Flubromazolam(Flub)is a novel psychoactive substance of benzodiazepines and the mechanism underlying its addiction still remains elusive.This study investigated the reward effect of Flub using conditioned place preference(CPP)mouse model.The neuronal activity was evaluated by c-Fos expression,and the neural circuit was tracked by virus tracing.This study also investigated the regulatory effect of neural circuits on Flub-induced reward effects through chemogenetic approach.The results showed that,at the dose of 3 mg/kg,Flub significantly increased CPP score and c-Fos expression in dopaminergic(DA)neurons of ventral tegmental area(VTA).Inhibition of VTA dopaminergic neuron activity dramatically decreased Flub-induced CPP score.Virus tracing verified GABAergic neuronal projection of medial rostrum tegmental nucleus(RMTg)to VTA dopaminergic neurons.Activation of RMTgGABA→VTADA circuit or blockade of benzodiazepine receptors(BZR)in RMTg significantly decreased Flub-induced CPP score.These results indicate that Flub produced reward effect via BZR-mediated RMTgGABA→VTADA circuit.

Background::Thoracic aortic aneurysm (TAA) is a fatal cardiovascular disease, the pathogenesis of which has not yet been clarified. This study aimed to identify and validate the diagnostic markers of TAA to provide a strong theoretical basis for developing new methods to prevent and treat this disease.Methods::Gene expression profiles of the GSE9106, GSE26155, and GSE155468 datasets were acquired from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using the "limma" package in R. Least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), random forest, and binary logistic regression analyses were used to screen the diagnostic marker genes. Single-sample gene set enrichment analysis (ssGSEA) was used to estimate immune cell infiltration in TAA.Results::A total of 16 DEGs were identified. The enrichment and functional correlation analyses showed that DEGs were mainly associated with inflammatory response pathways and collagen-related diseases. Collagen type I alpha 1 chain ( COL1A1) and synaptotagmin like 2 ( SYTL2) were identified as diagnostic marker genes with a high diagnostic value for TAA. The expression of COL1A1 and SYTL2 was considerably higher in TAA vascular wall tissues than in the corresponding normal tissues, and there were significant differences in the infiltration of immune cells between TAA and normal vascular wall tissues. Additionally, COL1A1 and SYTL2 expression were associated with the infiltration of immune cells in the vascular wall tissue. Single-cell analysis showed that COL1A1 in TAA was mainly derived from fibroblasts and SYTL2 mainly from cluster of differentiation (CD)8 + T cells. In addition, single-cell analysis indicated that fibroblasts and CD8 + T cells in TAA were significantly higher than those in normal arterial wall tissue. Conclusions::COL1A1 and SYTL2 may serve as diagnostic marker genes for TAA. The upregulation of SYTL2 and COL1A1 may be involved in the inflammatory infiltration of the vessel wall and poor extracellular matrix remodeling, promoting the progression of TAA.

Objective To explore the effect of depression in Parkinson's disease(PD)on the quality of life of patients.Methods The patients in this study were from the outpatient department and inpatients of PD specialty of Nanjing Brain Hospital from May 1,2022 to December 31,2022.The 199 patients were screened with Hamilton Depression Scale(HAMD-17)and 39 PD Quality of Life Questionnaire(PDQ-39).According to the HAMD-17 score,HAMD-17<14 was divided into PD group,and HAMD-17≥14 was divided into PD combined with depression group.The differences between the two groups in age,age of onset,course of disease,HAMD-17 score,PDQ-39 score,UPDRS-Ⅰ,UPDRS-Ⅱ,UPDRS-Ⅲwere compared,and the relationship between the PDQ-39 sub-dimension and HAMD-17 and the average score of the PDQ-39 sub-dimension of the two groups were further analyzed.Finally,the possible factors affecting the quality of life of patients were analyzed.Results The correlation analysis of each subdimension of HAMD-17 and PDQ-39 showed that except for physical discomfort,the other seven dimensions of PDQ-39 were positively correlated with HAMD-17 score,the differences were statistically significant(all P<0.05).Multiple linear regression analysis showed that in addition to HAMD-17,the influencing factors of quality of life were also associated with UPDRS-Ⅱ(activities of daily living).Conclusion PD complicated with depression is common,depressive symptoms can significantly affect the quality of life of patients.

Recent studies have shown that iron metabolism dysregulation and lipid peroxidation-induced ferroptosis, triggered by oxidative stress, play a key role in the development of aortic dissection. Dysregulated iron metabolism leads to excessive production of hydroxyl radicals due to abnormal iron levels and heme metabolism, while lipid peroxidation is linked to system Xc^－ dysfunction and accumulation of phospholipid hydroperoxides. These factors synergistically disrupt aortic homeostasis and drive ferroptosis in vascular cells, including endothelial and smooth muscle cells. Furthermore, disruptions in ferroptosis-related genes, along with risk factors such as smoking, epigenetic modifications such as protein methylation, and abnormalities in immune cells, particularly T cells, are closely linked to aortic dissection. Several small molecules and nanomaterials have shown potential in inhibiting ferroptosis in this context. This review elucidates the roles of ferroptosis in aortic dissection and proposes strategies for its targeted prevention and treatment.
Ferroptosis ; Humans ; Aortic Dissection/etiology* ; Lipid Peroxidation ; Iron/metabolism* ; Oxidative Stress ; Risk Factors ; Animals

Objective:To evaluate the clinical efficacy of metal braided stent deployed by fully protruding into the inferior vena cava for the treatment of iliac vein compression syndrome(IVCS).Methods:The clinical data of patients with IVCS treated with interwoven nitinol mesh stent protruding into the inferior vena cava and released from Jan 2018 to May 2021 in our center were retrospectively analyzed.Results:A total of 118 patients were included in this study. Among them, 7 cases were complicated with acute thrombosis, 3 cases were complicated with post thrombotic syndrome (PTS), and 108 cases were no more thrombotic iliac vein compression. The technical success rate was 100%, with an average of 2.03±0.77 stents implanted. Of the 23 ulcer patients, 18 ulcers healed after intervention, and the healing rate was 78.26%. The postoperative CEAP grade was significantly improved ( t=11.54, P<0.01), and the primary patency rate and second patency rate were 97.46% and 98.31% at 1 year after intervention. Conclusion:The fashion of fully protruding into inferior vena cava deployment in the treatment of iliac vein compressive disease has a high patency rate and satisfactory clinical efficacy.

Objective To analyze the prognostic factors in the patients with HER2-positive breast cancer adjuvant treated with trastuzumab.Methods We conducted a retrospective analysis of clinical data of 1 246 patients diagnosed with HER2-positive breast cancer between January 2009 and December 2019 who received treatment with trastuzumab.We investigated the factors impacting their prognosis by the Log-rank test univariate analysis and multivariate COX regression analysis.Results HER2-positive patients treated with trastuzumab had a poor prognosis in pT2-3(HR=2.10,P=0.003),pN2-3(HR=2.81,P<0.001),and no endocrine therapy(HR=2.50,P<0.001),and that had a better prognosis combined with taxane or other chemotherapy regimens(HR=0.40,P=0.017).We divided the patients into two subgroups according to the status of lymph node metastasis,and we found that in the negative lymph nodes group the patients with pT2-3 stage had poor prognosis(P=0.020),while the patients combined with taxane or other chemotherapy had better prognosis(P=0.032).In the positive lymph nodes group the patients with pT2-3 stage and no endocrine therapy had poor prognosis(P=0.012,P=0.001).Conclusions The patients with HER2-positive breast cancer treated with trastuzumab can be managed in different categories,for individuals without lymph node involvement and small tumor sizes,combining therapy with non-anthracycline chemotherapy is preferable for achieving improved outcomes,for patients with lymph node metastasis and large tumor sizes,if chemotherapy options are available,it is more recommended to use an anthracycline-free regimen to ensure the same prognosis while reducing the harm caused by the toxic side effects of chemotherapy.

We aimed to evaluate the effectiveness and safety of single-course initial regimens in patients with low-risk gestational trophoblastic neoplasia (GTN). In this trial (NCT01823315), 276 patients were analyzed. Patients were allocated to three initiated regimens: single-course methotrexate (MTX), single-course MTX + dactinomycin (ACTD), and multi-course MTX (control arm). The primary endpoint was the complete remission (CR) rate by initial drug(s). The primary CR rate was 64.4% with multi-course MTX in the control arm. For the single-course MTX arm, the CR rate was 35.8% by one course; it increased to 59.3% after subsequent multi-course MTX, with non-inferiority to the control (difference -5.1%,95% confidence interval (CI) -19.4% to 9.2%, P = 0.014). After further treatment with multi-course ACTD, the CR rate (93.3%) was similar to that of the control (95.2%, P = 0.577). For the single-course MTX + ACTD arm, the CR rate was 46.7% by one course, which increased to 89.1% after subsequent multi-course, with non-inferiority (difference 24.7%, 95% CI 12.8%-36.6%, P < 0.001) to the control. It was similar to the CR rate by MTX and further ACTD in the control arm (89.1% vs. 95.2%, P =0.135). Four patients experienced recurrence, with no death, during the 2-year follow-up. We demonstrated that chemotherapy initiation with single-course MTX may be an alternative regimen for patients with low-risk GTN.
Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Dactinomycin/adverse effects* ; Female ; Gestational Trophoblastic Disease/drug therapy* ; Humans ; Methotrexate/therapeutic use* ; Pregnancy ; Retrospective Studies

Digital and intelligent technology is an important driving force to promote the transformation and innovation of medical service mode and improve service quality. In February 2020, Peking Union Medical College Hospital established an intelligent outpatient pre-admission medical history collection system in order to improve the intelligent level of clinical application business system and the medical experience of outpatients.The system consisted of artificial intelligence capability layer, application service layer, capability resource layer and user application layer and hardware technology architecture. By docking with the hospital information system and using mobile terminal App, patients could submit pre-admission medical history information by themselves, and generate structured patient history for the visiting doctors to call. By November 2021, the pre-admission medical history collection system had covered 80% of the departments of the hospital, serving 1.68 million people in total, and the patient filling rate had reached 60%. The duration of patient′s medical history collection and the duration of doctor′s outpatient electronic medical record writing had been continuously shortened, greatly improving the efficiency of outpatient medical services.

Objective:To compare the efficacy between drug-coated balloon (DCB) combined with bare metal stenting (BMS) and plain old balloon angioplasty (POBA) with BMS placement in the treatment of femoral-popliteal TASC D lesions.Methods:According to the Trans-Atlantic Inter-Society Consensus (TASC) D grade femoral-popliteal lesions as the standard, we enrolled 115 cases (120 limbs) receiving DCB combined with BMS (group DCB, 37 limbs in 36 cases) and POBA combined with BMS (group POBA, 83 limbs in 79 cases) from Jan 2017 to Mar 2020 to observe patency rate, freedom from clinical-drived target lesion reintervention rate (FCD-TLR) and complications.Results:The mean follow-up time was 18.1 months and the average occlusion length was (29.1±6.5)mm. In group DCB vs group POBA, the primary patency rates at 3-month, 9-month, 1-year and 2-year were 89.2% vs. 86.7%, 86.4% vs. 76.9%, 66.8% vs. 70.9% and 63.1% vs. 56.9%, respectively ( P=0.73); FCD-TLRs were 100.0% vs. 95.1%, 94.3% vs. 82.3% , 78.5% vs. 80.6% and 74.1% vs. 68.9% ( P=0.69), respectively. Conclusion:The benefit of DCB combined with BMS over POBA combined with BMS in improving the early primary patency rate and reducing FCD-TLR was not definite.

Objective:To evaluate the application value of three-dimension digital subtraction angiography (3D-DSA) in the diagnosis and treatment of iliac vein compression syndrome (IVCS).Methods:A retrospective analysis was made on 171 patients with a tentative diagnosis of IVCS based on signs, symptoms, and finding of CTV or MRV, and iliac vein angiography. The diagnostic efficacy of MRV, 2D-DSA and 3D-DSA were analyzed. The imaging advantages of 3D-DSA in the diagnosis and treatment of IVCS were evaluated.Results:Ninty-three patients underwent MRV and 3D-DSA simultaneously, 101 patients had 2D-DSA and 3D-DSA simultaneously. 3D-DSA was taken as gold standard, the diagonotic sensitivity, specificity, Youden index of MRV was 75.61%, 72.73% and 0.48 respectively. The sensitivity, specificity, Youden index of 2D-DSA was 90.22%, 100% and 0.90 respectively. There are significant differences in the diagonotic sensitivity between MRV and 3D-DSA, 2D-DSA and 3D-DSA ( P<0.05). There is no significant difference in the diagonotic specificity between MRV and 3D-DSA, 2D-DSA and 3D-DSA ( P=1.000). In this study, we found that 3D-DSA has greater imaging evaluation advantages in preoperative evaluation, intraoperative guidance and immediate postoperative reexamination in the diagnosis and treatment of iliac vein disease. Conclusions:3D-DSA can improve the detection rate of IVCS, and has its advantage in imaging evaluation.