DNA methylation is the main profile of epigenetics .DNA methyltransferases ( DNMTs) is the main regulatory enzyme during DNA methylation .The activation of DNMTs ,the hypermethylation and low expres-sion of some tumor suppressor genes are involved in the carcinogenesis and development of various human canc -ers,which is a biomarker of poor prognosis .Both of the polymorphism of DNA methyltransferases ( DNMT3b) and tobacco smoking are risk factors of tumorgenesis .The targeted therapy of DNMTs is very popular due to its low cy-totoxity.This review will focus on new progress of the research on DNMTs in pathogenesis of carcinoma .

Objective To observe the biological activity of the recombinant immunotoxin hIL-2-LuffinP1 derived by gene engineering in vitro.Methods To observe the inhibitory effect on lymphocytes in vitro,the splenocytes isolated from C57 and BALB/c mice were used for mixed mouse lymphocyte response(MLR),and the lymphocyte proliferation was observed in vitro with BALB/c mice splenocytes stimulated by concanavalin A(ConA).Different concentrations of hIL-2-LuffinP1 was added into the reaction system,with LuffinP1 adopted as control.3H-TdR incorporation assay was used to detect the effects of hIL-2-LuffinP1 on lymphocyte proliferation,and its effects on CTLL-2 cells(IL-2 dependent cells) were also observed.The experiments consisted of six groups(PBS,IL-2,LuffinP1,LuffinP1+IL-2,hIL-2-LuffinP1 and hIL-2-LuffinP1+IL-2).CTLL-2 cells were cultured for 12h after being treated with different agents,and then the cells were stained by trypan blue to estimate the dead cells in every 100 cells.Results It was showed that CPM declined correspondingly to the gradually increased concentration of hIL-2-LuffinP1,and cell proliferation was inhibited obviously.The inhibition rate was up to 97% at the concentration of 10-6mmol/L of hIL-2-LuffinP1.The activity of inhibiting lymphocyte proliferation was proportional to the dosage.On the contrary,no obvious inhibition to lymphocyte proliferation was found in the control group treated with LuffinP1,the inhibition ratio only reached to 14% with the same concentration of hIL-2-LuffinP1.It was also found that,when hIL-2-LuffinP1 and LuffinP1 in different concentrations added to spleen cells stimulated by ConA,hIL-2-LuffinP1 still exhibited strong ability of inhibition on the splenocyte proliferation,while LuffinP1 has no obvious inhibiting effect on the lymphocyte proliferation in the two reaction systems mentioned above.MLR showed the same results.Furthermore,in the experiment of cytotoxic effects of IL-2-LuffinP1 on CTLL-2 cells,the inhibition rates of hIL-2-LuffinP1+IL-2 group and hIL-2-LuffinP1 group were 29.6% and 47.4% respectively,the difference was significant compared with IL-2 group(P

Objective To explore the effect of Acorus gramimeus and its major components ?-asarone on N-methyl-D-asperate recepter 1 (NMDAR1) mRNA levels of hippocamp neurons in epileptic animal models induced by pentylenetetrazol (PTZ). Methods PTZ 60 mg/kg was injected to the abdominal cavity of three weeks Wistar rats to prepare epileptic animal models. The animal models were randomly divided into three groups: epilepsy control, A. gramimeus and ?-asarone as well as the normal control. Each group was administered through intraperitoneal injection. Both of two control groups were injected physiologic saline 1.0 mL/d, and the rest groups were injected A. gramimeus 2 350 mg/(kg?d) or ?-asarone 29 mg/(kg?d) for 7 d, respectively. All rats were treated by PTZ 60 mg/kg through intraperitoneal injection next day. After their behaviors were observed for 24 h, animals were sacrificed. The expressions of NMDAR1 mRNA in hippocamp CA1 and CA3 of all rats were detected by in situ hybridization and semiquantitative RT-PCR. Results The results of in situ hybridization showed that positive staining granules were located in the cyptoplasm of hippocamp neurons. The number of positive cells and average absorbance of A. gramimeus group or ?-asarone group was markedly less than that of epilepsy control (P

Objective To observe the expression of nuclear factor-kappa B(NF-κ3)and monocyte chemnattractant protein-1(MCP-1),and the infiltration of mononuclear macrophage CD68 in lupus nephritis (LN).The association between NF-κB,MCP-1 and MΦ with kidney pathology and clinical manifestations is explored.MethodsNF-κB,MCP-1 and MΦ in renal biopsy specimens from 49 cases of LN were detected using immunohistochemical techeniques.Forty-nine cases of renal tissues were examined for NF-κB by in situ hybridization.The relationship between NF-κB,MCP-1 and MΦ with kidney pathology and clinical manifestations were analyzed.Results ①Compared with the control group ,the expression of NF-κB,MCP-1 and MΦ in LN was significantly higher(P＜0.01).The expression of MCP-1 positively correlated with MΦinfiltration and NF-κB(P＜0.01)in glomeruli and renal tubule and renal interstitium of LN.The expression of NF-κB,MCP-1 and the infiltration of MΦ in LN Ⅳ was significandy higher than non LN Ⅳ and the control group(P＜0.01,P＜0.05).There was no significant difference between renal NF-κB positive group and negative groups in the degree of the immunohistochemical and in situ hybridization examination(P＞0.05).②The histological activity index,urine protein volume(24 h)and serum creatinine in LN were significantly higher than the control group(P＜0.01),and the expression of NF-κB in LN was correlated with histological activity index,urine protein volume(24 h)and serum creatinine(P＜0.01,P＜0.01,P＜0.05).MCP-1 and CD68 expression in LN were correlated with histological activity index and urine protein volume(24 h),but not correlated with serum creatinine(P＞0.05).Conclusion NF-κB induced MΦ by activating MCP-1 may be one cause of kidney injury of LN.NF-κB signal pathway may act as a new therapeutic target for MΦinfiltration and proliferation inhibition in kidney.

Objective:The clinical manifestations, types of gene mutations, therapeutic effects and prognostic characteristics of 15 children with cblC type methylmalonic acidemia (MMA) and hydrocephalus were analyzed to improve the clinical understanding of the disease, so as to provide a basis for the treatment of the disease.Methods:From April 2015 to January 2019, 15 patients with MMA and hydrocephalus in Department of Pediatric Surgery, Peking University First Hospital were enrolled, and all gene detection showed clbC type.All the 15 patients underwent ventriculoperitoneal shunt.After surgery, the clinical manifestations and imaging findings were applied as the basis to adjust the pressure of the diverter valve appropriately.Clinical data and gene mutation characteristics of 15 children with cblC type and hydrocephalus were retrospectively analyzed, and the therapeutic effects and prognosis were summarized and analyzed as well.Results:There were 8 males (53.3%) and 7 females (46.7%), aged from 2 to 33 months.All the cases were followed up from 11 to 55 months, without death case and serious postoperative complications of hydroce-phalus.The head circumference of 3 cases (20.0%) was in the normal range, 1 case (6.7%) was greater than the normal range, and 11 cases (73.3%) were less than the normal range.Four patients (26.7%) were transferred to the pediatric intensive care unit after surgery.c.609G>A mutation was the most common in this study, with 7 cases (46.7%) of c. 609G>A homozygous mutation, and 5 cases (33.3%) of c. 609G>A heterozygous mutation.Clinical symptoms of intracranial hypertension were relieved or disappeared.The head circumference progressive enlargement was stopped.The anterior fontanelle tension greatly decreased, all " setting-sun" sign of eyes disappeared, and vision loss and hearing loss were better compared with the pre-operation.Four cases (26.7%) displayed normal intelligence and exercise, and 11 cases (73.3%) were left with mild to severe psychomotor retardation.During the follow-up pe-riod, the head CT showed that the ventricle was remarkably narrowed, and interstitial brain edema obviously improved.Conclusions:Ventriculoperitoneal shunt in the treatment of cblC type MMA with hydrocephalus has positive effects.The head circumference of most cblC type MMA with hydrocephalus is less than the normal range.c.609 G>A is the most common mutation in cblC type MMA with hydrocephalus.Perioperative " metabolic crisis" can result in serious complications.

Objective:To evaluate the pregnancy outcomes of fetal tethered cord (TC) prenatally diagnosed by MRI.Methods:Clinical data of 38 fetuses diagnosed as having TC by MRI, including 36 singletons and two fetuses who were both one of dichorionic diamniotic twins, were retrospectively collected and analyzed in the Obstetrics and Gynecology Hospital of Fudan University from January 2015 to August 2019. According to whether conus medullaris was located above the bladder or reached the lower edge of the bladder, all cases were divided into high or low groups. Pregnancy outcomes were compared between the two groups using Fisher's exact test and Student's t-test. Results:(1) The gestational age at MRI was (25.5±4.7) weeks. Among the 38 cases, 14 (36.8%) were isolated TC, 24 (63.2%) were complicated by other anomalies. The meningocele was responsible for the most (39.5%, n=15). The results of the ultrasound were consistent with those of MRI in 24 cases (63.2%). While in the other 14 cases (36.8%), the ultrasound only showed vertebral body's abnormal morphology, after which further MRI examination revealed a tethered cord. (2) Twenty-nine women (76.3%) chose to terminate the pregnancy. One patient (2.6%) underwent fetal reduction at 23 gestational weeks (one normal twin was delivered prematurely), and one (2.6%) was lost to follow-up. Seven (18.4%) cases continued the pregnancies to delivery. The postnatal follow-up period was 8.1 months (4.0 to 54.9 months). Two infants without comorbidities showed normal growth and development. Another three cases underwent surgeries after birth, and two cases died in the neonatal period. (3) The average width of the medullary cone was (2.5±0.8) cm. There was no significant difference in the spinal cord width between the high [(2.5±0.8) cm, n=34] and low group [(2.7±1.1) cm, n=4]. Six pregnancies (17.6%) in the high group was continued to delivery, and one of the neonates died of severe hydrocephalus. One patient in the low group (1/4) was delivered, while the baby died of neonatal asphyxia. Conclusions:Fetuses with isolated TC are prone to have a good prognosis. Further study should focus on the relation between the high or low position of the conus medullaris and pregnancy outcomes.

Objective: To explore the impact of PI3K-Akt-eNOS signaling on atrial fibrillation inducibility in diabetic rats. Method: Eight-week-old male diabetic rats were randomized assigned into GK group, IGF group and L-NAME group (n=8 each) which respectively received normal saline (NS), insulin like growth factor (IGF-1) or L-NAME+IGF-1 through tail vein daily for 4 weeks. Eight 8-week-old male homologous Wister-Kyoto(WKY) rats treated with intravenous NS served as control group (WKY group). Blood glucose was measured once per week. The left atrial diameter (LAD) was measured by echocardiography, the atrial electrical parameters, including the P-wave duration, the atrial effective refractory period (AERP) and its dispersion (AERP-d), the incidence and the duration of atrial fibrillation induced by atrial burst pacing, were evaluated by electro-physiological instrument at 4 weeks post various treatments. Rats were then sacrificed, left atrial (LA) cell morphology was determined on HE stained sections, LA interstitial collagen was determined on Masson stained sections. The protein expression of phosphatidylinositol 3-kinase (PI3K) and phosphate endothelial nitric oxide synthase (p-eNOS) were detected by Western blot. Results: (1) At the beginning of the study, the random blood glucose (GLU) level was significantly higher and LAD was large in GK, IGF and L-NAME groups than in WKY group;after 4 weeks, GLU level and LAD dimension of IGF group were lower than GK and L-NAME groups (P<0.01 or 0.05). (2) One rat in L-NAME group died during operation. Four weeks later, the incidence of atrial fibrillation in GK group, IGF group, L-NAME group and WKY group was 7/8, 2/8, 6/7 and 3/8. The median duration of atrial fibrillation in GK group, IGF group, L-NAME group and WKY group was 11.9(9.3, 13.1), 0(0, 1.8), 11.5(4.4, 12.0), and 0(0, 3.0) s. Compare with WKY group, the P-wave duration and PR interval were significantly longer, AERP-d, incidence, and duration of atrial fibrillation were significantly higher in GK group (P<0.01), these changed were significantly reversed in IGF group compared to GK and L-NAME groups (all P<0.01). Heart rate and AERP were similar among the 4 groups on (P>0.05). (3) Four weeks later, the CSA and CVF of LA were significantly larger in GK group than in WKY group (P<0.01), which were significantly reversed in IGF group (P<0.01 vs. GK group), and the beneficial effects of IGF disappeared by co-treatment with L-NAME (P<0.01 vs. IGF group). (4) Four weeks later, compare with WKY group, the protein expression of PI3K (P<0.01) and p-eNOS (P<0.05) of LA were significantly downregulated in GK group, which could be significantly upregulated by IGF (P<0.01 and 0.05 vs. GK group), these effects diminished by co-treatment with L-NAME (P<0.01 or 0.05 vs. IGF group). Conclusion Increased atrial fibrillation susceptibility in diabetic rat is linked with structural and electrical remodeling in LA, possibly mediated through downregulated PI3K-Akt-eNOS signaling.

Objective To study the dosimetric effect of two source patterns, including equal spacing and peripheral dense intermediate sparse by assuming a tumor shrinking speed of 20%per month after 125 I seed implantation. Methods A virtual cylindrical tumor with 4 cm in height and 5 cm in diameter was contoured on a three-dimensional treatment planning system ( TPS ) . Two groups of preoperative plans were made with 1. 85 × 107 Bq 125 I seeds using two source patterns respectively. It was assumed that the tumor height was unchanged, while the diameter of tumor would decrease at a speed of 20%per month, and the locations of seeds would concentrate towards the tumor core. The 90%target volume dose ( D90 ) , the ratio of 90%isodose volume over the target volume ( V90 ) , and the ratio of 150%isodose volume over the target volume (V150) were calculated at 0, 1, 2, 3 months after 125I implantation respectively. Results In equal spacing group, 85 seeds were implanted. The values of D90 were 126. 20, 130. 41, 133. 82 and 139. 48 Gy after 0, 1, 2 and 3 months respectively. The values of V90 were 97. 0%, 98. 1%, 99. 3%and 100%, while those of V150 were 70. 2%, 69. 9%, 71. 1% and 71. 5%. The dense in-periphery and sparse-in the middle group was loaded with 75 seeds. The D90 values were 126. 46, 125. 41, 123. 50 and 128. 83 Gy, the V9095. 2%, 95. 7%, 94. 9%and 97. 6%, and the V15052. 8%, 60. 4%, 62. 7%and 59. 3%after 0, 1, 2 and 3 months, respectiviely. Conclusions When the tumor diameter reduces at a rate of 20%per month after 125 I seed implantation, the expected tumor dose absorption will gradually increase using the equal spacing sources pattern. However, the expected dose does not vary withsource distribution of dense-in the-surrounding and sparse-in-middle, which also reduces high dose volume more than the equal spacing pattern.

Objective To systematically evaluate the efficacy and safety of 125I seed implantation on the treatment of refractory thyroid carcinoma.Methods A total of 14 patients with refractory thyroid carcinoma received CT and ultrasound image-guided 125I seed implantation in our hospital from Apr.2003 to Oct.2016.The radioactive activity ranged from 0.3 to 0.8 mCi,and the prescribed doses were 80 to 120 Gy.11 patients were diagnosed as differentiated thyroid carcinoma and 3 patients were medullary thyroid carcinoma.The local control rate,pain relief and complications were observed.Results The patients were followed up from 12 to 96 months.Two months after treatment,complete remission happened in three patients,partial remission in nine,and disease stability in two,no patients with progression.The half year,one year,two year local control rate was 100％,92％ and 42％,respectively.Seven patients were evaluated using number rating scales and obtained a score of 4.14±1.68 before therapy.Two months after treatment,the score was reduced to 2.00±1.15 (P＜0.000).No usual complications occurred during or after treatment except for I acute skin radio reaction in 4 cases.Conclusion 125I seed interstitial implantation for refractory thyroid carcinoma under guidance of ultrasound or CT is efficient and safe.