The poor prognosis of hepatocellular carcinoma (HCC) is strongly associated with invasion and metastasis.Recently,the epithelial-mesenchymal transition (EMT) has been confirmed to be the cytological foundation of invasion and metastasis.Yet,the molecular mechanism of inducing and maintaining EMT has not been expounded completely.However,it has been demonstrated that transforming growth factor-β (TGF-β),phosphatidyl inositol 3-kinase/protein kinase B (PI3K/AKT),nuclear factor-κB (NF-κB),Wnt/β-catenin signaling pathways play pivotal roles in the initiation and development of EMT.These signaling pathways can affect the prognosis of HCC by regulating EMT.From a drug development perspective,these signal pathways are potential and attractive targets for HCC treatment.

Objective:To study the effects of IL-8 on the polarization of monocytes and the effects of IL-8-induced tumor-associated macrophages(TAMs)on the invasion and metastasis of hepatocellular carcinoma(HCC).Methods:After exogenous IL-8 stimulation of THP-1 cells for 72h,the percentages of M1 and M2 TAMs were examined.RT-PCR and Western blot assays were used to study epitheli-al-mesenchymal transition(EMT),and wound-healing and transwell assays were preformed to study the invasion potential of HCC cells after co-culturing with TAMs and HCC cell lines in vitro.Lastly,100 cases of HCC tissue samples were used to validate the correlation among TAM numbers,IL-8,and EMT features of HCC cells via immunohistochemistry(IHC)staining methods.Results:Exogenous IL-8 induced significant M2 polarization of TAMs in THP-1 cells.TAMs further promoted EMT in HCC and enhanced the invasion potential of HCC in vitro.Finally,significant positive correlations among the numbers of TAMs,IL-8 expression,and N-cadherin expression were identified in primary HCC tissue samples(r=0.22,r=0.20,P<0.05).Conclusions:IL-8 locally attracted and activated TAMs,and promot-ed M2 polarization of TAMs,which further promoted the EMT and invasion potential of HCC cells both in vitro and in vivo.

Objective:To investigate the changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its role in predicting major adverse cardiac events (MACEs) in patients with end-stage heart failure (ESHF) before and after implanted a HeartCon left ventricular assist device (LVAD).Methods:The retrospective study included 30 ESHF patients [23 males and 7 females, aged 54.5 (40.8, 60.0) years], who were admitted to TEDA International Cardiovascular Disease Hospital from September 15, 2020 to June 20, 2023 to receive treatment with HeartCon LVAD implantation. Their clinical data were analyzed and NT-proBNP concentrations in their blood samples were measured preoperatively and during the follow-up period. Patients were followed regularly and MACEs, including cardiac death and rehospitalization for right heart failure, were recorded within 6 months of discharge; Logistic regression was used for prognostic analysis, and Receiver Operator Characteristic (ROC) curves were used to assess the adjunctive diagnostic value of NT-proBNP for poor prognosis in LVAD patients. The cut-off values for diagnosing poor prognosis by NT-proBNP were divided into two groups, and survival analysis was performed by Kaplan-Meier and tested by log rank; Cox regression was performed to analyze whether high levels of NT-proBNP at 6 months of follow-up wsa a risk factor for poor prognosis in patients with LVAD.Results:The median preoperative NT-proBNP level in 30 ESHF patients successfully implanted with HeartCon LVADs was 3 251.0 (1 544.5, 6 401.5) pg/ml. It decreased significantly 7 days postoperatively (3 251.0 vs. 1 815.0 pg/ml, P<0.05), and then the decreasing trend slowed. It decreased to 1 182.0 (620.0, 3 385.3) pg/ml on the 90th post-operative day. The preoperative NT-proBNP>3 251.0 pg/ml group had a longer postoperative hospital stay (47 d vs 33 d, Z=-2.138, P=0.032). Multivariate logistic regression analysis, only NT-proBNP at 7 days postoperatively was found to predict poor prognosis in LVAD patients, with an OR of 1.001 ( P=0.01); ROC curves were analyzed for the adjunctive diagnostic value of 7-day postoperative NT-proBNP levels for poor prognosis (cut-off value of 2 083.0 pg/ml), with an AUC of 0.833 ( P=0.002); The Kaplan-Meier survival analysis showed that the time to MACEs within 6 months was significantly shorter in the group with NT-proBNP>2 083.0 pg/mL on postoperative day 7 than in the group with NT-proBNP≤2 083.0 pg/ml (3.538±0.689 vs. 5.471±0.323 months, P=0.004); Cox regression analysis showed that the risk of MACEs was 4.25 times higher in the 7-day postoperative NT-proBNP>2 083.0 pg/ml group than in the NT-proBNP≤2 083.0 pg/ml group ( HR=4.25, P=0.035). Conclusions:The higher the preoperative NT-proBNP level, the longer the postoperative hospital stay in HeartCon LVAD patients. NT-proBNP levels decrease most significantly on postoperative day 7 and is a risk factor for MACEs. It may be used as a prognostic predictor in ESHF patients with implanted LVADs.

Objective: To detect eight highly related driver genes in non-small cell lung cancer (NSCLC), and to analyze the relationship between gene variations and clinical-pathological features. Methods: We collected 212 NSCLC samples from Tianjin Medical University Cancer Institute and Hospital, and sequenced eight genes which are EGFR, KRAS, BRAF, ALK, MET, ERBB2, ROS1 and RET. Results: EGFR gene variation rate was as high as 52.8%, followed by KRAS (8.5%), ALK (8.0%), ERBB2 (6.1%), MET (3.8%), BRAF (1.4%), RET (0.9%) and ROS1 (0.9%) in eight detecting genes, at least one driver gene variant was detected in 75% samples, and driver gene variant showed strong mutual exclusion. The most common EGFR mutations were 19 exon deletion and L858R mutation, and the mutation of EGFR T790M was accompanied by the above two mutations. The proportion of non-EGFR T790M mutations in patients with exon 19 dele-tion was lower than that of L858R mutations (P=0.04). There were 15.2% patients with EGFR mutation accompanied by EGFR amplifica-tion, and the proportion of patients with EGFR mutation frequency greater than 40% with EGFR amplification was higher than that without EGFR amplification (P<0.01). Women, non-smoking, patients with adenocarcinoma were prone to carry EGFR especially EGFR sensitive mutations (P<0.01). Patients with lung adenocarcinoma (P=0.013), late clinical stage (P=0.048), and lymph node metastasis (P=0.027) had a higher proportion of EGFR amplification. The incidence of KRAS mutation was higher in men, left lung cancer and smoking patients (P=0.009, P=0.048, P=0.037). Patients with non-KRAS mutations, ALK fusions were younger (P=0.005, P=0.031), and with KRAS mutations were older (P=0.055). Conclusions: Next-generation sequencing (NGS) can simultaneously detect eight highly re-lated driver genes in NSCLC patients to provide evidence for clinicians. NGS based on detection of multiple genes provides more possi- bilities for individualized diagnosis and treatment of NSCLC.