Depression (Dep) is one of the most common concomitant symptoms of Parkinson's disease (PD), but there is a lack of detailed pathologic evidence for the occurrence of PD-Dep. Currently, the management of symptoms from both conditions using conventional pharmacological interventions remains a formidable task. In this study, we found impaired activation of extracellular signal-related kinase (ERK), reduced levels of transcription and translation, and decreased expression of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC) of PD-Dep rats. We demonstrated that the abnormal phosphorylation of α-synuclein (pS129) induced tropomyosin-related kinase receptor type B (TrkB) retention at the neuronal cell membrane, leading to BDNF/TrkB signaling dysfunction. We chose SEW2871 as an ameliorator to upregulate ERK phosphorylation. The results showed that PD-Dep rats exhibited improvement in behavioral manifestations of PD and depression. In addition, a reduction in pS129 was accompanied by a restoration of the function of the BDNF/ERK signaling loop in the mPFC of PD-Dep rats.
Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; alpha-Synuclein/metabolism* ; Male ; Prefrontal Cortex/drug effects* ; Rats, Sprague-Dawley ; Depression/metabolism* ; MAP Kinase Signaling System/drug effects* ; Rats ; Parkinson Disease/metabolism* ; Receptor, trkB/metabolism* ; Phosphorylation ; Disease Models, Animal ; Signal Transduction

Mutations in ion channel genes have long been implicated in a spectrum of epilepsy syndromes. However, therapeutic decision-making is relatively complex for epilepsies associated with channelopathy. Therefore, in the present study, we used a patient-derived organoid model with a novel SCN2A mutation (p.E512K) to investigate the potential of utilizing such a model as a platform for preclinical testing of anti-seizure compounds. The electrophysiological properties of the variant Nav1.2 exhibited gain-of-function effects with increased current amplitude and premature activation. Immunofluorescence staining of patient-derived cortical organoids (COs) displayed normal neurodevelopment. Multielectrode array (MEA) recordings of patient-derived COs showed hyperexcitability with increased spiking and remarkable network bursts. Moreover, the application of patient-derived COs for preclinical drug testing using the MEA showed that they exhibit differential responses to various anti-seizure drugs and respond well to carbamazepine. Our results demonstrate that the individualized organoids have the potential to serve as a platform for preclinical pharmacological assessment.
Organoids/physiology* ; NAV1.2 Voltage-Gated Sodium Channel/genetics* ; Humans ; Anticonvulsants/pharmacology* ; Epilepsy/drug therapy* ; Mutation ; Cerebral Cortex/drug effects* ; Action Potentials/drug effects* ; Carbamazepine/pharmacology*

Objective:To observe the therapeutic effects of electroacupuncture(EA)stimulation on chronic pain and associated negative emotions,and to investigate the activity changes of glutamatergic neurons in the primary motor cortex(M1)following EA stimulation.Methods:Male C57BL/6J mice were randomly divided into four groups:sham surgery(Sham),pure electroacupuncture stimulation(EA),nerve injury(SNI)and electroacupuncture treatment of nerve injury(SNI+EA).Thirty days after the SNI model establishment,EA stimulation was administered bilaterally to the Zusanli(ST36)acupoints in mice.von Frey filaments and Hargreaves heat sensitivity testing were used to detect mechanical and thermal hyperalgesia.The elevated plus maze test was conducted to assess the impact on anxiety-like behaviors in mice.Dual immunofluorescence staining was employed to observe changes in c-Fos expression in M1 gluta-matergic neurons.Results:As compared to Sham group,SNI-treated mice exhibited significant mechanical and thermal hyperalgesia in bilateral hindpaws at 30 days post-modeling(P＜0.01)and displayed obvious anxiety-like behaviors(P＜0.01).The SNI+EA group showed significant relief in pain and anxiety-like behaviors(P＜0.01).c-Fos expression in M1 glutamatergic neurons was significantly decreased in SNI mice.Conversely,after electroacupuncture(EA)treatment,compared to the SNI group,M1 glutamatergic neurons in the SNI+EA group showed significantly in-creased c-Fos expression(P＜0.01).Conclusion:Electroacupuncture significantly alleviated chronic pain and associ-ated anxiety-like behaviors induced by SNI,which might involve the activation of glutamatergic neurons in the M1 in this process.

Objective:To investigate children's attention deficit hyperactivity disorder symptoms and their im-pact on parental anxiety and depression,as well as the mediating role of parent-child relationship.Methods:A total of 472 children with ADHD who met the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Dis-orders,Fourth Edition(DSM-Ⅳ)were selected.The severity of ADHD symptoms was assessed using the Attention Deficit Hyperactivity Disorder Rating Scale(ADHD-RS),parent-child relationships were assessed using the Parent-Child Relationship Test(PCRT),and parental anxiety and depression were assessed using the Generalized Anxiety Disorder 7-item Scale(GAD-7)and the Patient Health Questionnaire-9(PHQ-9),respectively.Mediation analysis was conducted following structural equation modeling construction.Results:There was a positive correlation be-tween ADHD-RS scores and PCRT scores,parental GAD-7 scores,and PHQ-9 scores(r=0.19-0.29,Ps＜0.001).PCRT scores significantly mediated the relationship between ADHD-RS total scores and parental GAD-7 and PHQ-9 scores(β=0.02-0.03,Ps＜0.05).PCRT scores did not significantly mediate the relationship between ADHD-RS inattention scores and parental GAD-7 and PHQ-9 scores(β=0.01-0.02,Ps＞0.05).PCRT scores significantly mediated the relationship between ADHD-RS hyperactivity/impulsivity scores and parental GAD-7 and PHQ-9 scores(β=0.02,Ps＜0.05).Conclusion:The symptoms of ADHD in children are associated with parental anxiety and depression symptoms,with parent-child relationships mediating this relationship.

Polycystic ovary syndrome （PCOS） is a common gynecological endocrine and reproductive disorder，with the main clinical manifestations including ovulation failure，insulin resistance，hyperandrogenism，and obesity. Its occurrence and development are closely related to cellular regulatory mechanisms such as apoptosis，autophagy，oxidative stress，and inflammatory response. Autophagy，as a clearance mechanism that maintains cellular homeostasis，plays a crucial role in maintaining the growth，development，and maturation of oocytes. Exploring the mechanism of autophagy during the occurrence and development of diseases can help develop treatment methods for PCOS by regulating autophagy. Studies have shown that autophagy plays an important role in the pathogenesis of PCOS，and it can affect the occurrence and development of PCOS through multiple pathways，levels，and targets. Traditional Chinese medicine （TCM） regulates autophagy in ovarian granulosa cells or endometrium of patients with PCOS by targeting the expression of autophagy signaling pathways，regulatory factors，and non-coding single-stranded RNA molecules，thereby alleviating inflammation，regulating metabolism disorders，and balancing hormone levels in PCOS. Accordingly，TCM can ameliorate pathological conditions such as insulin resistance，hyperandrogenism，and ovulation failure in PCOS. This article summarizes the TCM formulas and extracts for the treatment of PCOS，as well as the main autophagy pathways and regulatory factors involved，aiming to provide reference and suggestions for the future treatment of PCOS with TCM by regulating autophagy.

Objective:To explore the clinicopathological features and prognosis of double primary cancer of breast cancer and lung cancer.Methods:A total of 40 patients with breast cancer and lung cancer admitted to Beijing Friendship Hospital, Capital Medical University from December 2015 to December 2023 were retrospectively selected, and the clinicopathological characteristics and prognosis of patients with double primary cancer included in the study were analyzed. The count data were expressed as the number of cases and percentage, Chi-test was used for inter-group comparison or Fisher exact probability method was used for single frequency < 5, rank sum test was used for inter-group comparison of two-sample levels, and Kruskal-Walllis H test was used for inter-group comparison of three-sample levels. The survival rate and survival were analyzed by Kaplan-Meier method, and the survival curve was compared by Log-rank method. Results:Among the 40 patients, 50% were patients with simultaneous and metachronous double primary cancer. And there were statistically significant differences between the two groups in the number of lymph node metastases and whether to receive endocrine therapy ( P=0.025, 0.028). There were 32 patients firstly appear breast cancer, while 8 patients firstly appear lung cancer. And there were statistically significant differences in the body mass index and TNM stage of breast cancer between the two groups ( P=0.004, 0.015). The proportion of progesterone receptor positive patients with human epidermal growth factor receptor 2 low-expression in breast cancer was significantly higher than that in patients with HER2 non-expression and HER2 overexpression ( P=0.023). 92.5% of patients had lung adenocarcinoma, and 77.5% of patients were clinical stage I of lung cancer, and the overall survival of patients who received adjuvant therapy after lung cancer surgery was significantly lower than that of patients without adjuvant therapy, the difference was statistically significant ( P<0.001). Conclusion:The prognosis of patients receiving adjuvant therapy after lung cancer surgery is poor, and regular follow-up after breast cancer surgery is helpful for early detection and early treatment of lung cancer.

Objective:To analyze the transcriptomic features of breast cancer and its lymph node metastasis using single-cell RNA sequencing, to identify potential biomarkers for breast cancer.Methods:The GSE180286 single-cell RNA sequencing dataset was used to examine the transcriptomic characteristics of breast cancer and its lymph node metastasis. Following quality control, dimensionality reduction, clustering, and cell annotation of single-cell data, genes associated with breast cancer were identified. Dotplot, FeaturePlot, and other analytical methods were applied to investigate the expression profiles of target genes ( ALOX15B, FAAH, HDGF, KLF5, TLE3, TNS1) across different cell types and to assess their activity in immune and metabolic pathways. Statistical analysis was performed using the bilateral Student′s t-test. Results:ALOX15B, FAAH, HDGF, KLF5, TLE3, and TNS1 were differentially expressed across various cell types in breast cancer. ALOX15B was specifically expressed in macrophages and involved in immune responses, particularly with high activity in complement and inflammatory response pathways. HDGF was primarily expressed in epithelial cells and closely associated with breast cancer proliferation, migration, and angiogenesis. FAAH, KLF5, TLE3, and TNS1 were also closely related to the onset and progression of breast cancer. Co-expression analysis revealed relationships between these genes and breast cancer regulatory genes such as BRCA1 and BRCA2. Conclusions:This study identified 6 breast cancer-specific expressed potential biomarkers, and revealed their expression characteristics in different cell types and their differential activity in immune-metabolism-related pathways. These findings provide potential targets for understanding the molecular mechanisms of breast cancer and developing new therapeutic strategies.

Objective : To explore the effect of the addition of N-acetylcysteine ( NAC) on the abnormal increase of reactive oxygen species ( ROS) during platelet cold storage，and to clarify its function of preventing the platelets from being recognized and cleared by macrophages and hepatocytes． Methods : Platelets Concentrates were divided into room temperature group ( 22C) ，cold storage group ( 4C) and NAC addition group．In NAC addition group， the platelets were supplemented with 5 mmol / L ( N5) and 25 mmol / L ( N25) NAC．After 5-day storage，the levels of ROS，activation markers and other index of platelets in each group were detected by flow cytometry． Platelet phagocytosis was detected by PMA-activated THP-1 cells or by primary cultured HepG2 cells． Results : After 5 days of storage，ROS increased significantly in 4C group than those in 22C group ( P＜0. 05) ，and after NAC addi- tion，ROS level reduced significantly ( P＜0. 05) ．The expression of CD62P and PS and the exposure of β-GlcNAc on platelets in N5 group significantly decreased compared with those in 4C group ( P＜0. 05) ．The platelet phago- cytosis by THP-1 and HepG2 cells were also significantly lower in N5 group than those in 4C group ( P＜0. 05) ． However，the addition of 5 mmol / L NAC did not significantly affect the count，pH，CD42b expression，β-Gal ex- posure and coagulation function of cold-stored platelet after 5-day storage． Conclusion The addition of NAC to re- frigerated platelets can significantly decrease the level of platelet ROS and effectively reduce their phagocytosis by cells，suggesting that NAC addition may protect refrigerated platelets from being cleared by phagocytosis after trans- fusion．

Primary liver cancer is one of the most common causes of cancer-related deaths in China,with hepatocellular carcinoma(HCC)accounting for 75%-85%.Approximately 70%of HCC patients are in the advanced stage at the time of diagnosis and miss the opportunity for radical surgery,leading to a poor prognosis.Yttrium-90 microsphere selective internal radiation therapy(90Y-SIRT),an emerging therapeutic modality,delivers radioactive microspheres via the hepatic artery to target tumors and uses beta radiation for localized tumor ablation.Compared to conventional transarterial chemoembolization and pharmacotherapy,90Y-SIRT shows the advan-tages of significant clinical benefits,good safety profiles,and broad applicability across diverse patient populations.This article re-views the advances in the application of 90Y-SIRT in HCC treatment.

Primary liver cancer is a malignant tumor with high incidence and mortality rates worldwide,and the early diagnosis of pri-mary liver cancer and the optimization of precise treatment strategies have become critical issues in the healthcare field.Due to the in-sufficient capabilities for molecular characterization,it is increasingly difficult for traditional imaging techniques to meet clinical needs in the era of precision medicine.Multimodal molecular imaging technology integrates the advantages of imaging modalities such as ul-trasound imaging,magnetic resonance imaging,and optical imaging,thereby achieving synergistic enhancement between molecular bio-logical information of liver cancer and precise anatomical localization and demonstrating a significant value in the diagnosis and treat-ment of liver cancer.This article reviews the advances in the application of multimodal molecular imaging in the early diagnosis,pre-cise treatment,and therapeutic efficacy monitoring of liver cancer.