Efficacy and safety of immune checkpoint inhibitors combined with anti-VEGF therapy in the treatment of unresectable or advanced liver cancer: a systematic review.

OBJECTIVE: This study aimed to evaluate the clinical effects and safety of immune checkpoint inhibitors (ICIs) combined with anti-VEGF therapy for the treatment of unresectable or advanced liver cancer. METHOD: Related databases were searched from inception to December 2022 to identify randomized controlled studies and clinical trials that evaluated the combination of ICIs and anti-VEGF therapy for the treatment of unresectable liver cancer. The outcome index was extracted and analyzed by RevMan5.4.ResultsA total of 8 clinical trials were included. In terms of efficacy, the intervention group had longer OS and PFS for unresectable or advanced liver cancer than the control group. In terms of safety, (1) Adverse events of all grades showed that the combination treatment led to significantly higher risks of urinary system disorders, cardiovascular system disorder, blood system disorders and liver dysfunction than the control treatment. Compared with monotherapy, the combination treatment led to lower risks of gastrointestinal disorders. (2) Adverse events above grade 3 showed that, compared with the control treatment, the combination treatment led to significantly higher risks of urinary system disorders, blood systeam disorders, cardiovascular system disorders and liver dysfunction. Additionally, compared with monotherapy, the combination treatment led to significantly lower risks of gastrointestinal disorders. CONCLUSIONS: ICIs combined with anti-VEGF therapy exerts significant clinical effects in patients with unresectable or advanced liver cancer, can prolong the survival of these patients and can improve their quality of life. However, clinical attention should be given to the occurrence of adverse reactions.

Comparison of Efficacy and Safety Between Immunotherapy and Docetaxel Monotherapy in NSCLC Patients.

Objective: Meta analysis was used to compare the efficacy and safety of immune checkpoint inhibitor and docetaxel in the treatment of non-small cell lung cancer. Methods: CNKI, CBM, PubMed, EMBASE, Cochrane Library, web of science and other databases were searched by computer, and the randomized controlled trials of immune checkpoint inhibitors and docetaxel in the treatment of NSCLC published as of February 2022 were collected. Two researchers searched independently, screened the literature and extracted the data according to the nanodischarge criteria, and used Revman5.4. The included studies were statistically analyzed, and publication bias was analyzed with Egger test in Stata12. Results: A total of 8 RCTs were included, including 2444 cases treated with immune checkpoint inhibitors and 2097 cases treated with docetaxel. Compared with docetaxel, the overall survival (HR = 1.40, 95%CI: 1.30-1.50, P < 0.00001) and progression free survival (HR = 1.22, 95%CI: 1.13-1.32, P < 0.00001) of NSCLC treated with ICIs were longer. The risk ratio of any grade of adverse reactions (HR = 0.41, 95%CI: 0.32-0.52, P < 0.00001) and above grade III adverse reactions (HR = 0.27, 95%CI: 0.18-0.41, P < 0.00001) in the treatment of NSCLC with ICIs was lower. There was no publication bias in Egger test. Conclusion: Compared with docetaxel, immune checkpoint inhibitor treatment can improve the clinical efficacy of NSCLC patients and has a lower incidence of adverse reactions. This treatment may be a promising treatment for NSCLC patients.

Efficacy and Safety Evaluation of Sintilimab for Cancer Treatment: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Objective: Meta analysis was used to explore the efficacy and safety of Sintilimab in the treatment of cancer. Methods: The databases of CNKI, VIP, Wanfang Data, PubMed, ScienceDirect, the Cochrane Library and EMBASE were searched by computer to collect the randomized controlled trials published as of March 2022. The retrieval work was completed by two researchers alone. They screened the literature and extracted the data according to the nanodischarge standard, using Revman 5.4 software. The included studies were statistically analyzed. Results: Six RCTs were included in this study, including 1,048 cases of Sintilimab and 711 cases of other anticancer drugs. Compared with the control group, the overall survival (HR = 1.64, 95% CI: 1.35-1.99, p < 0.00001) and progression free survival (HR = 1.89, 95% CI: 1.59-2.25, p < 0.00001) of cancer treated with Sintilimab were longer and more effective. Moreover, the risk ratio of any grade of adverse reactions (HR = 0.87, 95% CI: 0.74-1.03, p = 0.11) and above grade III adverse reactions (HR = 0.84, 95% CI: 0.67-1.06, p = 0.14) in the treatment of cancer with Sintilimab was lower and the safety was better. Conclusion: Compared with non-Sintilimab group, Sintilimab treatment can improve the clinical efficacy of tumor patients and has a lower incidence of adverse reactions. This treatment may be a promising treatment for cancer patients.

Identification and Verification of Potential Therapeutic Target Genes in Berberine-Treated Zucker Diabetic Fatty Rats through Bioinformatics Analysis.

BACKGROUND: Berberine is used to treat diabetes and dyslipidemia. However, the effect of berberine on specific diabetes treatment targets is unknown. In the current study, we investigated the effect of berberine on the random plasma glucose, glycated hemoglobin (HbA1C), AST, ALT, BUN and CREA levels of Zucker diabetic fatty (ZDF) rats, and we identified and verified the importance of potential therapeutic target genes to provide molecular information for further investigation of the mechanisms underlying the anti-diabetic effects of berberine. METHODS: ZDF rats were randomly divided into control (Con), diabetic (DM) and berberine-treated (300 mg⋅kg-1, BBR) groups. After the ZDF rats were treated with BBR for 12 weeks, its effect on the random plasma glucose and HbA1C levels was evaluated. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), CREA and OGTT were measured from blood, respectively. The levels of gene expression in liver samples were analyzed using an Agilent rat gene expression 4x44K microarray. The differentially expressed genes (DEGs) were screened as those with log2 (Con vs DM) ≥ 1 and log2 (BBR vs DM) ≥ 1 expression levels, which were the genes with up-regulated expression, and those with log2 (Con vs DM) ≤ -1 and log2 (BBR vs DM) ≤ -1 expression levels, which were the genes with down-regulated expression; the changes in gene expression were considered significant at P<0.05. The functions of the DEGs were determined using gene ontology (GO) and pathway analysis. Furthermore, a protein-protein interaction (PPI) network was constructed using STRING and Cytoscape software. The expression levels of the key node genes in the livers of the ZDF rats were also analyzed using qRT-PCR. RESULTS: We found that 12 weeks of berberine treatment significantly decreased the random plasma glucose, HbA1C levels and improved glucose tolerance. There was a tendency for berberine to reduce AST, ALT, BUN except increase CREA levels. In the livers of the BBR group, we found 154 DEGs, including 91 genes with up-regulated expression and 63 genes with down-regulated expression. In addition, GO enrichment analysis showed significant enrichment of the DEGs in the following categories: metabolic process, localization, cellular process, biological regulation and response to stimulus process. After the gene screening, KEGG pathway analysis showed that the target genes are involved in multiple pathways, including the lysine degradation, glycosaminoglycan biosynthesis-chondroitin sulfate/dermatan sulfate and pyruvate metabolism pathways. By combining the results of PPI network and KEGG pathway analyses, we identified seven key node genes. The qRT-PCR results confirmed that the expression of the RHOA, MAPK4 and DLAT genes was significantly down-regulated compared with the levels in DM group, whereas the expression of the SgK494, DOT1L, SETD2 and ME3 genes was significantly up-regulated in the BBR group. CONCLUSION: Berberine can significantly improve glucose metabolism and has a protective effects of liver and kidney function in ZDF rats. The qRT-PCR results for the crucial DEGs validated the microarray results. These results suggested that the RHOA, MAPK4, SGK494, DOT1L, SETD2, ME3 and DLAT genes are potential therapeutic target genes for the treatment of diabetes.

[Protective effect of ß-asarone on PC12 cells injury induced by Aß1₋42 astrocytic activation].

This study was aimed to investigate the protective effect and mechanism of ß-asarone on PC12 cells injury induced byAß1₋42 activated astrocytes, and provide experimental basis for ß-asarone application in the prevention and control of Alzheimer's disease (AD). Firstly, RA-h and PC12 cells were co-cultured in the special transwell chamber, and the Real time cell analysis (RTCA) system was used to real-time observe its effect on PC12 cells survival rate in the co-culture system after astrocytes injury induced by Aß1₋42. The best intervention time of ß-asarone was selected according to the survival curve and parameters generated automatically. ß-asarone with different concentrations was used for intervention on astrocytes, then the changes of PC12 cells survival rate in the co-culture system were observed. Secondly, MTT assay was used to detect the effect of Aß1₋42 on PC12 cells survival rate as well as the intervention effect of ß-asarone, and verify the testing results of RTCA. The levels of IL-1ß, TNF-α and BDNF in culture media of the lower chamber were detected by ELISA. The NF-κB activity and phosphorylation levels of ERK, p38 and JNK were detected by Western blot. Results showed that ß-asarone (55.5 mg•L⁻¹) could significantly slowdown the decline of PC12 cells survival rate caused by Aß1₋42-induced RA-h activation (P<0.01), significantly reduce the levels of IL-1ß, TNF-α and the phosphorylation levels of ERK, p38 and JNK in culture media of the lower chamber (P<0.01). ß-asarone(166.7 mg•L⁻¹) could promote the release of BDNF in culture media of the lower chamber(P<0.05). These results indicated that Aß1₋42 could induce RA-h activation and its release of IL-1ß, TNF-α and other inflammatory factors to aggravate the PC12 cells injury; ß-asarone could reduce the levels of IL-1ß, TNF-α, promote the release of BDNF, and inhibit the NF-κB activity as well as phosphorylation levels of ERK, p38 and JNK protein in PC12 cells.