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High expression or aberrant activation of epidermal growth factor receptor (EGFR) is related to tumor progression and therapy resistance across cancer types, including non-small cell lung cancer (NSCLC). EGFR tyrosine kinase inhibitors (TKIs) are first-line therapy for NSCLC. However, patients eventually deteriorate after inevitable acquisition of EGFR TKI-resistant mutations, highlighting the need for therapeutics with alternative mechanisms of action. Here, we report that the elevated tribbles pseudokinase 3 (TRIB3) is positively associated with EGFR stability and NSCLC progression. TRIB3 interacts with EGFR and recruits PKCα to induce a Thr654 phosphorylation and WWP1-induced Lys689 ubiquitination in the EGFR juxtamembrane region, which enhances EGFR recycling, stability, downstream activity, and NSCLC stemness. Disturbing the TRIB3-EGFR interaction with a stapled peptide attenuates NSCLC progression by accelerating EGFR degradation and sensitizes NSCLC cells to chemotherapeutic agents. These findings indicate that targeting EGFR degradation is a previously unappreciated therapeutic option in EGFR-related NSCLC. Depletion of tribbles pseudokinase 3 (TRIB3) is known to suppress the expression of several tumor-promoting factors, including EGFR. Here, the authors show that TRIB3 interacts with EGFR and regulates its stability and activity, and perturbing EGFR-TRIB3 interaction attenuates NSCLC progression by accelerating EGFR degradation.

Jie He and colleagues report exome sequencing of 113 tumor-normal pairs of esophageal squamous cell carcinoma. They highlight mutations in genes involved in cell cycle and apoptosis regulation, histone modifier genes and genes encoding members of the Hippo and Notch pathways. Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers 1 . We performed exome sequencing on 113 tumor-normal pairs, yielding a mean of 82 non-silent mutations per tumor, and 8 cell lines. The mutational profile of ESCC closely resembles those of squamous cell carcinomas of other tissues but differs from that of esophageal adenocarcinoma. Genes involved in cell cycle and apoptosis regulation were mutated in 99% of cases by somatic alterations of TP53 (93%), CCND1 (33%), CDKN2A (20%), NFE2L2 (10%) and RB1 (9%). Histone modifier genes were frequently mutated, including KMT2D (also called MLL2 ; 19%), KMT2C ( MLL3 ; 6%), KDM6A (7%), EP300 (10%) and CREBBP (6%). EP300 mutations were associated with poor survival. The Hippo and Notch pathways were dysregulated by mutations in FAT1 , FAT2 , FAT3 or FAT4 (27%) or AJUBA ( JUB ; 7%) and NOTCH1 , NOTCH2 or NOTCH3 (22%) or FBXW7 (5%), respectively. These results define the mutational landscape of ESCC and highlight mutations in epigenetic modulators with prognostic and potentially therapeutic implications.

Despite the use of multimodal analgesia regimens following video-assisted thoracoscopic surgery (VATS), acute postoperative pain persists. Electroacupuncture (EA) may alleviate acute postoperative pain following VATS; however, current evidence remains insufficient. This trial will assess the feasibility and efficacy of EA as an adjunctive treatment compared with sham electroacupuncture (SA) for managing acute postoperative pain during coughing after VATS. In this pilot randomized controlled trial, 60 patients with non-small-cell lung cancer who will undergo VATS will be randomly assigned to either the EA or SA group in a 1:1 ratio. Patients will receive standard care combined with four sessions of EA or SA within 72 h after surgery. The primary outcome will be the average postoperative pain score during coughing, measured using a numeric rating scale within 72 h after surgery. Secondary outcomes will include the average daily pain scores at rest, during coughing, and while mobilizing; incidence of chronic post-surgical pain; quality of life; cough symptom score; and analgesic consumption. All adverse events will be recorded in detail. This study will determine whether EA as an adjunctive treatment can reduce acute postoperative pain during coughing following VATS. ClinicalTrial.gov ITMCTR2024000170 (http://itmctr.ccebtcm.org.cn/zh-CN/Home/ProjectView?pid=f1a344f7-7e06-4665-ad9d-0917d588eba6).

Background Hepatocellular carcinoma (HCC) with bile duct tumor thrombosis (BDTT) is a rare clinical condition with rapid disease progression and poor prognosis. This study aimed to evaluate the prognostic value of postoperative adjuvant transarterial chemoembolization (PA-TACE) among HCC-BDTT patients after radical resection (R0). Methods Between January 2002 and December 2010, 93 HCC-BDTT patients who underwent R0 resection were enrolled for a retrospective study, including 46 patients with PA-TACE and 47 patients without PA-TACE within two months postoperatively. The correlation between PA-TACE and the long-term prognosis of patients was analysed. Independent risk factors were identified by univariate and multivariate analysis. Results Overall, PA-TACE did not significantly improve disease-free survival (DFS) or overall survival (OS) in the entire cohort (median OS: 25 vs. 16 months, P  = 0.106). However, alpha fetoprotein (AFP)-negative patients receiving PA-TACE demonstrated significantly prolonged DFS (5-year: 50.8% vs. 11.6%, P  = 0.030) and OS (5-year: 64.0% vs. 26.3%, P  = 0.005). AFP (HR = 3.79, 95% CI 2.06–6.98, P  < 0.001) and ALP (HR = 2.12, 95% CI 1.11–4.06, P  = 0.023) were independent risk factors for OS. PA-TACE showed no benefit in AFP-positive patients (5-year OS: 0% vs. 9.4%, P  = 0.859). Elevated ALP (≥ 130 U/L) correlated with worse DFS (5-year: 3.1% vs. 19.6%, P  = 0.027) and OS (5-year: 8.8% vs. 22.3%, P  = 0.020). Conclusion Preoperative serum AFP and alkaline phosphatase were independent risk factors for evaluating the prognosis of HCC-BDTT. Postoperative prophylactic TACE can significantly prolong overall survival of HCC-BDTT in AFP-negative patients but not in AFP-positive cases, highlighting the need for tailored adjuvant therapies.

There is not yet a consensus regarding a difference in prognosis for patients with hepatocellular carcinoma (HCC) with and without bile duct invasion (BDI). The present study aimed to clarify the prognostic importance of BDI on the short and long-term outcome of patients with HCC who underwent surgical resection. The present study evaluated HCC with BDI, including peripheral microscopic biliary invasion and revealed that the prognosis of patients with BDI was poorer compared with those without BDI. It should be noted that peripheral BDI also had a negative impact on the prognosis of patients with HCC. The clinical prognosis assessment revealed that BDI should be considered when assigning a disease stage. BDI, either macroscopic or microscopic, indicated a poor prognosis in patients with HCC who underwent curative resection, however it was not a surgical contraindication. Macroscopic BDI and hyperbilirubinemia were significantly associated with a dismal prognosis, which should alert surgeons.

Aim： To determine the efficacy and toxicities of sorafenib in the treatment of patients with multiple recurrences of hepatocellular carcinoma （HCC） after liver transplantation in a Chinese population. Methods： Twenty patients with multiple recurrences of HCC after liver transplantation were retrospectively studied. They received either transarterial chemoembolization （TACE） or TACE combined with sorafenib. Results： The median survival times （MST） after multiple recurrences was 14 months （TACE＋sorafenib group） and 6 months （TACE only group）. The difference was significant in MST between the two groups （P=0.005）. The TACE ＋ sorafenib group had more stable disease （SD） patients than the TACE group. The most frequent adverse events of sorafenib were hand-foot skin reaction and diarrhea. In the univariate analysis, preoperative bilirubin and CHILD grade are found to be significantly associated with tumor-free survival time, the survival time after multiple recurrences and overall survival time. TACE＋sorafenib group showed a better outcome than single TACE treatment group. In the multivariate COX regression modeling, the preoperative high CHILD grade was found to be a risk factor of tumor-free survival time. In addition, the preoperative high bilirubin grade was also found to be a risk factor of survival time after recurrence and overall survival time. Furthermore, survival time after recurrence and overall survival time were also associated with therapeutic schedule, which was indicated by the GROUP. Conclusion： Treatment with TACE and sorafenib is worthy of further study and may have more extensive application prospects.

Increasing glucose transporter-1 (GLUT-1) activity is one of the most important ways to increase the cellular influx of glucose. We previously demonstrated that increased GLUT-1 expression was an independent predictor of survival in patients with laryngeal carcinoma. Thus, GLUT-1 may present a novel therapeutic target in laryngeal carcinoma. In this study, the expression of GLUT-1, P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) and glutathione S-transferase-π (GST-π) in laryngeal carcinomas was investigated by immunohistochemistry. Additionally, possible correlations between GLUT-1 and P-gp, MRP1 and GST-π and various clinicopathological parameters were analyzed. In this study, 52.9% (18/34), 58.8% (20/34), 20.6% (7/34) and 58.8% (20/34) of the laryngeal carcinomas were positive for GLUT-1, P-gp, MRP1 and GST-π, respectively. The expression of GLUT-1, P-gp, MRP1 and GST-π was higher in laryngeal carcinoma specimens when compared with laryngeal precancerous lesions (P<0.05). Pearson's correlation analysis showed correlations between GLUT-1 and P-gp (r=0.364; P=0.034), GLUT-1 and MRP1 (r=0.359; P=0.037) and P-gp and GST-π (r=0.426; P=0.012). GLUT-1 expression was found to significantly correlate with tumor-node-metastasis classification (P=0.02) and clinical stage (P=0.037). Furthermore, P-gp was found to significantly correlate with clinical stage (P=0.026). Univariate analysis showed that MRP1 expression was significantly associated with poor survival (c2=5.16; P=0.023). Multivariate analysis revealed that lymph node metastasis (P=0.009) and MRP1 overexpression (P=0.023) were significant predictors of poor survival. In the present study, the expression of GLUT-1, P-gp, MRP1 and GST-π in laryngeal carcinomas was investigated, as well as the correlations between these proteins. P-gp was found to significantly correlate with clinical stage, while MRP1 overexpression was significantly associated with poor survival.

Purpose The objective of this study was to provide the morphological details on small branches of the portal vein in transverse groove of hepatic hilum. Methods According to the surgery significance, the small branches of portal vein in transverse groove of hepatic hilum were named as “Short hepatic portal veins (SHPVs)”. SHPVs were minutely dissected in 30 adult cadaveric livers. The number, diameter, length, origin points, and entering liver sites of SHPVs were explored and measured. Results There were 181 SHPVs in 30 liver specimens, including 46 % (83/181) from the left portal vein, 31 % (56/181) from the bifurcation, and 23 % (42/181) from the right portal vein. At the entering liver sites of SHPVs, 22 % (40/181) supplied for segment IV, 9 % (17/181) for segment V, 4 % (7/181) for segment VI, 23 % (41/181) for segment VII, and 42 % (76/181) for segment I (caudate lobe). There were 6.0 ± 2.4 branches per liver specimen with range 3–12. The mean diameter of SHPVs was 2.25 ± 0.89 mm. The average length of SHPVs was 4.86 ± 2.12 mm. Conclusions SHPVs widely existed in each liver specimen. The detailed anatomical study of SHPVs could be useful to avoid damaging the short portal branches during hepatic operations, such as isolated or combined caudate lobectomy.

Highly sensitive phototransistors based on two-dimensional （2D） GaTe nanosheet have been demonstrated. The performance （photoresponsivity, detectivity） of the GaTe nanosheet phototransistor can be efficiently adjusted by using the applied gate voltage. The devices exhibit an ultrahigh photoresponsivity of 274.3 AW^-1. The detectivity of 2D GaTe devices is -10^12 Jones, which surpasses that of currently-exploited InGaAs photodetectors （10^11-10^12 Jones）. To reveal the origin of the enhanced photocurrent in GaTe nanosheets, theoretical modeling of the electronic structures was performed to show that GaTe nanosheets also have a direct bandgap structure, which contributes to the promotion of photon absorption and generation of excitons. This work shows that GaTe nanosheets are promising materials for high performance photodetectors.

The fermented Chinese formula Shuan-Tong-Ling is composed of radix puerariae（Gegen）,salvia miltiorrhiza（Danshen）,radix curcuma（Jianghuang）,hawthorn（Shanzha）,salvia chinensis（Shijianchuan）,sinapis alba（Baijiezi）,astragalus（Huangqi）,panax japonicas（Zhujieshen）,atractylodes macrocephala koidz（Baizhu）,radix paeoniae alba（Baishao）,bupleurum（Chaihu）,chrysanthemum（Juhua）,rhizoma cyperi（Xiangfu） and gastrodin（Tianma）,whose aqueous extract was fermented with lactobacillus,bacillus aceticus and saccharomycetes.ShuanTong-Ling is a formula used to treat brain diseases including ischemic stroke,migraine,and vascular dementia.Shuan-Tong-Ling attenuated H_2O_2-induced oxidative stress in rat microvascular endothelial cells.However,the potential mechanism involved in these effects is poorly understood.Rats were intragastrically treated with 5.7 or 17.2 m L/kg Shuan-Tong-Ling for 7 days before middle cerebral artery occlusion was induced.The results indicated Shuan-Tong-Ling had a cerebral protective effect by reducing infarct volume and increasing neurological scores.Shuan-Tong-Ling also decreased tumor necrosis factor-α and interleukin-1β levels in the hippocampus on the ischemic side.In addition,Shuan-Tong-Ling upregulated the expression of SIRT1 and Bcl-2 and downregulated the expression of acetylated-protein 53 and Bax.Injection of 5 mg/kg silent information regulator 1（SIRT1） inhibitor EX527 into the subarachnoid space once every 2 days,four times,reversed the above changes.These results demonstrate that Shuan-Tong-Ling might benefit cerebral ischemia/reperfusion injury by reducing inflammation and apoptosis through activation of the SIRT1 signaling pathway.