The prefrontal cortex (PFC) plays a pivotal role in orchestrating higher-order emotional and cognitive processes, a function that depends on the precise modulation of synaptic activity. Although pharmacological studies have demonstrated that dopamine signaling through dopamine D1 receptor (DRD1) in the PFC is essential for these functions, the cell-type-specific and molecular mechanisms underlying the neuromodulatory effects remain elusive. Using cell-type-specific knockout mice and patch-clamp recordings, we investigated the regulatory role of DRD1 on neurons and astrocytes in synaptic transmission and plasticity. Furthermore, we explored the mechanisms by which DRD1 on astrocytes regulate synaptic transmission and plasticity at the cellular level, as well as emotional and cognitive functions at the behavioral level, through two-photon imaging, microdialysis, high-performance liquid chromatography, transcriptome sequencing, and behavioral testing. We found that conditional knockout of the Drd1 in astrocytes (CKO^AST) increased glutamatergic synaptic transmission and long-term potentiation (LTP) in the medial prefrontal cortex (mPFC), whereas Drd1 deletion in pyramidal neurons did not affect synaptic transmission. The elevated level of d-serine in the mPFC of CKO^AST mice increased glutamatergic transmission and LTP through NMDA receptors. In addition, CKO^AST mice exhibited abnormal emotional and cognitive function. Notably, these behavioral changes in CKO^AST mice could be reversed through the administration of d-serine degrease to the mPFC. These results highlight the critical role of the astrocytic DRD1 in modulating mPFC synaptic transmission and plasticity, as well as higher brain functions through d-serine, and may shed light on the treatment of mental disorders.

Objective : To explore the causal relationship between 46 phenotypes ( including 15 seropositive case- control phenotypes and 31 quantitative antibody-measurement phenotypes) and ulcerative colitis( UC) using two- sample bidirectional Mendelian randomization( TSMR) . Methods: Single nucleotide polymorphisms ( SNPs) sig- nificantly associated with the relative abundance of the 46 antibody sera were extracted as instrumental variables ac- cording to preset thresholds . Summary statistics for UC were obtained from the OPEN GWAS database ( n = 47 745) . MR-Egger regression , weighted median method ( WME) , inverse variance weighting ( IVW) , the simple mode method (SM) , and weighted multitude method (WM) were used to estimate the causal relationship between antibody levels and UC , primarily using the IVW method . The results were assessed according to the effect indica- tor dominance ratios (OR) and 95% confidence intervals (CI) . Sensitivity analysis , heterogeneity test , gene plei- otropy test , and outlier test (MR-PRESSO) were combined to verify the stability and reliability of the results , and the causal association study was performed again using reverse Mendelian randomization(MR) . Results : IVW re- sults showed that Epstein-Barr( EB) virus EA-D antibody levels ( OR = 0. 806 , 95% CI = 0. 693 - 0. 939 , P < 0. 01) , Epstein-Barr virus EBNA-1 antibody levels ( OR = 1 . 870% , 95% CI = 1 . 480 - 2. 360 , P < 0. 000 1) , Anti-polyomavirus 2 IgG seropositivity (OR = 0. 570 , 95% CI = 0. 435 - 0. 746 , P < 0. 000 1) were associated with UC . The inverse MR analysis revealed a causal effect on anti-polyomavirus 2 IgG seropositivity , and none of the a- bove revealed genetic pleiotropy or significant heterogeneity of IVs . Conclusion EB virus EBNA-1 antibody levels are positively associated with the risk of UC , while EB virus EA-D antibody levels and anti-polyomavirus 2 IgG se- ropositivity are negatively associated with the risk of UC , indicating that they are protective factors for UC .

Objective To explore the authentic experiences of needle-related distress during arteriovenous fistula cannulation in hemodialysis patients and provide a basis for developing targeted assessment tools and intervention plans in clinical practice.Methods This study adopted a descriptive phenomenological research method.Using purposive sampling,13 hemodialysis patients with arteriovenous fistula from the blood purification center of a tertiary hospital in Changzhou were recruited for semi-structured interviews between November 2024 and January 2025.Data were analyzed using Colaizzi's 7-step method.Results Totally 4 themes and 10 sub-themes were extracted,namely dynamic evolution of distressing experiences(cognitive gaps and unfamiliar environments triggering distress,familiarity with procedures and self-management alleviating distress,sudden medical events reawakening distress),embodied cognition of distressing experiences(somatic distress,cognitive distress,mind-body dualistic interaction),subjective interaction in distress perception(subjective perceptions of differences in puncture skills,positive regulation through good communication attitudes),coping strategies for distressing experiences(empowerment-based coping,adaptive compromise).Conclusion The needle-related distress associated with arteriovenous fistula puncture in hemodialysis patients is not a single physical feeling,but a complex experience involving physical and mental interaction,nurse-patient interaction and coping strategies.Clinically,a dynamic assessment and precise intervention system should be constructed to improve patients' puncture experience and quality of life.

AIM:The aim of our study is to investigate the metabolic profile differences during cervical lesion progression and evaluate their potential clinical value in assisting the diagnosis of cervical cancer(CC).METHODS:Ul-tra-high-performance liquid chromatography coupled with high-resolution mass spectrometry(UHPLC-HRMS)was em-ployed to conduct non-targeted metabolomic analysis of cervical swab samples from 43 CC patients,34 high-grade squa-mous intraepithelial lesion(HSIL)patients,and 43 healthy controls.Based on the distinct features among the three groups,principal component analysis(PCA)was used to identify the metabolic differences among CC,HSIL and healthy groups.MetaboAnalyst 5.0 was then employed to perform KEGG pathway enrichment analysis on the differential metabo-lites.Finally,random forest machine learning algorithm was used to construct classification prediction models for distin-guishing CC from healthy,HSIL from healthy,and CC from HSIL.The performance of these models was evaluated using receiver operating characteristic(ROC)curve analysis.RESULTS:A total of 1 543 metabolites were identified across the healthy,HSIL and CC groups after filtration,with 407 metabolites differing between the groups.The study found that metabolite PGE2 was present in all three groups,with its expression levels progressively increasing with the progression of cervical lesions.Differential metabolite enrichment analysis demonstrated that CC is associated with specific cancer-relat-ed metabolic pathways,including the tricarboxylic acid cycle,tyrosine metabolism,tryptophan metabolism,and the pen-tose phosphate pathways.Additionally,the study developed three prediction models based on metabolic products for diag-nosing HSIL and CC:the full model,the simplified model,and the PGE2 model.The results indicated that metabolites ex-hibited strong diagnostic efficiency.Both the full model and the simplified model effectively distinguished CC from HSIL,CC from healthy,and HSIL from healthy.The AUC values for the full model were 0.90,0.92 and 0.84,respectively,while those for the simplified model were 0.81,0.95 and 0.85,respectively.Furthermore,the PEG2 model achieved AUC values of 0.74 and 0.80 for distinguishing CC from healthy and HSIL from healthy,respectively.CONCLUSION:The metabolic profiles of cervical cancer exhibit significant differences during the progression of cervical cancer,and these metabolites hold potential clinical value as biomarkers for cervical lesions.

Objective To explore surgical treatment efficacy for PAES.Methods A retrospective analysis was done on 12 PAES patients'surgery in our hospital from March 2018 to December 2023.Surgical plans included double popliteal artery exploration and repositioning with tendon transplantation,popliteal artery and vein release plus arterial thrombus removal,popliteal fossa exploration with popliteal artery release,and autologous vein patch angioplasty plus abnormal muscle bundle resection.Results Follow-up was 3 months to 5 years.11 patients had good affected limb skin temperature and blood supply,no symptom recurrence.One patient had left lower limb skin temperature decrease and pallor 2 years post-op(diagnosed as left popliteal fossa traumatic neuroma compressing popliteal artery),with blood supply restored after tumor removal.Conclusion Open surgery(tendon transplantation,vein patch)for PAES is effective.

Objective To explore surgical treatment efficacy for PAES.Methods A retrospective analysis was done on 12 PAES patients'surgery in our hospital from March 2018 to December 2023.Surgical plans included double popliteal artery exploration and repositioning with tendon transplantation,popliteal artery and vein release plus arterial thrombus removal,popliteal fossa exploration with popliteal artery release,and autologous vein patch angioplasty plus abnormal muscle bundle resection.Results Follow-up was 3 months to 5 years.11 patients had good affected limb skin temperature and blood supply,no symptom recurrence.One patient had left lower limb skin temperature decrease and pallor 2 years post-op(diagnosed as left popliteal fossa traumatic neuroma compressing popliteal artery),with blood supply restored after tumor removal.Conclusion Open surgery(tendon transplantation,vein patch)for PAES is effective.

Objective To explore the authentic experiences of needle-related distress during arteriovenous fistula cannulation in hemodialysis patients and provide a basis for developing targeted assessment tools and intervention plans in clinical practice.Methods This study adopted a descriptive phenomenological research method.Using purposive sampling,13 hemodialysis patients with arteriovenous fistula from the blood purification center of a tertiary hospital in Changzhou were recruited for semi-structured interviews between November 2024 and January 2025.Data were analyzed using Colaizzi's 7-step method.Results Totally 4 themes and 10 sub-themes were extracted,namely dynamic evolution of distressing experiences(cognitive gaps and unfamiliar environments triggering distress,familiarity with procedures and self-management alleviating distress,sudden medical events reawakening distress),embodied cognition of distressing experiences(somatic distress,cognitive distress,mind-body dualistic interaction),subjective interaction in distress perception(subjective perceptions of differences in puncture skills,positive regulation through good communication attitudes),coping strategies for distressing experiences(empowerment-based coping,adaptive compromise).Conclusion The needle-related distress associated with arteriovenous fistula puncture in hemodialysis patients is not a single physical feeling,but a complex experience involving physical and mental interaction,nurse-patient interaction and coping strategies.Clinically,a dynamic assessment and precise intervention system should be constructed to improve patients' puncture experience and quality of life.

AIM:The aim of our study is to investigate the metabolic profile differences during cervical lesion progression and evaluate their potential clinical value in assisting the diagnosis of cervical cancer(CC).METHODS:Ul-tra-high-performance liquid chromatography coupled with high-resolution mass spectrometry(UHPLC-HRMS)was em-ployed to conduct non-targeted metabolomic analysis of cervical swab samples from 43 CC patients,34 high-grade squa-mous intraepithelial lesion(HSIL)patients,and 43 healthy controls.Based on the distinct features among the three groups,principal component analysis(PCA)was used to identify the metabolic differences among CC,HSIL and healthy groups.MetaboAnalyst 5.0 was then employed to perform KEGG pathway enrichment analysis on the differential metabo-lites.Finally,random forest machine learning algorithm was used to construct classification prediction models for distin-guishing CC from healthy,HSIL from healthy,and CC from HSIL.The performance of these models was evaluated using receiver operating characteristic(ROC)curve analysis.RESULTS:A total of 1 543 metabolites were identified across the healthy,HSIL and CC groups after filtration,with 407 metabolites differing between the groups.The study found that metabolite PGE2 was present in all three groups,with its expression levels progressively increasing with the progression of cervical lesions.Differential metabolite enrichment analysis demonstrated that CC is associated with specific cancer-relat-ed metabolic pathways,including the tricarboxylic acid cycle,tyrosine metabolism,tryptophan metabolism,and the pen-tose phosphate pathways.Additionally,the study developed three prediction models based on metabolic products for diag-nosing HSIL and CC:the full model,the simplified model,and the PGE2 model.The results indicated that metabolites ex-hibited strong diagnostic efficiency.Both the full model and the simplified model effectively distinguished CC from HSIL,CC from healthy,and HSIL from healthy.The AUC values for the full model were 0.90,0.92 and 0.84,respectively,while those for the simplified model were 0.81,0.95 and 0.85,respectively.Furthermore,the PEG2 model achieved AUC values of 0.74 and 0.80 for distinguishing CC from healthy and HSIL from healthy,respectively.CONCLUSION:The metabolic profiles of cervical cancer exhibit significant differences during the progression of cervical cancer,and these metabolites hold potential clinical value as biomarkers for cervical lesions.

Atherosclerosis （AS） is a chronic inflammatory pathological process in which lipid and/or fibrous substances are deposited in the intima of arteries， and it is one of the pathological bases of many cardiovascular and cerebrovascular diseases. Endoplasmic reticulum stress （ERS） is a protective mechanism of cell adaptation. Moderate ERS can reduce abnormal protein aggregation and increase the degradation of misfolded proteins to repair and stabilize the internal environment， while excessive ERS can cause unfolded protein reaction， activate inflammation， oxidative stress， apoptosis， autophagy， and other downstream pathways， and lead to cell damage， or even apoptosis. A large number of studies have shown that ERS mediates a variety of pathological processes related to AS， affects endothelial cells， smooth muscle cells， macrophages， endothelial progenitor cells， and other cell components closely related to its occurrence and development， influences the progress of AS by regulating cell function， and promotes the formation of AS plaque， the transformation of stable plaque to unstable plaque， and the rupture of unstable plaque. Regulation of ERS may be a key target for the prevention and treatment of AS， and it is a research hotspot at present. Traditional Chinese medicine （TCM） believes that the origin of AS is the imbalance of Yin and Yang， the disharmony of Zangfu organs， and the abnormal operation of Qi， blood， and body fluid， which leads to the accumulation of phlegm， blood stasis， and other pathological products in the pulse channels， making the blood flow blocked or misfunction and causing the disease， which belongs to the syndrome of deficiency in origin and excess in superficiality. As the pathogenesis of AS is complex， and the symptoms are diverse， TCM has significant advantages in treating AS because of its multiple targets， multiple pathways， stable efficacy， strong individualization， and high safety. This paper systematically elaborated on the role of ERS in the occurrence and development of AS and summarized the mechanism research on the regulation and control of ERS by Chinese herbal monomer， Chinese herbal extract， Chinese herbal compound， and proprietary medicine， so as to provide a theoretical basis for clinical research and drug development in the prevention and treatment of AS.

Objective To investigate the association between electrode fusion error and improve-ment of depression during subthalamic nucleus-deep brain stimulation(STN-DBS)surgery for Parkinson's disease(PD).Methods A prospective trial was conducted on 240 PD patients under-going STN-DBS treatment in our hospital from January 2020 to December 2022.According to their clinical outcomes,they were divided into effective group(211 cases)and ineffective group(29 cases).The electrode fusion error was compared among the patients with different efficacy,psychological status,and cognitive status to analyze the correlation of electrode fusion error dur-ing STN-DBS surgery with improvement of depression and cognition.Results There were no sig-nificant differences between the effective group and ineffective group in terms of gender,age,body mass index,hypertension,diabetes,hyperlipidemia,disease duration,or preoperative MMSE and PDQ-39 scores(P＞0.05).STN-DBS treatment resulted in obviously improved clinical symptoms such as tremor,rigidity and bradykinesia,and higher UPDRSⅢ score when compared with the re-sults of preoperative impact test(P＜0.01).Before treatment,no statistical differences were ob-served in the scores of SAS,SDS,MoCA,MMSE,Alzheimer's disease assessment scale cognitive subscale(ADAS-Cog)or Chinese medicine syndrome change overall impression scale(CGIC-S)between the effective and ineffective groups(P＞0.05).After treatment,the scores of SAS,SDS,CGIC-S and ADAS-Cog were declined(P＜0.01),and these four scores was notably lower in the effective than the ineffective groups(P＜0.01).The scores of MoCA and MMSE were significant-ly elevated in both groups after surgery(P＜0.01),and the scores were higher in the effective group than the ineffective group(P＜0.01).The target coordinate deviation on the left and right was significantly higher in the patients with SDS≥53 and SAS≥50 than those of SDS＜53 and SAS＜50(P＜0.01).The target coordinate deviation on the left and right of the patients with MoCA＜26,MMSE＜27,ADAS-Cog≥36 and CGIC-S＞1 was statistically higher than that of the patients with MoCA≥ 26,MMSE≥27,ADAS-Cog＜36 and CGIC-S≤1(P＜0.01).Correlation analysis displayed that the bilateral fusion error of patients was negatively correlated with MoCA and MMSE scores(r=-0.678,P＜0.01;r=-0.653,P＜0.01;r=-0.448,P＜0.01;r=-0.704,P＜0.01),and positively with ADAS-Cog,CGIC-S,SDS and SAS scores(r=0.586,P＜0.01;r=0.501,P＜0.01;r=0.572,P＜0.01;r=0.601,P＜0.01;r=0.742,P＜0.01;r=0.667,P＜0.01;r=0.463,P＜0.01;r=0.381,P＜0.01).Conclusion In PD treatment,electrode fusion error during STN-DBS is significantly correlated with improvement of depression and cognitive score,which can be used as one of the important evidence for predicting clinical effectiveness.In the future,according to the intraoperative error,auxiliary treatment can be carried out timely and effectively to guide further clinical treatment.