[The characteristics and correlations of vaginal flora in women with cervical lesions].

Objective: To explore the characteristics and correlations of vaginal flora in women with cervical lesions. Methods: A total of 132 women, including 41 women diagnosed with normal cervical (NC), 39 patients with low-grade cervical intraepithelial neoplasia (CIN 1), 37 patients with high-grade cervical intraepithelial neoplasia (CIN 2/3) and 15 patients with cervical squamous cell carcinoma (SCC), who came from the gynecological clinic of Second Hospital of Shanxi Medical University during January 2018 to June 2018, were enrolled in this study according to the inclusive and exclusive criteria strictly. The vaginal flora was detected by 16S rDNA sequencing technology. Co-occurrence network analysis was used to investigate the Spearman correlations between different genera of bacteria. Results: The dominant bacteria in NC, CIN 1 and CIN 2/3 groups were Lactobacillus [constituent ratios 79.4% (1 869 598/2 354 098), 63.6% (1 536 466/2 415 100) and 58.3% (1 342 896/2 301 536), respectively], while Peptophilus [20.4% (246 072/1 205 154) ] was the dominant bacteria in SCC group. With the aggravation of cervical lesions, the diversity of vaginal flora gradually increased (Shannon index: F=6.39, P=0.001; Simpson index: F=3.95, P=0.012). During the cervical lesion progress, the ratio of Lactobacillus gradually decreased, the ratio of other anaerobes such as Peptophilus, Sneathia, Prevotella and etc. gradually increased, and the differential bacteria (LDA score >3.5) gradually evolved from Lactobacillus to other anaerobes. The top 10 relative abundance bacteria, spearman correlation coefficient>0.4 and P<0.05 were selected. Co-occurrence network analysis showed that Prevotella, Peptophilus, Porphyrinomonas, Anaerococcus, Sneathia, Atopobium, Gardnerella and Streptococcus were positively correlated in different stages of cervical lesions, while Lactobacillus was negatively correlated with the above anaerobes. It was found that the relationship between vaginal floras in CIN 1 group was the most complex and only Peptophilus was significantly negatively correlated with Lactobacillus in SCC group. Conclusions: The increased diversity and changed correlations between vaginal floras are closely related to cervical lesions. Peptophilus is of great significance in the diagnosis, prediction and early warning of cervical carcinogenesis.

[A nested case-control study on the relationship between red blood cell folate and the prognosis of low-grade cervical intraepithelial neoplasia].

Objective: To evaluate the relationship between red blood cell folate (RBC folate) and the prognosis of low-grade cervical intraepithelial neoplasia (CIN 1). Methods: In the married women cohort established in 2014, 564 women with CIN 1 diagnosed by pathology were recruited. The demographic characteristics and factors of cervical intraepithelial neoplasia were collected. Meanwhile, the infection status of human papillomavirus (HPV) was detected by molecular diversion hybridization, and the level of RBC folate was measured by chemical photoimmunoassay. After 24 months of follow-up, pathological examination was performed again to observe the prognosis of participants. The women with reversal were taken as the control group,and those with continuous and progressive CIN 1 were taken as the case group respectively. The relationship between RBC folate and CIN 1 outcome was evaluated by logistic regression model. Results: 453 women completed the follow-up, aged (49.72±6.84) years old. CIN 1 was reversed in 342 women, continued in 58 cases and progressed in 53 cases. The RBC folate level M (Q1,Q3) were 399.01 (307.10, 538.97) ng/ml, 316.98 (184.74, 428.49) ng/ml and 247.14 (170.54, 348.97) ng/ml, respectively. With the decrease of RBC folate, the risk of continuous and progressive CIN 1 increased (all P<0.001), while the risk of reversal CIN 1 decreased gradually (P<0.001). Combined with high-risk human papillomavirus (HR-HPV) infection status, low level of RBC folate could increase the risk of CIN 1 progression regardless of HR-HPV infection (HR-HPV infection: OR=21.34, 95%CI: 3.98-114.54; HR-HPV uninfection: OR=11.15, 95%CI: 2.34-53.13). Conclusion: Low level of RBC folate could increase the risk of CIN 1 persistence and progression regardless of HR-HPV infection.

[The effect of red blood cell folate on the prognosis of high-risk human papillomavirus infection: a community-based cohort study].

Objective: To investigate the effect of red blood cell folate on the prognosis of high-risk human papillomavirus (HR-HPV) infection. Methods: A total of 564 participants with low-grade cervical intraepithelial neoplasias (CINⅠ) were selected from the community-based married women cohort established in 2014. The general baseline information and factors related to HPV infection were collected. Meanwhile, HPV genotyping and levels of folate were measured. The subjects were divided into different levels of exposure group according to the folate levels and followed up for 24 months to observe the changes of HR-HPV infection status. There were four changes, including persistent infection, infection turned negative, from negative to positive and constant negative by comparing HR-HPV infection status at baseline and follow-up to 24 months. Results: 483 participators completed 24 months of follow-up observation, with a follow-up rate of 85.64% (483/564). The rates of persistent infection, infection turned negative, from negative to positive, and the constant negative were 52.45% (75/143), 47.55% (68/143), 19.71% (67/340), 80.29% (273/340), respectively. Our results demonstrated that the risk of persistent infection (aRR=2.50, 95%CI: 1.55-4.02) and from negative to positive (aRR=4.55, 95%CI: 2.52-8.23) in the low level of folate were significantly higher than that in the high level of folate, especially the risk of homotype persistent infection (aRR=2.72, 95%CI: 1.51-4.90). The risk of persistent infection (trend χ2=20.62, P<0.001), from negative to positive (trend χ2=31.76, P<0.001), persistent homotypic infection (trend χ2=20.09, P<0.001) increased with the decrease of red blood cell folate level. On the contrary, no similar results were found in persistent heterotypic infection. Conclusions: A low level of red blood cell folate could increase the risk of HR-HPV persistent infection and from negative to positive. In women with HR-HPV infection, the risk of persistent homotypic infection is higher.

[Effects of polycyclic aromatic hydrocarbons exposure on prognosis of high risk human papillomavirus infection: a prospective cohort study].

Objective: To investigate the effects of polycyclic aromatic hydrocarbons (PAHs) exposure on the prognosis of high risk human papillomavirus (HR-HPV) infection. Methods: In this prospective study, 564 patients with low-grade cervical intraepithelial neoplasia confirmed by pathology were selected from the natural cohort population established by our research group in Shanxi province in 2014. Based on the baseline data of demographic characteristics and factors related to HPV infection, the concentrations of 1-hydroxypyrene in urine samples of the patients were determined by high performance liquid chromatography to define the exposure level of PAHs. At baseline survey and follow-up after 24 months, flow-through hybridization was used to detect HPV infection types, and to evaluate the prognosis of HR-HPV (persistent infection, negative conversion, positive conversion and persistent negative status). Results: Of the 564 subjects, 483 completed the follow-up, with a follow-up rate of 85.6% (483/564). Among them, the persistent infection rate was 52.4% (75/143), the persistent homotype infection rate was 35.7% (51/143), the negative conversion rate was 47.6% (68/143), the positive conversion rate was 19.7% (67/340), and the persistent negative rate was 80.3% (273/340). The follow-up results showed that the persistent infection rate (aRR=3.22, 95%CI: 1.85-5.62) and positive conversion rate (aRR=2.84, 95%CI: 1.64-4.94) of HR-HPV in high PAHs exposure group were higher than those in low PAHs exposure group, while the persistent negative rate (aRR=0.55, 95% CI: 0.43-0.70) of HR-HPV in high PAHs exposure group were lower than those in low PAHs exposure group. Based on restrictive cubic spline analysis, the results showed that the effects of PAHs exposure on persistent HR-HPV infection and persistent homotype infection showed an ascending linear dose-response relationship, while on HR-HPV positive conversion and persistent negative status showed an ascending and declining nonlinear dose-response relationship respectively (P<0.01). Conclusions: High PAHs exposure could promote persistent HR-HPV infection and persistent homotypic infection. Reducing PAHs exposure might conducive to HR-HPV continuous negative maintenance. Active prevention and control of PAHs exposure is of great significance to prevent HR-HPV infection and persistent infection.

[Effect of dietary water-soluble vitamins on the poor prognosis of low-grade cervical intraepithelial neoplasia-a prospective cohort study].

Objective: To explore the effect of dietary water-soluble vitamins on the poor prognosis of low-grade cervical intraepithelial neoplasia (CINⅠ). Methods: A total of 564 participants with CINⅠ were selected from a community-based married women cohort established in 2014. The general baseline information was collected, and HPV genotyping was detected. A food frequency questionnaire was used to investigate dietary water-soluble vitamins' consumption and determine their exposure levels. The follow-up program was carried out for 12 months, and the regression, persistence, and progression of CINⅠ was determined according to histopathological results at 12-month. Results: The low-levels of dietary water-soluble vitamins could promote CINⅠ's persistence and progression, showing the increasing tendency of CINⅠ poor prognosis with the decrease of water-soluble vitamin levels. Especially folate, VB1, VB2, VB6, niacin, biotin, and VC (RR values were 15.22, 1.86, 1.92, 2.11, 2.98, 2.14, 2.19, respectively) played an important role. Considering the status of high-risk human papillomavirus (HR-HPV) infection, our results showed that the low levels of folate, niacin, biotin could promote the poor prognosis of CINⅠ. Conclusions: The low-level of dietary water-soluble vitamins could facilitate the poor prognosis of CINⅠ. In addition, folate, niacin, biotin were more effective on HR-HPV positive women.

[Prognosis of high-risk HPV infection and its influences by vaginal micro-environmental factors].

Objective: To describe the characteristics of high-risk human papillomavirus (HR-HPV) infection and its influences by vaginal micro-environmental factors. Methods: A total of 421 women with HR-HPV infection and normal cervix diagnosed by pathology were selected from a community cohort established earlier by our research group for a 24-month follow-up. The baseline data were collected at enrollment. The vaginal micro-environmental factors were detected by using the combined detection kit of aerobic vaginitis and bacterial vaginosis. And the HPV was detected by using the flow-through hybridization technology. According to the HR-HPV infection status in baseline and 24 months of follow-up, with the prognosis characteristics of HR-HPV infection described, the impact of vaginal micro-environmental factors on the prognosis of HR-HPV infection was explored as well. Results: Among 390 HR-HPV infected women who completed 24 months of follow-up, the top five types of persistent HR-HPV infection rate appeared as HPV16 (24.1%), HPV58 (22.2%), HPV53 (21.7%), HPV52 (20.0%), and HPV39 (11.8%), respectively. The results showed that women with abnormal vaginal pH (aOR=1.74, 95%CI: 1.08-2.80), abnormal neuraminidase (aOR=2.70, 95%CI: 1.52-4.83), or abnormal leucocyte esterase (aOR=3.41, 95%CI: 2.13-5.44), the risk of HR-HPV persistent infection increased. The abnormalities of neuraminidase and leukocyte esterase could increase the risk of persistent infection of homotype and heterotypic HR-HPV. Conclusions: HPV16 was prone to persistent infection. Abnormalities of vaginal pH, neuraminidase, and leukocyte esterase might increase the risk of HR-HPV persistent infection. Both the abnormalities of neuraminidase and leukocyte esterase play an essential role in the HR-HPV persistent infection.

[The optimal model of diagnosis to low-grade cervical intraepithelial neoplasia by combined detecting vaginal micro-environmental factors, based on the high-risk HPV infection].

Objective: To investigate the diagnostic value of different vaginal micro-environmental factors in low-grade cervical intraepithelial neoplasia (CIN Ⅰ) and determine the optimal model in high-risk human papillomavirus (HR-HPV) infection. Methods: A total of 926 women, including 623 with normal cervical (NC) condition and 303 CINⅠ patients, had undergone pathological examinations, and were enrolled in the study. All the women were from a community previously established cohort. Vaginal cleanliness, pH, H2O2, ß-glucuronidase, coagulase, sialidase, and leukocyte esterase (LE) were detected by the combined detection method aerobic vaginitis/bacterial vaginosis in vaginal secretions. HPV genotyping was performed by using the flow-through hybridization technology. The data were analyzed by SAS 9.2 and SPSS 23.0. Results: The vaginal cleanliness, pH, sialidase, and LE were determined as the representative vaginal micro-environment factors by principal component analysis. Based on logistic regression theory to analyze the ROC curve, the results showed that the highest sensitivity was with pH value (76.2%), and the highest specificity was with sialidase (90.9%). The area under ROC curve were higher in combination detection modes of sialidase+LE (0.714), pH+sialidase+LE (0.719), vaginal cleanness+sialidase+LE (0.713) and pH+vaginal cleanness+sialidase+LE (0.709). According to HR-HPV infection status, the TOPSIS method was used to analyze the combined detection optimal model. Specifically, we found that the best diagnostic model was pH+sialidase +LE (Ci=0.585) in the HR-HPV positive group and vaginal cleanness+sialidase+LE (Ci=0.641) in the negative group. Conclusions: The combined detection of vaginal microenvironment factors could be used for auxiliary diagnosis for CINⅠ. It would be more effective when detecting pH, sialidase, and LE in HR-HPV positive women while vaginal cleanness, sialidase, and LE in HR-HPV negative women at the same time.

[Relationship between serum folate and CIN1 prognosis and its interaction with HR-HPV infection].

Objective: To evaluate the relationship between serum folate and the prognosis of cervical intraepithelial neoplasia grade I (CIN1) and the interaction between folate and high risk human papillomavirus (HR-HPV) infection. Methods: From a community-based married women cohort established in Jiexiu and Yangqu County of Shanxi Province from June to December 2014, a total of 564 eligible women with CIN1 by pathologically diagnosed were recruited. The pathological examination was performed again 12 months later. According to the prognosis of CIN1, participants were divided into CIN1 regression group, persistence and progression group, respectively. Nested case-control study was used to explore the relationship between serum folate and CIN1 prognosis, and additive model was used to analyze the interaction between serum folate and HR-HPV infection. Results: Among 564 CIN1 patients, 479 cases underwent pathological examination again, 331 were divided in CIN1 regression group and other 148 in persistence and progression group. The levels of serum folate in CIN1 regression group and persistence and progression group were (18.890±8.360) and (15.640±5.550) nmol/L, respectively, and the difference was statistically significant (Z=-6.937, P<0.001). HPV infection was detected in 154 patients, including 148 cases of HR-HPV infection and 6 cases of low risk human papillomavirus (LR-HPV) infection. Univariate analysis showed that there were significant differences in the age, passive smoking, frequency of pudendal cleaning, frequency of cleaning after sex, frequency of changing underwear, serum folate and HR-HPV infection between regression group and persistence and progression group (P<0.05). Multivariate logistic regression analysis showed that the frequency of pudendal cleaning (OR=0.422, 95%CI: 0.238-0.750), frequency of changing underwear (OR=0.574, 95%CI: 0.355-0.928), serum folate (13.06-16.78nmol/L: OR=4.806, 95%CI: 2.355-9.810; ≤13.05nmol/L: OR=8.378, 95%CI: 4.024-17.445), HR-HPV infection (OR=1.852, 95%CI: 1.170-2.933) were the independent influencing factors of CIN1 prognosis. Interaction analysis showed that the relative excess risk of low serum folate level and HR-HPV infection for the CIN1 persistence and progression was 4.992 (95%CI: 0.189-9.796), attributable proportion due to interaction was 0.552 (95%CI: 0.279-0.824), synergy index was 2.632 (95%CI: 1.239-5.588), aOR of serum folate≤16.78 nmol/L and HR-HPV infection positive was 9.055 (95%CI: 4.878-16.807). Conclusion: Low serum folate level could increase the risk of CIN1 persistence and progression, and might enhance the risk when combined with HR-HPV infection.

[Relations of human papillomavirus infection, vaginal micro-environmental disorder with cervical lesion].

Objective: To study the relations of human papillomavirus (HPV) infection, vaginal micro-environmental disorder with cervical lesion. Methods: A total of 1 019 women including 623 with normal cervical (NC), 303 with low-grade cervical lesion (CIN Ⅰ) and 93 with high-grade cervical lesion (CIN Ⅱ/Ⅲ) were enrolled in this study from the communities in Shanxi province, China. Case-control method was adopted, with NC as the control group and CIN as the case group. Related information was collected including demographic characteristics and relevant factors related to cervical lesions. HPV genotypes were detected by flow-through hybridization technology. Vaginal pH was detected by the pH test paper. Vaginal H(2)O(2) was detected by the combined detection kit of aerobic vaginitis and bacterial vaginosis. Vaginal cleanliness was detected by smear method. Results: Data from the unconditional logistic regression analysis showed that HPV infection (CINⅠ: aOR=1.39, 95%CI: 1.01-1.90; CINⅡ/Ⅲ: aOR=11.74, 95%CI: 6.96-19.80), H(2)O(2) (CINⅠ: aOR=2.09, 95%CI: 1.47-2.98; CINⅡ/Ⅲ: aOR=4.12, 95%CI: 2.01-8.43), cleanliness (CIN Ⅱ/Ⅲ: aOR=2.62, 95%CI: 1.65-4.14), and composite indicators (CINⅠ: aOR=1.67, 95%CI: 1.24-2.25; CINⅡ/Ⅲ: aOR=4.24, 95%CI: 2.30-7.81) all had increased the risk of cervical lesion and the trend on the severity (P<0.001) of cervical lesions. Additionally, we observed a synergic effect between HPV infection and vaginal micro-environmental composite indicator in CINⅡ/Ⅲ. With or without HPV infection, the ORs value of CINⅠ caused by vaginal micro-environment disorder remained close. Conclusions: Results from our study revealed that vaginal micro-environmental composite indicator could increase the risk for cervical lesion, in particular with the high-grade ones which all posed stronger risks when combined with HPV infection. However, the role of vaginal micro-environment disorder in the occurrence of CIN Ⅰ should not be ignored.

[The role of human papillomavirus 16 early genes E2 and E6 and heterogeneous nuclear ribonucleoprotein E2 in cervical carcinogenesis and their interaction effect].

Objective: To investigate the role of human papillomavirus (HPV) 16 early genes E2 and E6 and heterogeneous nuclear ribonucleoprotein (hnRNP) E2 and their interaction effects in the progression of the cervical cancer. Methods: Women with normal cervix (NC), low cervical intraepithelial neoplasia (CIN Ⅰ) and high cervical intraepithelial neoplasia (CIN Ⅱ/Ⅲ) from the cervical lesions cohort in Jiexiu County of Shanxi Province from June 2014 to September 2014, and patients with cervical squamous cell carcinoma (SCC) treated at the Second Hospital of Shanxi Medical University in the same period were enrolled in this study. There were 257 participants, about 67 NC cases (26.07%), 69 CIN Ⅰ cases (26.85%), 68 CIN Ⅱ/Ⅲ cases (26.46%), and 53 SCC cases (20.62%), respectively. The information of demographic characteristics, life health habits and cervical lesions were collected by using the structured questionnaire. Cervical exfoliated cells and cervical biopsy tissues were collected to detect the infection of HPV16 and the protein expression levels of hnRNP E2, HPV16 E2 and E6. According to the median-value of the protein expression levels of hnRNP E2, HPV16 E2 and E6 and E2/E6 ratio in the NC group, the study participants were divided into the high and low expression groups/ratio groups. The multivariate logistic regression model was used to analyze the correlation between HPV16 early gene E2 and E6, hnRNP E2 and cervical cancer. The interaction effect was analyzed by using the generalized multifactor dimensionality reduction (GMDR) model. Results: The ages of NC, CIN Ⅰ, CIN Ⅱ/Ⅲ and SCC groups were (47.00±9.07), (47.64±7.35), (46.37±8.67) and (51.26±8.03) years old, respectively. The multivariate logistic regression model analysis showed that the HPV16 E2 low expression, E6 high expression and E2/E6 low ratio could increase the risk of CIN Ⅱ/Ⅲ, about OR (95%CI) values 11.11 (1.63-75.56), 8.00 (1.28-50.04), and 9.75 (1.22-77.72), respectively and SCC, about OR (95%CI) values 14.22 (2.11-95.88), 10.33 (1.67-64.00), and 12.38 (1.56-97.91), respectively. The hnRNP E2 low expression could increase the risk of CIN Ⅱ/Ⅲ and SCC, about OR (95%CI) values 3.35 (1.39-8.10) and 5.53 (1.54-19.88). The result of GMDR showed that there were interaction effects of the hnRNP E2 low expression, HPV16 E2 low expression and HPV16 E6 high expression in both CIN Ⅱ/Ⅲ and SCC groups. Conclusion: The HPV16 E2 low expression, HPV16 E6 high expression and hnRNP E2 low expression could increase the risk of high-grade cervical intraepithelial neoplasia and cervical cancer, and they might have an important interaction effect in the progression of the cervical cancer.

[Proteomic analysis of aqueous humor in acute primary angle-closure glaucoma].

Objective: To analyze the difference among expression of aqueous humor proteins in acute primary angle-closure glaucoma (APACG). Methods: Case-control study. The patients with APACG combined cataract (APACG with cataract group) and patients with cataract (cataract group), who had undertaken surgical treatment at the Tianjin Medical University Eye Hospital from October 2016 to June2017 were collected. Upon receipt of patient's consent, 50 µl of aqueous humor were collected with 1 ml syringe and No.1 needle through the surgical access during the surgery, and then injected into a sterile collection tube to be stored at -80 ℃. Those proteins extracted from aqueous humor were analyzed by quantitative proteomic mass spectrometry. The differential significance test was performed by Maxquant significances A approach. The differential proteins of the two groups were screened and determined with the conditions of P<0.05 and difference multiple>2. The functions and signal pathway of differential proteins in aqueous humor were annotated in biological big data, on the basis gene ontology (GO) and the Kyoto gene and genomic encyclopedia (KEGG) analyses. Results: There were 3 males and 7 females with an average age of (68±6) years in the APACG group. The cataract group included 2 males and 8 females with an average age of (71±8) years. There were no statistical differences in gender ratio and age between the two groups (both P>0.05). A total of 91 differential proteins were detected in this experiment, including 50 up-regulated proteins (annexinA1, vimentin, S100 calcium binding protein A8, interleukin 6, C reactive protein, laminin ß2, etc.) and 41 down-regulated (keratin 85, γ-crystallin D, syntaxin-binding protein 5, semaphoring 4B, matrilin 2, cathepsin O, cadherin 4, semaphoring 3B, platelet-derived growth factor D, transforming growth factor ß, etc.). On one hand, the functions of differential proteins involved in many aspects. AnnexinA1, CD163, S100 calcium-binding protein A8, C reactive protein, interleukin 6 are involved in the inflammatory reaction, cadherin 4 and laminin ß2 regulate cell adhesion, matrilin 2, vimentin and laminin ß2 participate in tissue fibrosis; on the other hand, KEGG analysis showed that the differential proteins participate diverse signaling pathways such as phosphatidylinositol-3-kinase-protein kinase B signaling pathway, transformation growth factor ß signaling pathway, mitogen activated protein kinase signaling pathway, Toll-like receptor signaling pathway, the nuclear factor κ-light chain enhancer of the activated B cells signaling pathway, focal adhension and extracellular matrix receptor interaction pathway and so on. Conclusions: The expression of annexin A1 is significantly up-regulated in the aqueous humor in APACG, while some other factors such as transformation growth factor ß, cadherin-4, and matrilin 2 are down-regulated. The change of proteins in aqueous humor is related with the outbreak of APACG. (Chin J Ophthalmol, 2019, 55: 687-694).

[Effects of hnRNP E1 and both early genes E2 and E6 of HPV16 together with their interactions on cervical carcinogenesis].

Objective: To explore the effects of hnRNP E1 and both early genes E2 and E6 of HPV16 as well as their interactions in the progression of cervical carcinogenesis. Methods: Subjects of this study included 56 women with normal cervix (NC), 58 patients with low-grade cervical intraepithelial neoplasm (CINⅠ) and 50 patients with high-grade cervical intraepithelial neoplasm (CINⅡ/Ⅲ) who were all recruited from the 'Cervical Lesions Study Cohort Project' in Jiexiu of Shanxi province from June to September, 2014. Another 40 patients with cervical squamous cell carcinoma (SCC) were from the Shanxi Tumor Hospital during the same period. Information related to cervical lesions were collected, using a structured questionnaire, with cervical tissues and cervical exfoliated cells gathered from all the participants. HPV infection was detected by flow-through hybridization, while the levels of expression on hnRNP E1, HPV16 E2 and E6 protein were measured by Western Blot. Kruskal-Wallis H test, χ(2) test, trend χ(2) test were analyzed by SPSS 22.0 software, while interaction was evaluated by generalized multifactor dimensionality reduction (GMDR). Results: The overall infection rates of HPV16 related to CINⅠ (15.52%, 9/58), CINⅡ/Ⅲ (40.00%, 20/50) and SCC (67.50%, 27/40) groups were all higher than that of the NC group (8.93%, 5/56) and with an increasing trend on the severity of cervical lesions (trend χ(2)=43.613, P<0.001). The levels of expression on hnRNP E1 protein were significantly different in the groups with different cervical lesions (H=9.98, P=0.019), showing a decreasing trend with the severity of cervical lesions (trend χ(2)=9.495, P=0.002). The levels of expression on HPV16 E2 (H=16.20, P=0.001) and HPV16 E6 (H=15.44, P=0.001) were significantly different in groups with different cervical lesions. Results of GMDR showed that the best interaction model in both groups of CINⅡ/Ⅲ and SCC appeared as hnRNP E1 low expression, HPV16 E2 low expression and HPV16 E6 high expression. However, no similar interaction was seen in CINⅠ (P>0.05). Conclusions: Both low expressions of hnRNP E1 and abnormal expression of HPV16 E2 and E6 could increase the risk of high-grade CIN and cervical cancer. It seemed that they might have an important synergistic effect on the progression of cervical cancer.

[Interaction between vaginal micro-environment alterations and HPV16 infection in cervical intraepithelial neoplasia].

Objective: To explore the effect of vaginal micro-environment alterations and HPV16 infection and their interaction in the progression of cervical intraepithelial neoplasia. Methods: The participants of this study came from the cervical lesions study cohort in Shanxi province, including 623 women with normal cervical (NC), 303 patients with pathogenically diagnosed low-grade cervical intraepithelial neoplasia (CINⅠ) and 93 patients with pathogenically diagnosed high-grade cervical intraepithelial neoplasia (CINⅡ/Ⅲ). The data of the demographic characteristics of the study subjects and factors related to cervical intraepithelial neoplasia were collected, and HPV16 infection were detected by using flow-through hybridization technology and H(2)O(2), ß-glucuronidase, clotting enzyme, neuraminidase and leucocyte esterase in vaginal secretions were detected by using the combined detection kit of aerobic vaginitis and bacterial vaginosis. pH value and vaginal cleanliness were also detected at the same time. The database was established and analyzed by SPSS statistical software (version 22.0). Results: The HPV16 infection rate (trend χ(2)=55.45, P<0.001) and the abnormal rates of H(2)O(2) (trend χ(2)=26.19, P<0.001), pH (trend χ(2)=5.06, P=0.024), vaginal cleanliness (trend χ(2)=19.55, P<0.001), ß-glucuronidase (trend χ(2)=17.52, P<0.001) and neuraminidase (trend χ(2)=14.90, P<0.001) increased gradually along with the severity of cervical intraepithelial neoplasia, but the abnormal rates of clotting enzyme and leucocyte esterase showed no same trend. The results of GMDR model analysis showed that there was interaction between HPV16 infection and abnormalities of H(2)O(2), ß-glucuronidase, clotting enzyme and neuraminidase in CINⅠ group, and the interaction between HPV16 infection and the abnormalities of vaginal cleanliness, H(2)O(2), ß-glucuronidase and neuraminidase in CIN Ⅱ/Ⅲ group. Conclusion: Our findings indicated that the vaginal micro-environment alterations and HPV16 infection could increase the risk of cervical intraepithelial neoplasia, and they might have an important synergistic effect in the progression of cervical intraepithelial neoplasia.

[Interaction between polycyclic aromatic hydrocarbons and high risk human papillomavirus infection on cervical intraepithelial neoplasia].

Objective: To evaluate the effects of polycyclic aromatic hydrocarbons (PAHs) and high risk human papillomavirus (HR-HPV) infection and their interaction on the progression of cervical intraepithelial neoplasia. Methods: A total of 486 patients, including 208 women with normal cervix (NC), 154 patients with low-grade cervical intraepithelial neoplasm (CINⅠ), 124 patients with high-grade cervical intraepithelial neoplasm (CINⅡ/Ⅲ), were selected from the cervical lesions cohort from June to December, 2014. HR-HPV was detected by using flow-through hybridization technology and the urine concentration of 1-hydroxypyrene (1-OHP) was detected with high performance liquid chromatography. By using software SPSS 22.0, the χ(2) test, trend χ(2) test, Kruskal-Wallis H test, Nemenyi rank test and Spearman rank correlation analysis were performed. And the interaction effects were evaluated by additive model. Results: The HR-HPV infection rates in NC, CINⅠ and CINⅡ/Ⅲ groups were 27.9%, 37.0% and 58.9%, respectively. The urine concentrations of 1-OHP (µmol/molCr) were 0.07±0.09, 0.11±0.10 and 0.17±0.15, respectively. With increasing severity of the cervical lesions, the HR-HPV infection rate gradually increased (trend χ(2)=29.89, P<0.001) and the high exposure rate of PAHs gradually increased (trend χ(2)=27.94, P<0.001). HR-HPV infection was positively correlated with 1-OHP exposure (r=0.680, P<0.001). There was a positive additive interaction between HPV infection and PAHs exposure in CIN Ⅱ/Ⅲ group, but it was not found in CIN Ⅰ group. Conclusion: Both HR-HPV infection and high exposure of PAHs might increase the risk of cervical intraepithelial neoplasm, and might have a synergistic effect on the progression of high-grade cervical intraepithelial neoplasia.

[Long-term effect of environmental cadmium exposure on human body's mineral metabolic balance].

OBJECTIVE: To investigate the effect of long-term exposure to environmental cadmium on eight mineral element's metabolic balance of human body. METHODS: To choose a high cadmium area polluted by smelting and mining north of Guangdong province and a cadmium-free area with a similar economic level, and living and eating habit of residents as a contrast from April 2011 to August 2012. Stratified random sampling and clustered sampling method were adopted to choose the non-occupationally cadmium-exposed respondents who have lived in local area for more than 15 years, older than 40 years, having local rice and vegetable as the main dietary source, with simple and relatively stable diet, and without diabetes, kidney disease, thyroid disease, liver disease or other history of chronic disease. This study included 298 respondents, of whom 155 were in cadmium exposure group and 143 in control group. Questionnaires was used to acquire their health status and their morning urine samples were collected. Electrolytically coupled plasma mass spectrometry (ICP-MS) was used to test the concentrations of sodium(Na), magnesium (Mg), phosphorus (P), potassium (K), calcium (Ca), copper (Cu), zinc (Zn) and iodine (I). The Mann-Whitney U test method was used to compare the differences of concentrations of urinary cadmium, Na, Mg, P, K, Ca, Cu, Zn, I, and the ratio of Na to K (Na/K), Ca to P (Ca/P) between exposed group and control group.χ(2) test was used to compare the abnormal rate of urinary cadmium between exposed group and control group. Pearson correlation and multiple regression method were used to investigate the relationship between urinary cadmium levels, gender, age, smoking, passive smoking, and minerals. RESULTS: The urinary cadmium level P50 (P25-P75) in exposed group was 5.45 (2.62-10.68) µg/g·cr, which was higher than that of the control group, which was 1.69 (1.22-2.36) µg/g·cr (Z=-10.49,P<0.001). The abnormal rate of urinary cadmium was 51.6% (80/155), which was higher than that of the control group (2.8 %(4/143)) (χ(2)= 87.56, P<0.001). The urinary Ca, Cu, Zn, and I level P50 (P25-P75) of exposed group were 173.80 (114.40-251.70), 20.55 (14.95-28.44), 520.23 (390.25-647.15), and 246.94 (203.65-342.97) µg/g·cr, which were higher than those in control group (142.42 (96.87-179.11), 15.44 (12.26-20.98), 430.09 (309.85-568.78) and 213.85 (156.70-281.63) µg/g·cr, respectively) (Z values were-4.33,-5.04,-3.47 and-4.24, all P values <0.001). The urinary P, K level P50 (P25-P75) of exposed group were 582.50 (463.20-742.8), 890.10(666.00-1 305.40) µg/g·cr, which were lower than control group (694.50 (546.20-851.17), 1 098.58(904.53-1 479.18) µg/g·cr) (Z values were-3.36,-4.02, all P values <0.001). on Based the results of Pearson correlation analysis, urinary cadmium was positively correlated with urinary Ca, Cu, Zn, and I, and the correlation coefficients were 0.31, 0.61, 0.38, and 0.25, respectively (all P values <0.05). Based on the results of multiple regression analysis, urinary cadmium levels contributed most to the metabolic balance of urinary Ca, Cu, Zn and I. The standardized regression coefficients were 0.31, 0.59, 0.39, and 0.24, respectively (all P values<0.001). CONCLUSION: Long-term environmental exposure to cadmium affected the metabolic balance of Ca, Cu, Zn and I in human body.

[Cadmium burden and renal dysfunction among residents in cadmium-polluted areas: A 3-year follow-up study].

OBJECTIVE: To investigate dynamic change of cadmium body burden and renal dysfunction among residents living in cadmium-polluted areas. METHODS: From April to July of 2011, the cadmium-polluted areas of northern Guangdong province in China was chosen as the study site. Based on the levels of cadmium pollution in soil and rice, the survey areas were divided into low exposed group (average concentration of cadmium was 0.15-0.40 mg/kg, 0.5-1.0 mg/kg in rice and soil, respectively) and high exposed group (average concentration of cadmium was >0.40 mg/kg, >1.0 mg/kg in rice and soil, respectively). Stratified random sampling and cluster sampling method of epidemiological investigations were carried out among 414 local residents who lived in cadmium exposure areas for more than 15 years, aged above 40, and without occupational cadmium exposure, including 168 and 246 residents in low and high exposed group, respectively. From March to June of 2014, 305 respondents of those who participated in 2011 were successfully traced, including 116 and 189 respondents in low and high exposed group, respectively. We used health questionnaires to acquire their health status. Home-harvested rice and vegetable samples were collected using quartering method for detection of cadmium level, including 190 rice samples, 161 vegetable samples in 2011 and 190 rice samples, 153 vegetable samples in 2014. Urine specimens of residents were collected for the detection of urinary cadmium and creatinine as well as renal dysfunction biomarkers, namely, N-acetyl-beta-D-glucosamidase (NAG) and ß2-microglobulin (ß2-MG), respectively. In 2011 and 2014, Chi-square test was used to investigate the differences of abnormality of cadmium concentration in rice, vegetables and urinary cadmium, ß2-MG, and NAG that were expressed as odds ratio(OR) and 95% confidence intervals (95%CI). RESULTS: In 2011 and 2014, cadmium concentration P50 (P25-P75) in rice was 0.43 (0.17-1.10) mg/kg, and 0.42 (0.20-1.14) mg/kg, respectively (Z=-0.77,P=0.440). In 2011 and 2014, cadmium concentrations P50 (P25-P75) in vegetables were 0.13 (0.07-0.34) mg/kg, and 0.25(0.12-0.59) mg/kg, respectively, with abnormal rates of 38.5%(62/161) and 60.8%(93/153), respectively. In 2014, both average concentration and abnormal rate of cadmium in vegetables were higher than those in 2011 (Z=-4.69, P<0.001 and χ(2)=15.58,P<0.001). Concentrations of urinary cadmium P50 (P25-P75) in high exposed group were 7.90 (3.96-14.91) µg/g creatinine, 8.64 (4.56-17.60) µg/g creatinine in 2011 and 2014, respectively. Contrary to that in 2011, urinary cadmium of high exposed group was significantly increased in 2014 (Z=-2.80, P=0.005). In 2011 and 2014, concentrations of ß2-MG, NAG P50 (P25-P75) were 0.15(0.07-0.29) µg/g creatinine, 0.15 (0.07-0.45) µg/g creatinine, and 7.12 (5.05-10.65) U/g creatinine, 13.55(9.1-19.84) U/g creatinine, respectively, with abnormal rates of 7.5% (23/305), 15.1% (46/305), 8.2% (25/305) , and 33.8% (103/305), respectively. Compared with baseline in 2011, average concentrations of ß2-MG, NAG significantly increased in 2014 (Z=-2.263, P=0.024 and Z=-12.52, P<0.001), and abnormal rates of ß2-MG, NAG were also higher in 2014 (χ(2)=15.61 , P<0.001 and χ(2)=64.72, P<0.001), with odds ratio(OR) of 2.00 (95%CI:1.23-3.24) and 4.12 (95%CI:2.87-5.92). CONCLUSION: Environmental cadmium pollution of crops such as rice and vegetables in survey areas continued to remain high. Body burden of cadmium might kept at sustainably high levels and renal dysfunction was worsened after continuous, long-term cadmium exposure. Our results suggested that NAG might be more sensitive than ß2-MG to serve as an indicator for an individual's future tubular function.