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 investigate research advance on the value of B-type RAF kinase (BRAF) gene mutation assisted diagnosis of papillary thyroid cancer (PTC) in thyroid nodule.MethodThe recent literatures on the BRAF gene mutation and its combination with fine needle aspiration cytology (FNAC) in the diagnosis of benign and malignant thyroid nodules and PTC were collected and reviewed.ResultsThe BRAFV600E gene mutation was the most common type of gene mutation in the genetic molecule of PTC. The combination of the FNAC and BRAF gene mutation detection could improve the diagnostic value of the benign and malignant thyroid nodules, especially the diagnostic accuracy of PTC. However, the negative detection of BRAF gene mutation did not rule out the possibility of PTC. It still remained controversial that the detection of BRAF gene mutation could differentiate between the benign and malignant thyroid nodules.ConclusionsBRAF gene mutation detection has different diagnostic values in different types of thyroid nodules. It has considerable diagnostic value in thyroid nodules with high BRAF mutation incidence (suspicious for malignancy, undetermined significance or follicular lesion of undetermined significance nodules) while presents false negative result in thyroid nodule with very low mutation incidence category to a large extent. BRAF gene detection might become a specific diagnostic molecular marker to promote diagnosis accuracy of PTC.
ObjectiveThe diagnostic efficacy of long non-coding RNA (lncRNA) for tuberculosis was evaluated by systematic review. MethodsData from PubMed, Web of Science, Cochrane Library, Embase, CMJFD, CNKI and WanFang Data were searched. Literatures on the diagnostic value of lncRNA in tuberculosis from the database establishment to August 20, 2024 were selected, and the quality of literatures was assessed using QUADAS-2 tool. Meta-Disc 1.0 software tested the threshold heterogeneity of the included studies. Stata 18.0 software calculated sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and other effect sizes, and performed subgroup analysis and meta regression to explore the source of heterogeneity. Deeks funnel plot evaluates publication bias. Results A total of 28 case-control studies were included in 14 literatures. The meta-results showed that the combined sensitivity was 0.88 (95%CI 0.81 to 0.93), the specificity was 0.90 (95%CI 0.84 to 0.94), and the PLR was 9.05 (95%CI 5.16 to 15.87). The NLR and DOR were 0.13 (95%CI 0.08 to 0.22) and 67.96 (95%CI 27.27 to 169.39), and the AUC were 0.95 (95%CI 0.93 to 0.97). Subgroup analysis showed that lncRNA was more effective in the diagnosis of tuberculosis when PMBC samples, lncRNA expression was down-regulation, the study sample size was ≤100, there was cut-off value, GAPDH was used as the internal reference, and RNA extraction kit was used. meta regression indicated that lncRNA expression level and sample size were the main sources of heterogeneity. Conclusion LncRNA has high accuracy in the diagnosis of tuberculosis, and is expected to become a new biomarker to assist the diagnosis of tuberculosis.
ObjectiveTo summarize the mechanism of long non-coding RNA (lncRNA) in signal pathways related to osteogenic differentiation. Methods Relevant domestic and foreign researches in recent years were consulted. The characteristics and biological functions of lncRNA were introduced, and the specific mechanism of lncRNA regulating related signal pathways in osteogenic differentiation was elaborated. Results The exertion and maintenance of normal function of bone requires the closed coordination of transcription networks and signal pathways. However, most of these signal pathways or networks are dysregulated under pathological conditions that affect bone homeostasis. lncRNA can regulate the differentiation of various bone cells by activating or inhibiting signal pathways to achieve the balance of bone homeostasis, thereby reversing the pathological state of bones and achieving the purpose of treating bone metabolic diseases. Conclusion At present, the research on the mechanism of lncRNA regulating various osteogenic differentiation pathways is still in the early stage. Its in-depth regulator mechanism, especially the cross-talk of complex signal pathways needs to be further studied. And how to apply these molecular targets to clinical treatment is also a big challenge.
ObjectiveTo compare the clinical therapeutic efficacy of radiofrequency ablation (RFA) and external beam radiation (XRT) in the treatment of early hepatocellular carcinoma (HCC). MethodsThe early HCC patients were collected in the SEER (Surveillance, Epidemiology, and End Results) database, from 2010 to 2015, according to the established inclusion and exclusion criteria. The patients were assigned into an XRT group and a RFA group according to according treatment plans. The propensity score matching (PSM) was performed at a ratio of 1∶4 based on age, gender, race, alpha-fetoprotein (AFP), cirrhosis, and tumor diameter. The overall survival of the patients of the two groups was compared, and the risk factors affecting the long-term prognosis for the early HCC patients were analyzed. ResultsA total of 2 861 early HCC patients were collected, including 2 513 in the RFA group and 348 in the XRT group. After PSM, a total of 1 582 patients were enrolled, including 343 in the XRT group and 1 239 in the RFA group. After PSM, the proportion of tumor with larger diameter (>5 cm) in the XRT group was still higher than that in the RFA group (P<0.001), but there were no statistically significant differences in the other clinical pathological characteristics between them (P>0.05). The Kaplan-Meier survival curves of the RFA group was better than that of the XRT group (HR=1.65, P<0.001); The stratified analysis based on the tumor diameter revealed that the survival curves of the RFA group were superior to those of the XRT group in the HCC patients with tumor diameters <3 cm, 3–5 cm, and >5 cm (<3 cm: HR=1.79, P<0.001; 3–5 cm: HR=1.50, P<0.001; >5 cm: HR=1.67, P=0.003). The results of the multivariate Cox regression model analysis showed that the older age (≥65 years), higher AFP level (≥400 μg/L), larger tumor diameter (≥3 cm), and later AJCC stage (stage Ⅱ) were the risk factors for overall survival in the early HCC patients (HR>1, P<0.05), while the XRT treatment was a risk factor for shortening overall survival in the HCC patients [HR(95%CI)=1.62(1.41, 1.86), P<0.001]. ConclusionThe data analysis results from the SEER database suggest that the long-term overall survival of RFA treatment is superior to XRT treatment for patients with AJCC stage Ⅰ or Ⅱ.
From 1978 to Dec. 1991, 50 cases of dilatation of the extrahepatic biliary duct in children were treated. They were classified as: cystic dilatation in 34 cases, arid fusiform dilatation in 16 cases. Types of reconstruction of the extrahepatic biliary duct included: excision of cystic dilatation and Rorx-en-Y hepatoductojejunostomy in 25 cases, and interposition of jejunum and hepatoductoduodenostomy in 9 eases. for those cases having fusiform dilatation, interposition of jejunum and hepatoductoduodenostomy，cases and Rorx-en-Y-hepatoductojejunostmy 5 cases.The follow-up period averajed 6.5 years. Forty nine patients were recoverwd from the teatment and 1 patient died.
Objective To study the effect of down-regulation of Claudin-3 mediated by adeno-associated virus (AAV) of shRNA on the cultured retinal ganglion cells (RGCs) in vitro. Methods RGCs isolated from mouse eyes were divided into normal control group, AAV-shScramble group, and AAV-shClaudin-3 group. The RGCs in AAV-shScramble group and AAV-shClaudin3 group were treated with AAV-shScramble and AAV-shClaudin-3 respectively 24 hours after cell seeding. Dynamic live cell fluorescence microscopy was used to observe the transfection efficiency 96 hours after transfection. Immunofluorescent staining of β-tubulin was used to measure the length of RGCs′ axon. 4′, 6-diamidino-2-phenylindole staining was used to observe the nuclei of apoptotic cells. The mRNA level of Claudin-3 and VEGF was measured by real-time polymerase chain reaction. The protein levels of Claudin-3, vascular endothelial growth factor (VEGF), Bcl-2 and Caspase-3 was determined by Western blot. Results The positive transfection rate was more than 50% in both AAV-shScramble group and AAV-shClaudin-3 group. The length of RGCs' axon in AAV-shClaudin-3 group was shorter than that in normal control group and AAV-shScramble group (F=22 363.274,P＜0.05). Down-regulation of Claudin-3 accelerated RGCs' apoptosis with nuclei shrinkage, tapering, and nucleolus formation of apoptotic bodies. The mRNA levels of Claudin-3 and VEGF in AAV-shClaudin-3 group were lower than those in normal control group and AAV-shScramble group (F=257.408, 160.533;P＜0.05). The protein levels of Claudin-3, VEGF and Bcl-2 in AAV-shClaudin-3 group were lower than those in normal control group and AAV-shScramble group (F=129.671, 420.552, 62.669;P＜0.05), while the protein level of Caspase-3 in AAV-shClaudin-3 group was higher than that in normal control group and AAV-shScramble group (F=231.348,P＜0.05). Conclusion Down-regulation of Claudin-3 increases the expression of Caspase-3, reduces the expression of VEGF and Bcl-2, accelerates RGCs' apoptosis and inhibit the RGCs' axon growth.
RCBTB1 gene associated hereditary retinopathy is an extremely rare inherited retinal disease (IRD) discovered recently. The mutation of RCBTB1 gene can lead to a variety of IRD clinical phenotypes, such as early retinitis pigmentosa and delayed chorioretinal atrophy. The hereditary mode of RCBTB1 gene associated retinopathy is autosomal recessive. RCBTB1 gene plays an important role in maintaining mitochondrial function and anti-oxidative stress defense mechanism of retinal pigment epithelium cells. In the future, it is necessary to further determine whether there is a genotypic and phenotypic correlation in the age of onset of RCBTB1 gene associated retinopathy or multi-organ involvement, and evaluate the safety and efficacy of adeno-associated virus-mediated RCBTB1 gene replacement therapy in animal models, to explore the feasibility of gene replacement therapy and stem cell therapy.
ObjectiveTo summarize the domestic and abroad articles related to the research on the relation between miRNA-221/222 and thyroid cancer, and explore the important effects of miRNA-221/222 in diagnosis and treatment of thyroid cancer. MethodsDomestic and international publications involving the relationship of miRNA-221/222 to thyroid cancer were screened and reviewed. ResultsMiRNA-221/222 is a tumor marker with high specificity and sensitivity in thyroid cancer. It has important significance for diagnosis, treatment and prognosis of thyroid cancer. ConclusionMiRNA-221/222 is not only related to diagnosis of thyroid cancer, but also have provided a new research direction and method for gene therapy of thyroid cancer．
Circular RNA (circRNA) is a non-coding RNA which exists widely in eukaryotic cells with a structure of covalently closed continuous loop. Its generation, characteristics and functions have received extensive attention, making it one of the hot spots in the field of non-coding RNA research. Many studies have found that circRNA plays an important role in the development of various diseases including cardiovascular disease, nervous system disease and cancer. Cardiovascular disease is a worldwide common disease with high incidence and poor prognosis. Its exact pathogenesis has not been found, which blocks the development of cardiovascular disease treatment. In this review, we summarize the loop-forming mechanisms, the functions and the progress of current researches of circRNA in cardiovascular diseases.