OBJECTIVE To provide guidance for the individualized use of antiepileptic drugs （AEDs） in patients with epilepsy or bipolar affective disorder.METHODS Clinical data of patients with epilepsy or bipolar affective disorder who received AEDs treatment and underwent therapeutic drug monitoring （TDM） at Xi’an International Medical Center Hospital from January 2023 to December 2025 were retrospectively collected. The baseline information， characteristics of AEDs utilization， implementation status of TDM and laboratory parameters were summarized. Spearman correlation analysis， univariate analysis and multivariate linear regression analysis were performed to identify the independent influencing factors for blood concentrations of AEDs.RESULTS A total of 1 572 patients were enrolled， including 660 males and 912 females. The majority were aged ≥60 years （30.15%）； 71.76% of patients were on monotherapy with AEDs， with valproic acid being the most commonly prescribed （51.97%）； combination therapy was predominantly a two-drug regimen （26.21%）， while three-drug regimens were rare （2.04%）. A total of 2 901 blood samples for TDM were collected， with the highest number of samples for valproic acid and levetiracetam （1 987 and 684 samples， respectively）. TDM for all five drugs was primarily conducted once； among which， the blood concentrations attainment rates exceeded 50% for patients taking valproic acid and levetiracetam， while the median blood concentrations for patients taking lamotrigine， oxcarbazepine， and carbamazepine were all below the lower limit of the therapeutic reference range. Based on the results of Spearman correlation analysis， univariate analysis， and multivariate linear regression analysis， patient gender， platelet count （PLT）， alanine transaminase （ALT）， aspartate transaminase （AST）， and total bilirubin （TBil） were found to be independent factors influencing blood concentration of valproic acid （unstandardized coefficients were －6.770 7， －0.078 6， －0.099 4， 0.083 2， －0.578 9， P ＜0.05）， while age and creatinine （CRE） were found to be independent factors influencing blood concentration of levetiracetam （unstandardized coefficients were 0.108 7， 0.047 8， P ＜0.05）.CONCLUSIONS Female gender and elevated AST levels are risk factors for increased blood concentration of valproic acid， while elevated PLT， ALT and TBil levels are associated with decreased blood concentration of valproic acid. Patients of advanced age and those with renal insufficiency bear a relatively high risk of in vivo levetiracetam accumulation.

ObjectiveTo unveil the mechanism of Jianpi Huogu prescription （JPHGP） in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head （SONFH） by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal， model， low-， medium-， and high-dose （2.5， 5， 10 g·kg^-1， respectively） JPHGP， and Jiangushengwan （1.53 g·kg^-1） groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg^-1 on days 1 and 2， and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg^-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection， and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head， and the number of adipocytes， the rate of empty bone lacunae， and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）， apolipoprotein A1 （ApoA1）， and apolipoprotein B （ApoB）. At the same time， the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed， and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking， immunohistochemistry， and Western blot. ResultsCompared with the normal group， the model group showcased thinning of the femoral head， trabecular fracture， karyopyknosis， subchondral cystic degeneration， increases in the number of adipocytes and the rate of empty bone lacunae （P<0.01）， a reduction in the trabecular area （P<0.01）， decreases in BMD， Tb.Th， Tb.N， and BV/TV， and increases in Tb.Sp and BS/BV （P<0.01）. Compared with the model group， the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae， an increase in the trabecular area （P<0.05， P<0.01）， rises in BMD， Tb.Th， Tb.N， and BV/TV， and decreases in Tb.Sp and BS/BV （P<0.05， P<0.01）. Compared with the normal group， the model group showcased raised serum levels of TG， TC， LDL， and ApoB and lowered serum levels of HDL and ApoA1 （P<0.01）. Compared with the model group， the JPHGP groups had lowered serum levels of TG， TC， LDL， and ApoB （P<0.05， P<0.01） and a risen serum level of ApoA1 （P<0.05， P<0.01）. Moreover， the serum level of HDL in the high-dose JPHGP group increased （P<0.01）. A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head， and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation， lipids， apoptosis， and osteoclast differentiation. Molecular docking， immunohistochemistry， and Western blot results showed that compared with the normal group， the model group displayed increased content of 5-lipoxygenase （5-LO） and peroxisome proliferator-activated receptor γ （PPARγ） in the femoral head （P<0.01）. Compared with the model group， medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ （P<0.05， P<0.01）. ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.

ObjectiveTo unveil the mechanism of Jianpi Huogu prescription （JPHGP） in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head （SONFH） by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal， model， low-， medium-， and high-dose （2.5， 5， 10 g·kg^-1， respectively） JPHGP， and Jiangushengwan （1.53 g·kg^-1） groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg^-1 on days 1 and 2， and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg^-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection， and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head， and the number of adipocytes， the rate of empty bone lacunae， and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）， apolipoprotein A1 （ApoA1）， and apolipoprotein B （ApoB）. At the same time， the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed， and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking， immunohistochemistry， and Western blot. ResultsCompared with the normal group， the model group showcased thinning of the femoral head， trabecular fracture， karyopyknosis， subchondral cystic degeneration， increases in the number of adipocytes and the rate of empty bone lacunae （P<0.01）， a reduction in the trabecular area （P<0.01）， decreases in BMD， Tb.Th， Tb.N， and BV/TV， and increases in Tb.Sp and BS/BV （P<0.01）. Compared with the model group， the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae， an increase in the trabecular area （P<0.05， P<0.01）， rises in BMD， Tb.Th， Tb.N， and BV/TV， and decreases in Tb.Sp and BS/BV （P<0.05， P<0.01）. Compared with the normal group， the model group showcased raised serum levels of TG， TC， LDL， and ApoB and lowered serum levels of HDL and ApoA1 （P<0.01）. Compared with the model group， the JPHGP groups had lowered serum levels of TG， TC， LDL， and ApoB （P<0.05， P<0.01） and a risen serum level of ApoA1 （P<0.05， P<0.01）. Moreover， the serum level of HDL in the high-dose JPHGP group increased （P<0.01）. A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head， and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation， lipids， apoptosis， and osteoclast differentiation. Molecular docking， immunohistochemistry， and Western blot results showed that compared with the normal group， the model group displayed increased content of 5-lipoxygenase （5-LO） and peroxisome proliferator-activated receptor γ （PPARγ） in the femoral head （P<0.01）. Compared with the model group， medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ （P<0.05， P<0.01）. ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.

Objective To explore the distribution characteristics and innervation patterns of pain-and itch-sensing nerves in dif-ferent regions of skin tissue.Methods Using Trpv1Cre;Ai9 and SstCre;Ai9 transgenic mouse systems,to analyze the distribution and in-nervation patterns of transient receptor potential vanilloid 1(TRPV1+)pain-sensing nerves and somatostatin(SST+)itch-sensing nerves in the skin of the forelimbs,hindlimbs and dorsal abdomen.Immunofluorescence staining was employed to quantitatively detect the distribution ratios of these two types of sensory neurons in the dorsal root ganglia(DRG).Results Free nerve terminal of both pain-and itch-sensing nerves were observed in the epidermal and dermal layers of skin tissue across all regions,but their morphological and distribution characteristics differed significantly.In the dermis,the two types of nerve fibers exhibited a parallel innervation pattern,while in the epidermis,their distribution tended to be more dispersed.Pain-sensing nerve terminal displayed a dense,filamentous distribu-tion,whereas itch-sensing nerve terminal were arranged in a sparse,bead-like pattern.In the DRG,the proportion of pain-sensing neuronal cell bodies was 76.13％±2.33％,while itch-sensing neuronal cell bodies accounted for only 7.58％±2.59％.Additionally,TRPV 1 was not only expressed in pain-sensing nerve fibers but also showed high expression in the stratum corneum,dermis,and inter-muscular layers of the plantar skin.In contrast,SST was primarily expressed in itch-sensing nerve fibers,with minor expression in peri-follicular cells.Conclusion Pain-and itch-sensing nerve fibers exhibit distinct innervation patterns in the skin.The widespread and dense distribution of pain-sensing nerve terminal may provide a structural basis for the rapid detection of potential noxious stimuli.This study offers morphological evidence to clarify the regulatory mechanisms of peripheral sensory nervous system function.

Objective To investigate the clinical features of chronic hepatitis C(CHC)patients with hepatitis C virus genotype 3(HCV GT3)infection and the risk factors for disease progression.Methods A multicenter retrospective cohort study was conducted among 1 002 CHC patients from 11 clinical centers in Northwest China from December 2017 to November 2023,and according to their genotype,they were divided into GT1,GT2,GT3,and GT6 groups.Clinical features were compared between the patients with different genotypes.The one-way analysis of variance was used for comparison of normally distributed continuous data between groups,and the Scheffe test was used for further comparison between two groups.The Kruskal-Wallis H test was used for comparison of data with skewed distribution between groups;the chi-square test or Fisher test was used for comparison of categorical data between groups.The multivariate logistic regression analysis was used to explore the influencing factors for the progression of CHC to liver cirrhosis.Results In terms of the genotype,there were 427 patients with GT1 infection,242 with GT2 infection,299 with GT3 infection(210 patients with GT3a infection,87 with GT3b infection,and 2 with unclassified genotype),and 34 with GT6 infection.The patients with GT3 infection had a significantly younger age than those with GT1 infection(51.3±0.5 years vs 53.2±0.6 years,P<0.05)or GT2 infection(51.3±0.5 years vs 53.7±0.8 years,P<0.05),and for the patients with liver cirrhosis,the patients with GT3 infection had a significantly younger age than those with GT1 infection(52.1±0.5 years vs 59.4±0.9 years,P<0.001)or GT2 infection(52.1±0.5 years vs 58.1±1.1 years,P<0.001).Among the patients with GT3 infection,male patients accounted for 77.9%and the patients with liver cirrhosis accounted for 46.2%,which were significantly higher than those among the patients with GT1,GT2 or GT6 infection(all P<0.001).At baseline,the patients with GT3 infection had significantly higher levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)than those with GT1 or GT2 infection,significantly higher aspartate aminotransferase-to-platelet ratio index(APRI)and fibrosis-4(FIB4)than those with GT1,GT2 or GT6 infection,a significantly lower platelet count(PLT)than those with GT2 or GT6 infection,a significantly higher level of alpha-fetoprotein than those with GT2 or GT6 infection,and a significantly lower level of albumin(Alb)than those with GT6 infection(all P<0.05).There were no significant differences between the patients with GT3a infection and those with GT3b infection in age,sex,the proportion of patients with liver cirrhosis,comorbidities,HCV RNA quantification,PLT,ALT,AST,alkaline phosphatase,Alb,APRI,and FIB-4(all P>0.05).The multivariate logistic regression analysis showed that PLT≤150×109/L(odds ratio[OR]=10.72,95%confidence interval[CI]:5.76-35.86,P<0.001)and Alb≤35 g/L(OR=3.74,95%CI:1.22-11.45,P=0.021)were risk factors for liver cirrhosis.Conclusion Most CHC patients with GT3 infection are male in Northwest China,and compared with the patients with other genotypes,such patients tend to have a younger age of onset and higher degrees of liver inflammation activity and fibrosis.Low PLT and a low level of Alb are risk factors for progression to liver cirrhosis in CHC patients with GT3 infection.

Objective To compare the application value of direct arteriovenous fistula(AVF),after ultrasound-guided percutaneous transluminal angioplasty(PTA)dilation of radial artery AVF formation and reverse"J"arteriovenous graft(AVG)in hemodialysis patients with small diameter vessels.Methods Totally 96 end-stage renal disease patients with distal radial artery＜1.5 mm and cephalic vein≥2.0 mm who planning to receive hemodialysis were retrospectively enrolled.The patients were divided into AVF group(n=30),PTA+AVF group(n=34)and AVG group(n=32)according to fistulization methods.The technical success rate,clinical success rate,primary patency rate and secondary patency rate were compared among groups.Results The technical success rate of AVF group,PTA+AVF group and AVG group was 80.00%,94.12%and 100%,respectively,and the clinical success rate was 30.00%,82.35%and 93.75%,respectively,with significant differences among 3 groups(both P＜0.05).The primary patency rate 1,3,6,9 and 12 months after fistulization in AVF group was 80.00%,30.00%,27.59%,27.59%and 24.14%,respectively,in PTA+AVF group was 94.12%,82.35%,78.79%,68.75%and 62.50%,respectively,while in AVG group was 100%,93.33%,83.33%,76.67%and 66.67%,respectively,all being significant different among 3 groups(all P＜0.05).The secondary patency rate 1,3,6,9 and 12 months after fistulization in AVF group was 83.33%,75.00%,75.00%,70.83%and 58.33%,respectively,in PTA+AVF group was 93.33%,93.33%,83.33%,83.33%and 80.00%,respectively,while in AVG group was 100%,100%,93.33%,90.00%and 80.00%,respectively,also being significant different among 3 groups(all P＜0.05).Conclusion Compared with direct and after ultrasound-guided PTA dilation of radial artery AVF formation,AVG formation was more valuable for hemodialysis patients with small diameter vessels.

Objective To investigate the impact and underlying mechanism of curcumin(Cur)on the aberrant proliferation and migration of VSMC.Methods VSMC was treated with Ang Ⅱ to establish a cell proliferation model.The experiment included blank control group,model group,and low-,medium-and high-dose Cur treatment groups(1.5,3.0 and 4.5 pmol/L,n=11).To explore the effect of Cur on the AMPK/mTOR signaling pathway,VSMC was also assigned into blank control,Ang Ⅱ(10-6 mol/L),Cur(3.0 μmol/L)and Ang Ⅱ+Cur groups(n=3).Western blotting was employed to detect the expression of VSMC differentiation markers(α-SMA),dedif-ferentiation marker(OPN),autophagy-related proteins(P62 and Beclin-1),and proteins involved in the AMPK/mTOR pathway(AMPK,p-AMPK,mTOR,p-mTOR,p70S6K,p-p70S6K).Results Exposure to Ang Ⅱ enhanced the proliferation and migration of VSMC when compared with the blank control group(155％vs 100％,66％vs 48％,P＜0.05).When compared with the model group,the proliferative rate was significantly lower in the medium-and high-dose Cur groups,and the migratory rate was obviously decreased in the three Cur groups(P＜0.05).The α-SMA expression was increased in the medium-and high-dose Cur groups,and that of OPN was decreased in the three Cur groups when compared with the model group(P＜0.05).Enhanced Be-clin-1 and p-AMPK/AMPK and down-regulated P62,p-mTOR/mTOR,and p-p70S6K/p70S6K were observed in the Ang Ⅱ and Cur groups than the blank control group(P＜0.05).The Cur Ang Ⅱ and Cur+AngⅡ groups had notably higher Beclin-1 and p-AMPK/AMPK but lower P62,p-mTOR/mTOR,and p-p70S6K/p70S6K than the Ang Ⅱ group(P＜0.05).Conclusion Cur in-hibits the proliferation and migration of VSMC induced by Ang Ⅱ,potentially through its activa-ting the AMPK/mTOR signaling pathway and enhancing autophagy in VSMC.