ObjectiveTo investigate the feasibility， safety， and efficacy of surgery-assisted transjugular intrahepatic portosystemic shunt （SA-TIPS） in the treatment of portal hypertension comorbid with complex portal vein thrombosis， including cavernous transformation of the portal vein （CTPV）. MethodsAn analysis was performed for the data of 36 patients with portal hypertension and complex portal vein thrombosis who underwent SA-TIPS in Beijing Shijitan Hospital， Capital Medical University， from November 2023 to January 2025， including general status， technical data of the surgical process （surgical success rate， puncture times， time of operation， the number of stents used， and the length of shunt）， perioperative complications， and surgical recovery. The change in portal pressure gradient （PPG） after shunt was compared， and the rate of reaching the standard for PPG reduction was calculated， as well as stent patency rate within 1 week after surgery. The paired samples t-test was used for comparison of continuous data between two groups. ResultsAmong the 36 patients， 34 （94.4%） underwent SA-TIPS successfully. The incidence rate of perioperative complications was 16.7% （6/36）， including 3 cases of thoraco-abdominal hemorrhage， 2 cases of intraoperative arrhythmia， and 1 case of incision infection. There was a significant reduction in PPG after SA-TIPS （t=19.85， P<0.01）， and the patients achieving a ≥50% reduction in PPG accounted for 76.5% （26/34）. Imaging reexamination within 1 week showed a shunt patency rate of 100%. ConclusionSA-TIPS has a high technical success rate， a favorable safety profile， and good efficacy in the treatment of portal hypertension comorbid with complex portal vein thrombosis （including CTPV）， and therefore， it holds promise for clinical application.

Objective To investigate the effects of LBL-007, a novel fully human lymphocyte activation gene 3 (LAG-3) monoclonal antibody, in combination with programmed cell death protein 1 (PD-1) antibody, on the invasion, migration and proliferation of tumor cells, and to elucidate the underlying mechanisms. Methods Human lymphocyte cells Jurkat were co-cultured with A549 and MGC803 tumor cell lines and treated with the isotype control antibody human IgG, LBL-007, anti-PD-1 antibody BE0188, or tumor necrosis factor-alpha (TNF-α, the NF-κB signaling pathway agonist). Tumor cell proliferation was assessed using a colony formation assay; invasion was measured by Transwell^TM assay; migration was evaluated using a wound healing assay. Western blotting was employed to determine the expression levels of NF-κB pathway-related proteins: IκB inhibitor kinase alpha (Ikkα), phosphorylated Ikkα (p-IKKα), NF-κB subunit p65, phosphorylated p65 (p-p65), NF-κB Inhibitor Alpha (IκBα), phosphorylated IκBα (p-IκBα), matrix metalloproteinase 9 (MMP9), and MMP2. Results Compared with the control and IgG isotype groups, LBL-007 and BE0188 significantly reduced tumor cell proliferation, invasion, and migration. They also decreased the phosphorylation of p-IKKα, p-p65 and p-IκBα, and the expression of MMP9 and MMP2 of tumor cells in the co-culture system. The combined treatment of LBL-007 and BE0188 enhanced inhibitory effects. Treatment with the NF-κB signaling pathway agonist TNF-α reversed the suppressive effects of LBL-007 and BE0188 on tumor cell proliferation, invasion, migration, and NF-κB signaling. Conclusion LBL-007 and anti-PD-1 antibody synergistically inhibit the invasion, migration, and proliferation of A549 and MGC803 tumor cells by blocking the NF-κB signaling pathway.
Humans ; Cell Proliferation/drug effects* ; Cell Movement/drug effects* ; Signal Transduction/drug effects* ; NF-kappa B/metabolism* ; Neoplasm Invasiveness ; Antibodies, Monoclonal/pharmacology* ; Programmed Cell Death 1 Receptor/antagonists & inhibitors* ; Cell Line, Tumor ; Antigens, CD/immunology* ; Lymphocyte Activation Gene 3 Protein ; A549 Cells ; I-kappa B Kinase/metabolism* ; Jurkat Cells ; Matrix Metalloproteinase 9/metabolism*

Magnetic stimulation has made significant strides in the treatment of psychiatric disorders. Nonetheless, current magnetic stimulation techniques lack the precision to accurately modulate specific nuclei and cannot realize deep brain magnetic stimulation. To address this, we utilized superparamagnetic iron oxide nanoparticles as mediators to achieve precise targeting and penetration. We investigated the effects of magnetic fields with varying frequencies on neuronal activity and compared the activation effects on neurons using a 10-Hz precise magneto-stimulation system (pMSS) with repetitive transcranial magnetic stimulation in mice. Oxytocin levels, dendritic morphology and density, and mouse behavior were measured before and after pMSS intervention. Our findings suggest that pMSS can activate oxytocinergic neurons, leading to upregulation of oxytocin secretion and neurite outgrowth. As a result, sociability was rapidly improved after a one-week pMSS treatment regimen. These results demonstrate a promising magneto-stimulation method for regulating neuronal activity in deep brain nuclei and provide a promising therapeutic approach for autism spectrum disorder.
Animals ; Autism Spectrum Disorder/physiopathology* ; Paraventricular Hypothalamic Nucleus/physiology* ; Disease Models, Animal ; Transcranial Magnetic Stimulation/methods* ; Male ; Social Behavior ; Mice ; Oxytocin/metabolism* ; Mice, Inbred C57BL ; Neurons/physiology*

Oral submucous fibrosis (OSF), characterized by excessive deposition of extracellular matrix (ECM) that causes oral mucosal tissue sclerosis, and even cancer transformation, is a chronic, progressive fibrosis disease. However, despite some advancements in recent years, no targeted antifibrotic strategies for OSF have been approved; likely because the complicated mechanisms that initiate and drive fibrosis remain to be determined. In this review, we briefly introduce the epidemiology and etiology of OSF. Then, we highlight how cell-intrinsic changes in significant structural cells can drive fibrotic response by regulating biological behaviors, secretion function, and activation of ECM-producing myofibroblasts. In addition, we also discuss the role of innate and adaptive immune cells and how they contribute to the pathogenesis of OSF. Finally, we summarize strategies to interrupt key mechanisms that cause OSF, including modulation of the ECM, inhibition of inflammation, improvement of vascular disturbance. This review will provide potential routes for developing novel anti-OSF therapeutics.
Humans ; Oral Submucous Fibrosis/immunology* ; Extracellular Matrix/metabolism* ; Myofibroblasts

Objective To study the predictive value of the Prognostic Assessment Scale for Patients with Spontaneous Intracerebral Hemorrhage(ICH-LR2S2)and the Prehospital Risk Assessment Scale for Prehospital Deterioration Risk Assessment Scale(ICH-APS)for the development of stroke-associated pneu-monia(SAP)in patients with spontaneous intracerebral hemorrhage.Methods A total of 349 patients with spontaneous intracerebral hemorrhage who were hospitalized for the first time in this hospital from July 2023 to July 2024 were selected as the research subjects.The general demographic data and medical documentations of the patients were collected,and ICH-LR2S2 score and ICH-APS score were carried out within 48 hours after admission.According to whether pneumonia occurred within 7 days after admission,the patients were divided into the SAP group and the non-SAP group,and the diagnostic efficiency of the ICH-LR2S2 score and ICH-APS score for SAP in patients with spontaneous intracerebral hemorrhage was evaluated.Results Among the 349 patients with spontaneous intracerebral hemorrhage,98 patients(28.08％)had pneumonia.The results of multivariate logistic regression analysis showed that age,history of chronic obstructive pulmonary disease(COPD),nasogastric tube,tracheal intubation,National Institutes of Health Stroke Scale(NIHSS)score,Glasgow Coma Scale(GCS)score,C-reactive protein,fasting blood glucose,dysphagia,ICH-LR2S2 score,ICH-APS-A score,and ICH-APS-B score were independent influencing factors for SAP in patients with spontane-ous intracerebral hemorrhage(P＜0.05).The results of the receiver operating characteristic(ROC)curve showed that the ICH-LR2S2 score had the highest diagnostic efficiency for SAP in patients with spontaneous intracerebral hemorrhage,with an area under the curve(AUC)of 0.837,a sensitivity of 0.827,a specificity of 0.783,and a Youden index of 0.610.Conclusion ICH-LR2S2 score has a high predictive value for the occur-rence of SAP in patients with spontaneous intracerebral hemorrhage.

Objective:To investigate the relationship between nerve growth factor (NGF) concentration in follicular fluid and abnormal menstrual cycle in infertile patients with polycystic ovary syndrome (PCOS).Methods:A retrospective cohort study was conducted on 100 infertile patients with PCOS who underwent in vitro fertilization and embryo transfer (IVF-ET) at Department of Obstetrics and Gynecology, Peking University Third Hospital from March 2017 to June 2019. For comparison, the 100 patients with PCOS were divided into low NGF group ( n=50) and high NGF group ( n=50) based on the median NGF concentration (1 644.03 ng/L) in follicular fluid. Baseline characteristics, menstrual status and clinical outcomes of assisted reproductive technology were compared. We performed multiple linear regression analysis to examine the effect of NGF in follicular fluid on menstrual cycle length for multivariate analysis. Results:1) PCOS patients in the low NGF group had significantly higher body mass index [(27.24±5.17) kg/m 2] and white blood cell count [7.31(5.99, 8.43)×10 9/L ] than those in the high NGF group [(25.03±4.46) kg/m 2, P=0.024; 5.95(5.08,7.01)×10 9/L, P=0.001], while high-density lipoprotein cholesterol [1.15 (0.98, 1.36) mmol/L] and basic follicle-stimulating hormone level [6.51 (5.10,7.95) U/L] in the low NGF group were significantly lower than those in the high NGF group [1.36 (1.09,1.52) mmol/L, P=0.039;6.51 (5.10,7.95)U/L, P=0.040]. 2) PCOS patients in the low NGF group had significantly higher menstrual cycle length [60.00 (35.00, 180.00) d] than the high NGF group [32.50 (27.00,67.50) d, P=0.001]. 3) Multiple linear regression analysis revealed that after adjustment for body mass index, age, infertility duration, infertility type, and glucose and lipid metabolic parameters, the NGF concentration in the follicular fluid independently and negatively correlated with menstrual cycle length ( P<0.05). 4) The NGF concentration in follicular fluid was not correlated with assisted reproductive outcomes. Conclusion:NGF concentration in follicular fluid is closely related to the degree of menstrual cycle abnormalities in patients with PCOS.

Objective Exploring the behavioral changes induced by quinpirole in obsessive-compulsive disorder(OCD)mouse,investigating the activation of neurons in different brain regions,and identifying differentially expressed genes(DEGs)and enriched biological pathways through transcriptome sequencing technology to elucidate the pathogenesis of OCD.Methods Randomly assign 32 male C57BL/6J mice,aged two months,to an OCD group and a control group(n=16).Administering quinpirole(0.75 mg/kg)via subcutaneous injection to the OCD group mice every other day for a total of 19 injections,while the control group mice received an equivalent volume of saline solution.Following the completion of the model construction,open field testing,elevated plus maze testing,and marble burying tests were conducted.After the completion of behavioral studies,tissue samples were collected.Neuronal damage was assessed using Nissl staining,while the expression of c-Fos and Iba1 proteins was examined through immunofluorescence staining.Transcriptome sequencing technology was utilized to screen for differentially expressed genes and to enrich relevant signaling pathways.The expression of inflammatory cytokines,including TNF-α,NF-κB p65,phosphorylated NF-κB p65(p-NF-κB p65),and IL-6,was detected using Western Blot analysis.Results Mouse induced with OCD by quinpirole exhibit anxiety-like behaviors and compulsive-like behaviors.Neurons in the hippocampal and hypothalamic regions exhibit signs of damage.The expression of c-Fos and Iba1 proteins is increased in the cortex,striatum,hypothalamus,and other brain regions.Western Blot result indicate a significant increase in the expression of pro-inflammatory cytokines such as TNF-α,p-NF-κB p65,and IL-6.Conclusions In OCD mouse,neurons in multiple brain regions are abnormally activated,microglia exhibit dysfunction,and neuroinflammation induced by the activation of the NF-κB signaling pathway accompanies the development of OCD.

Objective:To investigate the relationship between nerve growth factor (NGF) concentration in follicular fluid and abnormal menstrual cycle in infertile patients with polycystic ovary syndrome (PCOS).Methods:A retrospective cohort study was conducted on 100 infertile patients with PCOS who underwent in vitro fertilization and embryo transfer (IVF-ET) at Department of Obstetrics and Gynecology, Peking University Third Hospital from March 2017 to June 2019. For comparison, the 100 patients with PCOS were divided into low NGF group ( n=50) and high NGF group ( n=50) based on the median NGF concentration (1 644.03 ng/L) in follicular fluid. Baseline characteristics, menstrual status and clinical outcomes of assisted reproductive technology were compared. We performed multiple linear regression analysis to examine the effect of NGF in follicular fluid on menstrual cycle length for multivariate analysis. Results:1) PCOS patients in the low NGF group had significantly higher body mass index [(27.24±5.17) kg/m 2] and white blood cell count [7.31(5.99, 8.43)×10 9/L ] than those in the high NGF group [(25.03±4.46) kg/m 2, P=0.024; 5.95(5.08,7.01)×10 9/L, P=0.001], while high-density lipoprotein cholesterol [1.15 (0.98, 1.36) mmol/L] and basic follicle-stimulating hormone level [6.51 (5.10,7.95) U/L] in the low NGF group were significantly lower than those in the high NGF group [1.36 (1.09,1.52) mmol/L, P=0.039;6.51 (5.10,7.95)U/L, P=0.040]. 2) PCOS patients in the low NGF group had significantly higher menstrual cycle length [60.00 (35.00, 180.00) d] than the high NGF group [32.50 (27.00,67.50) d, P=0.001]. 3) Multiple linear regression analysis revealed that after adjustment for body mass index, age, infertility duration, infertility type, and glucose and lipid metabolic parameters, the NGF concentration in the follicular fluid independently and negatively correlated with menstrual cycle length ( P<0.05). 4) The NGF concentration in follicular fluid was not correlated with assisted reproductive outcomes. Conclusion:NGF concentration in follicular fluid is closely related to the degree of menstrual cycle abnormalities in patients with PCOS.

Alzheimer's disease(AD)is one of the most prevalent neurodegenerative disorders,and is increasingly becoming a global health challenge,in line with the intensification of population aging.The pathogenesis of AD is currently unclear and treatment options are limited.Currently available drugs can only alleviate the symptoms of AD to a certain extent,and cannot delay its progression.Numerous studies,however,have shown that a variety of micronutrients may play a positive role in the treatment of AD.Vitamins and trace metal elements have many functions,including anti-inflammation,anti-oxidation,and protection of mitochondria.Micronutrients can effectively reduce β-amyloid protein plaque deposition and Tau protein hyperphosphorylation to improve brain energy metabolism,thereby helping to prevent and treat AD.This article reviews and summarizes the roles of common vitamins and trace metal elements in the prevention and treatment of AD,with the goal of offering new perspectives for the clinical management and prevention of this disease.

Objective Exploring the behavioral changes induced by quinpirole in obsessive-compulsive disorder(OCD)mouse,investigating the activation of neurons in different brain regions,and identifying differentially expressed genes(DEGs)and enriched biological pathways through transcriptome sequencing technology to elucidate the pathogenesis of OCD.Methods Randomly assign 32 male C57BL/6J mice,aged two months,to an OCD group and a control group(n=16).Administering quinpirole(0.75 mg/kg)via subcutaneous injection to the OCD group mice every other day for a total of 19 injections,while the control group mice received an equivalent volume of saline solution.Following the completion of the model construction,open field testing,elevated plus maze testing,and marble burying tests were conducted.After the completion of behavioral studies,tissue samples were collected.Neuronal damage was assessed using Nissl staining,while the expression of c-Fos and Iba1 proteins was examined through immunofluorescence staining.Transcriptome sequencing technology was utilized to screen for differentially expressed genes and to enrich relevant signaling pathways.The expression of inflammatory cytokines,including TNF-α,NF-κB p65,phosphorylated NF-κB p65(p-NF-κB p65),and IL-6,was detected using Western Blot analysis.Results Mouse induced with OCD by quinpirole exhibit anxiety-like behaviors and compulsive-like behaviors.Neurons in the hippocampal and hypothalamic regions exhibit signs of damage.The expression of c-Fos and Iba1 proteins is increased in the cortex,striatum,hypothalamus,and other brain regions.Western Blot result indicate a significant increase in the expression of pro-inflammatory cytokines such as TNF-α,p-NF-κB p65,and IL-6.Conclusions In OCD mouse,neurons in multiple brain regions are abnormally activated,microglia exhibit dysfunction,and neuroinflammation induced by the activation of the NF-κB signaling pathway accompanies the development of OCD.