Ultrasound scoring system for prenatal diagnosis of placenta accreta spectrum.

BACKGROUND: To develop an ultrasound scoring system for placenta accreta spectrum (PAS), evaluate its diagnostic value, and provide a practical approach to prenatal diagnosis of PAS. METHODS: A total of 532 pregnant women (n = 184 no PAS, n = 120 placenta accreta, n = 189 placenta increta, n = 39 placenta percreta) at high-risk for placenta accreta who delivered in the Third Affiliated Hospital of Zhengzhou University between January 2021 and December 2022 underwent prenatal ultrasound to evaluate placental invasion. An ultrasound scoring system that included placental and cervical morphology and history of cesarean section was created. Each feature was assigned a score of 0 ~ 2, according to severity. Thresholds for the total ultrasound score that discriminated between no PAS, placenta accreta, placenta increta, and placenta percreta were calculated. RESULTS: Univariate and multivariate regression analysis identified seven indicators of PAS that were included in the ultrasound scoring system, including placental location, placental thickness, presence/absence of the retroplacental space, thickness of the retroplacental myometrium, presence/absence of placental lacunae, retroplacental myometrial blood flow and history of cesarean section. Using the final ultrasound scoring system, no PAS is diagnosed at a total score < 5, placenta accreta or placenta increta is diagnosed at a total score 5-10, and placenta percreta is diagnosed at a total score ≥ 10. CONCLUSIONS: This study identified seven indicators of PAS and included them in an ultrasound scoring system that has good diagnostic efficacy and clinical utility. TRIAL REGISTRATION: ChiCTR2300069261 (retrospectively registered on 10/03/2023).

Interaction effects of night-time temperature and PM2.5 on preterm birth in Huai River Basin, China.

Nocturnal temperature is observed increasing with global warming. However, evidence on night-time non-optimal temperature on the risk of preterm birth (PTB) is limited, and the potential interactions with air pollution on PTB has not been well clarified. We therefore conducted a population-based retrospective cohort study to evaluate the effect of night-time temperature extremes on the risk of PTB and its interaction with air pollution. Records of 196,780 singleton births from 4 counties in Huai River Basin (2013-2018) were obtained. Gridded data on night-time temperature were collected from a high-quality Chinese Air Quality Reanalysis dataset. We used a multivariate logistic regression to evaluate the effects of night-time heat and cold exposure on the risk of PTB as well as its subtypes. Potential interactions between night-time temperature extremes and fine particulate matter < 2.5 µm (PM2.5) were examined using the relative excess risk due to interaction (RERI). We found that the risk of PTB was positively associated with third trimester night-time extremely heat and cold exposure, with adjusted OR of 1.898 (95 %CI: 1.655-2.177) and 2.044 (95 %CI: 1.786-2.339). Similar effects were observed for PTB subtypes, moderately PTB (mPTB) and very PTB (vPTB). Synergistic effects (RERI greater than 0) of each trimester night-time temperature extremes exposure and PM2.5 on PTB were observed. We identified consistent positive interactions between night-time temperature extremes and PM2.5 on mPTB. No significant interaction of night-time temperature extremes and PM2.5 on vPTB was found. In conclusion, this large retrospective cohort study found that third trimester night-time heat and cold exposure significantly increased the risk of PTB and its subtypes. There is a synergistic effect between night-time temperature extremes and high PM2.5 levels on PTB and mPTB. In the context of climate warming, our results add new evidence to the current understanding of night-time non-optimal temperature exposure on PTB.

N-acetylcysteine alleviates fluoride-induced testicular apoptosis by modulating IRE1α/JNK signaling and nuclear Nrf2 activation.

We previously investigated excessive fluoride exposure elicited intracellular endoplasmic reticulum (ER) stress and led to Sertoli cells dysfunction in vitro. However, the mechanisms underlying fluoride-mediated male reproductive damage in vivo remain largely unknown. Considerable evidence has now revealed ER stress is closely linked with testicular oxidative damage. Hence, we aimed to explore whether ER stress signaling was involved in the testicular protective effects of antioxidant N-acetylcysteine (NAC) against testicular apoptosis induced by fluoride. Male SD rats were oral gavaged with sodium fluoride (NaF) for 7 weeks to induce fluorosis. The animals were pretreatment with or without NAC (150 mg/Bw•d). Our results demonstrated that sub-chronic NaF exposure triggered testicular apoptosis and sex hormonal disturbance in pituitary-testicular (PT) axis, promoted oxidative stress and the expression of ER stress mediators. Antioxidant NAC, however, prevented NaF-induced testicular apoptosis accompanied by activating Nrf2-mediated antioxidant potential. Simultaneously, NAC pretreatment downregulated XBP1 splicing, reduced JNK phosphorylation and further blocked cleavage of caspase-3, all these might contribute to the inhibition of testicular cell apoptosis. Collectively, the present results suggested that prolonged administration of NAC preserved testicular function and normalized sex hormonal disruption induced by NaF via the inhibition of Nrf2-associated oxidative damage and Ire1α-JNK-mediated apoptosis in rat testis.

Involvement of inducible nitric oxide synthase and mitochondrial dysfunction in the pathogenesis of enterovirus 71 infection.

Enterovirus71 (EV71) is recognized as the main causative agent of severe hand, foot and mouth disease (HFMD). However, the pathogenesis of EV71 infection has not been well characterized. Clinical evidence indicated that inducible nitric oxide synthase (iNOS) induction in the lung of HFMD patients contributes to the severe symptoms of pulmonary edema. In the present study, we recruited 142 subjects including HFMD patients and controls, and serum level of nitric oxide (NO) was determined. Next, cellular and animal model were used to further investigate the roles of iNOS and mitochondria damage during EV71 infection. Serum NO level in HFMD patients with mild or severe symptoms was higher than that in controls, and there was a trend towards an increase in the serum NO level of severe cases relative to mild cases. EV71 infection caused apoptosis and increased levels of NO, iNOS, superoxide dismutase (SOD) activity and malondialdehyde (MDA), and degraded mitochondrial membrane potential (ΔΨm) in vitro. Pathological alterations of mitochondrial morphology were observed in vitro and in vivo. Furthermore, the expression of iNOS levels in target organs including brain, spinal cord, skeletal muscle, lung and heart were increased with the progression of the pathogenesis of EV71 infection in mice. Taken together, iNOS and mitochondrial damage participate in the pathogenesis of EV71 infection.

Ameliorative effects of N-acetylcysteine on fluoride-induced oxidative stress and DNA damage in male rats' testis.

This study was to elucidate DNA damage in rats treated with sodium fluoride (NaF) by performing 8-Hydroxy-2-deoxyguanosine (8-OHdG) immunohistochemical staining assays on seminiferous tubules of rats' testis, and also to evaluate the protective effects of N-acetylcysteine (NAC) on spermatogenesis. Male Sprague Dawley (SD) rats were exposed to a single dose of NaF (25mg/kg/day) with or without NAC (150mg/kg/day) for 7 weeks (7W) by gastric gavage. Testicular fluorine content was detected by fluorine ion selective electrode method. Oxidative damage to DNA was evaluated by measuring the increase in 8-OHdG formation in testicular tissue through immunohistochemical staining assays and also the effects of NAC pretreatment. The biochemical indicators about oxidative stress were detected by colorimetric assays, sperm parameters and the morphological changes of testis were studied. NaF significantly increased serum levels of oxidative stress, markedly elevated testicular fluorine and 8-OHdG expression levels as well as the rate of sperm aberration compared to saline group. Testosterone in serum, sperm counts and the mobility of sperm were lower than those of the rats in control group. The pathological morphological changes in testicular seminiferous tubule were also obvious in the rats with NaF treatment. Pretreatment with NAC did not reduce the contents of fluoride content in testis, but significantly reduced 8-OHdG formation and lipid peroxidation. This study suggests that NAC may have certain antagonism on the reproductive damage induced by NaF.

Sodium fluoride induces apoptosis through reactive oxygen species-mediated endoplasmic reticulum stress pathway in Sertoli cells.

Excessive fluoride exposure is known to contribute to reproductive system dysfunction, ultimately leading to pathological damage and apoptosis in cells. Although both oxidative and endoplasmic reticulum (ER) stresses have been implicated in fluorosis, the signaling pathways and their roles in sodium fluoride (NaF)-induced apoptosis of Sertoli cells have been sparsely described. In this study, oxidative damage, ER stress, and apoptosis were analyzed after Sertoli cells were treated with varying doses of NaF for 24hr. Moreover, the antioxidant N-acetylcysteine (NAC) and pro-apoptotic transcription factor CHOP knockdown were used to clarify the precise interplay between reactive oxygen species (ROS), ER stress and their roles in NaF-induced apoptosis in Sertoli cells. The present study indicated that NaF significantly decreased cell viability and induced apoptosis in Sertoli cells. In addition, NaF exposure facilitated the accumulation of ROS and increased nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) in Sertoli cells. Treatment with NAC caused remarkable recovery from these NaF-induced responses. Meanwhile, excessive NaF triggered ER stress as evidenced by up-regulated glucose-regulated protein 78 kDa (GRP78), PKR-like ER kinase (PERK), phosphorylation of eukaryotic translation initiation factor 2α (p-eIF2α) and CCAAT/enhancer-binding protein-homologous protein (CHOP), without affecting total eukaryotic translation initiation factor 2α (eIF2α). NAC effectively blocked the activation of ER stress, suggesting that NaF-induced ROS is an early event that triggers ER stress. Taken together, the results demonstrate that the ROS-mediated ER stress pathway is the crucial mechanistic event involved in NaF-induced apoptosis of Sertoli cells.

[Effects of resveratrol on Nrf2 signal pathway of chronic lead-exposed mouse brain tissue].

OBJECTIVE: To evaluate the effect of resveratrol on NF-E2-related factor 2 (Nrf2) signal pathway in the process of oxidative stress of mice brain tissue induced by chronic lead exposure. METHODS: A total of 48 healthy weaned C57BL/6 male mice were randomly divided into four groups (12 mice each group), control group, lead poisoning model group, lead poisoning coupled with resveratrol intervention group and resveratrol group. The lead poisoning mice model had been made by exposed to 0.2% lead acetate solution in the drinking water for 12 weeks. At the same time, the mice in the intervention group and resveratrol group were fed with resveratrol (50 mg/(kg · d)) by oral gavage and the other two groups were treated with the same volume of solvent, sodium carboxymethylcellulose. The serum and brain tissues were removed and used for detecting the lead concentration and measuring the activity of GSH-Px and the content of GSH and MDA. The levels of protein Nrf2 and γ-GCS were determined by western blot. RESULTS: Compared with the poisoning model group, GSH-Px activity and GSH content were significantly increased (P < 0.05), and MDA content was significantly decreased in the brain tissue intervened by resveratrol (P < 0.05). The protein expression of Nrf2 and γ-GCS were induced in the brain tissue of the intervention group (P < 0.05). CONCLUSION: Resveratrol could reduce the oxidation damage caused by chronic lead exposure in drinking water which may due to the protein activation of Nrf2, further up-regulated expression of targeting γ-GCS and adjusted dynamic balance of GSH system.

[Effects. of N-acetylcysteine on fluoride-induced endoplasmic reticulum stress in sertoli cells].

OBJECTIVE: Investigated the effects of N-acetylcysteine (NAC) on endoplasmic reticulum stress of sertoli cells induced by sodium fluoride (NaF). METHODS: Rat sertoli cells were exposed to various concentration of (0, 6, 12, 24 µg/ml) sodium fluoride with or without 2 mmol/L NAC for 24 hours. The cell viability was evaluated using trypan blue exclusion test. Intracellular reactive oxygen species (ROS) was measured using the fluorescent probe DCFH-DA. Western blot was used to test the expression of GRP78, PERK and CHOP. RESULTS: It was found that treatment with NAC (2 mmol/L) restored the reduced cell viability and excessive oxidative stress (P < 0.01). Moreover, fluoride exposure upregulated the expression of GRP7 8, PERK and CHOP protein (P <0. 01 ). NAC was also found to suppress the levels of GRP78, PERK and CHOP expression in NaF-treated cells (p<0.01). CONCLUSION: Endoplasmic reticulum stress signaling pathways were activated by ROS, and NAC attenuate endoplasmic reticulum stress through inhibiting the levels of ROS in NaF-treated sertoli cells.

[Effects of fluoride on oxidative stress and apoptosis in primary culture of rat sertoli cells].

OBJECTIVE: To study effects of fluoride on oxidative stress and apoptosis in rat sertoli cells. METHODS: Intracellular reactive oxygen species (ROS) , malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, mitochondrial membrane potential and percentage of apoptosis were measured after the rat sertoli cells were incubated with 0, 6, 12 and 24 microg/ml sodium fluorides or 24 hours in vitro. RESULTS: Fluoride decreased the cell activity significantly (P < 0.01). The results suggested that exposure to fluoride significantly increased the level of ROS and MDA content (P < 0.01), fluoride also decreased SOD activity significantly (P < 0.05 or P < 0.01). In addition, with the NaF dose increased, there is a significantly decreasing in mitochondrial membrane potential and a significantly increasing in early apoptosis rate (P < 0.01). CONCLUSION: Fluoride can induce excessive oxidative stress and increased apoptosis rate in rat sertoli cells.