Dynamic network biomarker C1QTNF1 regulates tumor formation at the tipping point of hepatocellular carcinoma.

Identifying the precise moment before the onset of hepatocellular carcinoma (HCC) remains a significant challenge in the medical field. The existing biomarkers fall short of pinpointing the critical point preceding HCC formation. This study aimed to determine the exact tipping point for the transition from cirrhosis to HCC, identify the core Dynamic Network Biomarker (DNB), and elucidate its regulatory effects on HCC. A spontaneous HCC mouse model was established to mimic HCC formation in patients with chronic hepatitis. Using the DNB method, C1q and tumor necrosis factor (TNF) related 1 (C1QTNF1) protein was identified as the key DNB at the crucial tipping time of spontaneous HCC development. Both in vitro and in vivo studies showed that C1QTNF1 could inhibit tumor growth. Overexpression of C1QTNF1 before the tipping point effectively prevented HCC occurrence. Patients with elevated C1QTNF1 expression demonstrated improved overall survival (OS) (P = 0.03) and disease-free survival (DFS) (P = 0.03). The diagnostic value of C1QTNF1 was comparable to that of alpha-fetoprotein (AFP) (area under the curve [AUC] = 0.84; sensitivity 85%; specificity 80%). Furthermore, our research indicated that platelet-expressed C1QTNF1 is involved in cancer-associated signaling pathways. Our findings introduce a novel perspective by highlighting C1QTNF1 as the pivotal biomarker at the tipping point of primary HCC formation using DNB. We propose C1QTNF1 as a prognostic biomarker for HCC, potentially influencing tumor development through a platelet-related cancer signaling pathway.

Low-dose radiotherapy combined with dual PD-L1 and VEGFA blockade elicits antitumor response in hepatocellular carcinoma mediated by activated intratumoral CD8+ exhausted-like T cells.

Atezolizumab (anti-PD-L1) combined with bevacizumab (anti-VEGFA) is the first-line immunotherapy for advanced hepatocellular carcinoma (HCC), but the number of patients who benefit from this regimen remains limited. Here, we combine dual PD-L1 and VEGFA blockade (DPVB) with low-dose radiotherapy (LDRT), which rapidly inflames tumors, rendering them vulnerable to immunotherapy. The combinatorial therapy exhibits superior antitumor efficacy mediated by CD8+ T cells in various preclinical HCC models. Treatment efficacy relies upon mobilizing exhausted-like CD8+ T cells (CD8+ Tex) with effector function and cytolytic capacity. Mechanistically, LDRT sensitizes tumors to DPVB by recruiting stem-like CD8+ Tpex, the progenitor exhausted CD8+ T cells, from draining lymph nodes (dLNs) into the tumor via the CXCL10/CXCR3 axis. Together, these results further support the rationale for combining LDRT with atezolizumab and bevacizumab, and its clinical translation.

Prediction model for hepatocellular carcinoma recurrence after hepatectomy: Machine learning-based development and interpretation study.

Background: Identifying patients with hepatocellular carcinoma (HCC) at high risk of recurrence after hepatectomy can help to implement timely interventional treatment. This study aimed to develop a machine learning (ML) model to predict the recurrence risk of HCC patients after hepatectomy. Methods: We retrospectively collected 315 HCC patients who underwent radical hepatectomy at the Third Affiliated Hospital of Sun Yat-sen University from April 2013 to October 2017, and randomly divided them into the training and validation sets at a ratio of 7:3. According to the postoperative recurrence of HCC patients, the patients were divided into recurrence group and non-recurrence group, and univariate and multivariate logistic regression were performed for the two groups. We applied six machine learning algorithms to construct the prediction models and performed internal validation by 10-fold cross-validation. Shapley additive explanations (SHAP) method was applied to interpret the machine learning model. We also built a web calculator based on the best machine learning model to personalize the assessment of the recurrence risk of HCC patients after hepatectomy. Results: A total of 13 variables were included in the machine learning models. The multilayer perceptron (MLP) machine learning model was proved to achieve optimal predictive value in test set (AUC = 0.680). The SHAP method displayed that γ-glutamyl transpeptidase (GGT), fibrinogen, neutrophil, aspartate aminotransferase (AST) and total bilirubin (TB) were the top 5 important factors for recurrence risk of HCC patients after hepatectomy. In addition, we further demonstrated the reliability of the model by analyzing two patients. Finally, we successfully constructed an online web prediction calculator based on the MLP machine learning model. Conclusion: MLP was an optimal machine learning model for predicting the recurrence risk of HCC patients after hepatectomy. This predictive model can help identify HCC patients at high recurrence risk after hepatectomy to provide early and personalized treatment.

Double-Shock Compression Pathways from Diamond to BC8 Carbon.

Carbon is one of the most important elements for both industrial applications and fundamental research, including life, physics, chemistry, materials, and even planetary science. Although theoretical predictions on the transition from diamond to the BC8 (Ia3[over ¯]) carbon were made more than thirty years ago, after tremendous experimental efforts, direct evidence for the existence of BC8 carbon is still lacking. In this study, a machine learning potential was developed for high-pressure carbon fitted from first-principles calculations, which exhibited great capabilities in modeling the melting and Hugoniot line. Using the molecular dynamics based on this machine learning potential, we designed a thermodynamic pathway that is achievable for the double shock compression experiment to obtain the elusive BC8 carbon. Diamond was compressed up to 584 GPa after the first shock at 20.5 km/s. Subsequently, in the second shock compression at 24.8 or 25.0 km/s, diamond was compressed to a supercooled liquid and then solidified to BC8 in around 1 ns. Furthermore, the critical nucleus size and nucleation rate of BC8 were calculated, which are crucial for nano-second x-ray diffraction measurements to observe BC8 carbon during shock compressions. The key to obtaining BC8 carbon lies in the formation of liquid at a sufficient supercooling. Our work provides a feasible pathway by which the long-sought BC8 phase of carbon can be reached in experiments.

Tenofovir versus entecavir on decreasing risk of HBV-related hepatocellular carcinoma recurrence after liver transplantation.

BACKGROUND: Recent studies have proved that tenofovir disoproxil fumarate (TDF) is associated with a lower risk of hepatocellular carcinoma (HCC) occurrence in chronic hepatitis B (CHB) patients and HCC recurrence in patients who underwent hepatectomy when compared to ETV. However, it is unclear whether TDF and ETV treatment, which are both recommended as first-line antiviral agents to prevent the hepatitis B (HBV) recurrence after liver transplantation (LT), are associated with equivalent prognosis. We aim to compare risk of HCC recurrence and survival of patients recieving TDF or ETV after LT for HBV-related HCC. METHOD: We performed a retrospective study including 316 patients who received treatment with ETV or TDF after LT for HBV-related HCC from 2015 January to 2021 Augest. The Recurrence-free survival (RFS) and overall survival (OS) of TDF and ETV groups were analyzed and compared by propensity score-matched (PSM), multivariable Cox regression analysis, competing risk analysis, sensitivity analyses and subgroup analyses. RESULT: Compared with ETV, TDF therapy was associated with significantly higher RFS rates in the entire cohort (P < 0.01), PSM cohort (P < 0.01) and beyond-Milan cohort (P < 0.01). By multivariable analysis, TDF group was associated with significantly lower rates of HCC recurrence (HR, 0.33; 95%CI, 0.14-0.75; P < 0.01). In subgroup analyses, the similar results were observed in patients with following tumor characteristics: Maximum diameter plus number of viable tumor ≥ 5, with MIV or MAT, AFP at LT ≥ 20 ng/ml, and well or moderate tumor grade. CONCLUSION: Tenofovir decrease risk of HBV-Related Hepatocellular Carcinoma recurrence after liver transplantation compared to Entecavir.

Ginsenoside CK induces apoptosis and suppresses proliferation and invasion of human osteosarcoma cells through the PI3K/mTOR/p70S6K1 pathway.

Osteosarcoma is one of the most malignant bone tumors, and its major threats are aggressive invasion and early tumor metastasis, which result in a poor prognosis and high mortality. Accumulating evidence indicates that ginsenoside compound K (CK) has a significant antitumor effect, particularly on the inhibition of proliferation and invasion of numerous human tumors. In the present study, it was revealed that CK inhibited the viability and proliferation of osteosarcoma cells. Moreover, it was demonstrated that CK induced apoptosis and inhibited the migration and invasion of osteosarcoma cells via apoptotic staining, Annexin V/PI staining, and Transwell invasion assays. Furthermore, at the molecular level, the present results confirmed that apoptosis and invasion­related proteins were regulated by CK, which was possibly related to the blockade of the PI3K/mTOR/p70S6K1 signaling pathway. In summary, the present findings indicated that CK inhibited viability and proliferation, induced apoptosis, and inhibited the migration and invasion of osteosarcoma cells through the PI3K/mTOR/p70S6K1 signaling pathway.

Mechanism of miR-143-3p inhibiting proliferation, migration and invasion of osteosarcoma cells by targeting MAPK7.

Objective: To investigate the effects of miR-143-3p and MAPK7 on the proliferation, migration, and invasion of U2OS human osteosarcoma (OS) cells. Methods: The expression of miR-143-3p and MAPK7 in U2OS cells were detected by qRT-PCR, and the protein level of MAPK7 was measured by western blot assay. The targeting relationship between miR-143-3p and MAPK7 was predicted by TargetScan and verified by dual luciferase reporter assay. MTT and Transwell assays were used to detect cell viability, migrated cells and invaded cells of U2OS cells. Results: Compared with hFOB1.19 cells, the expression of miR-143-3p was down-regulated and MAPK7 was up-regulated in U2OS cells. Cell viability, migration and invasion ability significantly decreased induced by miR-143-3p overexpression or MAPK7 knockdown in U2OS cells. The results of dual luciferase reporter assay indicated that miR-143-3p interacted with MAPK7. Furthermore, overexpression of MAPK7 could reverse the inhibitory effects on cell proliferation, migration and invasion in U2OS cells induced by miR-143-3p mimics. Conclusion: miR-143-3p could inhibit proliferation, migration and invasion of U2OS cells by targeting MAPK7.

Anterior decompression and fusion versus laminoplasty for cervical myelopathy due to ossification of posterior longitudinal ligament: A meta-analysis.

BACKGROUND: Both anterior decompression and fusion (ADF) and laminoplasty (LAMP) are frequently used for the treatment of cervical myelopathy due to ossification of the posterior longitudinal ligament (OPLL). However, some controversies still remained in surgical options. We investigated whether ADF had better neurological outcome than LAMP in the treatment of cervical myelopathy due to OPLL. Secondary outcomes included operation time, blood loss, rate of complication and reoperation. METHODS: PubMed, EMBASE and the Cochrane Register of Controlled Trials database were searched to identify potential clinical studies compared ADF with LAMP for treatment of cervical myelopathy owing to OPLL. We also manually searched the reference lists of articles and reviews for possible relevant studies. Quality assessment was performed according to Cochrane Handbook and meta-analysis was conducted using Stata 12.0 software. RESULTS: Nine studies involving 712 patients were finally included in this analysis. Compared with LAMP, ADF was associated with an increase of the Japanese Orthopaedic Association (JOA) score (WMD = 1.86, 95% CI 0.43 to 3.29, P = .011) and recovery JOA score at final follow-up (WMD = 30.94, 95% CI 20.56 to 41.33, P = .000). And, ADF was associated with a decrease of the late neurologic deterioration than LAMP group (RR = 0.34, 95% CI 0.12 to 0.92, P = .003). However, ADF was associated with an increase of the postoperative cervical lordosis (WMD = 4.47, 95% CI 1.58 to 7.36, P = .002) than LAMP. There was no significant difference between the complication, reoperation rate (P > .05). What's more, ADF was associated with an increase of the operation time than LAMP (P < .05). CONCLUSIONS: ADF yields better neurological improvement, but higher cervical lordosis and longer operation time compared with LAMP for cervical myelopathy caused by OPLL. No significant difference was found in the complication and re-operation rate.

Synthesis of vertically aligned CaTiO3 nanotubes with simple hydrothermal method and its photoelectrochemical property.

Perovskite-type oxides have become the hotspots of functional materials due to their various excellent performances. As a typical material with a perovskite structure, CaTiO3 (CTO) possesses a similar band gap to TiO2 with less defects and recombination centers, which makes it a promising alternative material to TiO2. In particular, the CTO nanotube structure has a large specific surface area and unique photochemical and electron-transport properties, and these advantages further expand its application range. In this paper, a highly ordered and vertically aligned CTO nanotube array was successfully synthesized by a simple hydrothermal method with TiO2 nanotube (TNT) arrays as the precursor. It was found that the CTO nanotube had a higher optical absorption ability (3.4 eV), photovoltage (500 mV) and photocurrent density (0.004 A cm-1) under ultraviolet irradiation, compared to the TNT (350 mV and 0.0036 A cm-1). At the same time, the electrochemical impedance spectroscopy, Mott-Schottky and stability tests indicate that the CTO nanotube might be a promising alternative choice as the photoelectric material for a TNT.

Effect of arthroscopic internal fixation and fusion for the treatment of patients with advanced ankle arthritis and the influence of AOFAS and VAS score / 中国内镜杂志

Objective To study the effect of arthroscopic internal fixation combined with arthrodesis on patients with advanced ankle arthritis and American Orthopedic Ankle Association Scoring System (AOFAS) and visual analogue scale (VAS). Methods 84 patients with advanced ankle arthritis from January 2012 to January 2015 were randomly divided into experimental group (42 cases) and control group (42 cases) by random number method. The patients in the control group were treated with traditional open ankle arthrodesis, the experimental group under the arthroscopic assisted internal fixation joint fusion. Then compare the time of surgery, intraoperative blood loss, postoperative hospitalization time and complication. The follow-up period was 12 to 36 months. Used the AOFAS score system to evaluate the curative effect. Use VAS to evaluate the degree of ankle pain. Results The operation time and intraoperative blood loss were significantly lower in the experimental group than that in the control group (P < 0.05). The postoperative hospital stay and the time of joint fusion were lower in the experimental group than that in the control group (P < 0.05). The incidence of complication (9.52%) in the experimental group was significantly lower than that in the control group (25.57%) (P < 0.05). The results of follow-up showed that the VAS and AOFAS scores of the experimental group were better than those in the control group (P < 0.05). Conclusion The procedure of arthroscopic endoscopic fusion is short, the bleeding rate is low, the incidence of complications is low, the healing rate is high, and the follow-up effect is accurate. It is suitable for clinical use.