The interaction between m⁶A-methylated RNA and chromatin modification remains largely unknown. We found that targeted inhibition of bromodomain-containing protein 4 (BRD4) by siRNA or its inhibitor (JQ1) significantly decreases mRNA m⁶A levels and suppresses the malignancy of breast cancer (BC) cells via increased expression of demethylase AlkB homolog 5 (ALKBH5). Mechanistically, inhibition of BRD4 increases the mRNA stability of ALKBH5 via enhanced binding between its 3' untranslated regions (3'UTRs) with RNA-binding protein RALY. Further, BRD4 serves as a scaffold for ubiquitin enzymes tripartite motif containing-21 (TRIM21) and ALKBH5, resulting in the ubiquitination and degradation of ALKBH5 protein. JQ1-increased ALKBH5 then demethylates mRNA of extra spindle pole bodies like 1 (ESPL1) and reduces binding between ESPL1 mRNA and m⁶A reader insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3), leading to decay of ESPL1 mRNA. Animal and clinical studies confirm a critical role of BRD4/ALKBH5/ESPL1 pathway in BC progression. Further, our study sheds light on the crosstalks between histone modification and RNA methylation.

Objective:To assess the prognostic value of methylation of interferon regulatory factor 6 ( IRF6) gene promoter in patients diagnosed with Kidney renal clear cell carcinoma (KIRC). Methods:The primary lesions of fifty KIRC patients who were diagnosed at the First Affiliated Hospital of Nanjing Medical University from January 2016 to January 2020 were collected. The expression of IRF6 protein was determined with an immunohistochemical method. The correlation between the level of IRF6 expression and survival and/or metastasis status was analyzed. The mRNA and protein levels of the IRF6 in KIRC and normal renal tissues were compared by using bioinformatic tools. The difference in the methylation rate of the IRF6 gene promoter between tumor and adjacent tissues was analyzed by searching the online databases. Statistical analysis was carried out for the methylation status of the IRF6 gene promoter region to select those negatively correlated with the overall survival (OS) among the patients. In vitro experiments were conducted with cell lines to verify the correlation between the status of promoter methylation and transcription level of the IRF6 gene. Results:The mRNA and protein levels of the IRF6 gene in KIRC tissues were significantly lower than those of the normal controls, and this was more prominent in patients who had died or developed metastasis. The extent of IRF6 gene promoter methylation in the KIRC tissues was much higher compared with that of the adjacent normal renal tissues. There was a significant negative correlation between the methylation of the IRF6 gene promoter and mRNA level of the IRF6 ( R= -0.52). The higher methylation degree in the IRF6 gene promoter regions cg12034118 and cg16030177, the shorter the OS and worse prognosis in the patients. Only twenty CpG sites in cg12034118 were confirmed to be highly methylated in KIRC cell lines. The transcription level of the IRF6 gene was upregulated in a time- and dose-dependent manner after the treatment with demethylation reagent 5-azadeoxycytidine. Conclusion:The methylation of IRF6 gene promoter in the renal tissues of KIRC patients is closely correlated with the OS. Cg12034118 may provide a promising biomarker for laboratory detection, and its high methylation rate has certain reference value for the prognosis.

Pancreatic cancer is a disease with a high fatality rate， with a five-year survival rate of no more than 10% and a significantly increasing annual mortality rate. The common pathogenesis factors of pancreatic cancer are family inheritance， diet， pancreatitis， obesity， etc.， among which， family inheritance of pancreatic cancer is the main reason， and about 7%-10% of patients have family inheritance. Surgery is an effective way to treat pancreatic cancer in patients and improve their survival， but most people are diagnosed with pancreatic cancer at intermediate and advanced stages and lose the opportunity for surgical treatment. Therefore， radiotherapy， interventional therapy， supportive treatment， immunotherapy， and other treatments are used clinically to relieve symptoms and prolong the survival of patients. The commonly used clinical drug is gemcitabine. Although it can inhibit tumor growth and improve the condition， it can bring side effects such as bone marrow suppression， rash， digestive tract side effects， and drug resistance. The damage of these side effects to the human body is systemic. Chinese medicine can be used alone or in combination with other treatment methods to reduce the toxic and side effects of chemotherapy， restore the physical energy of patients， and reduce its related complications. Chinese medicine contains a large number of active ingredients， including alkaloids， flavonoids， saponins， phenolic acids， and organic acids， with anti-inflammatory， anti-viral， anti-tumor， and other curative effects. Many clinical studies of traditional Chinese medicine （TCM） on cancers have verified that TCM plays a positive role in tumor prevention and treatment， especially in improving and controlling clinical symptoms， and also plays a good detoxification effect on radiotherapy and chemotherapy， with good results achieved in improving bone marrow suppression， improving immunity， improving quality of life， and prolonging survival. This paper reviewed the anti-pancreatic cancer mechanism of Chinese medicine monomers based on literature in China and abroad， aiming to provide new potential drug candidates for the treatment of pancreatic cancer.

ObjectiveTo explore the meridian tropism of components in Bupleuri Radix （Chaihu， CH） based on the model of nonalcoholic steatohepatitis （NASH） and clarify the substance basis of the meridian tropism of CH in Xiaoyaosan （XYS） by means of principal component analysis. MethodEighty SPF male C57BL/6 mice were randomly assigned into 8 groups， with 10 mice in each group. Except that the blank group was fed with the methionine choline-sufficient （MCS） diet， the other mice were fed with methionine choline-deficient （MCD） diet for 4 weeks to establish the nonalcoholic steatohepatitis （NASH） model. After the established model was confirmed by hematoxylin-eosin （HE） staining， the mice were administrated with corresponding drugs by gavage once a day for 4 weeks. Specifically， the 8 groups were XYS group （2.874 g·kg^-1）， XYS-CH group （2.445 g·kg^-1）， XYS-CH+volatile oils （Vol， 0.163 mg·kg^-1） group， XYS-CH+polysaccharides （Pol， 24.067 mg·kg^-1） group， XYS-CH+flavones （Fla， 2.241 mg·kg^-1） group， and XYS-CH+saponins （Sap， 2.746 mg·kg^-1） group. The model group and the blank group were administrated with the same volume of normal saline. After the last administration， the mice were sacrificed for the collection of blood and liver tissue. The pathological changes of liver were observed by HE staining and oil red O staining. Enzyme linked immunosorbent assay （ELISA） kits were used to determine the levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein （HDL）， and low-density lipoprotein （LDL） in serum as well as malondialdehyde （MDA）， superoxide dismutase （SOD）， catalase （CAT）， and glutathione peroxidase （GSH-Px） in liver. SPSS Statistics 23 was used for principal component analysis and comprehensive evaluation to determine the substance basis of the meridian tropism of CH in NASH mice. ResultCompared with the blank control group， the modeling led to hepatocyte swelling， increased fat vacuoles， and appearance of inflammatory cells. Further， the modeling elevated the levels of ALT， AST， TG， TC， and LDL and lowered the HDL level in serum， and it increased the MDA level and decreased the SOD， CAT， and GSH-Px levels in liver. Compared with the model group， the administration of XYS and XYS-CH in combination with the components of CH alleviated the oxidative damage in liver （P<0.05）. The comprehensive score of the pharmacological efficacy was in a descending order as follows： XYS > XYS-CH+Sap > XYS-CH+Fla > XYS-CH+Pol > XYS-CH+Vol > XYS-CH. Among the chemical components of CH， Sap had the best effect. ConclusionSap lowers the blood lipid level， regulates the abnormal lipid metabolism， and alleviates the oxidative damage of liver， which is the substance basis for CH to exert the meridian tropism in liver.

Objective: To improve the diagnosis and therapy of childhood pulmonary thromboembolism (PTE) by analyzing the clinical features of this rare condition. Methods: A total of 8 pediatric patients (4 males, 4 females) with PTE diagnosed in the Children′s Hospital of Zhejiang University School of Medicine from March, 2014 to March, 2019 were enrolled. The clinical manifestation, laboratory results, imaging findings, diagnosis and treatment were summarized. Results: Among these 8 cases, aged from 9 hours to 14 years and 10 months. Fever was found in 4 cases, cough aggravation in 4, short of breath in 3, chest pain in 2, abdominal and back pain in one, hemoptysis in 2, cyanosis in 1, and edema of lower extremities in 2. Physical examination found decreased breath sound in 2 cases, phlegm rale in 3, and pleural friction rub in one. Pleural effusion was found in 5 cases by ultrasound. Plasma D-dimer increased in 6 cases (0.66-9.96 mg/L) and hypersensitive C-reactive protein elevated in 5 cases (10.78-78.00 mg/L). Chest enhanced CT showed pulmonary artery or venous filling defects, including pulmonary artery embolism in 7 cases and pulmonary vein embolism in one. The primary disease of these patients included Mycoplasma Pneumoniae pneumonia in 4 cases, nephritis in 2 and postoperative congenital heart disease in 2. Apart from one case who withdrew the treatment and was discharged, the other 7 patients received anticoagulant treatment had good outcome. Conclusions For children with Mycoplasma pneumoniae pneumonia, immune disorders, long-term hormone therapy, cardiovascular invasive operation or other high-risk factors, PTE should be considered when fever, cough aggravation, short of breath, chest and back pain with pleural effusion are present. Chest enhanced CT scan should be performed as soon as possible, and anticoagulation should be started once the diagnosis is confirmed.

Objective:To examine the clinical value of combining indocyanine green (ICG) fluorescence navigation with blue dye in sen-tinel lymph node biopsy (SLNB) for patients with breast cancer. Methods:A total of 89 patients with early-stage breast cancer who met the inclusion criteria were admitted at Shantou Central Hospital, Guangdong from May 2013 to April 2014. In phase one, ICG and blue dye were applied in all 53 patients, and then SLNB and axillary lymph node dissection (ALND) were performed based on fluores-cence signal or visual sense of the lymph nodes. In phase two, 36 patients with early-stage breast cancer were included. ALND was omitted when sentinel lymph nodes were frozen showing negative result. Rates of detection, accuracy, and false-negative were calcu-lated. Results:A total of 89 patients were monitored, of which the total rate of SLNB detection was 96.6%(86/89). In the validation pe-riod, the rates of detection, accuracy, and false-negative were 94.3%(50/53) 98.0%(49/50), and 2.6%(1/38), respectively. In the alter-ative period, the rates of detection reached 100%. Of the 196 sentinel lymph nodes, 179 showed fluorescence signal, 142 exhibited blue dying, 54 only demonstrated fluorescence signals, and 45 demonstrated metastasis with five signaling fluorescence. About 24.7%of patients were diagnosed with SLN metastasis (22/89), where SLNB in two patients showed fluorescence signal but without blue dye. No ipsilateral lymph node relapsed were observed during a median follow up of 25 months. Conclusion:Combination of ICG fluores-cence navigation with blue dye in SLNB is safe for patients with breast cancer.

Objective To explore the effect of nursing procedure on pressure sore in patients with brain tumor.Methods The nursing procedures were used in the nursing of 86 brain tumor patients.The procedures included assessment of pressure ulcer risk factors and regulations of nursing objective and the measures for preventing pressure ulcer.Result None of the patients contracted pressure ulcer during operation.Conclusion The nursing procedures for brain tumor patients can enable the nurses to plan nursing activities for specific purpose,avoid the occurrence of pressure sore and thus improve the quality of nursing.

BACKGROUNDPulmonary blastoma is a rare primary malignancy of the lung. It is now recognized in two forms: adult type pulmonary blastoma and childhood pleuropulmonary blastoma. The clinical characteristics, diagnosis and treatments of adult type pulmonary blastoma are discussed in this article.

METHODSThe clinical records of 5 patients with adult type pulmonary blastoma admitted in Cancer Center, Sun Yet-sen University from 1964 to 2004 were analyzed and the literature on pulmonary blastoma was reviewed.

RESULTSThree patients were male and two were female with the ages ranged from 22 years old to 70. Their symptoms consisted mainly of cough, hemoptysis and chest pain. The pulmonary blastomas were mainly manifested as a solitary parenchymal mass of the lung on chest radiograph and CT. None of these patients was diognosed by fibrobronchoscopy nor sputum cytology. Three patients underwent lobectomy, one underwent pneumonectomy, and these four patients underwent mediastinal lymph node resection also. The fifth one received wedge resection and postoperative chemotherapy. At the end of follow-up, three patients died and two was alive, and the survival time was from 6 months to 11 years.

CONCLUSIONSPulmonary blastoma is difficult to be diagnosed before operation. Surgery is the best therapeutic choice up to now. It has poor response to radiotherapy and chemotherapy. The prognosis of patient with pulmonary blastoma is variable.

Purperse:To study the effect of α interferon in the treatment of renal cell carcinoma after radical nephrectomy.Methods:From Jan 1988 to Jan 1998,46 cases of renal cell carcinoma were randomized into two groups: the study group were treated by radical nephrectomy and α-interferon while the control group with radical nephrectomy alone.Results:The T lymphocyte subsets CD3,CD4,CD8,the ratio of CD4/CD8 are significantly different berfore and after treatment in the study group (P＜0.05); the 3 year(90.5%) and 5 year (89.5%) survival rate in patients of the study group are higher than that of the control group (P＜0.05).Conclusions:α-interferon therapy after radical nephrectomy can restore celluar immunity so as to enhance the treatment efficacy.