BACKGROUND:Eucommia ulmoides has a certain osteogenic effect,which can promote the proliferation and differentiation of osteoblasts.However,it is unclear whether Eucommia ulmoides has effects on alveolar bone formation and Wnt/β-Catenin signaling pathway. OBJECTIVE:To investigate the mechanism by which Eucommia ulmoides promotes alveolar bone formation in ovariectomized rats based on the Wnt/β-Catenin signaling pathway. METHODS:Sixty female Sprague-Dawley rats were selected and randomly divided into five groups:blank control group,sham-operation group,model group,low-dose group Eucommia ulmoides group,and high-dose Eucommia ulmoides group,with twelve rats in each group.Osteoporosis animal models were constructed by bilateral oophorectomy in the model group and the low-dose and high-dose Eucommia ulmoides groups.The sham-operation group underwent the same method to remove adipose tissue of equal mass around the bilateral ovaries.Three months after surgery,the low-and high-dose Eucommia ulmoides groups were given 2.1 g/kg/d and 4.2 g/kg/d Eucommia ulmoides by gavage,respectively.The sham-operation group and model group were given the same amount of physiological saline by gavage.After 12 weeks of drug intervention,the changes in alveolar bone mass of rats in each group were observed through Micro-CT;hematoxylin-eosin staining was used to observe the pathological structural changes of alveolar bone in rats;enzyme linked immunosorbent assay was used to detect the expression levels of alkaline phosphatase and osteocalcin in the serum of rats;western blot was used to detect the expression levels of β-Catenin and Frizzled9 receptor proteins in the alveolar bone of rats;and real-time fluorescence quantitative PCR was used to detect the expression of osteocalcin,Runt-related transcription factor 2(Runx2),alkaline phosphatase,β-catenin,and frizzled9 mRNAs in alveolar bone tissues of rats. RESULTS AND CONCLUSION:Compared with the blank control group,bone volume fraction,trabecular number,trabecular thickness,and bone mineral density were reduced in the model group(P＜0.05),and trabecular separation was elevated(P＜0.05).Pathological observation showed that the arrangement of trabeculae was disordered and irregular,the trabeculae were thinned or broken,and the marrow cavity was enlarged in the model group,with a significant reduction in bone volume;the level of alkaline phosphatase in the serum was increased(P＜0.05),and the level of osteocalcin was decreased(P＜0.05);mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were decreased(P＜0.05);protein expression of β-Catenin and Frizzled9 was decreased(P＜0.05).Compared with the model group,the low-and high-dose Eucommia ulmoides groups showed an increase in bone volume fraction,trabecular number,trabecular thickness,and bone mineral density(P＜0.05)and a decrease in trabecular separation(P＜0.05).In the low-and high-dose Eucommia ulmoides groups,bone trabeculae were slightly aligned and thickened,with a significant increase in bone mass.Compared with the model group,the serum level of alkaline phosphatase was reduced(P＜0.05)and the serum level of osteocalcin was elevated(P＜0.05)in the low-and high-dose Eucommia ulmoides groups.Compared with the model group,the mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were increased in the low-and high-dose Eucommia ulmoides groups(P＜0.05).Compared with the model group,the protein expression of Frizzled9 was increased in the low-dose Eucommia ulmoides group(P＜0.05),while the protein expression of β-Catenin and Frizzled9 was increased in the high-dose Eucommia ulmoides group(P＜0.05).Compared with the low-dose Eucommia ulmoides group,the high-dose Eucommia ulmoides group had a more significant improvement in the above indexes.To conclude,Eucommia ulmoides can effectively promote the alveolar bone formation,and its mechanism of action might be related to the activation of the Wnt/β-catenin signaling pathway.

Pristimerin, which is one of the compounds present in Celastraceae and Hippocrateaceae, has antitumor effects. However, its mechanism of action in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo. The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays. Cell apoptosis was evaluated by flow cytometry. Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry. RNA sequencing (RNA-Seq) was employed to identify significantly differentially expressed genes (DEGs). Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin?s effect. Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo. Pristimerin inhibited cell growth and induced apoptosis in ESCC cells. Upregulation of Noxa was crucial for pristimerin-induced apoptosis. Pristimerin activated the Forkhead box O3a (FoxO3a) signaling pathway and triggered FoxO3a recruitment to the Noxa promoter, leading to Noxa transcription. Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis. Pristimerin treatment suppressed xenograft tumors in nude mice, but these effects were largely negated in Noxa-KO tumors. Furthermore, the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa. This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation. These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.
Forkhead Box Protein O3/genetics* ; Humans ; Apoptosis/drug effects* ; Esophageal Squamous Cell Carcinoma/physiopathology* ; Esophageal Neoplasms/physiopathology* ; Pentacyclic Triterpenes ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Mice ; Signal Transduction/drug effects* ; Mice, Nude ; Cell Proliferation/drug effects* ; Triterpenes/pharmacology* ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Male ; Gene Expression Regulation, Neoplastic/drug effects*

Sarcopenia is common in patients with cirrhosis and significantly impacts their quality of life and survival.Its pathogenesis involves multiple factors,including inadequate nutrient intake,abnormal hormone levels,high ammonia levels,abnormal levels of inflammatory factors,imbalanced gut bacteria,and physical inactivity.This study aims to review the epidemiological characteristics,pathogenesis,screening,diagnosis,and treatment of cirrhosis to assist doctors and patients in better preventing,monitoring,and addressing sarcopenia.

Objective To investigate the expression of microRNA-873-5p(miR-873-5p)and C-X-C motif chemokine ligand 16(CXCL16)in thyroid cancer tissue and their relationship with pathological parameters and prognosis.Methods A total of 125 patients with thyroid cancer who underwent surgery at Nanjing Sec-ond Hospital from January 2018 to June 2019 were selected as the research subjects.Some cancer tissues and corresponding adjacent tissues of the patients were collected,and the expressions of miR-873-5p and CXCL16 mRNA were detected by real-time fluorescence quantitative polymerase chain reaction.The binding sites of miR-873-5p and CXCL16 were predicted through the online database.Pearson correlation was used to analyze the correlation between miR-873-5p and CXCL16 mRNA expression,and the correlation between miR-873-5p,CXCL16 mRNA expression and pathological parameters.According to the median expression of miR-873-5p and CXCL16 mRNA in thyroid cancer tissues,they were classified as high expression and low expression.The survival curves of patients with high and low expression of miR-873-5p and CXCL16 mRNA were plotted by the Kaplan-Meier method.Taking the survival status of patients with thyroid cancer as the dependent varia-ble,Cox regression was used to determine the relationship between the expressions of miR-873-5p and CX-CL16 mRNA and the death of patients with thyroid cancer.Results The expressions of miR-873-5p and CX-CL16 mRNA in thyroid cancer tissues were 0.83±0.12 and 1.54±0.25,respectively,and those in adjacent tissues were 1.13±0.15 and 0.98±0.13,respectively,the differences were statistically significant(t=-18.160,21.089).P＜0.001).Pearson correlation analysis showed that the expression of miR-873-5p and CXCL16 mRNA in thyroid cancer tissues was negatively correlated(r=-0.722,P＜0.001).The expression of miR-873-5p in thyroid cancer tissues was negatively correlated with pathological type,TNM stage and lymph node metastasis(r=-0.510,—0.262,-0.315,P＜0.05).The expression of CXCL16 mRNA was positively correlated with pathological type,TNM stage and lymph node metastasis(r=0.593,0.275,0.314,P＜0.05).The Kaplan-Meier survival curve showed that the 5-year overall survival rate of patients with high expression of miR-873-5p was higher than that of patients with low expression of miR-873-5p.The 5-year o-verall survival rate of patients with high expression of CXCL16 mRNA was lower than that of patients with low expression of CXCL16 mRNA,and the difference was statistically significant(x2=11.328,10.514,all P=0.001).miR-873-5p≥0.84 was an independent protective factor for death in patients with thyroid cancer,and CXCL16 mRNA≥1.55 was an independent risk factor for death in patients with thyroid cancer(P＜0.05).Conclusion The expressions of miR-873-5p and CXCL16 mRNA in thyroid cancer tissues are related to patho-logical parameters and prognosis,and may become prognostic markers for patients with thyroid cancer.

Neoadjuvant therapy is the preferred treatment mode for locally advanced operable esophageal cancer, and its clinical value has been established through evidence-based medical evidence. Accurately identifying patients who can benefit before or during treatment is of great significance for formulating the overall treatment strategy. Clinical indicators such as age, gender, pathological characteristics, nutritional status, and hematological/histological indicators have certain value in predicting the efficacy of neoadjuvant therapy for esophageal cancer. However, the predictive effect of a single indicator is limited. It is necessary to comprehensively use multiple indicators and combine advanced technologies and methods to provide accurate and practical tools for clinical efficacy prediction.

Objective To investigate the effect and mechanism of cell migration-induced protein(KIAA1199)on the proliferation of osteosarcoma cells.Methods The KIAA1199 gene was knocked down or overexpressed in osteosarcoma cell lines(HOS and U2OS)with high KIAA1199 expression.The expression of KIAA1199 was confirmed by RT-PCR and Western blotting.CCK-8 and colony formation assays were used to determine the effect of KIAA1199 on cell proliferation.CCK-8 and cell viability assays were used to confirm that KIAA1199 promoted osteosarcoma cell proliferation by inhibiting ferroptosis.The BODIPY 581/591 probe was used to investigate the effect of KIAA1199 on cell lipid peroxidation.The effect of KIAA1199 on PTGS2 was investigated by RT-PCR,and the level of ferroptosis related proteins(GPX4,SLC7A11,DHODH,and FSP1)were determined by Western blotting.Results KIAA1199 knockdown inhibited osteosarcoma cell proliferation,which mainly worked by promoting ferroptosis in osteosarcoma cells.Ferrostatin-1(Fer-1,a ferroptosis inhibitor)could reverse the proliferation inhibition caused by KIAA1199 knockdown.Osteosarcoma cells with KIAA1199 knockdown were more sensitive to ferroptosis inducer Erastin,and their lipid peroxidation and PTGS2 mRNA increased significantly.KIAA1199 knockdown resulted in lower expression of GPX4 and SLC7A11 proteins and a lower GSH/GSSG ratio.On the other hand,KIAA1199 overexpression promoted osteosarcoma cell proliferation,made cells more tolerant to Erastin,significantly reduced lipid peroxidation and PTGS2 mRNA levels,and obviously increased the protein expression levels of GPX4 and SLC7A11.Conclusion KIAA1199 inhibits ferroptosis through SLC7A11/GSH/GPX4 pathway,thereby promoting osteosarcoma cell proliferation.

Objective To compare the technical indicators and clinical effect of catheter-directed thrombolysis(CDT)via two types of non-popliteal venous access in the treatment of acute mixed-type lower extremity deep vein thrombosis(DVT).Methods The clinical data of 119 patients with acute mixed-type lower extremity DVT,who were admitted to the Affiliated Jiangning Hospital of Nanjing Medical University and the Affiliated Nanjing Hospital of Nanjing Medical University of China to receive CDT treatment from January 2016 to June 2022,were retrospectively analyzed.Of the 119 patients,CDT via deep calf vein access was carries out in 45(calf vein group)and CDT via healthy-side femoral venous access was performed in 74(femoral vein group).The success rate of vascular puncture,success rate of catheterization technique,number of successful CDT venous puncturing,time spent for sheath placement,time spent for catheterization,thrombolysis time,used amount of thrombolytic agent and associated complications(including vein puncturing and anticoagulant thrombolysis-related complications),the thrombolytic effect of different anatomical segments,and the clinical efficacy during the follow-up period for at least 12 months were compared between the two groups.Results Successful catheterization via deep calf vein access and via healthy-side femoral vein access was obtained in 31 and 58 CDT patients respectively,with a technical success rate of 68.89％(31/45)and 78.38％(58/74)respectively,the difference between the two groups was not statistically significant(P=0.248).In 26 patients(67.74％)of the calf vein group,more than two times of puncturing were needed before the sheath placement could be successfully achieved.The time spent for sheath placement in the femoral vein group was(1.84±0.87)min,which was remarkably shorter than(10.52+6.13)min in the calf vein group(P＜0.001),but the time spent for catheterization in the femoral vein group was(41.60±13.31)min,which was obviously longer than(20.06+4.46)min in the calf vein group(P＜0.001).The thrombolysis time in the femoral vein group and the calf vein group was(5.34+1.43)days and(5.06±1.18)days respectively(P=0.354),and the used amount of thrombolytic agent in the femoral vein group was(352.16±71.98)×104 U,which was prominently larger than(284.68±77.64)× 104 U in the calf vein group(P＜0.001).The last follow-up check showed that the patency rate of the popliteal vein in the calf vein group was significantly higher than that in the femoral vein group(P=0.037).No statistically significant differences in the incidence of post-thrombotic syndrome(PTS)and the mean VEINES-QOL/Sym scores existed between the two groups(all P＞0.05).Conclusion Compared with CDT via healthy-side femoral vein access,CDT via deep calf vein access can better remove the thrombus in the popliteal vein and superficial femoral vein,and improve the femoropopliteal vein patency rate,although it has no obvious advantages in reducing the occurrence of PTS and in improving the VEINES-QOL/Sym score,moreover,the deep calf vein puncture and sheath placement require a high-level technique.

The traditional Chinese medicine(TCM) industry is a crucial part of China's pharmaceutical sector and plays a strategic role in ensuring public health and promoting economic and social development. In response to the practical demand for high-quality development of the TCM industry, this paper focused on the bottlenecks encountered during the digital and intelligent transformation of TCM production systems. Specifically, it explored technical strategies and methodologies for constructing the best TCM production mode. An innovative artificial intelligence(AI)-centered technical architecture for TCM production was proposed, focusing on key aspects of production management including process modeling, state evaluation, and decision optimization. Furthermore, a series of critical technologies were developed to realize the best TCM production mode. Finally, a novel AI-driven TCM production mode characterized by a closed-loop system of "measurement-modeling-decision-execution" was presented through engineering case studies. This study is expected to provide a technological pathway for developing new quality productive forces within the TCM industry.
Artificial Intelligence ; Drugs, Chinese Herbal ; Medicine, Chinese Traditional/methods* ; Humans