BACKGROUND:Studies have confirmed that Pterocarya hupehensis skan total flavonoids(PHSTF)can improve the level of collagen-induced arthritis in rats,but there is still a lack of research on the regulation of Wnt/β-catenin signaling pathway in fibroblast-like synoviocytes and its effect on related cell functions.OBJECTIVE:To investigate the effect and mechanism of PHSTF on lipopolysaccharide-induced proliferation,migration and apoptosis of fibroblast-like synoviocytes based on the Wnt/β-catenin signaling pathwayMETHODS:Fibroblast-like synoviocytes were divided into control group,lipopolysaccharide group,lipopolysaccharide+low-,medium-,and high-dose PHSTF groups(10,20,and 40 μg/mL),lipopolysaccharide+Wnt pathway inhibitor DKK1 group,and lipopolysaccharide+Wnt pathway inhibitor DKK1+high-dose PHSTF group(40 μg/mL).The cell counting kit-8 method was used to detect the effect of PHSTF on the viability of fibroblast-like synoviocytes,and the final drug concentration and time were screened.Flow cytometry was used to detect the apoptosis of fibroblast-like synoviocytes.Cell scratch assay,EDU staining and cell cloning assay were used to detect the migration and proliferation of fibroblast-like synoviocytes.Western blot assay was used to detect the protein expression levels of Wnt3a,β-catenin,tumorigenic genes,matrix metalloproteinase 2,matrix metalloproteinase 9,Bax and Bcl-2 in fibroblast-like synoviocytes.RESULTS AND CONCLUSION:(1)Compared with the control group,the cell viability decreased significantly when the concentration of PHSTF was＞40 μg/mL(P＜0.01).Therefore,the drug concentration of≤40 μg/mL was selected for subsequent experiments.(2)Compared with the lipopolysaccharide group,the wound healing rate,cell clone formation rate and the number of EDU-positive cells in the low-,medium-and high-dose PHSTF groups were significantly reduced,while the apoptosis rate was significantly increased(P＜0.05-0.01).(3)Western blot results showed that compared with the lipopolysaccharide group,low-,medium-and high-dose PHSTF significantly inhibited cellular Wnt3a,β-catenin,cellular tumorigenic genes,matrix metalloproteinase 2,matrix metalloproteinase 9,and Bcl-2 protein expression,and promoted the expression of Bax protein(P＜0.01).(4)Compared with the DKK1 group,the combination of DKK1 and high-dose PHSTF significantly inhibited the protein expression of Wnt3a,β-catenin,matrix metalloproteinase 2,matrix metalloproteinase 9 and Bcl-2 protein expression and promoted the protein expression of Bax(P＜0.01).To conclude,PHSTF may inhibit the proliferation and migration of fibroblast-like synoviocytes and promote apoptosis by inhibiting the Wnt/β-catenin signaling pathway.

BACKGROUND:Studies have confirmed that Pterocarya hupehensis skan total flavonoids(PHSTF)can improve the level of collagen-induced arthritis in rats,but there is still a lack of research on the regulation of Wnt/β-catenin signaling pathway in fibroblast-like synoviocytes and its effect on related cell functions.OBJECTIVE:To investigate the effect and mechanism of PHSTF on lipopolysaccharide-induced proliferation,migration and apoptosis of fibroblast-like synoviocytes based on the Wnt/β-catenin signaling pathwayMETHODS:Fibroblast-like synoviocytes were divided into control group,lipopolysaccharide group,lipopolysaccharide+low-,medium-,and high-dose PHSTF groups(10,20,and 40 μg/mL),lipopolysaccharide+Wnt pathway inhibitor DKK1 group,and lipopolysaccharide+Wnt pathway inhibitor DKK1+high-dose PHSTF group(40 μg/mL).The cell counting kit-8 method was used to detect the effect of PHSTF on the viability of fibroblast-like synoviocytes,and the final drug concentration and time were screened.Flow cytometry was used to detect the apoptosis of fibroblast-like synoviocytes.Cell scratch assay,EDU staining and cell cloning assay were used to detect the migration and proliferation of fibroblast-like synoviocytes.Western blot assay was used to detect the protein expression levels of Wnt3a,β-catenin,tumorigenic genes,matrix metalloproteinase 2,matrix metalloproteinase 9,Bax and Bcl-2 in fibroblast-like synoviocytes.RESULTS AND CONCLUSION:(1)Compared with the control group,the cell viability decreased significantly when the concentration of PHSTF was＞40 μg/mL(P＜0.01).Therefore,the drug concentration of≤40 μg/mL was selected for subsequent experiments.(2)Compared with the lipopolysaccharide group,the wound healing rate,cell clone formation rate and the number of EDU-positive cells in the low-,medium-and high-dose PHSTF groups were significantly reduced,while the apoptosis rate was significantly increased(P＜0.05-0.01).(3)Western blot results showed that compared with the lipopolysaccharide group,low-,medium-and high-dose PHSTF significantly inhibited cellular Wnt3a,β-catenin,cellular tumorigenic genes,matrix metalloproteinase 2,matrix metalloproteinase 9,and Bcl-2 protein expression,and promoted the expression of Bax protein(P＜0.01).(4)Compared with the DKK1 group,the combination of DKK1 and high-dose PHSTF significantly inhibited the protein expression of Wnt3a,β-catenin,matrix metalloproteinase 2,matrix metalloproteinase 9 and Bcl-2 protein expression and promoted the protein expression of Bax(P＜0.01).To conclude,PHSTF may inhibit the proliferation and migration of fibroblast-like synoviocytes and promote apoptosis by inhibiting the Wnt/β-catenin signaling pathway.

Objective To investigate the risk factors for postoperative recurrence and metastasis in patients with T1 stageⅢ/Ⅳ clear cell renal cell carcinoma(ccRCC), and to analyze the influence of surgical methods on prognosis, so as to provide prognostic evaluation and treatment guidance for clinical practice. Methods A retrospective analysis was conducted on 398 patients diagnosed with T1 stage Ⅲ/Ⅳ ccRCC who underwent either partial nephrectomy(PN)or radical nephrectomy(RN)at Jiangsu Province Hospital during Jan. 2008 and Sep. 2022. The patients were divided into recurrence group(n=49)and non-recurrence group(n=349)according to whether the tumor recurred during the follow-up period. The general, clinical data and prognosis were compared between the two groups. Univariate and multivariate Cox regression analyses were used to explore the factors influencing disease-free survival(DFS)and overall survival(OS)after surgery. Subgroup analysis using Kaplan-Meier curves was performed for T1a and T1b patients. Results During the median follow-up of 67(42, 98)months, the recurrence group was characterized by older age, larger tumor diameter, higher proportion of T1b stage, and more complex tumor anatomy. Univariate and multivariate Cox regression analyses showed that age ≥55 years and R.E.N.A.L. score ≥7 were independent risk factors for poorer DFS and OS(P＜0.05). Subgroup analysis revealed that PN or RN did not significantly affect DFS or OS in T1a patients and OS in T1b patients, while RN significantly improved DFS in T1b patients(P＜0.05). Conclusion Age ≥55 years and R.E.N.A.L. score ≥7 are independent risk factors for poor DFS and OS in highgrade T1 ccRCC patients. For T1b patients, RN may improve DFS.

Cholangiocarcinoma (CCA) is a malignancy characterized by tumor cells originating in the liver or bile ducts, exhibiting features of cholangiocyte differentiation. It poses a significant clinical challenge due to the limited diagnostic and therapeutic options available. Robust animal models are essential for advancing our understanding of CCA pathogenesis and developing effective treatments. This review provides a comprehensive overview of CCA mouse models, highlighting various approaches, including chemical induction, genetically engineered models, and tumor xenografts. Each model is discussed in terms of its establishment techniques, pathological characteristics, and research significance, with a focus on intrahepatic CCA. Chemical induction models, such as diethylnitrosamine- and azoxymethane-induced models, offer insights into tumorigenesis processes, whereas genetically modified models involving alterations in key genes such as Kirsten rat sarcoma viral oncogene homolog, tumor protein 53, and isocitrate dehydrogenase serve as important tools for studying the molecular mechanisms underlying CCA. Xenograft models, including patient-derived xenografts, bridge the gap between experimental research and clinical applications, allowing for precise therapeutic evaluations. By comparing these models, this review underscores their respective advantages and limitations, paving the way for future studies aiming to optimize and innovate CCA modeling strategies.

Objective:To investigate the completion rate of tumor evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients in the national multicenter real-world database.Methods:The prospective real-world study was conducted. The clinicopathological data of 1 074 patients who underwent surgical treatment for mid and low rectal cancer in 47 national medical institutions, including Peking Union Medical College Hospital et al, from May 12,2023 to May 11,2024 were collected. Observation indicators: (1) clinical characteristics of patients with mid and low rectal cancer; (2) initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer; (3) initial imaging evaluation of patients with mid and low rectal cancer; (4) imaging evaluation after neoadjuvant therapy for patients with mid and low rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absoluter numbers and/or percentages. Results:(1) Clinical characteristics of patients with mid and low rectal cancer. Of the 1 074 patients, there were 713 males and 361 females, aged 63(56,70)years. The body mass index of 1 074 patients was 24(21,26)kg/m 2.For American Society of Anesthesiologists classification, there were 147 cases of stage Ⅰ, 641 cases of stage Ⅱ, 157 cases of stage Ⅲ, 2 cases of stage Ⅳ, and there were 127 cases missing data. (2) Initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer. Of the 1 074 patients, there were 787 cases (73.28%) undergoing complete colonoscopy, and there were only 197 cases (18.34%) undergoing immunohistochemical evaluation of all four mismatch repair proteins. (3) Initial imaging evaluation of patients with mid and low rectal cancer. Of the 1 074 patients, there were 842(78.40%) patients completing magnetic resonance imaging (MRI) or ultrasound evaluation, and there were 914(85.10%) patients completing chest, abdomen, and pelvis enhanced computed tomography (CT) evaluation. In the 149 patients completing rectal ultrasound evaluation, there were 122 cases (81.88%) comple-ting T staging evaluation, and there were 81 cases (54.36%) completing N staging evaluation. In the 808 patients completing rectal MRI evaluation, there were 708 cases (87.62%) completing T staging evaluation, and there were 590 cases (73.02%) completing N staging evaluation. (4) Imaging evalua-tion after neoadjuvant therapy for patients with mid and low rectal cancer. Of the 388 patients with neoadjuvant therapy, there were 332 patients (85.57%) completing MRI or ultrasound evaluation, and there were 327 patients (84.28%) completing chest, abdomen, and pelvis enhanced CT evalua-tion. In the 70 patients completing rectal ultrasound evaluation, there were 65 cases (92.86%) com-pleting T staging evaluation, and there were 49 cases (70.00%) completing N staging evaluation. In the 327 patients completing rectal MRI evaluation, there were 246 cases (75.23%) completing T staging, and there were 228 cases (69.72%) completing N staging evaluation. Conclusion:The com-pletion rate of tumor imaging evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients on a national scale is relatively good.

AIM:To investigate the mechanism of Qianggu-Kangshu formula(QGKSF)in the treatment of rheumatoid arthritis(RA)bone destruction based on network pharmacology,molecular docking,and cell experiments.METHODS:The main active ingredients and potential targets of QGKSF were obtained through TCMSP database and litera-ture search.OMIM database and GeneCards database were used to search the targets related to RA bone destruction,and Venny 2.1.0 was employed to screen the intersected targets of QGKSF and RA bone destruction.The protein-protein inter-action network of potential intersected targets was constructed by STRING database,and topological analysis was carried out by Cytoscape software to screen core targets.The screened targets of QGKSF related to RA bone destruction were evalu-ated through the Metascape system.Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology were applied to complete enrichment analysis.AutoDock and PyMOL software was used to carry out molecular docking between the core components and the core proteins.Mouse RAW264.7 macrophages were cultured in vitro,and the cell viability was de-tected by CCK-8 assay.The number of tartrate-resistant acid phosphatase(TRAP)positive multinucleated cells in each group was calculated by TRAP staining.The enzyme activity of the cells was evaluated by determination of TRAP activity.F-actin ring formation was detected by phalloidin staining.Western blot analysis was conducted to detect the protein levels of nuclear factor of activated T cells 1(NFATc1),TRAP,cathepsin K(CTSK),c-Fos,matrix metalloproteinase 9(MMP9),osteoprotegerin(OPG),receptor activator of nuclear factor κB(RANK),RANK ligand(RANKL)and phos-phorylated protein kinase B(p-AKT).RESULTS:A total of 136 active ingredients and 126 targets were selected corre-lated with QGKSF,whil 207 intersected targets of QGKSF and RA bone destruction were screened,175 of which were core targets.There were 199 pathways obtained by GO enrichment,and 20 pathways related to osteoclasts were screened out,including phosphatidylinoinosiol 3-kinase/AKT signaling pathway and osteoclast differentiation,etc.The results of TRAP staining,TRAP enzyme activity determination and phalloidin staining showed less positive cell formation,de-creased enzyme activity and decreased F-actin ring formation in QGKSF and methotrexate(MTX)groups compared with model group.Western blot results showed that compared with model group,the protein levels of NFATc1,TRAP,CTSK,c-Fos,MMP9,p-AKT,RANK and RANKL were decreased(P＜0.05),while the expression of OPG protein was in-creased(P＜0.05)in QGKSF and MTX groups.CONCLUSION:Treatment with QGKSF inhibits RANKL-induced dif-ferentiation of RAW264.7 cells into osteoclasts possibly by inhibiting the over-differentiation of osteoclasts via regulating RANKL/RANK/OPG signaling pathway.

Lens injury is an important etiological factor in the reduction of visual function following ocular trauma.Currently, there are no clear standards for the classification of lens injury, and comprehensive diagnostic tools are lacking.This deficiency leads to numerous controversies and challenges in critical areas, such as diagnosis and preoperative evalution, timing of surgery, surgical strategy, and assessment of postoperative prognosis.Tomographic imaging technology, such as computed tomography, magnetic resonance imaging, optical coherence tomography, has introduced a new dimension to the evaluation of lens injury, which is crucial for assessing the transparency, texture, location, morphology, and integrity of the lens, as well as the zonules and nearby intraocular structures.However, the use of tomographic imaging technology is somewhat limited due to the limitations of relying on a single method.With the ongoing advancement of imaging technologies and the rapid development of big data and artificial intelligence, tomographic imaging will become an increasingly essential tool in the future management of lens injury.Our expert group reviewed the epidemiological characteristics and classification of lens injury and the major challenges currently faced in the diagnosis and treatment of lens injury, and provided expert recommendations mainly focusing on the application, shortcomings and limitations of current tomographic imaging technology in the diagnosis and treatment of lens injury, and future development directions.

AIM:To investigate the potential effect of Dabuyuan Jian(DBYJ)on peroxisome proliferator-acti-vated receptor γ(PPARγ)/nuclear factor-κB(NF-κB)signaling pathway and related inflammatory proteins in mice with mild cognitive impairment(MCI),and to explore the mechanism of DBYJ in improving the learning and memory ability of MCI mice.METHODS:Forty C57BL/6 male mice were randomly divided into 5 groups,including negative control(NC)group,D-galactose(D-Gal)group,D-Gal+DBYJ group,D-Gal+GW9662(PPARγ inhibitor)group and D-Gal+GW9662+DBYJ group,with 8 mice each.The mice in NC group were subcutaneously injected with 0.9%saline solution on the back of the neck for 8 weeks,while those in the remaining 4 groups were subcutaneously injected with D-Gal(100 mg·kg-1·d-1)on the back of the neck for 8 weeks to establish the MCI model.From week 5 to week 8,the mice in D-Gal+GW9662 and D-Gal+DBYJ+GW9662 groups were intraperitoneally injected with GW9662(1 mg·kg-1·d-1).From week 5,the mice in D-Gal+DBYJ and D-Gal+DBYJ+GW9662 groups were treated with DBYJ(13.2 g/kg)by gavage,while those in the re-maining 3 groups were administered an equal volume of purified water for 4 weeks.The Morris water maze(including posi-tioning navigation experiment and space exploration experiment)was used to assess the learning and memory ability of the mice.The structural integrity of the hippocampus of the mice was assessed by hematoxylin-eosin(HE)staining.Nissl staining was used to evaluate damage to hippocampal neurons in mice,and Western blot was applied to detect the protein levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),PPARγ,P65 and phosphorylated P65(p-P65)in the hippocampus of the mice.RESULTS:Compared with NC group,the escape latency of the mice in D-Gal+D-Gal and D-Gal+GW9662 groups significantly increased(P＜0.01),while the number of platform crossing and the duration of staying in the target quadrant within 60 s significantly decreased(P＜0.01).The number of neurons in the CA3 region remarkably decreased(P＜0.01),and pyramidal cell disarrangement and neuronal shrinkage were observed.The levels of TNF-α,IL-1β and p-P65 were up-regulated,while the expression of PPARγ was down-regulated(P＜0.05).Compared with D-Gal group,the escape latency of the mice in D-Gal+DBYJ group significantly decreased(P＜0.01),while the number of plat-form crossing and the duration of staying in the target quadrant within 60 s remarkably increased(P＜0.01).The number of neurons in the CA3 region increased(P＜0.01),the pyramidal cells were more neatly arranged,and the cytoarchitec-ture was intact.The levels of TNF-α,IL-1β and p-P65 were down-regulated,while the expression of PPARγ was up-regu-lated(P＜0.05).Compared with D-Gal+GW9662 group,significantly decreased escape latency was observed in D-Gal+DBYJ+GW9662 group(P＜0.01),and the number of platform crossing and the duration of staying in the target quadrant within 60 s remarkably increased(P＜0.05).The number of neurons in the CA3 region increased(P＜0.01),the pyrami-dal cells were arranged more neatly,and the cytoarchitecture was relatively intact.The levels of TNF-α,IL-1β and p-P65 were down-regulated,while the expression of PPARγ was up-regulated(P＜0.05).The effects shown in D-Gal+DBYJ+GW9662 group were inferior to those in D-Gal+DBYJ group,indicating that the therapeutic effect of DBYJ was inhibited after the addition of GW9662.CONCLUSION:Dabuyuan Jian improves the learning and memory ability of MCI mice,and the mechanism may be related to the expression of key proteins in the PPARγ/NF-κB signaling pathway.

Objective:To investigate the completion rate of tumor evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients in the national multicenter real-world database.Methods:The prospective real-world study was conducted. The clinicopathological data of 1 074 patients who underwent surgical treatment for mid and low rectal cancer in 47 national medical institutions, including Peking Union Medical College Hospital et al, from May 12,2023 to May 11,2024 were collected. Observation indicators: (1) clinical characteristics of patients with mid and low rectal cancer; (2) initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer; (3) initial imaging evaluation of patients with mid and low rectal cancer; (4) imaging evaluation after neoadjuvant therapy for patients with mid and low rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absoluter numbers and/or percentages. Results:(1) Clinical characteristics of patients with mid and low rectal cancer. Of the 1 074 patients, there were 713 males and 361 females, aged 63(56,70)years. The body mass index of 1 074 patients was 24(21,26)kg/m 2.For American Society of Anesthesiologists classification, there were 147 cases of stage Ⅰ, 641 cases of stage Ⅱ, 157 cases of stage Ⅲ, 2 cases of stage Ⅳ, and there were 127 cases missing data. (2) Initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer. Of the 1 074 patients, there were 787 cases (73.28%) undergoing complete colonoscopy, and there were only 197 cases (18.34%) undergoing immunohistochemical evaluation of all four mismatch repair proteins. (3) Initial imaging evaluation of patients with mid and low rectal cancer. Of the 1 074 patients, there were 842(78.40%) patients completing magnetic resonance imaging (MRI) or ultrasound evaluation, and there were 914(85.10%) patients completing chest, abdomen, and pelvis enhanced computed tomography (CT) evaluation. In the 149 patients completing rectal ultrasound evaluation, there were 122 cases (81.88%) comple-ting T staging evaluation, and there were 81 cases (54.36%) completing N staging evaluation. In the 808 patients completing rectal MRI evaluation, there were 708 cases (87.62%) completing T staging evaluation, and there were 590 cases (73.02%) completing N staging evaluation. (4) Imaging evalua-tion after neoadjuvant therapy for patients with mid and low rectal cancer. Of the 388 patients with neoadjuvant therapy, there were 332 patients (85.57%) completing MRI or ultrasound evaluation, and there were 327 patients (84.28%) completing chest, abdomen, and pelvis enhanced CT evalua-tion. In the 70 patients completing rectal ultrasound evaluation, there were 65 cases (92.86%) com-pleting T staging evaluation, and there were 49 cases (70.00%) completing N staging evaluation. In the 327 patients completing rectal MRI evaluation, there were 246 cases (75.23%) completing T staging, and there were 228 cases (69.72%) completing N staging evaluation. Conclusion:The com-pletion rate of tumor imaging evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients on a national scale is relatively good.

Objective To investigate the impact of county-level"Unified ECG Network"construction on the treatment efficiency and clinical outcomes of patients with acute ST-segment elevation myocardial infarction(STEMI).Methods A retrospective analysis was conducted on the clinical data of STEMI patients from Beichuan County and Yanting County in Mianyang City,and Jiange County in Guangyuan City,Sichuan Province,during the 18 months before(128 cases)and 18 months after(187 cases)the establishment of the"Unified ECG Network."Differences in demographic characteristics,treatment efficiency,therapeutic methods,and clinical outcomes between the two groups were compared.Results There was no statistically significant difference in general demographic characteristics between the two groups(all P＞0.05).Compared with the pre-construction group,the post-construction group showed significantly shorter times in initial ECG completion[5(3,7)min vs.6(4,8)min],initial ECG diagnosis[3(2,4)min vs.5(2,6)min],first medical contact to preliminary diagnosis[10(9,12)min vs.13(11,15)min],network hospital door-in-door-out time[21(19,23)min vs.26(23,30)min],and first medical contact to wire-crossing time[(94.82±11.87)min vs.(107.97±18.39)min](allP＜0.001).The proportion of patients bypassing the emergency department and coronary care unit significantly increased(64.17％vs.32.81％,P＜0.001).The proportion of patients undergoing emergency percutaneous coronary intervention significantly increased(72.73％vs.51.56％,P＜0.001),while the proportions of thrombolytic therapy and non-reperfusion therapy significantly decreased(both P＜0.05).Additionally,in-hospital mortality rate,Killip class≥Ⅱ proportion,incidence of major adverse cardiovascular events,and average length of hospital stay were all significantly reduced(all P＜0.05).There were no statistically significant differences among the three county-level chest pain centers in terms of major treatment efficiency,therapeutic strategies,or clinical outcomes(all P＞0.05).Conclusions The construction of the county-level"Unified ECG Network"can significantly improve the treatment efficiency of STEMI patients,optimize reperfusion therapy strategies,improve clinical outcomes,and demonstrate substantial clinical promotion value.