Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

Objective:To analyze clinical characteristics and genetic characteristics of children with ATP sensitive potassium passage (K ATP-HI). Methods:Forty-five children with genetically confirmed K ATP-HI and their families admitted to Beijing Children′s Hospital of Capital Medical University between February 2002 and December 2018 were selected as the study subjects. A detailed retrospective analysis of the patient's clinical characteristics, diagnosis and treatment process, disease-causing gene carrying status and later follow-up data was performed. ABCC8/KCNJ11 gene was sequenced by second-generation sequencing technology. Results:Among 45 children with K ATP-HI, 34 cases (75.6%) were neonatal onset, the first symptoms of 21 cases (46.7%) were convulsions. 39 cases had been treated with diazoxide, including 12 cases (30.8%) with good efficacy, 16 cases (41%) with poor efficacy and 11 cases with uncertain efficacy. Octreotide was further applied in 18 patients with uncertain or ineffective efficacy after diazoxide treatment, and 13 cases (72.2%) were effective, 3 cases were ineffective, and 2 cases were uncertain. 10 CHI patients who were ineffective to drug treatment or had clearly focal lesions confirmed by 18F-dopa positron emission by computed tomography ( 18F-DOPA PET) scans had undergone surgical treatment, 8 of which underwent partial pancreatectomy and blood glucose returned to normal after the operation; the other 2 cases underwent subtotal pancreatectomy and both had secondary diabetes after operation. Among 45 children with K ATP-HI, 1 case carried both ABCC8 and KCNJ11 mutations, 10 cases carried ABCC8 compound heterozygous mutations, and the remaining 34 cases carried ABCC8/KCNJ11 single genetic mutation. Among them, 21 cases had paternal inheritance, and 3 cases had maternal inheritance, 6 cases were identified with de novo mutations. Conclusions:Diazoxide treatment was ineffective for most K ATP-HI children, but octreotide had a higher effective rate. Partial pancreatectomy for focal type patients had a higher cure rate, and there was a risk of secondary diabetes after subproximal pancreatectomy, so it was very important to clarify the histological type of children before surgery. ABCC8 gene mutations and KCNJ11 gene mutations were the main pathogenic genes of K ATP-HI. Among patients carrying mutations in single ABCC8 or KCNJ11 gene mutation, K ATP-HI inherited by paternity were the majority. Some K ATP-HI children can relieve the hypoglycemia symptoms by themselves.

Objective:To explore the operability of the Chinese version of the All Aspects of Health Literacy Scale (C-AAHLS) and the Brief Health Literacy Screening (BHLS) for assessing the health literacy level of surgical patients.Methods:A total of 202 surgical patients were recruited in an acute care hospital. C-AAHLS and BHLS were used simultaneously to measure the health literacy of patients, and the consistency of their measurement results was compared.Results:The total health literacy scores of 202 surgical patients measured by C-AAHLS and BHLS were respectively (23.16±2.94) and (7.50±3.58), both were at a medium level, and they are consistent in differences in the health literacy levels of different ages, occupations, and educational levels, with statistical significance; the Bland-Altman graph shows that the maximum difference between the measurement results of the two tools is 1.68 <1.824 (average value), the average value of the difference is close to 0, and the results are highly consistent (P < 0.0001).Conclusions:The results of C-AAHLS and BHLS in measuring health literacy are consistent, and clinical medical staff can choose the suitable measurement tool according to the appropriate situation.

OBJECTIVE: To investigate the inhibitory effect of matrine on the proliferation of human non-small cell lung cancer (NSCLC) and explore the possible molecular mechanism. METHODS: Cultured human NSCLC A549 cells were treated with 0.4, 0.8, 1.2, 1.6, and 2.0 g/L matrine for 24, 48 or 72 h. CCK-8 assay was used for measuring the changes in A549 cell viability. The morphological changes of the cells were observed under a fluorescence microscope, and flow cytometry was employed for analyzing the cell apoptosis. The effects of matrine and the PI3K specific inhibitor LY294002 (10 nmol/L) on AKT pathway and autophagy-related proteins in A549 cells were investigated using Western blotting. RESULTS: Matrine significantly inhibited the proliferation of A549 cells in a time- and dose-dependent manner ( < 0.05). At the concentration of 1.6 g/L or higher, matrine caused obvious cell shrinkage and fragmentation and significantly increased floating cells; autophagy vacuoles could be observed in the cells after acridine orange staining. Within the concentrations range of 0.8-1.6 g/L, matrine time- and dosedependently increased the cell apoptosis. Treatment of the cells with 1.6 g/L matrine and 10 nmol/L LY294002 resulted in significantly lowered expressions of p-AKT and p-mTOR proteins and increased the expression of light chain 3B (LC 3B), an autophagy-related protein, as compared with those in the control cells ( < 0.05). CONCLUSIONS We demonstrate that matrine inhibits the proliferation and induces autophagy and apoptosis of A549 cells by deactivating AKT pathway, suggesting the potential of matrine as an anti-cancer agent for lung cancer.
Alkaloids ; Apoptosis ; Autophagy ; Carcinoma, Non-Small-Cell Lung ; Cell Proliferation ; Humans ; Lung Neoplasms ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; Quinolizines ; Signal Transduction ; TOR Serine-Threonine Kinases

Objective To study the clinical efficacy of the combination of sephedex and docetaxel used in transcatheter arterial chemoembolization (TACE) for clinical treatment of primary liver cancer.Methods 120 patients with primary liver cancer in our hospital were divided into the experimental group and the control group randomly and equally, the 60 cases in experimental group were treated with sephedex suspensoid (Sephedex, G-50, 300-500 μm) and docetaxel-iodized oil, while other 60 cases in control group were treated with docetaxel-iodized oil suspension liquid.Results The success rate of surgical intubation in the two groups was 100%.After an average follow-up of 12 months, the postoperative tumor diameter of the experimental group was reduced by (4.4±1.4) cm, while that of the control group was (1.8±1.0) cm;The overall response rate was 70% in the experimental group in contrast to 30% in the control group;the alpha fetal protein (AFP) value was decreased by (33.2±15.2) μg/L in the experimental group and (10.4±9.8) μg/L in the control group.Conclusion The combination of sephedex, docetaxel suspensoid and iodized oil shows great potential in TACE treatment of primary liver cancer, from which the treatment effect can be improved significantly.

Objective To screen the mutation of KATP channel mutations in Chinese pedigrees with infantile onset type 1 diabetes mellitus (T1DM) and neonatal diabetes mellitus.Methods A cohort of 12 children of infant onset T1DM and neonatal diabetes mellitus admitted into Beijing Children's Hospital between March 2004 and June 2013 were selected.PCR amplification and direct sequencing were used to analyze the 39 exons of ABCC8 gene and one exon of KCNJ11.And the mutational sites of the parents of the probands was sequenced in order to identify the inheritance.Results Analysis revealed ABCC8 mutation in 25％ (3/12 cases) of the patients,a case of transient neonatal diabetes (TNDM),a case of permanent neonatal diabetes mellitus (PNDM) and a case of infant onset T1DM.All positive patients showed a known heterozygosis mutation in the ABCC8 gene(R1182Q,c.3545G ＞ A,D209E,c.627C ＞ G,E208K c.622G ＞ A).The residue R1182Q,which was located at a position involved in joining transmembrane domain 2 to nucleotide binding domain 2,the mutations E208K and D209E were located in the intracellular region that links the transmembrane domain with the gatekeeper module.All the three mutations were located throughout the cytoplasm part of SUR1 protein.The TNDM successfully transferred from insulin to oral sulfonylureas therapy.Conclusions There is a complex genetic pathogenesis in neonatal and infant-onset diabetes.The KATP channel activating mutations is one of the main causes of neonatal diabetes mellitus and may cause T1DM in infants in China.Oral Glibenclamide therapy seems highly effective for some patients with the KATP channel activating mutations.

Objective To investigate the etiological agents of hand, foot and mouth disease (HFMD) in children in spring and summer from 2007 to 2008 in Beijing and the characteristics of the disease by virus isolation and to provide the scientific evidence for prevention and treatment for HFMD. Methods During April to August, 2007 and May to September, 2008, 356 clinical specimens including 255 throat swabs and 101 vesicle fluids were collected from 256 patients with HFMD who visited the Children's Hospital Affiliated to Capital Institute of Pediatrics and children with severe HFMD with neural system complications from Ditan Hospital and Youan Hospital All of the specimens were inoculated into Vero cells for virus isolation. After the cell pathogenic effects (CPE) appeared, the isolates were identified by RT-PCR with the universal primers within 5'untranslated region of enterovirus and typed by specific primers for VP1 gene of EV71 and CA16, respectively. The throat swabs from all of 10 severe HFMD were tested for enterovirus by RT-PCR addition to virus isolation. Results Out of 256 patients, 188 were positive for enterovirus by virus isolation, with the overall positive rate of 73.4%. Among the 356 clinical specimens collected from these 256 patients, 239 enterovirus strains were isolated with the overall positive rate of 67.1%. The positive rate for virus isolation from vesicle fluid samples was 75.2% which was higher than the positive rate of isolation from throat swabs (63.9%), but the time for CPE appearing in cell culture showed no significant difference. The positive rate of virus isolation from throat swabs from children with severe HFMD was 50% (5/10) which was lower than overall positive rate (73.4%) from regular HFMD. The RT-PCR typing for virus isolates revealed that among 45 enterevirus strains isolated from the specimens collected in 2007 by the universal primer pairs, 43 were CAI6 (95.6%, 43/45) and 2 were EV71 (4.4%, 2/45), whereas for the specimens collected in 2008, out of 143 enterovirus isolates by PCR with universal primers, 117 were EV71 (82.4%, 117/142) and 24 were CA16 (16.8%, 24/142). All of 10 severe cases were positive for EV71 by RT-PCR directly from clinical specimens. Conclusion CA16 and EVT1 were the etiological pathogens of HFMD in Beijing during 2007 to 2008 HFMD seasons. The dominant type of enterovirus was different between 2007 and 2008. Enterovirus type CA16 was predominant in 2007, whereas EV71 was predominant in 2008. All of severe cases of HFMD in children in this study were caused by EV71.

Objective To evaluate the clinical application of selective renal artery embolization (SRAE) for the treatment of kidney diseases. Methods Seventy-four cases of renal carcinomas, 11 cases of renal angiomyolipomas (RAML) and 72 cases of traumatic renal haemorrhages were first demonstrated by renal arteriography under Seldinger technique to ensure a site, range and neighbouring relation of lesions and then followed by percutaneous catheterized selective renal arterial embolization with embolic agents. Results The edema around the carcinomas and abscesses became obvious, and bleeding were reduced, which were convenient for operation after SRAE for the preoperative adjuvant treatment of renal carcinomas. The clinical symptoms were improved obviously in 9 eases with advanced renal carcinoma after palliative treatment. The tumour volumes of 11 RAML were decreased evidently by 15 %-65 % with the average of 42 %. The bleeding in 68 cases of traumatic renal haemorrhage were ceased completely in 1-4 days after embolism, 2 cases with serious renal fragmented injury and huge perirenal hematoma combined with shock received successful operation after SRAE, 2 cases bleeding again after SRAE were cured by the second SRAE. No severe complications occurred after embolization in all the patients. Conclusions As a minimal invasive technique,selective renal artery embolization is a safe, effective method with less complications and an adjuvant pre-op-erative therapy for renal carcinoma or a palliative treatment for advanced carcinoma and an effective treatment for RAML and traumatic renal haemorrhage.

Objective To evaluate the efficacy of X-ray guided choledochoscopy via T tube tunnel and interventional treatment of residual bile duct stones.Methods Cholangiography was performed in patients suspected of residual bile duct stone with choledochoscopy via the remaining T tube tunnel,and data of 45 patients who received endoscopically treatment for the residual bile duct stones and bile duct stricture were analyzed.Results Seven patients' with adhesive bile duct stenosis were resolved by repeat rinse and dilation,but the procedure failed in 2 cases of bile duct stricture caused by scar;seven cases of common bile duct stone combined with gradeHand Ⅲ multiple hepatic cholelith were removed within 1.5 h:six cases of hepatic bile duct narrowing with multiple cholelith were taken out in 1.0 hour;six cases of grade Ⅱ and Ⅲ multiple massive choledocholith were removed with lithotrity for over 2.0 h:six cases of grade Ⅱ-Ⅳ cholelith were eliminated within 1.5 h:six cases of hepatobiliary stone were removed successfully in 30 min.Stones in 3 cases of multiple stones with intrahepatie bile duct stenosis were not taken out due to bile duct stricture;stones in 2 cases of gradeⅡand Ⅲ multiple choledocholith were not removed for T tube tunnel bleeding.Conclusion X-ray guided choledochoscopy is convenient and effective to remove residue cholelith.

The physiological feedback regulation mechanism of the heart rate variation due to the blood pressure variation is studied. The continuous closed-loop mathematical model of the heart rate feedback regulation system is constructed. Numerical simulation is completed based on the above model. The simulation results demonstrate that the regulation system has the ability to constrain the fluctuation of the blood pressure to certain extent. The results are helpful for the pathological studies of some hypertensive diseases.
Blood Pressure ; physiology ; Computer Simulation ; Feedback, Physiological ; Heart Rate ; physiology ; Humans ; Mathematics ; Models, Cardiovascular