Pirfenidone inhibits TGF-ß1-induced metabolic reprogramming during epithelial-mesenchymal transition in non-small cell lung cancer.

Metastasis is an important contributor to increased mortality rates in non-small cell lung cancer (NSCLC). The TGF-ß signalling pathway plays a crucial role in facilitating tumour metastasis through epithelial-mesenchymal transition (EMT). Glycolysis, a key metabolic process, is strongly correlated with NSCLC metastasis. Pirfenidone (PFD) has been shown to safely and effectively inhibit TGF-ß1 in patients with lung diseases. Furthermore, TGF-ß1 and glycolysis demonstrate an interdependent relationship within the tumour microenvironment. Our previous study demonstrated that PFD effectively inhibited glycolysis in NSCLC cells, prompting further investigation into its potential antitumour effects in this context. Therefore, the present study aims to investigate the potential antitumour effect of PFD in NSCLC and explore the relationship among TGF-ß1, glycolysis and EMT through further experimentation. The antitumour effects of PFD were evaluated using five different NSCLC cell lines and a xenograft tumour model. Notably, PFD demonstrated a significant antitumour effect specifically in highly glycolytic H1299 cells. To elucidate the underlying mechanism, we compared the efficacy of PFD after pretreatment with either TGF-ß1 or a TGF-ß receptor inhibitor (LY2109761). The energy metabolomics analysis of tumour tissue demonstrated that PFD, a chemosensitizing agent, reduced lactate and ATP production, thereby inhibiting glycolysis and exerting synergistic antineoplastic effects. Additionally, PFD combined with cisplatin targeted TGF-ß1 to inhibit glycolysis during EMT and enhanced the chemosensitization of A549 and H1299 cells. The magnitude of the anticancer effect exhibited by PFD was intricately linked to its metabolic properties.

Pilot-scale investigation of performance and microbial community in a novel system combining fixed and suspended activated sludge.

The conventional activated sludge (CAS) process is a widely used method for wastewater treatment due to its effectiveness and affordability. However, it can be prone to sludge abnormalities such as sludge bulking/foaming and sludge loss, which can lead to a decrease in treatment efficiency. To address these issues, a novel bag-based fixed activated sludge (BBFAS) system utilizing mesh bags to contain the sludge was developed for low carbon/nitrogen ratio wastewater treatment. Pilot-scale experiments demonstrated that the BBFAS system could successfully avoid the sludge abnormalities. Moreover, it was not affected by mass transfer resistance and exhibited significantly higher nitrogen removal efficiency, surpassing that of the CAS system by up to 78%. Additionally, the BBFAS system demonstrated comparable organic matter removal efficiency to CAS system. 16S rRNA gene high-throughput sequencing revealed that the bacterial community structure within the BBFAS system was significantly different from that of the CAS system. The bacteria associated with ammonium removal were more abundant in the BBFAS system than in the CAS system. The abundance of Nitrospira in the BBFAS could reach up to 6% and significantly higher than that in the CAS system, and they were likely responsible for both ammonia-oxidizing and nitrite-oxidizing functions. Clear stratification of microbial communities was observed from the outer to inner layers of the bag components due to the gradients of dissolved oxygen and other substrates. Overall, this study presents a promising approach for avoiding activated sludge abnormalities while maintaining high pollutant removal performance.

[Children's dietary patterns and dietary networks in five regions in China].

OBJECTIVE: To analyze the dietary patterns and dietary networks of children in China, explore regional differences in dietary habits in each region. METHODS: The subjects of the study were children aged 3-17(n=5824) in North Coast Economic Zone, Northeast, Central China, East Coast Economic Zone and Southwest Economic Zone who participated in the China Health and Nutrition Survey. The dietary pattern was obtained by factor analysis. Using mutual information, a measure to detect both linear and non-linear correlations between food groups constructed the dietary networks. RESULTS: Factor analysis resulted in five dietary patterns. Pattern 1 was related to high intakes of wheat and other cereals, pattern 2 was related to high intakes of fruits, milk, eggs and fast foods, pattern 3 was associated with high intakes of tubers, snacks, cakes, beverages and fast foods. The Northeast, Central China and North Coast Economic Zone regions had higher pattern 1 score. Pattern 2 scored higher for North Coast Economic Zone and East Coast Economic Zone regions. Pattern 3 scores in the Northeast region were higher than North Coast Economic Zone and East Coast Economic Zone regions. North Coast Economic Zone, Central China and Southwest Economic Zone regions had focused networks. The network of Northeast and East Coast Economic Zone regions were multiple. All regions were characterized by vegetables, or cereals as the hub. CONCLUSION: The dietary patterns and networks of children in the five regions of China exhibit regional differences.

LncRNA XR_595552 inhibition alleviates intermittent hypoxia-induced cardiomyocyte damage via activating the PI3K/AKT pathway.

BACKGROUND: Although the long noncoding RNAs (lncRNAs) expression profiles have been observed in previous study, the biological functions and underlying mechanisms of lncRNAs in OSA-related cardiac injury have not been elucidated. In the present study, we investigated a novel lncRNA, lncRNA XR_595552, and evaluated its role in intermittent hypoxia (IH)-induced damage in H9c2 cardiomyocytes. METHODS: H9c2 cells were exposed to IH condition. Real-time quantitative polymerase chain reaction (RT-qPCR) was conducted to measure the expression changes of lncRNA XR_595552 in H9c2 cells stimulated by IH. H9c2 cells were subjected to IH after transfection. CCK-8 was used to evaluate cell viability, and apoptosis was analyzed by Western blotting. Additionally, the regulatory relationship between lncRNA XR_595552 and PI3K/AKT was tested by RT-qPCR and Western blot. RESULTS: IH significantly induced injury in H9c2 cells (inhibited cell viability and promoted cell apoptosis). lncRNA XR_595552 was upregulated in a cell model of IH. Inhibition of lncRNA XR_595552 protected H9c2 cells against IH-induced damage, as the viability was increased, Bax, Caspase-9, and Caspase-3 were downregulated, and Bcl-2 was upregulated. More interestingly, lncRNA XR_595552 downregulation activated the PI3K/AKT pathway. Blocking the PI3K/AKT signal pathway by the use of LY294002 eliminated the myocardioprotective effects of lncRNA XR_595552 in H9c2 cells under IH condition. CONCLUSIONS: The results show that lncRNA XR_595552, a novel lncRNA, may play a protective role in attenuating IH-induced injury in cardiomyocytes via a regulating PI3K/AKT pathway. The findings suggest that this lncRNA could serve as a therapeutic target to treat OSA-related cardiovascular disorders.

The association between obstructive sleep apnea and lung nodule, carcinoembryonic antigen.

PURPOSE: The association between obstructive sleep apnea (OSA) and cancer risks gaining more and more attention. Data on the association between OSA and lung cancer risk are limited. This study is to investigate whether a link exists between low-dose computed tomography (LDCT) scanning of the chest findings, carcinoembryonic antigen (CEA) and OSA in patients suspected of OSA. METHODS: The cross-sectional study included patients aged 18 years or older who underwent continuous nocturnal polysomnography at our sleep center between February 2019 and November 2020. All subjects underwent chest LDCT and CEA. Patients with an apnea-hypopnea index (AHI) of ≥ 15/h were classified as clinically significant OSA group, whereas patients with an AHI < 15/h were classified as control group. RESULTS: A total of 277 patients were enrolled in the study. 176 patients were categorized into the OSA group, while 101 patients were categorized into the control group. There is no relationship between any OSA-related parameter and presence of lung nodule or presence of ≥ 6 mm lung nodule in the binary logistic regression analysis. OSA group demonstrated a significant higher value of CEA than control group. Stepwise multiple linear regression analysis showed that lowest O2 saturation (ß = - 0.256, p < 0.001), smoking status (ß = 0.156, p = 0.007) and age (ß = 0.153, p = 0.008) were independent predictors of elevated CEA. CONCLUSIONS: OSA was independently related to the elevated of serum CEA level, but not with presence of pulmonary nodule or ≥ 6 mm pulmonary nodule in LDCT. Further well-designed longitudinal studies with pathology available are needed to identify the association between OSA and risk of lung cancer.

[Sugar-sweetened beverage intakes and age of menarche in Chinese girls in 2004-2015].

OBJECTIVE: To investigate the prospective association between sugar-sweetened beverage intakes and age at menarche among Chinese girls. METHODS: Based on China Health and Nutrition Survey(CHNS) from 2004 to 2015, 293 girls aged 7-16 years with both data on sugar-sweetened beverage intake 1-5 years before menarche and age of menarche were included in the present study. Multivariate linear regression analysis and Logistic regression analysis were used to explore the influence of the sugar-sweetened beverage consumption on menarcheal age of Chinese girls. RESULTS: The median age at menarche of girls was 12 years old. The consumption of sugar-sweetened beverages(SSBs) was 0.5(0.2, 1.0) L/week for sweetened soft drinks, 0.5(0.2, 0.9) L/week for sweetened fruit drinks and 0.6(0.3, 1.3) L/week for total. After adjusting age at baseline, residency, maternal educational, level, energy intake at baseline and body mass index standard deviation score, no significant association was found between sweetened soft drinks, sweetened fruit drinks, total sugar-sweetened beverage intake and age at menarche. CONCLUSION: The intake of sugary beverages may not be prospectively related to the age of menarche among Chinese girls.

Overexpression of SSR2 promotes proliferation of liver cancer cells and predicts prognosis of patients with hepatocellular carcinoma.

Signal Sequence Receptor Subunit 2 (SSR2) is a key endoplasmic reticulum gene involved in protein folding and processing. Previous studies found that it was upregulated in several cancers, but its precise role in hepatocellular carcinoma (HCC) remains unclear. To have a better understanding of this gene in HCC, we examined the expression of SSR2 in HCC tissues by analysing The Cancer Genome Atlas (TCGA) data and immunohistochemistry. We also assessed the association between SSR2 expression and clinicopathological characteristics of HCC patients and patient survival. Potential function of SSR2 was predicted through GSEA and protein-protein interaction analysis. MTT, flowcytometry, transwell and a nude mice xenograft model were employed to investigate the biological functions in vivo and in vitro. The results showed that the expression of SSR2 was significantly increased in HCC tissues, and SSR2 expression was associated with several clinical characteristics. In addition, patients with higher SSR2 expression had poorer survival. Enrichment analysis suggested that SSR2 was probably involved in biological process or signalling pathways related to G2/M checkpoint, passive transmembrane transporter activity, ATF2_S_UP. V1_UP and ncRNA metabolic process. Further experimental study showed that SSR2 knockdown inhibited cell proliferation, migration and invasion ability and promoted apoptosis and cell cycle arrest in vitro. Moreover, downregulation of SSR2 also repressed the growth of HepG2 cells in vivo. In conclusion, our study suggests that SSR2 may act as an oncogene in HCC.

Effects of mokF gene deletion and overexpression on the Monacolin K metabolism yields of Monascus purpureus.

Monascus purpureus is a fungus known for producing various physiologically active secondary metabolites. Of these, Monacolin K, a compound with hypocholesterolemic effects, is controlled by the biosynthetic gene mokF. Here, mokF deletion and overexpression strains (F2 and C3, respectively) were constructed using genetic engineering and compared with the M. purpureus wild strain (M1). The results showed that Monacolin K production was reduced by 50.86% in F2 and increased by 74.19% in C3. Of the three strains, C3 showed the highest production of Monacolin K and the most abnormal morphology. In addition, mokF influenced the expression level of mokA-mokI and might play an important role in regulating the biosynthesis of secondary metabolites in M. purpureus. Overall, our study verified the function of mokF in M. purpureus using gene deletion and overexpression technology. KEY POINTS: • The deletion and overexpression strains of mokF gene were successfully constructed. • The deletion or overexpression of mokF gene directly affected Monacolin K production. •The mokF gene had little effect on Monascus pigments and cell biomass.

A fluorescent screening method for optimization of conotoxin expression in Pichia pastoris.

Conotoxins are small cysteine-rich peptides secreted by the Conus venom glands, which act on ion channels or membrane receptors with high specificity and potency. Conotoxins are invaluable sources for neuroscience research and drug leads, but their application is hindered by the limited successes in quantitative engineering using either chemical or biotechnological approaches. Here, we explore the Pichia pastoris to express 23 selected conopeptides using a GFP-based fluorescence screen. We found that, in a protease-deficient strain PichiaPink™ Strain 4 (ade2 prb1 pep4), most of the recombinant conopeptides were expressed as two major folding variants including a compact form that was somehow resistant to reduction and high temperature. The GFP-αTxIA was the only one displaying a single band that showed a dose-dependent neurotoxicity on larvae of the insect Plutella xylostella, with a 48-h LD50 lower than 1.12 pmol mg-1 body weight. Furthermore, the recombinant αTxIA after cleavage from the fusion was able to inhibit cell proliferation of the LYCT and HEK293T cell lines with an appearance IC50 of 341 ± 8 and 235 ± 15 nM, respectively. This screening method is straightforward and easy to scale up, providing a versatile tool for further optimization of conotoxin production in the yeast cell.

Long non-coding RNA MALAT1 affects intermittent hypoxia-induced endothelial injury by regulating miR-142-3p/HMGB1.

BACKGROUND: Obstructive sleep apnea (OSA) is a risk factor for atherosclerosis. Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is strongly linked to endothelial cell functions. However, the function of MALAT1 in intermittent hypoxia (IH) associated vascular endothelial injury has not been explored yet. The current study makes great attempts to investigate the function of MALAT1 in IH-induced endothelial injury and its latent control network. METHODS: To mimic the effect of OSA, we cultured the human umbilical vein endothelial cells (HUVECs) under intermittent hypoxia. Western blot was applied to measure the expression level of associated proteins including capase-3, Bax, Bcl-2 while qRT-PCR was used in measurement of MALAT1 and miR-142-3p. Cell Counting Kit-8 (CCK-8) was carried out in assessing cell viability. Dual-luciferase reporter assay was applied to verify the relationships among high mobility group box (HMGB)1 and MALAT1, miR-142-3p. RESULTS: IH treatment significantly reduced cell viability but enhanced cell apoptosis in HUVECs. Concomitantly, MALAT1 was significantly upregulated in IH-treated HUVECs. Further experiment showed that MALAT1 knockdown augmented IH-induced injury of HUVECs. In addition, it was confirmed by dual-luciferase reporter assay that MALAT1 interacted with miR-142-3p directly. Besides, inhibition of miR-142-3p alleviated damage induced by MALAT1 knockdown in IH-treated HUVECs. Finally, miR-142-3p interacted with HMGB1 directly and inhibition of HMGB1 protein expression mediated by MALAT1 knockdown was reversed by miR-142-3p inhibitor. CONCLUSIONS: IH resulted in increased expression of MALAT1 in HUVECs. MALAT1 knockdown augmented IH-induced injury of HUVECs. MALAT1 exerted its effects on IH-treated HUVECs via miR-142-3p/HMGB1.

Obstructive sleep apnea and the risk of mortality in patients with lung cancer: a meta-analysis.

PURPOSE: Prior reports have examined the relationship between obstructive sleep apnea (OSA) and the mortality rate of lung cancer. However, the findings remain controversial. The present meta-analysis was performed to assess the relationship between OSA and increased risk of mortality in patients with lung cancer. METHODS: PubMed, Web of Science, and Embase were systematically searched for the correlative studies. Data were analyzed and pooled to evaluate odds ratios (ORs) of lung cancer mortality related to OSA. RESULTS: From 249 identified studies, 3 met inclusion criteria and were analyzed, including 67 patients with lung cancer and comorbid OSA and 45 patients with lung cancer and no OSA. The meta-analysis indicated that OSA was not significantly correlated with mortality rate in lung cancer (OR = 2.005, 95% CI = 0.703 to 5.715, z = 1.30, p = 0.193). There was no significant publication bias according to Begg's tests (p = 0.296) and Egger's tests (p = 0.097). CONCLUSION: This meta-analysis suggests that OSA is not significantly correlated with the mortality rate in lung cancer.

The role of ferroptosis in chronic intermittent hypoxia-induced lung injury.

PURPOSE: Chronic intermittent hypoxia (CIH) causes lung injury but the mechanism is unclear. Ferroptosis is a novel form of programmed cell death. In this research, we attempted to explore the role of ferroptosis in CIH-induced lung injury both in vitro and in vivo. METHODS: Sprague-Dawley rats were randomly separated into control group, CIH group and CIH + ferrostatin-1 group (CIH + Fer-1). Rats in the CIH group and CIH + Fer-1 group were exposed to intermittent hypoxia for 12 weeks. Human bronchial epithelial cell line (BEAS-2B) was cultivated for 24 h in either conventional culture medium or under CIH conditions. Fer-1 was applied to observe its treatment effects. Histological changes were evaluated by Hematoxylin-eosin (HE) staining and masson staining. The expression levels of Acyl-CoA synthetase long-chain family member 4 (ACSL4), glutathione peroxidase 4 (GPX4), interleukin-6 (IL-6) and tumour necrosis factor α (TNFα) were detected via qRT-PCR or Western blot. Cell counting kit-8 (CCK-8) was used to assess cell viability. The apoptotic rate and reactive oxygen species (ROS) was calculated by flow cytometry. RESULTS: Histology showed that CIH treatment induced lung injury and pulmonary fibrosis in lung tissue. After Fer-1 treatment, the pathological changes caused by CIH alleviated. The mRNA and protein levels of GPX4 decreased significantly in lung tissues of CIH-treated rats and BEAS-2B, (p < 0.05). The mRNA and protein levels of ACSL4 increased significantly in lung tissues of CIH-treated rats and BEAS-2B, (p < 0.05). The mRNA levels of IL-6 and TNFα in BEAS-2B increased after CIH treatment, (p < 0.05). Cell viability decreased, apoptosis rate and ROS increased in CIH-treated BEAS-2B, (p < 0.05). Cotreatment with Fer-1 reversed CIH-induced apoptosis, cell viability, ROS accumulation, mRNA and protein levels of GPX4, ACSL4, IL-6 and TNFα both in vitro and in vivo (p < 0.05). CONCLUSIONS: Ferroptosis occurred in CIH-induced lung injury, both in vitro and in vivo. The ferroptosis inhibitor Fer-1 alleviated cell injury and ferroptosis in CIH-treated BEAS-2B and lung tissues of rats.

The overall diet quality in childhood is prospectively associated with the timing of puberty.

PURPOSE: The influences of nutrition in childhood on puberty onset could have sustained consequences for health and wellbeing later in life. The aim of this study was to investigate the prospective association of diet quality prior to puberty with the timing of puberty onset. METHODS: We considered data from 3983 SCCNG (Southwest China Childhood Nutrition and Growth) study participants with dietary data, anthropometric measurement, and information on potential confounders at their baseline assessment (mean age: 7.1 years for girls and 7.3 years for boys; mean length of follow-up was 4.2 years). Cox proportional hazard regression estimating hazard ratios (HRs) and 95% confidence intervals (CIs) were used to examine the relationship between diet quality and puberty onset. Dietary intake at baseline was assessed using a validated food frequency questionnaire. Diet quality was determined using the Chinese Children Dietary Index (CCDI) which measures adherence to current dietary recommendations (theoretical range: 0-160 points). Age at Tanner stage 2 for breast/genital development (B2/G2), menarche or voice break (M/VB) were used as pubertal markers. RESULTS: The CCDI score ranged from 56.2 to 136.3 for girls and 46.1-131.5 for boys. Pubertal markers consistently indicate that girls and boys with higher diet quality were more likely to enter their puberty later than their counterparts with lower CCDI scores (higher vs. lower CCDI tertiles: adjusted HR for age at B2: 0.85 (95% CI, 0.81-0.94), p for trend = 0.02; G2: 0.86 (95% CI,0.80-0.96), p for trend = 0.02; M: 0.86 (95% CI,0.80-0.95), p for trend = 0.02; VB: 0.86 (95% CI,0.79-0.98), p for trend = 0.03), after adjustment for paternal education level, baseline energy intake, and pre-pubertal body fat. CONCLUSIONS: Our data suggested a later puberty onset and later timing of progressed puberty stages in children with a high diet quality, which were independent of pre-pubertal body fat.

Beyond protein intake: does dietary fat intake in the year preceding pregnancy and during pregnancy have an impact on gestational diabetes mellitus?

PURPOSE: Studies regarding the association between dietary fat intake and gestational diabetes mellitus (GDM) are limited and provide conflicting findings. Thus, the study aims to examine the association of dietary fat intake in the year preceding pregnancy and during pregnancy with the risk of GDM, taking the relevance of dietary protein intake on GDM into consideration. METHODS: A prospective study was conducted in 6299 singleton pregnancies, using the data from the Nutrition in Pregnancy and Growth in Southwest China (NPGSC). A validated food frequency questionnaire was used to assess dietary fat intake in the year preceding pregnancy and during the first and second trimesters of pregnancy. Logistic regression analysis was used to assess the prospective associations of dietary fat intake and the type and source of dietary fats in different time windows with GDM risk. RESULTS: Higher intake of total fat [OR (95% CI): 2.21 (1.19-4.20), P = 0.02] during 12-22 weeks of gestation was associated with higher GDM risk. However, adjustment for animal protein intake greatly attenuated this association [OR (95% CI): 1.81 (0.93, 3.64), P = 0.11]. Total fat intake neither in the year preceding pregnancy nor during the early pregnancy was associated with GDM risk. Moreover, insignificant associations were observed between intakes of vegetable fat, animal fat, cholesterol, saturated fatty acid, monounsaturated fatty acid and polyunsaturated fatty acid one year before pregnancy and during the first and second trimesters and GDM risk. CONCLUSION: Our study indicated that dietary fat intake one year before pregnancy and across the two pregnancy trimesters preceding the diagnosis of GDM has no relevance on GDM risk among Chinese women, particularly those with normal BMI, low, or normal calorie intake.

Decreased expression of PPARγ is associated with aortic endothelial cell apoptosis in intermittently hypoxic rats.

PURPOSE: Increasing medical researche shows that endothelial dysfunction is one of the important causes of various cardiovascular diseases related to chronic intermittent hypoxia (CIH). This study aimed to identify target proteins in CIH-related vascular dysfunction. METHODS: A comparative proteomics analysis was conducted in aortic samples of rats treated with CIH and controls with normoxia. Bioinformatics analyses were performed to determine the potential roles of major proteins. The expressions of target proteins were measured by western blotting. Cell apoptotic ratio was detected by flow cytometer. RESULTS: A total of 3,593 proteins in aortic tissues of rats were quantified. Ninety-two upregulated proteins and 468 downregulated proteins were identified when the cutoff of fold change was set at 1.5 (CIH vs. normoxia). The results of bioinformatics analysis revealed that the differentially expressed proteins were enriched in the processes of energy metabolism and lipid metabolism. The reduced expression level of peroxisome proliferator-activated receptor γ (PPARγ) protein was identified in thoracic aortic tissues of rats with CIH by proteomics analysis and western blotting. In intermittent hypoxia-treated rat aortic endothelial cells, PPARγ protein levels were reduced, and the apoptosis rate and caspase-3 and Bax protein levels were markedly elevated. Importantly, forced expression of PPARγ by rosiglitazone in intermittent hypoxia-treated rat aortic endothelial cells not only attenuated caspase-3 and Bax protein levels but also reduced the rate of apoptosis. CONCLUSION: PPARγ is critical in endothelial dysfunction of rats with CIH. Additional studies on these differentially expressed proteins associated with CIH-related endothelial dysfunction are necessary.

Relationship of cord blood IgE with maternal, fetal, and environmental factors in the Chinese population.

INTRODUCTION AND OBJECTIVES: Previous studies reported that history of pregnancy and delivery and family environment might influence cord blood IgE (CB-IgE) levels and development of allergies; however, the association between them is not well-established. This study aimed at investigating the IgE level in the newborn's umbilical cord blood and its relationship with maternal, fetal, and environmental factors. MATERIALS AND METHODS: A total of 989 mothers and their infants were analyzed in this study. Mothers were given a questionnaire that had a series of questions to evaluate demographic information, maternal allergic status, and environmental exposures during pregnancy. Neonatal cord blood samples were taken at the same time for IgE assay. RESULTS: By univariate analysis, we found statistically significant correlations between CB-IgE levels and gender (P = 0.000) and delivery mode (P = 0.017). By multivariate analysis, gender was found to have a significant association with CB-IgE levels (P = 0.001). No significant difference was found between CB-IgE levels and antenatal complications, the season of birth, birth weight, gestational age, and household income (P > 0.050). CONCLUSIONS: In this study, newborn gender was found to be a strong predictor of elevated CB-IgE. The delivery mode was a probable predictor.

Modern dietary pattern is prospectively associated with earlier age at menarche: data from the CHNS 1997-2015.

BACKGROUND: Early age at menarche is associated with risk of several chronic diseases. Prospective study on the association between dietary pattern and timing of menarche is sparse. We examined whether dietary patterns prior to the menarche onset were prospectively associated with menarcheal age in Chinese girls. METHODS: One thousand one hundred eighteen girls aged 6-13 y in the China Health and Nutrition Survey (CHNS) with three-day 24-h recalls and information on potential confounders at baseline were included in the study. Dietary patterns were identified using principal component analysis. Age at menarche was self-reported at each survey. Cox proportional hazard regression models were performed to examine the associations of premenarcheal dietary patterns and menarcheal timing. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. RESULTS: Three major dietary patterns were identified: modern dietary pattern, animal food pattern, and snack food pattern. After adjustment for age at baseline, region, ethnicity, maternal education level, energy intake at baseline, and body mass index Z-score at baseline, girls in the highest quartile of modern dietary pattern score had a 33% higher probability of experiencing menarche at an earlier age than those in the lowest quartile (HR: 1.33, 95% CI: 1.002-1.77, p for trend = 0.03). No significant association was found for the animal food pattern or snack food pattern. CONCLUSIONS: Higher adherence to modern dietary pattern during childhood is associated with an earlier menarcheal age. This association was independent of premenarcheal body size.

The role of ferroptosis in chronic intermittent hypoxia-induced liver injury in rats.

PURPOSE: Obstructive sleep apnea (OSA) has been related to an increased risk of liver injury. Ferroptosis is a form of programmed cell death implicated in multiple physiological and pathological processes. This study aimed to explore the role of ferroptosis in chronic intermittent hypoxia (CIH)-induced liver injury as well as to uncover the underlying mechanisms using a CIH rat model. METHODS: Fourteen male Sprague-Dawley rats were randomly allocated to either the normal control (NC) (n = 7) or the CIH group (n = 7). Rats were exposed to intermittent hypoxia for 8 weeks in CIH group. Liver function, histological changes, and markers of oxidative stress were evaluated. The protein levels of hypoxia-inducible factor-1α, nuclear factor E2-related factor 2 (Nrf2), Acyl-CoA synthetase long-chain family member 4 (ACSL4), and glutathione peroxidase 4 (GPX4) in liver were examined by Western blot analysis. RESULTS: CIH treatment caused significant increase of serum alanine aminotransferase, aspartate aminotransferase, and malondialdehyde (MDA). Liver MDA was significantly higher in CIH group than that in NC group. Histology showed that CIH treatment induced discernible swelled, disordered hepatocytes, necrosis, and infiltrated inflammatory cells. CIH treatment significantly reduced the expression of GPX4, while markedly up-regulated expression of ACSL4, indicating elevation in hepatic ferroptosis. In addition, the protein expression of Nrf2 in CIH group was significantly lower than that in NC group. CONCLUSIONS: Ferroptosis played a crucial role in CIH-induced liver injury. The hepatic ferroptosis in CIH rat model might be mediated by the dysregulation of Nrf2. This highlights a potential therapeutic target for the treatment of OSA-related liver injury.

The effect of continuous positive airway pressure on circulating malondialdehyde among obstructive sleep apnea patients: a meta-analysis.

BACKGROUND: Obstructive sleep apnea (OSA) has been demonstrated to be associated with an increase of oxidative stress. However, whether circulating malondialdehyde (MDA), a widely used biomarker of oxidative stress, could be reduced by the treatment of OSA by continuous positive airway pressure (CPAP) is debated. The present meta-analysis was performed to determine the effect of CPAP treatment on circulating MDA among patients with OSA. METHODS: A systematic search of PubMed, Embase, and Web of Science was performed for literature covering the period between 1967 and August 2019. Standardized mean difference (SMD) was calculated to estimate the treatment effects of pre- and post-CPAP therapy. RESULTS: A total of 10 studies with 220 patients were included in this meta-analysis. A significant decrease in circulating MDA was observed after CPAP treatment (SMD = 1.164, 95% CI = 0.443 to 1.885, z = 3.16, p = 0.002) in OSA patients. Subgroup analyses revealed that CPAP therapy was associated with a significant decrease of circulating MDA in elder (SMD = 1.629, 95% CI = 0.265 to 2.994, z = 2.34, p = 0.019), more obese patients (SMD = 0.954, 95% CI = 0.435 to 1.473, z = 3.61, p = 0.000), more severe OSA patients (SMD = 0.879, 95% CI = 0.421 to 1.336, z = 3.76, p = 0.000), patients with therapeutic duration ≥ 3 months (SMD = 1.867, 95% CI = 0.563 to 3.172, z = 2.80, p = 0.005), and patients with good compliance (SMD = 1.004, 95% CI = 0.703 to 1.305, z = 6.54, p = 0.000). CONCLUSIONS: This meta-analysis suggested that CPAP therapy exerted significant lowering effects on circulating MDA, especially in elder, more obese, and more severe OSA patients and patients with good compliance as well as longer duration of CPAP application.

[Associations of Pre-pregnancy Body Mass Index and Gestational Weight Gain with Gestational Diabetes Mellitus: a Cohort Study in Southwest China].

OBJECTIVE: To determine the associations of pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) with gestational diabetes mellitus (GDM). METHODS: A prospective cohort of pregnant women were screened for GDM at 24-28 weeks of gestation between 2013 and 2015, resulting in a sample of 3 593 with GDM and 15 346 without GDM. The body mass, plasma glucose, and height data of the participants were collected by the local medical workers. Multivariate logistic regression analyses were performed to determine the associations of pre pregnancy body mass index and weight gain during pregnancy with GDM. RESULTS: The participants with pre pregnancy overweight [odds ratio(OR)=2.44, 95% cofidence interval(CI)1.98-2.99] and obesity (OR=4.98, 95%CI 2.52-9.91) were more likely to develop GDM. According to the Institute of Medicine (IOM) criteria, excessive GWG in the first trimester occurred in 8.46% of the women, compared with 55.07% in the second trimester. After adjustment for age at delivery and pre pregnancy BMI, high GWG in the first trimesters in advanced maternal age (age at delivery≥35 yr.) group (OR=1.42, 95%CI 1.02-2.28) was a risk factor for GDM while the OR value of the non-advanced maternal age (age at delivery≤35 yr.) group was not statistically significant. In second trimesters, both advanced maternal age group (OR=1.59, 95%CI 1.14-1.88) and non-advanced maternal age group (OR=1.49, 95%CI 1.20-1.72) in high GWG were associated with high risk of GDM. CONCLUSION: Pre pregnancy overweight and obesity and excessive GWG during early and second trimesters of pregnancy may increase the risk of GDM in women in Southwestern China.