Objective To systematically review the risk of hepatotoxicity caused by vascular endothelial growth factor receptor tyrosine kinase inhibitor(VEGFR-TKI)in clinical practice.Methods PubMed,Embase,CENTRAL,CNKI,WanFang Data and SinoMed databases were electronically searched to collect randomized controlled trials(RCTs)of hepatotoxicity caused by VEGFR-TKI from inception to February 28,2024.Two reviewers independently screened the literature,extracted data and assessed the risk of bias of the included studies.Network Meta-analysis was then performed by Stata 15.0 software.Results A total of 32 RCTs were included,involving 9 kinds of VEGFR-TKI and 12 949 patients.The results of network Meta-analysis showed that compared with placebo,except for a non-significant increase in the risk of alanine aminotransferase(ALT)elevation due to anlotinib,a non-significant increase in the risk of aspartate aminotransferase(AST)elevation due to anlotinib and vandetanib,and a non-significant increase in the risk of total bilirubin(TBIL)elevation due to anlotinib,vandetanib,sorafenib,and lenvatinib,the risks of ALT,AST,and TBIL elevation due to the rest of the VEGFR-TKI were all significantly increased;Pazopanib and apatinib had remarkable increase in the risk of high-grade ALT elevation.Pazopanib,apatinib,sunitinib,sorafenib,and cabozantinib had a remarkable increase in the risk of high-grade AST elevation.Regorafenib had a remarkable increase in the risk of high-grade TBIL elevation.Conclusion VEGFR-TKI can increase the risk of hepatotoxicity in patients,the risks of elevated indicators caused by different VEGFR-TKI are not the same.

Objective To systematically review the risk of hepatotoxicity caused by vascular endothelial growth factor receptor tyrosine kinase inhibitor(VEGFR-TKI)in clinical practice.Methods PubMed,Embase,CENTRAL,CNKI,WanFang Data and SinoMed databases were electronically searched to collect randomized controlled trials(RCTs)of hepatotoxicity caused by VEGFR-TKI from inception to February 28,2024.Two reviewers independently screened the literature,extracted data and assessed the risk of bias of the included studies.Network Meta-analysis was then performed by Stata 15.0 software.Results A total of 32 RCTs were included,involving 9 kinds of VEGFR-TKI and 12 949 patients.The results of network Meta-analysis showed that compared with placebo,except for a non-significant increase in the risk of alanine aminotransferase(ALT)elevation due to anlotinib,a non-significant increase in the risk of aspartate aminotransferase(AST)elevation due to anlotinib and vandetanib,and a non-significant increase in the risk of total bilirubin(TBIL)elevation due to anlotinib,vandetanib,sorafenib,and lenvatinib,the risks of ALT,AST,and TBIL elevation due to the rest of the VEGFR-TKI were all significantly increased;Pazopanib and apatinib had remarkable increase in the risk of high-grade ALT elevation.Pazopanib,apatinib,sunitinib,sorafenib,and cabozantinib had a remarkable increase in the risk of high-grade AST elevation.Regorafenib had a remarkable increase in the risk of high-grade TBIL elevation.Conclusion VEGFR-TKI can increase the risk of hepatotoxicity in patients,the risks of elevated indicators caused by different VEGFR-TKI are not the same.

OBJECTIVETo characterize a new alternative splicing isoform of human vascular endothelial growth factor (VEGF) gene.

METHODSThe total RNA was extracted from the lung tissue of a legally aborted 4-month-old fetus and amplified by RT-PCR. The amplified product was cloned into the plasmid pMD18-T and plasmid pcDNA3.1- for sequence analysis.

RESULTSElectrophoresis of the RT-PCR products displayed one short band for VEGF(121) (487 bp) and a long band. The latter was characterized to contain two fragments: one was normal VEGF(165) (619 bp), and the other (639 bp) had an identical nucleotide sequence to VEGF(165) with a 20 bp fragment inserted between exons 3 and 4. Sequence analysis showed that this 20-bp nucleotide was inserted from the 3' end of the third intron containing a splicing signal, thus causing shift mutation in the reading frame of VEGF gene and early appearance of the stop codon UAG in the middle of exon 4.

CONCLUSIONA new alternative splicing isoform of VEGF probably exists in the lung tissue of a legally aborted human fetus, and its biological significance remains to be further investigated.

Alternative Splicing ; Amino Acid Sequence ; Exons ; Frameshift Mutation ; Gene Expression ; Humans ; Protein Isoforms ; classification ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Vascular Endothelial Growth Factor A ; classification ; genetics

AIM To observe Arg-Glu*ss activity of antiplatelet and anticoagulation in rats and to further explore its mechanism. METHODS Twenty four male sprague dewley rats were divided into three groups randomly (eight rats in each group).Each group was orally given Arg-Glu (61 4 mg?kg -1 ?d -1 ), ASA (36 mg?kg -1 ?d -1 ) and equal placebo solution respectively.Eight days later all rats were given anesthesia and blood was taken from abdominal aorta with a plastic catheter, then the indexes related to blood hemodynamics,coagulation and blood fibrinolysis were measured. Twenty four SD rats were treated in the same way mentioned above. Platelet aggregation was measured by turbidimetric method. Plasma level of cyclic GMP and prostacyclin was evaluated by radioimmunoassay and nitric oxide by spectrophotometric determination. Common carotid artery-external jugular vein bypass was established in another 24 rats, and the weight of wet thrombus was measured with high sensitive electrical scale. RESULTS In group of Arg-Glu, statistically significance decrease versus placebo group was observed on blood apparent viscosity, reduced viscosity, hematocrit and plasma viscosity, increase versus placebo was also observed on blood reciprocal calcium time, activated partial thromboplastin time and prothrombin time ( P 0 05). Platelet aggregation activation decreased compared with placebo 〔(0 75%?3.62%) vs (32 8%?6 62%) P 0 05)〕. CONCLUSION Arg-Glu with its properties of antiplatelet、anticoagulation and improvement of blood rheology status in rats could be regarded as one antiplatelet drug and one NO precursor .Its mechanism of action was thought to be by Arg-NO-cGMP metabolism pathway while other mechanism might be involved.