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*

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Hepatocellular adenoma(HCA)is a benign liver tumor with a low incidence.It mostly occurs in women of childbearing age,and often manifests as a single mass.This paper reported a case of multiple HCA in a middle-aged man.Serological examination showed elevated triglycerides level,and normal hepatic function.The patient had no history of viral hepatitis.Upper abdominal enhanced MRI examination showed multiple space-occupying lesions in liver,which tended to be benign.A total of 3 intrahepatic tumors were resected,and all of them were confirmed to be HCA by pathological examination.Both oncocytes and normal hepatocytes were found mild steatosis.The patient recovered well without tumor recurrence after surgery.

AIM: To investigate the correlation between the ocular demodex infection and the composition of meibum lipid flora.METHODS: A non-interventional and observational study was performed on recruited 39 patients in our hospital between July 2020 and February 2021. They were divided into control group(n=14), meibomian gland dysfunction(MGD)group(n=14), and demodex group(FM, n=11)according to the presence or absence of demodex infection or MGD. High-throughput sequencing of V3-V4 fragment of 16S rRNA gene was performed on the meibomian ester samples of the three groups of subjects, and bioinformatics analysis was performed on the sequencing data to study the composition and difference of meibum lipid flora in the subjects of ocular demodex.RESULTS: Pseudomonas and Comamonas in FM group were significantly higher than those in control group and MGD group(P<0.05), while Ralstonia in Demodex infection group was significantly lower than that in control group and MGD group(P<0.05). The microbial richness and community diversity of meibum lipid flora of the MGD group and the FM group were significantly higher than those of the control group(P<0.05).CONCLUSION: Ocular demodex infection changed the composition of meibum lipid flora and increased the microbial richness and community diversity of meibum lipid flora.

AIM:To explore the influence factors of the treatment zone diameter(TZD)and its correlation with axial length growth(ALG)after Paragon CRT orthokeratology.METHODS: Retrospective clinical study. The data of 226 myopic patients(226 eyes)wearing Paragon CRT orthokeratology from April 2020 to September 2022 were collect. The correlated factors of TZD after wearing lens for 1mo, and the relationship between the overlapping treatment zone/ pupil area ratio and the ALG after wearing lens for 1a were analyzed.RESULTS: After wearing lens for 1mo, the TZD was negatively correlated with central corneal thickness(CCT)and positively correlated with the flat corneal eccentricity. After wearing lens for 1a, the ALG of the small TZD group(0.25±0.18mm)was significantly smaller than that of the large TZD group(0.34±0.24mm, P=0.002), and the ALG of the small area ratio group(0.24±0.19mm)was significantly smaller than that of the large area ratio group(0.35±0.23mm,P<0.001). Age and overlapping treatment zone area/pupil area ratio were significantly associated with the ALG in multivariate linear regression(all P<0.05).CONCLUSION: The wearers with thicker CCT and smaller flat corneal eccentricity usually had smaller TZD, and both the TZD and the overlapping treatment zone area/pupil area ratio were correlated with the ALG.

Clostridioides difficile/genetics* ; Clostridioides ; Real-Time Polymerase Chain Reaction ; Feces ; Bacterial Proteins/genetics*

Aim To investigate the effects of CPD1, a novel phosphodiesterase 5 inhibitor, on liver pathological phenotype and hepatic stellate cells (HSCs) activation in hepatic fibrosis model mice caused by carbon tetrachloride ( CCl

Colchicine/therapeutic use* ; Coronary Artery Disease ; Coronary Disease/prevention & control* ; Humans ; Plaque, Atherosclerotic

OBJECTIVE: To explore the effect of inhibiting polyribonucleotide nucleotidyl-transferase 1 (PNPT1) on oxygen-glucose deprivation (OGD)-induced apoptosis of mouse atrial myocytes. METHODS: Cultured mouse atrial myocytes (HL-1 cells) with or without OGD were transfected with PNPT1-siRNA or a negative control siRNA (NC-siRNA group), and the cell survival rate was detected using CCK-8 assay. The expression levels of ACTB and TUBA mRNA were detected with qPCR, and the protein expression of PNPT1 was detected with Western blotting. The apoptosis rate of the treated cells was determined with flow cytometry, the mitochondrial membrane potential was detected using JC-1 kit, and the mitochondrial morphology was observed using transmission electron microscope. RESULTS: With the extension of OGD time, the protein expression levels of PNPT1 increased progressively in the cytoplasm of HL-1 cells (P < 0.05). Transfection with PNPT1-siRNA significantly reduced PNPT1 expression in HL-1 cells (P < 0.05). Exposure to OGD significantly enhanced degradation of ACTB and TUBA mRNA (P < 0.05) and markedly increased the apoptosis rate of HL-1 cells (P < 0.05), and these changes were significantly inhibited by transfection with PNPT1-siRNA (P < 0.05), which obviously increased mitochondrial membrane potential and improved mitochondrial morphology of HL-1 cells exposed to OGD. CONCLUSION Inhibition of PNPT1 improves mitochondrial damage and reduces degradation of apoptotic-associated mRNAs to alleviate OGD-induced apoptosis of mouse atrial myocyte.
Animals ; Apoptosis ; Cell Survival ; Glucose/pharmacology* ; Mice ; Myocytes, Cardiac ; Oxygen/metabolism* ; RNA, Messenger/metabolism* ; RNA, Small Interfering/metabolism*

OBJECTIVE: To study the effect of astragaloside IV (AS-IV) on NOD-like receptor protein 3 (NLRP3) inflammasome in neonatal rats with hypoxic-ischemic brain damage (HIBD). METHODS: A total of 24 Sprague-Dawley rats, aged 7 days, were randomly divided into a sham-operation group, an HIBD group, and an AS-IV treatment group, with 8 rats in each group. After 24 hours of modeling, brain tissue was collected for hematoxylin-eosin staining, yo-PRO-1 staining, and EthD-2 immunofluorescent staining in order to observe the cerebral protection effect of AS-IV in vivo. HT22 cells were used to prepare a model of oxygen-glycogen deprivation (OGD), and a concentration gradient (50-400 μmol/L) was established for AS-IV. CCK-8 assay was used to measure the viability of HT22 cells. RT-PCR and Western blot were used to observe the effect of different concentrations of AS-IV on the mRNA and protein expression of NLRP3, gasdermin D (GSDMD), caspase-1, and interleukin-1β (IL-1β). RESULTS: Yo-Pro-1 and EthD-2 staining showed that compared with the sham-operation group, the HIBD group had an increase in pyroptotic cells with a small number of necrotic cells, and the AS-IV group had reductions in both pyroptotic and necrotic cells. Compared with the sham-operation group, the HIBD group had significantly higher protein expression levels of NLRP3, IL-1β, caspase-1, and GSDMD ( CONCLUSIONS AS-IV may alleviate HIBD in neonatal rats by inhibiting the expression of NLRP3, GSDMD, caspase-1, and IL-1β.
Animals ; Animals, Newborn ; Brain ; Hypoxia-Ischemia, Brain/drug therapy* ; Inflammasomes ; NLR Proteins ; Rats ; Rats, Sprague-Dawley ; Saponins ; Triterpenes