Dysfunction of drug transporters significantly affects therapeutic outcomes and drug efficacy in patients with liver injury. Clinical and experimental evidence demonstrates that liver injury involves complex inter-organ interactions among the brain, eye, liver, intestine, and kidney. Recent advances in basic and clinical research have illuminated the physiologic and molecular mechanisms underlying transporter alterations in liver injury, particularly those associated with bilirubin, reactive oxygen species, ammonia, bile acid, and inflammatory factors. Notably, the influence of these transporter modifications on drug pharmacokinetics in liver injury patients remains inadequately understood. Additional research is necessary to fully comprehend these effects and their therapeutic implications. The documented alterations of transporters in distant organs across various liver diseases indicate that dosage modifications may be required when administering transporter-substrate drugs, including both traditional Chinese and Western medicines, to patients with liver dysfunction. This strategy helps maintain drug concentrations within therapeutic ranges while reducing adverse reactions. Furthermore, when utilizing transporter inducers or inhibitors clinically, consideration of their long-term effects on transporters and subsequent therapeutic impact is essential. Careful attention must be paid to avoid compromising the elimination of toxic metabolites and proteins when inhibiting these transporters. Similarly, prudent use of inducers or inducer-type therapeutic drugs is necessary to prevent enhanced drug resistance. This review examines recent clinical and experimental findings regarding the inter-organ interaction of drug transporters in liver injury conditions and their clinical relevance.
Humans ; Liver/drug effects* ; Animals ; Chemical and Drug Induced Liver Injury/metabolism* ; Membrane Transport Proteins/metabolism* ; Biological Transport ; Liver Diseases/drug therapy* ; Pharmaceutical Preparations/metabolism*

Objective To screen long non-coding RNA(lncRNA)associated with lymph node metasta-sis in papillary thyroid carcinoma(PTC)and verify its function in vitro,so as to provide a theoretical basis for elucidating the molecular mechanism of lymph node metastasis in PTC.Methods lncRNA+mRNA microar-ray was used to detect the differential expression of lncRNA and mRNA in PTC cancer tissues with and with-out lymph node metastasis.Real time fluorescence quantitative PCR(qPCR)verified target differential lncR-NAs.Lentivirus was used as vector to construct high and low lncRNA expression PTC cell lines.Cell counting kit-8(CCK-8),cell scratches assay,Transwell assay,cell clone formation assay were used to detect the effects of target lncRNA on proliferation,migration,invasion,clonal formation of PTC cells.Results Compared with 5 cases of PTC tissues without lymph node metastasis,gene chips detected 119 lncRNA and 53 mRNA expres-sion levels upregulated,while 263 lncRNA and 198 mRNA expression levels down regulated in 5 cases of PTC tissues with lymph node metastasis.Furthermore,21 lncRNAs were selected for validation in the original 10 PTC samples,and the results showed that,compared with PTC tissues without lymph node metastasis,lncR-NAs FLJ20444,DPP10-AS1 and ENST00000567197 were highly expressed in PTC tissues with lymph node metastasis,while uc021thd.1,LNC00944,ENST00000429730 and BLNK were lowly expressed(P＜0.05).In addition,qPCR results of another 30 fresh PTC tissues showed that compared with PTC tissues without lymph node metastasis,DPP10-AS1 was highly expressed and LNC00944 was lowly expressed in PTC tissues with lymph node metastasis(P＜0.05).Cell function experiments showed that the proliferation,migration,invasion,and colony formation abilities of PTC cells in the DPP10-AS1 high expression group were higher than those in the DPP10-AS1 low expression group,and the differences were statistically significant(P＜0.05).Conclusion lncRNA DPP10-AS1 may play a role in PTC metastasis through certain signaling pathways.

Purpose To investigate the genetic mutation characteristics and its correlation with clinicopathologic characteristics of radioactive iodine-refractory papillary thyroid cancer(RAIR-PTC).Methods PTC gene mutation detection kit was constructed based on the characteristics of PTC gene mutation.37 cases of RAIR-PTC tumor samples and 36 cases of radioiodine-avid thyroid papillary carcinoma tumor samples were detected by multiple PCR sequencing.The mutation of PTC tumor samples was identified by bioinformatics analysis,and the correlation between gene muta-tions and clinicopathological characteristics of patients was statistically analyzed.Results BRAF,TERT,TP53,AKT1 and NRAS gene mutations were detected in RAIR-PTC tumor samples,with BRAF V600E and TERT promoter mutation rates of 70.3％and 24.3％,respectively.Gene mutation of RAIR-PTC often manifested as the accumulation of multiple gene mutations,with co-mutations of BRAF or RAS and TERT promoter being the most common,and these co-mutations were significantly associated with patients'progression-free survival of PTC.Conclusion The accumula-tion of gene mutation can promote the occurrence of RAIR-PTC.TERT promoter mutation is a late event of PTC.TERT promoter mutation and co-mutations of BRAF or RAS and TERT promoter can help to evaluate the possibility of iodine refractory in PTC patients,in whom the therapeutic effect of radioactive iodine should be closely monitored and the ac-curate and effective treatment should be took as soon as possible.

Purpose To investigate the genetic mutation characteristics and its correlation with clinicopathologic characteristics of radioactive iodine-refractory papillary thyroid cancer(RAIR-PTC).Methods PTC gene mutation detection kit was constructed based on the characteristics of PTC gene mutation.37 cases of RAIR-PTC tumor samples and 36 cases of radioiodine-avid thyroid papillary carcinoma tumor samples were detected by multiple PCR sequencing.The mutation of PTC tumor samples was identified by bioinformatics analysis,and the correlation between gene muta-tions and clinicopathological characteristics of patients was statistically analyzed.Results BRAF,TERT,TP53,AKT1 and NRAS gene mutations were detected in RAIR-PTC tumor samples,with BRAF V600E and TERT promoter mutation rates of 70.3％and 24.3％,respectively.Gene mutation of RAIR-PTC often manifested as the accumulation of multiple gene mutations,with co-mutations of BRAF or RAS and TERT promoter being the most common,and these co-mutations were significantly associated with patients'progression-free survival of PTC.Conclusion The accumula-tion of gene mutation can promote the occurrence of RAIR-PTC.TERT promoter mutation is a late event of PTC.TERT promoter mutation and co-mutations of BRAF or RAS and TERT promoter can help to evaluate the possibility of iodine refractory in PTC patients,in whom the therapeutic effect of radioactive iodine should be closely monitored and the ac-curate and effective treatment should be took as soon as possible.

Objective:To investigate the role of miRNA-4298/PADI4/p53 signal axis in mediating 4f-induced apoptosis of leukemia cells.Methods:The cell growth density was observed under inverted microscope and the proliferation of leukemia cells was detected by CCK-8 counting assay. The expression of PADI4 and P53 at mRNA level was detected by qRT-PCR. Cell cycle and apoptosis were measured with flow cytometry. The expression of PADI4, P53, Bcl-2, Bax, caspase-3 and caspase-9 at protein level was detected by Western blot. Differential miRNA and mRNA expression profiles was detected by next generation sequencing. Databases such as TargetScan were used to predict the potential upstream and downstream genes of PADI4. A luciferase reporter assay was used to detect the 3′UTR of PADI4 targeted by miRNA-4298. Cell transfection assay was used to detect the effect siRNA, PADI4 vector, miRNA mimics and miRNA inhibitor in interference and rescue.Results:Nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor 4f could inhibit the proliferation of THP-1, K562 and U937 cells, and induce the apoptosis of these leukemia cells. It downregulated the expression of PADI4 mainly through the binding activity of miRNA-4298 to miRNA sponges, which resulted in the proliferation inhibition and apoptosis of leukemia cells. The inhibited proliferation and apoptosis of leukemia cells by 4f were associated with the increase of P53 expression after the decrease of PADI4 expression. The PADI4-dependent upregulation of P53 led to the ratio inversion of downstream Bcl-2/Bax, which activated caspase-3 or caspase-9 to induce the apoptosis of leukemia cells.Conclusions:The apoptosis of leukemia cells induced by Nrf2 inhibitor 4f was mainly associated with the miRNA-4298/PADI4/p53 axis, suggesting that it might be a novel signaling pathway for targeted therapy.

Objective:To preliminarily evaluate the myocardium of pilots by noninvasive and radiation free cardiac MRI mapping technology, and to explore its application value in evaluating the myocardium of pilots.Methods:Case-control study was adopted in this study. Pilots and normal personnel who had cardiac MRI in Air Force Medical Center from October of 2020 to July of 2022 were selected, and they were divided into 20-40 years group and >40 years group. The differences of myocardial longitudinal relaxation time T1, transverse relaxation time T2 and T2 * values between pilots and normal personnel at different ages were analyzed and compared. Pilots were divided into groups according to flying hours and aircraft types, and the differences of myocardial T1, T2 and T2 * values among pilots in different flying hours and aircraft types were analyzed and compared. Results:The average myocardial T1 value of pilots [(1 011.18±24.70) ms] was lower than that of normal personnel [(1 025.07±25.74) ms], and the difference was significant ( t=2.10, P=0.040). The myocardial T1 value of pilots >40 years old [(1 006.04±29.15)ms] was lower than that of normal personnel [(1 029.68±20.24) ms], and the difference was significant ( t=2.30, P=0.032). The myocardial T1 value of fighter pilots [(999.04±17.39)ms] was lower than that of the bomber, transporter, helicopter pilots [(1 023.33±25.53) ms], and the difference was significant ( t=2.73, P=0.012). There was no significant difference in myocardial T1, T2 and T2 * values between pilots and nornal personnel aged 20-40 years old; there was no significant difference in T2 and T2 * values between pilots and normal personnel in the age group of >40 years old (all P>0.05). There was also no significant difference in myocardial T1, T2 and T2 * values among the pilots in different flying hours (all P>0.05). Conclusions:The level of cardiomyocyte hypertrophy or myocardial fibrosis in fighter pilots might be lower than that in other aircraft types pilots. Cardiac MRI mapping has potential value in evaluating the myocardium of pilots.

Objective:To preliminarily evaluate the myocardium of pilots by noninvasive and radiation free cardiac MRI mapping technology, and to explore its application value in evaluating the myocardium of pilots.Methods:Case-control study was adopted in this study. Pilots and normal personnel who had cardiac MRI in Air Force Medical Center from October of 2020 to July of 2022 were selected, and they were divided into 20-40 years group and >40 years group. The differences of myocardial longitudinal relaxation time T1, transverse relaxation time T2 and T2 * values between pilots and normal personnel at different ages were analyzed and compared. Pilots were divided into groups according to flying hours and aircraft types, and the differences of myocardial T1, T2 and T2 * values among pilots in different flying hours and aircraft types were analyzed and compared. Results:The average myocardial T1 value of pilots [(1 011.18±24.70) ms] was lower than that of normal personnel [(1 025.07±25.74) ms], and the difference was significant ( t=2.10, P=0.040). The myocardial T1 value of pilots >40 years old [(1 006.04±29.15)ms] was lower than that of normal personnel [(1 029.68±20.24) ms], and the difference was significant ( t=2.30, P=0.032). The myocardial T1 value of fighter pilots [(999.04±17.39)ms] was lower than that of the bomber, transporter, helicopter pilots [(1 023.33±25.53) ms], and the difference was significant ( t=2.73, P=0.012). There was no significant difference in myocardial T1, T2 and T2 * values between pilots and nornal personnel aged 20-40 years old; there was no significant difference in T2 and T2 * values between pilots and normal personnel in the age group of >40 years old (all P>0.05). There was also no significant difference in myocardial T1, T2 and T2 * values among the pilots in different flying hours (all P>0.05). Conclusions:The level of cardiomyocyte hypertrophy or myocardial fibrosis in fighter pilots might be lower than that in other aircraft types pilots. Cardiac MRI mapping has potential value in evaluating the myocardium of pilots.

Objective:To study the value of ultrasound-guided endoscopic retrograde appendicitis therapy in children with uncomplicated appendicitis.Methods:This study was a single center, retrospective study, including all electronic cases of appendicitis diagnosed clinically in Department of Pediatrics, the Second Affiliated Hospital of Air Force Military Medical University from October 2018 to October 2020 and received ultrasound-guided endoscopic retrograde appendicitis therapy.The clinical features, treatment and prognosis of the children were retrospectively analyzed.Results:A total of 152 electronic cases were included, there were 77 males and 75 females, aged(6.84±3.09) years.All the 152 children were treated with ultrasound-guided endoscopic retrograde appendicitis therapy.Intubation success rate and clinical success rate was 98.03%(149/152 cases)and 97.99%(146/149 cases), respectively.The median time of endoscopic therapy was 42.50 (31.00, 56.00) minutes.Mean postoperative hospital stay was (2.81 ±1.41) days, and the mean total hospital stay was (4.19 ±1.71) days.A total of 139 patients were followed up with a median follow-up time of 5 (1, 26) months.During the follow-up, the recurrence rate was 7.19%(10/139 cases), and the median time of recurrence was 2 (1, 3) months.Conclusions:Ultrasound-guided endoscopic retrograde appendicitis therapy had high effective rate and low recurrence rate in children with uncomplicated appendicitis, preserved the physiological function of appendix and avoided radiation damage.It can be used as a safe and effective treatment for acute and chronic uncomplicated appendicitis in children.

Objective:To investigate the distribution of diseases in Air Force pilots by cranial MRI examination.Methods:Four hundred and twenty-four pilots were checked cranial MRI plain examination, magnetic resonance angiography (MRA) and susceptibility weighted imaging (SWI). The results of 424 pilots′ disease spectrum were statistically analyzed. The pilots were divided into 4 groups according to age: 20-30 years group, 31-40 years group, 41-49 years group and ≥50 years group. The positive detection rates of white matter hyperintensities (WMHs) among these groups were analyzed and compared.Results:The number of positive pilots during cranial MRI examination was 134 and the positive rate was 31.6%, of which 9 pilots had 2 kinds of lesions at the same time. The main diseases of 134 pilots were WMHs (24.29%), intracranial calcification (1.89%), arachnoid cyst (1.89%), venous malformation (1.65%), aneurysm (1.18%), moyamoya disease (0.71%), pituitary cyst (0.47%), cavernous hemangioma (0.47%), remote hemorrhage (0.24%), encephalomalacia foci (0.24%), intraventricular benign tumor (0.24%), pineal cyst (0.24%), choroid plexus cyst (0.24%). The differences of WMHs detection rates among different age groups were statistically significant ( χ2=86.457, P<0.01). Conclusions:Some potential cranial diseases of pilots could be found by MRI examination. Cranial MRI examination is very important in pilots′ physical examination.

Objective:To investigate the distribution of diseases in Air Force pilots by cranial MRI examination.Methods:Four hundred and twenty-four pilots were checked cranial MRI plain examination, magnetic resonance angiography (MRA) and susceptibility weighted imaging (SWI). The results of 424 pilots′ disease spectrum were statistically analyzed. The pilots were divided into 4 groups according to age: 20-30 years group, 31-40 years group, 41-49 years group and ≥50 years group. The positive detection rates of white matter hyperintensities (WMHs) among these groups were analyzed and compared.Results:The number of positive pilots during cranial MRI examination was 134 and the positive rate was 31.6%, of which 9 pilots had 2 kinds of lesions at the same time. The main diseases of 134 pilots were WMHs (24.29%), intracranial calcification (1.89%), arachnoid cyst (1.89%), venous malformation (1.65%), aneurysm (1.18%), moyamoya disease (0.71%), pituitary cyst (0.47%), cavernous hemangioma (0.47%), remote hemorrhage (0.24%), encephalomalacia foci (0.24%), intraventricular benign tumor (0.24%), pineal cyst (0.24%), choroid plexus cyst (0.24%). The differences of WMHs detection rates among different age groups were statistically significant ( χ2=86.457, P<0.01). Conclusions:Some potential cranial diseases of pilots could be found by MRI examination. Cranial MRI examination is very important in pilots′ physical examination.