Objective To explore the relationship between human papilloma virus (HPV) infected population and disease occur‐rence in order to provide evidence and some reasonable suggestions for people understanding this disease .Methods A total of 2 508 suspected patients in our hospital from August 2012 to August 2013 were performed the HPV subtype detection by using PCR‐re‐verse dot blot(RDB) ,including 18 kinds of high risk HPV subtypes(HPV16 ,18 ,31 ,33 ,35 ,39 ,45 ,51 ,52 ,53 ,56 ,58 ,59 ,66 ,68 ,73 , 83 ,MM4) and 5 kinds of low risk HPV subtypes (HPV6 ,11 ,42 ,43 ,44) .Finally ,the patients condition was tracked through the hospital information management system and the clinical laboratory information systems .Results The HPV detection rate was 12 .26% ,in which the high risk type was mainly HPV 52 ,accounting for 12 .66% ,followed by HPV 58 ,16 .The low risk types were mainly HPV 43 ,6 ,11 ,accounting for 14 .61% ,10 .39% and 8 .44% respectively .By the follow up observation of clinical outcomes , the homotype positive phenomena were repeatedly appeared in the patients infected by HPV 52 ,16 within 2 years .At the same time ,the thinprep cytologist test(TCT) results in 157 cases of high risk HPV infection (genotype 52 ,58 ,16 ,18 ,66 ,33 ,56 ,68) were performed the tracking analysis ,indicating that high risk HPV infection was closely associated with cervical intraepithelial ne‐oplasia (CIN)Ⅰ ,CIN Ⅱ and canceration .Meanwhile ,their leucorrhea routine detection were followed up ,which manifested by mild to moderate inflammation .Conclusion High risk HPV subtype infection is closely associated with CIN Ⅰ ,CIN Ⅱ and canceration , while the leucorrhea routine shows mild ,moderate inflammation .Therefore ,only conducting the simple leucorrhea routine analysis can not really reflect the infection status ,it is necessary to look for the ways to cooperate with the superior hospital for timely detec‐ting HPV infection situation ,moreover regular follow up of people with HPV positive is the effective pathway to prevent CIN and cervical cancer .

Objective To explore the associations of the genetic polymorphisms of cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6) and cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9) with early-onset severe pre-eclampsia and the efficacy of labetalol therapy. Methods Totally 105 gravidas diagnosed with early-onset severe pre-eclampsia (experimental group) and 103 healthy gravidas (control group) were recruited from Beijing Obstetrics and Gynecology Hospital between August 2013 and July 2016. Labetalol was given to control blood pressures in gravidas with early-onset severe pre-eclampsia. If labetalol administration alone did not exceed the mean dose (100 mg, one dose per eight hours) and effectively controlled the blood pressures, it would be considered to be valid (n=75), otherwise it would be viewed as an invalid treatment. Genotype and allele frequencies of CYP2C9 gene (rs1057910 and rs4918758) and CYP2D6 gene (rs1065852, rs28371725, rs35742686 and rs3892097) in the gravidas were analyzed by TaqMan probe polymerase chain reaction. Differences in the genotype and allele frequencies were compared between the experimental and control groups, and the valid and invalid labetalol treatment groups. Chi-square test, analysis of variance and LSD test were used as statistical methods. Results The gravidas in both experimental and control groups were AA genotype in CYP2C9 gene rs1057910, TT genotype in CYP2D6 gene rs35742686 and CC genotype in CYP2D6 gene rs3892097. Frequencies of CC and CT genotypes in CYP2D6 gene rs28371725 in the experimental group were higher than those in the control group [18.1% (19/105) vs 14.6% (15/103);56.2% (59/105) vs 42.7% (44/103); χ2=6.707], and higher C allele frequency in CYP2D6 gene rs28371725 was also observed in the experimental group [46.2% (97/210) vs 35.9% (74/206), χ2=4.529] (all P<0.05). No statistical differences in maternal age, diastolic pressure, body mass index before pregnancy, serum triglyceride, creatinine and neonatal birth weight were observed among women with CC, CT or TT genotype of CYP2D6 gene rs28371725 in the experimental group (all P>0.05). Compared with the gravidas with CT or TT genotype of CYP2D6 gene rs28371725, those with CC genotype had longer gestational age [(32.5±2.1) vs (29.5±1.8) and (29.8±2.2) weeks] and higher plasma albumin [(27.2±9.3) vs (20.3±10.4) and (22.5±7.4) g/L], but lower systolic pressure and 24 hours urine protein (LSD test, all P<0.05). The G allele frequency in CYP2D6 gene rs1065852 in invalid labetalol treatment group was higher than that in valid labetalol treatment group [93.3% (56/60) vs 76.0% (114/150), χ2=8.351, P=0.004]. Conclusions The polymorphism of CYP2D6 gene rs28371725 may be associated with early-onset severe pre-eclampsia, and the allele of G in CYP2D6 gene rs1065852 may be associated with the efficacy of labetalol in treatment of early-onset severe pre-eclampsia.

Three cyclotides were isolated from the whole plant of Viola yedoensis in this study. The two, vary peptide E and cycloviolacin Y5, were previously reported, and a novel cycloviolacin VY1 was characterized according to the interpretation of MS/MS fragmentation of peptides which were produced from the reduced and alkylated parent peptide with the digestion of Endo Lys-C, trypsin and chymotrypsin, separately. The stability of remarkable resistance to proteolytic degradation by trypsin and chymotrypsin, and that of thermal denaturation was confirmed again. Besides, the IC50 value of cycloviolacin VYI against influenza A H1N1 virus was (2.27 +/- 0.20) microg x mL(-1). It is the first cyclotide reported with anti-influenza A H1N1 virus activity in vitro assay.

Objective To investigate the clinical significance and changes of serum complement in lipid metabolism disorder in patients with fatty liver disease.Methods One hundred and forty patients with FLD from October 2015 to May 2017 were included in the study,in addition,120 patients with hyperlipidemia(the hyperlipidemia group)and 130 healthy subjects(the control group)in the same period were enrolled as controls.The differences in serum lipid,liver function enzymology,immunoglobulin,serum complement among the three groups were compared.Results There were significant differences in the levels of TC,TG,HDL-C,LDL-C,apoA and apoB among the three groups(TC:(5.7±1.6)mmol/L vs.(4.2±1.0)mmol/L vs.(3.5±1.1) mmol/L,F=105.01,P<0.05;TG:(2.8± 0.6)mmol/L vs.(1.5 ± 0.3)mmol/L vs.(1.1 ± 0.2)mmol/L,F=628.46,P<0.05;HDL-C:(1.2±0.3)mmol/L vs.(1.5±0.3)mmol/L vs.(1.8±0.4)mmol/L,F=107.10, P<0.05;LDL-C:(3.6±0.9)mmol/L vs.(3.0±0.8)mmol/L vs.(2.2±0.6)mmol/L,F=109.07,P<0.05;apoA:(1.0±0.2)g/L vs.(1.2±0.2)g/L vs.(1.4±0.3)g/L,F=95.20,P<0.05;apoB:(1.1±0.2)g/L vs.(0.9±0.2)g/L vs.(0.8±0.2)g/L,F=79.04,P<0.05).The levels of TC,TG,LDL-C and apoB in the FLD group were significantly higher than those in the hyperlipidemia group and the control group.The levels of HDL-C and apoA in the FLD groups were significantly lower than those in the hyperlipidemia group and control group.The levels of TC,TG,LDL-C and apoB in the hyperlipidemia group were significantly higher than those in the control group.The levels of HDL-C and apoA in the hyperlipidemia group were significantly lower than those in the control group.There were significant differences in the levels of GGT,ALT,AST,IgG and IgM among the three groups(GGT:(77.4±15.3)U/L vs.(43.3±10.6)U/L vs.(25.5±8.2)U/L,F=668.12,P<0.05;ALT:(61.5±18.8)U/L vs.(35.7±11.2)U/L vs.(18.9±5.4)U/L,F=355.67,P<0.05;AST:(55.3±12.2)U/L vs.(32.4±12.5)U/L vs.(14.4±4.7)U/L,F=521.80,P<0.05;IgG:(15.7±3.9)g/L vs.(11.6±3.2)g/vs.,(8.5±2.6)g/L,F=162.34,P<0.05;IgM:(1.9±0.6)g/L vs.(1.2±0.4)g/L vs.(0.8±0.3)g/L,F=201.38,P<0.05).The levels of GGT,ALT,AST,IgG and IgM in the FLD group were significantly higher than those in the hyperlipidemia group and the control group.The levels of GGT,ALT,AST,IgG and IgM in the hyperlipidemia group were significantly higher than those in the control group.There were significant differences in the levels of C3,C5,ASP and BF among the mild,moderate and severe fatty liver patients(C3:(2.1±0.4) g/L vs.(1.8±0.3)g/L vs.(1.0±0.2)g/L,F=436.37,P<0.05;C5:(92.3±10.7)mg/L vs.(71.8±8.8) mg/L vs.(58.9±6.5)mg/L,F=486.09,P<0.05; ASP:(51.4±6.8)nmol/L vs.(42.5±4.4)nmol/L vs.(32.8±5.2)nmol/L,F=369.29,P<0.05;BF:(0.48±0.13)g/L vs.(0.34±0.09)g/L vs.(0.23±0.04) g/L,F=233.39,P<0.05).The levels of C3,C5,ASP and BF in the FLD group were significantly higher than those in the hyperlipidemia group and the control group.The levels of C3,C5,ASP and BF in the hyperlipidemia group were significantly higher than those in the control group.There were significant differences in the levels of C3,C5,ASP and BF among patients with mild,moderate and severe fatty liver disease(C3:(1.8±0.3)g/L vs.(2.1±0.4)g/L vs.(2.5±0.4)g/L,F=30.85,P<0.05;C5:(80.5±9.6)mg/L vs.(92.3±10.5)mg/L vs.(100.7±8.)mg/L,F=39.39,P<0.05; ASP:(42.4±6.3)nmol/L vs.(52.8±5.7)nmol/L vs.(61.9±5.6) nmol/L,F=98.19,P<0.05;BF:(0.33±0.12)g/L vs.(0.45±0.11)g/L vs.(0.57±0.09)g/L,F=41.26,P<0.05).The levels of C3,C5,ASP and BF in the mild FLD patients were significantly lower than those in moderate and severe FLD patients.The levels of C3,C5,ASP and BF in the moderate FLD patients were significantly lower than those in severe FLD patients.Conclusion The detection of C3,C5,ASP and BF levels based on routine testes has important clinical value for the assessment of the condition,the treatment and the prognosis of FLD patients.

Objective:To evaluate the value and identify the prognosic factors of postoperative radiotherapy (PORT) in completely resected stage Ⅲ(pN 2) lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) wild-type who received adjuvant chemotherapy. Methods:Clinical data of 172 patients with stage Ⅲ(pN 2) EGFR wild-type lung adenocarcinoma who underwent radical resection and adjuvant chemotherapy from 2009 to 2016 were retrospectively analyzed. All patients received platinum-based adjuvant chemotherapy combining two drugs for>4 cycles, and divided into the PORT group and the non-PORT group. The survival rate was calculated by Kaplan- Meier method and log-rank test, and multivariate prognostic analysis was performed by Cox’s regression model. Results:Among 172 patients, the median overall survival (OS), 3-year and 5-year OS rates were 40 months, 55.9% and 28.3%, respectively. The median disease-free survival (DFS), 3-year and 5-year DFS rates were 17 months, 24.5% and 13.0%, respectively. DFS was significantly improved in the PORT group (29 months vs. 13 months, P=0.001), whereas OS did not significantly differ between two groups (51 months vs. 38 months, P=0.151). In subgroup analysis, DFS of patients with multistation N 2 or the number of N 2 metastases of≥3 or skip N 2 in the PORT group was significantly longer ( P<0.05), whereas PORT exerted no significant effect on OS ( P>0.05). Conclusions:For patients with completely resected stage Ⅲ(N 2) EGFR wild-type lung adenocarcinoma receiving adjuvant chemotherapy, PORT might increase DFS and have a trend toward longer OS. However, these findings remain to be validated by large sample size investigations.

Objective The study was to investigate the activation of tumor necrosis factor α (TNF-α) mRNA transcription and protein expression in peripheral blood and activation of signal path PI3K/AKT in patients with chronic heart failure. Methods From February 2015 to April 2018, 244 patients with heart failure in the cardiovascular department of our hospital were selected as heart failure group, while 244 healthy cases were enrolled as the control group at the same time. The peripheral blood samples of two groups were collected. We detected the transcription and protein expression of TNF-α mRNA and the activation of PI3K, AKT in peripheral blood. The left ventricular ejection fraction (LVEF) were measured in two groups. The correlations between influencing factors and LVEF were analyzed. Results The levels of PI3K, AKT in the heart failure group were higher than those in the control group. The differences were statistically significant respectively (P < 0.05). The mRNA relative content and protein content of TNF-α in peripheral blood mononuclear cells of heart failure group were higher compared with those of control group (P < 0.05). The LVEF of heart failure group was significantly lower than that of the control group (34.50 ± 6.33) ％ versus (55.60 ± 2.49) ％, P < 0.001). Among 244 patients with heart failure, Spearman correlation analysis showed that there were significant positive correlations between TNF-a mRNA and protein expression levels and the levels of PI3K, AKT respectively (P < 0.05). Multiple factors unconditional Logistic regression analysis showed that the TNF-α mRNA, protein expression and PI3K, AKT levels in peripheral blood were independent risk factors for LVEF (P < 0.05). Conclusion The expression levels of PI3K, AKT and TNF-α are all significantly increased in chronic heart failure patients, which could participate in the occurrence and development of heart failure.

Background As a complex organic pollutant, polycyclic aromatic hydrocarbons (PAHs) exposure shares the common exposure characteristics of multiple hydroxyl metabolites. Most studies have analyzed independent effect of each PAHs metabolite and have adjusted for the potential confounding effects induced by other metabolites concomitantly, without considering possible interactions among them. Proper statistical methods are needed to study their toxic effects. Objective To explore the applicability of logistic regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) in evaluating the correlation between mixed exposures to exogenous chemicals and health outcomes, compare the advantages and limitations of the three models, and propose analytical strategies for evaluating the health effects of mixed chemical exposure for application in the analysis of the association between PAHs exposure and cognition. Methods Urine samples were collected of workers from a coke oven plant and a water treatment plant in Shanxi Province, who participated in their routine employee healthexamination. Mono-hydroxylated PAHs were detected by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS), cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). A cut-off value of MoCA less than 26 was considered mild cognitive impairment (MCI). According to a predetermined inclusion and exclusion criteria, 1 051 cases were included in the final data analysis. Logistic regression, WQS regression, and BKMR were used to analyze the relationship between PAHs metabolites and MCI. Results The prevalence rate of reporting MCI among the 1 051 workers was 21.7% (228/1 051). The concentration of 2-hydroxynathalene (2-OHNAP) was the highest among the 11 PAHs metabolites with a median concentration of 0.30 μg·L⁻¹, followed by 9-hydroxyphenanthrene (9-OHPHE) (0.26 μg·L⁻¹). There were significant differences between the two groups in 2-OHNAP, 1-hydroxynaphthalene (1-OHNAP), 2-hydroxyfluorene (2-OHFLU), 9-OHPHE, 1-hydroxyphenanthrene (1-OHPHE), and 1-hydroxypyrene (1-OHPYR) (all Ps<0.05). In the logistic regression, 2-OHNAP and 2-OHPHE were associated with MCI, and the OR (95%CI) for reporting MCI was 1.28 (1.01-1.67) and 1.27 (1.00-1.72) for each 10-fold increase in 2-OHNAP and 2-OHPHE concentrations, respectively. In the WQS regression analysis, the WQS index was positively correlated with the prevalence rate of reporting MCI (OR=1.37, 95%CI: 1.10-1.72). In the BKMR analysis, compared with the median exposure levels of all chemicals, the overall effect was statistically significant when all PAHs metabolites concentrations were at or above their 30th percentile; when all exposures were at the 75th percentile, the risk of reporting MCI increased by 6%. Conclusion Based on the results of these three models, 2-OHNAP and 2-OHPHE are the most important factors related to cognitive. It is recommended to use a combination of traditional logistic regression and either WQS or BKMR to study the association between PAHs and MCI.

Tolerogenic dendritic cells (tolDCs) facilitate the suppression of autoimmune responses by differentiating regulatory T cells (Treg). The dysfunction of immunotolerance results in the development of autoimmune diseases, such as rheumatoid arthritis (RA). As multipotent progenitor cells, mesenchymal stem cells (MSCs), can regulate dendritic cells (DCs) to restore their immunosuppressive function and prevent disease development. However, the underlying mechanisms of MSCs in regulating DCs still need to be better defined. Simultaneously, the delivery system for MSCs also influences their function. Herein, MSCs are encapsulated in alginate hydrogel to improve cell survival and retention in situ, maximizing efficacy in vivo. The three-dimensional co-culture of encapsulated MSCs with DCs demonstrates that MSCs can inhibit the maturation of DCs and the secretion of pro-inflammatory cytokines. In the collagen-induced arthritis (CIA) mice model, alginate hydrogel encapsulated MSCs induce a significantly higher expression of CD39⁺CD73⁺ on MSCs. These enzymes hydrolyze ATP to adenosine and activate A_2A/2B receptors on immature DCs, further promoting the phenotypic transformation of DCs to tolDCs and regulating naïve T cells to Tregs. Therefore, encapsulated MSCs obviously alleviate the inflammatory response and prevent CIA progression. This finding clarifies the mechanism of MSCs-DCs crosstalk in eliciting the immunosuppression effect and provides insights into hydrogel-promoted stem cell therapy for autoimmune diseases.