PurposeTo investigate the efficacy and safety of transarterial chemoembolization (TACE) combined with lenvatinib plus PD-1 inhibitor (TACE-L-P) versus TACE combined with lenvatinib (TACE-L) for patients with advanced hepatocellular carcinoma (HCC).Materials and MethodsData of advanced HCC patients treated with TACE-L-P (TACE-L-P group) or TACE-L (TACE-L group) from January 2019 to December 2020 were prospectively collected and retrospectively analyzed. The differences in overall survival (OS), progression-free survival (PFS), tumor responses (based on modified Response Evaluation Criteria in Solid Tumors) and adverse events (AEs) were compared between the two groups. Potential factors affecting OS and PFS were determined.ResultsA total of 81 patients were included in this study. Among them, 41 received TACE-L-P and 40 received TACE-L. The patients in TACE-L-P group had prolonged OS (median, 16.9 vs. 12.1 months, P=0.009), longer PFS (median, 7.3 vs. 4.0 months, P=0.002) and higher objective response rate (56.1% vs. 32.5%, P=0.033) and disease control rate (85.4% vs. 62.5%, P=0.019) than those in TACE-L group. Multivariate analyses revealed that the treatment option of TACE-L, main portal vein invasion and extrahepatic metastasis were the independent risk factors for OS, while TACE-L and extrahepatic metastasis were the independent risk factors for PFS. In subgroup analyses, a superior survival benefit was achieved with TACE-L-P in patients with extrahepatic metastasis or tumor number >3 but not in those with main portal vein invasion. The incidence and severity of AEs in TACE-L-P group were comparable to those in TACE-L group (any grade, 92.7% vs. 95.0%, P=1.000; grade 3, 36.6% vs. 32.5%, P=0.699).ConclusionTACE-L-P significantly improved survival over TACE-L with an acceptable safety profile in advanced HCC patients, especially those with extrahepatic metastasis or tumor number >3 but without main portal vein invasion.

No abstract

Liver fibrosis currently represents a global health problem without effective pharmacotherapeutic strategies. The clinical translation of polydatin, a promising natural anti‐fibrotic drug candidate with broad anti‐inflammatory and antioxidant capabilities, remains a major challenge due to its limited water solubility and tissue absorption. Herein, a polydatin‐loaded micelle (PD‐MC) based on reactive oxygen species (ROS) and pH dual‐sensitive block polymer PEG‐P(PBEM‐co‐DPA) is developed. The micelle exerts great potential in improving the biocompatibility of polydatin and shows highly efficient liver‐targeted drug release in response to the fibrotic microenvironment. Both in vitro and in vivo studies demonstrate that PD‐MC can significantly suppress inflammatory response and oxidative stress, reduce hepatocyte apoptosis, and avert activation of macrophages and hepatic stellate cells. More excitingly, the blank micelle itself promotes the hepatic ROS consumption at the pathologic site to provide anti‐inflammatory benefits. These favorable therapeutic virtues of targeting multiple cell types endow PD‐MC with remarkable efficacy with minimal side effects in liver fibrosis treatment. Thus, PD‐MC holds great potential to push forward the clinical application of polydatin in pharmacotherapeutic approaches against liver fibrosis.

Purpose To evaluate the safety and efficacy of regorafenib combined with anti-PD-1 antibody sintilimab (rego-sintilimab) as a second-line treatment for advanced hepatocellular carcinoma (HCC). Methods This multicenter retrospective study evaluated consecutive patients with advanced HCC who received rego-sintilimab (rego-sintilimab group) or regorafenib alone (regorafenib group) as a second-line treatment from January 2019 to December 2020. Adverse events, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were compared between the two groups. Uni- and multi-variable analyses of prognostic factors for OS and PFS were performed using Cox proportional hazard regression models. Results In total, 113 patients were included in the study: 58 received rego-sintilimab and 55 received regorafenib. The rego-sintilimab group had higher ORR (36.2% vs 16.4%, P = 0.017), longer PFS (median 5.6 vs 4.0 months; P = 0.045), and better OS (median 13.4 vs 9.9 months; P = 0.023) than the regorafenib group. Regorafenib alone, Child-Pugh B, and neutrophil-to-lymphocyte ratio (NLR) > 3.6 were independent prognostic factors for poor OS. Regorafenib alone, α-fetoprotein level, and NLR > 3.6 were independent prognostic factors for poor PFS. Subgroup analyses showed a survival benefit of rego-sintilimab in patients with NLR ≤ 3.6 (hazard ratio 0.518 [95% CI, 0.257–0.955]) but not in those with NLR > 3.6 (0.852 [0.461–1.572]); P = 0.002 for interaction. The difference in incidence of grade 3/4 adverse events between the two groups was not statistically significant (39.7% vs 30.9%; P = 0.331). Conclusion Rego-sintilimab was tolerated and led to better OS than regorafenib as a second-line treatment for advanced HCC patients, especially in those with NLR ≤ 3.6.

Background:The application of chimeric antigen receptor (CAR) NK cells in solid tumors is hindered by lack of tumor-specific targets and inefficient CAR NK cell efficacy. It has been reported that mesothelin (MSLN) may be an ideal immunotherapy target for gastric cancer. However, the feasibility of using anti-MSLN CAR NK cells to treat gastric cancer remains to be studied. Methods: MSLN expression in primary human gastric cancer, normal tissues and cell lines were detected. MSLN and CD19 targeted CAR NK-92 (MSLN-and CD19-CAR NK) cells were constructed, purified and verified. N87, MKN-28, AGS and Huh-7 cells expressing the GFP and luciferase genes were transduced. Celland patient-derived xenograft (PDX) were established via NSG mice. The ability of MSLN-CAR NK cells to kill MSLN-positive gastric cancer cells were evaluated in vitro and in vivo. Results: MSLN-CAR NK cells can specifically kill MSLN-positive gastric cancer cells (N87, MKN-28 and AGS), rather than MSLN negative cell (Huh-7), in vitro. Moreover, compared with parental NK-92 cells and CD19-CAR NK cells, stronger cytokine secretions were secreted in MSLN-CAR NK cells cocultured with N87, MKN-28 and AGS. Furthermore, MSLN-CAR NK cells can effectively eliminate gastric cancer cells in both subcutaneous and intraperitoneal tumor models. They could also significantly prolong the survival of intraperitoneally tumor-bearing mice. More importantly, the potent antitumor effect and considerable NK cell infiltration were observed in the patient-derived xenograft treated with MSLN-CAR NK cells, which further warranted the therapeutic effects of MSLN-CAR NK cells to treat gastric cancer. Conclusion:These results demonstrate that MSLN-CAR NK cells possess strong antitumor activity and represent a promising therapeutic approach to gastric cancer.

With the increasing challenge of energy, resource, and environment, it is highly desired to develop renewable energy and corresponding efficient energy storage technologies basing on reproducible materials. Recently, using biomass and biotechnology to prepare electrode material for energy storage devices is gaining growing attention. Here, we use biomass, celery, as a material source and developed a new way to prepare highly qualified graphitized porous carbon. Besides, instead of direct carbonization, the celery is first freeze-dried to protect the original elements and structure of biomass. Furthermore, to sculpture more nanoscale pores in the produced material, the following carbonization process is also greatly modified by investigating proper carbonization temperature and time. Therefore, the interconnected hierarchical porous structure can be formed based on the protected original pores with size of micrometers and the newly formed pores with size of nanometers. The resulted interconnected hierarchical porous carbon is used to prepare supercapacitor electrode and exhibit excellent energy storage properties. Without any extra activating or doping process, the specific capacitance of the resulted electrode reached 350.0 F g −1 at 1 A g −1 , which is 5.28 times of that of directly carbonized material. And the power density reached 8.0 kW kg −1 with the energy density maintaining 16.3 Wh kg −1 . K E Y W O R D Sbiomass, eco-friendly, freeze-drying, porous carbon, supercapacitor | INTRODUCTIONSupercapacitors have attracted great attention because of their large specific capacitance(C s ), high power density, and excellent cycling stability. [1][2][3] The performances of supercapacitor mainly depend on the structure and property of electrode materials, including specific surface area (SSA), conductivity, structure stability, and electrochemical reaction activity. 4,5 At present, most of the researches have been focused on introducing metal oxides, such as RuO 2 , Fe 3 O 4 , and MnO 2 , conductive polymer, carbon nanomaterials, such as carbon nanotubes, graphene, porous carbon, and their composites. 1,[6][7][8][9][10][11][12] For example, the porous and hollow carbon spheres have been widely investigated as electrodes materials because of their high SSA, excellent structural stability, and good conductivity, Yingying Ma and Jinyong Tian contributed equally to this work.

The prognostic nutritional index (PNI) has been applied in acute myocardial infarction (AMI) recently.However, the application of PNI in AMI needs verification. This was a prospective cohort study. Patients diagnosed with AMI were enrolled. PNI was calculated as (serum albumin (SA in g/L)) + (5 × total lymphocyte count (TLC) × 109/L). Modified PNI (mPNI) was analyzed by logistic regression analysis to reset the proportion of SA and TLC. The primary outcome was all-cause death. A total of 598 patients were enrolled; 73 patients died during follow-up. The coefficient of SA and TLC in the mPNI formula was approximately 2:1. The area under the receiver operating characteristic curve of SA, TLC, PNI, mPNI and GRACE in predicting death for patients with AMI was 0.718, 0.540, 0.636, 0.721 and 0.825, respectively. Net reclassification improvement (NRI) between PNI and mPNI was 0.230 (p < 0.001). Integrated discrimination improvement (IDI) was 0.042 (p = 0.001). Decision curve analysis revealed that mPNI had better prognostic value for patients with AMI than PNI; however, it was not superior to SA. Thus, PNI may not a reliable prognostic predictor of AMI; after resetting the formula, the value of PNI in predicting prognosis of AMI is almost entirely due to SA.

No abstract