Objective To study the cell apoptosis and the dynamic expression and significance of apoptosis-related genes in graft veins. Methods A rat experimental model of autogenous graft vein was established by transplanting the right external jugular vein to infrarenal abdominal aorta in 100 Wistar rats. TUNEL and immunohistochemistry were used to detect the apoptosis, the expression of apoptosis related genes bcl 2 and bax in vascular smooth muscle cells (VSMCs) of graft veins. Results Within the 8 weeks after transplantation, the apoptotic VSMCs in the graft veins were much more than those in the control group with the apoptotic rate reaching the peak〔(28.5?16.6)%〕 on the 2nd week and dropping to (8.1?2.8)% during the 4th to 8th week. There was statistical difference compared to the control group 〔(0.5?0.2)%, P

BACKGROUND: T cells are believed to play an important role in anti-infection, anti-tumor and immune function. However, the mechanism underlying the differentiation and development remains poorly understood. OBJECTIVE: To investigate the distribution of T cells in nude mice that are jointly transplanted human thymus and cord blood and the reconstruction of the immune function. METHODS: Thirty Balb/c nu/nu nude mice were randomly divided into two groups: an experimental group and a control group. In the experimental group, human thymus tissue was transplanted into the renal capsule of nude mice. Two weeks later, freshly isolated human cord blood CD34+ cells suspension was back perfused into the nude mice via the vein. In the control group, CD34+ cells transplantation was performed directly without thymus transplantation. After 60 days of breeding, the immune function of nude mice was detected in two groups. RESULTS AND CONCLUSION: Human thymus tissue in the renal capsule of nude mice survived and expressed CD3 and HLA-DR molecule. In the experimental group, CD3+ cells which distributed in the form of dots were observed in the mouse spleen. The proportion of CD3+, CD4+, CD8+, and CD4+CD25+ cells were significantly higher in the experimental group than in the control group. The nude mice from the experimental group rejected human gastric cancer BGC823 cells, while those from the control group did not. These findings demonstrated that combined human thymus and CD34+ cell transplantation allow nude mice to acquire T cell-mediated cellular immune function and possess the ability of anti-tumor.

BACKGROUND:cAMP response element binding protein (CREB) is a key protein of memory, which is closely related to long-term memory. It wil provide a new way for the treatment of hypoxic ischemic brain damage (HIBD) to study the effects of dental pulp stem cel s transplantation on the long-term behavior and CREB protein via the lateral ventricle in neonatal HIBD rats. OBJECTIVE:To observe the changes in long-term behavior and CREB protein expression in neonatal HIBD rats after human dental pulp stem cel transplantation, thereby providing scientific evidence for clinical treatment of neonatal HIBD. METHODS:Thirty-six healthy 7-day-old Sprague-Dawley rats were randomly divided into normal, HIBD and cel transplantation group. The hypoxic ischemic brain damage models were established in the brain damage and cel transplantation groups. Twenty-four hours after HIBD, human dental pulp stem cel s were injected into the left lateral cerebral ventricle of rats in the cel transplantation group, total y 3×106 living cel s. Equal volume of normal saline was injected into the left lateral cerebral ventricle of rats in the normal control and HIBD groups. RESULTS AND CONCLUSION:The average time to seek water, the average escape latency and escape distance of the human dental pulp stem cel s group were significantly shorter than those of hypoxic ischemic brain injury group (P<0.01), but longer than those in the normal group (P<0.01). Nissl staining showed that the cel s in the hippocampal CA1 region in human dental pulp stem cel s group were more regular, the number of cel s was significantly higher than that of hypoxic ischemic brain injury group, but stil significantly less than that in the normal group (P<0.05). Immunohistochemical staining results showed that the number of CREB positive cel s in human dental pulp stem cel s group was significantly higher than those in HIBD group, but stil significantly less than those in the normal group (P<0.01). It is suggested that human dental pulp stem cel s transplantation could promote the expression of CREB protein in the hippocampal CA1 region, to improve the long-term learning and memory ability of hypoxic ischemic neonatal rats, and thus repair HIBD.

Objective:To study the antitumor activity and immunological mechanisms of rBCG including GM-CSF and EB virus LMP2A gene fusion.Methods: Animal models of EB virus-positive tumors was built.The formation time of tumors in mice,survival time,tumor weight was analyzed to detect rBCG anti-tumor activity;ELISA method was used to detect the specific antibodies which was produced in the mice stimulated by rBCG,specific CTL killing effect was detected by lactic dehydrogenase assay,ELISPOT was used to assay the secretion of IFN-γand flow cytometry, HE staining of tumor tissue was used to detected lymphocyte infiltration in mice immunized with recombinant BCG.Statistical methods were used for rBCG immunization effect preliminary analysis and evaluation.Results:Comparing to other control,tumor formation time was significantly delayed and tumor growth was slow, survival time of mice prolonged .ELISA test results showed that the rBCG immunization groups of mice could produce specific IgG antibodies of GM-CSF and LMP2A.Specific CTL activity was detected in mice immunized with rBCG.IFN-γsecretion was detected by ELISPOT method, flow cytometry and morphological observation detected tumor tissue infiltration of lymphocytes growth in mice immunized with rBCG.Conclusion:The rBCG induced a humoral and cellular immune responses and induced C57BL/6 mice to produce a strong anti-tumor effect and the EB virus-positive tumor cells was significantly inhibited.

Objective To assess the diagnostic value of 3D-enhanced T2 ? weighted angiography (ESWAN )in evaluating superficial siderosis of the central nervous system (SS-CNS)after traumatic subarachnoid hemorrhage (tSAH).Methods ESWAN and GRE T2 ? WI sequence were performed on 30 patients with tSAH,detection rate and the number of distribution areas of SS-CNS were compared between the two sequences.A McNemar’s test and Wilcoxon signed-rank test were used to analyze the differences between T2 ? WI and ESWAN images sequences. Results In the tSAH group,29 of 30 patients (96.7%)showed SS-CNS on ESWAN images,the total number of SS-CNS regions was 134.Identified SS-CNS positive rate respectively was 95.8% (23/24)on ESWAN images and 66.7% (1 6/24)on T2 ? WI in 24 patients simultaneously perform ESWAN and T2 ? WI sequences.A McNemar ’s test showed that there was significant difference between the positive rates of two sequences in detecting the SS-CNS (χ2 =7.0,P <0.05).The number of SS-CNS regions on ESWAN images and T2 ? WI was 106 and 34 respectively.The Wilcoxon signed rank test showed that the number of SS-CNS regions difference between two sequences was significant (Z =-4.225,P <0.01).Conclusion Various degress of SS-CNS are detected in a majority of tSAH atients.ESWAN sequence is a reliable and efficient method for assessment of SS-CNS.

Objective:To analyze clinical characteristics, treatment, and outcomes of 36 patients with pyoderma gangrenosum, and to compare and evaluate the applicability and consistency between the PARACELSUS score and Delphi criteria.Methods:From January 2000 to January 2022, clinical data were collected from 36 patients who were diagnosed with pyoderma gangrenosum in the Hospital of Dermatology, Chinese Academy of Medical Sciences. The PARACELSUS score and Delphi criteria were applied to their diagnosis, and the kappa test was used to evaluate the consistency between the two diagnostic criteria.Results:Among the 36 patients, 6 (16.67%) had definite precipitating factors before the onset, and 31 (86.11%) exhibited lesions with different degrees of pain. Ulcerative lesions predominatd in 31 (86.11%) patients, which mostly involved the lower extremities, while 16 (44.44%) presented with multiple lesions all over the body. Four (11.11%) patients were complicated by inflammatory bowel disease, and 3 (8.33%) with inflammatory arthritis. Glucocorticoids, Tripterygium wilfordii, and cyclosporin were the main systemic treatment options, and tumor necrosis factor-α antagonist was used in 8 (22.22%) patients. Twenty-two (64.71%) and 17 (50.00%) patients were diagnosed with pyoderma gangrenosum using the PARACELSUS score and Delphi criteria, respectively. The kappa test showed moderate agreement between the two diagnostic criteria (kappa value = 0.47, 95% CI: 0.19 - 0.76, P = 0.004) . Conclusions:Classic ulcerative subtype was the major subtype in the patients with pyoderma gangrenosum, who were usually complicated by inflammatory bowel disease and inflammatory arthritis. Glucocorticoids and immunosuppressants were the main therapeutic drugs. The PARACELSUS score and Delphi criteria focus on different aspects of pyoderma gangrenosum, and the PARACELSUS score is recommended in the context of absence of typical histopathological manifestations.

Objective:To analyze the drug survival rate and safety of dupilumab in the treatment of atopic dermatitis (AD) in elderly patients.Methods:Clinical data were collected from patients diagnosed with AD and treated with dupilumab at the Hospital of Dermatology, Chinese Academy of Medical Sciences from May 2021 to May 2023, and were retrospectively analyzed. The patients aged ≥ 60 years were selected as a study group, and disease severity-matched patients aged <60 years served as a control group. Follow-up was conducted from the start of treatment until 24 weeks after the start of treatment. Drug survival rate and safety were analyzed and compared between the two groups. Drug survival rate was determined through Kaplan-Meier survival analysis; differences in drug survival rate between the two groups were analyzed using the log-rank test; chi-square test was used to compare the reasons for treatment discontinuation between the two groups.Results:The study group and the control group each included 45 patients with AD, and the disease severity of patients in the study group was matched with that in the control group. At 24 weeks after the start of treatment, there was a significant difference in the overall drug survival rate of dupilumab between the study group (37.8%, 17/45) and the control group (57.8%, 26/45; P = 0.030). Among the 45 elderly patients with AD in the study group, a significant difference was observed in the proportion of patients with nodular prurigo phenotype between the patients who completed the 24-week treatment (4/17) and those who did not complete (0, P = 0.007). Main reasons for dupilumab withdrawal in the 28 patients in the study group were poor response (8/28, 28.6%), followed by unaffordability (5/28, 17.9%) and persistent clinical remission (4/28, 14.3%), and the adverse reactions included conjunctivitis (2 cases) and suspected systemic anaphylaxis (3 cases) ; the main reasons for dupilumab discontinuation in 19 patients in the control group were poor response (7/19, 36.8%) and persistent clinical remission (6/19, 31.6%), and the adverse reaction was injection site reaction in 1 case; there was no significant difference in the composition of reasons for drug withdrawal between the two groups. Conclusion:Dupilumab generally exhibited good safety in elderly patients with AD, but its drug survival rate was lower than that in the younger patients.

Objective:To evaluate the clinical efficacy and safety of omalizumab in the treatment of chronic spontaneous urticaria (CSU) .Methods:Clinical data were collected from 60 patients, who were diagnosed with CSU and received subcutaneous injections of omalizumab at a dose of 300 mg once every 4 weeks for 3 sessions in Hospital of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College from March 2020 to September 2020, and retrospectively analyzed. At weeks 0, 2, 4, 6, 8, 10 and 12, urticaria activity score over 7 days (UAS7) and chronic urticaria quality of life (CU-Q2oL) score were used to evaluate clinical symptoms and quality of life of patients. Changes in the use of other drugs were evaluated before and after the treatment with omalizumab. Paired t test was used to compare UAS7 or CU-Q2oL score before and after treatment. Results:All the 60 CSU patients received 12 weeks of omalizumab treatment. The baseline UAS7 score was 22.37 ± 8.88 points; after one session of the treatment, the UAS7 score dropped to 2.01 ± 5.13 points, reaching the treatment plateau; at week 12, it dropped to 0.6 ± 2.63 points, and 0 point (complete control) in 93.3% of the patients, 1-6 points (favorable control) in 3.3%; the time required for UAS7 score to decrease to 0 point was 22.4 ± 3.2 days. The baseline CU-Q2oL score was 34.10 ± 15.01 points; after one session of the treatment, the CU-Q2oL score dropped to 2.41 ± 7.18 points, reaching the treatment plateau; at week 12, it was 0.56 ± 2.90 points; the time required for CU-Q2oL score to drop to 0 point was 21.15 ± 16.02 days. After the combination treatment with omalizumab, a gradual decrease in dosage or withdrawal of previous therapeutic drugs was realized. At week 12, 39 patients (65%) achieved complete control, and withdrew all therapeutic drugs except omalizumab. During the treatment and follow-up, omalizumab showed good safety, and no adverse reactions were observed.Conclusion:Omalizumab at a dose of 300 mg once every 4 weeks is markedly effective and safe for the treatment of CSU, providing a new treatment option for CSU patients with poor response to traditional therapy.

OBJECTIVE: To investigate the effect of miR-204 on the invasion and metastasis of breast cancer by targeted regulation of HNRNPA2B1. METHODS: The bioinformatics database was used to obtain data of the expressions of miR-204 in breast cancer patients and the survival rate of the patients. RT-qPCR was used to detect the expression of miR-204 in breast cancer cell lines. The expression vector GV369-miR-204 was used to overexpress miR-204 in MDA-MB-231 cells. Transwell assay was performed to detect the effect of miR-204 on the migration and invasion ability of the breast cancer cells. The key genes (hub genes) of miR-204 were determined by bioinformatics method. A dual luciferase assay was used to analyze the targeting relationship between miR-204 and HNRNPA2B1. The expression of HNRNPA2B1 in MDA-MB-231 cells after miR-204 overexpression was detected by Western blotting, and Transwell assay was used to examine the changes in the cell invasion ability. RESULTS: The expression of miR-204 was decreased in both breast cancer tissues, and was significantly lower in breast cancer MDA-MB-231 cells than in MCF-10A cells ( < 0.05). The decreased expression of miR-204 was associated with poorer prognosis of breast cancer patients ( < 0.05). Upregulation of miR-204 in MDA-MB-231 cells significantly inhibited the invasion and migration of the cells ( < 0.05). Analysis of the data from the Starbase revealed that the expression of miR-204-5p was negatively correlated with the expression of HNRNPA2B1, and the expression of HNRNPA2B1 was increased in breast cancer patients ( < 0.05) in association with a poorer prognosis of the patients ( < 0.05). Dual luciferase assay demonstrated that miR-204 could bind to HNRNPA2B1 in a target-specific manner. Western blotting and Transwell assay showed that miR-204 significant inhibited the migration and invasion ability of breast cancer cells by targeting HNRNPA2B1 ( < 0.05). CONCLUSIONS miR-204 expression is decreased in breast cancer tissues and cells, and its overexpression can inhibit the invasion and metastasis of breast cancer cells by targeted regulation of HNRNPA2B1.
Breast Neoplasms ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs ; genetics ; Neoplasm Invasiveness ; Neoplasm Metastasis

BACKGROUND: Derlin 3 (DERL3) is downregulated in colorectal cancer (CRC) samples. Its level is closely linked to lymphatic metastasis or distant metastasis rate in CRC patients. However, its biological behavior in lung adenocarcinoma were rarely reported. The aim of this study is to investigate the ectopic expression of DERL3 in lung adenocarcinoma tissues and its effect on the invasion and metastasis of lung adenocarcinoma A549 cell line to reveal the possible mechanism of invasion and metastasis of lung adenocarcinoma. METHODS: Lung adenocarcinoma microarray gene chip data included 3 cases of lymph node metastasis and 3 cases of lung adenocarcinoma tissue without lymph node metastasis. The GEDS and Kaplan-Meier plot queries the survival curve and expression level of DERL3. Western blot was used to detect the expression of DERL3 in lung adenocarcinoma cells. The efficiency of knockdown DERL3 gene was detected by Western blot assay. Transwell detected the number of cells passing through the basement membrane of the transwell. EDU assay detected cell proliferation ability. Western blot detected the expression of epithelial-mesenchymal transition related proteins E-cadherin and Vimentin. RESULTS: The microarray gene chip results showed that compared with lung adenocarcinoma tissues without lymph node metastasis, 1,314 mRNAs in lung adenocarcinoma tissues with lymph node metastasis were up-regulated, 400 mRNAs were down (P<0.05). The expression of DERL3 increased in lung adenocarcinoma (P<0.05). The results of survival curve showed that the lung cancer patients with high expression of DERL3 with poor prognosis (P<0.05). Western blot results indicated that plasmid transfection was successful. Knockdown of DERL3 suppressed the ability of proliferation, invasion and migration in A549 cells (P<0.05). After knockdown of DERL3, the expression level of Vimentin was decreased, while E-cadherin expression increased (P<0.05). CONCLUSIONS Knockdown of DERL3 inhibited the proliferation, invasion and metastasis of A549 cells.