ObjectiveTo investigate the mechanism of modified Si Junzitang and Shashen Maidong Tang ［Yiqi Yangyin Jiedu prescription （YQYYJD）］ in enhancing the sensitivity of cisplatin in epidermal growth factor receptor tyrosine kinase inhibitor （EGFR-TKI）-resistant lung adenocarcinoma cells based on aerobic glycolysis. MethodsThe effects of different concentrations of YQYYJD （0， 2， 3， 4， 5， 6， 7， 8 g·L^-1） and cisplatin （0， 3， 6， 9， 12， 15， 18， 21， 24， 27 mg·L^-1） on the proliferation and activity of PC9/GR cells were detected by the cell counting kit-8 （CCK-8） assay after 24 hours of intervention. The half-maximal inhibitory concentration （IC₅₀） for PC9/GR cells was calculated to determine the concentrations used in subsequent experiments. PC9/GR cells were divided into blank group （complete medium）， YQYYJD group （5 g·L^-1）， cisplatin group （12 mg·L^-1）， and combined group （YQYYJD 5 g·L^-1 + cisplatin 12 mg·L^-1）. After 24 hours of intervention， cell viability was measured using CCK-8 assay. Cell proliferation was assessed by colony formation assay， and cell migration was evaluated by scratch and Transwell assays. Glucose consumption， lactate production， and adenosine triphosphate （ATP） levels were measured by colorimetric assays. The expression levels of glycolysis-related proteins， including hexokinase 2 （HK2）， phosphofructokinase P （PFKP）， pyruvate kinase M2 （PKM2）， lactate dehydrogenase A （LDHA）， glucose transporter 1 （GLUT1）， and monocarboxylate transporter 4 （MCT4）， were determined by Western blot. ResultsBoth YQYYJD and cisplatin inhibited the viability of PC9/GR cells in a concentration-dependent manner. The IC₅₀ of PC9/GR cells for YQYYJD and cisplatin were 5.15 g·L^-1 and 12.91 mg·L^-1， respectively. In terms of cell proliferation， compared with the blank group， the cell survival rate and the number of colonies formed in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group showed a further significant reduction in cell survival rate and colony formation （P<0.01）. In terms of cell migration， compared with the blank group， the cell migration rate and the number of cells passing through the Transwell membrane in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group exhibited a further significant reduction in cell migration rate and the number of cells passing through the Transwell membrane （P<0.01）. In terms of glycolysis， compared with the blank group， glucose consumption， lactate production， and ATP levels in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group showed a further significant reduction in glucose consumption， lactate production， and ATP levels （P<0.05）. Compared with the blank group， the protein expression levels of HK2， PFKP， PKM2， and LDHA in the YQYYJD， cisplatin， and combined groups were significantly decreased （P<0.01）. The combined group showed a further significant reduction in the expression levels of these proteins compared with the YQYYJD and cisplatin groups （P<0.01）. No significant differences were observed in the protein expression levels of GLUT1 and MCT4 among the groups. ConclusionYQYYJD can synergistically inhibit the proliferation and migration of PC9/GR cells and enhance their sensitivity to cisplatin. The mechanism may be related to the downregulation of the expression of glycolysis-related rate-limiting enzymes， including HK2， PFKP， PKM2， and LDHA， thereby inhibiting glycolysis.

In recent years, with the clinical application of minimally invasive surgical techniques and comprehensive preoperative treatment, the survival rate of locally advanced esophageal cancer has significantly improved. However, the treatment of metastatic esophagogastric cancer still relies mainly on systemic therapy, and immunotherapy combined with chemotherapy has become a first-line treatment option, prolonging the survival of patients with metastatic esophageal cancer. Oligometastatic esophageal cancer is expected to bring survival benefits through systemic therapy combined with local treatment. The 2024 European clinical practice guidelines for oligometastatic esophagogastric cancer have been officially released, which standardize the definition, diagnosis, and treatment of oligometastatic esophageal cancer for further prospective studies. The authors interpret this guideline, especially by reviewing the clinical evidence of oligometastatic esophageal squamous cell carcinoma, to provide reference for the diagnosis and treatment of oligometastatic esophageal cancer in China.

Rheumatoid Arthritis(RA)is a critical disease that endangers the health of the Chinese pop-ulation.At present,there are still many deficiencies in the diagnosis and treatment of RA in China.The 2024 Chinese Guidelines for the Diagnosis and Treatment of Rheumatoid Arthritis addresses 10 important clinical issues in the diagnosis and treatment of RA,and provides evidence-based recommendations based on the latest domes-tic and international literature,with consideration of the actual situation of RA diagnosis and treatment in China.The guidelines comprehensively cover the diagnosis of RA,imaging examinations,treatment goals,follow-up monitoring,initial treatment plans,treatment adjustments,the application of glucocorticoids,drug tapering,and health education.They will promote the RA diagnosis and treatment levels and improve the prog-nosis of RA patients in China.

BACKGROUND: The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown. METHODS: Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3'-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice. RESULTS: POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo . Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p , and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p , miR-29a-3p , PIK3R1 , and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1 , PIK3R1 , and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples. CONCLUSIONS The POU2F1 - miR-29b-3p / miR-29a-3p-PIK3R1 / PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.
MicroRNAs/metabolism* ; Humans ; Stomach Neoplasms/pathology* ; Cell Line, Tumor ; Cell Movement/physiology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Animals ; Mice ; Octamer Transcription Factor-1/metabolism* ; Mice, Nude ; Class Ia Phosphatidylinositol 3-Kinase/metabolism* ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic/genetics* ; Male ; Immunohistochemistry ; Female

Objective: To utilize machine learning(ML) algorithms to develop accurate and effective prediction models for TAC dose/weight-adjusted trough concentration(C0/D). Methods: Data were collected on 264 TAC blood concentration monitoring data from 72 patients undergoing kidney transplantation. The effects of population statistical data, clinical features, combined medication, and ultrasound feature parameters on TAC C0/D were analyzed. Features with a significance level less than 0.05 in the univariate analysis of TAC C0/D were selected for inclusion in the random forest(RF) algorithm to identify significant features. These features were interpreted using partial dependency plots. Five ML algorithms, including RF, support vector regression(SVR), extreme gradient boosting(XGBoost), decision trees(DT) and artificial neural networks(ANN), were employed to establish the TAC C0/D prediction model. Hyper-parameter tuning was performed on the RF model that performed the best. Results : Ten characteristic variables with importance scores>5 were retained and included in the ML model: transglutaminase, red blood cell count, blood urea nitrogen, weight, serum creatinine, renal segmental arterial resistance index, renal aortic resistance index, hematocrit, renal pelvic Young′s modulus value, and time after transplantation. The partial dependence plots showed that all 10 important variables screened were positively correlated with TAC C0/D. The tuned RF model outperformed the other models with aR2of 0.81, aRMSEof 43.93, and aMAEof 29.97. Conclusion The ML models demonstrate good performance in predicting TAC C0/D and provide innovative interpretations using partial dependence plot. The optimized RF model shows optimal performance and offers a novel tool for individualized medication adjustment for TAC in renal transplant patients.

Objective To study the management effect of the intelligent management mode of anesthet-ic medicine box.Methods The intelligent reconstruction of the management mode of anesthesia box in the de-partment of surgical anesthesiology was carried out,and the differences in the taking and return time in 3-month before and after applying the medicine box intelligent management,error rate,and information tracking were compared,and the management effect of the medicine box was compared between the intelligent manage-ment and the traditional mode.Results The prescription modification rate,accounting error rate,discrepancy rate of person and box,and omission rate of registration had statistical differences between the traditional management mode and intelligent management mode(P<0.05).The single medicine box management work-ing time for anesthetist getting the medicine box,returning the medicine box,taking the refrigerator medicine,generating prescription and charge in intteligent management mode was shortened compared with the tradi-tional management mode,and the difference was statistically significant(P<0.05);the working time of drug management such as drug counting,prescription checking,registration records checking,drug adding and daily inventory checking in the intelligent management mode was shortened compared with the traditional manage-ment mode,and the difference was statistically significant(P<0.05).Conclusion Compared with the tradi-tional mode,the anesthetic box management intelligent mode has high efficiency and strong reliability,moreo-ver is more conducive to the standardized management of anesthetic drugs in the operating room.

OBJECTIVES: To investigate YEATS2 expression in gastric cancer (GC), its prognostic value, and its regulatory role in epithelial-mesenchymal transition (EMT) of GC cells. METHODS: YEATS2 expression in GC was analyzed using publicly available databases. Paired GC and adjacent tissues were collected from 100 patients undergoing radical surgery for immunohistochemical detection of YEATS2 expression, and its correlations with the patients' clinicopathological parameters and Ki67 expression were analyzed. The prognostic value of YEATS2 was assessed using Kaplan-Meier analysis, Cox regression and ROC curves, and its regulatory mechanisms were analyzed using KEGG enrichment analysis. In cultured GC cell lines (HGC-27 and AGS), the effect of YEATS2 knockdown and overexpression on migration, invasion and EMT of the cells were examined with scratching assay, Transwell assay and Western blotting. RESULTS: YEATS2 was significantly overexpressed in GC tissues with a positive correlation with Ki67 (P<0.05). High YEATS2 expression was associated with elevated CEA (≥5 μg/L), CA19-9 (≥37 kU/L), T3-4 stage, and N2-3 stage (all P<0.05). Patients with high YEATS2 expression had significantly reduced 5-year survival (P<0.001); ROC analysis showed that YEATS2 expression levels had a sensitivity of 80.00% and a specificity of 66.67% for predicting patient survival (P<0.05). Cox regression identified high YEATS2 as an independent risk factor for poor postoperative 5-year survival outcome of GC patients (HR: 1.675, 95%CI: 1.013-2.771; P=0.045). KEGG enrichment analysis suggested involvement of YEATS2 in EMT in GC and Wnt/β-catenin signaling. In cultured GC cells, YEATS2 overexpression significantly promoted cell migration and invasion, upregulated the expressions of vimentin, N-cadherin, Wnt and active β-catenin, and downregulated E-cadherin expression, and these changes were obviously suppressed by treatment with XAV-939 (a Wnt/β-catenin inhibitor). CONCLUSIONS High YEATS2 expression activates Wnt/β-catenin signaling to promote EMT in GC and is correlated with poor prognosis of GC patients.
Humans ; Stomach Neoplasms/pathology* ; Epithelial-Mesenchymal Transition ; Wnt Signaling Pathway ; Cell Line, Tumor ; Prognosis ; Cell Movement ; Male ; Female ; beta Catenin/metabolism*

OBJECTIVES: To investigate the effect of hypaphorine (HYP) on Crohn's disease (CD)‑like colitis in mice and its molecular mechanism. METHODS: Thirty male C57BL/6J mice were equally randomized into WT, TNBS, and HYP groups, and in the latter two groups, mouse models of CD-like colitis were established using TNBS with daily gavage of 15 mg/kg HYP or an equivalent volume of saline. The treatment efficacy was evaluated by assessing the disease activity index (DAI), body weight changes, colon length and histopathology. The effect of HYP was also tested in a LPS-stimulated Caco-2 cell model mimicking intestinal inflammation by evaluating inflammatory responses and barrier function of the cells using qRT-PCR and immunofluorescence staining. GO and KEGG analyses were conducted to explore the therapeutic mechanism of HYP, which was validated in both the cell and mouse models using Western blotting. RESULTS: In the mouse models of CD-like colitis, HYP intervention obviously alleviated colitis as shown by significantly reduced body weight loss, colon shortening, DAI and inflammation scores, and expressions of pro-inflammatory factors in the colon tissues. HYP treatment also significantly increased the TEER values, reduced bacterial translocation to the mesenteric lymph nodes, liver, and spleen, lowered serum levels of I-FABP and FITC-dextran, increased the number of colonic tissue cup cells, and upregulated colonic expressions of MUC2 and tight junction proteins (claudin-1 and ZO-1) in the mouse models. In LPS-stimulated Caco-2 cells, HYP treatment significantly inhibited the expressions of pro-inflammatory factors and increased the expressions of tight junction proteins. Western blotting showed that HYP downregulated the expressions of the key proteins in the TLR4/MyD88 signaling pathway in both the in vitro and in vivo models. CONCLUSIONS HYP alleviates CD-like colitis in mice possibly by suppressing intestinal epithelial inflammation and improving gut barrier function.
Animals ; Male ; Mice, Inbred C57BL ; Crohn Disease/drug therapy* ; Mice ; Humans ; Caco-2 Cells ; Intestinal Mucosa/metabolism* ; Colitis/drug therapy* ; Disease Models, Animal ; Inflammation ; Toll-Like Receptor 4/metabolism* ; Myeloid Differentiation Factor 88/metabolism* ; Intestinal Barrier Function