Objective To summarize the advance in targeted therapy for radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC). Method The literatures relevant to the targeted therapy for RAIR-DTC were reviewed and summarized. Results Targeted therapy for RAIR-DTC mainly included multi-kinase inhibitors suppressing angiogenesis and mutation-specific kinase inhibitors targeting specific mutations. Representative multi-kinase inhibitors such as sorafenib and lenvatinib, which significantly prolonged progression-free survival, had been approved to put into clinical use, though there were shortcomings such as adverse effects and resistance. Mutation-specific kinase inhibitors acted on targets such as RET, mitogen-activated protein kinase pathway, phosphoinositide 3-kinase pathway respectively, with relatively small side effects, most of which had only been applied in clinical trials up to now. Conclusions Targeted therapy for RAIR-DTC has made rapid progress in recent years, filling the gap in treatment for RAIR-DTC. Further explorations and investigations are needed to establish a more effect and safer treatment mode.
目的 评估替比夫定与阿德福韦酯联合治疗优化阿德福韦酯单药治疗应答不佳的阳性慢性乙型肝炎患者的疗效。 方法 选择2008年6月－2009年8月间共26例阿德福韦酯治疗至少12个月且病毒学应答不佳的乙型肝炎病毒e抗原（HBeAg），阳性的慢性乙型肝炎患者，在10 mg阿德福韦酯治疗的基础上，加用600 mg替比夫定。肝功能和乙型肝炎病毒（HBV） DNA每3个月评估1次，乙型肝炎两对半和腹部B型超声每半年评估1次。 结果 在第1年的治疗期间，所有患者血清HBV DNA水平均呈进行性下降，其中24例（92.3%）血清HBV DNA水平在联合治疗12个月时低于检测值下限，有25例（96.2%）患者丙氨酸转氨酶水平复常。治疗6个月时，分别有7例（26.9%）和2例（7.7%）患者发生HBeAg消失和血清学转换；治疗12个月时，分别有11例（42.3%）和8例（30.8%）患者发生HBeAg消失和血清学转换。整个治疗期间，26例患者均未出现病毒学突破。 结论 阿德福韦酯单药治疗应答不佳时，加用替比夫定可有效控制病毒，使患者获得较好的病毒学、生化学和免疫学应答。Objective To evaluate the curative efficacy of telbivudine combined with defovir dipivoxil on positive-HBeAg chronic hepatitis B patients with suboptimal response to adefovir dipivoxil. Methods A total of 26 HBeAg-positive patients with suboptimal response to adefovir dipivoxil (treated with adefovir dipivoxil for more than 12 months) were treated with adefovir dipivoxil 10 mg in addition to telbivudine 600 mg between June 2008 and August 2009. Liver function and serum hepatitis B virus (HBV) DNA tests were assessed at the baseline and 3-month intervals, whereas HBV serological markers and abdominal ultrasonography were carried out every 6 months. Results During the first year of treatment, all patients showed a progressive decline of serum HBV DNA levels; while undetectable serum HBV DNA and normalization of alanine aminotransferase was achieved in 24(92.3%) and 25 (96.2%) patients, respectively, at the end of the first year of treatment. The 6- and 12-month cumulative rates of HBeAg loss were 26.9% (7/26) and 42.3% (11/26), respectively; and corresponding cumulative rates of HBeAg/anti-HBe seroconversion were 7.7% (2/26) and 30.8 (8/26), respectively. During the observation period, no virological breakthrough was detected. Conclusion Telbivudine combined with defovir dipivoxil may be a good choice for patients with suboptimal response to adefovir dipivoxil, which could induce effective viral inhibition and help patients obtain more virological, biochemical and immunological responses.
Spinal cord injury is one of severe complications after thoracic aortic surgery. The degree and time of spinal cord ischemia during surgery, reconstruction of the blood supply of spinal cord ,biochemistry factors ,ischemiareperfusion injury, etc. are considered as factors influence on the complication of spinal cord after surgery. At present, to improve the surgical technique, to increase the blood supply of spinal cord, such as the mechanical dynamic blood perfusion, arterial shunt and cerebrospinal fluid shunt, to degrade the metabolic rate of spinal cord using hypothermia, and to prevent the ischemia-reperfusion injury using drugs are the methods for spinal cord protection during the aortic surgery. The feature of blood circulation of spinal cord, mechanisms of spinal cord injury and the latest progress of spinal cord protection is reviewed in this article.
【摘要】 目的 分析腺苷蛋氨酸治疗慢性乙型肝炎高胆红素血症的临床疗效。 方法 回顾性分析2010年1-12月28例接受腺苷蛋氨酸（2 000 mg静脉滴注，1次/d）治疗慢性乙型肝炎高胆红素血症患者的临床资料，并对腺苷蛋氨酸治疗慢性重症乙型肝炎高胆红素血症后症状、体征及实验室检测指标的改变情况进行总结，利用多因素logistic回归分析方法探索与疗效相关的预测因素。根据相关症状、体征和实验室结果的不同，将疗效分为显效、有效和无效3类。 结果 28例患者使用腺苷蛋氨酸治疗4周后，显效20例（71.4%），有效4例（14.3%），无效4例（14.3%）。多因素logistic回归分析提示病程短、并发症少是影响腺苷蛋氨酸疗效的独立预测因素。 结论 腺苷蛋氨酸是治疗慢性乙型肝炎高胆红素血症有效，发病时间短及并发症少的患者退黄效果更好。【Abstract】 Objective To investigate the curative efficacy of ademetionine in the treatment of hyperbilirubinemia for chronic hepatitis B patients. Methods The clinical data of 28 chronic hepatitis B patients with intrahepatic cholestasis receiving intravenous ademetionine treatment (2 000 mg per day) were retrospectively analyzed. Patients’ symptoms, body signs and laboratory examination results were summarized, and predictors for efficacy were investigated using multiple regression analysis. In this study, the curative efficacy was classified into remarkable efficacy, efficacy and inefficacy, according to the clinical data. Results After one-month treatment with ademetionine, the percentage for remarkable efficacy, efficacy and inefficacy was 71.4%, 14.3%, and 14.3% respectively. Multivariate logistic regression analysis showed that short disease duration and fewer complications were independent predictors for remarkable efficacy of ademetionine treatment. Conclusion Ademetionine is an effective agent for the treatment of hyperbilirubinemia in chronic hepatitis B patients, and the result is especially good for patients with short duration and fewer complications.
Objective To investigate the proportions of CD4+ T cells, CD8+ T cells, and mutant of p53 gene in the microenvironment of breast infiltrating ductal carcinoma, and to explore its’ correlation with prognosis of breast infiltrating ductal carcinoma. Methods Eighty-five cases of breast infiltrating ductal carcinoma were collected who underwent surgery in the 371st Central Hospital of Peoples’ Liberation Army from 2010 to 2012, and then detected the proportion of CD4+ T cells and CD8+ T cells, ratio of CD4+ T cells to CD8+ T cells, and mutant of p53 gene in the cancer tissues with immunohistochemistry. Comparison between the sentinel lymph node metastasis group and non-sentinel lymph node metastasis group, mutant of p53 gene group and non-mutant of p53 gene group on the proportions of CD4+ T cells, CD8+ T cells, and ratio of CD4+ T cells to CD8+ T cells were performed, as well as the relationship between proportion of CD8+ T cells/mutant of p53 gene and prognosis of breast infiltrating ductal carcinoma. Results ① The relationship between proportion of CD4+ T cells/proportion of CD8+ T cells/ratio of CD4+ T cells to CD8+ T cells and situation of sentinel lymph node metastasis: at cluster, compared with the sentinel lymph node metastasis group, the proportion of CD8+ T cells was lower in the non-sentinel lymph node metastasis group (P<0.05), but there was no significant difference on the proportion of CD4+ T cells and ratio of CD4+ T cells to CD8+ T cells (P>0.05); at stroma, compared with the sentinel lymph node metastasis group, the proportions of CD4+ T cells and CD8+ T cells were lower, but the ratio of CD4+ T cells to CD8+ T cells was higher in the non-sentinel lymph node metastasis group (P<0.05). ② The relationship between proportion of CD4+ T cells/proportion of CD8+ T cells/ratio of CD4+ T cells to CD8+ T cells and mutant of p53 gene: both at the cluster and stroma, compared with the mutant of p53 gene group, the proportions of CD4+ T cells and CD8+ T cells were lower, but the ratio of CD4+ T cells to CD8+ T cells was higher in the non-mutant of p53 gene group (P<0.05). ③ The relationship between proportion of CD8+ T cells/mutant of p53 gene and prognosis of breast infiltrating ductal carcinoma: the prognosis was worse in patients with high degree of infiltration of CD8+ T cells and mutant of p53 gene than those patients with low degree of infiltration of CD8+ T cells and non-mutant of p53 gene (P<0.05). Conclusions The proportions of CD4+ T cells and CD8+ T cells, and ratio of CD4+ T cells to CD8+ T cells are associated with the situation of sentinel lymph node metastasis and mutant of p53 gene, and the degree of infiltration of CD8+ T cells and mutant of p53 gene are associated with the prognosis of breast infiltrating ductal carcinoma.
Recent advances in epigenetics indicate that several epigenetic modifications, including acetylation, methylatio, and microRNA (miRNA), play an important role in the pathogenesis of acute kidney injury (AKI). Our study reveales that enhancement of protein acetylation by pharmacological inhibition of class I histone deacetylases leads to more severe tubular injury, and delays the restoration of renal structure and function. The changes in promoter DNA methylation occurs in the kidney with ischemia/reperfusion. MiRNA expression is associated with the regulation of both renal injury and regeneration after AKI. Targeting the epigenetic process may provide a therapeutic treatment for patients with AKI. The purpose of this review is to summarize recent advances in epigenetic regulation of AKI and provide mechanistic insight into the role of acetylation, methylation, and miRNA expression in the pathological processes of AKI.
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.
ObjectiveTo explore the effects of elafin on the regulation of mucin5AC (MUC5AC) in airway epithelial cells.MethodsAfter cultivating epithelial cells in vitro, cells were stimulated by cigarette smoke extract (CSE) and lipopolysaccharide (LPS), the intracellular MUC5AC production and extracellular secretion were assayed by immunofluorescence and ELISA, respectively.ResultsThe level of MUC5AC protein was obviously increased in the LPS stimulation group [(0.785±0.005) μg/ml vs. (0.232±0.004) μg/ml] and the CSE stimulation group [(0.803±0.005) μg/ml vs. (0.255±0.003) μg/ml] than those in the blank control groups (both P<0.01). When pretreated with elafin then stimulated by LPS and CSE, the MUC5AC productions were evidently decreased than those in the single LPS and CSE stimulation groups [(0.363±0.003) μg/ml and (0.406±0.006) μg/ml, bothP<0.01]. As compared with the blank control groups, the MUC5AC protein secretion were significantly decreased after stimulated with single elafin [(0.176±0.002) μg/ml and (0.193±0.004) μg/ml, bothP<0.05].ConclusionElafin may inhibit MUC5AC hypersecretion by blocking MUC5AC production and secretion.
ObjectiveTo establish and internally validate a predictive model for poorly differentiated adenocarcinoma based on CT imaging and tumor marker results. MethodsPatients with solid and partially solid lung nodules who underwent lung nodule surgery at the Department of Thoracic Surgery, the Affiliated Brain Hospital of Nanjing Medical University in 2023 were selected and randomly divided into a training set and a validation set at a ratio of 7:3. Patients' CT features, including average density value, maximum diameter, pleural indentation sign, and bronchial inflation sign, as well as patient tumor marker results, were collected. Based on postoperative pathological results, patients were divided into a poorly differentiated adenocarcinoma group and a non-poorly differentiated adenocarcinoma group. Univariate analysis and logistic regression analysis were performed on the training set to establish the predictive model. The receiver operating characteristic (ROC) curve was used to evaluate the model's discriminability, the calibration curve to assess the model's consistency, and the decision curve to evaluate the clinical value of the model, which was then validated in the validation set. ResultsA total of 299 patients were included, with 103 males and 196 females, with a median age of 57.00 (51.00, 67.25) years. There were 211 patients in the training set and 88 patients in the validation set. Multivariate analysis showed that carcinoembryonic antigen (CEA) value [OR=1.476, 95%CI (1.184, 1.983), P=0.002], cytokeratin 19 fragment antigen (CYFRA21-1) value [OR=1.388, 95%CI (1.084, 1.993), P=0.035], maximum tumor diameter [OR=6.233, 95%CI (1.069, 15.415), P=0.017], and average density [OR=1.083, 95%CI (1.020, 1.194), P=0.040] were independent risk factors for solid and partially solid lung nodules as poorly differentiated adenocarcinoma. Based on this, a predictive model was constructed with an area under the ROC curve of 0.896 [95%CI (0.810, 0.982)], a maximum Youden index corresponding cut-off value of 0.103, sensitivity of 0.750, and specificity of 0.936. Using the Bootstrap method for 1000 samplings, the calibration curve predicted probability was consistent with actual risk. Decision curve analysis indicated positive benefits across all prediction probabilities, demonstrating good clinical value. ConclusionFor patients with solid and partially solid lung nodules, preoperative use of CT to measure tumor average density value and maximum diameter, combined with tumor markers CEA and CYFRA21-1 values, can effectively predict whether it is poorly differentiated adenocarcinoma, allowing for early intervention.
Objective To summarize our diagnostic and treatment experience for patients with acute Stanford type A aortic dissection （AAAD） during pregnancy. Methods Clinical data of 3 AAAD gravida （age of 30，32，35） who received surgical treatment in Beijing Anzhen Hospital of Capital Medical University from May 2008 to July 2010 were retros-pectively analyzed. One gravida received Sun’s procedure （total arch replacement combined with stented elephant trunk implantation） 3 days after cesarean section，but the fetus died in the uterus. Another gravida successfully underwent Bentall procedure and Sun’s procedure immediately after cesarean section and hysterectomy. The third gravida received cesarean section with the uterus in situ followed by ascending aorta replacement and Sun’s procedure. Results All the 3 puerperasrecovered uneventfully，and the 2 newborns of the second and third puerperas also lived well. The 3 puerperas were followedup for 6 months after discharge. CT scan showed organized thrombus in the aortic false lumen. During follow-up，the 3 puerperas recovered well，and the 2 infants had normal growth and development. Conclusions Management principles of AAAD during pregnancy firstly include timely and accurate diagnosis，which is of prime importance. Secondly，gravidas’hemodynamics should maintain stable. Thirdly，intraoperative hemorrhage should be satisfactorily controlled. Lastly，multi-modality treatment is very important to improve the prognosis of both gravidas and fetuses.