[Objective] To investigate the expression of eukaryotic translation initiation factor 5A2 (EIF5A2) and its clinical significance in esophageal squamous cell carcinoma (ESCC).[Methods] Immunohistochemistry was used to detect the expression of EIF5A2 protein in 135 cases of esophageal squamous cell carcinoma,and analyzed the correlation between the expression of EIF5A2 protein and clinicopathological parameters,and its prognosis value.[Results] Immunohistochemical analysis showed that 68 cases were overexpressed in 135 cases of ESCC.Pearson's chi-square test indicated that the expression of EIF5A2 in ESCC was significantly correlated with T stage (P =0.006),lymph node metastasis (P =0.031) and clinic stage (P =0.026).The Cox proportional hazard model analysis showed that EIF5A2 was an independent prognostic risk factor for ESCC patients.Kaplan-Meier analysis showed that the median survival time of patients with the low expression was 72.5 months,which was significantly higher than that of patients with the high expression,the median survival time of it are 51.7 months (P ＜ 0.05).[Conclusion] The overexpression of EIF5A2 may contribute to the development and progression of ESCC and EIFSA2 could be a novel potential prognostic marker for ESCC.

AIM: To verify the role of enhancing or suppressing the expression of glutathione peroxidase 1 (GPx1) in the growth, migration and invasion of glioblastoma multiforme cell lines U87MG and U118MG.METHODS:U87MG and U118MG cell lines were transfected with the vector containing specific siRNA or pcDNA3.1 recombinant plas-mid both targeting GPx1.The mRNA and protein expression levels of GPx1 were detected by real-time PCR and Western blotting.MTS assay was applied for determining the cell activity.The abilities of migration and invasion were examined by Transwell assay.RESULTS:Compared with blank control group and negative group, the inhibitory rate of the cell activity in U87MG cells in siRNA group was significantly reduced by 25.9%, 35.7%and 34.8%at 24 h, 48 h and 72 h, respec-tively (P<0.05).In contrast, the cell activity of U118MG cells in pcDNA3.1-GPx1 group was significantly increased by 22.7%, 45.8%and 39.8%at 24 h, 48 h and 72 h, respectively ( P<0.05) .In siRNA group, the inhibitory rate of mi-gration in U87MG cells was 41.6%±8.2%and the invasion was 41.6%±8.2%compared with blank control group and negative group (P<0.05).The cell migration and invasion rates of the U118MG cells in pcDNA-GPx1 group were in-creased by 55.8%±9.8% and 60.8% ±9.2%, respectively, compared with blank control group and negative group (P<0.05).CONCLUSION:The down-regulation of GPx1 by specific siRNA reduces the capability of cell growth, mi-gration and invasion of U87MG cells, while up-regulation of GPx1 by pcDNA3.1-GPx1 increases the capability of cell growth, migration and invasion of U118MG cells.

ObjectiveTo study the apoptosis of CD4 + T lymphocytes and the detection of immune function in patients with pulmonary tuberculosis and explore the clinical significance.MethodsThe mononuclear cells were separated from the blood of the tuberculosis patients or the healthy.The flow cytometry was used to measure the percentage of apoptotic CD4 + T lymphocytes,and the standard of T-lymphocyte subsets were detected by using SAP technology.The red cell immune function were determined by using yeast wreath way.Results The apoptosis rate of CD4 + T lymphocytes and CD8 + T lymphocyte was ( 15.882 ± 4.65 ) ％,and (27.69 ± 0.74) ％.The Immune complex positive rate ( 19.40 ± 0.58) ％ in patients with tuberculosis was significantly higher than those in controls ( P ＜ 0.01 ).C3b receptor positive rate in red blood cells was ( 17.73 ± 0.63 ) ％,( 46.48 ± 1.34 ) ％ in CD3 + T lymphocyte,( 28.12 ±0.69 ) ％ in CD4 + T lymphocyte,and the ratio of CD4/CD8 ( 1.0223 ± 0.09362) in the patients with tuberculosis was lower than the control group( P ＜ 0.01 ).There were certain relationships between the apoptosis rate of CD4 + T lymphocytes and the percentages of CD4 + T lymphocyte,the standard of T lymphocyte subsets and the red cell immune function.ConclusionsThe apoptosis rate of CD4 + T lympho,cytes in patients with tuberculosis were significantly higher than the healthy,which led to reducing the number of CD4 + T lymphocytes.There was positive correlation between red cell immunity and T-lymphocyte immunity,and the immunity in red cell and T- lymphocyte was lower than normal controls,which may be related to the immune pathogenesis of pulmonary tuberculosis.

Dilated cardiomyopathy is a main disease that causes heart failure and exhibits etiological heterogeneity.Nearly a quarter of dilated cardiomyopathy in patients is related to genetics,and ventricular dilation and myocardial systolic dysfunction are the main characteristics of the disease.LMNA mutation is a major cause of hereditary dilated cardiomyopathy,and arrhythmia is a major clinical manifestation of hereditary dilated cardiomyopathy with LMNA mutation.In recent years,establishment of a dilated cardiomyopathy model in C57/B6 mice and its treatment by focused gene therapy has been a research focus,and some important conclusion have been drawn from the establishment of large animal models in dogs and pigs.However,large animals,especially non-human primates,are closer to humans.At present,dilated cardiomyopathy is not involved in the heart disease model of non-human primates.Therefore,this article reviews studies on rodent and large animal models of dilated cardiomyopathy at the genetic level and proposes the idea of developing a dilated cardiomyopathy model in a non-human primate.It also provides new ideas to study the pathogenesis and clinical treatment.

Objective To clarify the intervention effect of Angelica Radix Astragali ultrafiltrate(RAS-RH)on radiation-induced myocardial fibrosis by inhibiting the overexpression of cardiac CILP1.Methods Forty SPF Wistar male rats were randomly divided into normal group,model group,Benazepril hydrochloride group,RAS-RH group and Benazepril hydrochloride +RAS-RH group.Cardiomyocytes were induced by X-ray.The rat model of myocardial fibrosis was prepared by injury.The benazepril hydrochloride group was given benazepril hydrochloride 1.0 mg·kg-1 by gavage;the RAS-RH group was given RAS-RH 0.6 g·kg-1 by gavage;benazepril hydrochloride was given by gavage Pril + RAS-RH group was given benazepril hydrochloride 1.0 mg·kg-1 and RAS-RH 0.6 g·kg-1 by gavage;model group and normal group were given equal volume of normal saline by gavage,once a day,After 4 weeks of drug intervention,the serum NT-ProBNP,CTnⅠ and CTnT contents of the rats in each group were detected by ELISA method;HE staining was used to evaluate the pathological changes of myocardial tissue of the rats in each group;Masson staining was used to evaluate the myocardial collagen deposition of the rats in each group and calculated Collagen volume fraction(CVF);immunohistochemistry to detect the expression levels of α-SMA,Col-Ⅰ,Col-Ⅲ protein in myocardial tissue of rats in each group;Western blot method to detect TGF-β1 and smad3 in myocardial tissue of rats in each group,CILP1 protein expression.Results Compared with the blank group,the serum levels of NT-ProBNP,CTnⅠ and CTnT in the model group were significantly increased(P<0.01).Blue-stained fibrous tissue increased significantly,myocardial CVF increased significantly,and myocardial tissue α-SMA,Col-Ⅰ,Col-Ⅲ,TGF-β1,Smad3,CILP1 protein expression increased(P<0.01);Serum contents of NT-ProBNP,cTnⅠ and CTnT in rats in napril group,RAS-RH group and benazepril hydrochloride + RAS-RH group were significantly decreased(P<0.01).Sexual cell infiltration was improved,myocardial CVF was significantly decreased(P<0.01),and the protein expressions of α-SMA,Col-Ⅰ,Col-Ⅲ,TGF-β 1,Smad3 and CILP1 in myocardial tissue were significantly decreased(P<0.05).Conclusion Angelica sinensis ultrafiltrate can alleviate X-ray radiation-induced myocardial fibrosis in rats by inhibiting the overexpression of CILP 1 in the heart.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a kind of autoimmune inflammatory connective tissue disease which seriously endangers human health. Genetic factors play a key role in the pathogenesis of SLE. This study aims to investigate a novel phospholipase D2 (PLD2) mutation associated with familial SLE, and further explore the underlying mechanism of the mutation in SLE. METHODS: The blood samples from a SLE patient, the patient's parents, and 147 normal controls were collected and DNA was extracted. Whole genome high-throughput sequencing was performed in the patient and her parents and the results were further analyzed by various bioinformatics methods. The wild type (wt), mutant type (mu), and negative control PLD2 plasmids were further constructed and transfected into 293 cells. The expression level of HRAS protein in 293 cells was detected by Western blotting. RESULTS: In this SLE family, the female SLE patient and her mother, 1 in generation II and 1 in generation III had typical clinical manifestations of SLE, and all of them had lupus nephritis at early stage. The genetic characteristics are consistent with autosomal dominant inheritance. A novel PLD2 heterozygous mutation (c.2722C>T) was found in the patient and her mother, but not in her father and other normal controls. Compared with wtPLD2 plasmid and negative control PLD2 plasmid, the expression of HRAS in 293 cells transfected with muPLD2 plasmid was significantly up-regulated (both CONCLUSIONS PLD2 c.2722C>T mutation may be one of the pathogeny of SLE in this family.
Case-Control Studies ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Lupus Erythematosus, Systemic/genetics* ; Lupus Nephritis ; Mutation ; Phospholipase D

AIM: To study the mechanism of Ginseng Yixin granules (QSYXG) in treating ejection fraction preserved heart failure (HFpEF) based on network pharmacology. METHODS: Effective chemical composition information of QSYXG particles was collected through TCMSP database; DisGeNET, GeneCards, OMIM database for obtaining HFpEF related targets; Metascape GO and KEGG enrichment analysis of the intersection targets of HFpEF; STRING Construction and analysis of the database PPI network; Cytoscape3.7.2 Software construction network diagram; Docking of the major active components to the core target with the AutoDock Vina software molecules, the results were visualized and analyzed with pymol. RESULTS: A total of 66 components and corresponding targets were obtained, HFpEF corresponds to 1 931 targets, The intersection of 127 targets, the main active ingredients are quercetin, kaempferol, β-sitosterol, etc.; TNF, AKT1, IL-6, P53 and JUN as the core targets, Good docking of the key components with the core targets; Mainly involving the positive regulation of gene expression, signal transduction, negative regulation of apoptotic process, positive regulation of cell proliferation and senescence, hypoxia response, negative regulation of gene expression, inflammatory response and so on, PI3K-Akt, AGE-RAG, MAPK, TNF, IL-17, and HIF-1 are the main associated signaling pathways. CONCLUSION: QSYXG may treat HFpEF by activating targets of TNF, AKT1, IL-6, P53, JUN, and regulating apoptotic process, cell proliferation, hypoxia response, and inflammatory response.

Background: Anti-programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) immunotherapy has been proved to be effective on gastric cancer in ongoing clinical trials. However, the value of PD-L1 in predicting responses of patients with gastric cancer to anti-PD-1/PD-L1 immunotherapy is controversial. Some studies suggested that intra- and inter-tumoral heterogeneity of PD-L1 expression might explain the controversy. This study aimed to analyze the expression of PD-L1, PD-L2, and PD-1 as well as CD8(+) T-cell density in primary tumors and lymph nodes from patients with stage T1-4N+M0 gastric adenocarcinoma to explore the heterogeneity of PD-1 signaling pathway molecules. Methods: In primary tumors and metastatic as well as non-metastatic lymph nodes from patients with stage T1-4N+M0 gastric adenocarcinoma, we detected PD-L1 and PD-L2 expression with immunohistochemistry. CD8(+) T-cell density in primary tumors and PD-1 expression on CD8(+) T cells were detected with immunofluorescence. Uni-variate analysis was used to determine the prognostic values of them. Cox proportional hazard regression model was used to identify independent risk factors that affect patients' overall survival and disease-free survival. Results: Among 119 eligible patients who had undergone surgical resection, the positive rate of PD-L1 was higher in metastatic lymph nodes than in primary tumors (45.4％ vs. 38.7％,P= 0.005); the positive rate of PD-1 on CD8(+) T cells was significantly higher in primary tumors and metastatic lymph nodes than in tumor-free lymph nodes (both P < 0.001). The intensity of PD-1 expression on CD8(+) T cells in primary tumors and in metastatic lymph nodes were stronger than that in tumor-free lymph nodes from the same patient. Beside, the positive rate of PD-L2 did not show any differences between primary tumors and metastatic lymph nodes. In multivariate analysis, PD-L1 expression, PD-L2 expression, a low density of CD8(+) T cells in primary tumors, and PD-1 expression on CD8(+) T cells in primary tumors were associated with poor prognosis.Conclusion: The expression of PD-L1 is heterogeneous in primary tumors and in metastatic lymph nodes from patients with stage T1-4N+M0 gastric adenocarcinoma, which might explain the inconsistent results in assessing the prognostic value of PD-L1 expression in previous studies.

Objective:To summarize the clinical, pathological and molecular characteristics of various types of pediatric glioma, and to explore the differences in the morphology and clinical significance among various types of pediatric glioma.Methods:Based on the fifth edition of the World Health Organization classification of central nervous system tumors, this study classified or reclassified 111 pediatric gliomas that were diagnosed at Guangzhou Medical University Affiliated Women and Children′s Medical Center from January 2020 to June 2023. The clinical manifestations, imaging findings, histopathology, and molecular characteristics of these tumors were analyzed. Relevant literature was also reviewed.Results:The 111 patients with pediatric glioma included 56 males and 55 females, with the age ranging from 10 days to 13 years (average age, 5.5 years). Clinically, manifestations presented from 5 days to 8 years before the diagnosis, including epilepsy in 16 cases, increased intracranial pressure in 48 cases and neurological impairment in 66 cases. MRI examinations revealed tumor locations as supratentorial in 43 cases, infratentorial in 65 cases, and spinal cord in 3 cases. There were 73 cases presented with a solid mass and 38 cases with cystic-solid lesions. The largest tumor diameter ranged from 1.4 to 10.6 cm. Among the 111 pediatric gliomas, there were 6 cases of pediatric diffuse low-grade glioma (pDLGG), 63 cases of circumscribed astrocytoma glioma (CAG), and 42 cases of pediatric diffuse high-grade glioma (pDHGG). Patients with pDLGG and CAG were younger than those with pDHGG. The incidence of pDLGG and CAG was significantly lower in the midline of the infratentorial region compared to that of pDHGG. They were more likely to be completely resected surgically. The pDLGG and CAG group included 4 cases of pleomorphic xanthoastrocytoma, showing histological features of high-grade gliomas. Among the high-grade gliomas, 13 cases were diffuse midline gliomas and also showed histological features of low-grade glioma. Immunohistochemical studies of H3K27M, H3K27ME3, p53, ATRX, BRAF V600E, and Ki-67 showed significant differences between the pDLGG and CAG group versus the pDHGG group ( P<0.01). Molecular testing revealed that common molecular variations in the pDLGG and CAG group were KIAA1549-BRAF fusion and BRAF V600E mutation, while the pDHGG group frequently exhibited mutations in HIST1H3B and H3F3A genes, 1q amplification, and TP53 gene mutations. With integrated molecular testing, 2 pathological diagnoses were revised, and the pathological subtypes of 35.3% (12/34) of the pediatric gliomas that could not be reliably classified by histology were successfully classified. Conclusions:There are significant differences in clinical manifestations, pathological characteristics, molecular variations, and prognosis between the pDLGG, CAG and pDHGG groups. The integrated diagnosis combining histology and molecular features is of great importance for the accurate diagnosis and treatment of pediatric gliomas.

Objective: To study the clinical reference pulpal blood flow(PBF) values detected by laser doppler flowmetry(LDF) in healthy young population and to analyze their possible affected factors. Methods: Undergraduate students at the age of 17-23 years were enrolled. PBF of 12-22 were detected by LDF based on the standard procedure. Difference of the test results between different sex was analyzed by T test and variance homogeneity test, and the correlation with age was analyzed by the chi-square test, and the difference between the different teeth was analyzed by the random group analysis. Results: 400 students(250 males and 150 females with the average age of 19. 83 years) met the inclusion criteria. The clinical reference values of PBF of different anterior teeth were obtained by the detection of LDF. For the same tooth, PBF values of females were higher than that of males (P＜ 0. 05). PBF values of different ages shared no statistical significance(P＞ 0. 05). For the same gender, PBF values of middle incisor were higher than that of lateral incisors(P＜ 0. 05). Conclusion: The determination of the clinical reference values of PBF detected by LDF may promote the clinical use of this technology.