Evaluation of the efficacy of aparatinib and carrilizumab combined with transcatheter arterial chemoembolization in the treatment of primary hepatocellular carcinoma.

OBJECTIVE: The study aimed to analyze the efficacy of aparatinib and carrilizumab combined with transcatheter arterial chemoembolization (TACE) in the treatment of primary hepatocellular carcinoma (HCC). PATIENTS AND METHODS: A total of 150 patients with primary HCC admitted to our hospital from March 1, 2019, to March 1, 2022 was chosen and randomized as the control and treatment group. The control group went through TACE treatment, and the treatment group experienced apatinib + karilizumab + TACE treatment. The near and long-term efficacy of the two groups were compared. The total survival time (OS), time to progression (TTP), and hospital costs were compared between the two groups. Fasting venous blood was collected before and one month after treatment in the two groups, and liver and kidney functions were tested using automatic biochemical analyzer. The levels of CD3+, CD4+ and CD8+ were detected by flow cytometry, and CD4+/CD8+ was calculated. The levels of cysteinyl aspartate specific protease-8 (Caspase-8), vascular endothelial growth factor (VEGF) and alpha fetoprotein (AFP) were detected by enzyme-linked immunosorbent assay (ELISA). The patients' conditions were closely observed and the adverse reaction rates of diarrhea, hand foot syndrome, bone marrow suppression, proteinuria, fever and pain were compared between the two groups. RESULTS: The disease control rate (DCR) of short-term treatment in the treatment group was 97.33%, which was much higher than 88.00% in the control group. The survival ratios of the treatment group in September and December were 65.33% and 42.67% respectively, which were also much higher than 48.00% and 20.00% in the control group (p < 0.05). The TTP and OS of patients in the treatment group were significantly longer than those in the control group (p < 0.05), and the hospital expenses were significantly higher than those in the control group (p < 0.05). The levels of liver function indicators such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) were largely decreased in both groups after treatment, and more significant difference was detected in the treatment group (p < 0.05). Renal function between the two groups had no significant difference after treatment (p > 0.05). After treatment, the levels AFP and VEGF were strongly decreased and the level of Caspase-8 was markedly increased in both groups, and the treatment group had lower levels of AFP and VEGF and higher level of Caspase-8 than the control group (p < 0.05). The CD3+ and CD4+/CD8+ levels in two groups were dramatically elevated after treatment, and the treatment group had much higher CD3+ and CD4+/CD8+ levels than the control group (p < 0.05). There was no statistically significant difference in the rates of adverse reactions such as diarrhea, hand-foot syndrome, bone marrow suppression, proteinuria, fever, and pain between the two groups (p > 0.05). CONCLUSIONS: The combination of apatinib and carrilizumab with TACE had better near- and long-term efficacy in the treatment of primary HCC by effectively inhibiting tumor vascular regeneration, inducing tumor cell apoptosis, and improving patients' liver function and immune function with higher safety, which could be widely used in clinical practice.

Stent pretreatment for internal carotid artery exposed to necrotic lesions in nasopharyngeal carcinoma.

BACKGROUND: Post radiation nasopharyngeal necrosis (PRNN) invading the internal carotid artery (ICA) contributes to the death of 69.2-72.7% of PRNN patients. ICA occlusion is an effective treatment to avoid fatal bleeding, while some patients are intolerant. We present a novel method that allows for these patients without interrupting blood flow through the ICA. METHODOLOGY: This study enrolled patients with PRNN-invaded ICA who were not suitable for ICA occlusion from April 2020 to November 2022. ICA stent pretreatment was performed in the 36 patients and followed the endoscopic nasopharyngectomy (ENPG) or conservative treatment for PRNN. We report the survival outcome and incidence of complications after stent implantation and compare the survival outcomes of ENPG and conservative treatment for PRNN followed by stent implantation. RESULTS: ICA stent pretreatment was performed in the 36 enrolled patients, among which 14 underwent ENPG, and 22 received conservative treatment. 27.8% patients died after a median follow-up of 15 months. The Kaplan-Meier estimates of overall survival were higher in the ENPG group than in the conservative treatment group. Karnofsky performance status (KPS) was significantly higher in the ENPG group than in the non-ENPG group. CONCLUSIONS: The innovative application of ICA stents is a promising treatment to improve outcomes in patients with PRNN invading the ICA who are unsuitable for ICA embolization, especially when followed by endoscopic surgery. However, methods to avoid postoperative cerebral ischemia and nasopharyngeal hemorrhage still require further study.

Tacrolimus alleviates Ox-LDL damage through inducing vascular endothelial autophagy.

OBJECTIVE: To study the protective effect of tacrolimus on vascular endothelium injured by oxidized low-density lipoprotein (ox-LDL) and its mechanism. MATERIALS AND METHODS: Human umbilical vein endothelial cells were used as objects of study, and divided into control group, tacrolimus group and autophagy inhibition group. Control group received no ox-LDL, while tacrolimus group and autophagy inhibition group were treated with ox-LDL (100 µg/mL) for 3 h. Tacrolimus group was pre-treated with tacrolimus (100 nM) for 0.5 h, and the autophagy inhibition group was pre-treated with 3-methyladenine (3-MA) (10 mM) and tacrolimus (100 nM) for 0.5 h. The cell viability was detected via cell counting kit 8 (CCK8) assay, the cell apoptosis ratio was detected via flow cytometry and Hoechst staining, and the releases of superoxide dismutase (SOD), reactive oxygen species (ROS) and other cytokines were detected using the kit. Moreover, the autophagy level was detected via LC3 fluorescence staining, and the autophagy- and apoptosis-related molecules were detected via polymerase chain reaction (PCR) and Western blotting. RESULTS: In the absence of ox-LDL, neither tacrolimus nor 3-MA had an effect on the cell viability. After the addition of ox-LDL, the cell viability was significantly decreased, whereas tacrolimus could alleviate such damage to cells. Flow cytometry and Hoechst staining proved that tacrolimus could reduce the proportion of apoptotic cells induced by ox-LDL, while PCR and Western blotting confirmed the decreased expression of apoptosis-related proteins in tacrolimus group. 3-MA could up-regulate the ratio of apoptosis and the expressions of apoptosis-related proteins. The detection of SOD and ROS showed that ox-LDL could induce the cell oxidative stress injury, whereas tacrolimus could inhibit such an effect. The addition of 3-MA inhibited the effect of tacrolimus. Besides, LC3 fluorescence staining, PCR and Western blotting revealed that ox-LDL could induce the autophagy, while tacrolimus could enhance the autophagy. After the addition of 3-MA, the intracellular autophagy level was significantly inhibited. CONCLUSIONS: Tacrolimus protects vascular endothelial cells from ox-LDL damage through inducing the autophagy.