Autoimmune encephalitis(AE)generally refers to a group of encephalitides mediated by autoimmune mechanisms.The current treatment for AE relies on immunotherapy,typically following a stepwise escalation regimen.A minority of patients may still be refractory to treatment,thus posing a major clinical challenge.In the pathogenesis of AE,B cells play a role through antibody secretion and cytokine regulation,whereas T cells contribute by promoting B cell differentiation and mediating neuronal attack.In recent years,immunotherapies targeting different antigens have become a research focus and emerged as a new treatment option for AE patients.This article summarizes the mechanisms of action of different targeted drugs and the progress of their clinical application in AE,and provides an outlook on future research directions.

Autoimmune encephalitis(AE)generally refers to a group of encephalitides mediated by autoimmune mechanisms.The current treatment for AE relies on immunotherapy,typically following a stepwise escalation regimen.A minority of patients may still be refractory to treatment,thus posing a major clinical challenge.In the pathogenesis of AE,B cells play a role through antibody secretion and cytokine regulation,whereas T cells contribute by promoting B cell differentiation and mediating neuronal attack.In recent years,immunotherapies targeting different antigens have become a research focus and emerged as a new treatment option for AE patients.This article summarizes the mechanisms of action of different targeted drugs and the progress of their clinical application in AE,and provides an outlook on future research directions.

Objective: To explore the treatment options for congenitally missing teeth in patients with ectodermal dysplasia and provide a clinical reference. Methods: A patient with ectodermal dysplasia with a concave midface, anterior protrusion of the chin, and underdevelopment of the lower third of the face presented with congenital loss of multiple maxillary teeth, malocclusion of the remaining teeth, congenital loss of mandibular dentition, small dental arches, and upper and lower alveolar bone hypoplasia. The patient was treated by means of a removable partial maxillary prosthesis, implants in the anterior region of the lower mandible designed with the assistance of digital guides, and bar-clamped implant-overlay prostheses. A literature review of the protocol for the treatment of this condition was also conducted. Results: In addition to good retention and stability after denture wear, an excellent occlusal relationship, improvement of the patient's facial appearance, including upper and lower lip fullness, more equal balancing of the lower and middle 1/3 of the face, and improved masticatory function were achieved. The results of the literature review showed that patients with ectodermal dysplasia who are congenitally edentulous usually have a complex intraoral situation that makes restoration difficult, and common restorative modalities for these patients include fixed bridges, removable partial dentures, complete dentures, overdentures, and implant prostheses, which need to be selected according to the actual intraoral situation of each patient. Currently, there is no consensus on the treatment of congenitally missing teeth in patients with ectodermal dysplasia, and some scholars have suggested that fixed restorations be recommended for patients with fewer missing teeth, while the option of removable or implant-covered denture restorations should be given to patients with more missing teeth, with removeable prostheses for underage patients that are replaced with permanent fixed prostheses when the jaws have stabilized. Conclusion In patients with ectodermal dysplasia with congenital tooth loss, all factors should be taken into account, and an individualized restorative plan should be developed.

A case of paraneoplastic cerebellar ataxia syndrome caused by immune checkpoint inhibitors(ICI)was treated with ofatumumab(OFA).The patient is a 57-year-old male.He used"Camrelizumab"immunotherapy for his previous history of small cell lung cancer.The main reason was"walking unsteadily for more than one year and shaking his head involuntarily for more than one month".After admission,the head MRI,chest CT,electroencephalogram,lumbar puncture and other related examinations were improved.The antibody spectrum of paraneoplastic neurological syndrome was anti-GAD65 antibody IgG(+),and the case was then diagnosed as the immune checkpoint inhibitor-related paraneoplastic neurological syndromes(PNS)of nervous system.After OFA treatment(20 mg/time),the symptoms were obviously improved.This paper analyzes the clinical features and diagnosis and treatment approaches of this case,in order to improve clinicians'understanding of the disease and provide reference for clinical diagnosis and treatment of similar cases.

Autoimmune glial fibrillary acidic protein astropathy(GFAP-A)is an autoimmune inflammatory disease of the central nervous system,with a prevalence rate of 0.6 per 100,000.Its clinical manifestations include subacute meningitis,encephalitis,myelitis,or combinations thereof.Approximately 40%of patients exhibit symptoms and signs of prodromal infection such as fever and headache,while 30%may develop tumors.Currently,diagnosis primarily relies on the presence of GFAP-IgG in cerebrospinal fluid.Differential diagnosis must exclude conditions such as central nervous system vasculitis,inflammatory demyelinating diseases,lymphoma,glioma,and brain metastases,posing significant challenges in clinical practice.This paper summarizes the clinical manifestations,diagnosis,and treatment of GFAP-A to enhance understanding of the disease and prevent misdiagnosis.

Autoimmune glial fibrillary acidic protein astropathy(GFAP-A)is an autoimmune inflammatory disease of the central nervous system,with a prevalence rate of 0.6 per 100,000.Its clinical manifestations include subacute meningitis,encephalitis,myelitis,or combinations thereof.Approximately 40%of patients exhibit symptoms and signs of prodromal infection such as fever and headache,while 30%may develop tumors.Currently,diagnosis primarily relies on the presence of GFAP-IgG in cerebrospinal fluid.Differential diagnosis must exclude conditions such as central nervous system vasculitis,inflammatory demyelinating diseases,lymphoma,glioma,and brain metastases,posing significant challenges in clinical practice.This paper summarizes the clinical manifestations,diagnosis,and treatment of GFAP-A to enhance understanding of the disease and prevent misdiagnosis.

Deficiencies in the clearance of peripheral amyloid β (Aβ) play a crucial role in the progression of Alzheimer's disease (AD). Previous studies have shown that the ability of blood monocytes to phagocytose Aβ is decreased in AD. However, the exact mechanism of Aβ clearance dysfunction in AD monocytes remains unclear. In the present study, we found that blood monocytes in AD mice exhibited decreases in energy metabolism, which was accompanied by cellular senescence, a senescence-associated secretory phenotype, and dysfunctional phagocytosis of Aβ. Improving energy metabolism rejuvenated monocytes and enhanced their ability to phagocytose Aβ in vivo and in vitro. Moreover, enhancing blood monocyte Aβ phagocytosis by improving energy metabolism alleviated brain Aβ deposition and neuroinflammation and eventually improved cognitive function in AD mice. This study reveals a new mechanism of impaired Aβ phagocytosis in monocytes and provides evidence that restoring their energy metabolism may be a novel therapeutic strategy for AD.
Animals ; Mice ; Alzheimer Disease ; Amyloid beta-Peptides ; Monocytes ; Cognition ; Energy Metabolism ; Phagocytosis

Objective:To investigate the occurrence of catheter fracture in totally implantable venous access ports (TIVAP) and analyze its influencing factors.Methods:A retrospective nested case-control study was used to establish a cohort of 3 517 patients with TIVAP and infusion port maintenance in Affiliated Hospital of Qingdao University from January 2012 to December 2021, and they were divided into the fracture group and the control group. The general information questionnaire, TIVAP Catheter Fracture Related Factors Questionnaire and TIVAP Catheter Fracture Clinical Characteristics Questionnaire were used to collect general and clinical data of patients in two groups. The risk factors of TIVAP catheter fracture were analyzed by Logistic regression.Results:The incidence of TIVAP catheter fracture was 0.6% (21/3 517) . Logistic regression analysis showed that the operator's experience of placing ports, whether the patient performed TIVAP maintenance regularly, time for patients carrying the infusion port and whether TIVAP were repeatedly blocked were influencing factors for the occurrence of catheter fracture in TIVAP.Conclusions:Nursing staff should fully understand the risk factors of TIVAP catheter fracture, identify high-risk groups in the early stage and carry out targeted nursing interventions to reduce the incidence of TIVAP catheter fracture.

Objective: To investigate the value of MDM2 RNA in situ hybridization (RNA-ISH) in diagnosing atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) and dedifferentiated liposarcoma (DDL). Methods: A total of 26 ALT/WDL/DDLs diagnosed from March 2017 to May 2019 in West China Hospital, Sichuan University, Chengdu, China and 18 control cases were included. MDM2 RNA-ISH was performed on all samples and compared with the fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) regarding their performance in detecting MDM2. Results: All samples were detected successfully using the three methods. Among 26 ALT/WDL/DDLs, all cases showed MDM2 amplification and positivity for MDM2 RNA-ISH (26/26, 100%). Twenty-four (24/26, 92.3%) of the 26 tested cases were positive for MDM2 IHC while two of them were negative. Eighteen control cases were all negative for MDM2 FISH and RNA-ISH, and 15 (15/18) cases were negative for MDM2 IHC. The sensitivity and specificity of RNA-ISH were both 100%, and those of MDM2 IHC were 92.3% and 83.3%, respectively. Diffuse staining was identified in all MDM2 RNA-ISH positive ALT/WDL/DDLs, but identified in only 8/24 (33.3%) of the MDM2 IHC positive cases. Among the 11 ALT/WDL/DDL samples evaluated on tissue microarray, the positive rate of MDM2 RNA-ISH was 100% with diffuse staining in all cases. The positive rate of MDM2 IHC was 9/11 while only 1 of the 9 cases showed diffuse staining. The result of MDM2 RNA-ISH was identical to that of MDM2 FISH and was overall consistent with that of MDM2 IHC (Kappa=0.763, P<0.001). Conclusions: In ALT/WDL/DDLs, results of MDM2 RNA-ISH are highly consistent with those of FISH. MDM2 RNA-ISH is more sensitive and more specific and has more diffuse positive signals than the IHC. The findings indicate that MDM2 RNA-ISH is highly valuable for the diagnosis and differential diagnosis of ALT/WDL/DDLs.
Biomarkers, Tumor/genetics* ; Gene Amplification ; Humans ; In Situ Hybridization, Fluorescence ; Liposarcoma/genetics* ; Proto-Oncogene Proteins c-mdm2/genetics* ; RNA

Objective:To observe the effect of bone morphogenetic protein 4 (BMP4) on the proliferation and migration of human retinal microvascular endothelial cells (hRMEC) under oxidative stress.Methods:The hRMEC cultured in vitro were divided into control group, 4-hydroxynonenal (HNE) treatment group (4-HNE group), 4-HNE+BMP4 group (BMP4 group). Cell culture medium of 4-HNE treatment group was added with 10 μmmol/L 4-HNE; cell culture of BMP4 group was cultured with 10 μmmol/L 4-HNE, and after stimulation for 6 h, 100 ng/ml recombinant human BMP4 was added. The effects of 4-HNE and BMP4 on hRMEC viability was detected by thiazole blue colorimetric method. The effects of 4-HNE and BMP4 on cell migration was determined by cell scratch test. The relative expression of BMP4 mRNA in the cells of the control group and 4-HNE treatment group and the mRNA expression of the control group, the fibronectin (FN) of BMP4 group, laminin (Laminin), α-smooth muscle contractile protein (α-SMA), and collagen type Ⅰ (Collagen Ⅰ), vascular endothelial growth factor (VEGF), and connective tissue growth factor (CTGF) were detected by real-time quantitative polymerase chain reaction (qRT-PCR). Western blot was used to detect the relative expression of BMP4 protein in the control group and 4-HNE group. The control group and 4-HNE group were compared by t test. Results:Compared with the control group, cell viability ( t=12.73, 16.26, P=0.000 2, <0.000 1), cell migration rate ( t=28.17, 37.48, P<0.000 1, <0.000 1) in 4-HNE group and BMP4 group were significantly increased, and the difference was statistically significant; the relative expression of BMP4 mRNA and protein in the 4-HNE group was significantly increased, and the difference was statistically significant ( t=16.36, 69.35, P=0.000 1, <0.000 1). The qRT-PCR test results showed that compared with the control group, the relative expression of VEGF, FN, Laminin, α-SMA, Collagen Ⅰ, and CTGF mRNA in the cells of the BMP4 group was significantly increased, and the difference was statistically significant ( t=10.61, 17.00, 14.85, 7.78, 12.02, 10.61, P=0.0004, <0.000 1, 0.000 1, 0.001 5, 0.000 1, 0.000 4). Conclusion:BMP4 can induce the proliferation and migration of hRMEC; it can also regulate the expression of angiogenesis factors and fibrosis-related factors in hRMEC.