Vascular damage plays a significant role in the onset and progression of Alzheimer's disease (AD). However, the precise molecular mechanisms underlying the induction of neuronal injury by vascular damage remain unclear. The present study aimed to examine the impact of fibrinogen (Fg) on tau pathology. The results showed that Fg deposits in the brains of tau P301S transgenic mice interact with tau, enhancing the cytotoxicity of pathological tau aggregates and promoting tau phosphorylation and aggregation. Notably, Fg-modified tau fibrils caused enhanced neuronal apoptosis and synaptic damage compared to unmodified fibrils. Furthermore, intrahippocampal injection of Fg-modified tau fibrils worsened the tau pathology, neuroinflammation, synaptic damage, neuronal apoptosis, and cognitive dysfunction in tau P301S mice compared to controls. The present study provides compelling evidence linking Fg and tau, thereby connecting cerebrovascular damage to tau pathology in AD. Consequently, inhibiting Fg-mediated tau pathology could potentially impede the progression of AD.
Animals ; tau Proteins/metabolism* ; Alzheimer Disease/metabolism* ; Fibrinogen/metabolism* ; Mice, Transgenic ; Mice ; Disease Models, Animal ; Memory Disorders/metabolism* ; Male ; Mice, Inbred C57BL ; Brain/metabolism* ; Hippocampus/metabolism* ; Protein Aggregation, Pathological/metabolism* ; Apoptosis ; Phosphorylation

Objective: To investigate the clinicopathological features and differential diagnosis of adamantinoma of long bone. Methods: Seven cases of adamantinoma on long bone were selected at Jiangsu Province People′s Hospital from June 2012 to May 2018. Clinicopathologic details, immunohistochemical and molecular analysis were performed,and the relevant literature reviewed. Results: There were 6 males and 1 female patients,age ranging from 21 to 60 years (mean 38 years). Six cases were on the right side and one case was on the left; in five cases the tumors arose from tibia, one from patella and one from humerus. Microscopically,tumour cells were mainly composed of spindle cells arranged in bundles or braids,with irregular epithelial island. Immunohistochemically,the epithelial island expressed high molecular weight cytokeratin but not CK8/18. Both epithelial and spindle components expressed vimentin. One case that was microscopically similar to intraosseous synovial sarcoma did not show SYT gene rearrangement. Clinical follow-up was available for five patients: one patient had axillary metastases seven months after operation, one patient had recurrence 34 months after surgery, 3 patients were uneventful with follow up duration from half a month to 32 months. Conclusion Adamantinoma occurring in long bones is very rare. The correct diagnosis requires adequate sample selection, careful morphologic observation, immunohistochemistry and molecular genetics.

Objective To investigate the clinicopathological features and differential diagnosis of adamantinoma of long bone. Methods Seven cases of adamantinoma on long bone were selected at Jiangsu Province People′s Hospital from June 2012 to May 2018. Clinicopathologic details, immunohistochemical and molecular analysis were performed,and the relevant literature reviewed. Results There were 6 males and 1 female patients,age ranging from 21 to 60 years (mean 38 years). Six cases were on the right side and one case was on the left; in five cases the tumors arose from tibia, one from patella and one from humerus. Microscopically,tumour cells were mainly composed of spindle cells arranged in bundles or braids,with irregular epithelial island. Immunohistochemically,the epithelial island expressed high molecular weight cytokeratin but not CK8/18. Both epithelial and spindle components expressed vimentin. One case that was microscopically similar to intraosseous synovial sarcoma did not show SYT gene rearrangement. Clinical follow?up was available for five patients: one patient had axillary metastases seven months after operation, one patient had recurrence 34 months after surgery, 3 patients were uneventful with follow up duration from half a month to 32 months. Conclusion Adamantinoma occurring in long bones is very rare. The correct diagnosis requires adequate sample selection, careful morphologic observation, immunohistochemistry and molecular genetics.

OBJECTIVE:To observe clinical efficacy and safety of Mailuoning injection combined with benazepril in the treat-ment of chronic glomerulonephritis. METHODS:130 patients with chronic glomerulonephritis were randomly divided into observa-tion group and control group,with 65 cases in each group. Both groups received rountine treatment as low salt and fat diet. Control group was additionally given Benazepril tablet 10 mg,qd;observation group was additionally given Mailuoning injection 20 ml added into 5% Sodium chloride injection 250 ml,ivgtt,qd,on the basis of control group,20 days of drug withdrawal every 10 days. Both group received 4 months of treatment. Clinical efficacy of 2 groups were observed as well as the levels of BUN,UCr, SCr and 24 h urine protein quantitative (UPE) before and after the treatment. The incidence of ADR was compared between 2 groups. RESULTS:Total effective rate of observation group was 83.1%,which was significantly higher than 67.7% of control group,with statistical significance (P<0.05). There was no statistical significance in BUN,UCr,SCr and 24 h UPE between 2 groups before treatment (P>0.05);those indexes of 2 groups decreased significantly after treatment,and the observation group were lower than the control group,with statistical significance(P<0.05). There was no statistical significance in the incidence of ADR between 2 groups (P>0.05). CONCLUSIONS:Mailuoning injection combined with benazepril is effective for chronic glo-merulonephritis,and can effectively improve renal function with good safety.

Objective To explore the HLA-A2 restriction and immunogenicity of 5 previously identified HCV-speeific CTL epitopes. Methods Based on T2 cell, to explore the HLA-A2 restriction of previously identified HCV-specific CTL epitopes by MHC-peptide complex stabilization assay;To detect pep-tide-specific CTL in HLA-A2~+ PBMC stimulated by HLA-A2-restricted peptides by intracellular cytokine staining(ICS) and ELISPOT; To explore the cytotoxicity of peptide-specific CTL to same peptide-loaded T2 cells (target cells) by CTL cytotoxicity test. Results Among 5 previously identified CTL epitopes NS4b_78 (SMMAFSAAL) and NS5a_367 (TVSSALAEL) have high-affinity for HLA-A2 molecules(FI 1) ;ELISPOT results shown that NS4b_78(SMMAFSAAL) and NSSa_367(TVSSALAEL) induced high levels of IFN-γ-se-creting cells [(60±6) SFC/10~4 PBMC vs (4±1 ) SFC/10~4 PBMC, P < 0.01 ; (10 ± 3 ) SFC/10~4 PBMC vs (2±1 ) SFC/10~4 PBMC, P <0.01, respectively] ;ICS results indicated that there were high percentages of CD8~+ IFN-γ~+ T cells in total CD8~+T cells stimulated by these peptides [(2.33 ±0.22 ) % vs (0.05±0.01)%, P <0.001 ; (0.36±0.06)% vs (0.03±0.01)%, P <0.001, respectively]. Furthermore,peptide-specific CTL could effectively kill same peptide-loadcd T2 cells. Conclusion NS4b_78 (SMMAF-SAAL) and NSSa_367 (TVSSALAEL) were identified as HLA-A2-restricted CTL epitopes which could in-duce immune response in vitro.

Objective To summarize clinical manifestations and diagnostic criteria of ischemic reperfusion (IR) injury to the spinal cord. Method The clinical manifestations and management of 15 cases of spinal cord IR injury after operation during 2000 to 2005 were retrospectively analyzed. Result All the patients with spinal cord IR injury presented progressive ascending motor and sensory functional impairment beginning from lower extremities 3h post operation, and they were all treated immediately with methylprednisolone and neurotrophy drugs to restore spinal cord function. However, mechanical compression with organic lesion should be ruled out to establish the diagnosis of spinal cord IR injury in the retrospective analysis. Different stages of spinal cord IR injury occurred in these 15 cases. Through symptomatic treatment, 8 patients recovered completely; the clinical symptoms were basically improved in 4 cases who could lead a normal life; in 3 patients clinical symptoms were improved but not satisfactory. Conclusion Though spinal cord IR injury seldom occurs in the clinic, its damage is disastrous. Proper management is critical to save patients from poor life quality.