MLL4 Regulates the Progression of Non–Small-Cell Lung Cancer by Regulating the PI3K/AKT/SOX2 Axis / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Mixed-lineage leukemia protein 4 (MLL4/KMT2D) is a histone methyltransferase, and its mutation has been reported to be associated with a poor prognosis in many cancers, including lung cancer. We investigated the function of MLL4 in lung carcinogenesis. @*Materials and Methods@#RNA sequencing (RNA-seq) in A549 cells transfected with control siRNA or MLL4 siRNA was performed. Also, we used EdU incorporation assay, colony formation assays, growth curve analysis, transwell invasion assays, immunohistochemical staining, and in vivo bioluminescence assay to investigate the function of MLL4 in lung carcinogenesis. @*Results@#We found that MLL4 expression was downregulated in non–small cell lung cancer (NSCLC) tissues compared to adjacent normal tissues and tended to decrease with disease stage progression. We analyzed the transcriptomes in control and MLL4- deficient cells using high-throughput RNA deep sequencing (RNA-seq) and identified a cohort of target genes, such as SOX2, ATF1, FOXP4, PIK3IP1, SIRT4, TENT5B, and LFNG, some of which are related to proliferation and metastasis. Our results showed that low expression of MLL4 promotes NSCLC cell proliferation and metastasis and is required for the maintenance of NSCLC stem cell properties. @*Conclusion@#Our findings identify an important role of MLL4 in lung carcinogenesis through transcriptional regulation of PIK3IP1, affecting the PI3K/AKT/SOX2 axis, and suggest that MLL4 could be a potential prognostic indicator and target for NSCLC therapy.

Correlation analysis between short-term invasive recurrence and functional MRI after radiofrequency ablation of hepatocellular carcinoma / 中华放射学杂志

Objective:To explore and clarify the correlation between short-term aggressive intrasegmental recurrence (AIR) and functional magnetic resonance imaging after radiofrequency ablation of hepatocellular carcinoma (HCC).Methods:A retrospective analysis of 1 262 patients with HCC who underwent radiofrequency ablation (RFA) in our hospital from January 2012 to June 2018, all patients were confirmed by pathology as HCC, of which 30 patients were found to have AIR during radiographic follow-up within 3 months after surgery, another 35 patients with disease progression who were controlled in a short period of time were randomly selected as the control group. All the enrolled patients underwent dynamic enhanced magnetic resonance imaging (DCE-MRI) and diffusion weighted imaging (DWI) scanning before surgery, and the differences in clinical data, lesion location, and functional magnetic resonance parameters between the two groups were compared, and their correlation with AIR after RFA was analyzed. Chi-square test, t test and Pearson test were used. Results:The lesions in the AIR group were significantly more in the Ⅰand Ⅳsegments than that in the control group ( P<0.05), and there was no significant difference in other liver segments ( P>0.05). There was no significant difference in the lesion morphology between the two groups ( P>0.05), and there was a significant difference in the early enhancement pattern of the lesions ( P<0.05), and the early arterial enhancement rate and apparent diffusion coefficient (ADC) value of the AIR group were significantly lower than the control group ( P<0.05). Further correlation analysis found that early enhancement of the arterial artery, early arterial enhancement rate, ADC value and lesion location were associated with AIR and were positively correlated, r values were 0.455, 0.633, 0.518, 0.375 and 0.287 ( P<0.05). Conclusion:The short-term AIR and functional imaging parameters (arterial early enhancement, early arterial enhancement rate, ADC value) and the liver segment (Ⅰ and Ⅳ) were highly correlated with radiofrequency ablation.

Correlation analysis between short-term invasive recurrence and functional MRI after radiofrequency ablation of hepatocellular carcinoma / 中华放射学杂志

Objective@#To explore and clarify the correlation between short-term aggressive intrasegmental recurrence (AIR) and functional magnetic resonance imaging after radiofrequency ablation of hepatocellular carcinoma (HCC).@*Methods@#A retrospective analysis of 1 262 patients with HCC who underwent radiofrequency ablation (RFA) in our hospital from January 2012 to June 2018, all patients were confirmed by pathology as HCC, of which 30 patients were found to have AIR during radiographic follow-up within 3 months after surgery, another 35 patients with disease progression who were controlled in a short period of time were randomly selected as the control group. All the enrolled patients underwent dynamic enhanced magnetic resonance imaging (DCE-MRI) and diffusion weighted imaging (DWI) scanning before surgery, and the differences in clinical data, lesion location, and functional magnetic resonance parameters between the two groups were compared, and their correlation with AIR after RFA was analyzed. Chi-square test, t test and Pearson test were used.@*Results@#The lesions in the AIR group were significantly more in the Ⅰand Ⅳsegments than that in the control group (P<0.05), and there was no significant difference in other liver segments (P>0.05). There was no significant difference in the lesion morphology between the two groups (P>0.05), and there was a significant difference in the early enhancement pattern of the lesions (P<0.05), and the early arterial enhancement rate and apparent diffusion coefficient (ADC) value of the AIR group were significantly lower than the control group (P<0.05). Further correlation analysis found that early enhancement of the arterial artery, early arterial enhancement rate, ADC value and lesion location were associated with AIR and were positively correlated, r values were 0.455, 0.633, 0.518, 0.375 and 0.287 (P<0.05).@*Conclusion@#The short-term AIR and functional imaging parameters (arterial early enhancement, early arterial enhancement rate, ADC value) and the liver segment (Ⅰ and Ⅳ) were highly correlated with radiofrequency ablation.

Treatment of left accessory cardiac pathway conduction disorders using radiofrequency catheter ablation under the guidance of the Ensite NavX 3D mapping system: a retrospective study.

To investigate the effectiveness and safety of using the Ensite NavX three-dimensional (3D) mapping system during Radiofrequency catheter ablation (RFCA) of left accessory pathway (AP) disorders. A total of 227 patients having their left AP treated by RFCA, were classified into study group (n = 112) and the control group (n = 115). X-ray irradiation time and exposure doses during the course of the operations were recorded. Time taken to place the mapping catheter along with total duration of operations and procedural complications were compared. The X-ray irradiation time and exposure doses in the course of manipulating the ablation catheters were significantly lower in the study group compared to control (5.1 ± 2.3 min vs. 13.1 ± 3.1 min; P < 0.05 and 5.7 ± 2.6 mGy vs. 17.8 ± 4.3 mGy; P < 0.05, respectively). The total duration of operation was also significantly shorter in the study group compared to control (53.1 ± 18.8 min vs. 62.3 ± 20.6 min; P < 0.05). No procedural complications were reported in both groups. The irradiation time and exposure dose along with total operation duration was significantly reduced when the Ensite NavX mapping system was used during RFCA in comparison with traditional X-ray fluoroscopy method.

A discussion of reasons and methods of prevention and cure for serious complications of radiofrequency ablations in the treatments of hepatocellular carcinomas / 中华放射学杂志

Objective To investigate the reasons and the methods of prevention and cure for serious complications of radiofrequency ablations in the treatments of hepatocellular carcinomas. Methods A total of 410 patients with BCLC at A or B stage of hepatocellular carcinomas in our hospital were enrolled between November 2014 and June 2009. These patients underwent a total of 504 times radiofrequency ablations for the treatments of liver lesions. This retrospective study analysed the reasons and the strategies of prevention and cure for the serious complications. Results In the patients with a total of 504 times radiofrequency ablations, 2 patients had massive hemorrhage caused by puncture injuries, 2 patients had the tumors which were close to the liver capsules and 1 patient had bile peritonitis caused by the injury of thermal ablation on the gallbladder. The maximum diameter of tumor was 5 cm. That tumor was close to the gallbladder. 2 patients had needle tract metastases caused by incompletely needle path ablations. 1 of the 2 patients had a tumor near the liver capsule, and the other patient had un-enough temperature for needle path ablation. Tumor outbreaks were happened in 2 patients. 1 of the 2 patients had a tumor which was located in the liver capsule and close to the portal vein. The other patient had a 12 cm diameter tumor with rich blood supplement. 2 patients had liver abscesses. 1 of the 2 patients had a tumor near the ascending colon, and the other patient had diabetes. 1 patient had colonic perforation caused by thermal ablation. The tumor in that patient was located in the right hepatic lobe segment and adjacent to the ascending colon. The incidence of serious complications was 1.98% (10/504). Conclusions The incidence of the serious complications of radiofrequency ablations for the treatments of hepatocellular carcinomas is relatively low. The main reasons for the serious complications were direct injuries caused by punctures, heat radiation injuries, tumors adjacent to large blood vessels, gallbladders and intestines, tumors with abundant blood supplement, needle paths fail to cross normal liver tissues, low scores of liver function, weak immune system and diabetes. The key points for avoiding and reducing the serious complications are preoperative evaluations of patients' basic situations, choices of appropriate puncture channels and control ranges of ablations when tumors are close to important blood vessels, intestines and gallbladders.

Recent progress in the application of radiofrequency ablation in treating benign thyroid nodules / 介入放射学杂志

Thyroid nodules are common clinical disease, and most of the nodules are benign. After radiofrequency ablation (RFA) treatment, the volume of benign thyroid nodules will significantly shrink or the nodules will even disappear, thus, the related clinical symptoms induced by the thyroid nodules will be improved. For recent years, radiofrequency ablation has become the treatment of first choice for benign thyroid nodules. This paper aims to make a comprehensive review about the research situation concerning the radiofrequency ablation in the treatment of the benign thyroid nodules so as to provide scientific guidance and basis for the relevant clinical research and treatment.

EGFR-TKIS combined with radioactive 125I seed implantation for the treatment of advanced non-small-cell lung cancer：analysis of clinical effect / 介入放射学杂志

Objective To evaluate the short-term efficacy, safety and effectiveness of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) combined with radioactive 125I seed implantation in treating advanced non-small-cell lung cancer (NSCLC). Methods A total of 48 patients with inoperable and EGFR mutation-positive advance NSCLC were included in this study. The patients were divided into study group (n = 26) and control group (n = 22). Patients in the study group were treated with EGFR-TKIs combined with radioactive 125I seed implantation; while patients in the control group only received EGFR-TKIs treatment, which was kept on until the disease progressed. The clinical efficacy, and the incidence of side effect as well as the survival rate were determined, and the results were compared between the two groups. Results Local disease control rate of the study group and the control group was 92.3% and 68.2%respectively, the difference was statistically significant (P= 0.033), while the effective rate was 76.9% and 54.5%respectively, the difference was not significant (P=0.101). Progression-free survival (PFS) time of the study group and the control group was 14.1 months and 9.7 months respectively (P< 0.05). The one-year survival rate of the study group and the control group was 80.8%and 63.6%respectively (P<0.05), and the median survival time was 26.9 months and 17.1 months respectively (P < 0.05). The major complication caused by radioactive 125I seed implantation was pneumothorax. Conclusion For EGFR mutation-positive advance NSCLC, EGFR-TKIs together with radioactive 125I seed implantation is a safe and effective treatment.Its short-term efficacy is superior to pure EGFR-TKIs therapy. At present, this combination therapy is a new alternative for the treatment of EGFR mutation-positive advance NSCLC.

Diagnosis and treatment of the neurofibroma of the common bile duct / 中华消化外科杂志

Neurofibroma is an autosomal dominant genetic disease which is originated from the abnormal differentiation of neural crest cells and would cause system damage.NF can occur at most organs in the body,while it is rarely seen in the common bile duct.In February 2007,1 old patients with NF was admitted to the Lishui Central Hospital of Zhejiang Province.The results of preoperative magnetic resonance cholangiopancreatography (MRCP) revealed that the common bile duct was slightly dilated,and the diameter of the common bile duct was 1.2 cm.A nodular short T2 signal lesion was detected at the middle part of the common bile duct with the size of 1.4 cm × 1.6 cm.The results of intraoperative rapid frozen section pathological examination showed that the lesion was cholangiocarcinoma,then cholangiocarcinoma resection + biliojejunal Roux-en-Y anastomosis was applied to the patient.Postoperative pathological examination confirmed that the lesion was neurofibroma.The patient was followed up for 7 years and died of pulmonary infection in June 2014.The clinical presentation of neurofibroma of the common bile duct is untypical.Space-occupying lesions detected in the patients with history of bile duct injury or operation should be considered to be diagnosed as neurofibroma.Special attention should be paid to the accuracy of the results of rapid frozen section pathological examination in order to avoid missdiagnosis.

Effects of terguride on protein and mRNA expressions of dopamine D2 receptor and dynorphin in different brain regions of rats after heroin self administration / 中国药理学与毒理学杂志

OBJECTIVE To study mechanisms of terguride on the treatment of herion dependence. METHODS Adult male SD rats were randomly assigned into 5 groups: normal control group, saline treatment during heroin use period group, terguride treatment during heroin use period group, saline treatment during heroin reinstatement period group, terguride treatment during heroin reinstatement period group, the last 4 groups established heroin intravenous self administration and cue induced reinstatement models, and after interfernce and perfusion to get the following five brain regions [including ventral tegmental area (VTA)]sections. The expression of dopamine D2 receptor protein and mRNA, prodynorphin protein and preprodynorphin mRNA was detected by immunohistochemistry and hybridization in situ. RESULTS The expression of dopamine D2 receptor was downregulated during heroin use period and upregulated during heroin reinstatement period in nucleus accumbens shell (AcbSH) region, the expression of dopamine D2 receptor mRNA was parallelled with the protein expression approximately, terguride could downregulate the high expression of receptor protein during reinstatement. The expression of dopamine D2 receptor protein and mRNA was upregulated during heroin reinstatement period in central nucleus amygdalae (CeA) region, and terguride could downregulate this high expression. The expression of dopamine D2 receptor protein and mRNA was upregulated during heroin use period and downregulated during heroin reinstatement period in CA1 region of hippocampus and prefrontal cortex (PFC), terguride could downregulate the high expression of mRNA during heroin reinstatement period. The expression of dynorphin protein and mRNA was upregulated during heroin reinstatement period, terguride could downregulate this high expression. The expression of dynorphin protein was upregulated during heroin reinstatement period, and terguride could downregulate this high expression. CONCLUSION The activity of mesolimbic dopamine is boosted up during heroin use period and depressed during reinstatement period, terguride can regulate this dysregulation. The activity of dynorphin is boosted up during cue induced reinstatement, and terguride has the downregulation effect. So the preclinic study demonstrated that terguride has the potential benefit in heroin dependence.