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 investigate the regulatory effects of transcutaneous auricular vagus nerve stimulation (taVNS) on functional connectivity (FC) of thalamic subregions in patients with premenstrual syndrome (PMS).Methods:This study was a cross-sectional investigation. Clinical, laboratory, and imaging data were retrospectively collected from 56 PMS patients (PMS group) and 66 healthy controls (control group) recruited from various universities and hospitals in Nanning between November 2021 and June 2024. Resting-state functional MRI (fMRI) data and fMRI data during taVNS immediate stimulation (2 Hz, 25 Hz) were acquired from subjects during their late luteal phase. Using thalamic subregions (anterior thalamic nucleus, lateral nucleus, ventral nucleus, medial nucleus, central nucleus, posterior nucleus) as seeds, two-sample t-tests or paired t-tests were employed to analyze alterations in thalamic subregion FC in PMS patients and the regulatory effects of taVNS on these changes. Independent samples t-test were used to compare the differences in clinical and laboratory indicators between the PMS group and the control group. The relationship between taVNS regulation of thalamic subregion FC in PMS patients and thalamic internal functional connectivity were analyzed using mediation effect analysis. Results:Compared to the control group, patients in the PMS group showed increased scores on the Daily Record of Severity of Problems, Pittsburgh Sleep Quality Index, Self-Rating Anxiety Scale, Self-Rating Depression Scale, Hamilton Anxiety Rating Scale 17, and Hamilton Depression Rating Scale 14 during the late luteal phase ( P<0.05). At baseline, PMS patients exhibited higher FC between the left thalamic lateral nucleus and the left insula, and lower FC between the left medial nucleus, posterior nucleus, and ventral nucleus of the thalamus and the right middle frontal gyrus (MFG) compared to the control group (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). During 2 Hz taVNS immediate stimulation in PMS group, FC between the left thalamic medial nucleus, posterior nucleus, ventral nucleus and the right MFG, as well as the FC between the left thalamic ventral nucleu and the left MFG increased compared to baseline levels; meanwhile, FC between the left thalamic posterior nucleus, ventral nucleus and the left insula decreased compared to baseline levels (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). During 25 Hz taVNS immediate stimulation, the FC between the left thalamic ventral nucleus and the right MFG decreased compared to the baseline level (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). Mediation effect analysis showed that the FC between the left thalamic posterior nucleus and the left lateral nucleus mediated part of the association between the FC of the left lateral thalamic nucleus-left insula and the FC of the left ventral thalamic nucleus-left putamen/insula; there were significant direct effects between the FC of the left lateral thalamic nucleus-the left posterior nucleus and FC of the left lateral thalamic nucleus-the left insula, as well as between the FC of the left ventral thalamic nucleus-the left MFG and FC of the left ventral thalamic nucleus-the right MFG. Conclusions:taVNS can modulate abnormal FC of the left thalamic subregions in PMS patients, restoring it toward normalization. The regulatory effects of 2 Hz stimulation are more pronounced than those of 25 Hz stimulation. This modulation primarily operates through two pathways: the left thalamic lateral nucleus-left insula-left thalamic ventral nucleus pathway and the left MFG-left thalamic ventral nucleus-right MFG.

Ultrasonography（US）is the first-line imaging modality recommended by domestic and international guidelines for liver tumor screening，owing to its non-invasive nature，real-time dynamic imaging capability，cost-effectiveness，and operational convenience. In recent years，the integration of artificial intelligence（AI）and medical imaging has emerged as a major research focus. By leveraging large-scale data training，AI models can automatically recognize and analyze input imaging data and generate predictive outcomes. Notably，AI-based ultrasound imaging technology has achieved breakthrough advancements in the diagnosis and treatment of liver tumors. These innovations significantly improve diagnostic accuracy，optimize treatment strategies，predict disease progression and prognosis，and monitor therapeutic response. This article provides a comprehensive review of the latest applications and research progress of AI in ultrasound-based diagnosis and treatment of liver tumors.

Objective To evaluate the efficacy of elastic appliances in the early correction of Class Ⅱmalocclusions in the replacement dentition.Methods A total of 15 children aged 7-9 years who were admit-ted to the Affiliated Stomatology Hospital of Southwest Medical University from June 2018 to August 2023 were selected as the observation group,and 15 children who were consulted but not treated in the hospital dur-ing the same period were selected as the control group.The changes of bone tissue,dental and alveolar tissue,soft tissue and occlusal relationship before and after treatment were evaluated in the two groups.In addition,X-ray images of the observation group were collected every 8 to 10 months for the whole process dynamic mo-nitoring.Results Before treatment,there was no significant difference in all indexes between the two groups(P＞0.05).After treatment,there were statistical significances in the upper and lower alveolar base Angle(ANB),mandibular branch length(GO-CO),mandibular height(ANS-Me),mandibular position(S-GO),up-per central incisor inclination(U1-NA Angle),upper central incisor inclination convexity(U1-NA),lower central incisor process distance(L1-APo),the Z Angle and FH-N'Pg'Angle of soft tissue between the two groups(P＜0.05).After treatment,the covering OB and covering OJ in the observation group were lower than those in the control group,and the proportion of ClassⅠ patients in molar relationship was higher than that in the control group,with statistical significance(P＜0.05).After 3-4 years of treatment,ANB gradual-ly decreased,and the anterior-basilar plane-mandibular plane Angle(SN-MP)remained basically stable,and had a slight decreasing trend in the later period.The U1-NA Angle and the lower central incisor inclination(L1-NB Angle)were close to the normal mean during the whole treatment.Conclusion Using elastic appli-ances to treat patients with early replacement Class Ⅱ malocclusion,after 3-4 years monitoring and guid-ance,it can effectively improve the molar relationship,promote forward jaw growth,and create a harmonious and aesthetically pleasing facial soft tissue.

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.

Objective:To investigate the regulatory effects of transcutaneous auricular vagus nerve stimulation (taVNS) on functional connectivity (FC) of thalamic subregions in patients with premenstrual syndrome (PMS).Methods:This study was a cross-sectional investigation. Clinical, laboratory, and imaging data were retrospectively collected from 56 PMS patients (PMS group) and 66 healthy controls (control group) recruited from various universities and hospitals in Nanning between November 2021 and June 2024. Resting-state functional MRI (fMRI) data and fMRI data during taVNS immediate stimulation (2 Hz, 25 Hz) were acquired from subjects during their late luteal phase. Using thalamic subregions (anterior thalamic nucleus, lateral nucleus, ventral nucleus, medial nucleus, central nucleus, posterior nucleus) as seeds, two-sample t-tests or paired t-tests were employed to analyze alterations in thalamic subregion FC in PMS patients and the regulatory effects of taVNS on these changes. Independent samples t-test were used to compare the differences in clinical and laboratory indicators between the PMS group and the control group. The relationship between taVNS regulation of thalamic subregion FC in PMS patients and thalamic internal functional connectivity were analyzed using mediation effect analysis. Results:Compared to the control group, patients in the PMS group showed increased scores on the Daily Record of Severity of Problems, Pittsburgh Sleep Quality Index, Self-Rating Anxiety Scale, Self-Rating Depression Scale, Hamilton Anxiety Rating Scale 17, and Hamilton Depression Rating Scale 14 during the late luteal phase ( P<0.05). At baseline, PMS patients exhibited higher FC between the left thalamic lateral nucleus and the left insula, and lower FC between the left medial nucleus, posterior nucleus, and ventral nucleus of the thalamus and the right middle frontal gyrus (MFG) compared to the control group (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). During 2 Hz taVNS immediate stimulation in PMS group, FC between the left thalamic medial nucleus, posterior nucleus, ventral nucleus and the right MFG, as well as the FC between the left thalamic ventral nucleu and the left MFG increased compared to baseline levels; meanwhile, FC between the left thalamic posterior nucleus, ventral nucleus and the left insula decreased compared to baseline levels (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). During 25 Hz taVNS immediate stimulation, the FC between the left thalamic ventral nucleus and the right MFG decreased compared to the baseline level (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). Mediation effect analysis showed that the FC between the left thalamic posterior nucleus and the left lateral nucleus mediated part of the association between the FC of the left lateral thalamic nucleus-left insula and the FC of the left ventral thalamic nucleus-left putamen/insula; there were significant direct effects between the FC of the left lateral thalamic nucleus-the left posterior nucleus and FC of the left lateral thalamic nucleus-the left insula, as well as between the FC of the left ventral thalamic nucleus-the left MFG and FC of the left ventral thalamic nucleus-the right MFG. Conclusions:taVNS can modulate abnormal FC of the left thalamic subregions in PMS patients, restoring it toward normalization. The regulatory effects of 2 Hz stimulation are more pronounced than those of 25 Hz stimulation. This modulation primarily operates through two pathways: the left thalamic lateral nucleus-left insula-left thalamic ventral nucleus pathway and the left MFG-left thalamic ventral nucleus-right MFG.

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.

Ultrasonography（US）is the first-line imaging modality recommended by domestic and international guidelines for liver tumor screening，owing to its non-invasive nature，real-time dynamic imaging capability，cost-effectiveness，and operational convenience. In recent years，the integration of artificial intelligence（AI）and medical imaging has emerged as a major research focus. By leveraging large-scale data training，AI models can automatically recognize and analyze input imaging data and generate predictive outcomes. Notably，AI-based ultrasound imaging technology has achieved breakthrough advancements in the diagnosis and treatment of liver tumors. These innovations significantly improve diagnostic accuracy，optimize treatment strategies，predict disease progression and prognosis，and monitor therapeutic response. This article provides a comprehensive review of the latest applications and research progress of AI in ultrasound-based diagnosis and treatment of liver tumors.

Objective To evaluate the potential clinical value of T2 mapping and mDixon Quant in the diagnosis of early interver-tebral disc degeneration.Methods A total of 79 volunteers who underwent lumbar MRI examination were enrolled.All subjects were examined for 3.0T MR with T2WI,T2 mapping,and mDixon Quant while recording the condition of low back pain.The differ-ences between T2 mapping(map)value and fat fraction(FF)values of the vertebral(V)and nucleus pulposus(NP)within the Pfir-rmann Ⅰ and Pfirrmann Ⅱ intervertebral disc(grade Ⅰ 76,grade Ⅱ 87)were statistically analyzed.Receiver operating characteristic(ROC)curve analyses were performed for meaningful parameters.Results V-FF showed a mild positive correlation with degenera-tive intervertebral disc lesions,and NP-FF and NP-map values showed a mild negative correlation with lesions.There were statistically significant differences between the two groups in V-FF(P＜0.001),NP-FF(P=0.005),and NP-map(P＜0.001).Some measure-ments had statistically significant differences when different intervertebral disc segments were compared.Conclusion V-FF,NP-FF,and NP-map are associated with intervertebral disc degeneration.T2 mapping and mDixon Quant are potentially valuable as diagnostic tools to quantitatively assess early intervertebral disc degeneration and help diagnose.