Study protocol for the Sino-Canadian Healthy Life Trajectories Initiative (SCHeLTI): a multicentre, cluster-randomised, parallel-group, superiority trial of a multifaceted community-family-mother-child intervention to prevent childhood overweight and obesity.

INTRODUCTION: Childhood overweight and obesity (OWO) is a primary global health challenge. Childhood OWO prevention is now a public health priority in China. The Sino-Canadian Healthy Life Trajectories Initiative (SCHeLTI), one of four trials being undertaken by the international HeLTI consortium, aims to evaluate the effectiveness of a multifaceted, community-family-mother-child intervention on childhood OWO and non-communicable diseases risk. METHODS AND ANALYSIS: This is a multicentre, cluster-randomised, controlled trial conducted in Shanghai, China. The unit of randomisation is the service area of Maternal Child Health Units (N=36). We will recruit 4500 women/partners/families in maternity and district level hospitals. Participants in the intervention group will receive a multifaceted, integrated package of health promotion interventions beginning in preconception or in the first trimester of pregnancy, continuing into infancy and early childhood. The intervention, which is centred on a modified motivational interviewing approach, will target early-life maternal and child risk factors for adiposity. Through the development of a biological specimen bank, we will study potential mechanisms underlying the effects of the intervention. The primary outcome for the trial is childhood OWO (body mass index for age ≥85th percentile) at 5 years of age, based on WHO sex-specific standards. The study has a power of 0.8 (α=0.05) to detect a 30% risk reduction in the proportion of children with OWO at 5 years of age, from 24.4% in the control group to 17% in the intervention group. Recruitment was launched on 30 August 2018 for the pilot study and 10 January 2019 for the formal study. ETHICS AND DISSEMINATION: The study has been approved by the Medical Research Ethics Committee of the International Peace Maternity and Child Health Hospital in Shanghai, China, and the Research Ethics Board of the Centre Intégré Universitaire de Santé et Services Sociaux de l'Estrie-CHUS in Sherbrooke, Canada. Data sharing policies are consistent with the governance policy of the HeLTI consortium and government legislation. TRIAL REGISTRATION NUMBER: ChiCTR1800017773. PROTOCOL VERSION: November 11, 2020 (Version #5).

Association between gestational anemia in different trimesters and neonatal outcomes: a retrospective longitudinal cohort study.

BACKGROUND: Previous studies investigated the association between gestational anemia and neonatal outcomes. However, few studies explored whether the effects of gestational anemia could be eliminated by subsequent correction of anemia in the later stages of pregnancy. This study aimed to investigate the relationship between anemia in different trimesters and neonatal outcomes. METHODS: The study was conducted in Shanghai, China, with a sample of 46,578 pregnant women who delivered between January 1, 2016 and July 1, 2019. A multivariable logistic regression model was adopted to analyse the associations between maternal anemia and neonatal outcomes. RESULTS: The incidence of gestational anemia was 30.2%, including 4.4% in the first trimester, 9.6% in the second trimester, and 16.2% in the third trimester. Only 24.5% (507/2066) of anemia that occurred in the first trimester and 29.6% (1320/4457) that occurred in the second trimester could be corrected in the later stages of pregnancy. Anemia occurring in the first trimester was associated with small for gestational age [odds ratio (OR) 1.46; 95% confidence interval (CI) 1.20-1.78] and with fetal distress (OR 1.23; 95% CI 1.08-1.40). Anemia corrected in the first trimester also was associated with a higher risk of small for gestational age. CONCLUSIONS: Gestational anemia is a public health problem in China impacting neonatal health. Anemia in pregnancy could be corrected in only about a quarter of the women. Anemia in the first trimester, whether corrected or not, still led to lower birth weight; therefore, the prevention of anemia prior to pregnancy is important.

Dose-dependent Cardiac Dysfunction and Structural Damage in Rats after Shortwave Radiation.

OBJECTIVE: To detect the effects of shortwave radiation on dose-dependent cardiac structure and function in rats after radiation and to elucidate the mechanism of shortwave radiation induced cardiac injury to identify sensitive indicators and prophylactic treatment. METHODS: One hundred Wistar rats were either exposed to 27 MHz continuous shortwave at a power density of 5, 10, and 30 mW/cm 2 for 6 min or undergone sham exposure for the control (the rats had to be placed in the exposure system with the same schedules as the exposed animals, but with an inactive antenna). The Ca 2+, glutamic oxaloacetic transaminase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) content in the peripheral serum of the rats were detected by an automatic blood biochemical analyser. The electrocardiogram (ECG) of standard lead II was recorded by a multi-channel physiological recording and analysis system. The cardiac structure of rats was observed by light and electron microscopy. RESULTS: The results showed that the 5, 10, and 30 mW/cm 2 shortwave radiation caused a significant increased in the levels of Ca 2+, AST, CK, and LDH in the peripheral serum of rats. The cardiac structure was damaged by radiation and showed a disordered arrangement of myocardial fibres, the cavitation and swelling of myocardial mitochondria. These injuries were most significant 7 d after radiation and were not restored until 28 d after radiation. CONCLUSION: Shortwave radiation of 5, 10, and 30 mW/cm 2 can damage rat cardiac function, including damage to the tissue structure and ultrastructure, especially at the level of the myocardial fibres and mitochondria. Shortwave radiation at 5, 10, and 30 mW/cm 2 induced damage to rat heart function and structure with a dose-effect relationship, i.e., the greater the radiation dose was, the more significant the damage was.

A novel microcurrent dressing for wound healing in a rat skin defect model.

BACKGROUND: The exogenous application of low-intensity electric stimulation (ES) may mimic a natural endogenous bioelectric current and accelerate the repair process of skin wounds. This study designed a novel microcurrent dressing (MCD) and evaluated its potential effects on wound healing in a rat skin defect model. METHODS: First, wireless ES was integrated into a medical cotton cushion to fabricate the MCD, and its electrical property was examined by using a universal power meter. Then, animal experiments were conducted to evaluate the MCD's effect. Forty-five rats were randomized into control (Con) group, Vaseline gauze (VG) group and MCD group. A full-thickness round skin incision 1.5 cm in diameter was made on the back of each animal. Apart from routine disinfection, the Con rats were untreated, whereas the other two groups were treated with VG or MCD. On days 3, 7 and 14 post injury, the wound areas were observed and measured using image analysis software following photography, and the skin samples were harvested from wound tissue. Then, histopathological morphology was observed routinely by hematoxylin and eosin (HE) staining; tumor necrosis factor α (TNF-α) and interleukin (IL)-1ß expression were detected by Western blotting. Vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) expression were detected with immunohistochemistry. RESULTS: The MCD generated a sf electric potential greater than 0.95 V. Animal experiments showed that the wound-healing rate in the MCD group was significantly increased compared with the Con and VG groups (P < 0.05 or P < 0.01). Histopathological observation revealed an alleviated inflammatory response, induced vascular proliferation and accelerated epithelization in the MCD group. Moreover, samples from the MCD group expressed reduced TNF-α and IL-1ß levels and increased VEGF and EGF levels compared with those of the other two groups (P < 0.05 or P < 0.01). However, no significant difference was noted between the Con and VG groups at each time point. CONCLUSIONS: The MCD generates a stable and lasting ES and significantly promotes wound healing by reducing inflammation duration and increasing growth factors expression. Thus, MCD may act as a promising biomaterial device for skin wound healing.

Behavioral Abnormality along with NMDAR-related CREB Suppression in Rat Hippocampus after Shortwave Exposure.

OBJECTIVE: To estimate the detrimental effects of shortwave exposure on rat hippocampal structure and function and explore the underlying mechanisms. METHODS: One hundred Wistar rats were randomly divided into four groups (25 rats per group) and exposed to 27 MHz continuous shortwave at a power density of 5, 10, or 30 mW/cm2 for 6 min once only or underwent sham exposure for the control. The spatial learning and memory, electroencephalogram (EEG), hippocampal structure and Nissl bodies were analysed. Furthermore, the expressions of N-methyl-D-aspartate receptor (NMDAR) subunits (NR1, NR2A, and NR2B), cAMP responsive element-binding protein (CREB) and phosphorylated CREB (p-CREB) in hippocampal tissue were analysed on 1, 7, and 14 days after exposure. RESULTS: The rats in the 10 and 30 mW/cm2 groups had poor learning and memory, disrupted EEG oscillations, and injured hippocampal structures, including hippocampal neurons degeneration, mitochondria cavitation and blood capillaries swelling. The Nissl body content was also reduced in the exposure groups. Moreover, the hippocampal tissue in the 30 mW/cm2 group had increased expressions of NR2A and NR2B and decreased levels of CREB and p-CREB. CONCLUSION: Shortwave exposure (27 MHz, with an average power density of 10 and 30 mW/cm2) impaired rats' spatial learning and memory and caused a series of dose-dependent pathophysiological changes. Moreover, NMDAR-related CREB pathway suppression might be involved in shortwave-induced structural and functional impairments in the rat hippocampus.

HIF-1α regulates COXIV subunits, a potential mechanism of self-protective response to microwave induced mitochondrial damages in neurons.

Anxiety and speculation about potential health hazards of microwaves exposure are spreading in the past decades. Hypoxia-inducible factor-1α (HIF-1α), which can be activated by reactive oxygen species (ROS), played pivotal roles in protective responses against microwave in neuron-like cells. In this study, we established 30 mW/cm2 microwave exposed animal model, which could result in revisable injuries of neuronal mitochondria, including ultrastructure and functions, such as ROS generation and cytochrome c oxidase (COX) activity. We found that the ratio of COXIV-1/COXIV-2, two isoforms of COXIV, decreased at 1 d and increased from 3 d to 14 d. Similar expression changes of HIF-1α suggested that COXIV-1 and COXIV-2 might be regulated by HIF-1α. In neuron-like cells, 30 mW/cm2 microwave down-regulated COX activity from 30 min to 6 h, and then started to recover. And, both HIF-1α transcriptional activity and COXIV-1/COXIV-2 ratio were up-regulated at 6 h and 9 h after exposure. Moreover, HIF-1α inhibition down-regulated COXIV-1 expression, promoted ROS generation, impaired mitochondrial membrane potentials (MMP), as well as abolished microwave induced ATP production. In conclusion, microwave induced mitochondrial ROS production activated HIF-1α and regulated COXIV-1 expression to restore mitochondria functions. Therefore, HIF-1α might be a potential target to impair microwave induced injuries.

Microwave-induced Apoptosis and Cytotoxicity of NK Cells through ERK1/2 Signaling.

OBJECTIVE: To investigate microwave-induced morphological and functional injury of natural killer (NK) cells and uncover their mechanisms. METHODS: NK-92 cells were exposed to 10, 30, and 50 mW/cm2 microwaves for 5 min. Ultrastructural changes, cellular apoptosis and cell cycle regulation were detected at 1 h and 24 h after exposure. Cytotoxic activity was assayed at 1 h after exposure, while perforin and NKG2D expression were detected at 1 h, 6 h, and 12 h after exposure. To clarify the mechanisms, phosphorylated ERK (p-ERK) was detected at 1 h after exposure. Moreover, microwave-induced cellular apoptosis and cell cycle regulation were analyzed after blockade of ERK signaling by using U0126. RESULTS: Microwave-induced morphological and ultrastructural injury, dose-dependent apoptosis (P < 0.001) and cell cycle arrest (P < 0.001) were detected at 1 h after microwave exposure. Moreover, significant apoptosis was still detected at 24 h after 50 mW/cm2 microwave exposure (P < 0.01). In the 30 mW/cm2 microwave exposure model, microwaves impaired the cytotoxic activity of NK-92 cells at 1 h and down regulated perforin protein both at 1 h and 6 h after exposure (P < 0.05). Furthermore, p-ERK was down regulated at 1 h after exposure (P < 0.05), while ERK blockade significantly promoted microwave-induced apoptosis (P < 0.05) and downregulation of perforin (P < 0.01). CONCLUSION: Microwave dose-dependently induced morphological and functional injury in NK-92 cells, possibly through ERK-mediated regulation of apoptosis and perforin expression.

Benchmark Doses Based on Abnormality of WBC or Micronucleus Frequency in Benzene-Exposed Chinese Workers.

OBJECTIVES: The aim of the study was to calculate benchmark dose for chromosomal damage and reduced white blood cell (WBC) associated with exposure to benzene (BZ). METHODS: A group of 317 exposed workers and 102 controls were examined for WBC count and genotoxicity by micronucleus (MN) frequency. The cumulative exposure concentration of BZ was calculated by ambient air BZ concentration at worksites in conjunction with job type and associated service duration. RESULTS: MN frequency (P < 0.01) was higher and WBC count was lower (P < 0.01) in exposed workers on average than in the controls. MN frequency was a more sensitive than WBC; workers older than 30 were more susceptible to abnormal MN frequency and WBC count reduction than those younger than 30. CONCLUSIONS: Benchmark dose estimates indicated that BZ exposure at levels below the current occupational exposure standard can induce genotoxicity and hematotoxicity.

Effects of microwave radiation on brain energy metabolism and related mechanisms.

With the rapid development of electronic technologies, anxiety regarding the potential health hazards induced by microwave radiation (MW) has been growing in recent years. The brain is one of the most sensitive target organs for microwave radiation, where mitochondrial injury occurs earlier and more severely than in other organs. Energy metabolism disorders do play an important role during the process of microwave radiation-induced brain damage. In this paper, we will review the biological effects of microwave radiation, the features of brain energy supply and consumption and the effects of microwave radiation on mitochondrial energy metabolism and potential related mechanisms.

Effect of polymorphic metabolizing genes on micronucleus frequencies among benzene-exposed shoe workers in China.

It is well-known that metabolism of benzene is required for the induction of toxicity and consequent health problems. Therefore, genetic variation in benzene (BZ) metabolism genes can influence health outcomes. However, large population studies are needed to provide more evidence for such relationship. We have conducted a large population investigation (385 BZ-exposed shoe workers and 197 matched healthy controls) on the association between inheritance of certain BZ metabolizing genes and the expression of micronuclei (MN). The latter was based on the cytokinesis-blocked MN assay. We analyzed the polymorphisms of GSTM1, GSTT1, GSTP1 (rs1695), CYP2E1 (rs3813867), CYP2E1 (rs2031920), CYP2E1 (rs6413432), mEH exon 3 (rs1051740), mEH exon 4 (rs2234922). Univariate Poisson regression analysis demonstrated that the BZ-exposed workers had significantly increased MN frequency compared with the controls (FR=1.84, 95% CI: 1.56-2.18; P<0.001), and showed a cumulative exposure dose-response relationship. The CYP2E1 rs3813867 mutant allele (CC+GC) (FR 1.15, 95% CI 1.02-1.29; P=0.020) and rs2031920 variant allele (CT+TT) (FR=1.23, 95% CI: 1.09-1.37, P<0.01) was associated with higher MN frequency significantly compared with the wild genotype separately. Furthermore, the MN frequency in rs2031920 variant allele (CT+TT) (FR=1.17, 95% CI: 1.04-1.31, P<0.01) was also higher than the wild genotype when the age, gender and cumulative exposure dose was adjusted in Poisson regression. In addition, the CYP2E1, however, GSTM1null, GSTT1null, GSTP1 rs1695, rs6413432, rs1051740 and rs2234922 polymorphisms showed no association with MN frequency. Our results indicate that two promoter polymorphisms in the CYP2E1 gene, especially the rs2031920 variant allele, were involved with the BZ-induction of MN and may contribute to risk of cancer among exposed workers.

Advances in the biological effects of terahertz wave radiation.

The terahertz (THz) band lies between microwave and infrared rays in wavelength and consists of non-ionizing radiation. Both domestic and foreign research institutions, including the army, have attached considerable importance to the research and development of THz technology because this radiation exhibits both photon-like and electron-like properties, which grant it considerable application value and potential. With the rapid development of THz technology and related applications, studies of the biological effects of THz radiation have become a major focus in the field of life sciences. Research in this field has only just begun, both at home and abroad. In this paper, research progress with respect to THz radiation, including its biological effects, mechanisms and methods of protection, will be reviewed.

Polymorphisms in the p53 pathway genes and micronucleus occurrence in Chinese vinyl chloride-exposed workers.

OBJECTIVES: To investigate the association between polymorphisms in the p53 pathway genes and chromosomal damage in vinyl chloride (VC)-exposed workers. MATERIALS AND METHODS: Cytokinesis block micronucleus test was performed in 310 VC-exposed workers and 149 non-exposed workers to determine chromosomal damage. The polymerase chain reaction and restriction fragment length polymorphism technique were used to detect six SNPs in the p53 pathway genes involved in the cell cycle. RESULTS: There was a highly significant dose-response relationship between VC exposure and chromosomal damage. Individuals carrying the variant genotypes were at higher risk for chromosomal damage compared with their wild type genotype: p53rs1042522, MDM2 Del1518rs3730485, MDM2rs2279744 and GADD45Ars532446. On the other hand, individuals possessing the variant genotype of CDKN2A rs3088440 had significantly decreased risk compared with the corresponding wild-type. CONCLUSIONS: Genetic polymorphisms in P53 pathway genes may have an impact on VC-induced chromosomal damage.