Alzheimer's disease(AD)is a common degenerative disease of the central nervous system in which neuropathological changes precede cognitive dysfunction and behavioral impairment. Currently, early diagnosis of AD is based on invasive and expensive testing techniques that are difficult to use widely in the clinical setting. Therefore, there is an urgent need for new markers to detect AD at an early stage. The eye, as an extension of the brain, has been found to show earlier onset of ocular pathologic changes in patients with AD compared to brain pathologic changes, such as retinal structural abnormalities, visual dysfunction, retinal abnormal protein accumulation, choroidal thickness changes, decreased corneal nerve fiber density, deposition of abnormal Aβ proteins in the lens, and pupillary light decreased sensitivity of response, etc. This article reviews the ocular pathologic changes in AD patients in recent years to provide new ideas for the early clinical diagnosis of AD.

BACKGROUND:The content of serum thrombin in patients with osteoarthritis is significantly higher than that in normal individuals,and thrombin can induce inflammatory degeneration of rat chondrocytes,suggesting that inhibiting the function of thrombin may become a method for treating osteoarthritis.Celecoxib is a common therapeutic drug for the clinical treatment of osteoarthritis.It is not yet known whether it improves chondrocyte degeneration by inhibiting the activity of thrombin. OBJECTIVE:To investigate the effect of celecoxib on thrombin-induced degeneration of rat chondrocytes. METHODS:Thrombin levels in the serum of osteoarthritis patients and normal individuals were detected by an ELISA kit.Primary chondrocytes of neonatal Sprague-Dawley rats were isolated,and all experiments were performed with cells from passage one.Chondrocytes were randomly divided into three groups:control group,thrombin group,and celecoxib group.The cell morphology of the three groups was observed under an inverted microscope,and an Edu kit was used to detect the cell proliferation.qRT-PCR was used to detect the expression of extracellular matrix components(aggrecan,elastin,cartilage oligomeric matrix proteins),inflammatory factors(interleukin-1,interleukin-6,and tumor necrosis factor-α),and chemokines(monocyte chemotactic protein 2,monocyte chemotactic protein 7,granulocyte chemotactic protein 6).The expression of type 2 collagen α1 was detected by immunofluorescence.Western blot method was used to detect the expression of catabolic metabolism genes,such as matrix metalloproteinase 9,matrix metalloproteinase 13,and cyclooxygenase 2. RESULTS AND CONCLUSION:Patients with osteoarthritis had higher levels of thrombin in the serum compared with normal individuals.Under the microscope,celecoxib was found to significantly inhibit fibroid changes in chondrocytes.Compared with the thrombin group,celecoxib inhibited the proliferation of chondrocytes.The downregulation of extracellular matrix gene expression,such as type II collagen α1,in the thrombin group was inhibited by celecoxib(P<0.05).Thrombin promoted the expression of inflammatory factors(interleukin-1,interleukin-6,and tumor necrosis factor-α),chemokines(monocyte chemotactic protein 2,monocyte chemotactic protein 7,granulocyte chemotactic protein 6),as well as catabolic genes(matrix metalloproteinase 9,matrix metalloproteinase 13,and cyclooxygenase 2),and under the intervention of celecoxib,the expression of these genes could be downregulated(P<0.05).Overall,these findings indicate that celecoxib inhibits the pro-inflammatory effects of thrombin and thereby ameliorates chondrocyte degeneration in rats.

Objective To investigate the relationship between coagulation indicators and early prognosis in patients with acute respiratory distress syndrome (ARDS).Methods The data of ARDS patients receiving the treatment in the intensive care unit (ICU) from 2008-2019 were selected from the Critical Care Medicine Open Database (MIMIC-Ⅳ V2.0 version) jointly published by MIT,Beth Israel Deaconess Medical Center,and Philips Medical,the data were categorized according to the severity of the patients' disease and the causes of lung damage.The coagulation indexes and 28 d mortality (m28d) rates were compared among different ARDS patients.The receiver operating characteristic (ROC) curve was drawn.The area under the curve was calculated to evaluate the predictive values of the related indicators.The univariate and multivariate logistic re-gression was adopted to analyze the risk factors affecting m28d in the patients with ARDS.Results Maximum prothrombin time (PTmax) in the patients with pulmonary origin ARDS was significantly lower than that in the patients without pulmonary origin ARDS,and the difference was statistically significant (P<0.05).PLTmin,PLTmax and Sequential Organ Failure Assessment (SOFA) score had statistical difference among dif-ferent severity degrees of ARDS patients (P<0.05).Minimum international normalized ratio (INRmin),maxi-mum international normalized ratio (INRmax),minimum prothrombin time (PTmin),PTmax,maximum activated partial thromboplastin time (APTTmax) and SOFA score had statistical differences between the survival group and death group (P<0.05).AUC of INRmin,INRmax,PTmin,PTmax and APTTmax were 0.607,0.624,0.610,0.620 and 0.648 respectively.The multivariate logistic regression analysis showed that APTTmax (OR=1.011,95%CI:1.001-1.022,P=0.029) was an independent risk factor for affecting m28d in the ARDS patients.Conclu-sion Plasma PLT levels in different severities of ARDS patients have the difference and APTTmax on the first day in ICU is an independent risk factor for affecting early prognosis in ARDS patients.

Purpose: Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal malignancy that occurs primarily in children and adolescents. The clinical and pathological features of IMT in adult patients are not well understood. Materials and Methods: We retrospectively searched for records of adult patients with IMT at Fudan University Shanghai Cancer Center from 2006 to 2021. Clinicopathological data, treatments, and outcomes were collected and analyzed. Results: Thirty adult patients with IMT, mostly women (60.0%), were included. The median age of the patients was 38 (21-77). The most common primary site was abdominopelvic region (53.3%), followed by lungs (20.0%). Seven patients had an abdominal epithelioid inflammatory myofibroblast sarcoma (EIMS). The positivity rate of anaplastic lymphoma kinase (ALK) was 81.5% (22/27). Sixteen patients with advanced ALK-positive disease received crizotinib, with an objective response rate (ORR) of 81.3% and a disease control rate of 87.5%. The median progression-free survival was 20.8 months. EIMS was associated with more aggressive behavior; however, the prognosis was similar to that of non-EIMS patients after treatment with an ALK inhibitor. At a median follow-up time of 30 months (95% confidence interval [CI], 13.6 to 46.4), the 5-year overall survival was 77% (95% CI, 66 to 88) in all patients. Conclusion Adult IMTs appeared more aggressive, with a higher incidence of recurrence and metastases, and patients with EIMS had more aggressive cases. Treatment with ALK inhibitors resulted in a high ORR and a durable response, which suggested that ALK inhibitors could be used as a first-line treatment option in adult patients with ALK-positive advanced IMT.

Esophageal cancer is one of the most lethal digestive system cancers, and its pathogenic factors have always been the focus of research. Recently, it has been found that microorganisms and their metabolites in the esophagus may also represent one of the pathogenic factors. Because of their continuity in anatomical structure, the oral cavity and esophagus have a certain correlation in terms of the composition of flora. In recent years, many scholars have studied the relationship between oral microorganisms and esophageal cancer to monitor changes in oral microorganisms as well as to diagnose and treat esophageal cancer more effectively. In this paper, the research status of oral microorganisms and esophageal cancer was reviewed. The Results of the literature review show that the diversity of bacteria in the esophagus is affected by oral flora in terms of the occurrence and development of esophageal cancer. Among these bacteria, the periodontal red complex, which includes Porphyromonas gingivalis, forsythia and Treponema dentata, as well as common oral microorganisms, such as Streptococcus viridis and Fusobacterium nucleatum, are all related to the occurrence and development of esophageal cancer to a certain extent. At present, there are few studies on the mechanism of microorganisms and esophageal cancer, but scholars have found that lipopolysaccharides and endotoxins, the products of Gram-negative bacteria in the esophagus, may participate in the innate immune response of the host, and the relevant mechanism of action needs further study in order to find new targets for monitoring and treatment.

Information-based teaching was applied in the experimental teaching of nuclear protection medicine based on its own features.The teaching content was sent to students as micro-video via an information platform before class for preview;during the class,the teaching was performed in the form of lectures by students and experiments in groups;after class,students were required to submit reports of experimental improvement or innovative experimental design.A comprehensive assessment was performed for preview,classroom operation,question answering in class,and experimental reports.The results of teaching practice showed that this teaching mode can effectively stimulate the students' interests in learning,enhance their research and innovation abilities,and improve the experimental teaching effect of nuclear protection medicine.

Objective To study the influence of radiation on autophagy and its protective effect on radiation injury of hepatic cells.Methods Autophagy in mouse liver tissues was examined by GFP-LC3 staining and Western blot.Radiation-induced hepatic injury was evaluated by ALT and AST in mouse serum,protein expressions,and H & E and TUNEL staining of liver tissue.L02 cells were used for in vitro study.Chloroquine and rapamycin were used to manipulate the level of autophagy.Results Total body irradiation (TBI) of 8 Gy caused an increase of autophagy in mouse liver tissue and AST level in serum (t =-7.47,P ＜0.05) at 12 h after irradiation.Irradiation significantly increased the apoptotic level in liver tissue as well.Inhibition of autophagy by chloroquine caused a further increases of AST [IR:(345.42±35.25)U/L vs.IR +CQ:(433.42 ±40.07)U/L,t =-2.86,P＜0.05] and ALT [IR:(35.67 ± 8.08) U/L vs.IR+CQ:(98.5±26.67)U/L,t=-3.09,P＜0.05] in the serum,and it also promoted apoptosis in live tissue.However,rapamycin as an autophagy promoter showed protective effect for radiation-induced hepatic injury [AST:IR:(345.42 ± 35.25) U/L vs.IR + Rap:(278.42 ± 20.09)U/L,t =-2.86,P ＜ 0.05].Similar changes of autophagy and apoptosis in L02 cells were also observed in the cells treated with chloroquine and rapamycin.Inhibition of autophagy by CQ caused an increase of ROS in vitro and in vivo and further increased ALT and AST levels in serum,reduced L02 cell viability.Activation of autophagy by Rap effectively reversed those changes.Conclusions Autophagy protects hepatic cells from radiation injury by decreasing ROS induction,which provides a potential target for the development of new clinical regimens against radiation induced liver injury.

Objective; To investigate the expression levels of matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) in dentin of healthy adults under different adhesion conditions, and to provide the basis for improving the binding effect of matrix metalloproteinases (MMPs) inhibitors in clinic. Methods; A total of 20 adult freshlyextracted molars were collected and ground into dentin powder under liquid nitrogen cooling. The oral condition was simulated. The dentin was treated with self-etching bonding (Single Bond Universal) and totaletching bonding (35% phosphate gel +Adpter Single Bond 2). The dentin without any treatment was regarded as negative control group, the dentin treated with 10% phosphoric acid (self-etching bonding) or 10% phosphoric acid+ 35% phosphate gel (total-etching bonding) was regarded as positive control group, the dentin treated with Single Bond Universal (self-etching bonding) or 35% phosphate gel+Adper Single Bond 2 (total-etching bonding) was regarded as blank control group; the dentin pretreated with the MMPs inhibitors chlorhexidine (CHX) and minocycline (MI) during the bonding process respectively was regarded as CHX group and MI group, and the dentin treated with 10 % sodium hypochlorite was regarded as aging group; on the basis of aging group, the dentin treated with CHX and MI was regarded as CHX aging group and MI aging group. Gelatin zymography was used to perform the polyacrylamide gel electrophoresis; after incubating, staining and decoloring, the bands were analyzed by gel image analysis system, and the expression levels of MMP-2 and MMP-9 in dentin were calculated. Results: Under the condition of self-etching bonding, compared with blank control group, the expression levels of MMP-2 and MMP-9 in dentin in CHX group were decreased (P<0. 05), and the expression levels of MMP-2 and MMP-9 in the dentin powder in MI group were decreased (P<0. 05); compared with aging blank control group, the expression levels of MMP-2 and MMP-9 in dentin in CHX aging group were decreased (P<0. 05), and the expression levels of MMP-2 and MMP-9 in dentin in MI aging group were decreased (P<0. 05). Under the condition of total-etching bonding, compared with blank control group, the expression levels of MMP-2 in dentin in CHX group and MI group were decreased (P<0. 05); compared with aging blank control group, the expression levels of MMP-2 in dentin in CHX aging group and MI aging group were decreased (P<0. 05). Conclusion; In the process of dentin bonding, CHX and MI could slow down the enzymatic reaction and improve the bonding strength by decreasing the expression levels of MMP-2 and MMP-9.

OBJECTIVE:To study the spectrum-effect relationship of the antipyretic effect of Radix Bupleuri injection. METH-ODS:HPLC method was used to establish the fingerprint of Radix Bupleuri injection. The antipyretic effect of 10 batches of Radix Bupleuri injection on fever rats induced by dried yeast were determined respectively. The fingerprint peaks were screened,along with the temperature value of different time points(0,10,15,30,40,55,70 min). The principal components were extracted by principal component method and the indirect relationship between the fingerprint and antipyretic effect was analyzed,depending on the principal component correlation coefficient matrix. RESULTS:There were 39 common peaks in fingerprint(similarity>0.85), No. 8,12,14,19,26,31,34,35 and 39 common peaks with large peak area were included in the study. Four principal compo-nents were extracted by principal component analysis(87% of total variant). First principal component showed that the active com-ponents of the 12th peak may be related to the antipyretic effect of 6 to 13 hours. The second principal component showed that the active components of the 26th peak may be related to the antipyretic effect of 0.5 to 5 hours. The third principal component showed that the similar effect of the active components could be caused by 34th,35th and 39th peaks. The fourth principal component sug-gested that there were some similarities between the 14th and the 31st peaks. CONCLUSIONS:Radix Bupleuri injection have obvi-ous improvement for fever rats. There is certain corresponding relation between HPLC fingerprint and antipyretic effect of Radix Bu-pleuri injection .

Gastrointestinal stromal tumor (GIST) is the most common gastrointestinal mesenchymal tumors, mainly due to the onset of the proto-oncogene receptor tyrosine kinase, or platelet-derived growth factor receptor gene activating mutations. Molecular targeted therapy drug of imatinib mesylate inhibit KIT, platelet-derived growth factor receptor aloha (PDGFRA) gene tyrosine kinase activity, which is effective in patients with advanced GIST. However, a growing number of studies have found the presence of imatinib mesylate in primary and secondary drug resistance in the treatment of GIST process. With the in-depth study of the physiological function and mechanism of action of non-coding RNA in recent years, making it gradually realized extensive regulation of non-coding RNA gene expression, which occurs in tumor development, invasion and metastasis, drug resistance and other processes plays an important role. Non-coding RNA has the potential to explore GIST pathogenesis and resistance mechanisms to provide new ideas and direction.