BACKGROUND:Previous studies of the research group have found that icariin-containing serum can delay the progression of knee osteoarthritis,promote chondrocyte proliferation and stem cell cartilage differentiation in rats,but there is still a lack of sufficient basis for clinical application.OBJECTIVE:To investigate the repair effect of icariin-containing serum on lipopolysaccharide-induced inflammatory damage of human chondrocytes.METHODS:The effect of icariin-containing serum on chondrocyte viability was detected by cell counting kit-8 method,and the optimal volume fraction and time of icariin-containing serum were screened.The cells were then divided into blank group,lipopolysaccharide group,icariin-containing serum group and lipopolysaccharide+icariin-containing serum group.After grouping,immunofluorescence was used to detect the secretion of type Ⅱ collagen in chondrocytes in each group.Real-time PCR was used to detect the expression of related genes.RESULTS AND CONCLUSION:(1)Icariin-containing serum showed good biosafety characteristics for human chondrocytes,and the cell viability reached the highest level after 48 hours of intervention when the icariin-containing serum volume fraction was 15％,and the follow-up experiments were carried out according to the conditions.(2)Compared with the blank group,lipopolysaccharide significantly inhibited the expression of type Ⅱ collagen in chondrocytes,while icariin-containing serum showed a positive mobilization effect,which could effectively promote the secretion of type Ⅱ collagen in chondrocytes under normal and inflammatory conditions.(3)The mRNA expression of type Ⅱ collagen and Aggrecan in chondrocytes decreased significantly under lipopolysaccharide stimulation,and the mRNA expression levels of matrix metalloproteinase 13 and a disintegrin-like and metalloproteinase with thrombospondin motifs-5 increased significantly.Icariin-containing serum promoted the mRNA expression of type Ⅱ collagen in human chondrocytes under inflammatory conditions and reduced the mRNA expression of matrix metalloproteinase 13 and a disintegrin-like and metalloproteinase with thrombospondin motifs-5 in chondrocytes after lipopolysaccharide intervention.Therefore,these findings indicate that the icariin-containing serum has good safety for human chondrocytes and plays an important role in maintaining the normal physiological functions of chondrocytes,promoting the synthesis of extracellular matrix,and inhibiting the secretion of inflammatory factors.

BACKGROUND:Previous studies of the research group have found that icariin-containing serum can delay the progression of knee osteoarthritis,promote chondrocyte proliferation and stem cell cartilage differentiation in rats,but there is still a lack of sufficient basis for clinical application.OBJECTIVE:To investigate the repair effect of icariin-containing serum on lipopolysaccharide-induced inflammatory damage of human chondrocytes.METHODS:The effect of icariin-containing serum on chondrocyte viability was detected by cell counting kit-8 method,and the optimal volume fraction and time of icariin-containing serum were screened.The cells were then divided into blank group,lipopolysaccharide group,icariin-containing serum group and lipopolysaccharide+icariin-containing serum group.After grouping,immunofluorescence was used to detect the secretion of type Ⅱ collagen in chondrocytes in each group.Real-time PCR was used to detect the expression of related genes.RESULTS AND CONCLUSION:(1)Icariin-containing serum showed good biosafety characteristics for human chondrocytes,and the cell viability reached the highest level after 48 hours of intervention when the icariin-containing serum volume fraction was 15％,and the follow-up experiments were carried out according to the conditions.(2)Compared with the blank group,lipopolysaccharide significantly inhibited the expression of type Ⅱ collagen in chondrocytes,while icariin-containing serum showed a positive mobilization effect,which could effectively promote the secretion of type Ⅱ collagen in chondrocytes under normal and inflammatory conditions.(3)The mRNA expression of type Ⅱ collagen and Aggrecan in chondrocytes decreased significantly under lipopolysaccharide stimulation,and the mRNA expression levels of matrix metalloproteinase 13 and a disintegrin-like and metalloproteinase with thrombospondin motifs-5 increased significantly.Icariin-containing serum promoted the mRNA expression of type Ⅱ collagen in human chondrocytes under inflammatory conditions and reduced the mRNA expression of matrix metalloproteinase 13 and a disintegrin-like and metalloproteinase with thrombospondin motifs-5 in chondrocytes after lipopolysaccharide intervention.Therefore,these findings indicate that the icariin-containing serum has good safety for human chondrocytes and plays an important role in maintaining the normal physiological functions of chondrocytes,promoting the synthesis of extracellular matrix,and inhibiting the secretion of inflammatory factors.

Objective To analyze the motion,deformation,and adhesion behavior of circulating tumor cells(CTCs)in bifurcated microvessels,reveal their mechanical properties under different flow conditions and explore their role in the process of cancer metastasis.Methods A cell-scale modeling approach was adopted,combining the immersed boundary-lattice Boltzmann method(IB-LBM)and the adhesive-dynamics model to simulate the motion and adhesion behavior of circulating tumor cells in microvessels.Results The adhesion behavior of CTCs was significantly influenced by the Reynolds number(Re)and the surface elastic moduli of cells.Under the condition of Re=0.003,the adhesion behavior of CTCs was the most stable;CTCs with a lower surface elastic modulus exhibited greater deformation during adhesion and demonstrated stronger adhesive forces.Conclusions The mechanical properties of CTCs and flow field conditions jointly determine their transport and adhesion behavior in microvessels.The levels of Re and surface elastic modulus play a critical role in the deformation and adhesion of CTCs.The study of the adhesion characteristics of CTCs provides mechanistic insights and new potential directions for cancer prevention and treatment research.

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Objective To explore the mechanism of ubiquitin specific peptidase 21 (USP21) increasing the stability of forkhead box protein M1 (FOXM1) and promoting M2 polarization of macrophages in endometriosis (EM). Methods Eutopic endometrial stromal cells (EESC) collected from patients and normal endometrial stromal cells (NESC) from routine health examiners were cultured in vitro, and the expression levels of USP21 and FOXM1 were detected using RT-qPCR and Western blot. EESCs were co-cultured with macrophages. M1 polarization markers of interleukin 6 (IL-6) and CXC chemokine ligand 10 (CXCL10) and M2 polarization markers of CD206 and fibronectin 1 (FN1) were tested using RT-qPCR. M2 marker CD206 was further detected by flow cytometry. IL-6, tumor necrosis factor-alpha (TNF-α), IL-10, and transforming growth factor-beta (TGF-β) levels in cell supernatant were detected by ELISA. Co-immunoprecipitation was used to assess the interaction between USP21 and FOXM1, and the ubiquitination level of FOXM1. FOXM1 protein stability was detected through cycloheximide (CHX) assay. Results USP21 and FOXM1 expression levels in the EESC group were significantly increased compared with those in the NESC group; compared with the NESC + M0 group, the EESC + M0 group showed no significant difference in the expression of M1 polarization markers (IL-6 and CXCL10), but increased expression of M2 polarization markers (CD206 and FN1), along with notably increased number of M2 macrophages; there was no significant difference in IL-6 and TNF-α levels, but increased levels of IL-10 and TGF-β in the cell supernatant. The above findings indicated that the deubiquitinase USP21 was highly expressed in EM, promoting M2 polarization of macrophages. Knocking down USP21 or FOXM1 can inhibit M2 polarization of EM macrophages. USP21 interacted with FOXM1 in EESC, leading to a decrease in FOXM1 ubiquitination level and an increase in FOXM1 protein stability. Overexpression of FOXM1 reversed the inhibitory effect of knocking down USP21 on M2 polarization of EM macrophages. Conclusion The deubiquitinase USP21 interacts with FOXM1 to increase the stability of FOXM1 and promote M2 polarization of EM macrophages.
Humans ; Forkhead Box Protein M1/genetics* ; Female ; Macrophages/cytology* ; Endometriosis/genetics* ; Ubiquitin Thiolesterase/genetics* ; Cells, Cultured ; Endometrium/metabolism* ; Ubiquitination ; Adult ; Interleukin-10/metabolism* ; Interleukin-6/metabolism* ; Protein Stability ; Stromal Cells/metabolism*

Objective:To investigate the application value of needle-knife accurate fistulo-tomy (NKAF) for difficult biliary cannulation during endoscopic retrograde cholangiopancreato-graphy (ERCP).Methods:The retrospective and descriptive study was conducted. The clinicopatho-logical data of 137 patients with difficult biliary cannulation during ERCP at Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine between January 2021 and December 2022 were collected. There were 51 males and 86 females, aged (69±13)years. All 137 patients received NKAF for cannulation during ERCP. Observation indicators: (1) surgical situations; (2) complications. Measurement data with normal distribution were represented as Mean± SD. Count data were repre-sented as absolute numbers. Results:(1) Surgical situations. Of 137 patients, 136 cases had succe-ssful cannulation, 1 case had failed cannulation with NKAF following unsuccessful double-guidewire technique. In the 136 successful cases, the endoscope was straightened in 42 cases, left in a long position in 37 cases, and maintained in the standard position in 57 cases. The cannulation time was (90±8)s. (2) Complications. The serum amylase at postoperative 6 hours in the 136 successful cases was (163±23)U/L. No patient developed post-ERCP pancreatitis. Of the 136 patients with successful cannulation, one case experienced post-sphincterotomy bleeding, which was observed oozing from the papillary orifice on emergency gastroscopy. The patient was successfully controlled with endoscopic clips.Conclusion:NKAF is safe and effective for difficult biliary cannulation during ERCP.

Objective Jiangtang Tiaozhi Formula(JTTZF)is highly effective in improving glycolipid metabolism disorder.However,its exact mechanism of action has not been fully elucidated.This study aims to explore the potential targets and mechanisms of JTTZF in improving glycolipid metabolism disorder through network pharmacology,molecular docking,molecular dynamics simulations,and experimental validation.Methods Glycolipid metabolism disorder-related targets were obtained from the GeneCards database,while the relevant action targets of the main active ingredients of JTTZF were obtained from the CTD and SwissTargetPrediction databases.Protein-protein interaction(PPI)networks were constructed using STRING and Cytoscape.After selecting the potential key targets,Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were conducted through the Metascape database,and a network map of"herb-active ingredient-target-pathway"was constructed.Molecular docking was carried out using AutoDock vina and PyMOL software to verify the correlation between the main components of JTTZF and the core targets.Molecular dynamics simulation was conducted for optimal core protein-compound complexes obtained by molecular docking.A mouse glycolipid metabolism disorder model was established,and the results of network pharmacology were verified by in vivo experiments.Results Topological analysis of the PPI network revealed ten core targets,including TNF,CTNNB1,AKT1,NF-κB1,ESR1,FN1,TP53,IL-1β,IL-6,and EGFR.GO functional enrichment analysis showed that these targets were mainly related to signal transduction and transcriptional regulation.KEGG pathway analysis showed that these targets were related to lipid and atherosclerosis pathway.Molecular docking results reported that the core active ingredient of JTTZF has a certain binding affinity with AKT1,FN1,and IL-6.Molecular dynamics simulations revealed good binding ability between lovastatin,coptisine,salvianolic acid B,and AKT1.Animal experiments showed that JTTZF may reduce blood glucose and blood lipid levels and improve glycolipid metabolism disorder by down-regulating the expression of AKT1,TP53,and inflammatory regulators in lipid and atherosclerotic pathway,inhibiting the expression of FN1 and EGFR,and increasing the expression of CTNNB1 and ESR1.Conclusion JTTZF participates in the regulation of lipid and atherosclerotic pathway,and comprehensively regulates glucose and lipid metabolism and improves atherosclerotic lesions,thereby preventing and treating the occurrence and development of glycolipid metabolism disorder and its complications.

Objective To evaluate the therapeutic efficacy for surgical treatments among patients with hepatic cystic echinococcosis in Gansu Province from 2006 to 2023, so as to provide insights into optimization of the diagnosis and treatment strategies against hepatic cystic echinococcosis. Methods The demographic and clinical data of all echinococcosis cases included in central government fiscal transfer payment program for echinococcosis control and undergoing surgical treatments in Gansu Province from 2006 to 2023 were captured. Hepatic cystic echinococcosis patients with complete medical records and follow-up data were included in the study, and patients’ characteristics, including hospital where patients received diagnosis and treatment, methods of case identification, year of surgery, classification of lesions, number of lesions, size of lesions, course of disease, surgical methods, and post-surgical follow-up data. The cure and recurrence of hepatic cystic echinococcosis were evaluated according to the Guidelines for Management of Echinococcosis Patients in the Central Government Fiscal Transfer Payment Program, and the cure and recurrent rates were calculated. Results Data were collected from 1 686 surgical patients with hepatic cystic echinococcosis. According to the inclusion and exclusion criteria, 1 222 hepatic cystic echinococcosis patients undergoing surgical treatments were included during the period from 2006 to 2022, including 1 166 cured patients (95.42%) and 88 patients with postsurgical recurrence (7.20%), and the cure rate of surgical treatments appeared a tendency towards a rise among patients with hepatic cystic echinococcosis from 2008 to 2022 (χ²_trend = 19.39, P < 0.05). The cure rates of hepatic cystic echinococcosis were 100% (177/177), 94.81% (128/135) and 94.62% (861/910) among patients detected through regular physical examinations, screened by the central government fiscal transfer payment program for echinococcosis control, and those who passively sought healthcare services, respectively (χ² = 9.95, P < 0.05). The cure rates of hepatic cystic echinococcosis were 95.96% (1 046/1 090) among patients with a disease course of 2 years and less and 90.90% (120/132) among patients with a disease course of over 2 years (χ² = 6.87, P < 0.05), and there were significant differences in the cure rates among patients with hepatic cystic echinococcosis in terms of number of lesions (χ² = 24.44, P < 0.05) and surgical methods (P < 0.05). The cure rate of hepatic cystic echinococcosis patients was significantly higher following initiation of the central government fiscal transfer payment program for echinococcosis control (96.06%, 1 096/1 141) than before the program (86.42%, 70/81) (χ² = 16.06, P < 0.05), and the cure rate of hepatic cystic echinococcosis patients was significantly higher in designated hospitals (96.48%, 741/768) than in non-designated hospitals (93.37%, 366/392) (χ² = 5.78, P < 0.05). The median follow-up period was 4 (interquartile range, 7) years among 1 222 hepatic cystic echinococcosis patients undergoing surgical treatments. The recurrent rate of hepatic cystic echinococcosis appeared a tendency towards a decline from 2008 to 2022 (χ²_trend = 36.86, P < 0.05), with a reduction from 23.08% (9/39) in 2008 to 1.85% (1/54) in 2021, and the post-surgical recurrence rate of hepatic cystic echinococcosis was lower following initiation of the central government fiscal transfer payment program for echinococcosis control (5.87%, 67 / 1 141) than before the program (25.93%, 21/81) (χ² = 45.51, P < 0.05). In addition, the post-surgical recurrence rate of hepatic cystic echinococcosis was higher in non-designated hospitals (10.46%, 41/392) than in designated hospitals (5.60%, 43/768) (χ² = 9.12, P < 0.05), and there was a significant difference in the post-surgical recurrence rate among patients with hepatic cystic echinococcosis in terms of surgical methods (P < 0.05), with the highest recurrence rate (11.54%) seen among patients undergoing percutaneous fine-needle aspiration of cyst fluids-based surgical procedures (P < 0.05). Conclusion Since the initiation of the central government fiscal transfer payment program for echinococcosis control in Gansu Province in 2006, an increase in the surgical cure rate and a reduction in the recurrence of hepatic cystic echinococcosis had been found among patients with hepatic cystic echinococcosis, indicating a high overall therapeutic efficacy.

Objective:To explore the short- and medium-term clinical outcomes of covered stent implantation in the treatment of transplant renal artery stenosis (TRAS).Methods:A retrospective analysis was conducted on the clinical data of 12 consecutive patients with TRAS (transplant renal artery stenosis) who underwent covered stent implantation in Henan Provincial People′s Hospital from January 2021 to December 2024. The changes in indicators such as serum creatinine (Cr), blood urea nitrogen (BUN), mean arterial pressure (MAP), peak systolic velocity (PSV), intrarenal resistance index (RI), and the diameter of the stenotic site were analyzed before the operation, one week after the operation, six months after the operation, and 12 months after the operation. Repeated measures analysis of variance was used to investigate the changes of each observation index over time.Results:The surgery was successfully performed on all 12 patients, with a technical success rate of 100%. Among them, 8 cases used self-expanding covered stents, and 4 cases used balloon-expandable covered stents. One week, six months and twelve months after the surgery, the levels of Cr, BUN, PSV and MAP were all lower than those before the surgery. The RI and the diameter of the stenotic site were significantly increased compared with those before the surgery, the difference was statistically significant ( P<0.05). During the perioperative period and the postoperative follow-up period, no surgery-related complications were found. Conclusion:The implantation of the covered stent can effectively relieve the stenosis of the transplant renal artery, significantly improve renal function, and reduce blood pressure levels in TRAS patients, while maintaining excellent short-to medium-term clinical outcomes.

Objective To investigate the value of stress hyperglycemia ratio(SHR)in predicting symptomatic intracranial hemorrhage(sICH)after successful recanalization of endovascular ther-apy(EVT)in patients with non-diabetic acute large vascular occlusive(LVO)stroke.Methods A total of 150 non-diabetic patients with acute stroke due to LVO admitted in our hospital from June 2022 to June 2024 were recruited,and all of them underwent EVT and obtained successful recanalization.According to whether sICH occurred 24 h after surgery,they were divided into a sICH group(15 cases)and a non-sICH group(135 cases).They were also assigned into a poor prognosis group(55 cases)and a good prognosis group(95 cases)according to the prognosis in 3 months after surgery.The general clinical data were compared between groups,and multivariate logistic regression analysis was used to identify the influencing factors for sICH and prognosis after successful EVT recanalization in the non-diabetic acute stroke patients.ROC curves were plotted to analyze the predictive value of SHR in sICH and prognosis after successful EVT reca-nalization in the patients.Results Significantly larger proportion of embolic occlusion,higher NIHSS score at admission and SHR were observed in the sICH group than the non-SICH group(66.67％vs 37.04％,P＜0.05;20.15±3.68 vs 15.62±3.10,P＜0.01;1.25±0.25 vs 1.01±0.28,P＜0.01).The poor prognosis group had obviously larger female ratio,advanced age,higher NIHSS score at admission,larger proportion of previous stroke history and higher SHR than the good prognosis group(49.09％vs 29.47％,P＜0.05;75.41±5.38 years old vs 72.56±5.63 years old,P＜0.01;18.65±3.71 vs 16.27±3.21,P＜0.01;32.73％vs 14.74％,P＜0.05;1.16±0.23 vs 1.02±0.25,P＜0.01).Multivariate logistic regression analysis showed that embolic occlusion,NIHSS score at admission and SHR were risk factors for sICH after successful EVT recanaliza-tion in non-diabetic acute stroke due to LVO(OR=2.038,95％CI:1.138-4.234,P=0.000;OR=2.026,95％CI:1.173-4.317,P=0.000;OR=1.996,95％CI:1.101-4.027,P=0.000),while gender,age,NIHSS score at admission,previous stroke history,and SHR were risk factors for poor prognosis in the patients(OR=2.004,95％CI:1.085-3.407,P=0.000;OR=2.075,95％CI:1.138-4.067,P=0.000;OR=2.010,95％CI:1.208-4.106,P=0.000;OR=2.034,95％CI:1.137-4.821,P=0.000;OR=2.038,95％CI:1.138-4.234,P=0.000).ROC curve analysis showed that the AUC value of SHR in predicting sICH and prognosis of the non-diabetic patients with acute stroke due to LVO after successful EVT recanalization was 0.797 and 0.823,with a sensitivity of 80.00％and 81.82％,and a specificity of 82.22％and 80.00％,respectively.Conclusion SHR can affect sICH and prognosis after successful EVT recanalization in non-diabetic acute LVO stroke patients,and it has a certain predictive value for sICH and poor prog-nosis of the patients.