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.

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.

Objective To explore the effect of esketamine combined with butorphanol on hemodynamics in painless gastroenteroscopy for elderly patients with obesity and the anesthetic efficacy and safety of this combined anesthesia regimen.Methods The subjects of this study,124 elderly patients with obesity who received painless gastroenteroscopy from January 2022 to March 2024,were randomly divided into two groups,each with 62 cases.Both groups were administrated with propofol 1.50 mg/kg for anesthesia induction.The observation group was given esketamine 0.20 mg/kg combined with butorphanol 10 μg/kg intravenously prior to propofol injection,while the control group was given saline of the same volume as esketamine combined with butorphanol 10 μg/kg intravenously before propofol injection.Vital signs indicators[mean arterial pressure(MAP),heart rate(HR),and percutaneous arterial oxygen saturation(SpO2)]were compared between the two groups at the time of entry(T0),immediately after anesthesia induction(T1),immediately after gastroscopy placement(T2),immediately upon completion of gastroscopy(T3),immediately after colonoscopy insertion(T4),and immediately upon completion of colonoscopy examination(T5).The anesthesia effect was evaluated for the two groups during painless gastroenteroscopy examination.The duration of gastroenteroscopy and propofol dosage were compared between the two groups as well.Visual analogue scale(VAS)score was used to evaluate the postoperative pain level for patients from the two groups 1,2,3,and 4 h after surgery.Intraoperative and postoperative adverse reactions in two groups were recorded.Results The MAP at T3,T4,and T5 time points in observation group were lower than that at T0 time point,the HR at T4 and T5 time point in observation group was lower than that at T0 time point,the differences were statistically significant(P＜0.05),there was no significant difference in SpO2 at each time point in observation group(P＞0.05).While the MAP,HR,and SpO2 at T1,T2,T3,T4,and T5 time points in control group were significantly lower than those at T0 time points,the differences were statistically significant(P＜0.05).The MAP,HR,and SpO2 at T1,T2,T3,T4,and T5 time points in control group were lower than those in observation group,the differences were statistically significant(P＜0.05).The excellent and good rate of anesthesia in observation group was better than that in control group,the difference was statistically significant(P＜0.05).The propofol dosage in observation group was less than that in control group,the recovery time in observation group was shorter than that in control group,the differences were statistically significant(P＜0.05).There were no significant differences in duration of gastroenteroscopy examination,postanesthesia care unit(PACU)stay and leave hospital time between the two groups(P＞0.05).1,2,3,and 4 h postoperative pain VAS scores in observation group were less than those in control group,the differences were statistically significant(P＜0.05).The incidence of respiratory depression was 3.23％,which was significantly lower than 19.35％in control group,the incidence of hypotension was 4.84％,which was significantly lower than 25.81％in control group,the incidence of bradycardia was 0.00％,which was significantly lower than 17.74％in control group,the incidence of nausea and vomiting was 1.61％,which was significantly lower than 12.90％in control group,the differences were statistically significant(P＜0.05).There were no significant differences in the incidence of tachycardia,coughing,body movement,and dizziness between the two groups(P＞0.05).Conclusion Application of esketamine combined with butorphanol in painless gastroenteroscopy for elderly patients with obesity can effectively improve sedative and analgesic effects,stabilize hemodynamics,and reduce adverse reactions.It is worthy clinical application.

Objective To explore the effect of esketamine combined with butorphanol on hemodynamics in painless gastroenteroscopy for elderly patients with obesity and the anesthetic efficacy and safety of this combined anesthesia regimen.Methods The subjects of this study,124 elderly patients with obesity who received painless gastroenteroscopy from January 2022 to March 2024,were randomly divided into two groups,each with 62 cases.Both groups were administrated with propofol 1.50 mg/kg for anesthesia induction.The observation group was given esketamine 0.20 mg/kg combined with butorphanol 10 μg/kg intravenously prior to propofol injection,while the control group was given saline of the same volume as esketamine combined with butorphanol 10 μg/kg intravenously before propofol injection.Vital signs indicators[mean arterial pressure(MAP),heart rate(HR),and percutaneous arterial oxygen saturation(SpO2)]were compared between the two groups at the time of entry(T0),immediately after anesthesia induction(T1),immediately after gastroscopy placement(T2),immediately upon completion of gastroscopy(T3),immediately after colonoscopy insertion(T4),and immediately upon completion of colonoscopy examination(T5).The anesthesia effect was evaluated for the two groups during painless gastroenteroscopy examination.The duration of gastroenteroscopy and propofol dosage were compared between the two groups as well.Visual analogue scale(VAS)score was used to evaluate the postoperative pain level for patients from the two groups 1,2,3,and 4 h after surgery.Intraoperative and postoperative adverse reactions in two groups were recorded.Results The MAP at T3,T4,and T5 time points in observation group were lower than that at T0 time point,the HR at T4 and T5 time point in observation group was lower than that at T0 time point,the differences were statistically significant(P＜0.05),there was no significant difference in SpO2 at each time point in observation group(P＞0.05).While the MAP,HR,and SpO2 at T1,T2,T3,T4,and T5 time points in control group were significantly lower than those at T0 time points,the differences were statistically significant(P＜0.05).The MAP,HR,and SpO2 at T1,T2,T3,T4,and T5 time points in control group were lower than those in observation group,the differences were statistically significant(P＜0.05).The excellent and good rate of anesthesia in observation group was better than that in control group,the difference was statistically significant(P＜0.05).The propofol dosage in observation group was less than that in control group,the recovery time in observation group was shorter than that in control group,the differences were statistically significant(P＜0.05).There were no significant differences in duration of gastroenteroscopy examination,postanesthesia care unit(PACU)stay and leave hospital time between the two groups(P＞0.05).1,2,3,and 4 h postoperative pain VAS scores in observation group were less than those in control group,the differences were statistically significant(P＜0.05).The incidence of respiratory depression was 3.23％,which was significantly lower than 19.35％in control group,the incidence of hypotension was 4.84％,which was significantly lower than 25.81％in control group,the incidence of bradycardia was 0.00％,which was significantly lower than 17.74％in control group,the incidence of nausea and vomiting was 1.61％,which was significantly lower than 12.90％in control group,the differences were statistically significant(P＜0.05).There were no significant differences in the incidence of tachycardia,coughing,body movement,and dizziness between the two groups(P＞0.05).Conclusion Application of esketamine combined with butorphanol in painless gastroenteroscopy for elderly patients with obesity can effectively improve sedative and analgesic effects,stabilize hemodynamics,and reduce adverse reactions.It is worthy clinical application.

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.

[Objective]To analyze the annotation features of Jingui Yuhan Yaolue Shuyi,hoping to provide a reference for the study of Jingui Yaolue.[Methods]By using the method of bibliography the annotation texts in the book of Jingui Yuhan Yaolue Shuyi are classified and sorted out,the annotation features of Jingui Yuhan Yaolue Shuyi are systematically analyzed in combination with the relevant works such as Shuowen Jiezi,Shuowen Jiezi Judou and Liji.[Results]Tanba Motokata was a leading authority of Japanese textual criticism,Jingui Yuhan Yaolue Shuyi was to supplement his father's Jingui Yuhan Yaolue Jiyi in collation and annotation.The annotations in the book extensively collected the classics of the ancients,the coexistence of the examination and the collection of notes;proficient in elementary school,precisely analyzing the interchangeable words and ancient and modern characters;with a wide variety of schools,analyzing and commenting on the annotations of the predecessors;explaining the experience of treatment to provide reference for clinical operation.[Conclusion]Jingui Yuhan Yaolue Shuyi was an excellent annotation of Jingui Yaolue,which was collection of Tanba Motokata nearly thirty years of Zhongjing academic research essence,systematic studying this book has high reference significance for the study of Jingui Yaolue.

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.