A national survey of iodine nutrition in children aged 3-6 years in China and its relationship with children's physical growth.

Iodine, an essential trace element for the human body, plays a pivotal role in sustaining health. Malnutrition has emerged as a pressing public health concern, posing a significant threat to human well-being. Iodine deficiency poses a substantial threat to the development of children, potentially leading to neurological developmental disorders and mental retardation. Conversely, excessive iodine intake can result in structural and functional abnormalities in the thyroid gland. In this study, we selected children aged 3-6 years through a stratified cluster sampling approach in six regions across China to explore the correlation between iodine nutrition and their physical growth. A total of 5920 preschool children participated in this study, with a median urinary iodine concentration (UIC) of 177.33 [107.06, 269.92] µg/L. Among these children, 250 (4.2%) exhibited stunting, 180 (3.0%) were underweight, 198 (3.3%) experienced wasting, 787 (3.3%) were overweight and 414 (7.0%) were classified as obese. The multivariate linear regression revealed that UIC exhibited a positive correlation with body mass index z-Score (BMIZ) in overweight children (ß = 0.038; 95% CI: 0.001, 0.075). In normally growing children, the associations between UIC and height-for-age z-score, weight-for-age z-score and BMIZ displayed nonlinear patterns. Our findings suggest that iodine nutrition is adequate for Chinese children aged 3-6 years. Furthermore, iodine nutrition is intricately linked to the growth and development of these children. Consequently, it is imperative to implement decisive measures to prevent both iodine deficiency and excess.

Series of Viologen-Based Metal-Organic Polyhedra with Photo/Electrochromic Behavior for Inkless Printing and UV Detection.

The fabrication of molecular crystalline materials with fast, multistimuli-responsive behavior and the construction of the corresponding structure-activity relationship are of extraordinary significance for the development of smart materials. In this context, three multistimuli-responsive functional metal-organic polyhedra (MOP), {[Dy2(bcbp)3(NO3)1.5(H2O)7]·Cl4.2·(NO3)0.3·H2O}n (1), {[Dy2(bcbp)4(H2O)8]Cl6}n (2), and {[Eu2(bcbp)4(H2O)10]Cl6·H2O}n (3; bcbp = 1,1'-bis(4-carboxyphenyl)-4,4'-bipyridinium), were successfully prepared and characterized. All of the compounds exhibit rapid and reversible photochromic and electrochromic dual-responsive behaviors. Furthermore, benefiting from the well-defined crystal structure and different responsive behaviors, the photoinduced electron transfer (PIET) process and structure-activity relationship were explored. In addition, considering the excellent photochromic performance, function filter paper and smart organic glass were successfully prepared and used for ink-free printing and UV light detection.

Iodine status and associated dietary factors among preschool children in Shanghai.

Children aged 3-6 years undergo a critical stage of growth and development and are irreversibly affected by their iodine status. In order to reveal iodine status in preschool children, we detected iodine concentrations in urine samples from 1382 children aged 3-6 years based on a cross-sectional study. The median urinary iodine concentration (UIC) of children was 193.36 µg/L and was 336.96 µg/g·Cr corrected for creatinine. The study developed a link between dietary habits and iodine status, revealing that regular calcium supplement (OR: 1.79, (95% CI: 1.03, 3.12)) increased deficiency risk, while moderate seafood consumption (OR: 0.60, (95% CI: 0.38, 0.95)) decreased it. Additionally, modest intake of shellfish (OR: 0.58, (95% CI: 0.33, 1.00)), vegetables (OR: 0.61, (95% CI: 0.38, 0.97)), and eggs (OR: 0.53, (95% CI: 0.30, 0.95)) was found to protect against excess iodine. The findings underline the importance of balanced diets and various nutrients' roles in preschoolers' iodine status.

Cordycepin delays postovulatory aging of oocytes through inhibition of maternal mRNAs degradation via DCP1A polyadenylation suppression.

Postovulatory aging leads to the decline in oocyte quality and subsequent impairment of embryonic development, thereby reducing the success rate of assisted reproductive technology (ART). Potential preventative strategies preventing oocytes from aging and the associated underlying mechanisms warrant investigation. In this study, we identified that cordycepin, a natural nucleoside analogue, promoted the quality of oocytes aging in vitro, as indicated by reduced oocyte fragmentation, improved spindle/chromosomes morphology and mitochondrial function, as well as increased embryonic developmental competence. Proteomic and RNA sequencing analyses revealed that cordycepin inhibited the degradation of several crucial maternal proteins and mRNAs caused by aging. Strikingly, cordycepin was found to suppress the elevation of DCP1A protein by inhibiting polyadenylation during postovulatory aging, consequently impeding the decapping of maternal mRNAs. In humans, the increased degradation of DCP1A and total mRNA during postovulatory aging was also inhibited by cordycepin. Collectively, our findings demonstrate that cordycepin prevents postovulatory aging of mammalian oocytes by inhibition of maternal mRNAs degradation via suppressing polyadenylation of DCP1A mRNA, thereby promoting oocyte developmental competence.

Effects of food-borne docosahexaenoic acid supplementation on bone lead mobilisation, mitochondrial function and serum metabolomics in pre-pregnancy lead-exposed lactating rats.

Large bone lead (Pb) resulting from high environmental exposure during childhood is an important source of endogenous Pb during pregnancy and lactation. Docosahexaenoic acid (DHA) attenuates Pb toxicity, however, the effect of DHA on bone Pb mobilisation during lactation has not been investigated. We aimed to study the effects of DHA supplementation during pregnancy and lactation on bone Pb mobilisation during lactation and its potential mechanisms. Weaning female rats were randomly divided into control (0.05% sodium acetate) and Pb-exposed (0.05% Pb acetate) groups, after a 4-week exposure by ad libitum drinking and a subsequent 4-week washout period, all female rats were mated with healthy males until pregnancy. Then exposed rats were randomly divided into Pb and Pb + DHA groups, and the latter was given a 0.14% DHA diet, while the remaining groups were given normal feed until the end of lactation. Pb and calcium levels, bone microarchitecture, bone turnover markers, mitochondrial function and serum metabolomics were analyzed. The results showed that higher blood and bone Pb levels were observed in the Pb group compared to the control, and there was a significant negative correlation between blood and bone Pb. Also, Pb increased trabecular bone loss along with slightly elevated serum C-telopeptide of type I collagen (CTX-I) levels. However, DHA reduced CTX-I levels and improved trabecular bone microarchitecture. Metabolomics showed that Pb affected mitochondrial function, which was further demonstrated in bone tissue by significant reductions in ATP levels, Na+-K+-ATPase, Ca2+-Mg2+-ATPase and CAT activities, and elevated levels of MDA, IL-1ß and IL-18. However, these alterations were partially mitigated by DHA. In conclusion, DHA supplementation during pregnancy and lactation improved bone Pb mobilisation and mitochondrial dysfunction in lactating rats induced by pre-pregnancy Pb exposure, providing potential means of mitigating bone Pb mobilisation levels during lactation, but the mechanism still needs further study.

Metabolomics insights into the effects of pre-pregnancy lead exposure on bone metabolism in pregnant rats.

Today's women of childbearing age with a history of high lead (Pb) exposure in childhood have large Pb body burdens, which increases Pb release during pregnancy by promoting bone Pb mobilisation. The purpose of this study was to investigate the metabolic mechanisms underlying bone Pb mobilisation and explore the bone metabolism-related pathways during pregnancy. Drinking water containing 0.05% sodium acetate or Pb acetate was provided to weaned female rats for 4 weeks followed by a 4-week washout period, and then rats were co-caged with healthy males of the same age until pregnancy. Blood and bone tissues of the female rats were collected at gestational day (GD) 3 (early pregnancy), GD 10 (middle pregnancy), and GD 17 (late pregnancy), respectively. Pb and calcium concentrations, biomarkers for bone turnover, bone microstructure, serum metabolomics, and metabolic indicators were intensively analyzed. The results demonstrated that pre-pregnancy Pb exposure elevated blood lead levels (BLLs) at GD17, accompanied by a negative correlation between BLLs and trabecular bone Pb levels. Meanwhile, Pb-exposed rats had low bone mass and aberrant bone architecture with a larger number of mature osteoclasts (OCs) compared to the control group. Moreover, the metabolomics uncovered that Pb exposure caused mitochondrial dysfunction, such as enhanced oxidative stress and inflammatory response, and suppressed energy metabolism. Additionally, the levels of ROS, MDA, IL-1ß, and IL-18 involved in redox and inflammatory pathways of bone tissues were significantly increased in the Pb-exposed group, while antioxidant SOD and energy metabolism-related indicators including ATP levels, Na+-K+-ATPase, and Ca2+-Mg2+-ATPase activities were significantly decreased. In conclusion, pre-pregnancy Pb exposure promotes bone Pb mobilisation and affects bone microstructure in the third trimester of pregnancy, which may be attributed to OC activation and mitochondrial dysfunction.

Methylmercury induced ferroptosis by interference of iron homeostasis and glutathione metabolism in CTX cells.

Environmental methylmercury (MeHg) exposure has gained global attention owing to its serious health hazards, especially neurotoxicity. Ferroptosis is a novel form of programmed cell death characterized by lipid peroxidation and iron overload. However, the occurrence of ferroptosis and its underlying mechanisms have not been fully elucidated in the methylmercury-induced neurotoxicity and the role of Nrf2 in MeHg-induced ferroptosis remains unexplored. In this study, we verified that MeHg decreased cell viability in a dose- and time-dependent manner in the Rat Brain Astrocytes cells (CTX cells). MeHg (3.5 µmol/L) exposure induced CTX cells to undergo ferroptosis, as evidenced by glutathione (GSH) depletion, lipid peroxidation, and iron overload, which was significantly rescued by the ferroptosis-specific inhibitors Ferrostatin-1 and Deferoxamine. MeHg directly disrupted the process of GSH metabolism by downregulating of SLC7A11 and GPX4 and interfered with intracellular iron homeostasis through inhibition of iron storage and export. Simultaneously, the expression of Nrf2 was upregulated by MeHg in CTX cells. Hence, the inhibition of Nrf2 activity further downregulated the levels of GPX4, SLC7A11, FTH1, and SLC40A1, which aggravated MeHg-induced ferroptosis to a greater extent. Overall, our findings provided evidence that ferroptosis played a critical role in MeHg-induced neurotoxicity, and suppressing Nrf2 activity further exacerbated MeHg-induced ferroptosis in CTX cells.

Effects of food-borne cholesterol supplementation on lead-induced neurodevelopmental impairments of rats based on BDNF signaling pathway and cholesterol metabolism.

Despite the ubiquity and prevalence of lead (Pb) in the environment and industry, the mechanism of lead-induced neurotoxicity in the brain remains unclear, let alone its prevention and treatment. In this study, we hypothesized that exogenous cholesterol supplementation acts as an effective remedy for lead-induced neurodevelopmental impairments caused by lead. Forty 21-day-old male rats were randomly divided into four groups and administered 0.1 % lead water and/or 2 % cholesterol-containing feed for 30 d. Ultimately, rats in the lead group lost weight, accompanied by spatial learning and memory impairments as verified by the Morris water maze test, in which the escape latency of rats was prolonged, and the number of crossings in the target platform and the residence time in the target quadrant were significantly diminished compared to the control group. Hematoxylin-Eosin (H&E) staining and Nissl staining illustrated that typical pathological morphology occurred in the brain tissue of the lead group, where the tissue structure was loose, the number of hippocampal neurons and granulosa cells decreased significantly and were arranged loosely, along with enlarged intercellular space, light matrix staining, and decline in Nissl bodies. In addition, inflammatory response and oxidative stress were significantly induced by lead. Immunofluorescence experiments showed apparent activation of astrocytes and microglia, followed by the enhancement of TNF-α and IL-ß levels. Moreover, the MDA content in the lead group was elevated dramatically, whereas the activities of SOD and GSH were significantly inhibited. As for the mechanism, western blot and qRT-PCR experiments were performed, where lead could significantly inhibit the BDNF-TrkB signaling pathway, lowering the protein expression of BDNF and TrkB. Cholesterol metabolism was also affected by lead exposure, in which cholesterol metabolism-related protein expression and gene transcription, including SREBP2, HMGCR, and LDLR, were downregulated. However, cholesterol supplementation efficiently detoxified the negative effects of lead-induced neurotoxicity, reversing the inflammatory response, oxidative stress, inactivation of the BDNF signaling pathway, and imbalance of cholesterol metabolism, thus improving the learning and memory ability of rats. In brief, our study demonstrated that cholesterol supplementation could ameliorate the deficiency of learning and memory induced by lead, which is closely associated with the initiation of the BDNF/TrkB signaling pathway and regulation of cholesterol metabolism.

Chronic environmental inorganic arsenic exposure causes social behavioral changes in juvenile zebrafish (Danio rerio).

Arsenic (As) is a metalloid commonly found worldwide. Environmental As exposure may cause potential health hazards and behavioral changes in humans and animals. However, the effects of environmental As concentrations on social behavior, especially during the juvenile stage, are unclear. In this study, we observed behavioral changes in juvenile zebrafish after 28 days of exposure to inorganic As (NaAsO2 100 and 500 ppb) in water, especially anxiety and social deficits. Additionally, the level of oxidative stress in the zebrafish brain after As treatment increased, the content of dopamine (DA) decreased, and the transcription level of genes involved in DA metabolism with the activity of monoamine oxidase (MAO) increased. Oxidative stress is a recognized mechanism of nerve damage induced by As exposure. The zebrafish were exposed to N-acetylcysteine (NAC) to reduce As exposure-induced oxidative stress. The results showed improvements in social behavior, DA content, MAO activity, and gene transcription in zebrafish. In conclusion, environmental As exposure can induce behavioral abnormalities, such as anxiety and social deficits in zebrafish, which may be caused by As-induced oxidative stress altering gene transcription levels, causing an increase in MAO activity and a decrease in DA.

Sex-specific associations between cord blood lead and neurodevelopment in early life: The mother-child cohort (Shanghai, China).

The extent to which neurodevelopment is affected by prenatal lead exposure has not been conclusive. In addition, studies on the effects of sex on these relationships are inconsistent. The aim of this study was to investigate the impact of cord blood lead on neurodevelopment in children within sex subgroups. A total of 275 mother-child pairs from the Shanghai mother-child cohort were included. Umbilical cord blood lead was measured using graphite furnace atomic absorption spectrophotometry. The Bayley Scales for Infant Development-III (BSID-III) was used to measure the neurodevelopment of infants at the age of 18 ± 1.5 months. The median and interquartile range of cord blood lead levels in the total participants, male, and female children were 44.0 (24.5) µg/L, 44.0 (24.3) µg/L, and 46.0 (24.0) µg/L, respectively. According to multiple linear regression, cord blood lead concentrations showed a negative association with fine motor scores in all models associated with female children (ß = -1.5; 95%confidence interval: -2.6, -0.4). However, prenatal lead levels were not associated with any of the BSID-III scores in male children. In addition, cord serum DHA was found positively related to fine motor scores in male children. Our findings suggest that prenatal lead exposure could lead to decreased motor function, although this phenomenon was only observed in female children. And DHA may be a protective factor against lead exposure in boys. Thus, further studies are needed to investigate the associations between prenatal lead exposure and neurobehavioral development, as well as the mechanism of sex differences.

LAMC2 as a prognostic biomarker in human cancer: a systematic review and meta-analysis.

OBJECTIVES: Accumulating evidence suggested that the laminin γ2 (LAMC2) expression level was upregulated in various cancers. However, the potential prognostic value of LAMC2 in cancers remains unclear. We conducted a meta-analysis to clarify the association of LAMC2 expression with prognosis. DESIGN: We searched Embase, Web of Science and PubMed (up to 25 November 2021) to collect all eligible studies, and meta-analysis was performed to interpret the association of LAMC2 expression with clinicopathological parameters, overall survival (OS), disease-specific survival (DSS) and progression-free survival (PFS). ELIGIBILITY CRITERIA FOR INCLUDING STUDIES: We included studies that investigate the relationship between LAMC2 and prognosis of cancers, patients were divided into two groups, and associations of LAMC2 expression with clinicopathological features were described. RESULTS: Seven studies were finally included. We found that increased LAMC2 expression was significantly associated with lymph node metastasis (log OR 0.88, 95% CI 0.38 to 1.38, p<0.001), tumour-node-metastasis stages (log OR: 0.95, 95% CI 0.39 to 1.50, p<0.001) and tumour status (log OR 1.26, 95% CI 0.84 to 1.68, p<0.001), but not with age (log OR -0.05, 95% CI -0.37 to 0.27, p=0.75) or gender (log OR -0.07, 95% CI -0.52 to 0.38, p=0.75). In addition, higher LAMC2 expression was found to be significantly associated with OS/PFS/DSS (HR 1.85, 95% CI 1.31 to 2.40, p<0.001). A similar result was found in The Cancer Genome Atlas database. High LAMC2 expression was significantly associated with OS in lung adenocarcinoma, mesothelioma, skin cutaneous melanoma, neck squamous cell carcinoma and brain lower grade glioma. CONCLUSION: Our results suggested that higher LAMC2 expression was correlated with worse survival, lymph node metastasis, tumour-node-metastasis stages and tumour status. This study was subject to inherent limitations, but the results presented here provide insights regarding the potential use of LAMC2 as a biomarker for human cancer. STUDY REGISTRATION: researchregistry.com (researchregistry1319).

Amelioration of cholesterol sulfate for lead-induced CTX cell apoptosis based on BDNF signaling pathway mediated cholesterol metabolism.

Lead (Pb), as a deleterious heavy metal, ubiquitously exists in environment and industry, which engenders multi-organ disfunction, especially the brain of infants who are vulnerable to attack from lead-induced neurotoxicity. Although cholesterol sulfate (CS) is crucial constituent of cell membranes and precursor of neurosteroids, which maintains the function and survival of neurons, the role of CS in lead-induced neurological damage still remains incomplete. In this work, Rat Brain Astrocytes cell line (CTX cells) was applied into exploration that protective effects of CS on CTX cell apoptosis induced by lead via the regulation of BDNF/TrkB signaling pathway mediated cholesterol metabolism. We found that CTX cells exposed to lead manifested apparent cytotoxicity, where the viability of CTX cells was significantly suppressed, accompanied with the elevation of apoptosis, in response to a trend towards increases in reactive oxygen species (ROS) production and pro-apoptotic protein Cleaved-caspase3, synchronized with the decline in anti-apoptotic protein Bcl-2. Moreover, accumulation of lead in CTX cells showed a dose-dependent increase, and meanwhile, decrements in cholesterol content occurred along with increase in lead exposure, in which expressions of cholesterol metabolism related proteins and transcriptions of its genes (SREBP2, LDLR, and HMGCR) were diminished. Furthermore, BDNF signaling pathway was obviously blocked after lead exposure, down-regulating expressions of proteins BDNF and TrkB. However, pretreatment with CS detoxified the negative impacts of lead-invoked CTX cell damage, acting as an effective remedy for apoptosis, imbalance of cholesterol metabolism and inhibition of BDNF signaling pathway. In addition, the relationship between BDNF signaling pathway and cholesterol metabolism was further verified, in which cholesterol metabolism related proteins and genes were promoted significantly after the activation of BDNF/TrkB signaling pathway using 7,8-Dihydroxyflavone (7,8-DHF), thereby detoxifying lead-induced CTX cell injury. However, the pretreatment of TrkB inhibitor ANA-12 offset the promotion of 7,8-DHF and ultimately inhibit cholesterol metabolism. Overall, our study demonstrated that CS could initiate the BDNF/TrkB signaling pathway, regulating the cholesterol metabolism against CTX cell apoptosis invoked by lead.

Relationship between thyroid hormone parameters and exposure to a mixture of organochlorine pesticides, mercury and nutrients in the cord blood of newborns.

The fetus is prenatally exposed to a mixture of organochlorine pesticides (OCPs), mercury (Hg), docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and selenium (Se) through maternal seafood consumption in real-life scenario. Prenatal exposure to these contaminants and nutrients has been suggested to affect thyroid hormone (TH) status in newborns, but the potential relationships between them are unclear and the joint effects of the mixture are seldom analyzed. The aim of the study is to investigate the associations of prenatal exposure to a mixture of OCPs, Hg, DHA, EPA and Se with TH parameters in newborns. 228 mother-infant pairs in Shanghai, China were included. We measured 20 OCPs, total Hg, DHA, EPA and Se in cord blood samples as exposure variables. The total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3), free triiodothyronine (FT3), and thyroid-stimulating hormone (TSH) levels and the FT3/FT4 ratio in cord serum were determined as outcomes. Using linear regression models, generalized additive models and Bayesian kernel machine regression, we found dose-response relationships of the mixture component with outcomes: among the contaminants, p,p'-DDE was the most important positive predictor of TT3, while HCB was predominantly positively associated with FT3 and the FT3/FT4 ratio, indicating different mechanisms underlying these relationships; among the nutrients, EPA was first found to be positively related to the FT3/FT4 ratio. Additionally, we found suggestive evidence of interactions between p,p'-DDE and HCB on both TT3 and FT3, and EPA by HCB interactions for TT3, FT3 and FT3/FT4 ratio. However, the overall effects of the mixture on thyroid hormone parameters were not significant. Our result suggests that prenatal exposure to p,p'-DDE, HCB and EPA as part of a mixture might affect thyroid function of newborns in independent and interactive ways. The potential biological mechanisms merit further investigation.

Diagnostic and prognostic value of secreted protein acidic and rich in cysteine in the diffuse large B-cell lymphoma.

BACKGROUND: Secreted protein acidic and rich in cysteine (SPARC) is an extracellular matrix-associated protein. Studies have revealed that SPARC is involved in the cell interaction and function including proliferation, differentiation, and apoptosis. However, the role of SPARC in cancer is controversial, as it was reported as the promoter or suppressor in different cancers. Further, the role of SPARC in lymphoma is unclear. AIM: To identify the expression and significance of SPARC in lymphoma, especially in diffuse large B-cell lymphoma (DLBCL). METHODS: The expression analysis of SPARC in different cancers was evaluated with Oncomine. The Brune, Eckerle, Piccaluga, Basso, Compagno, Alizadeh, and Rosenwald datasets were included to evaluate the mRNA expression of SPARC in lymphoma. The Cancer Genome Atlas (TCGA)-DLBCL was used to analyze the diagnostic value of SPARC in DLBCL. The Compagno and Brune DLBCL datasets were used for validation. Then, the diagnostic value was evaluated with the receiver operating characteristic (ROC) curve. The Kaplan-Meier plot was conducted with TCGA-DLBCL, and the ROC analysis was performed based on the survival time. Further, the overall survival analysis based on the level of SPARC expression was performed with the GSE4475 and E-TABM-346. The Gene Set Enrichment Analyses (GSEA) was performed to make the underlying mechanism-regulatory networks. RESULTS: The pan-cancer analysis of SPARC showed that SPARC was highly expressed in the brain and central nervous system, breast, colon, esophagus, stomach, head and neck, pancreas, and sarcoma, especially in lymphoma. The overexpression of SPARC in lymphoma, especially DLBCL, was confirmed in several datasets. The ROC analysis revealed that SPARC was a valuable diagnostic biomarker. More importantly, compared with DLBCL patients with low SPARC expression, those with higher SPARC expression represented a higher overall survival rate. The ROC analysis showed that SPARC was a favorable prognostic biomarker for DLBCL. Results of the GSEA confirmed that the high expression of SPARC was closely associated with focal adhesion, extracellular matrix receptor interaction, and leukocyte transendothelial migration, which suggested that SPARC may be involved in the regulation of epithelial-mesenchymal transition, KRAS, and myogenesis in DLBCL. CONCLUSION: SPARC was highly expressed in DLBCL, and the overexpression of SPARC showed sound diagnostic value. More interestingly, the overexpression of SPARC might be a favorable prognostic biomarker for DLBCL, suggesting that SPARC might be an inducible factor in the development of DLBCL, and inducible SPARC was negative in some oncogenic pathways. All the evidence suggested that inducible SPARC might be a good diagnostic and prognostic biomarker for DLBCL.

Clinical Efficacy of Corticosteroids in the Early Stages of Deterioration in COVID-19 Pneumonia.

BACKGROUND: The World Health Organization (WHO) strongly suggests using corticosteroids in patients with severe coronavirus disease 2019 (COVID-19). Similarly, a large randomized controlled clinical trial (RCT) in the UK found that dexamethasone effectively reduced the mortality rate in severe COVID-19 patients. However, the safety profile of corticosteroids has been a controversial area of study. CASE DESCRIPTION: A case of a COVID-19 patient is described and the clinical characteristics are observed as the mildly symptomatic patient progresses into a critically ill patient and during their dramatic improvement with corticosteroid therapy in the early stage of the deterioration process with COVID-19 pneumonia. CONCLUSION: The most suitable timing and dosage for the use of corticosteroids to maximize its effect during the worsening of COVID-19 pneumonia are discussed. One of the main pathophysiological hypotheses for severe COVID-19 patients is related to cytokine storm and virus load, which can be effectively treated with corticosteroid therapy.

Prolonged interval time between blastocyst biopsy and vitrification compromised the outcomes in preimplantation genetic testing.

This study aimed to evaluate to what extent the different interval times between trophectoderm (TE) biopsy and vitrification influence the clinical outcomes in preimplantation genetic testing (PGT) cycles. Patients who underwent frozen embryo transfer (FET) after PGT between 2015 and 2019 were recruited. In total, 297 cycles with single day 5 euploid blastocyst transfer were included. These cycles were divided into three groups according to the interval times: <1 h group, 1-2 h group, and ≥2 h group. Blastocyst survival, clinical pregnancy, miscarriage, and ongoing pregnancy rates were compared. The results showed that, in PGT-SR cycles, survival rate in the ≥2 h group (96.72%) was significantly lower than in the <1 h group (100%, P = 0.047). The clinical pregnancy rate in the ≥2 h group was 55.93%, significantly lower than in the <1 h group (74.26%, P = 0.017). The ongoing pregnancy rates in the 1-2 h group and the ≥2 h group were 48.28% and 47.46%, respectively, significantly lower than that in the <1 h group (67.33%, P < 0.05). The miscarriage rate in the 1-2 h group was 18.42%, significantly higher than that in the <1 h group (5.33%, P = 0.027). In PGT-A cycles, the clinical pregnancy and ongoing pregnancy rates in the <1 h group were 67.44% and 53.49%, respectively, higher than that in the 1-2 h group (52.94%, 47.06%, P > 0.05) and the ≥2 h group (52.63%, 36.84%, P > 0.05). In conclusion, vitrification of blastocysts beyond 1 h after biopsy significantly influences embryo survival and clinical outcomes and is therefore not recommended.

The expressions and significance of B7-H3 and CTLA-4 in the clinical stages of non-small-cell lung cancer.

The aim of this study was to analyze the expressions and significance of B7-H3 and CTLA-4 in the clinical stages of non-small-cell lung cancer (NSCLC). Seventy patients with NSCLC who underwent surgical resection or biopsy between January 2016 and February 2018 were enrolled. Among them, 30 were cases of paracancerous tissues and were assigned to the control group (CON). These cases were analyzed using immunochemical methods. Of the 70 cases, 48 were of adenocarcinoma, 19 were of squamous cell carcinoma, and 3 were of adenosquamous carcinoma. The expression rates of B7-H3 and CTLA-4 in the observation group (OBS) were 64.2% and 57.1% respectively, and those in the CON group were 6.7% and 0%, respectively (χ2=27.988, 28.571, P<0.001). The expression levels of B7-H3 and CTLA-4 in patients with poor differentiation, in stages III-IV, or with lymph node metastasis were significantly higher than those in patients with good-to-moderate differentiation, in stages I-II, and without lymph node metastasis (P<0.05). There was a positive correlation between the expressions of B7-H3 and CTLA-4 in the OBS group (r=0.74, P<0.05). B7-H3 and CTLA-4 are highly expressed and positively correlated with each other in NSCLC patients and are also closely related to clinical stages.

Effects of lead, mercury, aluminium and manganese co-exposure on the serum BDNF concentration of pre-school children in Taizhou, China.

Previous studies have shown that toxic metal exposure can have adverse effects on the nervous system of children, but the toxicology of metal co-exposure on neurodevelopment remains to be clarified. Brain derived neurotrophic factor (BDNF) plays an important role in nervous system development, but the possible effects of metal co-exposure on the serum BDNF concentrations of children remain unknown. A total of 561 children living in Taizhou City, China were recruited to participate in our cross-sectional multicenter survey. We measured their blood Pb, Hg, Al and Mn levels and serum BDNF concentrations as well as determined their associations in the total and within sex subgroups. The geometric means of the blood Pb, Hg, Al and Mn levels in all the participants were 67.18 µg/L, 1.01 µg/L, 52.03 µg/L and 18.26 µg/L, respectively. The serum BDNF concentration in children was 19.45 ng/mL. After adjusting for confounders, the blood Pb levels were significantly negatively associated with the serum BDNF concentrations in all the subjects and boys but not in girls. In addition, a significantly negative interaction between blood Pb and blood Hg and a positive interaction between blood Pb and blood Al on serum BDNF concentrations were also observed in boys but not in girls. Our findings highlight the toxic effects of metal co-exposure on serum BDNF levels in pre-school children and indicate that these effects might differ by gender, which suggest that special attention should be paid to the sex-specific effects of metal exposure.

Effect of the emphysema subtypes of patients with chronic obstructive pulmonary disease on airway inflammation and COTE index.

The aim of the present study was investigate the association of the severity of emphysema of patients with chronic obstructive pulmonary disease (COPD) with airway inflammation and the COPD-specific comorbidity test (COTE) index. A total of 94 patients with COPD were divided into four groups according to the severity of their emphysema; in each patient, comorbidities were recorded and inflammatory biomarkers, including MMP-9 and TIMP-1 were determined in circulating blood. The unbalanced proportion of MMP-9 and its inhibitor, TIMP-1, led to the airway inflammation and lung remodeling in the patients with COPD. A total of 80.85% of the patients had emphysema of different degrees. The quantity of male patients and the smoking index in the three emphysema groups were significantly higher than those in the non-emphysema group (F=7.67 and 5.42, P<0.05). The level of the predicted percent offorced expiratory volume in 1 sec in the non-emphysema group were significantly higher than those in the emphysema group (4.33; P<0.05), and the level of D-dimer in the non-emphysema group was significantly lower than that in the mild and moderate emphysema groups (F=9.38, P<0.05). The low-attenuation area score was negatively correlated with inhaled bronchodilators (r=-0.240, P=0.007) but positively correlated with the frequency of acute exacerbations in the previous year (r=0.211, P=0.001). In terms of treatment, the use of systemic hormone therapy in the emphysema group was more frequent than that in the non-emphysema group (F=6.21, 12.92 and 4.08, P<0.05). The level of MMP-9 was significantly higher in COPD patients with >3 comorbidities, a COTE index of ≥4 and cardiovascular disease as well as coronary heart disease (t=6.40, 2.53, 3.65 and 2.90, P<0.05). The level of MMP-9 was positively correlated with the neutrophilic granulocyte percentage, the number of comorbidities and the COTE index (r=0.193, 0.402 and 0.311, P<0.01). The severity of emphysema in patients with COPD was correlated with the persistence of inflammatory factors in the circulating blood and the frequency of acute exacerbations. It was indicated that MMP-9 has a critical role in numerous comorbidities of COPD.

Lead exposure induces Alzheimers's disease (AD)-like pathology and disturbes cholesterol metabolism in the young rat brain.

Lead exposure has been evidenced as a risk factor for Alzheimer's disease (AD), mainly affecting the ageing. However, the early manifestation and mechanisms of AD-like pathology induced by lead exposure remains to be elucidated. Considering the fact that impaired cholesterol metabolism is associated with many neurodegenerative disorders including AD, in this study we focused on the role of cholesterol metabolism in lead induced premature AD-like pathology. We treated weaning rats with lead at different concentrations for 4 weeks. We found that developmental lead exposure increased amyloid-beta (Aß) accumulation and amyloid plaque deposition in the cortex and hippocampus. Lead exposure increased amyloid precursor protein (APP) expression and activated the sterol regulatory element binding protein 2 (SREBP2)-beta secretase (BACE1) pathway. In addition, we found that lead exposure decreased cholesterol levels by upregulating the expression of liver X receptor-a (LXR-a) and ATP-binding cassette transporter protein family member A1 (ABCA1) and decreasing the expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CR) and low density lipoprotein receptor (LDL-R) in young rat brain tissues. Taken together, our data demonstrated that developmental lead exposure induced early manifestation of AD-like pathology and disturbed cholesterol metabolism in young rat brains.