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.

A 63-year-old male patient with glucose-6-phosphate dehydrogenase (G6PD) deficiency and type 2 diabetes mellitus received long-term use of glimepiride (2 mg once daily) and no adverse reactions occurred. He underwent percutaneous coronary intervention (PCI) followed by drug-eluting stent (DES) implantation because of acute inferior myocardial infarction. After the operation, dual antiplatelet therapy with oral aspirin enteric-coated tablets (100 mg once daily) and ticagrelor (90 mg twice daily) was given. Clinical pharmacists participated in the ward round and learned that the patient had a history of G6PD deficiency. After consulting the list of unsafe drugs for G6PD deficiency patients, the pharmacists found that glimepiride and aspirin were high-risk drugs that could induce hemolysis in G6PD deficiency patients. It was believed that the combination of the 2 drugs might increase the patient′s risk of hemolysis. They recommended that glimepiride should be discontinued and routine aspirin after PCI and DES should be continued. The physician adopted the pharmacists′ advice and the hypoglycemic agent was replaced by metformin hydrochloride. The patient recovered soon after surgery. At a 3-month follow-up, no hemolytic reaction occurred in the patient.

A 63-year-old male patient with glucose-6-phosphate dehydrogenase (G6PD) deficiency and type 2 diabetes mellitus received long-term use of glimepiride (2 mg once daily) and no adverse reactions occurred. He underwent percutaneous coronary intervention (PCI) followed by drug-eluting stent (DES) implantation because of acute inferior myocardial infarction. After the operation, dual antiplatelet therapy with oral aspirin enteric-coated tablets (100 mg once daily) and ticagrelor (90 mg twice daily) was given. Clinical pharmacists participated in the ward round and learned that the patient had a history of G6PD deficiency. After consulting the list of unsafe drugs for G6PD deficiency patients, the pharmacists found that glimepiride and aspirin were high-risk drugs that could induce hemolysis in G6PD deficiency patients. It was believed that the combination of the 2 drugs might increase the patient′s risk of hemolysis. They recommended that glimepiride should be discontinued and routine aspirin after PCI and DES should be continued. The physician adopted the pharmacists′ advice and the hypoglycemic agent was replaced by metformin hydrochloride. The patient recovered soon after surgery. At a 3-month follow-up, no hemolytic reaction occurred in the patient.

To research the expression of key enzymes in saikosaponin biosynthesis and the content of saikosaponin under the drought stress, the study focused on the gene-level and the end product responses to environmental change. Taking the five months of Bupleurum chinense as research materials, the contents of saikosaponin A and saikosaponin D under different stress levels were measured by HPLC. The drought was simulated by poly ethylene glycol. The real-time fluorescence quantitative PCR was used to analyze the expression of four key enzymes genes HMGR, IPPI, FPS, β-AS and the expression of β-tubulin was set as a reference gene. The results showed that drought stress significantly improved the content of saikosaponin. The contents of SSa and SSd were highest researching 0.648% and 0.781%, respectively when the concentration of PEG was 10%. Meanwhile, the results reflected that the expression of four key enzymes had risen differently and FPS, β-AS raised significantly(P<0.01). In addition, the results of correlation analysis showed that there was a significant positive correlation between the expression of the four key enzymes genes and the content of saikosaponin. In a word, the contents of secondary metabolites were regulated by the expression of key enzymes genes under the drought stress in B. chinense.

Ebstein malformation is a congenital heart disease characterized pathologically by displacement of the septal leaflet of the tricuspid valve towards the apex of the right ventricle of the heart. Hypoplasia, dysfunction of the right ventricle and tricuspid regurgitation cause an increased volume load of the right heart and result in the clinical manifestations of chest tightness, shortness of breath and fatigue after activities, palpitation, cyanosis and heart failure. We report a case of Ebstein's anomaly with refractory right heart failure and leg ulcers.
Ebstein Anomaly ; Heart Failure ; Heart Ventricles ; physiopathology ; Humans ; Leg Ulcer ; Tricuspid Valve Insufficiency

Ebstein malformation is a congenital heart disease characterized pathologically by displacement of the septal leaflet of the tricuspid valve towards the apex of the right ventricle of the heart. Hypoplasia, dysfunction of the right ventricle and tricuspid regurgitation cause an increased volume load of the right heart and result in the clinical manifestations of chest tightness, shortness of breath and fatigue after activities, palpitation, cyanosis and heart failure. We report a case of Ebstein’s anomaly with refractory right heart failure and leg ulcers.

Ebstein malformation is a congenital heart disease characterized pathologically by displacement of the septal leaflet of the tricuspid valve towards the apex of the right ventricle of the heart. Hypoplasia, dysfunction of the right ventricle and tricuspid regurgitation cause an increased volume load of the right heart and result in the clinical manifestations of chest tightness, shortness of breath and fatigue after activities, palpitation, cyanosis and heart failure. We report a case of Ebstein’s anomaly with refractory right heart failure and leg ulcers.

OBJECTIVETo explore the mechanism of lumen loss of the left circumflex ostium after main vessel stent implantation.

METHODSTwenty-eight patients undergoing provisional T technique were enrolled in this study. Intravascular ultrasound (IVUS) examination was performed before and after main vessel stenting and kissing balloon post-dilatation to evaluate the geometrical changes of the vessels.

RESULTSThe CSA of LCX ostium lumen decreased significantly from 5.9∓2 mm(2) to 4.9∓1.9 mm(2) (P<0.01) after the procedure, and the CSA of LCX ostium P and M increased from 5.4∓2.9 mmmm(2) to 5.7∓2.9 mm(2) (P=0.21) after the main vessel stenting. The changes in LCX ostium lumen CSA was correlated with the changes of LCX ostium EEM CSA but not the LCX ostium P and M CSA. After kissing balloon post-dilatation, the CSA of LCX ostium lumen increased from 4.9∓1.9 mm(2) to 5.5∓1.9 mm(2) (P<0.01) , and the CSA of LCX ostium P and M showed no obvious changes (5.7∓2.9 mmmm(2) vs 5.7∓2.6 mmmm(2), P=0.89). The changes of LCX ostium lumen CSA were correlated with the those of the LCX ostium EEM CSA (R=0.432, P=0.02).

CONCLUSIONAfter stent implantation from the LMCA to the LAD, most of lumen losses of the LCX are due to carina shift, and in occasional cases, plaque shift occurs from the distal LMCA to the ostium of the LCX. Kissing balloon technique can adjust carina shift but can not improve plaque shift.

Aged ; Angioplasty, Balloon, Coronary ; Coronary Artery Disease ; diagnostic imaging ; therapy ; Coronary Stenosis ; diagnostic imaging ; Female ; Humans ; Male ; Middle Aged ; Stents ; Treatment Outcome ; Ultrasonography, Interventional

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