1,4,5,6,7,8­Hexahydropyrido[4,3­d]pyrimidine inhibits HepG2 cell proliferation, migration and invasion, and induces apoptosis through the upregulation of miR­26b­5p by targeting CDK8.

1,4,5,6,7,8-Hexahydropyrido[4,3-d]pyrimidine (PPM) promotes apoptosis of HepG2 cells and serves a role in tumor suppression. However, the role of microRNA (miRNA) regulation in initiating apoptosis remains unclear. Therefore, the present study performed reverse transcription-quantitative PCR to investigate the association between PPM and miRNA, which demonstrated that PPM upregulated the expression of miR-26b-5p. Wound healing and Transwell assays showed that PPM inhibited the migration and invasion of HepG2 cells, and EdU staining experiments showed that PPM inhibited the proliferation of HepG2 cells. Transfection with miR-26b-5p inhibitor reversed the effects of PPM on HepG2 cells. Flow cytometry results showed that PPM promoted apoptosis of HepG2 cells by upregulating miRNA (miR)-26b-5p, and Western blotting results showed that PPM promoted the expression of apoptosis-associated protein Bax and inhibited the expression of Bcl-2 by upregulating miR-26b-5p. Using a proteomic approach combined with bioinformatics analysis, CDK8 was identified as a potential target of miR-26b-5p and was downregulated by miR-26b-5p overexpression. However, PPM induced HepG2 cell cycle arrest without the involvement of miR-26b-5p. Western blotting results showed that PPM upregulation of miR-26b-5p suppresses NF-κB/p65 signaling pathway in HepG2 cells by targeting of CDK8. The present results suggested that miR-26b-5p may function as a target gene of PPM and may serve a role in hepatocellular carcinoma treatment.

Synthesis and Characterization of Random Block Hydroxyl-Terminated Polyfluoroether-Based Polyurethane Elastomers with Fluorine-Containing Side Chains.

Polype ntafluoropropane glycidyl ether (PPFEE), a new random block hydroxyl-terminated polyfluoroether, was synthesized successfully by cationic ring-opening polymerization of 2-(2,2,3,3,3-pentafluoropropoxymethyl) oxirane, and its molecular structure was confirmed by Fourier transform infrared spectroscopy, nuclear magnetic resonance spectrometry, and gel permeation chromatography. The PPFEE-based polyurethane elastomers featuring fluorine in their side chains were prepared using PPFEE as soft segments, polyisocyanate polyaryl polymethylene isocyanate as hard segments, and dibutyltin dilaurate as catalysts under different curing conditions. The microphase separation, mechanical performance, and thermal behavior of the elastomers were investigated by differential scanning calorimetry, uniaxial tensile test, and thermal gravimetric analysis, respectively. Based on the results, the percentage of hard segments dissolved into the soft segments of elastomers was opposite to the change in breaking strength. The PPFEE-based polyurethane elastomer cured with 20 wt% PAPI at the curing temperature of 50 °C displayed the maximum tensile elongation of 2.26 MPa with an elongation at break of nearly 150%. The increased contents of PAPI can effectively strengthen the tensile strength, and the maximum tensile elongation was 3.04 MPa with an elongation at break of nearly 90% when the content of PAPI was 26 wt%. In addition, the PPFEE-based polyurethane elastomers exhibited excellent resistance to thermal decomposition and a sharp weight loss temperature at around 371 °C. All the results demonstrated that the PPFEE may be a potential polymeric binder as one of the ingredients applied to future propellant formulations.

Complex metabolic interactions between ovary, plasma, urine, and hair in ovarian cancer.

Ovarian cancer (OC) is the third most common malignant tumor of women accompanied by alteration of systemic metabolism, yet the underlying interactions between the local OC tissue and other system biofluids remain unclear. In this study, we recruited 17 OC patients, 16 benign ovarian tumor (BOT) patients, and 14 control patients to collect biological samples including ovary plasma, urine, and hair from the same patient. The metabolic features of samples were characterized using a global and targeted metabolic profiling strategy based on Gas chromatography-mass spectrometry (GC-MS). Principal component analysis (PCA) revealed that the metabolites display obvious differences in ovary tissue, plasma, and urine between OC and non-malignant groups but not in hair samples. The metabolic alterations in OC tissue included elevated glycolysis (lactic acid) and TCA cycle intermediates (malic acid, fumaric acid) were related to energy metabolism. Furthermore, the increased levels of glutathione and polyunsaturated fatty acids (linoleic acid) together with decreased levels of saturated fatty acid (palmitic acid) were observed, which might be associated with the anti-oxidative stress capability of cancer. Furthermore, how metabolite profile changes across differential biospecimens were compared in OC patients. Plasma and urine showed a lower concentration of amino acids (alanine, aspartic acid, glutamic acid, proline, leucine, and cysteine) than the malignant ovary. Plasma exhibited the highest concentrations of fatty acids (stearic acid, EPA, and arachidonic acid), while TCA cycle intermediates (succinic acid, citric acid, and malic acid) were most concentrated in the urine. In addition, five plasma metabolites and three urine metabolites showed the best specificity and sensitivity in differentiating the OC group from the control or BOT groups (AUC > 0.90) using machine learning modeling. Overall, this study provided further insight into different specimen metabolic characteristics between OC and non-malignant disease and identified the metabolic fluctuation across ovary and biofluids.

Associations of benzotriazoles and benzothiazoles with estrogens and androgens among pregnant women: A cohort study with repeated measurements.

People are extensively exposed to benzotriazoles (BTRs) and benzothiazoles (BTHs) derivatives, which are environmental pollutants that may possess endocrine-disrupting potential; however, no epidemiological evidence is available on the associations of BTRs and BTHs with estrogens and androgens. This study aimed at investigating the associations of BTRs and BTHs with estrogens and androgens among pregnant women. Based on a prospective cohort study, we included 459 pregnant women who donated a complete serial of urine samples at each trimester and had repeated measurements of four BTRs, four BTHs, three estrogens (estrone, 17ß-estradiol, and estrio), and two androgens (dehydroepiandrosterone and testosterone) in the urine samples. Associations of repeatedly measured BTRs and BTHs with maternal urinary estrogens and androgens were analyzed, and the cross-sectional associations were also analyzed. Tolyltriazole (TTR) (≥59.3%) and benzothiazole (BTH) (≥93.5%) had the highest detection rate among the BTRs and BTHs, respectively. Repeated measurement analysis and cross-sectional analysis consistently found the target BTRs and BTHs were positively associated with 17ß-estradiol, estriol, and testosterone, while the trend of the associations with estrone and dehydroepiandrosterone was inconsistent. Among the positive associations with 17ß-estradiol, estriol, and testosterone, the percent of change in estriol associated with TTR was the most prominent [28.5% (95% confidential interval: 24.2%, 32.9%) for each doubling in TTR]. The significant associations with estrone, estriol, testosterone, and dehydroepiandrosterone were stronger among pregnant women who gave birth to a boy than those who gave birth to a girl. These findings add epidemiological evidence on the endocrine-disrupting potential of BTRs and BTHs and highlight the importance of focusing on the health outcomes of BTRs and BTHs related to disturbed estrogens and androgens. Future studies are needed to validate these findings and explore the underlying mechanisms.

Aflatoxin B1 induces microglia cells apoptosis mediated by oxidative stress through NF-κB signaling pathway in mice spinal cords.

Many studies have shown that aflatoxin B1 (AFB1) can cause cytotoxicity in numerous cells and organs induced by oxidative stress. However, the toxic effects and related mechanism of AFB1 on the microglia cells in the spinal cords have not been studied yet. Our results showed that AFB1 significantly reduced the number of microglia cells, increased the oxidants (malonaldehyde and hydrogen peroxide) but decreased the anti-oxidants (superoxide dismutase and total antioxidant capacity) in a dose dependent manner in mice spinal cords. In addition, AFB1 significantly increased the oxidative stress, promoted apoptosis and cell cycle arrest in G2-M phase, and activated NF-κB phosphorylation in BV2 microglia cells. However, the addition of active oxygen scavenger N-acetylcysteine can significantly reduce the ROS production, improve cell cycle arrest, reduce apoptosis, and the expression of phosphorylated NF-κB in BV2 microglia cells. These results indicate that AFB1 induces microglia cells apoptosis through oxidative stress by activating NF-κB signaling pathway.

Epidemiological and co-infection characteristics of common human coronaviruses in Shanghai, 2015-2020: a retrospective observational study.

The coronavirus disease (COVID-19) pandemic is a major challenge worldwide. However, the epidemic potential of common human coronaviruses (HCoVs) remains unclear. This study aimed to determine the epidemiological and co-infection characteristics of common HCoVs in individuals with influenza-like illness (ILI) and severe acute respiratory infection (SARI). This retrospective, observational, multicentre study used data collected from patients admitted to nine sentinel hospitals with ILI and SARI from January 2015 through December 2020 in Shanghai, China. We prospectively tested patients for a total of 22 respiratory pathogens using multi-real-time polymerase chain reaction. Of the 4541 patients tested, 40.37% (1833/4541) tested positive for respiratory pathogens and 3.59% (163/4541) tested positive for common HCoVs. HCoV infection was more common in the non-endemic season for respiratory pathogens (odds ratio: 2.33, 95% confidence interval: 1.64-3.31). HCoV-OC43 (41.72%, 68/163) was the most common type of HCoV detected. The co-infection rate was 31.29% (51/163) among 163 HCoV-positive cases, with HCoV-229E (53.13%, 17/32), the HCoV type that was most frequently associated with co-infection. Respiratory pathogens responsible for co-infections with HCoVs included parainfluenza virus, rhinovirus/enterovirus, influenza A virus, and adenovirus. Furthermore, we identified one patient co-infected with HCoV-OC43 and HCoV-NL63/HKU1. The prevalence of common HCoVs remains low in ILI/SARI cases, in Shanghai. However, the seasonal pattern of HCoVs may be opposite to that of other respiratory pathogens. Moreover, HCoVs are likely to co-exist with specific respiratory pathogens. The potential role of co-infections with HCoVs and other pathogenic microorganisms in infection and pathogenesis of ILI and SARI warrants further study.

Discovery of anti-hepatoma agents from 1,4,5,6,7,8-hexahydropyrido[4,3-d]pyrimidine by inhibiting PI3K/AKT/NF-κB pathway activation.

In order to obtain new anti-hepatoma drugs with low toxicity, some 1,4,5,6,7,8-hexahydropyrido[4,3-d]pyrimidines (PPMs, 4a-t) were synthesized in this study. Many of them showed significant anti-hepatoma effects against HCC cells and low toxicity toward HHL-5 cells. Combined with their anti-hepatoma activity and toxicity, 4-CF3-substituted 4k was selected as an effective lead compound. Preliminary mechanistic studies revealed that 4k could up-regulate the expression levels of Bax and caspase-3 proteins, down-regulate the expression levels of Bcl-2 protein, promote significant apoptosis of HepG2, and block cells in G2-M phase to prevent cells from completing mitosis. Also, 4k could significantly inhibit the activation of PI3K/AKT/NF-κB pathway by blocking the phosphorylation of PI3K, AKT, NF-κB/p65 and IFN-γ-induced nuclear transport. Docking analysis showed that 4k could reasonably bind to the active sites of Bcl-2, NF-κB/p65, PI3K and AKT. This result suggested that 4k could be used as a new type of NF-κB inhibitor, which provides a scientific basis for further research into the treatment of hepatoma.

Association between urinary paraben concentrations and gestational weight gain during pregnancy.

Parabens, a group of endocrine-disrupting chemicals, have been associated with obesity in previous studies. However, there is a paucity of literature regarding the effects of paraben exposures on gestational weight gain (GWG), a considerable predictor of obesity risk in both mothers and offspring later in life. The aim of the present study was to evaluate the associations between urinary paraben concentrations and GWG during the three trimesters of pregnancy. We collected urine samples from 613 pregnant women during the first, second, and third trimesters of their pregnancies between 2014 and 2015 in Wuhan, China. The urine concentrations of five parabens, including methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), butylparaben, and benzylparaben, were measured. Gestational weight in each trimester and prepregnancy weight were used to calculate trimester GWG. Linear mixed models were used to evaluate the trimester-specific and overall associations between paraben exposures and GWG rate (trimester GWG divided by the gestational week of the weight measurement, kg/week). We performed stratified analysis to further explore the potential effect modification by prepregnancy BMI. In the trimester-specific association analyses, the first-trimester concentrations MeP, EtP, PrP, and ∑parabens (sum of all five parabens's molar concentrations) were associated with an increased first-trimester GWG rate, and these associations were stronger than those of the second or third trimesters. The overall association analysis showed that increased trimester GWG rates were associated with the combined effects of exposure to MeP, PrP, or ∑parabens during all three trimesters. Stratified analysis showed that higher paraben exposures were associated with higher trimester GWG rates among overweight/obese women that among normal-weight or underweight women. Our results showed that paraben exposures were positively associated with trimester GWG rate during pregnancy, especially during the first trimester. Replicated research in populations exposed to higher paraben levels is needed in the future.

Determination of hormones in human urine by ultra-high-performance liquid chromatography/triple-quadrupole mass spectrometry.

Steroid hormones play a critical role in maintaining the homeostasis of human metabolism. Urine as a noninvasive sample has been extensively used in clinical diagnosis for hormones homeostasis. In this study, the simultaneous characterization of fourteen hormones in urine was performed based on ultra-high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (UPHLC/ESI(+)-MS/MS) with multiple reaction monitoring in the positive ionization mode. The target hormones were cortisone, cortisol, 11-deoxycortisol, aldosterone, corticosterone, 11-deoxycorticosterone, progesterone, 17-OH-progesterone, pregnenolone, estrone, estradiol, estriol, testosterone and dehydreopiandrosterone. ß-Glucuronidase/sulfatase deconjugation and liquid-liquid extraction (LLE) were conducted for the determination of urinary hormones (free + conjugated forms). The limits of detection (LODs) ranged from 0.2 ng/mL (11-deoxycortisol and testosterone) to 1 ng/mL (cortisone). The extraction recovery of the targeted compounds ranged from 87% to 127%, indicating sufficient extraction efficiency for the LLE process. Intraday precision was below 10% and the accuracy ranged from 84% to 122%. The profiling analysis of hormones in urine samples helps to understand the metabolic state of biological systems and can be employed as a diagnostic tool in diseases developed by endocrine-disrupted systems.

Trimester-specific, gender-specific, and low-dose effects associated with non-monotonic relationships of bisphenol A on estrone, 17ß-estradiol and estriol.

BACKGROUND: Bisphenol A (BPA) may cause some adverse effects on human health by mimicking estrogen activities. In vitro andanimalstudies have observed the non-monotonic associations between BPA and natural estrogens, but the evidence in human study is lacking, particularly at multiple points in time during pregnancy. OBJECTIVE: We aimed to examine the relationships between BPA and estrogens in the three trimesters among Chinese pregnant women and their gender variations. METHODS: This study included 851 participants from a birth cohort conducted in Wuhan, China between 2014 and 2015. We measured concentrations of BPA and three estrogens (estrone (E1), 17ß-estradiol (E2) and estriol (E3)) in urine samples collected in the three trimesters of pregnancy (mean for each visit: 13.0, 23.6, and 35.9 weeks' gestation). We calculated the estimated daily intakes using urinary BPA concentrations and compared them with the tolerable intake value to assess potential health risks. We used multivariate linear regression models stratified by trimester and gender to explore trimester-specific and gender-specific associations of BPA with E1, E2, and E3. RESULTS: We found the decreased levels of estrogens (ß < 0, P < 0.05) in the upper BPA quartiles over three trimesters, except for the elevated levels of E3 (ß = 0.20, 95% CI: 0.02, 0.38) in the highest BPA quartile in the 2nd trimester. There were significant non-linear associations (overall associations P < 0.05, non-linear associations P < 0.05) between BPA and E3 in the three trimesters. In the gender-stratified analysis, we observed significant negative relationships (ß < 0, P < 0.05) between BPA and E2 among mothers carrying male fetuses in the 1st trimester and significant associations between BPA and E3 among mothers carrying female fetuses in the 2nd trimester. However, we found no significant relationship between BPA and E2 among mothers carrying female fetuses over three trimesters. CONCLUSIONS: Our findings support experimental evidence of non-monotonic relationships between BPA and three major estrogens, even at low doses of BPA. Mothers delivering male fetuses may be more sensitive to E2 at early pregnancy, and those delivering female fetuses may be more susceptive to E3 at mid-pregnancy.

Association of in utero hexachlorocyclohexane exposure with gestational age.

As endocrine disrupting chemicals, hexachlorocyclohexane (HCH) isomers were reported to impair the intrauterine growth. Although the findings of HCHs with preterm birth were well established, the associations with gestational age were limited. In the present study, we examined whether exposure to HCHs would influence gestational age. The study population included 1028 pregnant women and their offspring who were born in 2014-2015 from a birth cohort in Wuhan, China. Associations of the cord serum HCH levels with gestational age were estimated using generalized linear models. We found higher HCH levels in pregnant women, who were elder, had higher body mass index (BMI) before pregnancy, received higher education, or were exposed to smoking passively. For term birth, the 3rd tertiles of α-HCH and γ-HCH were significantly associated with shorter gestational age [crude ß = -1.017, confidence interval (CI): - 2.017, - 0.018 for α-HCH, crude ß = -1.068, CI: - 2.067, - 0.070 for γ-HCH], and relationships were similar after adjusted by covariates. Stratified analysis showed positive associations between α-HCH and gestational age for mothers younger than 25 years old (adjusted ß = 0.610, CI: 0.061, 1.158), while showing negative relationships for mothers elder than 35 years old (adjusted ß = -1.365, CI: -2.414, -0.317). In summary, our results indicated cord serum levels of HCHs were associated with gestational age at birth.

Chaperonin containing TCP1 subunit 5 is a tumor associated antigen of non-small cell lung cancer.

Novel tumor antigens and their related autoantibodies have tremendous potential for early diagnosis of non-small cell lung cancer (NSCLC). In this study, we identify antigens from NSCLC tissue and autoantibodies in sera of patients with NSCLC using a modified proteomics-based approach. We seperated and identified four NSCLC-associated proteins extracted from the cytosol in tumor tissues by mini-two-dimensional gel electrophoresis, followed by Western blot and hybridization with individual sera for confirmation of antibody binding. Of the proteins we identified, we selected 58 kDa chaperonin containing TCP1(T-Complex Protein 1) subunit 5 (CCT5) for validation. Serum levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragments (CYFRA 21-1) were measured in all serum samples with an immunoluminometric assay and a receiver operating characteristic (ROC) curve was analyzed for autoantibodies against CCT5, CEA and CYFRA 21-1. The results show that CCT5 can induce an autoantibody response in NSCLC sera and show higher expression in NSCLC tissues by immunohistochemistry and Western blot. Anti-CCT5 autoantibody was found in 51% (23/45) of patients with NSCLC, but only 2.5% (1/40) in non-tumor individual controls. A receiver operating characteristic curve constructed with a panel of autoantibodies against CCT5 (AUC=0.749), CEA (AUC=0.6758), and CYFRA 21-1(AUC=0.760) show a sensitivity of 51.1% and 97.5% specificity in discriminating NSCLC from matched controls. These results indicate the potential utility of screening autoantibodies in sera, show that CCT5 could be used as a biomarker in cancer diagnosis.

Curative effect of 1.88-mg and 3.75-mg gonadotrophin-releasing hormone agonist on stage III-IV endometriosis: Randomized controlled study.

AIM: To compare the therapeutic effect of 1.88-mg and 3.75-mg gonadotrophin-releasing hormone agonist (GnRHa) in the treatment of stage III-IV endometriosis after laparoscopic surgery. METHODS: Fifty patients with stage III-IV endometriosis diagnosed on laparoscopy were randomized into two groups according to GnRHa dose. Sex hormone level, symptoms of estrogen deficiency and lumbar vertebrae bone density were compared and analyzed between the two groups. RESULTS: Bone density was decreased in both groups at 20 weeks after treatment, and the degree of bone density loss in the full-dose group (5.6%) was higher than in the half-dose group (1.2%; P < 0.05). Surgery combined with the 3.75-mg GnRHa or with the 1.88-mg GnRHa relieved the degree of dysmenorrhea, although one case of light dysmenorrhea occurred in each group, but there was no significant difference (P > 0.05) after resumption of menstruation. Both groups had symptoms of perimenopause at 8 weeks after treatment (P > 0.05), but change in Kupperman score with time differed between the groups. At 16, 20 weeks after treatment, the symptoms of perimenopause in the half-dose group were improved, and Kupperman score was lower than at 8 weeks after treatment. In the full-dose group, however, Kupperman score was higher than at 8 weeks after treatment and higher than in the half-dose group (P < 0.05). After treatment, follicle-stimulating hormone and luteinizing hormone both decreased in both groups (P < 0.05), but there was no difference between the two groups (P > 0.05). Estradiol (E2) in the full-dose group was significantly lower than in the half-dose group (P < 0.05). CONCLUSION: The 1.88-mg GnRHa treatment can be used in III-IV endometriosis patients after laparoscopic surgery, to reduce perimenopausal symptoms, significantly improve bone loss, and achieve a good clinical effect.

Critical Windows of Prenatal Exposure to Cadmium and Size at Birth.

Prenatal cadmium (Cd) exposure has been associated with adverse birth outcomes, but the findings of previous studies are inconsistent. We measured Cd concentrations in urine samples at or near 13, 24, and 35 gestational weeks from 282 women in Wuhan, China. We used generalized estimating equation models to assess the associations between maternal creatinine adjusted urinary Cd concentrations at each trimester and birth size. A significant inverse association was observed between higher maternal Cd levels measured during the 1st trimester and birth size in girls. For each log unit increase in Cd (µg/g creatinine) levels from the 1st trimester, there was a decrease in birth weight by 116.99 g (95% confidence interval (CI): -208.87, -25.11 g). The Cd levels from the 1st and 2nd trimesters were also borderline significantly associated with ponderal index in girls. Joint estimation of trimester-specific effects suggested that associations with Cd levels for ponderal index (pint = 0.02) were significantly different across trimesters, and differences for effects across trimesters for birth weight were marginally significant (pint = 0.08) in girls. No significant associations were observed between Cd levels from any trimester and birth size in boys. Maternal Cd exposure during earlier periods of pregnancy may have a larger impact on delayed fetal growth.

Urinary metabolomics revealed arsenic exposure related to metabolic alterations in general Chinese pregnant women.

Arsenic exposure is considered a major environmental threat to human health. It is already known that high-level arsenic exposure has adverse effects on human health. Since the pregnant women are known to be more susceptible to some chemical exposures than ordinary people, the understanding regarding the health effects of low-level arsenic exposure on pregnant women is critical and remains unclear. The aim of this study is to investigate the urinary metabolic changes of pregnant women exposed to low-dose arsenic, and to identify biomarkers from metabolomics analysis. Urine samples of 246 pregnant women were collected in the first trimester of pregnancy and were divided into three groups based on the tertile distribution of urinary arsenic concentrations which were determined using inductively coupled plasma mass spectrometry (ICP-MS). Changes in the metabolite profile were measured using ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF MS). Arsenic- related metabolic biomarkers were investigated by comparing the samples of the first and third tertiles of arsenic exposure classifications using a partial least-squares discriminant model (PLS-DA). Nine urine potential biomarkers were putatively identified, including LysoPC (14:0), glutathione, 18-carboxy-dinor-LTE4, 20-COOH-LTE4, cystathionine ketimin, 1-(beta-d-ribofuranosyl)-1,4-dihydronicotinamide, thiocysteine, p-cresol glucuronide and vanillactic acid. The obtained results showed that environmental arsenic exposure, even at low levels, could cause metabolite alterations in pregnant women which might be associated with adverse health outcomes. This is the first report on metabolic changes in pregnant women for arsenic exposure. The findings may be valuable for the arsenic risk assessment for pregnant women.

An Evaluation of the Cobas4800 HPV Test on Cervico-Vaginal Specimens in Liquid versus Solid Transport Media.

OBJECTIVES: Determine the ability of the Cobas 4800 assay to detect high-risk human papillomavirus (HrHPV) and high-grade cervical lesions when using cervico-vaginal samples applied to liquid medium and solid media cards compared to a direct cervical sample. METHODS: Two cervico-vaginal specimens (pseudo self-collected) were obtained from 319 women. One was applied to an iFTA Card (FTA) then the brush placed in liquid-based medium (LSELF); the other was applied to a new solid media: POI card (POI). The clinical performance of Cobas4800 assay using the three aforementioned specimens was compared to direct collected endocervical specimens in liquid media (LDOC). RESULTS: The overall agreements of HrHPV detection were 84.2% (LSELF vs. LDOC), 81.0% (FTA vs. LDOC), and 82.3% (POI vs. LDOC). LSELF, FTA and POI identified 98.0%, 79.6%, and 97.5% positive cases of LDOC. Sensitivity to identify CIN2+ were 98.4% (LSELF), 73.8% (FTA), 95.1% (POI), and 93.4% (LDOC) respectively. FTA had 78.1% and 90.4% agreement with the LSELF samples for all HrHPV and HPV16/18 detection respectively, while POI had 91.6% for both. CONCLUSIONS: Cobas4800 HPV test combined with cervico-vaginal specimens applied to both liquid media and POI solid card are accurate to detect HrHPV infection and high-grade cervical lesions as compared with direct endocervical samples in liquid media.

Serum GROß: a potential tumor-associated biomarker for colorectal cancer.

OBJECTIVE: This study aimed to confirm the potential of growth-related gene product ß (GROß) as a biomarker for colorectal cancer. We compared serum GROß levels in patients with colorectal cancer, healthy individuals and individuals with non-tumor diseases. METHODS: We measured serum GROß levels with enzyme-linked immunosorbent assay in patients with colorectal cancer (123 preoperative samples and 66 postoperative samples), 88 healthy controls and 125 individuals with other diseases. Serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were measured in all samples with an immunoluminometric assay. Statistical analyses were performed to determine associations between serum GROß levels and clinical parameters for colorectal cancer. A receiver operating characteristic (ROC) curve was analyzed for GROß, CEA and CA19-9. RESULTS: The serum GROß levels were much higher in patients with colorectal cancer (median: 96.15 pg/ml) than those in healthy controls (median: 43.28 pg/ml, P < 0.01) and other disease controls (median: 57.30 pg/ml, P < 0.01). Serum GROß levels in colorectal cancer were correlated positively with tumor-node-metastasis staging (P < 0.01) and the depth of infiltration (P < 0.05), but not with the histological grade, tumor embolus, lymph node metastasis, gross pathologic tumor type, or patient gender. The sensitivity and specificity of the assay for serum GROß were 56.1% (69/123) and 95.31% (203/213), respectively. The area under the ROC curve constructed with GROß (0.834) was larger than that constructed with CEA (0.739) or CA19-9 (0.676) for discriminating colorectal cancer from matched controls. CONCLUSION: These preliminary results suggested that the serum GROß level could be a useful biomarker for colorectal cancer diagnoses.

[Investigation on the prevalence of high risk human papillomavirus and cervical cancer among adult women, in Shenzhen].

OBJECTIVE: To investigate the prevalence of high risk human papillomavirus (HPV) genital infection and cervical cancer in adult women from Shenzhen. METHODS: Cluster sampling was used to investigate the prevalence of HPV infection and cervical cancer from women aged 20 - 59 years old living in Luohu, Futian, Nanshan, Longgang and Baoan districts in Shenzhen from April 2006 to April 2010. All women were detected for liquid-based cytology test (LCT) or Thinprep cytologic test (TCT) and high-risk HPV-DNA test with hybrid capture II (HC-II). All women with ≥ ASC-US by cytology and/or a positive HC-II test were asked to return for colposcopy and four-quadrant biopsy. Endocervical curettage was performed. Pathological finding were used as the gold standard of the diagnosis of cervical intraepithelial neoplasia. RESULTS: 10 210 women were involved in the study and 10 017 of them having completed data. The overall positive rate of high-risk HPV-DNA was 16.29%. HPV positive rates in 20-, 30-, 35-, 40-, 45-, 50-59 age groups were 17.37%, 15.59%, 16.33%, 14.74%, 17.16% and 17.98%, respectively. The curve of HPV infection rates in different age groups appeared a 'W' shape. HPV infection rates in the 25-years-olds and 50-59 year-olds groups were significantly higher than the other age groups (χ(2) = 4.50, P = 0.03). The overall prevalence rate of cervical intraepithelial lesions (CIN) was 7.52%, of which the prevalence rates of low-grade cervical intraepithelial lesions (CIN I) was 5.32% high-grade cervical intraepithelial lesions (CIN II/III) was 2.21%, cervical cancer was 0.12%. The prevalence of CIN I was significantly higher than the CIN II/III (χ(2) = 134.15, P < 0.001). The prevalence of cervical cancer in 45-age group was 0.12%, the highest. HPV infection rates increased with the grades of cervical lesions including women without CIN as 44.31%, in CINI as 70.73%, in CINII as 86.73%, and in CIN III as 96.75% and in cancer as 100.00%. The HPV infection rates were different in districts (χ(2) = 17.81, P = 0.03), with Futian and Luohu higher than those of Nanshan, Longgang and Baoan district. The prevalence rate of CIN in Baoan was lower than other districts. The CIN prevalence rates were not significantly different among the other districts of Shenzhen (χ(2) = 4.84, P = 0.18). CONCLUSION: The prevalence of cervical cancer was low in adult women living in Shenzhen, with cervical lesions still in the early stage. Prevention of HPV infection and treatment of CIN were the key points for the prevention of cervical cancer.

A population-based clinical trial comparing endocervical high-risk HPV testing using hybrid capture 2 and Cervista from the SHENCCAST II Study.

Our objective was to directly compare the accuracy of the high-risk human papillomavirus (HPV) assays, Hybrid Capture 2 (hc2; Qiagen, Gaithersburg, MD) and Cervista (Hologic, Bedford, MA), in diagnosing cervical intraepithelial neoplasia (CIN) 3 or worse (cancer). A population-based, cross-sectional study (The Shenzhen Cervical Cancer Screening Trial II) was conducted in Guangdong Province in China. Three high-risk HPV assays, self and direct cervical sampling and cytology, were studied. Abnormal results on any of 6 study tests (33%) resulted in referral to colposcopy. At colposcopy, every patient had at least 5 cervical biopsy specimens obtained. For 8,556 women between the ages of 25 and 59 years (mean, 38.9 years), the rate for CIN 3 or worse was 1.6% (141/8,556). The sensitivity (confidence interval) values for CIN 3 or worse were 97.9% (94.0%-99.6%) and 95.1% (90.0%-98.0%) for hc2 and Cervista, respectively (P > .05). The specificity (confidence interval) values were 87.8% (87.1%-88.5%) and 90.3% (89.6%-90.9%), respectively (P < .05). Differences in accuracy in diagnosing CIN 3 or worse with the hc2 and Cervista tests are minor and result from the decisions made in selecting the cut points.