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 評估替比夫定與阿德福韋酯聯合治療優化阿德福韋酯單藥治療應答不佳的陽性慢性乙型肝炎患者的療效。 方法 選擇2008年6月－2009年8月間共26例阿德福韋酯治療至少12個月且病毒學應答不佳的乙型肝炎病毒e抗原（HBeAg），陽性的慢性乙型肝炎患者，在10 mg阿德福韋酯治療的基礎上，加用600 mg替比夫定。肝功能和乙型肝炎病毒（HBV） DNA每3個月評估1次，乙型肝炎兩對半和腹部B型超聲每半年評估1次。 結果 在第1年的治療期間，所有患者血清HBV DNA水平均呈進行性下降，其中24例（92.3%）血清HBV DNA水平在聯合治療12個月時低于檢測值下限，有25例（96.2%）患者丙氨酸轉氨酶水平復常。治療6個月時，分別有7例（26.9%）和2例（7.7%）患者發生HBeAg消失和血清學轉換；治療12個月時，分別有11例（42.3%）和8例（30.8%）患者發生HBeAg消失和血清學轉換。整個治療期間，26例患者均未出現病毒學突破。 結論 阿德福韋酯單藥治療應答不佳時，加用替比夫定可有效控制病毒，使患者獲得較好的病毒學、生化學和免疫學應答。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.
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.
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 分析腺苷蛋氨酸治療慢性乙型肝炎高膽紅素血癥的臨床療效。 方法 回顧性分析2010年1-12月28例接受腺苷蛋氨酸（2 000 mg靜脈滴注，1次/d）治療慢性乙型肝炎高膽紅素血癥患者的臨床資料，并對腺苷蛋氨酸治療慢性重癥乙型肝炎高膽紅素血癥后癥狀、體征及實驗室檢測指標的改變情況進行總結，利用多因素logistic回歸分析方法探索與療效相關的預測因素。根據相關癥狀、體征和實驗室結果的不同，將療效分為顯效、有效和無效3類。 結果 28例患者使用腺苷蛋氨酸治療4周后，顯效20例（71.4%），有效4例（14.3%），無效4例（14.3%）。多因素logistic回歸分析提示病程短、并發癥少是影響腺苷蛋氨酸療效的獨立預測因素。 結論 腺苷蛋氨酸是治療慢性乙型肝炎高膽紅素血癥有效，發病時間短及并發癥少的患者退黃效果更好。【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.
ObjectiveTo systematically review the clinical risk factors, mechanisms, diagnostic strategies, and therapeutic advances in spontaneous rupture of hepatocellular carcinoma (SR-HCC), aiming to optimize clinical decision-making. MethodA comprehensive analysis of recent literature on SR-HCC was conducted to summarize the latest advancements in its epidemiological characteristics, risk factors, underlying mechanisms, diagnostic approaches, and treatment modalities. ResultsRisk factors for SR-HCC included tumor diameter >5 cm, exophytic tumor growth, moderate-to-massive ascites, elevated alpha-fetoprotein level, portal vein invasion, and chronic liver disease. The pathogenesis involved the following aspects. ① Tumor-specific growth dynamics: rapid proliferation causing tissue destruction, vascular compression, and intratumoral ischemia-necrosis. ② Tumor microenvironment alterations: chronic inflammation, thin-walled neovessels, hypoxia-induced matrix degradation increased the risk of SR-HCC. ③ Vascular injury: elastin degeneration, collagen degradation, and deposition of immune complexes led to increased vascular fragility. ④ Background of underlying liver diseases: cirrhosis-related hemodynamic instability and tissue fragility caused rupture. Diagnosis relied on clinical manifestations (acute abdominal pain, shock, intraperitoneal hemorrhage) and imaging. Contrast-enhanced CT showed 100% accuracy for active bleeding detection, ultrasound aided screening, and MRI was used for stable patients. Treatment strategies encompassed conservative therapy, interventional procedures (hemostasis success rate: 53%–100%, preferred for hemodynamically unstable cases but risk hepatic failure in patients with MELD ≥13 points), emergency surgery (high mortality: 16.5%–100%), staged resection (transcatheter arterial embolization followed by elective surgery with 45% of 5-year survival rate vs. 12-month median survival for conservative therapy), and radiofrequency ablation (limited evidence for hemostasis, safety/efficacy required further validation). Conclusions SR-HCC is a life-threatening complication influenced by multifactorial risks and complex molecular mechanisms. Early identification of high-risk patients, combined interventional and staged surgical approaches, and personalized treatment are critical for improving outcomes. Future research should focus on elucidating molecular pathways and refining risk assessment models and integrated therapeutic strategies.
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 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.
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.