Positive Correlation Between Motor Function and Neuropathic Pain-Like Behaviors After Spinal Cord Injury: A Longitudinal Study of Mice.

Abstract With the recovery of motor function, some spinal cord injury (SCI) patients still suffer from severe pain-like behaviors symptoms. Whether motor function correlates with neuropathic pain-like behaviors remain unclear. In this study, a longitudinal cohort study of mice with moderate thoracic 10 contusion was performed to explore the characteristics of neuropathic pain-like behaviors and its correlation with motor function in different sexes. Pain-like behaviors data up to 42 days post-injury (dpi) were collected and compared. Mice of both sexes were divided into three groups based on their Basso Mouse Scale at 42 dpi. There was no significant difference in motor function recovery between the sexes. Female mice showed more significant mechanical allodynia than males at 14 dpi, which was sustained until 42 dpi without significant dynamic changes. However, males showed a gradually worsening state and more severe mechanical allodynia than females at 28 dpi, and then the differences disappeared. Interestingly, male mice obtained more severe cold hyperalgesia symptoms than females. Additionally, we found that there was a correlation between the occurrence of mechanical allodynia and cold and thermal hyperalgesia. Importantly, motor function recovery was positively associated with the outcomes of neuropathic pain-like behaviors after SCI, which was more obvious in female mice. Our data not only revealed the characteristics of neuropathic pain-like behaviors but also clarified the correlations between motor function recovery and neuropathic pain-like behaviors after SCI. These findings may provide new opinions and suggestions for promoting the clinical diagnosis and treatment of neuropathic pain-like behaviors after SCI.

Maternal blood concentrations of toxic metal(loid)s and trace elements from preconception to pregnancy and transplacental passage to fetuses.

Intrauterine exposure to heavy metals may adversely affect the developing fetus and health later in life, while certain trace elements may be protective. There is limited data on their dynamic fluctuation in circulating concentration of women from preconception to pregnancy and the degree of transplacental passage to fetus. Such information is critically needed for an optimal design of research studies and intervention strategies. In the present study, we profiled the longitudinal patterns and trajectories of metal(loid)s and trace elements from preconception to late pregnancy and in newborns. We measured whole blood metal(loid)s in women at preconception, 16, 24 and 32 weeks of gestation and in cord blood in 100 mother-newborn pairs. Our data showed that the mean concentrations of mercury (Hg), lead (Pb), rubidium (Rb), manganese (Mn), and iron (Fe) were lower during early-, mid-, and late-pregnancy than at preconception. Copper (Cu), and calcium (Ca) concentrations increased after pregnancy (Cu 798 versus 1353, 1488, and 1464 µg/L). Concentrations at preconception were correlated with those during pregnancy for all examined metal(loid)s. Maternal Hg, Pb, and Se concentrations at late-pregnancy were correlated with those in newborn cord blood in various degrees (correlation coefficients: Hg 0.66, Pb 0.29, Se 0.39). The estimated placental transfer ratio for toxic metal(loid)s ranging from 1.68 (Hg) to 0.18 (Cd). Two trajectory groups were identified for Hg, Pb, Cd, Se concentrations. Hg concentrations may be correlated with maternal education levels. The study is the first to present longitudinal circulating concentration trajectories of toxic metal(loid)s and trace elements from preconception to pregnancy stages. A high degree of transplacental passage was observed in toxic metals Pb and Hg which may pose hazards to the developing fetus.

The association between maternal urinary Bisphenol A levels and neurodevelopment at age 2 years in Chinese boys and girls: A prospective cohort study.

The impact of maternal exposure to Bisphenol A on child cognitive development as well as its sex dimorphism remains uncertain. This study used data of 215 mothers and their children from a birth cohort in Shanghai. Urinary BPA were measured in spot urine samples of mothers at late pregnancy and children at age 2 years. Cognitive development was evaluated by Ages & Stages Questionnaires, Third Edition (ASQ-3) at age 2 years. Urinary BPA was detectable in 98.9% of mothers (geometric mean, GM: 2.6 µg/g. creatinine) and 99.8% children (GM: 3.4 µg/g. creatinine). Relative to the low and medium BPA tertiles, high tertile of maternal urinary BPA concentrations were associated with 4.8 points lower (95% CI: -8.3, -1.2) in gross motor and 3.7 points lower (95% CI: -7.4, -0.1) in problem-solving domain in girls only, with adjustment for maternal age, maternal education, pre-pregnancy BMI, passive smoking during pregnancy, parity, delivery mode, birth-weight for gestational age, child age at ASQ-3 test. This negative association remained with additional adjustment for child urinary BPA concentrations at age 2 years. No association was observed in boys. These results suggested the sex-dimorphism on the associations of maternal BPA exposure with gross motor and problem-solving domains in children at age 2 years. This study also indicated that optimal early child development should start with a healthy BPA-free "in utero" environment.

Urinary antibiotics concentrations, their related affecting factors and infant growth in the first 6 months of life: A prospective cohort study.

Antibiotic exposure even in low-dose could have potential adverse health effects, especially during early life. There is a lack of data on antibiotic burdens in early infancy. We aim to assess antibiotic exposure in infants from birth to 6 months of age, their related affecting factors and the association between antibiotic exposure and infancy growth. Urine samples were collected at ages of 3 days, 42 days, 3 months and 6 months from 197 term-born Chinese infants. A total of 33 representative antibiotics were measured by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Urinary antibiotics were detectable in 69.4%, 63.2%, 75.0% and 84.3% of infants at ages of 3 days, 42 days, 3 and 6 months, respectively. The dominant antibiotic categories detected were: Preferred as Veterinary Antibiotics (PVAs), Human Antibiotics (HAs), and Veterinary Antibiotics (VAs). The detectable rates were 30.6%, 45.8%, 58.9%, and 81.4% for PVAs, 34.1%, 20.8%, 28.6%, and 45.1% for HAs, and 36.5%, 12.5%, 6.3%, and 5.9% for VAs, at age 3 days, 42 days, 3 and 6 months, respectively. Urinary concentrations of HAs and preferred as human antibiotics (PHAs) in newborns at age 3 days were not associated with maternal intrapartum antibiotic prophylaxis. Similarly, no associations were observed between urinary antibiotics concentration and antibiotics use in infants at age 42 days or 6 months. The numbers and concentrations of urine detectable antibiotics were similar between infants with exclusive breastfeeding and infants fed with formula or mixed-feeding at all ages of 42 days, 3 and 6 months. At age of 42 days, infants in the low tertile of total antibiotics concentration or with one antibiotic detected had higher weight-for-length Z score and greater head circumference, compared to infants with no antibiotics detected. No associations were found between urinary antibiotics and any of the infant anthropometric measures at age 6 months. In conclusion, urinary antibiotics were detectable in most infants during the first 6 months of life, and PVAs, HAs and VAs were the most commonly detected antibiotics. This suggested the possibility of a foods-originated antibiotics exposure in children. No strong nor consistent associations were found between urinary antibiotic concentration and infant growth at the first six months of life. Still, attention is needed on the adverse health effect of early life exposure to antibiotics in future studies.

The impact of maternal depression, anxiety, and stress on early neurodevelopment in boys and girls.

OBJECTIVE: To examine the effects of prenatal maternal depression, anxiety and stress, and postnatal depression on infant early neurodevelopment, and the sex dimorphism. STUDY DESIGN: We used data from 3379 mother-infant pairs from the Shanghai Birth Cohort. Maternal mental health was assessed using the Center for Epidemiological Studies-Depression Scale, Zung Self-Rating Anxiety Scale, Perceived Stress Scale at mid-pregnancy, and the Edinburgh Postnatal Depression Scale at postpartum. Infant neurodevelopment was evaluated using the Ages & Stages Questionnaires and Bayley Scales at ages 6, 12, and 24 months, respectively. Linear mixed models and linear regression models were used. RESULTS: Among 3379 mothers, 11.07 %, 5.42 %, and 34.85 % of women experienced depression, anxiety, and elevated stress, separately. As maternal prenatal mental scores increased per 1SD, infant social-emotional scores decreased -2.82 (-3.86, -1.79) vs -2.86 (-3.94, -1.79) for depression, -2.34 (-3.38, -1.31) vs -2.72 (-3.81, -1.64) for anxiety, and -2.55 (-3.60, -1.50) vs -3.41 (-4.48, -2.35) for stress among boys and girls at age 24 months, respectively. Associations were also observed on social-emotional and communication scores in boys and girls, and fine motor in girls at age 6 and 12 months. These associations were not observed for postpartum depression. LIMITATION: Generalizability of the results to other population remains to be determined. CONCLUSIONS: Prenatal maternal depression, anxiety, and stress were negatively associated with infant early neurodevelopment, which were not observed for postpartum depression. We underscore the importance of maternal prenatal mental health in optimizing infant neuropsychiatric development.

Maternal Thyroid Dysfunction and Neuropsychological Development in Children.

CONTEXT: Thyroid hormones are essential for fetal brain development. The potential effects of maternal gestational thyroid dysfunction on offspring neuropsychological development remain inconclusive. OBJECTIVE: This work aimed to estimate effects of maternal thyroid dysfunction during pregnancy on offspring neuropsychological development in the first 2 years. METHODS: We prospectively examined 1903 mothers and their children from the Shanghai Birth Cohort. Thyroid hormones were assessed at about 12 gestational weeks. Maternal thyroid function was classified into 7 categories: euthyroid, overt/subclinical hyperthyroidism, overt/subclinical hypothyroidism, hyperthyroxinemia, and hypothyroxinemia. Neuropsychological development was assessed by the Ages and Stages Questionnaire at age 6 months, and Bayley Scales at age 24 months. RESULTS: Compared with children of euthyroid mothers, maternal overt hypothyroidism was associated with 7.0 points (95% CI, 1.7-12.4) lower scores in personal-social domain in girls aged 6 months, 7.3 points (95% CI, 2.0-12.6) lower in motor domain, and 7.7 points (95% CI, 1.1-14.2) lower social-emotional scores in boys at age 24 months; maternal subclinical hypothyroidism was associated with 6.5 points (95% CI, 1.0-12.1) poorer social-emotional domain in boys at age 6 months, and 7.4 points (95% CI, 0.1-14.8) poorer adaptive behavior domain in boys at age 24 months; maternal hypothyroxinemia was associated with 9.3 points (95% CI, 3.5-15.1) lower motor scores in boys at age 24 months; and maternal subclinical hyperthyroidism was associated with 6.9 points (95% CI, 0.1-13.7) lower language scores in girls at age 24 months. CONCLUSION: Maternal overt hypothyroidism, subclinical hypothyroidism/hyperthyroidism, and hypothyroxinemia during early pregnancy were associated with weakened neuropsychological development in infancy, and some effects may be sex specific.

The Effect of Early Life Exposure to Triclosan on Thyroid Follicles and Hormone Levels in Zebrafish.

Triclosan (TCS) is an antimicrobial chemical widely used in personal care products. Most of the TCS component is discharged and enters the aquatic ecosystem after usage. TCS has a similar structure as thyroid hormones that are synthesized by thyroid follicular epithelial cells, thus TCS has a potential endocrine disrupting effect. It is still not clear how the different levels of the environmental TCS would affect early development in vivo. This study examines the effects of TCS on thyroid hormone secretion and the early development of zebrafish. The fertilized zebrafish eggs were exposed to TCS at 0 (control), 3, 30, 100, 300, and 900 ng/mL, and the hatching rate and the larvae mortality were inspected within the first 14 days. The total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3), and free thyroxine (FT4) were measured at 7, 14, and 120 days post-fertilization (dpf). The histopathological examinations of thyroid follicles were conducted at 120 dpf. TCS exposure at 30-300 ng/mL reduced the hatching rate of larvae to 34.5% to 28.2 % in the first 48 hours and 93.8 .7 % to 86.8 % at 72 h. Extremely high TCS exposure (900 ng/mL) strongly inhibited the hatching rate, and all the larvae died within 1 day. Exposure to TCS from 3 to 300 ng/mL reduced the thyroid hormones production. The mean TT3 and FT3 levels of zebrafish decreased in 300 ng/mL TCS at 14 dpf (300 ng/mL TCS vs. control : TT3 , 0.19 ± 0.08 vs. 0.39 ± 0.06; FT3, 19.21 ± 3.13 vs. 28.53 ± 1.98 pg/mg), and the FT4 decreased at 120 dpf ( 0.09 ± 0.04 vs. 0.20 ± 0.14 pg/mg). At 120 dpf , in the 300 ng/mL TCS exposure group, the nuclear area and the height of thyroid follicular epithelial cells became greater, and the follicle cell layer got thicker. This happened along with follicle hyperplasia, nuclear hypertrophy, and angiogenesis in the thyroid. Our study demonstrated that early life exposure to high TCS levels reduces the rate and speed of embryos hatching, and induces the histopathological change of thyroid follicle, and decreases the TT3, FT3, and FT4 production in zebrafish.

Effects of Long-Term Triclosan Exposure on Microbiota in Zebrafish.

Background: Triclosan (TCS) is a widely used antibacterial agent in personal care products and is ubiquitous in the environment. We aimed to examine whether TCS exposure affects microbiota in the gastrointestinal tract of zebrafish. Methods: After exposure to TCS 0 (Dimethyl Sulphoxide, DMSO control), 0.03, 0.3, 3, 30, 100, and 300ng/ml, respectively, from day 0 to 120days post fertilization (dpf), or for 7days in adult 4-month zebrafish, the long- and short-term impact of TCS exposure on the microbiome in the gastrointestinal tract was evaluated by analyzing 16S rRNA gene V3-V4 region sequencing. Results: The top two most dominant microbiota phyla were Proteobacteria and Fusobacteria phylum in all zebrafish groups. In TCS exposure 0-120 dpf, compared with DMSO control, the mean number of microbial operational taxonomic units (OTUs) was 54.46 lower (p<0.0001), Chao indice 41.40 lower (p=0.0004), and Ace indice 34.10 lower (p=0.0044) in TCS 300ng/ml group, but no change was observed in most of the other TCS concentrations. PCoA diagram showed that the microbial community in the long-term TCS 300ng/ml exposure group clustered differently from those in the DMSO control and other TCS exposure groups. A shorter body length of the zebrafish was observed in the long-term TCS exposure at 0.03, 100, and 300ng/ml. For 7-day short-term exposure in adult zebrafish, no difference was observed in alpha or beta diversity of microbiota nor the relative abundance of Proteobacteria or Fusobacteria phylum among DMSO control and any TCS levels, but a minor difference in microbial composition was observed for TCS exposure. Conclusions: Long-term exposure to high TCS concentration in a window from early embryonic life to early adulthood may reduce diversity and alter the composition of microbiota in the gastrointestinal tract. The effect of short-term TCS exposure was not observed on the diversity of microbiota but there was a minor change of microbial composition in adult zebrafish with TCS exposure.

Poor Status of Vitamin D: A Survey of Area With Lowest Sunlight Radiation in Sichuan, China.

Objective: Vitamin D plays an important role in bone and mineral metabolism. Ultraviolet B (UVB) is the primary determinant for vitamin D synthesis. However, population-based data of vitamin D status was sparse in areas with sunlight deprivation in China. This study aimed to assess serum 25-hydroxyvitamin D [25(OH)D] levels among adult women in Sichuan basin with the lowest sunlight radiation in China, and the associations with sunlight exposure and age. Methods: In the context of the same ethnicity, similar latitude and lifestyle in sunlight-limited basin and sunlight-abundant plateau, 1,057 women in basin and 337 in plateau aged 29-95 years were included in this study, from November 2012 to February 2013. Daily sunlight exposure duration of previous month was obtained using questionnaires. Serum 25(OH)D was measured by enzyme-linked immunosorbent assay. Results: The prevalence of vitamin D severe deficiency [25(OH)D <30 nmol/L] and deficiency [30 ≤ 25(OH)D <50 nmol/L] was significantly higher in basin than plateau (21.85% vs. 10.09%, and 59.32% vs. 40.36%; P<0.0001). Women from basin exhibited lower serum 25(OH)D levels than those from plateau (40.66 ± 15.62 vs. 52.54 ± 19.94 nmol/L, P<0.0001). In basin, women more than 50 years old had higher 25(OH)D than younger counterparts, and 25(OH)D level of these groups was not associated with sunlight exposure duration. While in plateau, women younger than 60 years old had higher 25(OH)D than the older women. Furthermore, for those younger groups, women with long sunlight exposure (≥3 h daily) had higher 25(OH)D concentration than those with short sunlight exposure (<3 h daily). Serum PTH was negatively associated with 25(OH)D in basin, but not in plateau. Conclusions: Alarmingly high prevalence of vitamin D deficiency was observed in women in sunlight-deprived basin in Sichuan. Only the vitamin D status of younger women from plateau with adequate solar radiation could benefit from sunlight exposure. Vitamin D supplementation and vitamin D-fortified food should be encouraged to improve vitamin D status for women living in sunlight-limited areas, or with old age.

Cord Blood Thyroid Hormones and Neurodevelopment in 2-Year-Old Boys and Girls.

Objective: Thyroid hormones are essential for neurodevelopment in early life. However, the impact of mild alterations in neonatal thyroid hormones on infant neurodevelopment and its sex dimorphism is unclear. We aimed to assess whether mild variations in neonatal thyroid hormones of term-born newborns with maternal euthyroid are related to neurodevelopment in 2-year-old boys and girls. Methods: This study used data from 452 singleton term-born infants of mothers with normal thyroid function in Shanghai, China, and their follow-up measure at the age of 2 years. Cord serum concentrations of free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), and thyroid peroxidase antibody (TPOAb) were measured by chemiluminescent microparticle immunoassays and classified into three groups: the low (1st, Q1), middle (2nd-4th, Q2-Q4), and high (5th, Q5) quintiles. Neurodevelopment indices were assessed using the Ages and Stages Questionnaire, third edition (ASQ-3), at 24 months of age. Results: Compared to infants with thyroid hormones in the middle (Q2-Q4), boys with FT4 in the lowest quintile had 5.08 (95% CI: 1.37, 8.78) points lower scores in the communication domain, 3.25 (0.25,6.25) points lower scores in the fine motor domain, and 3.84 (0.04, 7.64) points lower scores in the personal-social domain, respectively. Boys with FT3 in the highest quintile had 4.46 (0.81, 8.11) points increase in the personal-social domain. These associations were not observed in girls. No associations were observed between cord blood serum TSH and ASQ-assessed neurodevelopment in the boys or the girls. Conclusions: Mild alterations in thyroid hormones of newborns were associated adversely with neurodevelopment in boys, suggesting the importance of optimal thyroid hormone status for neurodevelopment in early life.

The Association Between Gestational Diabetes and Microbiota in Placenta and Cord Blood.

Objective: Early life is a critical period for gut microbial development. It is still controversial whether there is placental microbiota during a healthy pregnancy. Gestational diabetes mellitus (GDM) is associated with increased risk of metabolic syndrome in the offspring, and the mechanisms are unclear. We sought to explore whether microbiota in placenta and cord blood may be altered in GDM. Methods: Placenta and cord blood samples were collected from eight GDM and seven euglycemic (control) term pregnancies in cesarean deliveries without evidence of clinical infections. The Illumina MiSeq Sequencing System was used to detect the microbiota based on the V3-V4 hypervariable regions of the 16S ribosomal RNA gene. Results: The microbiota were detectable in all placental samples. Comparing GDM vs. controls, there were more operational taxonomic units (OTUs) (mean ± SE = 373.63 ± 14.61 vs. 332.43 ± 9.92, P = 0.024) and higher ACE index (395.15 ± 10.56 vs. 356.27 ± 8.47, P = 0.029) and Chao index (397.67 ± 10.24 vs. 361.32 ± 8.87, P = 0.04). The placental microbiota was mainly composed of four phyla: Bacteroidetes, Firmicutes, Actinobacteria, and Proteobacteria at the phylum level and 10 dominant genera at the genus level in both GDM and controls. Despite the dominant similarity in microbiota composition, at the OTU level, the abundance of Ruminococcus, Coprococcus, Paraprevotella, and Lactobacillus were higher, whereas Veillonella was lower in the placentas of GDM vs. controls. The microbiota was detected in one of the 15 cord blood samples, and its components were similar as to the corresponding placental microbiota at both phylum and genus levels suggesting placental microbiota as the potential source. Conclusions: The most abundant phyla and genus of placental microbiota were similar in GDM and euglycemic pregnancies, but GDM was associated with higher diversity of placental microbiota. Further study is needed to confirm the existence of microbiota in cord blood in pregnancies without clinical infection.

Maternal urinary bisphenol A concentration and thyroid hormone levels of Chinese mothers and newborns by maternal body mass index.

Animal studies indicated that bisphenol A (BPA) exposure during pregnancy may disrupt thyroid function which is critical for fetal development. However, few epidemiological studies have examined this topic and the results were inconsistent. We aimed to evaluate whether prenatal BPA exposure is associated with thyroid hormone levels in Chinese mothers and newborns with stratification by maternal body mass index (BMI). BPA concentration were measured in urine samples collected from 555 women at late pregnancy. Maternal serum free thyroxin (FT4), thyroid-stimulating hormone (TSH) and thyroid peroxidase antibody (TPO-Ab) concentrations at the third trimester were abstracted from medical records. Cord serum-free triiodothyronine (FT3), FT4, TSH, and TPO-Ab levels were measured in 398 newborns. Prenatal urinary BPA was detected in 98.5% of mothers with a geometric mean of 1.32 ng/mL (95% CI 1.17-1.49 ng/mL). With each 10-fold increase in BPA concentrations, maternal log10_(TSH) mIU/L was 0.10 lowered (95% CI - 0.20, - 0.005, p < 0.05) among pre-pregnancy BMI > 23 kg/m2, with adjustment for maternal age, maternal education, gestation diabetes mellitus (GDM), husband smoking during pregnancy, parity, and gestational age at thyroid parameters measured, but no association was observed in pre-pregnancy BMI < 18.5, or 18.5-22.9 kg/m2 stratum. No BPA-associated changes were observed in maternal FT4 level or odds of positive TPO-Ab in all BMI stratum. Also, no associations were observed between prenatal urinary BPA concentration and cord serum FT4, FT3, TSH levels, and odds of positive TPO-Ab in both male and female newborns among pre-pregnancy BMI < 18.5, 18.5-22.9 or > 23 kg/m2 stratum. In this study, prenatal urinary BPA concentration was associated with lower maternal TSH among women with overweight, but not associated with other maternal thyroid parameters or cord serum thyroid parameters across maternal BMI categories. More research on pregnant women and newborns cohort with BPA exposure are warranted.

New parathyroid function index for the differentiation of primary and secondary hyperparathyroidism: a case-control study.

BACKGROUND: Patients with primary hyperparathyroidism (PHPT) may be asymptomatic, and some may present with normocalcemic PHPT (NPHPT). Patients with vitamin D deficiency may also be asymptomatic, with normal calcium and elevated PTH concentrations. These latter patients are usually diagnosed with vitamin D deficiency-induced secondary hyperparathyroidism (VD-SHPT). Therefore, it is very difficult to distinguish PHPT and NPHPT from VD-SHPT based on calcium or PTH concentrations in clinical settings. In this case-control study, we aimed to verify the diagnostic power of a new parathyroid function index (PFindex = Ca*PTH/P). METHODS: This study enrolled 128 patients with surgically and pathologically confirmed PHPT, including 36 with NPHPT, at a hospital in West China between January 2009 and September 2017. Thirty-seven patients with VD-SHPT and 45 healthy controls were selected from the population of a cross-sectional epidemiological study as the SHPT and healthy groups, respectively. We used the PFindex to describe the characteristics of PHPT, NPHPT, and VD-SHPT.. Differences between the four groups were compared, and a receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic power of PFindex. RESULTS: The PHPT group had the highest PFindex (454 ± 430), compared to the other three groups (NPHPT: 101 ± 111; SHPT: 21.7 ± 6.38; healthy: 12.2 ± 2.98, all p < 0.001). A PFindex cut-off value of 34 yielded sensitivity and specificity rates of 96.9 and 97.6% and of 94.4 and 94.6% for the diagnoses of PHPT and NPHPT, respectively. The use of a PFindex > 34 to differentiate NPHPT from VD-SHPT yielded the highest positive likelihood ratio and lowest negative likelihood ratio. CONCLUSION: The PFindex provided excellent diagnostic power for the differentiation of NPHPT from VD-SHPT. This simple tool may be useful for guiding timely decision-making processes regarding the initiation of vitamin D treatment or surgery for PHPT.

Advanced Maternal Age, Mode of Delivery, and Thyroid Hormone Levels in Chinese Newborns.

Objective: Thyroid hormones are essential for fetal growth and neurodevelopment, however, data on cord blood thyroid hormones are sparse in China where maternal age at childbearing is increasing in recent decades. We aimed to assess cord blood levels of free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) in full-term Chinese newborns, and examine potential related perinatal factors. Methods: This study included 922 mother-newborn pairs from a prospective birth cohort enrolled in 2012-2013, Shanghai, China. Cord serum concentrations of FT3, FT4, TSH, and TPOAb were measured in newborns. Results: Newborns born via cesarean section had higher cord serum FT3 (mean ± SD: 1.90 ± 1.16 pmol/L) and lower cord serum TSH (5.15 ± 2.60 mIU/L) than those born via vaginal delivery (FT3: 1.62 ± 0.93 pmol/L; TSH: 9.27 ± 6.76 mIU/L). In cesarean section deliveries, the concentration of cord serum FT3 was 0.15 (95%CI: -0.03, 0.33; p = 0.10) pmol/L lower in infants of mothers aged 30-34 years, and 0.57 (95%CI: 0.22, 0.92; p = 0.002) pmol/L lower in infants of mothers ≥35 years compared to infants of mothers <30 years. Large-for-gestational-age (birth weight >90th percentile) was associated with higher TSH (p = 0.02). Similar results were also found in vaginal deliveries. Conclusions: In this Chinese term birth cohort, newborns born via cesarean section had higher cord serum FT3 and lower TSH than those born via vaginal delivery. Advanced maternal age was associated with lower fetal FT3. Further research is needed to understand whether this association may mediate the adverse impact of advanced maternal age on neurodevelopment in early life.

Thioredoxin-interacting protein links endoplasmic reticulum stress to inflammatory brain injury and apoptosis after subarachnoid haemorrhage.

BACKGROUND: Early brain injury (EBI) is considered a major contributor to the high morbidity and mortality associated with subarachnoid haemorrhage (SAH). Both of sterile inflammation and apoptosis are considered the important causes of EBI. Recently, it was confirmed that thioredoxin-interacting protein (TXNIP) not only participates in inflammatory amplification but also stimulates the apoptosis signalling cascade pathway. However, whether the effects of TXNIP influence the pathogenesis of SAH remains unclear. Here, we hypothesize that TXNIP activity induced by endoplasmic reticulum stress (ER stress) may contribute to the pathogenesis of EBI through pro-inflammatory and pro-apoptotic mechanisms. METHODS: A total of 299 male Sprague-Dawley rats were used to create SAH models. Resveratrol (RES, 60 mg/kg) and two TXNIP small interfering RNA (siRNA) were used to inhibit TXNIP expression. The specific inhibitors of ER stress sensors were used to disrupt the link between TXNIP and ER stress. SAH grade, neurological deficits, brain water content and blood-brain barrier (BBB) permeability were evaluated simultaneously as prognostic indicators. Fluorescent double-labelling was employed to detect the location of TXNIP in cerebral cells. Western blot and TUNEL were performed to study the mechanisms of TXNIP and EBI. RESULTS: We found that TXNIP expression significantly increased after SAH, peaking at 48 h (0.48 ± 0.04, up to 3.2-fold) and decreasing at 72 h after surgery. This process was accompanied by the generation of inflammation-associated factors. TXNIP was expressed in the cytoplasm of neurons and was widely co-localized with TUNEL-positive cells in both the hippocampus and the cortex of SAH rats. We discovered for the first time that TXNIP was co-localized in neural immunocytes (microglia and astrocytes). After administration of RES, TXNIP siRNA and ER stress inhibitors, TXNIP expression was significantly reduced and the crosstalk between TXNIP and ER stress was disrupted; this was accompanied by a reduction in inflammatory and apoptotic factors, as well as attenuation of the prognostic indices. CONCLUSIONS: These results may represent the critical evidence to support the pro-inflammatory and pro-apoptotic effects of TXNIP after SAH. Our data suggest that TXNIP participates in EBI after SAH by mediating inflammation and apoptosis; these pathways may represent a potential therapeutic strategy for SAH treatment.

Generalized high bone mineral density on bone density scanning: a case of gastric carcinoma with bone metastasis.

Generalized high bone mineral density (BMD) on Dual-energy X-ray absorptiometry (DXA) scanning most commonly reflects metabolic bone disease. However, some malignancies could also stimulate the underlying processes. We reported that a 41-year-old female was referred for lumbago. She did not complain of any symptoms in the digestive system. DXA revealed high BMD in the lumbar vertebras. Marked increase in bone mass was observed in an X-ray of chest compared with one conducted 6 months previously. Additionally, an X-ray of the axial skeleton showed diffuse sclerotic change. Laboratory data revealed hypocalcemia and high osteoblastic activity. A bone biopsy of the pelvis confirmed metastatic undifferentiated adenocarcinoma. Further research for the primary site revealed gastric signet ring cell carcinoma via endoscopic biopsy. The patient refused treatment and died 2 months after the diagnosis. In clinical practice, high BMD could be the initial feature of gastric cancer. Due to its poor prognosis, adequate clinical management is of paramount value.