Epigenetic changes are important etiological factors of human tumor. The integrity of the genome is frequently challenged by the damage of DNA. However, the highly condensed structure of chromatin imposes significant obstacles on the repair processes. Eukaryotes have developed intricate mechanisms to overcome this repressive barrier imposed by chromatin. Covalent histone modifications and ATP-dependent chromatin remodeling play important roles in the process of DNA repair. Recent advances of the epigenetic regulations in the repair process were summarized. New findings in the cellular responses to DNA double strand breaks and how histone modifications and chromatin remodeling contributes to DNA double strand break repair were introduced. Future challenges in this field are also discussed.

Objective To investigate the risk factors related to mortality in human avian influenza A (H7N9)cases in Hangzhou.Methods The clinical and epidemiological data of 61 H7N9 patients whose diagnoses were confirmed by laboratory tests between 1st March,2013 and 2nd March,2014 in Hangzhou were collected.Descriptive analysis and univariate analysis were used to analyze the demographic,clinical and epidemiological characteristics and treatment outcomes.Patients were classified into improvement group and death group according to treatment outcomes,and risk factors for death were explored.Chi square test and t test were used for statistical analysis.Results A total of 61 patients were included in this study,among which 20(32.8%)patients died.The ratio of men to women for death attributed to H7N9 infection was three to one.The mean age of patients in death group was (63.6 ±3.8)years,which was older than that in improvement group ([55 .4±2.2]years,t =1 .97,P =0.05 ).The univariate analysis showed that the risk factors of mortality included over 60 years (χ2 =5 .16,P =0.02;OR =3.65 ,95 %CI :1 .19-11 .13 ),low education level (χ2 = 5 .42,P =0.02;OR =4.20,95 %CI :1 .24 - 14.00 ), chronic diseases (χ2 =4.67,P =0.03;OR=3.81 ,95 %CI :1 .12-12.69),bad hand hygiene (χ2 =4.05 , P =0.04;OR=4.67,95 %CI :1 .04 -11 .56 ),C-reactive protein (CRP)≥120 mg/L (χ2 =4.04,P =0.04;OR=6.00,95 %CI :1 .04-35 .33),increased initial neutrophil count (χ2 =3.90,P =0.05 ;OR=4.58,95 %CI :1 .01 -34.22)and decreased initial lymphocyte count (χ2 =7.12,P =0.01 ;OR =7.53, 95 %CI :1 .63 - 24.51 ).Conclusion Over 60 years,low education level,chronic diseases,bad hand hygiene,CRP≥ 120 mg/L,increased initial neutrophil count and decreased initial lymphocyte count are identified as risk factors for death in H7N9 cases in Hangzhou.

Objective To investigate the risk of atopic disease in infants with a atopic mothers. Methods The level of CCL22 and total IgE in the cord blood were measured using ELISA for 33 newborns with atopic mothers and for 44 newborns with non-atopic mothers. Correlation between the two factors was examined. Periodic follow-ups were conducted on the newborns to observe the risk of atopic diseases. Results The atopic group showed a higher level of CCL22 than that in non-atopic group, and the difference was statistically significant (Z=5.20, P=0.000). When 0.9 kU/L was taken as the threshold of an elevated IgE level in cord blood, the positive rates of the atopic group (11/33) was much higher than that of the non-atopic group (4/44) (χ2=7.07, P=0.008). Furthermore, the level of CCL22 and the level of IgE were significantly positively correlated (r=0.808, P=0.000; r=0.348, P=0.021) in the atopic group and the non-atopic group, respectively. During the 12 months of follow-up, the number of atopic diseases occurred in the infants in the atopic group (24/33) was much higher than that in the non-atopic group (10/44) (χ2=19.12, P<0.001).Significant correlation exists between levels CCL22 and total IgE in cord blood and infant atopic diseases (Z=5.36, P=0.000; Z=4.44, P=0.000). Conclusions At birth, the infants with an atopic mother are already in a sensitization state and have a tendency to develop potential atopic diseases. There is a correlation between the history of atopic diseases in the mothers and the elevated level of CCL22 in the cord blood of the newborns, and the probability of developing atopic diseases for the newborns is significantly higher when the level of CCL22 is elevated. The combined detection of CCL22 and IgE levels impact significantly on the prediction of the risk of atopic diseases clinically.

Objective To develop and validate a mortality risk prediction model for patients infected with avian influenza A H 7N9 virus.Methods A stratified and random sampling method was adopted for selection of subjects .A total of 102 patients infected with avian influenza A H7N9 virus, who were admitted to the designated hospitals in Zhejiang Province during March 2013 and March 2015, were enrolled.Standard questionnaires were used to collect data about demographic , epidemiologic and clinical characteristics , and the data were retrospectively reviewed . Univariate analysis and stepwise logistic regression analysis were used to identify the mortality risk factors of patients infected with avian influenza A H7N9 virus, and nomogram was applied to develop the risk prediction model .The accuracy of the prediction model was assessed using Concordance index (C-index) and receiver operating characteristic (ROC) curve. Results Stepwise multiple logistic regression analysis showed that age ≥60 years (χ2 =3.98, OR=2.99, 95%CI:1.05-9.21, P<0.05), increased initial neutrophil count (χ2 =6.66,OR=5.06, 95%CI:1.56-18.83, P<0.05), C-reactive protein≥120mg/L (χ2 =8.63, OR=5.15, 95%CI:1.79-16.31, P<0. 01), poor hand hygiene (χ2 =6.83, OR =10.29, 95%CI:2.18-81.49, P <0.01) and 5 days of incubation period or shorter (χ2 =7.23, OR=4.75, 95%CI:1.59-15.80, P<0.01) were independent risk factors for mortality of patients .Based on the above study , a risk prediction model of nomogram was developed.Poor hand hygiene (grade A, 100.0 points) ranked on the top of all risk factors, followed by C-reactive protein≥120 mg/L (grade B, 76.5 points), increased initial neutrophil count (grade C, 70.5 points), 5 days of incubation period or shorter (grade D, 62.0 points) and age ≥60 years (grade E, 51.0 points).The C-index and the area under the curve were 0.833 and 0.817 for the nomogram model , respectively;and the nomogram model fitted well .Conclusion Nomogram model can effectively predict and estimate the risk of death for patients infected with avian influenza A H 7N9 virus.

Objective To evaluate the effect of a pilot intervention on setting up a hospital-based neonatal resuscitation leading group in 12 hospitals. Methods One provincial-level, two prefecturelevel and one county-level hospitals in Jiangxi, Liaoning and Hunan province were selected to participate in the intervention. A neonatal resuscitation leading group was set up in each hospital to investigate the mode of resuscitation practice training and re-training, improve and carry on the cooperation between obstetricians and pediatricians, record the steps of neonatal resuscitation of asphyxia cases and lead the exploration of the problems occurred during the process in their own hospital. The changes of asphyxia incidence and neonatal resuscitation process were analyzed to evaluate the effect of the intervention. Results (1) Incidence of neonatal asphyxia during intervention period: 315 neonatal asphyxia cases were recorded, among which 89.5 % (n = 282) were mild and 10. 5% (n=33) cases were severe asphyxia. The mean one-minute Apgar score was the lowest in county-level hospitals (5. 40±1.56), followed by provincial-level hospitals (5.63 ±1.67)and prefecture-level hospitals (6.03 ± 1.41). (2) Resuscitation was not performed according to the guidelines in 47. 9% (151/315) of asphyxia cases. Bag and mask ventilation was not performed according to guideline in 36. 5% (115/315) of cases. (3) Changes of asphyxia incidence after the intervention: the incidence of asphyxia in provincial-level (4.23 % vs 2.66 %, χ2 = 5. 021, P＜0.05)and prefecture-level (2.83% vs 1.67%, χ2 = 4. 948, P＜0.05) hospitals decreased significantly after the intervention. The incidence of severe asphyxia in both provincial-level (χ2 =3. 001, P＞0.05) and prefecture-level (χ2= 0. 966, P＞ 0. 05) hospitals decreased with no statistical significance. The asphyxia incidence in county-level hospitals decreased from 2. 48% to 1. 22% (χ2 = 2. 989, P =0. 084). The incidence of severe asphyxia in county-level hospitals decreased from 0.39% to 0. 00%(χ2=2. 567, P= 0. 035). Conclusions Setting up a hospital-based neonatal resuscitation leading group is an effective method to strengthen resuscitation practice training, promote the cooperation between departments, improve the level of neonatal resuscitation practice and therefore decrease the incidence of neonatal asphyxia in the hospital.

Objective:To observe the clinical efficacy of ultrasound cycloplasty (UCP) in the treatment of uncontrolled intraocular pressure (IOP) after glaucoma surgery.Methods:An observational case series study was carried out.Twenty-eight consecutive patients (28 eyes) with uncontrolled IOP after glaucoma surgery who received UCP treatment in The First Affiliated Hospital of Zhengzhou University from July 2018 to October 2019 were enrolled.The IOP of these patients was ≥21 mmHg (1 mmHg=0.133 kPa) under the maximum tolerated dose.According to preoperative IOP and visual acuity, the patients were divided into 8-sector group (17 eyes) and 10-sector group (11 eyes). The duration of UCP operation, preoperative and postoperative 1-day, 1-week, 2-week, 1-month and 3-month IOP and BCVA, the types of drugs for lowering IOP preoperatively and postoperatively, preoperative and postoperative 3-month ocular pain grading and corneal endothelial cell counts, and adverse reactions during the operation and after surgery were recorded.This study adhered to the Declaration of Helsinki.The study protocol was approved by an Ethics Committee of The First Affiliated Hospital of Zhengzhou University (No.2020-KY-154). Written informed consent was obtained from each subject prior to any medical examination.Results:The duration of UCP operation was 3 to 7 minutes, with an average of (4.30±1.26) minutes.The IOP at 1 day, 1 week, 2 weeks, 1 month and 3 months after operation was (32.96±10.49), (25.89±7.25), (24.50±6.23), (24.07±6.59), (24.32±6.52)mmHg, respectively, which were significantly lower than (45.82±8.81) mmHg before operation (all at P<0.05). There was no significant difference in IOP between the 8-sector group and 10-sector group ( Fgroup=1.271, P=0.270), but there was a significant difference in IOP between the two groups before and after operation ( Ftime=54.388, P<0.01), and the postoperative IOP at various time points in the two groups were lower than the preoperative IOP, showing statistical significances (all at P<0.05). There was no significant difference in BCVA before and after surgery ( F=2.562, P=0.075). There was a statistically significant difference in BCVA between the 8-sector group and 10-sector group ( Fgroup=12.602, P=0.001), but no statistically significant difference was found in BCVA between the two groups before and after surgery ( Ftime=1.701, P=0.139), and the BCVA in the 8-sector group was better than the 10-sector group at various time points (all at P<0.05). The types of IOP lowering drugs used in the 8-sector group and 10-sector group were 3 (2, 3) and 3 (2, 4) before operation respectively, and 0 (0, 1) and 0 (0, 0) at 3 months after operation respectively.The preoperative ocular pain grade was 2 (2, 2), and the postoperative 3-month ocular pain grade was reduced to 1 (0, 1), and the difference was statistically significant ( Z=-4.824, P<0.05). The postoperative 3-month pain grading in the 8-sector and 10-sector groups were significantly lower than the preoperative pain grading ( Z=-3.739, -3.127; both at P<0.05). The corneal endothelial cell count was significantly decreased from (1 967.15±186.06) cells/mm 2 before operation to (1 861.08±206.63) cells/mm 2 at 3 months after operation ( t=2.781, P=0.017). No serious complications occured during the operation.Postoperative adverse reactions included chemosis and bulbar hyperemia, corneal edema, headache, ocular pain, anterior chamber inflammation, etc.Serious complications such as low IOP, macular edema, vision loss or eyeball atrophy were not observed. Conclusions:UCP has no surgical incision.Treatment of both 8 sectors and 10 sectors can effectively reduce IOP, reduce the types of IOP lowering drugs, and relieve ocular pain in patients with uncontrolled IOP after glaucoma surgery with few intraoperative and postoperative adverse reactions.

Objective: To observe the material basis and mechanism of action of Kai-Xin-San (KXS) in regulating antidepression of neurotrophic factors. Methods: KXS eluted by ethanol on macroporous resin was prepared. The antidepressive effect of different components was compared by tailing suspension test and forced swimming test of mice. The levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in hippocampus were determined by ELISA. The rat astrocyte glioma C6 cell line and the rat adrenal pheochromocytoma PC12 cell line were used to evaluate the effects of different ethanol elution sites on the expression of NGF and BDNF and the differentiation of PC12 cells.Results: All of the ethanol elution components from KXS exerted anti-depressive effects by shorting the immobile time of tailing suspension and forced swimming of mice and 70％ ethanol elution components exerted best efficacy. This site also could increase expressions of NGF and BDNF on C6 glioma cell line. The 10％ ethanol elution site had the strongest ability to promote PC12 cell differentiation. Ginsenosides were the main effectuve ingredients for promoting the expression of neurotrophic factors. Conclusion: Regulation of neurotrophic factors might be the prominent action mechanism of KXS exerting anti-depressive effects.

OBJECTIVE：To desig n and sy nthesize poly （γ-glutamic acid ）-ampelopsin（γ-PGA-AMP），and to characterize it and evaluate its anti-tumor activity in vitro . METHODS ：Synthetic product was produced through an esterification reaction between γ-PGA and ampelopsin. The structure of synthetic product was characterized by the UV spectrophotometry ，Fourier transform infrared（FT-IR）spectroscopy，1H-NMR spectra and the quantitative elemental analysis. The content of ampelopsin in synthetic product was determined by UV absorption spectrometry at 292 nm. Using 5-FU as positive control ，MTT assay was used to determine inhibitory effects of γ-PGA-AMP and ampelopsin on human breast cancer cell MCF- 7，human liver cancer cell HepG 2 and human lung cancer cell A 549. The IC 50 was calculated. RESULTS ：The results showed that the free 7-hydroxyl group of ampelopsin and the a-carboxyl group of γ-polyglutamic acid had been esterified to obtain γ-PGA-AMP；the yield of γ-PGA-AMP was 55.7％，and the content of ampelopsin was 32.3％. The inhibitory effect of γ-PGA-AMP and ampelopsin on MCF- 7，HepG2 and A 549 cells was obvious. IC 50 of γ-PGA-AMP（to 3 above tumor cells ）were 40.19，28.29 and 55.23 μg/mL，those of ampelopsin were 105.30，81.23，130.10 μg/mL，those of 5-FU were 24.72，87.98，30.99 μg/mL，respectively. CONCLUSIONS ：γ-PGA-AMP with anti-tumor effect in vitro is synthesized successfully ，and its anti-tumor effect is stronger than that of ampelopsin.

OBJECTIVE： To study the effects of ethanol extract of Sanguis Draconis on the survival of perforating flap model in rats and PI3K/Akt/eNOS pathway. METHODS： Perforating flap model was established by cutting off surrounding vessels and keeping one perforator. After modeling， the rats were divided into model group （external use， normal saline） and ethanol extract of Sanguis Draconis （EESD， the content of dracorhodin was 75.08 mg/g） group （external use， 0.21 g/cm2）， with 10 rats in each group. They were given relevant medicine for consecutive 7 days， once a day. The flap survival rate and flap microvessel density were determined after given relevant medicine 7 days. Human umbilical vein endothelial cells （HUVECs） were reoxygenated and glycoconjugated 16 h after hypoxia and hypoglycemia to establish oxygen-glucose deprivation/oxygen-glucose recovery model of HUVECs. After modeling， model cells were divided into normal group， model group， dracorhodin high-concentration， medium- concentration and high-concentration groups （2.5， 1.0， 0.5 μg/mL）. After reoxygenated and glycoconjugated for 24 h， cells morphology was observed by microscope； cell viability and the content of NO were detected by MTT assay and colorimetry. mRNA expression of Akt， PI3K and eNOS， PI3K protein expression， the phosphorylation of Akt and eNOS protein were determined by RT-PCR and Western blot assay. RESULTS： In rat experiment， compared with model group， flap survival rate and microvessel density of rats were increased significantly in EESD group （P＜0.01）. In cell experiment， compared with normal group， the survival rate of HUVEC， NO content， mRNA expression of PI3K， Akt， eNOS，PI3K protein expression， the phosphorylation of Akt and eNOS protein were decreased significantly （P＜0.05 or P＜0.01）. Compared with model group， dracorhodin high-concentration， medium-concentration and high-concentration groups survival rate of HUVEC cells， NO content， mRNA expression of PI3K， Akt and eNOS， PI3K protein expression， the phosphorylation of Akt and eNOS protein were increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： The survival rate of perforating flap model in rat can be increased by treating with EESD， the mechanism of which may be associated with the activation of PI3K/Akt/eNOS pathway to protect endothelial cells.

OBJECTIVETo comprehend the epidemiologic of hepatitis E and genetic characteristics of hepatitis E virus (HEV) in Hangzhou from 2004 to 2011.

METHODSUsing China information system for disease control and prevention, the incidence of hepatitis E from 2004 to 2011 in Hangzhou city, and the basic information of patients were collected. In 2011, 65 hepatitis E laboratory confirmed cases were selected by random number table sampling method from the hospitals designated infectious diseases in Hangzhou city, and acquisition of the 60 blood specimens and stool specimens of 18 copies. One city and two surrounding counties were selected by cluster random sampling method in the context of Hangzhou city, and the pig slaughters and farmers were selected as the sampling point, and acquisition of pig gallbladder specimens of 52 copies, and 30 stool samples of scatter-feed pigs, 15 stool specimens of scatter-feed rabbits. HEV was tested in samples, gene extraction and analysis of gene sequence were conducted which were compared with gene bank HEV gene sequence, and a phylogenetic tree was formed. The epidemic characteristics of hepatitis E of Hangzhou city from 2004 to 2011 were described. The difference of incidence of hepatitis E was analyzed between years and sexes in Hangzhou city.

RESULTSThere were reported a total of 3 490 cases of hepatitis E in Hangzhou from 2004 to 2011, and 3 cases of death; The average annual incidence rate was 5.79/100 000 (3 490/60 276 338). There was the overall upward trend in incidence between different years (χ² = 52.38, P < 0.01) , which the highest was 8.10/100 000 (705/8 700 373) in 2011, and the lowest incidence rate was 4.19/100 000 in 2005. The incidence of males (8.12/100 000 (2 474/30 450 990) ) was significantly higher than that of the females (3.46/100 000 (1 016/29 384 491) ) (χ² = 558.45, P < 0.05). 78 specimens of blood and stool were collected, including 16 positive samples, with positive rate 21%. There were a total of 97 specimens of pig gallbladder, pig manure and rabbit stool, including 2 positive rabbit stool samples, with positive rate of 2%. HEV genes isolated from Hangzhou were mainly type IV, with homology of 91.8% to 100%; compared with human type IV strains, the homology of nucleotide was 84.6%-96.7%; compared with type IV strain of pig genome sequence alignment, homology was 82.6%-95.2%.

CONCLUSIONHepatitis E's incidence showed an increasing trend year by year in Hangzhou. HEV of type IV was dominant, and HEV strains in the human and swine were highly homologous.

Adolescent ; Animals ; China ; epidemiology ; Disease Vectors ; Feces ; Female ; Hepatitis E ; epidemiology ; etiology ; Hepatitis E virus ; Humans ; Incidence ; Male ; Rabbits ; blood ; microbiology ; Rural Population ; statistics & numerical data ; Sequence Alignment ; Sequence Homology, Nucleic Acid ; Sex Factors ; Swine ; blood ; microbiology ; Urban Population ; statistics & numerical data