerted the opposite outcomes (P<0.05). LncRNA SNHG11 could bind to LIN28A. Overexpression of SNHG11 significantly increased the stemness of pancreatic cancer cells, and interference with LIN28A greatly reduced the stemness of pancreatic cancer cells, downregulating LIN28A in pancreatic cancer cells with over-expression of SNHG11 markedly inhibited the stemness promotion of pancreatic cancer cells (P<0.05). By silencing SNHG11, the stemness ability of pancreatic cancer cells was significantly reduced, while overexpression of LIN28A significantly enhanced the stemness ability of pancreatic cancer cells. Upregulating the expression of LIN28A in pancreatic cancer cells with low expression of SNHG11 could significantly reverse the stemness inhibition of pancreatic cancer cells (P<0.05). Conclusion: LncRNA SNHG11 may promote the proliferation and enhance the stemness of pancreatic cancer cells by up-regulating the expression of LIN28A.

Objective: To explore the antidepressant effect and underlying mechanism of Wenyang Jieyu granule (WYJY) by constructing a corticosterone (CORT) injury-induced depression model in mouse hippocampal neurons (HT22) in vitro. Methods: HT22 cells were divided into normal group, model group, WYJY group,and fluoxetine group. Except for the normal group, HT22 cells in the other groups were treated with CORT. WYJY group and fluoxetine group were treated with corresponding drug-containing serum for 24 hours. The HT22 cells in model group added 10% blank serum for 24 hours. CCK-8 method was used to detect cell survival rate. Cell morphology was observed under a microscope. Enzyme linked immunosorbent assay was used to detect LDH release. Hoechst staining was used to observe the survival number of cells. Immunofluorescence assay was used to detect the fluorescence expression of Brdu and Neun and observe the regeneration of HT22 cells. Flow cytometry was used to detect the apoptosis rate of cells. Results: Compared with the normal group, HT22 cells in the model group were severely damaged, the number of cells decreased, and the survival rate was significantly decreased (P<0.01)，LDH release was significantly increased (P<0.01)，the fluorescence intensity of Brdu/Neun double staining decreased significantly (P<0.01), and the apoptosis rate increased significantly (P<0.01). Compared with the model group, the survival rate of HT22 cells was increased after the effect of serum containing WYJY on CORT injury (P<0.05)，the LDH release and apoptosis rate were decreased (P<0.05, P<0.01)，the fluorescence intensity of Brdu/Neun and the number of positive cells were significantly increased (P<0.05, P<0.01). Conclusion: WYJY may play an antidepressant role by repairing damaged hippocampal neuron cells, regulating nerve plasticity, inhibiting apoptosis of hippocampal neuron cells and differentiating into new neurons.

Objective: To investigate the influencing factors of the risk of sepsis-associated liver injury (SALI) in patients with sepsis, and establish and verify a model for predicting the risk of SALI. Methods: A total of 415 patients with sepsis admitted to the Intensive Care Unit (ICU), the Affiliated Huai′an No.1 People′s Hospital of Nanjing Medical University, from January 2019 to January 2022 were enrolled and divided into SALI group (n=97) and non-SALI group (n=318), according to clinical diagnosis. Basic information and clinical data of patients were collected. Least absolute shrinkage and selection operator (LASSO) regression was used for univariate screening. Then, multivariate Logistic regression was used to further select the risk factors and construct the model based on the nomogram. The performance of the nomogram, including differentiation, accuracy and clinical utility, was evaluated through internal validation by using bootstrap method. Results: Nine variables were selected by LASSO regression for multivariate analysis. Multivariate Logistic regression further showed that total bilirubin, alanine aminotransferase, γ-glutamyl transpeptidase, mechanical ventilation, renal failure, international normalized ratio, and acute respiratory failure were independent risk factors for SALI. The internal validation of the constructed model showed that the area under the ROC curve was 0.823 (95%CI: 0.773-0.873), and the model demonstrated satisfactory accuracy (P>0.05). Decision curve analysis indicated that the prediction model could generate a net benefit within the threshold range of 5% to 100% for predicting the risk of developing SALI in sepsis patients. Conclusion: Total bilirubin, alanine aminotransferase, γglutamyl transpeptidase, mechanical ventilation, renal failure, international normalized ratio, and acute respiratory failure were independent risk factors for SALI in patients with sepsis, and the nomogram model established based on above factors had good predictive value.

Objective: To investigate the effect of O-linked N-acetylglucosamine (O-GlcNAc) glycosylation on the adhesion between gastric cancer cells and extracellular matrix and its potential mechanisms. Methods: The mRNA expressions of glutamine-fructose-6-phosphate transaminase 1 (GFPT1), glucosamine-phosphate N-acetyltransferase 1 (GNPNAT1), phosphoglucomutase 3 (PGM3), UDP-N-acetylglucosamine pyrophosphorylase 1 (UAP1), N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA) in pan-cancer and human gastric cancer tissues were analyzed by UALCAN database. The relative mRNA expression levels of GFPT1, GNPNAT1, PGM3, UAP1, OGT and OGA in gastric cancer HGC-27, AGS, and SNU-1 cells were analyzed by DepMap database. The relative expression levels of GFPT1, OGT and OGA proteins and the glycosylation modification levels of O-GlcNAc in human gastric mucosal epithelial GES-1 cells and gastric cancer HGC-27, AGS and SNU-1 cells were detected by Western blotting. The signaling pathways enriched by the gastric cancer samples with differential expression of OGT and OGA were explored by Gene Set Enrichment Analysis (GSEA). The adhesion ability of human gastric mucosal epithelial GES-1 cells and gastric cancer HGC-27, AGS, and SNU-1 cells was detected by cell adhesion assay. OGT inhibitor OSMI-1 and OGA inhibitor Thiamet G (TMG) were used to decrease or increase O-GlcNAc glycosylation modification levels of gastric cancer cells HGC-27 and SNU-1 cells, respectively, and their adhesion ability was detected by adhesion assay. Results: The mRNA expression levels of GFPT1, GNPNAT1, PGM3, OGT, and OGA were significantly elevated in pan-cancer tissues, especially gastric cancer, compared with those in adjacent tissues (P<0.05). Compared with HGC-27 and SNU-1 cells, the mRNA expressions of GFPT1, GNPNAT1, PGM3 and UAP1 in AGS cells of gastric cancer were higher, but the mRNA expressions of OGT and OGA were lower. The expression of GFPT1 protein was not significantly different among human gastric mucosal epithelial cells and three gastric cancer cell lines, but the expression of OGT and OGA protein was significantly increased in HGC-27 and SNU-1 cells compared with human gastric mucosal epithelial GES-1 cells (P<0.01). The relative expression level of O-GlcNAc in SNU-1 cells was significantly higher than that in GES-1 cells and HGC-27 and AGS cells (P<0.01). GSEA enrichment analysis indicated that OGT and OGA may regulate the adhesion ability of gastric cancer cells by regulating the level of O-GlcNAc modification. Decreasing the O-GlcNAc modification level of gastric cancer cells could significantly reduce the adhesion ability of gastric cancer cells. Conclusion: The level of O-GlcNAc glycosylation in gastric cancer HGC-27 and SNU-1 cells was significantly increased, which may enhance the adhesion ability of gastric cancer HGC-27 and SNU-1 cells by affecting the expression of related adhesion proteins in HBP.

在肿瘤微环境中，血管生成的加强不仅是肿瘤生长和存活至关重要的条件，同时也构成了肿瘤治疗所面临的严峻挑战。间充质干细胞通过分泌生长因子和释放细胞外囊泡等方式，激活一系列信号通路，从而诱导内皮细胞发生功能性改变，调控血管生成过程。深入理解和干预肿瘤血管生成的分子机制对于制定更为有效的抗肿瘤治疗策略至关重要。本文主要对间充质干细胞在肿瘤微环境中调节内皮细胞血管生成的主要分子机制及相关信号通路作一概述。

溃疡性结肠炎（ulcerative colitis，UC）的发病率在世界范围内逐步上升且呈现年轻化的趋势。UC症状持续，会诱发焦虑和抑郁，而目前对于UC诱发的焦虑和抑郁症状的具体机制研究较少。本文以肠脑轴为出发点，从免疫反应、肠道菌群和肠道代谢物三个方面进行分析，梳理UC导致焦虑和抑郁症状的具体机制，旨在为新的治疗方案提供参考。

Objective: To construct a prognostic risk model for predicting bone metastasis in prostate cancer (PCa) based on bioinformatics approach, and to investigate the effect of risk score on prognosis and immune infiltration. Methods: Clinical information and microarray expression data of PCa patients were downloaded from the Gene Expression Omnibus (GEO), and genes related to the bone morphogenetic protein (BMP) pathway were downloaded from the Molecular Signature Database (MSigDB). The differential expression genes (DEGs) of PCa bone metastasis samples and primary PCa samples were screened by differential analysis, and the intersection with BMP pathway-related genes was taken to obtain BMP-related DEGs, and the prognostic risk model was constructed by screening risk genes through LASSO regression analysis, and independent prognostic factors of PCa were screened by multifactorial regression analysis. The risk scores of patients were calculated according to the risk model and subsequently divided into two groups of high and low risk scores by corresponding score median values, and DEGs were identified for functional enrichment analysis to compare the differences in immune infiltration between high and low risk groups. Results: After the intersection of DEGs and BMP-related gene sets in 3 055 differentially expressed genes of PCa bone metastasis samples, 13 BMP-related DEGs were obtained. Four gene were screened by LASSO regression to construct a prognostic risk model, in which secreted frizzled-related proteins 2 (SFRP2), endoglin (ENG), and follistatin-like protein 1 (FSTL1) were risk genes and chordin like 1 (CHRDL1) was a protective gene. Kaplan-Meier analysis showed that metastasis-free survival and biochemical recurrence-free survival of patients in the high-risk group were significantly lower than that of patients in the low-risk group. Multifactorial regression analysis identified risk score as an independent prognostic factor for PCa bone metastasis, and patients in the high-risk group were more likely to develop bone metastasis and biochemical recurrence, and the risk score was positively correlated with the PSA value, the Gleason score, and the T stage. The DEGs of high-risk group were mainly involved in the activation of the WNT/BMP signaling pathway, and were significantly enriched in the proliferation of epithelial cells and extracellular matrix bioprocesses. GSEA analysis showed that, the differentially expressed genes were upregulated in the gene sets of mesenchymal transition, inflammatory response, angiogenesis, and multiple tumor metastasis gene sets. Immune infiltration analysis showed that PCa bone metastasis samples and patients in the high-risk group possessed a higher degree of immune cell infiltration, cancer associated fibroblasts (CAFs), macrophages, Estimate scores, stromal scores, and immune scores than the lowrisk group, and lower tumor purity than the low-risk group. Conclusion: The prognostic risk model of BMP-related DEGs constructed based on the LASSO regression analysis can effectively predict the occurrence of PCa bone metastasis, and the high-risk score is closely related to the prognosis and immune infiltration of PCa.
［Key words］prostate cancer; bone metastasis; BMP signaling pathway; prognostic risk model; immune invasion