Our previous research demonstrated that the Wenxia Changfu Formula (WCF), as a neoadjuvant therapy, inhibits M2 macrophage infiltration in the tumor microenvironment and prevents lung cancer metastasis. Given tumor-associated macrophages (TAMs) in epithelial-mesenchymal transition (EMT), this study investigated whether WCF impedes lung cancer metastasis by attenuating TAM-induced EMT in non-small cell lung cancer (NSCLC) cells. Utilizing a co-culture model treated with or without WCF, we observed that WCF downregulated cluster of differentiation 163 (CD163) expression in macrophages, reduced CCL18 levels in the conditioned medium, and inhibited the growth, invasion, and EMT of NSCLC cells induced by macrophage co-culture. Manipulation of CCL18 levels and Src overexpression in NSCLC cells revealed that WCF's effects are mediated through CCL18 and Src signaling. In vivo, WCF inhibited recombinant CCL18 (rCCL18)-induced tumor metastasis in nude mice by blocking Src signaling. These findings indicate that WCF inhibits NSCLC metastasis by impeding TAM-induced EMT via antagonistic modulation of CCL18, providing evidence for its potential development and clinical application in NSCLC patients.
Epithelial-Mesenchymal Transition/drug effects* ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Humans ; Animals ; Lung Neoplasms/metabolism* ; Chemokines, CC/antagonists & inhibitors* ; Mice ; Mice, Nude ; Drugs, Chinese Herbal/administration & dosage* ; Cell Line, Tumor ; Neoplasm Metastasis ; Tumor-Associated Macrophages/drug effects* ; Mice, Inbred BALB C ; Signal Transduction/drug effects*

Objective: This study investigated the value of multiparametric MRI (mpMRI) in predicting Gleason score (GS) upgrading and downgrading in radical prostatectomy (RP) compared with presurgical biopsy. Materials and Methods: Clinical and mpMRI data were retrospectively collected from 219 patients with prostate disease between January 2015 and December 2021. All patients underwent systematic prostate biopsy followed by RP. MpMRI included conventional diffusion-weighted and dynamic contrast-enhanced imaging. Multivariable logistic regression analysis was performed to analyze the factors associated with GS upgrading and downgrading after RP. Receiver operating characteristic curve analysis was used to estimate the area under the curve (AUC) to indicate the performance of the multivariable logistic regression models in predicting GS upgrade and downgrade after RP. Results: The GS after RP was upgraded, downgraded, and unchanged in 92, 43, and 84 patients, respectively. The AUCs of the clinical (percentage of positive biopsy cores [PBCs], time from biopsy to RP) and mpMRI models (prostate cancer [PCa] location, Prostate Imaging Reporting and Data System [PI-RADS] v2.1 score) for predicting GS upgrading after RP were 0.714 and 0.749, respectively. The AUC of the combined diagnostic model (age, percentage of PBCs, tPSA, PCa location, and PIRADS v2.1 score) was 0.816, which was larger than that of the clinical factors alone (P < 0.001). The AUCs of the clinical (age, percentage of PBCs, ratio of free/total PSA [F/T]) and mpMRI models (PCa diameter, PCa location, and PI-RADS v2.1 score) for predicting GS downgrading after RP were 0.749 and 0.835, respectively. The AUC of the combined diagnostic model (age, percentage of PBCs, F/T, PCa diameter, PCa location, and PI-RADS v2.1 score) was 0.883, which was larger than that of the clinical factors alone (P < 0.001). Conclusion Combining clinical factors and mpMRI findings can predict GS upgrade and downgrade after RP more accurately than using clinical factors alone.

Objective: This study investigated the value of multiparametric MRI (mpMRI) in predicting Gleason score (GS) upgrading and downgrading in radical prostatectomy (RP) compared with presurgical biopsy. Materials and Methods: Clinical and mpMRI data were retrospectively collected from 219 patients with prostate disease between January 2015 and December 2021. All patients underwent systematic prostate biopsy followed by RP. MpMRI included conventional diffusion-weighted and dynamic contrast-enhanced imaging. Multivariable logistic regression analysis was performed to analyze the factors associated with GS upgrading and downgrading after RP. Receiver operating characteristic curve analysis was used to estimate the area under the curve (AUC) to indicate the performance of the multivariable logistic regression models in predicting GS upgrade and downgrade after RP. Results: The GS after RP was upgraded, downgraded, and unchanged in 92, 43, and 84 patients, respectively. The AUCs of the clinical (percentage of positive biopsy cores [PBCs], time from biopsy to RP) and mpMRI models (prostate cancer [PCa] location, Prostate Imaging Reporting and Data System [PI-RADS] v2.1 score) for predicting GS upgrading after RP were 0.714 and 0.749, respectively. The AUC of the combined diagnostic model (age, percentage of PBCs, tPSA, PCa location, and PIRADS v2.1 score) was 0.816, which was larger than that of the clinical factors alone (P < 0.001). The AUCs of the clinical (age, percentage of PBCs, ratio of free/total PSA [F/T]) and mpMRI models (PCa diameter, PCa location, and PI-RADS v2.1 score) for predicting GS downgrading after RP were 0.749 and 0.835, respectively. The AUC of the combined diagnostic model (age, percentage of PBCs, F/T, PCa diameter, PCa location, and PI-RADS v2.1 score) was 0.883, which was larger than that of the clinical factors alone (P < 0.001). Conclusion Combining clinical factors and mpMRI findings can predict GS upgrade and downgrade after RP more accurately than using clinical factors alone.

Objective: This study investigated the value of multiparametric MRI (mpMRI) in predicting Gleason score (GS) upgrading and downgrading in radical prostatectomy (RP) compared with presurgical biopsy. Materials and Methods: Clinical and mpMRI data were retrospectively collected from 219 patients with prostate disease between January 2015 and December 2021. All patients underwent systematic prostate biopsy followed by RP. MpMRI included conventional diffusion-weighted and dynamic contrast-enhanced imaging. Multivariable logistic regression analysis was performed to analyze the factors associated with GS upgrading and downgrading after RP. Receiver operating characteristic curve analysis was used to estimate the area under the curve (AUC) to indicate the performance of the multivariable logistic regression models in predicting GS upgrade and downgrade after RP. Results: The GS after RP was upgraded, downgraded, and unchanged in 92, 43, and 84 patients, respectively. The AUCs of the clinical (percentage of positive biopsy cores [PBCs], time from biopsy to RP) and mpMRI models (prostate cancer [PCa] location, Prostate Imaging Reporting and Data System [PI-RADS] v2.1 score) for predicting GS upgrading after RP were 0.714 and 0.749, respectively. The AUC of the combined diagnostic model (age, percentage of PBCs, tPSA, PCa location, and PIRADS v2.1 score) was 0.816, which was larger than that of the clinical factors alone (P < 0.001). The AUCs of the clinical (age, percentage of PBCs, ratio of free/total PSA [F/T]) and mpMRI models (PCa diameter, PCa location, and PI-RADS v2.1 score) for predicting GS downgrading after RP were 0.749 and 0.835, respectively. The AUC of the combined diagnostic model (age, percentage of PBCs, F/T, PCa diameter, PCa location, and PI-RADS v2.1 score) was 0.883, which was larger than that of the clinical factors alone (P < 0.001). Conclusion Combining clinical factors and mpMRI findings can predict GS upgrade and downgrade after RP more accurately than using clinical factors alone.

Objective: This study investigated the value of multiparametric MRI (mpMRI) in predicting Gleason score (GS) upgrading and downgrading in radical prostatectomy (RP) compared with presurgical biopsy. Materials and Methods: Clinical and mpMRI data were retrospectively collected from 219 patients with prostate disease between January 2015 and December 2021. All patients underwent systematic prostate biopsy followed by RP. MpMRI included conventional diffusion-weighted and dynamic contrast-enhanced imaging. Multivariable logistic regression analysis was performed to analyze the factors associated with GS upgrading and downgrading after RP. Receiver operating characteristic curve analysis was used to estimate the area under the curve (AUC) to indicate the performance of the multivariable logistic regression models in predicting GS upgrade and downgrade after RP. Results: The GS after RP was upgraded, downgraded, and unchanged in 92, 43, and 84 patients, respectively. The AUCs of the clinical (percentage of positive biopsy cores [PBCs], time from biopsy to RP) and mpMRI models (prostate cancer [PCa] location, Prostate Imaging Reporting and Data System [PI-RADS] v2.1 score) for predicting GS upgrading after RP were 0.714 and 0.749, respectively. The AUC of the combined diagnostic model (age, percentage of PBCs, tPSA, PCa location, and PIRADS v2.1 score) was 0.816, which was larger than that of the clinical factors alone (P < 0.001). The AUCs of the clinical (age, percentage of PBCs, ratio of free/total PSA [F/T]) and mpMRI models (PCa diameter, PCa location, and PI-RADS v2.1 score) for predicting GS downgrading after RP were 0.749 and 0.835, respectively. The AUC of the combined diagnostic model (age, percentage of PBCs, F/T, PCa diameter, PCa location, and PI-RADS v2.1 score) was 0.883, which was larger than that of the clinical factors alone (P < 0.001). Conclusion Combining clinical factors and mpMRI findings can predict GS upgrade and downgrade after RP more accurately than using clinical factors alone.

Objective: This study investigated the value of multiparametric MRI (mpMRI) in predicting Gleason score (GS) upgrading and downgrading in radical prostatectomy (RP) compared with presurgical biopsy. Materials and Methods: Clinical and mpMRI data were retrospectively collected from 219 patients with prostate disease between January 2015 and December 2021. All patients underwent systematic prostate biopsy followed by RP. MpMRI included conventional diffusion-weighted and dynamic contrast-enhanced imaging. Multivariable logistic regression analysis was performed to analyze the factors associated with GS upgrading and downgrading after RP. Receiver operating characteristic curve analysis was used to estimate the area under the curve (AUC) to indicate the performance of the multivariable logistic regression models in predicting GS upgrade and downgrade after RP. Results: The GS after RP was upgraded, downgraded, and unchanged in 92, 43, and 84 patients, respectively. The AUCs of the clinical (percentage of positive biopsy cores [PBCs], time from biopsy to RP) and mpMRI models (prostate cancer [PCa] location, Prostate Imaging Reporting and Data System [PI-RADS] v2.1 score) for predicting GS upgrading after RP were 0.714 and 0.749, respectively. The AUC of the combined diagnostic model (age, percentage of PBCs, tPSA, PCa location, and PIRADS v2.1 score) was 0.816, which was larger than that of the clinical factors alone (P < 0.001). The AUCs of the clinical (age, percentage of PBCs, ratio of free/total PSA [F/T]) and mpMRI models (PCa diameter, PCa location, and PI-RADS v2.1 score) for predicting GS downgrading after RP were 0.749 and 0.835, respectively. The AUC of the combined diagnostic model (age, percentage of PBCs, F/T, PCa diameter, PCa location, and PI-RADS v2.1 score) was 0.883, which was larger than that of the clinical factors alone (P < 0.001). Conclusion Combining clinical factors and mpMRI findings can predict GS upgrade and downgrade after RP more accurately than using clinical factors alone.

The term"heat stroke"originates from the integration of modern traditional Chinese and Western medicine.In clinical practice,the complementary advantages of the two medical systems can significantly enhance the clinical diagnosis and treatment level of heat stroke.Through comprehensively analyzes the traditional Chinese medicine(TCM)nomenclature for heat stroke,proposing that heat stroke is a type of sunstroke characterized by intense and pure yang nature,specifically referring to symptoms caused directly or indirectly by hot weather.It can be referenced under the categories of Zhongye,Shuwen,Yinshu/Yangshu,Shujue,and Shufeng for treatment.The article reviews the TCM diagnostic and therapeutic thinking for heat stroke,summarizing its etiology and pathogenesis,including summerheat directly entering the Yangming,heat entering the heart and nutrient-blood aspects,evil combined with water(post-emergency),dual injury of qi and fluid(post-mild recovery),and phlegm-stasis obstructing collaterals(post-severe recovery).Based on years of clinical experience and combining the different clinical manifestations of heat stroke with TCM's four diagnostic methods,the article proposes a treatment plan that integrates Chinese and Western medicine,combining disease differentiation with syndrome differentiation.The main syndromes summarized include high fever with spasms(Yangming heat excess syndrome),diarrhea(Yangming fu syndrome-intestinal sweating),high fever with coma(heat entering the heart-nutrient syndrome),high fever with convulsions(extreme heat generating wind syndrome),heat stroke-induced coagulopathy(heat entering the blood aspect syndrome),edema after fluid resuscitation(Taiyang water retention syndrome),recovery phase(dual injury of qi and fluid syndrome),and sequelae(phlegm-stasis obstructing collaterals syndrome).For treatment,Baihu Jia Renshen decotion combined with Zengye Chengqi decotion is used for nourishing yin and increasing fluids,relaxing tendons,and stopping spasms for Yangming heat excess syndrome;Baihu decotion combined with Zengye decotion for clearing summerheat and nourishing yin for Yangming fu syndrome-intestinal sweating;Qingying decotion for clearing the nutrient aspect and cooling blood,penetrating heat,and nourishing yin for heat entering the heart-nutrient syndrome;Lingjiao Gouteng decotion for clearing heat and cooling the liver,extinguishing wind,and calming spasms for extreme heat generating wind syndrome;Wuling powder for draining and eliminating water retention for Taiyang water retention syndrome;Wang's Qing Shu Yiqi decotion for clearing summerheat and reducing fever,benefiting qi,and generating fluids for dual injury of qi and fluid syndrome;and Sanjia powder for clearing residual heat,resolving phlegm,and removing stasis from collaterals for phlegm-stasis obstructing collaterals syndrome.Starting from TCM theory and linking it with practice,the article combines Western disease differentiation with TCM syndrome differentiation,aiming to provide new ideas for the clinical treatment of heat stroke.

Objective To explore the expression level,clinical significance of protein disulfide isomerase A3(PDIA3)in endome-trial cancer(EC)tissues,and its effects on Ishikawa cells.Methods Using the TCGA database to analyze the differential expression levels of PDIA3 in different endometrial tissues and explore its relationship with clinical pathological parameters and prognosis of EC pa-tients;Using immunohistochemistry(IHC)to detect the expression level of PDIA3 in clinical endometrial tissue,analyze the clinical pathological parameters,prognosis,and risk factors affecting the prognosis of EC patients with different expression levels;Using Transwell assay,scratch assay,and CCK-8 assay to detect the proliferation,invasion,and migration ability of Ishikawa cells with knockdown PDIA3 expression.Results The expression level of PDIA3 in EC tissue was higher than that in normal endometrial tissue in the TCGA database and clinical specimens(P＜0.05).The expression level of PDIA3 in EC tissue in the G3 grade group was higher than that in the G1 and G2 grade groups in the TCGA database(P＜0.05).The expression level of PDIA3 in EC tissue in FIGO stage Ⅱ-Ⅳ group was higher than that in the stage Ⅰ group,the group with lymph node metastasis was higher than that without lymph node metastasis,and the highly differentiated group was higher than the poorly differentiated group in clinical specimens(P＜0.05);COX regression analysis showed that Federation International of Gynecology and Obstetrics(FIGO)staging and PDIA3 expression level were the independent risk factors of prognosis in EC patients;the survival time of EC patients with high expression of PDIA3 in the TCGA database was shorter than that of the low expression group(P＜0.05),and the survival rate of clinical patients with positive PDIA3 was shorter than that of the neg-ative group(P＜0.05);Transwell assay,scratch assay,and CCK-8 assay showed that the invasion and migration ability of cells in the PDIA3 inhibition group was significantly reduced compared to the normal group and negative control group(P＜0.05).Conclusion PDIA3 is highly expressed in EC tissues and is associated with the malignancy of tumors and poor prognosis of patients;targeted inhibition of PDIA3 expression can reduce the proliferation,invasion,and migration ability of Ishikawa cells.

Objective·To explore the biological functions and underlying mechanisms of anaphase-promoting complex subunit 10(ANAPC10)in the development and progression of liver hepatocellular carcinoma(LIHC,often abbreviated as HCC).Methods·By integrating data from The Cancer Genome Atlas(TCGA)_LIHC,the hepatitis B virus-related subgroup(HBV)of the China Hepatocellular Carcinoma Genome Project(CHCC),and the Gene Expression Omnibus(GEO),the expression pattern of ANAPC10 in HCC was analyzed.Western blotting and quantitative real-time PCR(q-PCR)were used to verify the findings in HCC cell lines.shRNA-mediated knockdown of ANAPC10 was performed in MHCC-97H and SNU-398 cell lines to investigate the effect of ANAPC10 depletion on the in vitro proliferation of HCC cells.An orthotopic liver cancer model with Anapc10 knockout was constructed using the hydrodynamic tail-vein injection technique in mice to further confirm the impact of ANAPC10 deficiency in the liver on the development and progression of HCC.Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)enrichment analyses were performed on the RNA-sequencing data from TCGA_LIHC and CHCC_HBV.Results·ANAPC10 was highly expressed in tumor tissues,and its expression level was closely related to patient survival.Downregulation of ANAPC10 in vitro and in vivo effectively inhibited HCC progression.ANAPC10 mainly reprogrammed the metabolism of tumors by affecting the PI3K-AKT-mTOR pathway.In the tumor tissues of the orthotopic liver cancer mouse model in the Anapc10 knockout group,the phosphorylation levels of Akt and S6k were decreased,and changes in the key downstream lipid metabolism proteins Fasn and Scd1 were verified.Conclusion·ANAPC10 is highly expressed in HCC and is positively correlated with poor prognosis.It promotes HCC occurrence and progression by activating the PI3K-AKT-mTOR signaling pathway and enhancing lipid metabolism reprogramming,thereby promoting tumor cell proliferation.These findings expand the understanding of ANAPC10 in tumor progression and suggest potential therapeutic targets for HCC.

Objective·To explore the function and potential mechanism of suppressor of zeste 12(SUZ12)in hepatocellular carcinoma(HCC).Methods·The expression of SUZ12 in HCC patients was analyzed using R language in liver cancer datasets,and relevant survival curves were drawn.Stable knockdown of SUZ12 was established in the liver cancer cell lines LM3 and Huh7.The knockdown efficiency of SUZ12 was assessed using quantitative real-time PCR(qPCR)and Western blotting.Cell proliferation ability was assessed using CCK-8 assay and colony formation assay.Using the hydrodynamic tail vein injection(HTVI)method,Suz12 was knocked out in the livers of fully immunocompetent mice to explore its tumorigenic function in vivo.The molecular mechanism of SUZ12 regulating HCC was explored using The Cancer Genome Atlas(TCGA)database.R language was used to analyze the relationship between SUZ12 and the expression of cancer stem cell(CSC)markers as well as key glycolysis-related genes.Findings were validated in liver cancer cell lines and mouse tumor tissues.Results·The expression of SUZ12 in liver cancer tissues was higher than in adjacent non-tumor tissues,and its expression increased with higher tumor stage.HCC patients with high SUZ12 expression had poorer prognoses.In LM3 and Huh7 liver cancer cell lines,stable knockdown of SUZ12 reduced cell proliferation ability.In the de novo MYC/Trp53-/-mouse liver cancer model,tumor nodule number and size,and tumor burden in liver tissue were reduced after endogenous knockout of Suz12.TCGA analysis showed that high SUZ12 expression in HCC was enriched in multiple tumor proliferation-and metabolism-related pathways.The expression of SUZ12 was positively correlated with CSC markers and key genes in glycolysis pathway.The mRNA levels of CSC markers and key genes in glycolysis pathway were decreased in liver cancer cell lines with stable SUZ12 knockdown and Suz12 knockout mouse HCC tissues.Conclusion·The expression of SUZ12 is significantly increased in HCC patients and is associated with poor prognosis.Stable knockdown of SUZ12 weakens the proliferative ability of liver cancer cells.Knockout of Suz12 in mice in vivo can suppress the occurrence and development of HCC.The high expression of SUZ12 maintains the CSC pool,induces metabolic reprogramming,and promotes the occurrence and progression of HCC.SUZ12 can serve as a potential biomarker for poor prognosis and a novel target for potential therapeutic intervention in HCC.