Autocross-linked hyaluronic acid gel and adipose-derived mesenchymal stem cell composites for the treatment intrauterine adhesions.

OBJECTIVE: To evaluate the effect of adding adipose-derived mesenchymal stem cells (ASCs) to autocross-linked hyaluronic acid (HA) gel for intrauterine adhesion (IUA) treatment. METHODS: A rat IUA model was established by mechanical curettage and infection, and then different treatments were administered to the rats on day 7 after modeling. Ninety-six rats were randomly divided into the following groups: IUA model group, gel therapy group, and combination therapy group (HA gel combined with ASCs). Eight rats per group were sacrificed on days 7, 10, 14 and 21 for the subsequent experiments. Morphological changes were determined by hematoxylin-eosin staining and Masson staining. Smad3 and leukocyte inhibitory factor (LIF) were analyzed by quantitative real-time polymerase chain reaction and immunohistochemistry. RESULTS: The endometrial lines in the gel therapy group and the combination therapy group were more complete than those in the model group. Masson staining showed that fibrosis area rates in the gel therapy group and the combination therapy group were significantly lower than those in the model group on day 7(P < 0.05). During the observation period, the fibrosis area rates in the combination therapy group remained lower than those in the model group (P < 0.05). The mRNA expression of Smad3 in the combination therapy group was lower than that in the model group and gel therapy group during the observation period (P < 0.05). The mRNA expression level of LIF in the combination therapy group was higher than that in the model group and the gel therapy group throughout the observation period (P < 0.05). CONCLUSIONS: HA gel was effective in preventing the IUA adhesion formation at the early stage of the observation period, while ASC enhanced this effect throughout the observation period. Gel and ASC composites helped to improve endometrial receptivity.

A Stereological Study of Mouse Ovary Tissues for 3D Bioprinting Application.

INTRODUCTION: The use of 3D-bioprinted ovaries has been proven to be a promising technique for preserving fertility. Stereology is an accurate method to obtain quantitative 3D information and the stereological data is the basis for 3D bioprinting ovaries. METHODS: In this study, six female mice were used to acquire the ovarian tissues. One of the two paraffin-embedded ovaries of each mouse was cut into 5 µm sections, and the other was cut into 15 µm sections and then subjected to haematoxylin and eosin staining and anti-follicle stimulating hormone receptor antibody immunohistochemistry. The volume and volume fractions of ovaries were measured by the Cavalieri method. Then, the numerical densities and total numbers of ovarian granulosa cells (OGCs) and primordial, preantral and antral follicles in serial sections were estimated using design-based stereology. RESULTS: The ovarian volume was 2.50 ± 0.32 mm3. The volume fractions of the cortex, medulla, follicles and OGCs were 86.80% ± 2.82, 13.20% ± 2.82%, 5.60% ± 0.25% and 81.19% ± 2.57%, respectively. The numerical densities of OGCs, the primordial, preantral and antral follicles were 2.11 (± 0.28) × 106/mm3, 719.57 ± 18.04/mm3, 71.84 ± 3.93/mm3 and 17.29 ± 3.54/mm3, respectively. The total number of OGCs and follicles per paraffin-embedded ovary were 5.26 (± 0.09) × 106 and 2013.66 ± 8.16. CONCLUSIONS: The study had obtained the stereological data of the mice ovaries, which contribute to a deeper understanding of the structure of the ovaries. Meanwhile, the data will supply information for 3D bioprinting ovaries.

Liver function biomarkers disorder is associated with exposure to perfluoroalkyl acids in adults: Isomers of C8 Health Project in China.

Exposure to chemicals may affect liver enzyme to increase the risk of liver diseases. Perfluoroalkyl acids (PFAAs) are one kind of persistent organic pollutants with hepatotoxic effect in organism. However, data is scarce to characterize the hepatotoxic effects of specific structural PFAA isomers in general population. To address this data gap, we evaluated the association between serum PFAAs concentration and liver function biomarkers in the Isomers of C8 Health Project in China. High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to measure 18 serum PFAAs, except for linear and branched isomers of PFOA/PFOS, nine perfluorinated carboxylic acids (PFCAs) and two perfluorinated sulfonic acids (PFSAs) were also included, in 1605 adult residents of Shenyang, China. Values for nine serum liver function biomarkers were determined by full-automatic blood biochemical analyzer. Linear regression was used to evaluate associations between PFAAs and continuous liver function biomarkers and logistic regression to assess markers dichotomized per clinical reference intervals. Results indicated that serum PFAAs concentrations were associated with liver biomarker levels suggestive of hepatotoxicity, especially for liver cell injury. For example, a 1 ln-unit increase in total- perfluorooctanoic acid (PFOA) exposure was associated with a 7.4% [95% confidence interval (CI): 3.9%, 11.0%] higher alanine aminotransferase (ALT) level in serum. Interestingly, we observed association between branched PFAA isomers and liver biomarkers. For example, one ln-unit increase in branched perfluorooctane sulfonate (PFOS) isomers exposure was associated with a 4.3% increase in ALT level (95% CI: 1.2%, 7.4%) and a 33.0% increased odds of having abnormal ALT (95% CI: 5.0%, 67.0%). Also, we found that PFNA had positive association with ALT [(6.2%, 95% CI: 3.1%, 9.4%) and AST levels (2.5%, 95% CI: 0.5%, 4.5%)]. Logistic regression results showed that PFPeA, PFHxA, PFNA, PFDoDA, PFTrDA and PFTeDA had statistically association with abnormal prealbumin. Conclusively, our results support previous studies showing association between PFAAs exposure and liver function biomarkers. We found new evidence that branched PFAAs isomer exposure is associated with the risk of clinically relevant hepatocellular dysfunction.

Renal function and isomers of perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS): Isomers of C8 Health Project in China.

Perfluoroalkyl substances (PFASs) are widely-utilized synthetic chemicals commonly found in industrial and consumer products. Previous studies have examined associations between PFASs and renal function, yet the results are mixed. Moreover, evidence on the associations of isomers of PFASs with renal function in population from high polluted areas is scant. To help to address this data gap, we used high performance liquid chromatography-mass spectrometry to measure serum isomers of perfluorooctanoate (PFOA), perfluorooctanesulfonate (PFOS), and other PFASs from 1612 adults residing in Shenyang, China, and characterized their associations with estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD). Results showed that after adjusted for multiple confounding factors, most of the higher fluorinated PFASs, except for PFOA and PFDA, were negatively associated with eGFR and positively associated with CKD. Compared with linear PFOS (n-PFOS), branched PFOS isomers (Br-PFOS) were more strongly associated with eGFR (Br-PFOS; ß = -1.22, 95%CI: 2.02, -0.42; p = 0.003 vs. n-PFOS; ß = -0.16, 95%CI: 0.98, 0.65; p = 0.691) and CKD (Br-PFOS; OR = 1.27; 95% CI: 1.02, 1.58; p = 0.037 vs. n-PFOS; OR = 0.98; 95% CI: 0.80, 1.20; p = 0.834). In conclusion, branched PFOS isomers were negatively associated with renal function whereas their linear counterparts were not. Given widespread exposure to PFASs, potential nephrotoxic effects are of great public health concern, Furthermore, longitudinal research on the potential nephrotoxic effects of PFASs isomers will be necessary to more definitively assess the risk.

Isomers of perfluoroalkyl substances and overweight status among Chinese by sex status: Isomers of C8 Health Project in China.

Previous investigations on the associations of polyfluoroalkyl substances (PFASs) with overweight/obesity are mixed. Moreover, little information has been reported about the association between isomers of PFASs with body mass index (BMI), waist circumference (WC) or overweight. To address this shortcoming in the literature, we conducted a study involving 1612 Chinese adults (1204 men and 408 women), ages 22-96 years old, from Shenyang, China, to analyze serum isomers of perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and other PFASs. Height, weight and WC were measured by a standardized protocol of WHO. Results indicated that increased serum concentrations of all (both branched and linear) isomers of PFASs were associated with a higher prevalence of overweight, and these associations were more pronounced in women. The adjusted odds ratios (ORs) from logistic regression analyses among women were 1.45 (95% confidence interval [CI]: 1.06, 1.99) for linear PFOS isomers, 1.33 (95% CI: 1.00, 1.77) for branched PFOS isomers, 1.39 (95% CI: 1.06, 1.81) for 3 + 4 + 5m PFOS, 1.54 (95% CI: 1.08, 2.21) for linear PFOA isomers, and 1.62 (95% CI: 1.05, 2.51) for branched PFOA isomers, respectively. Associations with increased WC were yielded a similar pattern. Linear regression models also showed positive associations between PFASs and BMI or WC. In conclusion, this study suggests that PFASs and their isomers are positively associated with overweight or increased WC, and the associations are stronger in women. Furthermore, PFOA and its isomers displayed the most robust obesogenic associations.

Overweight modifies the association between long-term ambient air pollution and prehypertension in Chinese adults: the 33 Communities Chinese Health Study.

BACKGROUND: Research regarding the interaction of ambient air pollution and overweight on prehypertension is scarce. We aimed to test whether overweight modifies the association between long-term exposure to ambient air pollution and prehypertension in Chinese adults. METHODS: A total of 16,188 Chinese adults, aged 18-74 years old, from 33 communities in 3 Northeastern Chinese cities were evaluated. Three-year average levels of particles with an aerodynamic diameter ≤ 10 µm (PM10), sulfur dioxides (SO2), nitrogen dioxides (NO2), and ozone (O3) were calculated at monitoring stations. Generalized additive models and 2-level regression analyses were applied. RESULTS: We observed significant interactions between air pollutants and overweight on prehypertension and blood pressure. The associations of PM10, SO2, NO2, and O3 with prehypertension were significant among overweight participants (Prevalence Rate Ratios (PRRs) per interquartile range (IQR) of air pollutants: 1.14-1.20), but not among normal weight participants (PRRs: 0.98-1.04). PM10, SO2, and O3 were significantly associated with systolic blood pressure (SBP), and the magnitudes of these associations were higher among overweight adults (increases in SBP per IQR of air pollutants: 1.82-4.53 mmHg) than those among normal weight adults (increases in SBP: 0.42-0.61 mmHg). For diastolic blood pressure (DBP), significant associations were mainly observed in overweight participants (increases in DBP: 0.80-1.63 mmHg). Further stratified analyses showed that all these interactions were stronger in women, the older, and participants living in areas with lower income levels or higher population density. CONCLUSIONS: Being overweight may enhance the effects of ambient air pollution on prehypertension and blood pressure in Chinese adults.

Positive association between short-term ambient air pollution exposure and children blood pressure in China-Result from the Seven Northeast Cities (SNEC) study.

The impact of ambient air pollution on health causes concerns in China. However, little is known about the association of short-term air pollution exposure with blood pressure (BP) in children. The goal of present study was to assess the association between short-term air pollution and BP in children from a highly polluted area in China. This study enrolled 9354 children in 24 elementary and middle schools (aged 5-17 years) from the Seven Northeast Cities (SNEC) study, respectively, during the period of 2012-2013. Ambient air pollutants, including particulate matter with an aerodynamic diameter of ≤10 µm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2) and ozone (O3) on the days (1-5 days) preceding BP examination were collected from local air monitoring stations. Generalized additive models and two-level regression analyses were used to evaluate the relationship between air pollution and BP after adjusting for other covariates. Results showed that with an interquartile range (IQR) increase in PM10 (50.0 µg/m3) and O3 (53.0 µg/m3) level during the 5-day mean exposure, positive associations with elevated BP were observed, with an odds ratio of 2.17 (95% CI, 1.61-2.93) for PM10 and 2.77 (95% CI, 1.94-3.95) for O3. Both systolic BP and diastolic BP levels were positively associated with an IQR increase of four air pollutants at different lag times. Specifically, an IQR increase in the 5-day mean of PM10 and O3 was associated with elevation of 2.07 mmHg (95% CI, 1.71-2.44) and 3.29 mmHg (95% CI, 2.86-3.72) in systolic BP, respectively. When stratified by sex, positive relationships were observed for elevated BP with NO2 exposure only in males. This is the first report on the relationship between ambient short-term air pollution exposure and children BP in China. Findings indicate a need to control air pollutants and protect children from heavy air pollution exposure in China.

Isomers of perfluorooctanesulfonate (PFOS) in cord serum and birth outcomes in China: Guangzhou Birth Cohort Study.

Prior investigations on the associations of polyfluoroalkyl substances (PFASs) with fetal growth are mixed. Moreover, little research has accrued pertaining to the association between isomers of PFASs with gestational age and birth weight. To address this gap and present novel information, we conducted a study including 321 pairs of mothers and their infants recruited from Guangzhou, China. High performance liquid chromatography-mass spectrometry was utilized to analyze isomers of perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA) along with other PFAS levels in cord serum samples. Mothers' and infants' characteristics were gathered from medical records. The resulting data revealed that higher PFOS, PFOA and isomers of PFOS were associated with lower birth weight. Per ln-unit (ng/mL) increase in cord serum total branched PFOS isomers was associated with a 126.3g (95% CI: -195.9, -56.8) reduction in the weight of infants at birth, while an ln-unit (ng/mL) increase of serum linear PFOS isomers (n-PFOS) was associated with a 57.2g (95% CI: -103.1, -11.3) reduction in the weight of infants at birth upon the subsequent adjustment for potential confounding variables. Notably, the association between cord PFAS level and birth weight was more pronounced in male infants. Furthermore, a positive association among branched PFOS isomers (1m-PFOS and 3+4+5m-PFOS) and gestational age was found. No associations could be found among other PFASs in conjunction with gestational age or birth weight. In conclusion, this investigation suggests that higher PFAS concentrations are associated with lower birth weight, and branched PFOS isomers show greater impact on infant birth weight than linear PFOS.

Association of perfluoroalkyl substances exposure with impaired lung function in children.

Previous studies have demonstrated associations between serum levels of perfluoroalkyl substances (PFASs) and asthma or asthma related-biomarkers. However, no studies have reported a possible relationship between PFASs exposure and lung function among children. The objective of the present study is to test the association between PFASs exposure and lung function in children from a high exposure area by using a cross-sectional case-control study, which included 132 asthmatic children and 168 non-asthmatic controls recruited from 2009 to 2010 in the Genetic and Biomarkers study for Childhood Asthma. Structured questionnaires were administered face-to-face. Lung function was measured by spirometry. Linear regression models were used to examine the influence of PFASs on lung function. The results showed that asthmatics in our study had significantly higher serum PFAS concentrations than healthy controls. Logistic regression models showed a positive association between PFASs and asthma, with adjusted odds ratios (ORs) ranging from 0.99 (95% confidence interval [CI]: 0.80-1.21) to 2.76 (95% CI: 1.82-4.17). Linear regression modeling showed serum PFASs levels were significantly negatively associated with three pulmonary function measurements (forced vital capacity: FVC; forced expiratory volume in 1s: FEV1; forced expiratory flow 25-75%: FEF25-75) among children with asthma, the adjusted coefficients between lung function and PFASs exposure ranged from -0.055 (95%CI: -0.100 to -0.010) for FVC and perfluorooctane sulfonate (PFOS) to -0.223 (95%CI: -0.400 to -0.045) for FEF25-75 and perfluorooctanoic acid (PFOA). PFASs were not, however, significantly associated with pulmonary function among children without asthma. In conclusion, this study suggests that serum PFASs are associated with decreased lung function among children with asthma.

Prenatal and postnatal exposure to pet ownership, blood pressure, and hypertension in children: the Seven Northeastern Cities study.

OBJECTIVE: There is little information about how exposure to pets impacts blood pressure (BP) in children. The objective of the present study was to investigate the association between pet exposure and BP in children. METHODS: A total of 9354 children, aged 5-17 years, from 24 elementary schools and 24 middle schools in the Seven Northeastern Cities were evaluated during 2012-2013. BP measurements were taken using a mercury sphygmomanometer. Hypertension in children was defined as having an average DBP or SBP in the 95th percentile or higher for the child's sex, age, and height. RESULTS: Overall, 2127 of the 9354 participants (22.7%) had current exposures to pets, with 989 of all participants having dogs (10.6%). Pet exposure was negatively associated with hypertension and BP in men and women. Keeping dogs in the home was related to a significantly lower prevalence of hypertension in men [adjusted odds ratio (aOR) = 0.68; 95% confidence interval (CI): 0.49-0.94] and women (aOR = 0.66; 95% CI: 0.48-0.90). When the analysis was stratified by sex, in-utero exposure to pets was negatively associated with hypertension in men (aOR = 0.66; 95% CI: 0.45-0.97), and the associations with lower BP strengthened with higher levels of current pet exposure. As for BP, the associations between pet exposure and DBP were detected more in women; estimated decreases in mean DBP was 1.10 mmHg (95% CI: -1.75 to -0.45) for current pet exposure. CONCLUSION: Pet ownership reduces the odds of hypertension and elevated BP in children.