Pathological features and diagnostic significance of lung biopsy in occupational lung diseases / 中华病理学杂志

Objective: To investigate the clinicopathological characteristics of occupational lung diseases, to reduce the missed diagnoses and misdiagnoses of the diseases and to help standardize the diagnosis and treatment of these patients. Methods: A total of 4 813 lung biopsy specimens (including 1 935 consultation cases) collected at the Department of Pathology, Nanjing Drum Tower Hospital, Nanjing, China from January 1st, 2017 to December 31th, 2019 were retrospectively analyzed. Among them, 126 cases of occupational lung diseases were confirmed with clinical-radiological-pathological diagnosis. Special staining, PCR and scanning electron microscopy were also used to rule out the major differential diagnoses. Results: The 126 patients with occupational lung diseases included 102 males and 24 females. All of them had a history of exposure to occupational risk factor(s). Morphologically, 68.3% (86/126) of the cases mainly showed pulmonary fibrotic nodules, dust plaque formation or carbon end deposition in pulmonary parenchyma. 16.7% (21/126) of the cases mainly showed welding smoke particle deposition in the alveolar cavity and lung interstitium while 15.1% (19/126) of the cases showed granulomas with fibrous tissue hyperplasia, alveolar protein deposition or giant cell interstitial pneumonia. The qualitative and semi-quantitative analyses of residual dust components in the lung under scanning electron microscope were helpful for the diagnosis of welder's pneumoconiosis and hard metal lung disease. Conclusions: The morphological characteristics of lung biopsy tissue are important reference basis for the clinicopathological diagnosis and differential diagnosis of occupational lung diseases. Recognizing the characteristic morphology and proper use of auxiliary examination are the key to an accurate diagnosis of occupational lung diseases on biopsy specimens.

Mass COVID-19 testing of asymptomatic health-care workers in a tertiary hospital during an outbreak in another hospital in Singapore: an effective strategy?

@#In response to a COVID-19 outbreak within a hospital in Singapore, a single mass swab exercise was conducted at another tertiary hospital to detect possible inter-hospital transmission. The exercise yielded no positive results, demonstrating non-targeted mass testing as an impractical strategy to track inter-hospital transmission.

Relationship between urinary cadmium and type 2 diabetes mellitus in adults / 中华流行病学杂志

Objective: To explore the relationship between environmental factors as urinary cadmium and type 2 diabetes mellitus (DM) in adults. Methods: Case-control study was adopted, including 166 cases and 427 controls. General characteristics of the subjects were collected by a structured questionnaire. FPG, biochemical indexes and urinary cadmium (UCd) were detected respectively, while UCd was corrected with creatinine. Unconditioned logistic regression model was applied to analyze the relationship between UCd and DM. Results: Levels of UCd appeared higher in cases with the following characteristics as: having primary school education (P=0.016), being female (P=0.013), being non-smokers (P=0.014) or non-alcoholic (P=0.025), and with BMI>25.00 kg/m(2) (P=0.040, P=0.025) than those appeared in the control group. Same results were shown in the 60-69 years (P=0.024) old group. Data from the unconditional logistic regression analysis showed that family history of DM (OR=3.19, 95%CI: 1.45-7.03), education status (OR=1.50,95%CI: 1.08-2.08) and UCd (OR=1.61, 95%CI: 1.08-2.41) were influencing factors on DM. Conclusion: A close association between UCd and DM was noticed. UCd appeared a risk factor on DM that called for setting up related prevention program to reduce the exposure of Cd and to control the risk on DM.

Interaction between polycyclic aromatic hydrocarbons and high risk human papillomavirus infection on cervical intraepithelial neoplasia / 中华流行病学杂志

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.

Interaction between abnormal expression of fragile histidine triad and methyl-CpG-binding protein 2 on cervical cancerization / 中华流行病学杂志

Objective: To explore the relationship between abnormal expression of fragile histidine triad (FHIT) gene and methyl-CpG-binding protein 2 (MeCP2) as well as their interaction on cervical cancerization. Methods: A total of 73 patients with cervical squamous cell carcinoma (SCC), 113 patients with cervical intraepithelial neoplasia (CIN Ⅰ, n=45; CINⅡ/Ⅲ, n=68) and 60 women with normal cervix (NC) were included in the study. Real time PCR and Western blot were performed to detect the expression levels of mRNA and protein about FHIT and MeCP2, respectively. The methylation status of FHIT gene CpG island was tested by methylation-specifc PCR (MSP). Kruskal-Wallis H test, χ(2) test, trend χ(2) test and Spearman correlation analysis were conducted with software SPSS 20.0. The interaction was evaluated by generalized multifactor dimensionality reduction (GMDR) model. Results: With the deterioration of cervical lesion, the methylation rates of FHIT gene CpG island (χ(2)=18.64, P<0.001; trend χ(2)=18.08, P<0.001) increased gradually, while the expression levels of FHIT mRNA (H=27.32, P<0.001; trend χ(2)=12.65, P<0.001) and protein (H=47.10, P<0.001; trend χ(2)=29.79, P<0.001) decreased gradually. There was a negative correlation between the methylation rates of FHIT gene CpG island and the expression level of FHIT protein (r=-0.226, P<0.001). The levels of MeCP2 mRNA (H=26.19, P<0.001; trend χ(2)=11.81, P=0.001) and protein (H=69.02, P<0.001; trend χ(2)=47.44, P<0.001) increased gradually with the aggravation of cervical lesions. There was a positive correlation between the expression level of MeCP2 protein and the FHIT mRNA Ct ratio (r=0.254, P<0.001). Expression of proteins were negatively correlated between MeCP2 and FHIT (r=-0.213, P=0.001). The results analyzed by GMDR model showed that there were interactions among high MeCP2 protein expression, the CpG island methylation of FHIT and mRNA and protein expression in CINⅡ/Ⅲ group, and among high MeCP2 mRNA and protein expression, the CpG island methylation of FHIT and low mRNA and protein expression in SCC group. Conclusion: High expression of MeCP2 mRNA and protein, the CpG island methylation and low mRNA and protein expression of FHIT could increase the risk of cervical carcinogenesis, and there might be a synergistic effect on cervical carcinogenesis.

Relationship between daily exposure to bisphenol A and male sexual function-a study from the reproductive center / 中华流行病学杂志

Objective: To explore the relationship between male sexual function and daily exposure to bisphenol A (BPA) at a reproductive center in Taiyuan. Methods: Male patients who were seeking treatment of infertility due to problems caused by either of the spouse were selected from the Shanxi reproductive center between September 2014 and April 2015. Information on general characteristics, sexual function and fasting venous blood samples were collected. Total scores of sexual function were evaluated by Delphi expert scoring method. Levels of serum BPA were measured by high-performance liquid chromatography. Data was analyzed by Spearman rank correlation, rank sum test, multivariate logistic regression analysis and χ(2) trend test. Relationship between BPA and sexual function was presented as OR and corresponding 95%CI. Results: Among the 353 participants, 45.0% was defined as sexual dysfunction with low sexual desire (47.3%) as the major reason. BPA was detected in all the 353 patients, with a range of concentration as 0.38-21.93 ng/ml and an average as 5.79 ng/ml. Results from the Spearman rank correlation analysis revealed significant negative correlations between serum BPA and sexual function, sexual desire, erectile ability and ejaculation intensity, while serum BPA was positively correlated with premature ejaculation. According to the four percentile of BPA concentration (ng/ml), the subjects were divided into four groups. Compared with the low concentration group (0.38-3.79 ng/ml), the risk of sexual dysfunction significantly increased in the groups with higher BPA levels. Particularly, in the highest BPA group (8.68-21.93 ng/ml), more obvious effects were seen on sexual dysfunction (OR=1.55, 95%CI:1.00-3.23), reduced sexual desire (OR=4.75, 95%CI: 2.44-9.22), reduced erection ability (OR=2.40, 95%CI: 1.18-4.88), reduced ejaculation intensity (OR=2.53, 95%CI: 1.25-5.16) and premature ejaculation (OR=1.95, 95%CI: 1.02-3.72). Conclusion: Low sexual desire appeared as the main type of male sexual dysfunction, the exposure to higher levels of BPA in daily life might lead to male sexual dysfunction.

Interaction between vaginal micro-environment alterations and HPV16 infection in cervical intraepithelial neoplasia / 中华流行病学杂志

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), β-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), β-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), β-glucuronidase, clotting enzyme and neuraminidase in CINⅠ group, and the interaction between HPV16 infection and the abnormalities of vaginal cleanliness, H(2)O(2), β-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.

Effect of hnRNP K and its interaction with HPV16 on cervical intraepithelial neoplasia / 中华流行病学杂志

Objective: To investigate the effect of heterogeneous nuclear ribonucleoprotein K (hnRNP K) and its interaction with human papillomavirus 16 (HPV16) on cervical intraepithelial neoplasia (CIN). Methods: The participants included 67 women with normal cervix (NC), 69 women with CINⅠ and 68 women with CINⅡ/Ⅲ in a community cohort of pathologically diagnosed women established in Jiexiu of Shanxi province, from June 2014 to June 2015. A structured questionnaire was used to collect the demographic data of the subjects and the related factors of cervical lesions. Cervical exfoliated cells and cervical tissues from biopsy or surgery were selected. The infection status of HPV16 was detected by flow-through hybridization. The protein expression levels of hnRNP K were evaluated by Western blot. SPSS 23.0 software was used to collate and analyze the data. To study the differences in demographic characteristics, related factors, hnRNP K protein and HPV16 infection among NC, CINⅠand CINⅡ/Ⅲgroups, χ(2) test, trend χ(2) test, and Kruskal-Wallis H test were conducted. Multiple comparisons of hnRNP K protein in three groups were completed by using the Bonferroni method. The OR and its 95%CI of hnRNP K, HPV16 and CIN were calculated by using the unconditional logistic regression models. Two-way interactions between hnRNP K protein and HPV16 infection on CIN were analyzed by using additive model and related indicators. Results: HPV16 infection rates were 10.4% in women with normal cervix, 14.5% in women with CINⅠ and 41.2% in women with CINⅡ/Ⅲ, respectively. The differences among three groups were significant (P<0.001). Moreover, the infection rates of HPV16 gradually increased with the increasing severity of CIN (trend χ(2)=18.512, P<0.001). The differences in protein expression of hnRNP K among three groups were significant (H=48.138, P<0.001) and the expressionincreased with the development of cervical lesionss (trend χ(2)=21.765, P<0.001). Results from the interaction analysis indicated that there were additive effects between high expression of hnRNP K protein and HPV16 in CINⅡ/Ⅲ group compared with normal group (API=0.639, 95%CI: 0.083-1.196). In contrast, no such additive effect was found in CINⅠ group. Conclusions: HPV16 infection and over-expression of hnRNP K protein were associated with the increased risk of cervical intraepithelial neoplasia. There might be interaction between hnRNP K protein overexpression and HPV16 infection existed on the progress of CINⅡ/Ⅲ.

Effects of temperature and additives on stability and spectrum of a therapeutic fibroblast growth factor

Human fibroblast growth factor 20 [FGF20] is a 16.5 kDa protein containing 154 amino acid residues with reportedly poor thermal stability, and low stability, which are considered to be major factors that can limit its pharmacological applications. Thus, the aim of this study was to enhance the thermal stability and bio activity of a therapeutic FGF20 by addition of sucrose or heparin as additives and also at different temperatures. A variety of biophysical techniques such as far-UV circular dichroism [CD], fluorescence and high resolution derivative UV absorption spectroscopy, were employed to characterize FGF20 and study the effects of heparin and sucrose on its thermal stability and bio activity at pH 7.0. Results of this study suggest that human FGF20 is significantly unstable and induction of heat by increased temperatures results in aggregation and precipitation at pH 7.0. Great changes in the fluorescence intensity and shape were achieved by addition of heparin and sucrose at different temperatures compared to the control. From 10 °C to 60 °C, no significant changes were observed in far-UV CD spectrum compared to the control, but significant changes were observed by adding sucrose when these temperatures are above 45 °C. Upon addition of heparin and sucrose, the mitogenic activity increased significantly at all tested temperatures, and these changes may be related to the roles of heparin and sucrose on the structure and conformation of FGF20. Results of this study suggest that heparin and sucrose as additives seems to benjm sufficient to prevent thermal inactivation of FGF20 and also maintain its conformation stability and bio activity