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.

Aim To construct a diabetic atherosclerosis mouse model and study the pathological characteristics of diabetic atherosclerosis.Methods Fifty 8-week-old male LDLR-/-mice were fed with standard diet for 2 weeks and then changed to high-fat diet,they were randomly divided into two groups.The diabetic atherosclerosis group was given intraperitoneal injection of low dose streptozotocin(STZ)for 5 days continuouly to establish the model,and the atheroscle-rosis group was given citrate buffer injection at the same time.The body mass,blood glucose and blood lipids of the mice in the two groups were detected for many times.At the age of 23 weeks,the mice were euthanized after glucose tolerance test.HE staining and oil red O staining were used to detect the gross and aortic root atherosclerosis,immunohistochemical staining was used to detect CD4,α-smooth muscle actin(α-SMA),EGF-like module-containing mucin-like hormone re-ceptor-like 1(EMR1),monocyte chemotactic protein-1(MCP-1),NOD-like receptor protein 3(NLRP3),vascular cell adhesion molecule-1(VCAM-1),matrix metalloproteinase-2(MMP-2)and tissue inhibitor of metalloproteinase-1(TIMP-1),Western blot was used to detect α-SMA,CD4,tumor necrosis factor-α(TNF-α),NLPR3,intercellular adhesion molecule-1(ICAM-1),and type Ⅰ and Ⅲ collagen.Results Compared with the atherosclerosis group,the body mass decreased,the levels of total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDLC)increased,and the levels of high density lipoprotein cholesterol(HDLC)decreased(P＜0.05)in the diabetic atherosclerosis group.Compared with the atherosclerosis group,the distribution of atherosclerotic plaques was diffuse and the area was increased in the diabetic atherosclerosis group,and the contents of lipids,T cells,macrophages,smooth muscle cells,type Ⅰ and Ⅲ colla-gen were increased(P＜0.05);the protein levels of TNF-α,MCP-1,MMP-2,NLRP3,ICAM-1 and VCAM-1 in vascular tissues were increased,while the content of TIMP-1 were decreased and MMP2/TIMP-1 were increased(P＜0.05).Conclusions LDLR-mouse model of diabetic atherosclerosis can be successfully established by STZ induction combined with high-fat diet,which can reflect the plaque composition and inflammatory characteristics of diabetes promoting atheroscle-rosis.It can be used as a relatively ideal pathological model for the study of diabetic macroangiopathy.

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.

Opsoclonus-myoclonus syndrome （OMS） is a rare neurological syndrome associated with tumors， which is more common in children than in adults. It is characterized by involuntary， arrhythmic， chaotic， multidirectional saccades， usually accompanied by limb and trunk myoclonic seizures and ataxia. Case reports are even rare on OMS complicated by autoimmune encephalitis with overlapping antibodies against the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor （AMPAR） and N-methyl-D-aspartate receptor （NMDAR）， and its clinical manifestations and treatment are poorly understood. We report a case of autoimmune encephalitis with OMS positive for both NMDAR and AMPAR antibodies， and also review relevant literature to help improve the understanding of the condition.

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.

At present, clinical interventions for chronic kidney disease are very limited, and most patients rely on dialysis to sustain their lives for a long time. However, studies on the gut-kidney axis have shown that the gut microbiota is a potentially effective target for correcting or controlling chronic kidney disease. This study showed that berberine, a natural drug with low oral availability, significantly ameliorated chronic kidney disease by altering the composition of the gut microbiota and inhibiting the production of gut-derived uremic toxins, including p-cresol. Furthermore, berberine reduced the content of p-cresol sulfate in plasma mainly by lowering the abundance of g_Clostridium_sensu_stricto_1 and inhibiting the tyrosine-p-cresol pathway of the intestinal flora. Meanwhile, berberine increased the butyric acid producing bacteria and the butyric acid content in feces, while decreased the renal toxic trimethylamine N-oxide. These findings suggest that berberine may be a therapeutic drug with significant potential to ameliorate chronic kidney disease through the gut-kidney axis.

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

Specnuezhenide(SNZ)is among the main components of Fructus Ligustri Lucidi,which has anti-inflammation,anti-oxidation,and anti-tumor effect.The low bioavailability makes it difficult to explain the mechanism of pharmacological effect of SNZ.In this study,the role of the gut microbiota in the metabolism and pharmacokinetics characteristics of SNZ as well as the pharmacological meaning were explored.SNZ can be rapidly metabolized by the gut microbiome,and two intestinal bacterial metabolites of SNZ,salidroside and tyrosol,were discovered.In addition,carboxylesterase may be the main intestinal bacterial enzyme that mediates its metabolism.At the same time,no metabolism was found in the incubation system of SNZ with liver microsomes or liver homogenate,indicating that the gut microbiota is the main part involved in the metabolism of SNZ.In addition,pharmacokinetic studies showed that salidroside and tyrosol can be detected in plasma in the presence of gut microbiota.Interestingly,tumor development was inhibited in a colorectal tumor mice model administered orally with SNZ,which indicated that SNZ exhibited potential to inhibit tumor growth,and tissue distribution studies showed that salidroside and tyrosol could be distributed in tumor tissues.At the same time,SNZ modulated the structure of gut microbiota and fungal group,which may be the mechanism governing the antitumoral activity of SNZ.Furthermore,SNZ stimulates the secretion of short-chain fatty acids by intestinal flora in vitro and in vivo.In the future,targeting gut microbes and the interaction between natural products and gut microbes could lead to the discovery and development of new drugs.

Objective:To investigate the expression of HBV X, gene mutation in M type phospholipase 2 receptor (PLA 2R) in hepatitis B associated membranous nephropathy (HBV-MN) and its possible pathogenesis. Methods:According to the result of PLA 2R immunofluorescence detection in renal tissue, 103 patients with HBV-MN confirmed by renal biopsies were divided into two groups: PLA 2R positive group (n=66) and PLA 2R negative group (n=37). T test was used to compare the clinical biochemical measurements between the two groups. According to MN I stages (mild pathological injury) and MN II-III stage (severe pathological injury) of HBV-MN pathological stage, One-way ANOVA analysis was used to compare the pathological injury of kidney between the two groups. Spearman correlation analysis was used to compare the expression intensity of PLA 2R and pathological injury of kidney. Finally, the mutation sites of HBx gene in the two groups were analyzed. Results:There was significant difference in 24 h urinary protein between the two groups ( t=2.803, P=0.006). However, there was no significant difference in serum albumin level ( t=-0.313, P=0.755), serum creatinine ( t=-0.332, P=0.741), cholesterol ( t=0.312, P=0.756) and complement C3 ( t=0.589, P=0.557) between the two groups. There was significant difference between the two groups in MN stage I ( X2=7.449, P=0.006) and MN stage II-III ( X2=10.15, P=0.034). Secondly, the correlation analysis of Spearman between PLA 2R staining intensity and different MN pathological stages was statistically significant ( r=0.325, P=0.008). Finally, the mutation of HBx gene sequence between the two groups was analyzed, and it was found that the mutation at nt1753 site might be related to the expression of PLA2R. Conclusions:The positive expression of PLA 2R in renal tissue was found in 2/3 HBV-MN patients. The PLA 2R positive group was accompanied by the increase of urinary protein excretion and the aggravation of renal pathological injury. At the same time, nt1753 site mutations in HBx gene are related to the expression of PLA 2R, which may be an important pathogenesis of PLA 2R positive HBV-MN.

Adult ; Female ; Gene Expression ; Glomerulonephritis, Membranous ; etiology ; genetics ; pathology ; Hepatitis B ; complications ; Hepatitis B virus ; genetics ; metabolism ; Humans ; Male ; Middle Aged ; Mutation ; Receptors, Phospholipase A2 ; genetics ; metabolism ; Trans-Activators ; genetics ; metabolism ; Viral Regulatory and Accessory Proteins ; genetics ; metabolism