Histone methylation is one of the epigenetic modifications. Histone methylation influences constitutive heterochromatin, genomic imprinting, inactivation of X-chromosome and gene transcription regulation. Abnormality of histone methylation is associated with several carcinomas. The discovery of enzymes that reverse histone methylation challenges the current understanding that histone methylation is a stable epigenetic marker and provides a novel way to study histone modifications.

Objective To investigate the activation and clinical significance of the mammalian target of rapamycin (mTOR) pathway related protein and eukaryotic translation factor 4E-binding protein 1 (4E-BP1) in gastric cancer.Methods The activation of mTOR and 4E-BP1 in gastric cancer tissues of 38 surgical patients were detected by immunohistochemical method.The differences of phosphorylated mTOR and 4E-BP1 expression among cancerous tissues,para-cancerous tissues and normal gastric mucosa tissues and dinicopathological variables were analyzed by Chi square test and Kruskal-Wallis test.Results The positive expression rate of phosphorylated mTOR in the gastric cancerous tissues was significantly higher than that of para-cancerous tissues and normal tissues [71.1％ (27/38),50.0 ％ (19/38) and 44.7 ％ (17/38),x2 =11.031,P =0.026].The positive expression rate of downstream protein 4E-BP1 in the gastric cancer tissues was also significantly higher than that of paracancerous tissues and normal tissues [68.4％(26/38),57.9％(22/38) and 28.9％ (11/38),x2 =13.943,P=0.007].There was no correlation between phosphorylated mTOR and 4E-BP1 expression and tumor Lauren's sub-type,infiltration,differentiation degree,lymph node metastasis and patient's age.There was statistical significant difference between activated 4E-BP1 expression and tumor size in gastric cancer (H=3.86,P＜0.05).Conclsions mTOR pathway was over activated in gastric cancer.There was difference between phosphorylation degree of its downstream protein 4E-BP1 and the tumor size.

Objective To investigate the combined inhibition effect and the potential mechanism of rapamycin (mammalian target of rapamycin inhibitor) and PD98059 (mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) inhibitor) on mouse colorectal cancer (CRC). Methods S-ICR mice were subcutaneously injected with 20 mg/kg of 1,2-dimethylhydrazine dihydrochloride in the nape for 20 weeks to induce CRC. From the 16th week, the mice were treated with alone or combined injection with 0.25 mg/kg rapamycin and 2.5 mg/kg PD98059. The drugs were administered for 8 weeks. Subsequently, the animals were sacrificed and dissected, the tumor sizes were measured, and the tumors were harvested for pathological assay. Furthermore, the phosphorylation of mTOR, p70S6K, and 4E-BPl proteins was detected by using immunohistoehemistry. Results The mice treated with rapamycin (44. 44 %) or PD 98059 (either alone (38.89%) or combination treatment (6.67%) were significantly less likely to develop cancer compared with mice receiving none of them (77.78%, P<0. 05). The average size of tumors was (6.15±2. 192), (8.85±3. 983), (2.917±0. 191), (16.36±6.855) mm3 respectively (P<0.05).The anti-cancer effect of the combination treatment was substantially significant. The proteins of phospho-mTOR, phospho-p70s6K and phospho-4E-BPl were significantly down-regulated after treatments (all P values < ,0.05). Conclusions Combined treatment was more effective than single-drug treatments of rapamycin or PD98059 alone for the prevention and treatment of mouse CRC. The mTOR signal pathway might be involved in the inhibitory mechanism.

Totally, 102 general practitioners (GPs) from 40 community health-care service centers in a district of Beijing were investigated for their awareness of diagnosis, treatment and prevention for chronic hepatitis B and evaluating effectiveness of their training with self-designed questionnaire before and after professional training.Before training, higher awareness of knowledge about prevention for hepatitis B had been achieved in GPs, such as "hepatitis C is communicable" (78/102, 76.5% ), "hepatitis B can be prevented by protective antibody" ( 76/102, 74.5% ), whereas only 3.9% ( 4/102 ) of GPs knew indications of antiviral therapy for chronic hepatitis B, 4.9% (5/102) could describe complications of decompensated cirrhosis and 19.6% (20/102) knew methods for screening primary hepatocellular carcinoma.After training, their awareness increased significantly to 93.1% (95/102), 49.0% (50/102)and 86.3% (88/102), respectively (all P ＜0.01 ).Now, GPs' knowledge about diagnosis and treatment for hepatitis B is still insufficient at community health-care centers and professional training can improve their awareness.It is an important assurance for patients with chronic hepatitis B to be better managed in both of specialized hospitals and community health-care centers by enhancing professional training for GPs indiagnosis and treatment for hepatitis B.

Objective:To understand the relationship between the disease condition of patients with coal-burning-borne endemic arsenic poisoning (abbreviated as coal-burning-borne arsenic poisoning) and serum lipid metabolism indicators.Methods:Using a case-control study method, in the coal-burning-borne arsenic poisoning village of Yuzhang Town, Qianxinan Prefecture, Guizhou Province, 204 patients with arsenic poisoning diagnosed according to the standard of "Diagnosis of Endemic Arsenicosis" (WS/T 211-2015) were included in case group, including 87 males and 117 females, aged(53.37 ± 8.06) years old; and they were divided into mild arsenic poisoning group (71 cases), moderate arsenic poisoning group (59 cases) and severe arsenic poisoning group (74 cases) according to the clinical grading. Another 63 residents were selected into control group in a non-arsenic-exposed village about 12 km away from the diseased village, including 23 males and 40 females, aged (53.78 ± 9.10) years old. A face-to-face questionnaire survey was conducted for each group of people, including basic information such as general demographic characteristics, smoking status, and drinking status; fasting peripheral blood was collected, and an automatic biochemical analyzer was used to detect serum total cholesterol (TC) and triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels.Results:There were significant differences of serum TC [(4.94 ± 1.00), (5.00 ± 0.99), (5.27 ± 0.94), (5.57 ± 1.07) mmol/L], TG [(2.17 ± 0.90), (2.25 ± 1.31), (2.66 ± 1.43), (2.78 ± 1.40) mmol/L], LDL-C [(2.51 ± 0.79), (2.74 ± 0.64), (2.97 ± 0.66), (3.15 ± 0.80) mmol/L], and HDL-C levels [(1.57 ± 0.55), (1.42 ± 0.43), (1.36 ± 0.42), (1.30 ± 0.38) mmol/L] in control group, mild, moderate and severe arsenic poisoning groups ( F = 5.83, 3.64, 9.72, 4.41, P < 0.01 or < 0.05). Among them, the serum TC level in severe arsenic poisoning group, serum TG and LDL-C levels in moderate and severe arsenic poisoning groups were significantly higher than those in control group ( P < 0.05); the serum HDL-C level in moderate and severe arsenic poisoning groups were lower than that in control group ( P < 0.05); the serum TC, TG and LDL-C levels in severe arsenic poisoning group were significantly higher than those in mild arsenic poisoning group ( P < 0.05). After linear trend test, serum TC, TG and LDL-C levels all showed an upward trend with the degree of arsenic poisoning ( Ftrend = 15.77, 10.14, 29.15, P < 0.05), and serum HDL-C level showed a downward trend with the degree of arsenic poisoning ( Ftrend = 12.75, P < 0.05). There were significant differences in the abnormal rates of serum TC, TG and LDL-C levels among control group and mild, moderate and severe arsenic poisoning groups (χ 2 = 21.16, 16.60, 8.29, P < 0.01 or < 0.05). Among them, the serum TC and TG levels abnormal rates in moderate and severe arsenic poisoning groups and serum LDL-C level abnormal rate in severe arsenic poisoning group were higher than those in control group ( P < 0.05), the serum TC, TG and LDL-C levels abnormal rates in severe arsenic poisoning group were higher than those in mild arsenic poisoning group ( P < 0.05). There was no significant difference of the serum HDL-C level abnormal rate among four groups (χ 2 = 2.11 , P > 0.05). The results of trend chisquare analysis showed that the abnormal rates of serum TC, TG and LDL-C levels presented an increasing trend with the degree of arsenic poisoning (χ 2trend = 19.90, 15.25, 7.63, P<0.05). The results of logistic regression analysis showed that the risk of abnormal serum TC level in patients with severe arsenic poisoning was 2.90 times that in control group [odds ratio ( OR) = 2.90, 95% confidence interval ( CI): 1.43 - 5.91], and the risk of abnormal serum LDL-C level in patients with severe arsenic poisoning was 2.87 times that in control group ( OR = 2.87, 95% CI: 1.22 - 6.71). Conclusion:There is a correlation between the disease condition of patients with coal-burning-borne arsenic poisoning and their dyslipidemia.

Objective To investigate the prognosis factors of patients with non-functional pancreatic neuroendocrine carcinoma (NF-PanNEC).Methods The patients with NF-PanNEC confirmed by pathology from 2004 to 2015 were collected from the Surveillance,Epidemiology,and End Results (SEER) database of the American National Cancer Institute.The MatchIt package in the R software was used to perform propensitymatching analysis of surgery,radiotherapy and chemotherapy.The Kaplan-Meier method was used to calculate the cumulative survival rate,and the significant difference was evaluated by the log-rank test.Then the Cox multivariate regression analysis was applied to evaluate the prognostic factors of NF-PanNEC patients.Results A total of 2 603 NF-PanNEC patients were included in the analysis.Univariate analysis showed that the age of diagnosis (x2 =123.8,P ＜ 0.001),gender (x2 =7.3,P =0.007),marital status (x2 =26.7,P ＜ 0.001),primary site of tumor (x2 =47.8,P ＜ 0.001),degree of tumor differentiation (x2 =628.7,P ＜ 0.001),American Joint Committee on Cancer (AJCC) stage (x2 =811.7,P ＜0.001),T stage (x2 =425.9,P ＜ 0.001),N stage (x2 =272.3,P ＜ 0.001),M stage (x2 =779.8,P ＜ 0.001),surgery (x2 =962.6,P ＜ 0.001),chemotherapy (x2 =21.9,P ＜ 0.001) were associated with the prognosis of NF-PanNEC patients.No correlation was observed between radiotherapy and the prognosis of NF-PanNEC patients (x2 =0.1,P =0.750).Multivariate Cox regression analysis showed that older diagnostic age (≥74 years old vs.≤56 years old,HR =2.20,95 ％ CI:1.84-2.62,P ＜ 0.001),male (male vs.female,HR =1.14,95 ％ CI为1.01 ～1.29,P =0.035),single or divorced or widowed (single or divorced vs.married,HR =1.26,95 ％ CI:1.10-1.45,P =0.001;widowed vs.married,HR =1.29,95％ CI:1.04-1.61,P =0.022),head of pancreas (tail of pancreas vs.head of pancreas,HR =0.85,95％ CI:0.73-0.99,P =0.033),poor differentiation (grade Ⅳvs.grade Ⅰ,HR=3.75,95％CI:2.70-5.20,P＜0.001),late AJCC stage (stage Ⅳ vs.stage Ⅰ,HR =5.72,95％ CI:4.23-7.73,P ＜ 0.001),no surgery treatment (yes vs.no,HR =0.37,95％ CI:0.30-0.44,P ＜ 0.001) were significant prognostic risk factors for NF-PanNEC patients,and chemotherapy was not independent prognostic factor (yes vs.no,HR=1.00,95％CI:0.88-1.13,P=0.958).Conclusion The older diagnostic age,single or divorced or windowed,head of pancreas,poor differentiation,late AJCC stage and no surgery treatment are significant prognostic risk factors for NF-PanNEC patients.Radiotherapy and chemotherapy may not improve the prognosis of NF-PanNEC patients.

Platelets play important roles in tumor progression.Increased platelets count is associated with poor overall survival and prognosis.Tumor cell-induced platelet activation and platelet-induced tumor growth form a malignant amplification loop which plays a crucial role in tumor cell proliferation,metastasis and angiogenesis.Antiplatelet therapy may break the platelet-tumor amplification loop and play a key role in reducing tumor metastasis.

Circulating tumor cells (CTCs)are cancerous cells that shed from the primary tumor or metastases into the bloodstream. The currently clinical applicability of CTCs approved by the US Food and Drug Administration (FDA)is that CTCs can be prognostic biomarker for patients with metastatic breast cancer, prostate cancer and colorectal cancer. CTCs also have great potential in the prognosis assessment of other meta-static or localized tumors,as well as early screening of tumors,analysis of molecular profiling,guiding treat-ment decisions,and monitoring of treatment response. Currently,various studies are being carried out to further explore the clinical application of CTCs,and provide new strategies and new prospects for individualized and precise treatment of cancer patients.

Objective · To investigate the clinical characteristics of initial peritoneal dialysis (PD) patients with different peritoneal transport status, and analyze risk factors of high peritoneal transport status in PD patients. Methods · A total of 455 consecutive PD patients newly starting PD between January 2007 to October 2015 were retrospectively analyzed. According to the results of the first sPET, patients were divided into H/HA (4h D/Pcr ≥ 0.65) and L/ LA (4h D/Pcr<0.65) groups. Clinical and biochemical characteristics between the two groups were compared. Multivariate logistic regression model was established to investigate risk factors of higher peritoneal transport status of incident PD patients. Results · The study included 372 incident PD patients. The L/LA group and H/HA group had 264 cases (71.2%) and 108 cases (28.8%) respectively. The H/HA group had higher proportion of male patients (63.0% vs 50.8%, P=0.03), lower residual renal function [RRF, (4.26±2.77) mL/min vs (5.79±4.53) mL/min, P<0.01], lower serum albumin level [(29.34±6.89) g/L vs (32.08±5.86) g/L, P=0.00], and more frequent diabetic nephropathy (19.4% vs 9.5%, P=0.00), compared with L/LA group. Univariate and multivariate logistic regression analysis showed that higher peritoneal transport status was associated with lower serum albumin level (OR=0.96, 95% CI 0.28-0.99; P=0.02), male (OR=1.92, 95% CI 1.19-3.12; P=0.00), presence of diabetic nephropathy (OR=2.52, 95% CI 1.26-5.05; P=0.00) and lower residual renal function (OR=0.90,95% CI 0.83-0.96; P=0.00). The level of hsCRP in patients with hypoalbuminemia was higher than that in patients with normal albumin level (1.69 mg/L vs 0.69 mg/L, P=0.00). Conclusion · Low and low average peritoneal transport status accounted for the majority of the patients in this study. Low serum albumin levels, male, diabetic nephropathy, RRF were risk factors of initial high peritoneal solute transport status. Chronic inflammatory status might partially explain for the correlation between hypoalbuminemia and high peritoneal solute transport status in PD patients.

Objective: To examine the prospective association between peripubertal diet quality and pubertal timing. Methods: Multivariate regression analyses were performed using data obtained from 1 588 SCCNG (Southwest China Childhood Nutrition and Growth) study participants, which included dietary data, anthropometric parameters, and information about potential confounders during peri puberty, two and four years before the onset of menarche or voice break. Dietary intake in peri puberty was assessed using a validated food frequency questionnaire. Diet quality was determined using the Chinese Children Dietary Index (CCDI), which measures adherence to current dietary recommendations. Age at menarche or voice break (M/VB) were used as pubertal markers. Results: The CCDI score ranged from 58.0 to 132.5 for girls and from 48.3 to 129.9 for boys. The pubertal markers consistently indicated that girls and boys with a higher peripubertal diet quality entered puberty later than their counterparts with lower CCDI scores (higher vs. lower CCDI tertiles: age at M was 13.1 years (11.2-13.3) and 12.5 years (12.0-13.9)(P<0.01); VB was 13.8 years (12.1-14.8) and 13.4 years (12.5-15.1)（P=0.03), after adjusting for paternal education level, energy intake, and pre pubertal body fat. Conclusion Children with a higher diet quality during peri puberty entered puberty at a later age. Dietary guidance and intervention are needed for better dietary quality among children during pubertal transition.