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The role of alkali metals in the development of neural tube defects (NTDs) is little known. We examined the associations between placental concentrations of lithium (Li), sodium (Na), potassium (K), rubidium (Rb), and cesium (Cs), and the occurrence of NTDs in fetuses.408 women who had NTD-affected pregnancies and 593 women who delivered healthy infants were included. Logistic regression, weight quantile sum regression (WQSR), and Bayesian kernel machine regression (BKMR) were applied to assess whether these metals are associated with the occurrence of NTDs.Cs showed an inverse association with the odds of NTDs [adjusted odds ratio (aOR): 0.58, 95% confidence interval (CI): 0.36-0.91] in single-metal logistic model. Estimates did not change much in the multiple-metal logistic model. In WQSR, the WQS index was inversely associated with the odds of NTDs (aOR: 0.62, 95%CI: 0.51-0.75), in which Cs (weighted 0.45) had the highest weight. In BKMR, the odds of NTDs decreased with the levels of the five-metal mixtures. Cs was associated with decreased odds of NTDs when the remaining four metals were fixed at their 25A high concentration of Cs and Na in placental tissue was respectively associated with decreased and increased odds of NTDs. In addition, the occurrence of NTDs decreased with the levels of the five-metal mixtures.

Previous epidemiological studies have shown that prenatal exposure to organochlorine pesticides (OCPs) entails a variety of adverse impacts on fetal health, but it is not yet known whether it is associated with risk for orofacial clefts (OFCs). This study of 103 fetuses or newborns with a diagnosis of OFCs (cases) and 103 healthy newborns without malformations (controls) examined whether prenatal exposure to OCPs, as indicated by their concentrations in placental tissue, is a risk factor for OFCs. No differences were found in the median concentrations of OCPs between cases and controls, with exception of o,p'-dichlorodiphenyldichloroethylene, o,p'-dichlorodiphenyldichloroethane, and total o,p'-dichlorodiphenyltrichloroethane (DDTs), whose concentrations were higher in controls than in cases (Ps 0.05). Although higher concentrations of placental δhexachlorocyclohexane and isodrin were found to be associated with decreased risk for OFCs in logistic regression, no association was observed in the Bayesian kernel machine regression, a novel statistical model in analyzing exposure mixtures. Women who reported periconceptional folic acid supplementation had lower placental concentrations of DDTs than women who did not. In conclusion, no association between levels of OCPs in placental tissue and risk for OFCs was observed in this population. Supplementation with folic acid may help decrease the levels of DDTs in placental tissue, but further studies are needed to confirm this unexpected finding.

Growing evidence suggests that essential trace element imbalance during pregnancy may contribute to fetal malformations, but the role of essential trace elements in the occurrence of orofacial clefts (OFCs) is unknown. We aimed to examine the association between concentrations of zinc (Zn), manganese (Mn), selenium (Se), cobalt (Co), molybdenum (Mo), and nickel (Ni) in placental tissues and the risk for OFCs in offspring in a rural population in northern China with a high prevalence of OFCs.The case-control study subjects were 103 OFC infants and 206 non-malformed infants. The concentrations of selected trace elements in placental tissues were determined using inductively coupled plasma-mass spectrometry. Sociodemographic information was collected from the mothers through face-to-face interviews using a structured questionnaire. The risk for OFCs in association with higher concentrations of the trace elements was estimated using the odds ratio (OR) with its 95% confidence interval (95% CI).The placental median concentrations of Se and Ni were significantly lower, but those of Mo were significantly higher in OFC cases than in controls (all P 0.05). A Se concentration above the median of all subjects was associated with a 58% reduced risk for OFCs (adjusted OR 0.42, 95% CI 0.23, 0.77) after adjusting for potential confounding factors. The risk for OFCs decreased with increases in placental Se concentrations, with adjusted ORs of 0.45 (95% CI 0.22, 0.92) for the second tertile and 0.22 (95% CI 0.10, 0.49) for the top tertile of Se concentration, with the lowest tertile concentration as the referent (PThe concentration of Se in placental tissues was dose-dependently associated with decreased risk for OFCs in offspring. This finding suggests that maternal Se intake during pregnancy may protect against OFCs in offspring.

Uranium and thorium are common radioactive elements that exist in the environment. However, few environmental epidemiological studies have focused on their possible effects on congenital malformations. Here, we explored the association between uranium and thorium concentrations in maternal scalp hair grown from 3 months before to 3 months after conception, namely during the periconceptional period and the risk of orofacial clefts (OFCs) in offspring. Our study included 153 women whose pregnancies were affected by OFCs (cases) and 601 women who delivered infants without birth defects (controls) from four provinces in China. Face-to-face interviews were used to collect sociodemographic characteristics with a structured questionnaire. Concentrations of uranium and thorium in maternal scalp hair grown during the periconceptional period were detected using inductively coupled plasma-mass spectrometry. The risk of OFCs in association with higher concentrations of the two radioactive elements was estimated using odds ratios (ORs) and 95% confidence intervals (CIs) while adjusting for potential confounding factors. The levels of uranium and thorium in maternal hair were in agreement with the published literature. After adjusting for several confounders, the ORs of thorium in the highest, upper, and lower quartile versus the lowest quartile were 2.63 (95% CI, 1.41-4.92), 1.98 (95% CI, 1.03-3.79), and 2.73 (95% CI, 1.46-5.12), respectively. No association was found between levels of uranium and the risk of OFCs. Maternal periconceptional exposure to thorium may be a risk factor for OFCs in offspring.

Natural exposure to and increasing use of barium and aluminum in various products, such as plastics, rubber, and food additives, raise concerns for their potential health impacts on pregnant women and vulnerable fetuses. We investigated whether there are associations between barium and aluminum concentrations in placental tissues and the risk for orofacial clefts (OFCs) in offspring. In this case-control study, we recruited 103 women with OFC-affected pregnancies and 206 women who delivered healthy newborns. Concentrations of barium and aluminum in placental tissues were measured using inductively coupled plasma-mass spectrometry. Information on maternal sociodemographic characteristics and diet was collected via face-to-face interviews using a structured questionnaire. Aluminum concentrations in placental tissues were not associated with OFC risk. However, a higher concentration of barium in placental tissues was associated with an increased risk for OFCs, with an adjusted odds ratio (OR) of 2.42 (95% confidence interval [95% CI] 1.34–4.40) for total cleft lip with or without cleft palate (CL ± P), and 1.90 (95% CI 1.03–3.50) for isolated CL ± P. There was a positive dose–response relationship between placental barium concentrations and OFC risk. Maternal exposure to barium may increase the risk for OFCs in offspring.

Aluminum (Al)1 is ubiquitously present in the environment, and human exposure to Al is common. Al has been reported to be involved in various human diseases and adverse pregnancy outcomes, including neural tube defects (NTDs). This study aimed to examine the association between prenatal Al exposure and the risk for NTDs using Al concentrations in maternal serum and placental tissue. The subjects were recruited from six counties/cities in the Shanxi province of northern China from 2003 to 2016. Al concentrations in both types of specimens were assessed using inductively coupled plasma-mass spectrometry. In the maternal serum cohort (200 cases and 400 controls), compared to the lowest tertile concentration of Al, the highest Al tertile was associated with 2.42-fold (95% confidence interval, 1.23-4.87) increased risk after adjustment for confounding factors. In the placental tissue cohort (408 cases and 593 controls), the highest tertile of Al also tended to be associated with an elevated risk for NTDs [adjusted odds ratio, 1.60 (0.94-2.70)]. When analyzed by NTD subtypes, the highest Al tertile was associated with an increased risk for anencephaly in both cohorts after adjustment for confounders [odds ratio, 1.97 (1.15-3.48) in the maternal serum cohort; odds ratio, 4.75 (2.01-12.00) in the placental tissue cohort]. Taken together, using concentrations of Al in maternal serum and placental tissue as exposure markers, we found that prenatal exposure to higher levels of Al is a risk factor for fetal NTDs, especially for the anencephaly subtype.

Background To examine whether exposure to secondhand smoke (SHS) during the periconceptional period among nonsmoking women is associated with an increased risk for orofacial clefts (OFCs) in offspring in a population with low rates of maternal active smoking but high rates of SHS exposure. Methods We recruited 240 women with OFC-affected pregnancies and 1420 women who delivered healthy infants from a population-based case-control study in northern China during 2002 and 2016. Data including self-reported SHS exposure were collected by trained health care workers through face-to-face interviews. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were used to estimate the association between SHS exposure and OFC risk. Results The unadjusted ORs for OFCs and cleft lip with or without cleft palate (CL±P) in association with SHS exposure were both 1.6 (95% CI 1.2, 2.1). After adjusting for maternal fever or flu, farming occupation, infant sex, and history of pregnancy affected by birth defects, the adjusted ORs were both 1.6 (95% CI 1.2, 2.2). Frequent SHS exposure (>6 times/week) was associated with an even higher risk for OFCs (adjusted OR 2.6, 95% CI 1.8, 3.8) and for CL±P (adjusted OR 2.5, 95% CI 1.7, 3.7). Conclusions Maternal SHS exposure during the periconceptional period increases the risk for OFCs in offspring among nonsmoking mothers.

Rare earth elements (REEs) are ubiquitous in the environment. Animal experiments have shown that many REEs have adverse impacts on the health of fetuses. However, data from humans are scarce. In this study, we examined the associations between concentrations of 10 REEs in maternal serum and the risk for fetal neural tube defects (NTDs). The study included 200 pregnant women with pregnancies affected by NTDs and 400 pregnant women with healthy fetuses/infants. Fifteen REEs in maternal serum were assessed; 10 of them were detectable in over 60% of samples and were included in statistical analyses, including lanthanum (La), cerium (Ce), praseodymium (Pr), neodymium (Nd), samarium (Sm), europium (Eu), terbium (Tb), dysprosium (Dy), lutetium (Lu), and yttrium (Y). When the elements were considered individually with the use of Logistic regression model, the risk for NTDs increased by 2.78-fold (1.25–6.17) and 4.31-fold (1.93–9.62) for La, and 1.52-fold (0.70–3.31) and 4.73-fold (2.08–10.76) for Ce, in the second and third tertiles, respectively, compared to the lowest concentration tertile. When Bayesian kernel machine regression was used to examine the joint effect of exposure to all 10 REEs, the risk for NTDs increased with overall levels of these REEs and the association between La and NTD risk remained when other nine elements were taken into consideration simultaneously. Taken together, this study shows that the risk for NTDs increases with La concentrations when single REEs are considered and with concentrations of all 10 REEs when these REEs are considered as a co-exposure mixture. Keywords: Rare earth element, Neural tube defect, Serum, Pregnancy, Bayesian kernel machine regression

Orofacial clefts (OFCs) have multifactorial etiologies. Prenatal exposure to heavy metals can induce OFCs in animal models, but evidence from studies of human subjects is scarce. We examined whether concentrations of mercury (Hg), cadmium (Cd), lead (Pb), and arsenic (As) in placental tissues are associated with risk for OFCs in offspring. This population-based case-control study included 103 newborns affected by OFCs with available placental tissues and 206 controls randomly selected from 509 non-malformed newborns with available placenta samples, recruited in five rural counties in northern China. Sociodemographic information was collected using a structured questionnaire in face-to-face interviews. The concentrations of Hg, Cd, Pb, and As in placental tissues were analyzed using an inductively coupled plasma-mass spectrometry in helium mode. The median concentrations of Hg (7.4 ng/g), Cd (57.1 ng/g), and Pb (96.1 ng/g) were all statistically significantly higher in OFC cases than in controls (Hg 5.5 ng/g, Cd 38.6 ng/g, and Pb 67.9 ng/g, respectively); no differences were observed between the two groups in median concentrations of As. Concentrations above the median for all subjects were associated with a 2.33-fold (95% confidence interval [CI] 1.33–2.09) increased OFC risk for Cd and a 3.08-fold (95% CI 1.74–5.47) increased risk for Pb. The risk for OFCs increased with concentration tertiles, with an adjusted odds ratio of 3.06 (95% CI 1.36–6.88) for the second tertile and 8.18 (95% CI 6.64–18.37) for the highest tertile of Cd, and 3.88 (95% CI 1.78–8.42) for the second tertile and 5.17 (95% CI 2.37–11.29) for the highest tertile of Pb. The association between Hg concentration and OFC risk was borderline nonsignificant after adjusting for confounding factors. Prenatal exposure to Cd and Pb, as reflected by their concentrations in placental tissues, is associated with an increased risk for neonatal OFCs.

Urinary volatile organic compounds (VOCs) profiling has recently received considerable attention because it can be obtained noninvasively and conveniently while it can be successfully used in a variety of diseases and can provide unique biomarkers. The aim of current study was to investigate potential biomarkers between minimal change type nephrotic syndrome (MCNS) and normal. Urinary samples were collected from 38 minimal change type nephrotic syndrome patients and 15 healthy controls. Solid phase microextraction (SPME) and chromatography- mass spectrometry (GC-MS) were used to analysis the urinary metabolites. To deal with the final data, the statistical methods principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLSDA) were performed. Six specific VOC biomarkers were present at abnormal levels in the urine of MCNS patients. These VOCs included trans-2,2-dimethyl-4-decene; pyrrole; carbamic acid, monoammonium salt; 1-butyne, 3,3-dimethyl-; diisopropylamine; and 4-heptanone. These biomarkers may be useful as a new diagnostic method and for monitoring the prognosis for MCNS patients.

Amyotrophic lateral sclerosis (ALS) is an incurable neurological degenerative disease. It can cause irreversible neurological damage to motor neurons; typical symptoms include muscle weakness and atrophy, bulbar paralysis and pyramidal tract signs. The ALS-mimicking disease cervical spondylotic myelopathy (CSM) presents similar symptoms, but analysis of breath volatile organic compounds (VOCs) can potentially be used to distinguish ALS from CSM. In this study, breath samples were collected from 28 ALS and 13 CSM patients. Subsequently, gas chromatography/mass spectrometry (GCMS) was used to analyze breath VOCs. Principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLSDA) were the statistical methods used to process the final data. We identified 4 compounds with significantly decreased levels in ALS patients compared with CSM controls: (1) carbamic acid, monoammonium salt; (2) 1-alanine ethylamide, (S)-; (3) guanidine, N,N-dimethyl-; and (4) phosphonic acid, (p-hydroxyphenyl)-. Currently, the metabolic origin of the VOCs remains unclear; however, several pathways might explain the decreasing trends observed. The results of this study demonstrate that there are specific VOC profiles associated with ALS and CSM patients that can be used to differentiate between the two. In addition, these metabolites could contribute to a better understanding of the underlying pathophysiological mechanisms of ALS.

Urinary volatile organic compounds (VOCs) analysis for kidney diseases has attracted a large amount of scientific interest recently and urinary metabolite analysis has already been applied to many diseases. Urine was collected from 15 mesangial proliferative glomerulonephritis (MsPGN) patients, 21 IgA nephropathy (IgAN) patients and 15 healthy controls. Solid phase microextraction–chromatography– mass spectrometry (SPME-GC-MS) was used to analyse the urinary metabolites. The statistical methods principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLSDA) were performed to process the final data. Five metabolites were significantly greater in the group of MsPGN patients than in the normal control group (P

To identify the best lung ventilation strategy for acute respiratory distress syndrome (ARDS), we performed a network meta-analysis. The Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE, CINAHL and the Web of Science were searched and 36 eligible articles were included. Compared with higher tidal volumes with FiO2-guided lower positive end-expiratory pressure [PEEP], the hazard ratios (HRs) for mortality were 0.624 (95% confidence interval (CI) 0.419–0.98) for lower tidal volumes with FiO2-guided lower PEEP and prone positioning and 0.572 (0.34–0.968) for pressure-controlled ventilation with FiO2-guided lower PEEP. Lower tidal volumes with FiO2-guided higher PEEP and prone positioning had the greatest potential to reduce mortality and the possibility of receiving the first ranking was 61.6%. Permissive hypercapnia, recruitment maneuver and low airway pressures were most likely to be the worst in terms of all-cause mortality. Compared with higher tidal volumes with FiO2-guided lower PEEP, pressure-controlled ventilation with FiO2-guided lower PEEP and lower tidal volumes with FiO2-guided lower PEEP and prone positioning ventilation are associated with lower mortality in ARDS patients. Lower tidal volumes with FiO2-guided higher PEEP and prone positioning ventilation and lower tidal volumes with pressure-volume (P–V) static curve-guided individual PEEP are potential optimal strategies for ARDS patients.

Exhaled nitric oxide (eNO) has been suggested to be a marker of small airway injury. We investigated the effects of different ventilation strategies on eNO. Sixty-nine patients who received elective open abdominal surgery under general anesthesia with more than 2 h of surgery duration were randomly divided into three groups: high tidal volume of 10-12 ml kg(-1) predicted body weight (PBW) with zero end-expiratory pressure (ZEEP) (high VT + ZEEP group); low tidal volume of 6-8 ml kg(-1) PBW with 8 cm H2O positive end-expiratory pressure (PEEP) (low VT + PEEP group); and low tidal volume of 6-8 ml kg(-1) PBW with 8 cm H2O PEEP and recruitment maneuvers (low VT + PEEP + RMs group). eNO, respiratory system compliance (Crs), oxygenation index, inflammatory mediators tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), IL-8, prostaglandin E2 (PGE2) and PGF2a as well as pulmonary function were measured during the perioperative period. The postoperative eNO decreased in 78.3% of patients in the high VT + ZEEP group and low VT + PEEP group, and increased in 56.5% of patients in the low VT + PEEP + RMs group (P = 0.016). The Crs level in the high VT + ZEEP group significantly decreased with time but significantly increased in the low VT + PEEP + RMs group (P 0.05). The oxygenation index, inflammatory mediators and pulmonary function did not statistically differ among the three groups. Compared with the low VT + PEEP + RMs group, the decreasing rate of postoperative eNO in the high VT + ZEEP and low VT + PEEP groups was higher, which may imply small airway injury during geriatric abdominal surgery.

The potentially harmful effects of short-term mechanical ventilation during surgery have been examined in recent years. An optimal strategy for mechanical ventilation of patients during non-laparoscopic abdominal surgery must be devised. A total of 63 patients undergoing elective open abdominal surgery with more than 2 h of ventilation time were selected for this randomized, open-label, clinical study. They were divided into three ventilation groups: high volume of 9 ml/kg IBW (ideal body weight) with ZEEP (zero end-expiratory pressure); low volume of 7 ml/kg IBW with 8 cm H2O PEEP (positive end expiratory pressure); and low volume of 7 ml/kg IBW with 8 cm H2O PEEP and recruitment. Intraoperative PaO2/FiO2 ratio and pulmonary compliance and postoperative pulmonary function were measured. There were no significant differences in intraoperative PaO2/FiO2 ratio among the three groups (P=0.31). The pulmonary compliance of three groups showed different changes over time (group effect over time P=0.0006). There were no significant differences in FEV1 or FVC among the three groups (P=0.32 and 0.09, respectively), but both of these measurements showed different changes over time (group effect over time P0.001). On the first postoperative day, the low volume with high PEEP and recruitment group had significantly higher FEV1 than the other two groups (mean ± SD): 1.52 ± 0.37 versus 0.95 ± 0.38 (P0.001) and 1.52 ± 0.37 versus 0.95 ± 0.34 (P0.001), respectively. Low tidal volume with PEEP and recruitment showed advantages in maintaining the pulmonary compliance and expediting the recovery of the 1(st) postoperative day's pulmonary function in patients undergoing non-laparoscopic abdominal surgery.

To investigate the distribution and drainage of lymphatic vessels of tongue, and to provide anatomical evidence for treatment of tongue cancer.Indirect lymphatic injection was employed, combined with clearing method with winter green oil and corrosive cast technique, to study the distribution of lymphatic vessels of tongue. Anatomical methods were used to detect the sentinel lymph nodes in different region of tongue.The lymphatic vessels of dorsal mucosa composed of lymphocapillary vessels and anstomosing side branches were present by superficial and deep capillary networks. The distribution of lymphatic networks extend from tip to base and from one board to another, and was not influenced by the sulcus tenninalis and median lingual sulcus. Lymphatic vessels in the muscular portion communicated with lymphocapillary network of dorsal and ventral mucosa, which made the lymphatic vessels of tongue to be an integrity network structure. These characters of distribution influenced the lymphatic drainage of tongue. The results showed principal sentinel lymph nodes (SLNs) for anterior part of tongue were submental lymph nodes, submandibular lymph nodes and juguloomohyoid lymph nodes, for lateral part and middle part of tongue were submandibular lymph nodes, jugulodigastric lymph nodes and thyroid lymph nodes, and for root part of tongue were jugulodigastric lymph nodes. SLNs for every injection region were all presented at bilatral neck, but the frequency of stained SLNs at homolateral neck was more than that at contralateral neck.The lymphatic vessels of tongue arranged like a network, which made the lymphatic drainage at various ways and made the distribution of sentinel lymph nodes to be bilateral and dispersive.