OBJECTIVES: To compare the anti-inflammatory, antibacterial and analgesic effects of Yinqiao Powder (YQS) formulated granules and decoction. METHODS: We first evaluated the anti-inflammatory effects of the two dosage forms of YQS in a LPS-induced RAW 264.7 cell model using RT-qPCR and Western blotting. We further constructed zebrafish models of inflammation by copper sulfate exposure, caudal fin transection, or LPS and Poly (I:C) microinjection, and evaluated anti-inflammatory effects of YQS granules and decoction by examining neutrophil aggregation and HE staining findings. In a mouse model of acute lung injury (ALI) induced by intratracheal LPS instillation, the effects of YQS gavage at 10, 15, and 20 g/kg on lung pathologies were evaluated by calculating lung wet-dry weight ratio and using HE staining, ELISA and Western blotting. The microbroth dilution method was used to evaluate the antibacterial effect of YQS. Mouse pain models established by hot plate and intraperitoneal injection of glacial acetic acid were used to evaluate the analgesic effects of YQS at 10, 15, and 20 g/kg. RESULTS: Both YQS granules and decoction significantly reduced TNF-α, IL-6, and IL-1β expressions and p-STAT3 (Tyr 705) phosphorylation level in LPS-induced RAW 264.7 cells, and obviously inhibited neutrophil aggregation in the zebrafish models. In ALI mice, YQS granules and decoction effectively ameliorated lung injury, lowered lung wet-dry weight ratio, and reduced p-STAT3 (Tyr 705) expression and TNF-α and IL-6 levels. YQS produced obvious antibacterial effect at the doses of 15.63 and 31.25 mg/mL, and significantly reduced body torsion and increased pain threshold in the mouse pain models. CONCLUSIONS The two dosage forms of TQS have similar anti-inflammatory, antibacterial and analgesic effects with only differences in their inhibitory effect on TNF-α, IL-6 and IL-1β mRNA expressions in LPS-induced RAW 264.7 cells.
Animals ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Anti-Inflammatory Agents/pharmacology* ; Analgesics/pharmacology* ; RAW 264.7 Cells ; Zebrafish ; Anti-Bacterial Agents/pharmacology* ; Powders ; Tumor Necrosis Factor-alpha/metabolism* ; Acute Lung Injury/drug therapy* ; Interleukin-6/metabolism* ; Lipopolysaccharides

AIM:To investigate how the stearoyl-CoA desaturase-1(SCD1)inhibitor CAY-10566 induc-es ferroptosis in oral squamous cell carcinoma(OS-CC)cells and enhances their sensitivity to cisplatin,with preliminary exploration of the underlying mo-lecular mechanisms.METHODS:Bioinformatics analysis and clinical specimens were used to evalu-ate SCD1 expression in OSCC tissues.OSCC cell lines(Cal27 and HSC3)were treated with CAY-10566,cis-platin,the ferroptosis inhibitor Ferrostatin-1(Fer-1),or their combinations.Cell viability was assessed using the CCK-8 assay,while reactive oxygen spe-cies(ROS)and lipid ROS levels were measured by flow cytometry.Malondialdehyde(MDA)and re-duced glutathione(GSH)levels were quantified us-ing commercial assay kits.Western blotting was performed to analyze the protein expression of glu-tathione peroxidase 4(GPX4),mechanistic target of rapamycin(mTOR),mature sterol regulatory ele-ment-binding protein 1(m-SREBP1),SCD1,and heme oxygenase 1(HMOX1).RESULTS:SCD1 was significantly overexpressed in OSCC tissues(P＜0.01).Combined treatment with CAY-10566 and cis-platin markedly reduced OSCC cell viability(P＜0.01)and increased lipid peroxidation(P＜0.001),while suppressing GPX4 expression-effects that were re-versed by Fer-1(P＜0.001).CAY-10566 upregulated HMOX1 expression and inhibited mTOR,m-SREBP1,and SCD1 protein levels(P＜0.001).CONCLUSION:CAY-10566 promotes ferroptosis and cisplatin sensi-tivity in OSCC cells,potentially through HMOX1 up-regulation and suppression of the mTOR/SREBP1/SCD1 axis.

Xiaoaiping (XAP) Injection demonstrates the anti-prostate cancer (PCa) effects, yet the underlying mechanism remains unclear. This study aims to investigate the impact of XAP on PCa and elucidate its mechanism of action. PCa cell proliferation was evaluated using a cell counting kit-8 (CCK-8) assay. Cell apoptosis was assessed through Hoechst staining and Western blotting assays. Proteomics technology was employed to identify key molecules and significant signaling pathways modulated by XAP in PCa cells. To further validate potential key genes and important pathways, a series of assays were conducted, including acridine orange (AO) staining, transmission electron microscopy, and immunofluorescence assays. The molecular mechanism of XAP against PCa in vivo was examined using a PC3 xenograft mouse model. Results demonstrated that XAP significantly inhibited cell proliferation in multiple PCa cell lines. In C4-2 and prostate cancer cell line-3 (PC3) cells, XAP induced cellular apoptosis, evidenced by reduced B-cell lymphoma 2 (Bcl-2) levels and elevated Bcl-2-associated X (Bax) levels. Proteomic, immunofluorescence, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) investigations revealed a strong correlation between forkhead box O3a (FoxO3a) autophagic degradation and the anti-PCa action of XAP. XAP hindered autophagy by reducing the expression levels of autophagy-related protein 5 (Atg5)/autophagy-related protein 12 (Atg12) and enhancing FoxO3a expression and nuclear translocation. Furthermore, XAP exhibited potent anti-PCa action in PC3 xenograft mice and triggered FoxO3a nuclear translocation in tumor tissue. These findings suggest that XAP induces PCa apoptosis via inhibition of FoxO3a autophagic degradation, potentially offering a novel perspective on XAP injection as an effective anticancer therapy for PCa.
Male ; Humans ; Prostatic Neoplasms/physiopathology* ; Autophagy/drug effects* ; Animals ; Drugs, Chinese Herbal/pharmacology* ; Proteomics ; Mice ; Apoptosis/drug effects* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Forkhead Box Protein O3/genetics* ; Xenograft Model Antitumor Assays ; Mice, Nude ; Mice, Inbred BALB C

Acute large vessel occlusion stroke(ALVOS)of anterior circulation is associated with severe clinical manifestations and high rates of disability and mortality.Mechanical thrombectomy has emerged as the primary therapeutic intervention.However,post-procedural outcomes remain highly variable,and patients continue to face elevated risks of poor prognosis.Machine learning,a transformative tool in medical research,enables comprehensive analysis of multimodal data to identify specific biomarkers and improve the accuracy of predictions for clinical outcomes and adverse events.This review summarized the latest developments in machine learning applications aim at predicting post-thrombectomy prognosis and risk of adverse event,including futile recanalization,hemorrhagic transformation,and malignant cerebral edema in patients with anterior circulation ALVOS in order to provide a basis for developing personalized treatment plan and improve their clinical prognosis.

AIM:To investigate how the stearoyl-CoA desaturase-1(SCD1)inhibitor CAY-10566 induc-es ferroptosis in oral squamous cell carcinoma(OS-CC)cells and enhances their sensitivity to cisplatin,with preliminary exploration of the underlying mo-lecular mechanisms.METHODS:Bioinformatics analysis and clinical specimens were used to evalu-ate SCD1 expression in OSCC tissues.OSCC cell lines(Cal27 and HSC3)were treated with CAY-10566,cis-platin,the ferroptosis inhibitor Ferrostatin-1(Fer-1),or their combinations.Cell viability was assessed using the CCK-8 assay,while reactive oxygen spe-cies(ROS)and lipid ROS levels were measured by flow cytometry.Malondialdehyde(MDA)and re-duced glutathione(GSH)levels were quantified us-ing commercial assay kits.Western blotting was performed to analyze the protein expression of glu-tathione peroxidase 4(GPX4),mechanistic target of rapamycin(mTOR),mature sterol regulatory ele-ment-binding protein 1(m-SREBP1),SCD1,and heme oxygenase 1(HMOX1).RESULTS:SCD1 was significantly overexpressed in OSCC tissues(P＜0.01).Combined treatment with CAY-10566 and cis-platin markedly reduced OSCC cell viability(P＜0.01)and increased lipid peroxidation(P＜0.001),while suppressing GPX4 expression-effects that were re-versed by Fer-1(P＜0.001).CAY-10566 upregulated HMOX1 expression and inhibited mTOR,m-SREBP1,and SCD1 protein levels(P＜0.001).CONCLUSION:CAY-10566 promotes ferroptosis and cisplatin sensi-tivity in OSCC cells,potentially through HMOX1 up-regulation and suppression of the mTOR/SREBP1/SCD1 axis.

Acute large vessel occlusion stroke(ALVOS)of anterior circulation is associated with severe clinical manifestations and high rates of disability and mortality.Mechanical thrombectomy has emerged as the primary therapeutic intervention.However,post-procedural outcomes remain highly variable,and patients continue to face elevated risks of poor prognosis.Machine learning,a transformative tool in medical research,enables comprehensive analysis of multimodal data to identify specific biomarkers and improve the accuracy of predictions for clinical outcomes and adverse events.This review summarized the latest developments in machine learning applications aim at predicting post-thrombectomy prognosis and risk of adverse event,including futile recanalization,hemorrhagic transformation,and malignant cerebral edema in patients with anterior circulation ALVOS in order to provide a basis for developing personalized treatment plan and improve their clinical prognosis.

Objective:To evaluate the safety and efficacy of enhanced recovery after surgery(ERAS) in the perioperative period of congenital choledochal cysts in children.Methods:This is a multicenter prospective randomized controlled study. The clinical data of 273 pediatric congenital choledochal cysts(CCC) patients who underwent surgery at 14 medical centers with complete follow-up data were collected through the medical data analysis platform. Among them, 123 cases in ERAS group were managed perioperatively in strict accordance with ERAS mode, and 150 cases in conventional group were managed according to traditional mode. The length of hospital stay,time to first farting, time to complete feeding, the incidence of complications, cost and readmission rate within 30 days,stress indexes and liver function were compared between the two groups.Results:Compared with the conventional group, median time to start farting (2.0 d vs. 3.0 d, P<0.001), median time to complete feeding (5.0 d vs. 7.0 d, P<0.001), median postoperative hospitalization time (6.0 d vs. 9.0 d, P<0.001),the median total length of stay(13.0 d vs. 15.0 d, P<0.001) were shorter,the median hospitalization cost (37,000 yuan vs.43,000 yuan P<0.001) was lower, and stress indexes recovered quickly. The incidence of postoperative hospital stay and readimission rate within 30 d were not statistically different between the two groups. Conclusion:It is safe and feasible to implement ERAS for children with CCC in the perioperative period, which can reduce stress response, speed up recovery,and save medical costs.

Marsdenia tenacissima injection, a standard Marsdenia tenacissima extract (MTE), has been approved as an adjuvant therapeutic agent for various cancers. Our previous study showed that MTE inhibited the proliferation and metastasis of prostate cancer (PCa) cells. However, the underlying mechanisms and active ingredients of MTE against PCa were not completely understood. This study revealed that MTE induced significant decreases in cell viability and clonal growth in PCa cells. In addition, MTE induced the apoptosis of DU145 cells by reducing the mitochondrial membrane potential and increasing the expression of Cleaved Caspase 3/7, Cyt c, and Bax. In vivo, DU145 xenografted NOD-SCID mice treated with MTE showed significantly decreased tumor size. TUNEL staining and Western blot confirmed the pro-apoptotic effects of MTE. Network pharmacology analysis collected 196 ingredients of MTE linked to 655 potential targets, and 709 PCa-associated targets were retrieved, from which 149 overlapped targets were screened out. Pathway enrichment analysis showed that the HIF-1, PI3K-AKT, and ErbB signaling pathways were closely related to tumor apoptosis. Western blot results confirmed that MTE increased the expression of p-AKT^Ser473 and p-GSK3β^Ser9, and decreased the expression of p-STAT3^Tyr705in vitro and in vivo. A total of 13 compounds in MTE were identified by HPLC-CAD-QTOF-MS/MS and UPLC-QTOF-MS/MS. Molecular docking analysis indicated that six compounds may interact with AKT, GSK3β, and STAT3. In conclusion, MTE induces the endogenous mitochondrial apoptosis of PCa by regulating the AKT/GSK3β/STAT3 signaling axis, resulting in inhibition of PCa growth in vitro and in vivo.
Mice ; Animals ; Male ; Humans ; Mice, Inbred NOD ; Mice, SCID ; Marsdenia ; Proto-Oncogene Proteins c-akt ; Glycogen Synthase Kinase 3 beta ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases ; Tandem Mass Spectrometry ; Prostatic Neoplasms ; Apoptosis ; STAT3 Transcription Factor

With the widespread use of Internet, the amount of data in the field of traditional Chinese medicine (TCM) is growing exponentially. Consequently, there is much attention on the collection of useful knowledge as well as its effective organization and expression. Knowledge graphs have thus emerged, and knowledge reasoning based on this tool has become one of the hot spots of research. This paper first presents a brief introduction to the development of knowledge graphs and knowledge reasoning, and explores the significance of knowledge reasoning. Secondly, the mainstream knowledge reasoning methods, including knowledge reasoning based on traditional rules, knowledge reasoning based on distributed feature representation, and knowledge reasoning based on neural networks are introduced. Then, using stroke as an example, the knowledge reasoning methods are expounded, the principles and characteristics of commonly used knowledge reasoning methods are summarized, and the research and applications of knowledge reasoning techniques in TCM in recent years are sorted out. Finally, we summarize the problems faced in the development of knowledge reasoning in TCM, and put forward the importance of constructing a knowledge reasoning model suitable for the field of TCM.

Objective:To evaluate endoscopic retrograde appendicitis therapy in treatment of children with acute uncomplicated appendicitis.Methods:Sixty children patients were admitted at the Affiliated Hospital of Zhengzhou University from Oct 2019 to Jun 2021 and were divided into ERAT group ( n=30) and LA group ( n=30). Results:All operations were successfully performed . ERAT children started oral feeding earlier [(6.8±2.0) h vs. (12.3±2.0) h, t=-10.636, P<0.001], postoperative hospital stay was shorter [(3.2±1.3) d vs. (5.0±1.3) d, t=-5.360, P<0.001]. After 14 months follow up, the recurrence rate in the ERAT group was 6%. The complication rate of LA was 10%. Conclusion:ERAT is a safe and effective therapy in treating children with acute uncomplicated appendicitis with low,acceptable recurrence rate.