Association of polycyclic aromatic hydrocarbons exposure with child neurodevelopment and adult emotional disorders: A meta-analysis study.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) have been demonstrated to be neurotoxic. OBJECTIVES: To summarize the existing epidemiological studies to quantify the effects of PAHs exposure on child neurodevelopment and adult emotional disorders. DATA SOURCES AND STUDY ELIGIBILITY CRITERIA: We conducted a systematic literature search for studies of child neurodevelopment and adult emotional disorders published in English up to April 2022 in the databases of PubMed, Web of Science and Embase using combinations of MeSH terms and Entry terms, and the articles were filtered out according to data availability. A variety of common PAHs were included in the meta-analysis: 1-hydroxynaphthalene, 2-hydroxynaphthalene, 2-hydroxyfluorene, 3-hydroxyfluorene, 9-hydroxyfluorene, 1-hydroxyphenanthrene, 2-hydroxyphenanthrene, 3-hydroxyphenanthrene, 4-hydroxyphenanthrene, 9-hydroxyphenanthrene, 1-hydroxypyrene and benzoapyrene (BaP). STUDY EVALUATION AND SYNTHESIS METHODS: We extracted the content of each article, summarized its design characteristics and performed quality evaluation. We combined the odds ratio (OR) available in various studies to obtain the risk of PAHs exposure and adaptive, language, social, attention, motor skills and child depression/anxiety in children ≤ 15 years old. In addition, we also conducted a meta-analysis on the relationship between PAHs exposure and the risk of depression in adults. RESULTS: We included a total of 16 epidemiological studies (4 cross-sectional studies and 12 cohort studies). The sample size of all included studies ranged from 110 to 9625. Prenatal exposure to PAHs was found to be associated with increased risk of social behavior (OR = 1.60, 95% CI: 1.00-2.54), attention (OR = 2.99, 95% CI: 1.48-6.02), motor skill problems (OR = 1.91, 95% CI: 1.27-2.86) and any adverse neurodevelopmental outcome in children (OR = 2.10, 95% CI: 1.69-2.62). In addition, we found that PAHs exposure could increase the risk of adult depression, with 2-hydroxyfluorene exposure showing the highest combined OR (OR = 1.48, 95% CI: 1.10-2.00). CONCLUSIONS: The results suggested that PAHs exposure are associated with increased risk of child neurodevelopment and adult depression. The neurotoxic effects of PAHs exposure in human being should be paid more attention. The results suggested that PAHs exposure are associated with increased risk of child neurodevelopment and adult depression. The neurotoxic effects of PAHs exposure in human being should be paid more attention. Steps should be taken to enhance the biomonitoring of PAHs and to reduce the exposure in general population.

Clinical utility and effectiveness of a training programme in the application of a new classification of narrow-band imaging for vocal cord leukoplakia: A multicentre study.

OBJECTIVE: To analyse the application of a new narrow-band imaging (NBI) classification in the diagnosis of vocal cord leukoplakia by laryngologists with different levels of laryngoscopic experience and to explore the impact of NBI training programmes on laryngologists' identification of benign and malignant leukoplakia. DESIGN: Prospective multicentre study. SETTING: Tertiary hospitals. PARTICIPANTS: Sixteen laryngologists were divided into less-experienced and experienced groups and received NBI training course. Thirty cases of vocal cord leukoplakia were investigated. MAIN OUTCOME MEASURES: Diagnostic accuracy and interobserver agreement under white light imaging (WLI), before and after NBI training, were analysed among doctors with varying levels of experience. RESULTS: The accuracy in the less-experienced group was significantly lower than that of experience group (0.59 vs 0.69) under WLI. There was no significant difference in the diagnostic accuracy between the less-experienced group and the experienced group before NBI training (0.75 vs 0.74) and after NBI training (0.79 vs 0.83). NBI training could improve the interobserver agreement from fair or moderate to good agreement. CONCLUSION: The new NBI diagnostic classification is helpful for identifying benign and malignant vocal cord leukoplakia. In addition, the NBI training programme can improve the diagnostic accuracy and interobserver agreement of less-experienced doctors to the level of experienced laryngologists.

Low Dose of 5-Aminolevulinic Acid Hydrochloride Alleviates the Damage in Cardiomyocytes Induced by Lenvatinib via PI3K/AKT Signaling Pathway.

BACKGROUND: Lenvatinib is an oral tyrosine kinase inhibitor (TKI), and has been applied in the clinical trials for the treatment of hepatocellular carcinoma (HCC). The function of 5-aminolevulinic acid hydrochloride (ALA) treatment in protecting cardiomyocytes under lenvatinib stimulation was investigated. METHODS: H9c2 cells were treated with 2 mg/mL lenvatinib for 48 h and 1 mM ALA in the lenvatinib with low dose 5-aminolevulinic acid treatment group (LL) group, 10 mM ALA in the lenvatinib with high-dose 5-aminolevulinic acid treatment group (LH) group and cells without treatment were used as an internal control. C57/BL mice were treated with 10 mg/kg lenvatinib and 200 mg/kg ALA in the LL group and 400 mg/kg ALA in the LH group by gavage once per day for 4 weeks. The proliferation ability of cells was detected using the methyl thiazolyl tetrazolium (MTT) assay. Target gene expression was calculated through real-time quantitative PCR (qPCR), and target protein expression was calculated through Western blotting analysis. The concentrations of cardiovascular protective factors were detected using enzyme linked immunosorbent assay (ELISA). RESULTS: In these experiments, 10 mM ALA significantly increased the viability rate of cardiomyocytes (105.4 ± 8.0%) compared with the single lenvatinib treatment group (73.2 ± 6.5%). We also noticed that activation of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathways were activated after low-dose ALA treatment. 5-ALA treatment led to the downregulation of intercellular cell adhesion molecule-1 (ICAM-1) (0.81- and 0.71-fold), vascular cell adhesion molecule (VCAM) (0.63- and 0.66-fold), angiotensin I (ANGI) (0.88- and 0.66-fold), ANGII (0.66- and 0.48-fold) and upregulation of endothelial nitric oxide synthases (eNOS) (1.25- and 1.89-fold) compared with non 5-ALA treatment group. CONCLUSIONS: With more experiments on animal models, low-dose of ALA treatment might be a therapeutic strategy to alleviate the damage to cardiomyocytes induced by lenvatinib.

SLC7A11, a potential immunotherapeutic target in lung adenocarcinoma.

SLC7A11 has significant translational value in cancer treatment. However, there are few studies on whether SLC7A11 affects the immune status of lung adenocarcinoma (LUAD). Information on SLC7A11 expression and its impact on prognosis was obtained from the cancer genome atlas and gene expression omnibus databases. The differentially expressed genes (DEGs) were analysed by GO and KEGG. GSEA enrichment analysis was performed in the SLC7A11-high and SLC7A11-low groups. The relationship between SLC7A11 and tumour immunity, immune checkpoints, and immune cell infiltration was studied using R language. We analysed the correlation between SLC7A11 and chemotactic factors (CFs) and chemokine receptors using the TISIDB database. SLC7A11 is overexpressed in many tumours, including LUAD. The 5-year overall survival of patients in the SLC7A11-high group was lower than in the SLC7A11-low group. KEGG analysis found that the DEGs were enriched in ferroptosis signaling pathways. GSEA analysis found that the survival-related signaling pathways were enriched in the SLC7A11-low group. The SLC7A11-low group had higher immune scores and immune checkpoint expression. SLC7A11 was negatively correlated with many immune cells (CD8+ T cells, immature dendritic cells), CFs, chemokine receptors (such as CCL17/19/22/23, CXCL9/10/11/14, CCR4/6, CX3CR1, CXCR3) and MHCs (major histocompatibility complex). SLC7A11 may regulate tumour immunity and could be a potential therapeutic target for LUAD.

Shift work and menstruation: A meta-analysis study.

Background: Shift work is a potential risk factor for women's reproductive health. Evidence suggests that shift work is associated with menstrual disorders, reproductive disturbances, and adverse pregnancy outcomes. However, previous studies did not systematically examine the results of menstrual irregularities, dysmenorrhea, and early menopause at the same time. Objective: To determine the relationship between shift work and women's menstrual characteristics (e.g., irregular menstruation, dysmenorrhea, and early menopause). Methods: Four databases (PubMed, Embase, Cochrane, and Web of Science) were searched up to December 2022. The study characteristics and risk assessment values of the literature were extracted from 21 studies that met the criteria. Odds ratios (ORs), relative risks (RRs), hazard ratios (HRs), and 95% confidence intervals (CIs) were calculated to assess the relationship between shift work exposure and menstruation. The included studies were evaluated for heterogeneity, publication bias, sensitivity analysis, and subgroup analysis. Results: A total of 21 studies with 195,538 female participants, including 16 cross-sectional studies and 5 cohort studies, were included in this meta-analysis. According to the quality evaluation, the included research had high methodological quality. The overall ORs of shift work for the likelihood of irregular menstruation and dysmenorrhea were 1.30 (95% CI, 1.23-1.36) (I2 = 41.9%, P < 0.05) and 1.35 (95% CI, 1.04-1.75) (I2 = 73.0%, P < 0.05), respectively. There was a significant positive association between shift work and the risk of early menopause (HR = 1.09, 95% CI, 1.04-1.14), without significant heterogeneity (I2 = 0.0%, P > 0.05). Conclusions: This meta-analysis indicated that shift workers have significantly higher odds of menstrual disorders, dysmenorrhea, and early menopause. This study focuses on female reproductive health and has broad implications for adjusting optimal working hours and shift schedules for female workers.

Clinical efficacy of Gualou Xiaoyong Decoction and painless lactation manipulation in treating lactation acute mastitis and breast abscess: An observational study.

Information on the effects of Chinese medicine in the treatment of lactational acute mastitis and breast abscess is limited; thus, we conducted an observational study to analyze the clinical efficacy of Gualou Xiaoyong Decoction combined with painless lactation manipulation in the treatment of lactational acute mastitis and breast abscess. A total of 41 patients with lactational acute mastitis and breast abscess who were treated with Gualou Xiaoyong Decoction and painless lactation manipulation from October 2021 to October 2022 were included in this study. The age, fetal times(primiparous/multiparous), delivery mode (cesarean section/vaginal delivery), onset time, breast lump diameter, skin rash diameter, body temperature, visual analogue score, blood routine, C-reactive protein, procalcitonin, bacterial culture in milk, B ultrasound and other data of these patients were statistically analyzed. After treatment, the breast lump diameter of these patients decreased significantly, the skin rash diameter was reduced or disappeared, the body temperature decreased or returned to a normal range, and the visual analogue score also decreased. Besides, these patients had a decreased total number of white blood cells and a reduced percentage of neutrophils, C-reactive protein, and procalcitonin after treatment. In addition, bacteria in the milk of most patients disappeared, and there was no abnormality in B ultrasonic imaging. Except for 2 patients with breast abscess who stopped breastfeeding on the affected side for 1 day and 3 days respectively, all other patients continued to provide breast milk for their infants, and no adverse reactions were observed in these infants. The combination of Gualou Xiaoyong Decoction and painless lactation manipulation can achieve favorable clinical effects in the treatment of lactational acute mastitis and breast abscess. This combined therapy has good efficacy, short course of treatment, low costs, and great convenience with the avoidance of pain, hospitalization, influence on lactation, breast scar and other adverse outcomes.

A new method for preparing a rat intracerebral hemorrhage model by combining focused ultrasound and microbubbles.

BACKGROUND: We aimed to prepare a non-invasive, reproducible, and controllable rat model of intracerebral hemorrhage with focused ultrasound (FUS). METHODS: A rat intracerebral hemorrhage (ICH) model was established by combining FUS and microbubbles (µBs), and edaravone was used to verify whether the free radical scavenger had a protective effect on the model. The brain tissue of each group was sectioned to observe the gross histology, blood-brain barrier (BBB) permeability, cerebral infarction volume, and histopathological changes. RESULTS: Compared with the FUS group, the BBB permeability was significantly increased in the FUS + µBs (F&B) group (p = 0.0021). The second coronal slice in the F&B group had an obvious hemorrhage lesion, and the FUS + µBs + edaravone (F&B&E) group had smaller hemorrhage areas; however, ICH did not occur in the FUS group. The cerebral infarction volume in the F&B group was significantly larger than that in the FUS group (p = 0.0030) and F&B&E group (p = 0.0208). HE staining results showed that nerve fibrinolysis, neuronal necrosis, microglia production, and erythrocytes were found in both the F&B group and the F&B&E group, but the areas of the nerve fibrinolysis and neuronal necrosis in the F&B group were larger than the F&B&E group. CONCLUSIONS: A rat ICH model was successfully prepared using the µBs assisted FUS treatment, and edaravone had a therapeutic effect on this model. This model can be used to study the pathophysiological mechanism of ICH-related diseases and in preclinical research on related new drugs.

Di-(2-ethylhexyl) phthalate exposure induces liver injury by promoting ferroptosis via downregulation of GPX4 in pregnant mice.

As one kind of endocrine disrupting chemical, di-(2-ethylhexyl) phthalate (DEHP) has been reported to cause liver dysfunction in epidemiological and experimental studies. Abnormal liver function in pregnancy is associated with adverse maternal and perinatal outcomes. Few studies have investigated the potential effect of gestational DEHP exposure on the liver in pregnant mice, and the underlying mechanisms remain unclear. In the present study, pregnant ICR mice were exposed to doses (0, 500, 1,000 mg/kg/day) of DEHP in the presence or absence of 5 mg/kg/day ferrostatin-1 (Fer-1, ferroptosis inhibitor) by oral gavage from gestation day 4 to day 18. HepG2 cells were exposed to different doses of monoethylhexyl phthalate (MEHP, a major metabolite of DEHP) in vitro. Hepatic function and pathologic changes were observed. Oxidative stress, iron metabolism, and ferroptosis-related indicators and genes were evaluated both in vivo and in vitro. The results showed that gestational DEHP exposure induced disordered liver function and hepatocyte morphology changes in pregnant mice, along with increased malondialdehyde (MDA) and Fe2+ content and decreased glutathione (GSH) levels. The expression levels of the selected ferroptosis-related genes Slc7a11, Gpx4, and Nfr2 were significantly decreased, and Ptgs2 and Lpcat3 were significantly increased. Notably, Fer-1 attenuated DEHP-induced liver injury and ferroptosis. Furthermore, MEHP exhibited a synergistic effect with RSL3 (a GPX4 inhibitor) in promoting ferroptosis in vitro. Taken together, the results demonstrated that DEHP induced liver injury and ferroptosis in pregnant mice, probably by inhibiting the GPX4 pathway through lipid peroxidation and iron accumulation.

Effect of Myrcene on Th17/Treg Balance and Endocrine Function in Autoimmune Premature Ovarian Insufficiency Mice through the MAPK Signaling Pathway.

BACKGROUND: Premature ovarian insufficiency (POI) is a defect of ovarian functions in women younger than 40 years old. Although a large number of studies have focused on investigating autoimmune POI, its detailed pathogenesis is still largely unknown. Several studies have indicated that Myrcene exerted a part in the biological processes of various diseases. Nonetheless, whether Myrcene could influence the development of autoimmune POI remains to be elucidated. METHODS: POI model was established by injecting zona pellucida glycoprotein 3 (pZP3). Hematoxylin and eosin (H&E) staining was applied to evaluate the pathological features of ovarian tissues. Enzymelinked immunosorbent assay (ELISA) was used for assessing the concentrations of estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH) and interleukin (IL)-17. Flow cytometry analysis was conducted for assessing the balance of Th17/Treg cells. RESULTS: The results showed that decreased levels of body weight, ovarian weight and ovarian index were reversed by Myrcene in POI model mice. The estrous cycles in mice were extended in pZP3 mice and Myrcene administration restored it to normal. The reduced number of primordial, primary, and secondary follicles as well as the increased number of atretic follicles in POI mice were offset by Myrcene administration. Moreover, Myrcene could modulate the Th17/Treg balance in autoimmune POI. Besides, Myrcene suppressed the MAPK signaling pathway in pZP3 mice. CONCLUSION: Myrcene regulated the Th17/Treg balance and endocrine function in autoimmune POI mice through the MAPK signaling pathway, which might provide a reference for improving the treatment of autoimmune POI.

Paeonol prevents migration and invasion, and promotes apoptosis of cervical cancer cells by inhibiting 5­lipoxygenase.

Cervical cancer is a common public health issue with high morbidity worldwide. Paeonol (Pae) has been recognized as a traditional Chinese medicine used for the treatment of various cancer types. However, whether Pae could exert a protective effect on cervical cancer remains to be investigated. The aim of the present study was to explore the role of Pae in cervical cancer cells and identify the potential mechanism. Cell Counting Kit­8 and colony­formation assays were conducted to test the proliferation of HeLa cells. Additionally, wound healing and transwell assays were used to detect the migratory and invasive abilities of cells. The plasmid that overexpressed 5­lipoxygenase (5­LO) or control vector was constructed and transfected into the cells. Subsequently, flow cytometry was used to monitor the apoptotic rate of cells. The expression levels of apoptosis­associated proteins and 5­LO were detected using western blot analysis. Reverse transcription­quantitative PCR analysis detected the expression of 5­LO. Pae inhibited the proliferation, invasion and migration of HeLa cells, promoted cell apoptosis and downregulated the expression of 5­LO. Overexpression of 5­LO, however, attenuated these effects. Thus, Pae could inhibit the proliferation, migration and invasion, as well as promote apoptosis of HeLa cells by regulating the expression of 5­LO.