Immune cell dynamics and the impact on the efficiency of transvascular antitumor interventional therapies in hepatocellular carcinoma patients.

Objective: This study investigates the impact of transvascular antitumor interventional therapies on immune cell dynamics and its correlation with disease control and progression-free survival (PFS) in hepatocellular carcinoma (HCC) patients. Methods: A single-center observational case-control study was conducted with 119 HCC patients. Transvascular antitumor interventional therapy were administered based on patient-specific evaluations. Peripheral blood samples were collected before and within 28 days after the first treatment to analyze lymphocyte subsets and other immune cells. Results: Higher counts of total white blood cells (WBCs), lymphocytes, monocytes, and basophils were significantly associated with disease control rate. Subgroup analysis revealed that abnormal BMI, diabetes, infection, and multiple lesions were significantly associated with T cell abnormalities. Age, abnormal BMI, hypertension, and abnormal AFP were linked to total T cell abnormalities. NK cells, B cells, Th cells, Tc/Ts cells, and CD4/CD8 ratios did not show significant differences in PFS probabilities. Conclusion: Higher counts of WBCs, lymphocytes, monocytes, and basophils, play a crucial role in the effectiveness of HCC interventional therapy.

Application of combined ablation and immunotherapy in NSCLC and liver cancer: Current status and future prospects.

This review examines combining tumor ablation therapy with immunotherapy for respiratory and digestive system tumors, particularly NSCLC and liver cancer. Despite advancements in traditional methods, they face limitations in advanced-stage tumors. Ablation techniques like RFA, MWA, and cryoablation offer minimally invasive options, while immune checkpoint inhibitors enhance the immune system's tumor-fighting ability. This review highlights their synergistic effects, clinical outcomes, and future research directions, including optimizing protocols, exploring new combinations, uncovering molecular mechanisms, advancing precision medicine, and improving accessibility. Combined therapy is expected to improve efficacy and patient outcomes significantly.

An efficient DNAzyme-locked leakless enzyme-free amplification system for alpha-foetoprotein detection in liver cancer and breast cancer.

Alpha-foetoprotein (AFP) is taken as a diagnostic tumor marker for the screening and diagnosis of cancer. Nucleic acid-based isothermal amplification strategies are emerging as a potential technology in early screening and clinical diagnosis of AFP. The leakages between hairpins dramatically increase the background and reduce the sensitivity. Thus, it is necessary to develop some strategies to reduce the leakage for isothermal amplification strategies. A DNAzyme-locked leakless enzyme-free amplification system was developed for AFP detection in liver cancer and breast cancer. AFP could open the apt-hairpin and initiate the catalytic hairpin assembly (CHA) reaction to produce a Y-shaped duplex. Two tails of a Y-shaped duplex cleaved the two kinds of leakless hairpins. Then, the third tail of the Y-shaped duplex catalyzed the second CHA between the cleaved leakless hairpins to recover the fluorescent intensity. The limit of detection reached 5 fg/mL by the two levels of signal amplifications. Importantly, the leakless hairpin design effectively reduced leakage between hairpins and weakened the background. In addition, it also showed a great promising potential for AFP detection in early screening and clinical diagnosis.

Machine learning-based decision support model for selecting intra-arterial therapies for unresectable hepatocellular carcinoma: A national real-world evidence-based study.

IMPORTANCE: Intra-arterial therapies(IATs) are promising options for unresectable hepatocellular carcinoma(HCC). Stratifying the prognostic risk before administering IAT is important for clinical decision-making and for designing future clinical trials. OBJECTIVE: To develop and validate a machine learning(ML)-based decision support model(MLDSM) for recommending IAT modalities for unresectable HCC. DESIGN, SETTING, AND PARTICIPANTS: Between October 2014 and October 2022, a total of 2,959 patients with HCC who underwent initial IATs were enroled retrospectively from 13 tertiary hospitals. These patients were divided into the training cohort (n = 1700), validation cohort (n = 428), and test cohort (n = 200). MAIN OUTCOMES AND MEASURES: Thirty-two clinical variables were input, and five supervised ML algorithms, including eXtreme Gradient Boosting (XGBoost), Categorical Gradient Boosting (CatBoost), Gradient Boosting Decision Tree (GBDT), Light Gradient Boosting Machine (LGBM) and Random Forest (RF), were compared using the areas under the receiver operating characteristic curve (AUC) with the DeLong test. RESULTS: A total of 1856 patients were assigned to the IAT alone Group(I-A), and 1103 patients were assigned to the IAT combination Group(I-C). The 12-month death rates were 31.9% (352/1103) in the I-A group and 50.4% (936/1856) in the I-C group. For the test cohort, in the I-C group, the CatBoost model achieved the best discrimination when 30 variables were input, with an AUC of 0.776 (95% confidence intervals [CI], 0.833-0.868). In the I-A group, the LGBM model achieved the best discrimination when 24 variables were input, with an AUC of 0.776 (95% CI, 0.833-0.868). According to the decision trees, BCLC grade, local therapy, and diameter as top three variables were used to guide clinical decisions between IAT modalities. CONCLUSIONS AND RELEVANCE: The MLDSM can accurately stratify prognostic risk for HCC patients who received IATs, thus helping physicians to make decisions about IAT and providing guidance for surveillance strategies in clinical practice.

CircVIRMA enhances cell malignant behavior by governing the miR-452-5p/CREBRF pathway in cervical cancer.

Our current study aimed to investigate the role and mechanism of circVIRMA in cervical cancer (CC) progression. CircVIRMA, microRNA-452-5p (miR-452-5p) and CREB3 regulatory factor (CREBRF) mRNA levels were examined in CC via quantitative real-time PCR (qRT-PCR). The protein level of CREBRF in CC was checked by Western blot. Cell Counting Kit-8 (CCK-8), colony formation, 5-Ethynyl-2'-deoxyuridine (EdU) staining, cell cycle, flow cytometry and transwell assays were conducted to estimate the effects of circVIRMA on malignant phenotypes of CC tumors. Western blot was used to measure related marker protein levels. The interaction between miR-452-5p and circVIRMA or CREBRF was predicted by bioinformatics analysis and verified by dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. Xenograft assay was used to assess the effect of circVIRMA on tumor growth in vivo. Immunohistochemistry (IHC) assay was performed to detect Ki-67 expression in tissues of mice. CircVIRMA and CREBRF levels were upregulated, while miR-452-5p was downregulated in CC tissues and cells. CircVIRMA silencing restrained CC cell proliferation, migration and invasion whereas induced apoptosis in vitro. In addition circVIRMA knockdown markedly attenuated xenograft tumor growth in vivo. circVIRMA was an efficient molecular sponge for miR-452-5p, and negatively regulated miR-452-5p expression. circVIRMA regulated CREBRF expression to modulate CC progression via miR-452-5p. MiR-452-5p downregulation reversed the effects of circVIRMA knockdown on CC progression. MiR-452-5p directly targeted CREBRF, and CREBRF overexpression partly restored the impact of miR-452-5p mimics on CC progression. circVIRMA mediated CC progression via regulating miR-452-5p/CREBRF axis, providing a novel therapeutic target for CC treatment.

Correction: Identification of serum prognostic marker miRNAs and construction of microRNA-mRNA networks of esophageal cancer.

[This corrects the article DOI: 10.1371/journal.pone.0255479.].

Large rectangular cross-section tunnel undercrossing urban road by micro pipe jacking and joint assembly structure (MPJ & JAS) method in soft soils.

With the continuous construction of urban traffic roads, more and more new roads are cut off by existing roads to form "dead end roads". There is an urgent need for a trenchless method suitable for urban ultra-shallow overburden to build the undercrossing tunnel. To solve this problem, this paper proposed the micro pipe jacking and joint assembly structure (MPJ & JAS) method, which has the characteristics of shallow burial depth, low cost, short construction time, flexible cross-section setting and high space utilization. The MPJ & JAS method construct a large cross-section tunnel through assembling small cross-section elements, quite different from traditional methods. Therefore, this paper designed a CT-shaped integrated joint, the mechanical performance of which was verified and clarified by tensile test. The bending test and finite element (FE) analysis proved the reliability of MPJ & JAS tunnel structure, and confirmed the structure performances such as the failure models, crack behaviors, load-deflection response and stress-strain distribution. Moreover, the influences of the steel plate thickness, concrete strength and shear connector spacing were determined by the FE analysis. On the basis of test results and reasonable assumptions, a theoretical design method considering the influence of the CT-shaped integrated joint was proposed, which can effectively predict the bending strength of the MPJ & JAS tunnel structure with an error of less than 10%. Finally, in view of the characteristics of the MPJ & JAS method, the suitable micro pipe jacking machine, soil reinforcement measure, hydraulic traction construction technology, high-precision guidance system and concrete construction quality detection method based on the phased array ultrasonic imaging technology were developed, supporting the accurate and efficient construction of the MPJ & JAS tunnel.

Abnormal metabolism in hepatic stellate cells: Pandora's box of MAFLD related hepatocellular carcinoma.

Metabolic associated fatty liver disease (MAFLD) is a significant risk factor for the development of hepatocellular carcinoma (HCC). Hepatic stellate cells (HSCs), as key mediators in liver injury response, are believed to play a crucial role in the repair process of liver injury. However, in MAFLD patients, the normal metabolic and immunoregulatory mechanisms of HSCs become disrupted, leading to disturbances in the local microenvironment. Abnormally activated HSCs are heavily involved in the initiation and progression of HCC. The metabolic disorders and abnormal activation of HSCs not only initiate liver fibrosis but also contribute to carcinogenesis. In this review, we provide an overview of recent research progress on the relationship between the abnormal metabolism of HSCs and the local immune system in the liver, elucidating the mechanisms of immune imbalance caused by abnormally activated HSCs in MAFLD patients. Based on this understanding, we discuss the potential and challenges of metabolic-based and immunology-based mechanisms in the treatment of MAFLD-related HCC, with a specific focus on the role of HSCs in HCC progression and their potential as targets for anti-cancer therapy. This review aims to enhance researchers' understanding of the importance of HSCs in maintaining normal liver function and highlights the significance of HSCs in the progression of MAFLD-related HCC.

Circ_0001982 aggravates breast cancer development through the circ_0001982-miR-144-3p-GSE1 axis.

This study was designed to explore the role of circ_0001982 in breast cancer (BC) development. Quantitative real-time polymerase chain reaction and western blot analysis assays were used to determine circ_0001982, miR-144-3p, and gse1 coiled-coil protein (GSE1) expression. Functional assays were performed to evaluate cell proliferation, apoptosis, migration, and invasion. The glycolysis was analyzed with commercial kits. Dual-luciferase reporter assay and RNA immunoprecipitation assays were conducted to analyze the relationships among circ_0001982, miR-144-3p, and GSE1. A murine xenograft model assay was performed to determine circ_0001982-induced effects on BC cell tumor properties in vivo. Circ_0001982 expression was upregulated, but miR-144-3p was reduced in BC tissues and cells in comparison with normal breast tissues and normal human mammary epithelial cells. Circ_0001982 knockdown or miR-144-3p overexpression inhibited BC cell proliferation, glycolysis, migration and invasion, and promoted apoptosis. Circ_0001982 sponged miR-144-3p and negatively regulated miR-144-3p expression in BC cells. In addition, GSE1 was identified as a target mRNA of miR-144-3p. Ectopic GSE1 expression relieved circ_0001982 depletion-induced effects on BC cell tumor properties. Furthermore, circ_0001982 absence suppressed BC cell tumor properties in vivo. Circ_0001982 contributed to the BC cell tumor properties by regulating the miR-144-3p-GSE1 axis.

Drug-eluting bead transarterial chemoembolization (DEB-TACE) versus conventional transarterial chemoembolization (cTACE) in colorectal liver metastasis: Efficacy, safety, and prognostic factors.

OBJECTIVE: To comparatively evaluate drug-eluting bead transarterial chemoembolization (DEB-TACE) and conventional transarterial chemoembolization (cTACE) for efficacy, safety, and related prognostic factors in the treatment of colorectal liver metastasis (CRLM). MATERIALS AND METHODS: This study retrospectively analyzed 75 patients with CRLM-administered DEB-TACE (n = 36) or cTACE (n = 39) between January 2016 and December 2017. Local control, survival outcome, and complications were compared between the two groups. Univariate and multivariate analyses of prognostic factors affecting progression-free survival (PFS) and overall survival (OS) were performed. RESULTS: The median follow-up in the two groups was 10.5 months (range, 0.5-22). Median PFS and OS in the DEB-TACE group were 10.0 and 13.0 months, respectively, and 6.0 and 8.5 months in the cTACE group, respectively (P = 0.009 and P = 0.008). The 3-, 6-, and 12-month OS rates in the DEB-TACE group were 100.0%, 94.4%, and 55.6%, respectively, and 92.3%, 71.8%, and 35.9% in the cTACE group, respectively. The 3-month OS rate (P = 0.083) showed no significant difference between the two groups, but significant differences were found in the 6- and 12-month OS rates (P = 0.008 and P = 0.030). Univariate and multivariate survival analyses showed that treatment method, tumor size, and tumor number were independent prognostic factors affecting PFS and OS. CONCLUSION: DEB-TACE has advantages over cTACE in prolonging PFS and OS in patients with CRLM. Treatment method, tumor number, and tumor size are important prognostic factors affecting PFS and OS. However, further multicenter and prospective trials are needed to confirm a deeper comparison between DEB-TACE and cTACE in patients with CRLM.

The high-quality sequencing of the Brassica rapa 'XiangQingCai' genome and exploration of genome evolution and genes related to volatile aroma.

'Vanilla' (XQC, brassica variety chinensis) is an important vegetable crop in the Brassica family, named for its strong volatile fragrance. In this study, we report the high-quality chromosome-level genome sequence of XQC. The assembled genome length was determined as 466.11 Mb, with an N50 scaffold of 46.20 Mb. A total of 59.50% repetitive sequences were detected in the XQC genome, including 47 570 genes. Among all examined Brassicaceae species, XQC had the closest relationship with B. rapa QGC ('QingGengCai') and B. rapa Pakchoi. Two whole-genome duplication (WGD) events and one recent whole-genome triplication (WGT) event occurred in the XQC genome in addition to an ancient WGT event. The recent WGT was observed to occur during 21.59-24.40 Mya (after evolution rate corrections). Our findings indicate that XQC experienced gene losses and chromosome rearrangements during the genome evolution of XQC. The results of the integrated genomic and transcriptomic analyses revealed critical genes involved in the terpenoid biosynthesis pathway and terpene synthase (TPS) family genes. In summary, we determined a chromosome-level genome of B. rapa XQC and identified the key candidate genes involved in volatile fragrance synthesis. This work can act as a basis for the comparative and functional genomic analysis and molecular breeding of B. rapa in the future.

RAB10 promotes breast cancer proliferation migration and invasion predicting a poor prognosis for breast cancer.

RAB10, a member of the small GTPase family, has complex biological functions, but its role in breast cancer (BC) remains unclear. The aim of this study was to investigate the relationship between RAB10's role in BC, its biological functions, and BC prognosis. An online database was used to analyze the correlation between differential expression of RAB10 in BC and prognosis. The results of immunohistochemical assays in clinical cohorts were combined with the database analysis. The chi-square test and COX regression were employed to analyze the correlation between RAB10 and pathological features of BC. MTT, Transwell, and wound healing assays were conducted to detect BC cell proliferation, invasion, and metastatic ability. Bioinformatics techniques were employed to explore the correlation between RAB10 and BC tumor immune cell infiltration, and to speculate the biological function of RAB10 in BC and related signaling pathways. Our findings suggest that RAB10 expression is elevated in BC and is associated with HER2 status, indicating a poor prognosis for BC patients. RAB10 can promote the proliferation, migration, and invasion ability of BC cells in vitro. RAB10 is also associated with BC immune cell infiltration and interacts with multiple signaling pathways. RAB10 is a potential biomarker or molecular target for BC.

Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma (CHANCE001).

There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4-11.0) versus 8.0 months (95% CI, 6.6-9.5) (adjusted hazard ratio [HR], 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1-27.3] vs. 15.7 months [13.0-20.2]; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile.

A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial of olanzapine plus triple antiemetic regimen for the prevention of multiday highly emetogenic chemotherapy-induced nausea and vomiting (OFFER study).

Background: Evidence supports prophylactic use of olanzapine for the treatment of chemotherapy-induced nausea and vomiting (CINV). However, most studies to date have focused on patients with single-day highly emetogenic chemotherapy (HEC). Currently, administration of antiemetic therapies for nausea and vomiting induced by multiday chemotherapy regimens remains a challenge. In this study, we evaluated the efficacy of olanzapine combined with triple antiemetic therapy for the prevention of CINV in patients receiving multiday chemotherapy. Methods: We performed a randomized, double-blind, placebo-controlled phase 3 trial in 22 hospitals. Eligible patients were between 18 and 75 years old, were diagnosed with malignant solid tumors, and they had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. All the study participants were scheduled to be treated with chemotherapy regimens containing 3-day cisplatin (3-day total dose ≥75 mg/m2). Randomization was computer generated and stratified by gender and chemotherapy treatment history. Allocation was done via an interactive web response system. Enrolled patients were randomly assigned 1:1 to receive either 5 mg olanzapine or placebo orally before bedtime for 5 days combined with intravenous fosaprepitant (150 mg) 1 h before the administration of cisplatin on day 1, ondansetron hydrochloride intravenously, and dexamethasone orally 30 min before cisplatin from days 1 to 3. Dexamethasone was also administered at the same time on days 4 and 5. The primary endpoint was the proportion of subjects with complete response (no vomiting and no rescue therapy) within the overall phase (days 1-8) after starting chemotherapy. Baseline plasma concentrations of P-substance and 5-HT were measured for exploratory analysis. This study was registered at ClinicalTrials.gov, number NCT04536558. Findings: Between December 2020 and September 2021, 349 patients with malignant solid tumors were enrolled in the study, with 175 participants randomly assigned to receive olanzapine and 174 participants assigned to receive placebo. The proportion of patients who achieved a complete response in the overall phase was significantly higher in the olanzapine group than in the placebo group (69% vs. 58%, P = 0.031). A complete response benefit was observed in the olanzapine group versus the placebo group in almost all the subgroups. Four factors were considered significantly associated with complete response in multivariable analysis: treatment group, gender, baseline plasma concentration of 5-HT, and prior radiotherapy. All the reported adverse events associated with olanzapine administration were grades 1 and 2. Interpretation: Olanzapine (5 mg) combined with fosaprepitant, ondansetron, and dexamethasone was better than triple antiemetic therapy alone for patients receiving multiday chemotherapy regimens. Based on these results, the four-drug combination should be recommended as the best antiemetic regimen given to patients receiving multiday cisplatin-based chemotherapy and baseline plasma concentration of 5-HT may be used to identify individuals who are prone to CINV. However, all these findings need to be further validated in future studies. Funding: Jiangsu Hansoh Pharmaceutical Group Co., Ltd. provided research grant and study drugs for this investigator-initiated study.

MiR-30c facilitates natural killer cell cytotoxicity to lung cancer through targeting GALNT7.

BACKGROUND: MicroRNAs (miRNAs) have been reported to play important roles in regulating natural killer (NK) cell cytotoxicity to cancer cells. OBJECTIVE: This study aimed to investigate the effects and potential mechanism of miR-30c in regulating NK cell cytotoxicity to lung cancer cells. METHODS: Primary NK cells were derived from the peripheral blood of lung cancer and normal participants. Exosomes were isolated and validated via transmission electron microscopy and nanoparticle tracking analysis. The levels of miR-30c, polypeptide N-acetylgalactosaminyltransferase 7 (GALNT7) and proteins in PI3K/AKT pathway were determined using quantitative real-time polymerase chain reaction or western blot. Tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) levels and the cytotoxicity of effector NK cells to target lung cancer cells were measured via enzyme linked immunosorbent assay, cell apoptosis or xenograft experiments. The relationship between miR-30c and GALNT7 was analyzed by luciferase activity, RNA pull-down and RNA immunoprecipitation assays. And a xenograft mice model was established to verify the effect of miR-30c in regulating NK cell cytotoxicity to lung cancer cells in vivo. RESULTS: NK cell-derived exosomes carrying miR-30c, and miR-30c level was significantly downregulated in primary NK cells of lung cancer patients. MiR-30c overexpression promoted TNF-α and IFN-γ secretion and enhanced the cytotoxicity of interleukin 2 (IL-2)-treated NK cells to lung cancer cells, while knockdown of miR-30c played an opposite effect in regulating the cytotoxicity of NK cells to lung cancer cells. GALNT7 was a target of miR-30c and was negatively regulated by miR-30c. Besides, miR-30c targeted GALNT7 to exert its function in regulating NK cell cytotoxicity. Furthermore, GALNT7 prompted the activation of PI3K/AKT pathway in NK cells. Additionally, miR-30c overexpression enhanced NK cell cytotoxicity to lung cancer cells and inhibited tumor growth in vivo. CONCLUSION: miR-30c enhanced NK cell cytotoxicity to lung cancer cells via decreasing GALNT7 and inactivating the PI3K/AKT pathway, suggesting that regulating miR-30c expression maybe a promising approach for enhancing NK cell-based antitumor therapies.

A systematic review and meta-analysis comparing tumor progression and complications between radiofrequency ablation and thyroidectomy for papillary thyroid carcinoma.

Background: Papillary thyroid cancer (PTC) is the most frequent thyroid cancers worldwide. The efficacy and acceptability of radiofrequency ablation (RFA) in the treatment of PTC have been intensively studied. The aim of this study is to focus on extra detailed that may influent for PTC or papillary thyroid microcarcinoma (PTMC). Materials and methods: We identified a total of 1,987 records of a primary literature searched in PubMed, Embase, Cochrane Library, and Google Scholar by key words, from 2000 to 2022. The outcome of studies included complication, costs, and local tumor progression. After scrutiny screening and full-text assessment, six studies were included in the systematic review. Heterogeneity was estimated using I2, and the quality of evidence was assessed for each outcome using the GRADE guidelines. Results: Our review enrolled 1,708 patients reported in six articles in the final analysis. There were 397 men and 1,311 women in the analysis. Two of these studies involved PTC and four focused on PTMC. There were 859 patients in the RFA group and 849 patients in the thyroidectomy group. By contrast, the tumor progression of RFA group was as same as that surgical groups [odds ratio, 1.31; 95% CI, 0.52-3.29; heterogeneity (I2 statistic), 0%, p = 0.85]. The risk of complication rates was significantly lower in the RFA group than that in the surgical group [odds ratio, 0.18; 95% CI, 0.09-0.35; heterogeneity (I2 statistic), 40%, p = 0.14]. Conclusions: RFA is a safe procedure with a certain outcome for PTC. RFA can achieve a good efficacy and has a lower risk of major complications.

Transarterial chemoembolization combined with metformin improves the prognosis of hepatocellular carcinoma patients with type 2 diabetes.

Objective: The study aims to investigate the effect of metformin on Hepatocellular carcinoma (HCC) patients with type 2 diabetes mellitus (T2DM) who received transarterial chemoembolization (TACE) for the first time. Methods: From January 2016 to December 2019, T2DM patients diagnosed with HCC in Shandong Cancer Hospital and treated with TACE were included in this retrospective study. Overall survival (OS) and Progression-free survival (PFS) were compared between patients treated with metformin and other antidiabetics. Univariate and multivariate Cox regression models were used to evaluate the independent risk factors associated with OS and PFS. And sub-analysis was performed to investigate whether metformin could give a survival advantage in each Barcelona Clinic Liver Cancer (BCLC) stage of HCC. Propensity score matched (PSM) analyses based on patient and tumor characteristics were also conducted. Results: A total of 123 HCC patients with T2DM underwent TACE, of which 50 (40.65%) received treatment with metformin. For the whole cohort, the median OS (42 vs 32 months, p=0.054) and PFS (12 vs 7 months, P=0.0016) were longer in the metformin group than that in the non-metformin group. Multi-analysis revealed that BCLC stage, BMI (Body Mass Index), and metformin use were independent predictors of OS. Metformin use was independently associated with recurrence. After PSM, 39 matched pairs were identified. The use of metformin was associated with a numerically longer m OS (43 vs 35 months, P=0.183) than the use of other anti-diabetics. And the difference in median PFS (13 vs 7 months, p=0.018) between the metformin group and non-metformin group remained significant. Conclusion: The combination of transarterial chemoembolization and metformin may be associated with better OS and PFS in HCC patients with T2DM.

Learning to detect boundary information for brain image segmentation.

MRI brain images are always of low contrast, which makes it difficult to identify to which area the information at the boundary of brain images belongs. This can make the extraction of features at the boundary more challenging, since those features can be misleading as they might mix properties of different brain regions. Hence, to alleviate such a problem, image boundary detection plays a vital role in medical image segmentation, and brain segmentation in particular, as unclear boundaries can worsen brain segmentation results. Yet, given the low quality of brain images, boundary detection in the context of brain image segmentation remains challenging. Despite the research invested to improve boundary detection and brain segmentation, these two problems were addressed independently, i.e., little attention was paid to applying boundary detection to brain segmentation tasks. Therefore, in this paper, we propose a boundary detection-based model for brain image segmentation. To this end, we first design a boundary segmentation network for detecting and segmenting images brain tissues. Then, we design a boundary information module (BIM) to distinguish boundaries from the three different brain tissues. After that, we add a boundary attention gate (BAG) to the encoder output layers of our transformer to capture more informative local details. We evaluate our proposed model on two datasets of brain tissue images, including infant and adult brains. The extensive evaluation experiments of our model show better performance (a Dice Coefficient (DC) accuracy of up to [Formula: see text] compared to the state-of-the-art models) in detecting and segmenting brain tissue images.

The hypoxia-inducible factor 1 inhibitor LW6 mediates the HIF-1α/PD-L1 axis and suppresses tumor growth of hepatocellular carcinoma in vitro and in vivo.

The low survival rate of hepatocellular carcinoma (HCC) remains a major challenge for clinicians and patients, and its progression may be related to hypoxia-inducible factor (HIF) and PD-L1. LW6 is a drug that inhibits hypoxia by reducing HIF-1α accumulation and gene transcriptional activity. However, its effect and regulatory mechanism in HCC remain to be revealed, especially under hypoxic conditions. The HIF-1α and PD-L1 expression in HCC specimens and paracarcinoma tissues was evaluated by a tissue microarray (TMA). The effects of LW6 were evaluated by cell viability, colony formation, and Transwell assays and xenografted nude mice. Cell cycle and apoptosis of HCC cells were detected by flow cytometry. The effects of LW6 on HIF-1α signaling and its targets PD-L1 and VEGF were evaluated through qRT-PCR, Western blots, Cell transfection, Transwell migration and invasion assays, immunohistochemistry, immunofluorescence and luciferase assays. In this study, we found that LW6 had antiproliferative effects on HCC and promoted HCC cell apoptosis, inhibited their migration and invasion, and affected their cell cycle. LW6 dramatically decreased HIF-1α expression through the VHL-dependent proteasome system pathway, inhibited HIF-1α transcriptional activation, and reduced PD-L1 expression by inhibiting EGFR pathway activation. These results suggest that LW6 can promote apoptosis of HCC cells by inhibiting HIF-1α, inhibit tumor angiogenesis, and downregulate the expression of PD-L1, which is an effective choice for the treatment of HCC. Moreover, inhibiting the hypoxic microenvironment combined with immunotherapy is expected to be a potentially effective strategy.