Efficacy and safety of PD-1/PD-L1 inhibitor-based immune combination therapy versus sorafenib in the treatment of advanced hepatocellular carcinoma: a meta-analysis

ObjectiveTo systematically evaluate the safety and efficacy of PD-1/PD-L1 inhibitor-based immunotherapy (hereafter referred to as “combination immunotherapy”) compared with that of sorafenib in the treatment of hepatocellular carcinoma (HCC).MethodsDatabases such as PubMed, Embase, and the Cochrane Library were searched from the date of their establishment to September 2023 to identify randomized controlled trials (RCTs) of combination immunotherapy versus sorafenib for the treatment of advanced HCC. Two reviewers independently evaluated the quality of the included studies, extracted the data, and cross-checked the information. The meta-analysis was performed using RevMan 5.3 software.ResultsA total of 5 RCTs were included. The results of the meta-analysis showed the following: (1) Effectiveness. Compared to sorafenib, combination immunotherapy significantly improved overall survival (OS, HR = 0.69, 95% CI: 0.58 ~ 0.82, p < 0.01) and progression-free survival (PFS, HR = 0.62, 95% CI: 0.50 ~ 0.78, p < 0.001) in patients with advanced HCC. (2) Safety. Both groups had comparatively high incidences of adverse events (AEs), but the difference in any treatment-related adverse events was not significant between the two arms (OR = 0.98, 95% CI: 0.95 ~ 1.02, p = 0.34). The difference in the incidence of grade 1–2 adverse reactions was statistically significant (OR = 0.66, 95% CI = 0.49–0.90, p = 0.001). There were no differences in grade 3/4 TRAEs or grade 5 TRAEs (OR = 1.46, 95% CI = 0.78 ~ 2.71, p = 0.24; OR = 1.08, 95% CI = 0.73 ~ 1.58, p = 0.71).ConclusionCombined immunotherapy can significantly prolong the OS and PFS of patients with advanced HCC without increasing the incidence of adverse effects in terms of safety, but the incidence of AEs in different systems is different

Sestrin2 Modulates AMPK Subunit Expression and Its Response to Ionizing Radiation in Breast Cancer Cells

Background: The sestrin family of stress-responsive genes (SESN1-3) are suggested to be involved in regulation of metabolism and aging through modulation of the AMPK-mTOR pathway. AMP-activated protein kinase (AMPK) is an effector of the tumour suppressor LKB1, which regulates energy homeostasis, cell polarity, and the cell cycle. SESN1/2 can interact directly with AMPK in response to stress to maintain genomic integrity and suppress tumorigenesis. Ionizing radiation (IR), a widely used cancer therapy, is known to increase sestrin expression, and acutely activate AMPK. However, the regulation of AMPK expression by sestrins in response to IR has not been studied in depth. Methods and Findings: Through immunoprecipitation we observed that SESN2 directly interacted with the AMPKa1b1c1 trimer and its upstream regulator LKB1 in MCF7 breast cancer cells. SESN2 overexpression was achieved using a Flag-tagged SESN2 expression vector or a stably-integrated tetracycline-inducible system, which also increased AMPKa1 and AMPKb1 subunit phosphorylation, and co-localized with phosphorylated AMPKa-Thr127 in the cytoplasm. Furthermore, enhanced SESN2 expression increased protein levels of LKB1 and AMPKa1b1c1, as well as mRNA levels of LKB1, AMPKa1, and AMPKb1. Treatment of MCF7 cells with IR elevated AMPK expression and activity, but this effect was attenuated in the presence of SESN2 siRNA. In addition, elevated SESN2 inhibited IR-induced mTOR signalling and sensitized MCF7 cells to IR through an AMPK-dependent mechanism

Sestrin2 promotes Unc‐51‐like kinase 1 mediated phosphorylation of p62/sequestosome‐1

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108630/1/febs12905.pd

Preparation and characterization of superhydrophobic surfaces based on hexamethyldisilazane-modified nanoporous alumina

Superhydrophobic nanoporous anodic aluminum oxide (alumina) surfaces were prepared using treatment with vapor-phase hexamethyldisilazane (HMDS). Nanoporous alumina substrates were first made using a two-step anodization process. Subsequently, a repeated modification procedure was employed for efficient incorporation of the terminal methyl groups of HMDS to the alumina surface. Morphology of the surfaces was characterized by scanning electron microscopy, showing hexagonally ordered circular nanopores with approximately 250 nm in diameter and 300 nm of interpore distances. Fourier transform infrared spectroscopy-attenuated total reflectance analysis showed the presence of chemically bound methyl groups on the HMDS-modified nanoporous alumina surfaces. Wetting properties of these surfaces were characterized by measurements of the water contact angle which was found to reach 153.2 ± 2°. The contact angle values on HMDS-modified nanoporous alumina surfaces were found to be significantly larger than the average water contact angle of 82.9 ± 3° on smooth thin film alumina surfaces that underwent the same HMDS modification steps. The difference between the two cases was explained by the Cassie-Baxter theory of rough surface wetting

Clinical application of indocyanine green fluorescence navigation technique in laparoscopic common bile duct exploration for complex hepatolithiasis

Abstract Background This study investigated the clinical application of the indocyanine green (ICG) fluorescence navigation technique in bile duct identification during laparoscopic common bile duct exploration (LCBDE) for complex hepatolithiasis. Methods Eighty patients with complex hepatolithiasis were admitted to our department between January 2022 and June 2023 and randomly divided into control and observation groups. The control group underwent conventional LCBDE, while the observation group underwent LCBDE guided by ICG fluorescence. Results Intraoperatively, the observation group had shorter operation and search times for the common bile duct (CBD), as well as reduced intraoperative blood loss and fewer complications, such as conversion to laparotomy and various injuries (gastroduodenal, colon, pancreatic, and vascular) than the control group, with statistical significance (P < 0.05). Postoperatively, the observation group had lower rates of postoperative bile leakage, abdominal infection, postoperative hemorrhage, and residual stone than the control group. Additionally, the observation group demonstrated significantly shorter times for resuming flatus, removal of the abdominal drainage tube, and hospitalization than the control group, with statistical significance (P < 0.05). Conclusion ICG fluorescence navigation technology effectively visualizes the bile duct, improves its identification rate, shortens the operation time, prevents biliary tract injury, and reduces the occurrence of complications