OBJECTIVE To study the immunosuppressive effect of combined therapy with FK506 and RS-61443 in rat limb allotransplantation. METHODS: A total of 101 male SD rats were randomly divided into seven groups and used as recipients, and 101 Wistar rats were used as donors. All SD rats were performed limb allotransplantation without using immunosuppressants in control group. In experimental groups (Groups 1-6), the recipients were immunosuppressed with various dosages of FK506, RS-61443 or FK506 + RS61443, after transplantation for 5 weeks. To evaluate the results, we observed circulation of the transplanted limb, the mean rejection time, the histologic grading of skin rejection of limb grafts and the survival time of limb grafts. RESULTS: The control group showed rejection signs (edema and erythema of the skin) after a mean time of 3.36 +/- 1.15 days, and the mean survival time of the allografts was only 7.00 +/- 0.78 days. In the groups only using FK506 or RS-61443, the survival time were prolonged to varying degrees, but rejection occurred even in the period of using drug. As dosage increased, the rejection could not be prevented and the damage to liver and kidney could be induced. In the group using FK506 in combination with RS-61443, only skin and muscle of limb allografts showed slight rejection sign, function of liver and kidney was not obviously affected, the mean survival time of limb allografts was prolonged to 58.76 +/- 6.81 days. CONCLUSIONS: A combination of FK506 and RS-61443 is a more potent immunosuppressive agent than FK506 oro RS-61443 in preventing the rejection of limb allografts, and it can obviously prolong the survival time of limb allografts.
ObjectiveTo explore the key genes and potential molecular mechanisms of liver and lymph node metastases relevant to duodenal neuroendocrine tumors (DNET). MethodsThe tissues of paracancerous duodenal epithelial, primary lesion, liver metastasis lesion, and lymph node metastasis lesion of a rare DNET accompanied by liver and lymph node metastases were sequenced and analyzed. The differentially expressed genes (DEGs) were screened for different tissues and the functional enrichment analysis was performed. ResultsThe tissues of paracancerous duodenal epithelial was used as the control, a total of 2 053 DEGs expressed only in the liver metastases lesion tissues and 742 DEGs expressed only in the lymph node metastases lesion tissues were screened out, and the top 5 genes expressed in the liver metastases lesion tissues were ORM1, C4BPA, AHSG, C9, and LBP, which in the lymph node metastases lesion tissues were ABHD12B, AC100850.1, HOXC9, AC083967.1, and HOXC8. Kyoto Encyclopedia of Genes and Genomes enrichment analysis found that the DEGs were mainly enriched in the phosphatidylinosiol 3 kinase / protein kinase B pathway, mitogen-activated protein kinase pathway, human papillomavirus infection, etc. ConclusionMultiple DEGs and pathways in metastatic lesions are found in this patient with DNET accompanied by liver metastasis and lymph node metastasis, which provides a new direction for treatment and prophylaxis of DNET.
Objective To evaluate the inhibited effects of small interfering RNA targeting Rac1 (Rac1-siRNA) on rat retinal neovascularization in retinae. Methods Retinal vein occlusion was induced by retinal photodynamic medthod in 25 Sprague-Dawley rats. Rac1-siRNA vector DNA was injected into the vitrous of one eye of those rats (gene intervention group), and empty vector DNA was injected into the fellow eye (blank control group). Rac1-siRNA vector was injected in other 25 SD rats without retinal vein occlusion (blank intervention group). Two weeks after injection, fluorescein isothiocyanate (FITC)-dextran was perfused into the hearts of all the rats, and the retinal wholemount was made to observe the neovascularization. The numbers of endothelial cells which break through the internal limiting membrane were counted after hematoxylin-eosin staining. Results A massive of neovascularization and FITC leakage were found in blank control group. Small part of neovascularization and a little FITC leakage were observed in the gene intervention group. Retinal vessels were normal in blank intervention group. Compared with blank contrast group and blank intervention group, the difference of the mean numbers of endothelial cells which broke through the internal limiting membrane in the gene intervention group was significant（t=? P=0.000??lt;0.05）. Conclusion Rac1-siRNA can inhibit retinal neovascularization induced by retinal vein occlusion in rats.
Network meta-analysis (NMA) is a statistical technique that integrates data from multiple clinical studies and compares the efficacy and safety of multiple interventions, which can provide pro and con ranking results for all intervention options in the evidence network and provide direct evidence support for clinical decision-making. At present, NMA is usually based on the aggregation of the same type of data set, and there are still methodological and software difficulties in achieving cross-study design and cross-data format data set merging. The crossnma package of R programming language is based on Bayesian framework and Markov chain Monte Carlo algorithm, extending the three-level hierarchical model to the standard NMA data model to achieve differential merging of varied data types. The crossnma package fully considers the impact of risk bias caused by the combination of different types of data on the results by introducing model variables. In addition, the package provides functions such as result output and easy graphing, which makes it possible to combine NMA across study designs and evidence across data formats. In this study, the model based on crossnma package method and software operation will be demonstrated and explained through the examples of four individual participant datasets and two aggregate datasets.
Circular RNA (circRNA) is a new group of endogenous non-coding RNAs produced by back-splicing, which has multiple molecular functions such as acting as microRNA sponges, regulators of transcription and splicing, adaptors for protein-protein interaction. Recent studies have shown that circRNA play an essential role in development and progression of retinal microvascular dysfunction, diabetic retinopathy, age-related macular degeneration, proliferative vitreoretinopathy, eye diseases caused by hyperhomocysteine and ocular malignancy. In pathological conditions, the differential expression of circRNA alters the transcription and translation of corresponding genes, thus changing the activity and function of cells. CircRNA may become a new marker and prognostic indicator of fundus diseases, and its targeted intervention may also become a potential treatment for fundus diseases.
Objective To investigate the association of the expression of CD15 mRNA with the invasion and prognosis of hepatocellular carcinoma (HCC) and the expression of nm23H1 mRNA. Methods In situ hybridization and immunohistochemistry methods were used to detect the expression of CD15 mRNA and protein nm23H1 mRNA in HCC.Results In 99 cases of HCC, the positive rate of CD15 mRNA,its protein and nm23H1 mRNA were 38.4%, 36.4% and 76.8%, respectively. The expression of CD15 mRNA was consistent with its protein and negatively correlated with the expression of nm23H1 mRNA. The expression of CD15 mRNA and its protein, nm23H1 mRNA were associated with the invasiveness and metastasis of HCC and the prognosis of HCC patients. Conclusion The detection of CD15 expression could be a new pathological biology index to judge the metastasis and prognosis of HCC.
Objective To investigate the prognostic value of ERBB2 Exon20ins (Exon20ins) in advanced non-small cell lung cancer (NSCLC) patients receiving first-line chemotherapy combined with immunotherapy. Methods A retrospective analysis was conducted on clinical data from ERBB2-mutant stage IV NSCLC patients who received first-line chemotherapy combined with immunotherapy at West China Hospital of Sichuan University between 2020 and 2024. ERBB2 wild-type patients were matched using propensity score matching. Clinical pathological characteristics, distant metastatic sites, and treatment outcomes were compared among patients with different mutation statuses. The primary endpoint was progression-free survival (PFS), and Kaplan-Meier method was used to plot survival curves. Cox regression analysis was performed to adjust for confounding factors. Results This study included 41 ERBB2-mutant stage IV NSCLC patients, of whom 22 had Exon20ins mutations, and 19 had other ERBB2 mutations. Forty-one ERBB2 wild-type patients were matched for comparison. The mean age of all patients was 60.0±9.3 years, with 61 males (74.4%). A total of 67 patients (81.7%) received chemotherapy combined with immunotherapy, and 15 patients (18.3%) received chemotherapy combined with immunotherapy and anti-angiogenesis therapy. The Exon20ins group showed a higher incidence of lymph node metastasis compared with the ERBB2 other mutation group and the wild-type group (36.4% vs. 15.8% vs. 9.8%, P=0.045). The median PFS in the Exon20ins group was significantly shorter than in the other mutation group (5.8 months vs. 10.3 months, P=0.025) and the wild-type group (5.8 months vs. 8.3 months, P=0.023). Univariate Cox regression analysis indicated that the ERBB2 Exon20ins mutation was an adverse prognostic factor (Exon20ins vs. other ERBB2 mutations, HR=2.9, 95%CI 1.18 - 7.1, P=0.014; Exon20ins vs. wild-type, HR=2.6, 95%CI 1.25 - 5.6, P=0.014). The combination with anti-angiogenesis therapy did not significantly affect the prognosis of PFS (HR=0.66, 95%CI 0.28 - 1.6, P=0.363). Multivariate Cox regression analysis revealed that the ERBB2 Exon20ins mutation was an independent adverse prognostic factor for PFS (Exon20ins vs. other ERBB2 mutations, HR=3.3, 95%CI 1.27 - 8.3, P=0.015; Exon20ins vs. wild-type, HR=2.7, 95%CI 1.2 - 5.88, P=0.014). For the 67 patients receiving chemotherapy combined with immunotherapy, Cox regression analysis showed that the ERBB2 Exon20ins mutation was still associated with poor prognosis in advanced NSCLC (Exon20ins vs. other ERBB2 mutations, HR=3.2, 95%CI 1.12 - 9.1, P=0.030; Exon20ins vs. wild-type, HR=2.5, 95%CI 1 - 5.88, P=0.040). Conclusions Advanced NSCLC patients with ERBB2 Exon20ins mutation have a worse prognosis compared with those with other ERBB2 mutation subtypes or ERBB2 wild-type when treated with first-line chemotherapy combined with immunotherapy. This suggests that ERBB2 Exon20ins mutation, as a particularly refractory mutation, requires the exploration of new combination strategies based on molecular subtyping to improve survival outcomes.
ObjectiveTo analyze the clinicopathologic features of thyroid tumors with RAS gene mutation.MethodThe clinicopathologic data of thyroid tumor patients who underwent surgical treatment or biopsy and were diagnosed pathologically at the Department of Pathology of the Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2021 to June 2023, were collected. ResultsA total of 798 patients with thyroid tumors who met the inclusion criteria were collected, including 747 cases of follicular epithelial tumors and 51 cases of medullary thyroid carcinoma (MTC). Among 798 patients, the RAS gene mutations were detected in 36 cases (4.5%), including 25 (69.4%) patients with NRAS mutations, 8 (22.2%) patients with HRAS mutations, 3 (8.3%) patients with KRAS mutations, and 4 (1.1%) patients accompanied with TERT promoter mutations. Among 36 patients with RAS mutant thyroid tumors, the male to female ratio was 7∶11, with a median age of 48.5 years, with an average tumor diameter of 2 cm. The mutation rate of RAS gene in different histological types of thyroid tumors, from high to low, was highest in the thyroid follicular carcinoma (FTC, 25.9%), followed by differentiated high grade thyroid carcinoma (20.0%), anaplastic thyroid carcinoma (20.0%), noninvasive follicular thyroid neoplasm with papillary like nuclear features (18.2%), follicular variant of papillary thyroid carcinoma (FVPTC, 16.0%), and well-differentiated thyroid tumour of uncertain malignant potential (WT-UMP, 12.8%), the mutation rates of RAS gene in the FTC, FVPTC, and WT-UMP were significantly higher than that of the classical papillary thyroid carcinoma (P<0.001 1), and the mutation rate of RAS gene was the lowest in the classical papillary thyroid carcinoma (1.5%). A total of 35 patients were effectively followed up with an average follow-up period of 21.4 months, 6 of whom had cervical lymph node metastasis, 4 patients developed distant metastasis, and 1 patient with anaplastic thyroid carcinoma died. ConclusionsRAS gene mutation can occur in thyroid follicular differentiated tumors and MTC. NRAS mutation is more common. The mutation rate is the highest in FTC, is the lowest in classical papillary thyroid carcinoma. Differential diagnosis combined with tissue morphology and other molecular changes can provide a reference for guiding treatment and evaluating prognosis.
Objective To systematically review the effectiveness and model building process of heparin treatment for animal model with smoke inhalation injury. Methods Databases including PubMed, EMbase, CBM, CNKI, VIP and WanFang Data were searched to collect animal experiments about the treatment of heparin for animal model with smoke inhalation injury from inception to November 2016. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then meta-analysis was conducted by RevMan 5.3 software. Results A total of nine studies involving 11 animal experiments were included. The results showed that building animal model with smoke inhalation injury were through burning of cotton towels or pine sawdust by sheep or rats below 40℃. The results of meta-analysis showed that there was no significant difference in mortality rate between two groups (heparin group vs. control group: RR=0.38, 95%CI 0.14 to 1.05, P=0.06; heparin plus DMSO group vs. DMSO group: RR=0.10, 95%CI 0.01 to 1.51, P=0.10). In addition, the pulmonary artery pressure (MD=–3.31, 95%CI –4.51 to –2.11, P<0.000 01), wet to dry weight ratio (MD=–0.90, 95%CI –1.19 to –0.61, P<0.000 01), and lung water content (MD=–1.18, 95%CI –1.67 to –0.70, P<0.000 01) of the experimental group were lower than those in the control group. PaO2/FiO2 after 12 hours (MD=131.00, 95%CI 59.54 to 202.46, P=0.000 3), PaO2/FiO2 after 24 hours (MD=114.00, 95%CI 60.56 to 167.44, P<0.000 1), PaO2/FiO2 after 48 hours (MD=46.00, 95%CI 20.62 to 71.38, P=0.000 4) were higher than those in the control group. However, there was no significant difference in coagulation function between both groups. Conclusion The current evidence shows that the establishment of animal model of smoke inhalation injury is still lack of standard method. Heparin can decrease pulmonary artery pressure and lung water content in animal models with smoke inhalation injury. Due to the limited quality and quantity of included studies, the above conclusions are still needed to be verified by more high quality studies.
Breast cancer is a malignant tumor from normal breast epithelial. In recent years, many literature reports sought to determine the expression of predicted target genes of microRNA and their potential function, pathways and networks, which are involved in the tumorigenesis, metastasis and prognosis of breast cancer. The miR-21 has recently been found to be highly expressed in solid tumors than normal tissue, and it has exposed some layers of gene expression regulation that becomes a hot topic of breast cancer. This paper briefly reviews advances in research on miR-21 in breast cancer.