Polystyrenenanoplastics lead to ferroptosis in the lungs.

INTRODUCTION: It has been shown that polystyrenenanoplastic (PS-NP) exposure induces toxicity in the lungs. OBJECTIVES: This study aims to provide foundational evidence to corroborate that ferroptosis and abnormal HIF-1α activity are the main factors contributing to pulmonary dysfunction induced by PS-NP exposure. METHODS: Fifty male and female C57BL/6 mice were exposed to distilled water or 100 nm or 200 nm PS-NPs via intratracheal instillation for 7 consecutive days. Hematoxylin and eosin (H&E) and Masson trichrome staining were performed to observe the histomorphological changes in the lungs. To clarify the mechanisms of PS-NP-induced lung injury, we used 100 µg/ml, 200 µg/ml and 400 µg/ml 100 or 200 nm PS-NPs to treat the human lung bronchial epithelial cell line BEAS-2B for 24 h. RNA sequencing (RNA-seq) of BEAS-2B cells was performed following exposure. The levels of glutathione, malondialdehyde, ferrous iron (Fe2+), and reactive oxygen species (ROS) were measured. The expression levels of ferroptotic proteins were detected in BEAS-2B cells and lung tissues by Western blotting. Western blotting, immunohistochemistry, and immunofluorescence were used to evaluate the HIF-1α/HO-1 signaling pathway activity. RESULTS: H&E staining revealed substantial perivascular lymphocytic inflammation in a bronchiolocentric pattern, and Masson trichrome staining demonstrated critical collagen deposits in the lungs after PS-NP exposure. RNA-seq revealed that the differentially expressed genes in PS-NP-exposed BEAS-2B cells were enriched in lipid metabolism and iron ion binding processes. After PS-NP exposure, the levels of malondialdehyde, Fe2+, and ROS were increased, but glutathione level was decreased. The expression levels of ferroptotic proteins were altered significantly. These results verified that PS-NP exposure led to pulmonary injury through ferroptosis. Finally, we discovered that the HIF-1α/HO-1 signaling pathway played an important role in regulating ferroptosis in the PS-NP-exposed lung injury. CONCLUSION: PS-NP exposure caused ferroptosis in bronchial epithelial cells by activating the HIF-1α/HO-1 signaling pathway, and eventually led to lung injury.

mTOR signaling in hair follicle and hair diseases: recent progress.

Mammalian target of rapamycin (mTOR) signaling pathway is a major regulator of cell proliferation and metabolism, playing significant roles in proliferation, apoptosis, inflammation, and illness. More and more evidences showed that the mTOR signaling pathway affects hair follicle circulation and maintains the stability of hair follicle stem cells. mTOR signaling may be a critical cog in Vitamin D receptor (VDR) deficiency-mediated hair follicle damage and degeneration and related alopecia disorders. This review examines the function of mTOR signaling in hair follicles and hair diseases, and talks about the underlying molecular mechanisms that mTOR signaling regulates.

Effects of Natural Polyphenols on Skin and Hair Health: A Review.

The skin is the largest organ of the body and plays multiple essential roles, ranging from regulating temperature, preventing infections, to ultimately affecting human health. A hair follicle is a complex cutaneous appendage. Skin diseases and hair loss have a significant effect on the quality of life and psychosocial adjustment of individuals. However, the available traditional drugs for treating skin and hair diseases may have some insufficiencies; therefore, a growing number of researchers are interested in natural materials that could achieve satisfactory results and minimize adverse effects. Natural polyphenols, named for the multiple phenolic hydroxyl groups in their structures, are promising candidates and continue to be of scientific interest due to their multifunctional biological properties and safety. Polyphenols have a wide range of pharmacological effects. In addition to the most common effect, antioxidation, polyphenols have anti-inflammatory, bacteriostatic, antitumor, and other biological effects associated with reduced risk of a number of chronic diseases. Various polyphenols have also shown efficacy against different types of skin and hair diseases, both in vitro and in vivo, via different mechanisms. Thus, this paper reviews the research progress in natural polyphenols for the protection of skin and hair health, especially focusing on their potential therapeutic mechanisms against skin and hair disorders. A deep understanding of natural polyphenols provides a new perspective for the safe treatment of skin diseases and hair loss.

Prenatal exposure to endocrine-disrupting chemicals and thyroid function in neonates: A systematic review and meta-analysis.

Thyroid hormone homeostasis is essential for normal brain development in fetuses and infants. Exposure to endocrine-disrupting chemicals (EDCs) during pregnancy is associated with compromised maternal thyroid homeostasis, and thus may lead to adverse neurodevelopmental outcomes in newborns. However, evidence regarding the association of prenatal EDC exposure and thyroid hormones in newborns is controversial. Therefore, a meta-analysis to elucidate the relationship between maternal exposure to EDCs and neonatal THs was performed. A systematic search of PubMed, EMBASE, and the Cochrane Library (CENTRAL) for relevant published studies that provided quantitative data on the association between prenatal EDC exposure and neonatal thyroid hormones was conducted in August 2021. To calculate the overall estimates, we pooled the adjusted ß regression coefficients with 95% confidence intervals (CIs) from each study by the inverse variance method. The pooling results indicated that prenatal EDC exposure had no significant influence on neonatal TSH, TT3, FT3, TT4 or FT4 level in the global assessment. However, in the specific exposure and outcome assessment, we found that prenatal exposure to organochlorine (ß coefficient, -0.022; 95% CI, -0.04 to -0.003) and PFAS (ß coefficient, -0.017; 95% CI, -0.033 to 0) was negatively associated with neonatal TT4 level. In conclusion, prenatal exposure to organochlorine and PFAS may be associated with lower neonatal TT4 level.

[Comparison of ED50 of intranasal dexmedetomidine sedation in children with acyanotic congenital heart disease before and after cardiac surgery].

OBJECTIVE: To compare the median effective dose (ED50) of intranasal dexmedetomidine for procedural sedation in uncooperative pediatric patients with acyanotic congenital heart disease before and after cardiac surgery. METHODS: We prospectively recruited 47 children (22 in preoperative group and 25 in postoperative group) who needed sedation for transthoracic echocardiography (TTE). A modified up-and-down sequential study design was employed to determine dexmedetomidine dose for each patient with a starting dose of 2 µg/kg in both groups; dexmedetomidine doses for subsequent subjects were determined according to the responses from the previous subject using the up-and-down method at a 0.25 µg/kg interval. The ED95 was determined using probit regression. The onset time, examination time, wake-up time and adverse effects were measured, and the safety was evaluated in terms of changes in vital signs every 5 min. RESULTS: The ED50 value of intranasal dexmedetomidine for sedation was 1.84 µg/kg (95% CI: 1.68-2.00 µg/kg) in children with congenital heart disease before cardiac surgery, and 3.38 µg/kg (95% CI: 3.21-3.54 µg/kg) after the surgery. No significant difference was found between the two groups in the demographic variables, onset time, examination time, wake-up time, or adverse effects. CONCLUSIONS: In children with acyanotic congenital heart disease, the ED50 of intranasal dexmedetomidine for TTE sedation increases to 3.38 µg/ kg after cardiac surgery from the preoperative value of 1.84 µg/kg.

The gut-microbiota-testis axis mediated by the activation of the Nrf2 antioxidant pathway is related to prepuberal steroidogenesis disorders induced by di-(2-ethylhexyl) phthalate.

Di-(2-ethylhexyl) phthalate (DEHP) is a common plasticizer, which is known to be an environmental endocrine-disrupting chemical that can jeopardize the male reproductive system. Prepuberal exposure to DEHP leads to steroidogenesis disorders. However, the specific mechanism remains ambiguous. Therefore, Sprague Dawley (SD) rats underwent prepuberal DEHP exposure at a dose of 500 mg/kg per day through gavage. Additionally, the resulting testicular injury was evaluated to confirm the disturbed steroidogenesis. Changes in testicular histology, significant reduction of serum testosterone (P < 0.01) and luteinizing hormone (P < 0.001), and significantly decreased expressions of steroidogenic acute regulatory protein (P < 0.01) and 3-beta-hydroxysteroid dehydrogenase (P < 0.05) were found in DEHP-treated rats. DEHP exposure resulted in obvious intestinal damage and oxidative stress imbalance, primarily in the jejunum. Both the activation of the nuclear factor-E2-related factor 2 (Nrf2) signaling pathway and alterations of microbiota profiles were observed in all three gut specimens, but were most notable in the jejunum. We hypothesize that the gut-microbiota-testis axis, which is mediated by the activation of the Nrf2 antioxidant pathway, could be involved in the dysfunction of prepuberal steroidogenesis induced by DEHP.

A Comparison of Intranasal Dexmedetomidine and Dexmedetomidine-Ketamine Combination Sedation for Transthoracic Echocardiography in Pediatric Patients With Congenital Heart Disease: A Randomized Controlled Trial.

OBJECTIVES: To compare the effects of intranasal dexmedetomidine (DEX) and DEX-ketamine (KET) on hemodynamics and sedation quality in children with congenital heart disease. DESIGN: A randomized controlled, double-blind, prospective trial. SETTING: A tertiary care teaching hospital. PARTICIPANTS: The study comprised 60 children undergoing transthoracic echocardiography (TTE). INTERVENTIONS: Patients were randomly allocated into the DEX group (group D [n = 30]) or the DEX-KET group (group D-K [n = 30]). Group D received 2 µg/kg of intranasal DEX; group D-K received 2 µg/kg of DEX and 1 mg/kg of KET intranasally. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the change in hemodynamics, measured using mean arterial pressure (MAP) and heart rate (HR). Secondary outcomes were onset time, wake-up time, and discharge time. No differences were found in mean arterial pressure or heart rate. The onset time was significantly shorter in group D-K than in group D (9.6 ± 2.9 minutes v 14.3 ± 3.4 minutes; p = 0.031). The wake-up time was longer in group D-K than in group D (52 ± 14.7 minutes v 39.6 ± 12.1 minutes; p = 0.017). The discharge time was longer in group D-K than in group D (61.33 ± 11.59 minutes v 48.17 ± 8.86 minutes; p < 0.001). No differences in hemodynamics were found between the 2 groups. Intranasal DEX was found to be as effective for TTE sedation as intranasal DEX-KET, with longer onset time and shorter recovery and discharge times. CONCLUSION: No differences in hemodynamics were found between the 2 groups. Intranasal DEX was found to be as effective for TTE sedation as is intranasal DEX-KET, with longer onset time and shorter recovery and discharge times.

The effects of repeated propofol anesthesia on spatial memory and long-term potentiation in infant rats under hypoxic conditions.

Propofol is widely used as an intravenous drug for induction and maintenance in general anesthesia. Hypoxemia is a common complication during perianesthesia. We want to know the effect of propofol on spatial memory and LTP (Long-term potentiation) under hypoxic conditions. In this study, 84 seven-day-old Sprague-Dawley rats were randomly assigned into six groups (n = 14)-four control groups: lipid emulsion solvent + 50% oxygen (CO), lipid emulsion solvent + room air (CA), lipid emulsion solvent + 18% oxygen (CH), and propofol + 50% oxygen (propofol-oxygen, PO); and two experiment groups: propofol + room air (propofol-air, PA), and propofol + 18% oxygen (propofol-hypoxia, PH). After receiving propofol (50 mg/kg) or the same volume of intralipid intraperitoneal (5.0 ml/kg), injected once per day for seven consecutive days, the rats were exposed to 18% oxygen, 50% oxygen and air, until recovery of the righting reflex. We found that the apoptotic index and activated caspase-3 increased in the PH group (P < 0.05) compared with the PA group, fEPSP (field excitatory postsynaptic) potential and success induction rate of LTP reduced in all propofol groups (P < 0.05). Compared with the PO group, the fEPSP and success induction rate of LTP reduced significantly in the PA and PH groups (P < 0.05). Moreover, compared with CH group, the average time of escape latency was longer, and the number of platform location crossings was significantly reduced in the PH group (P < 0.05). Thus, we believe that adequate oxygen is very important during propofol anesthesia.

The 95% effective dose of intranasal dexmedetomidine sedation for pulmonary function testing in children aged 1-3 years: A biased coin design up-and-down sequential method.

STUDY OBJECTIVE: Intranasal dexmedetomidine (DEX) can provide adequate sedation during short examinations in children. However, we found no data regarding the 95% effective dose (ED95) of intranasal DEX for children's pulmonary function testing (PFT). DESIGN: Prospective study and a biased coin design up-and-down sequential method. SETTING: Sedation center of Children's Hospital of Chongqing Medical University. PATIENTS: Children aged 1-3 years undergoing pulmonary function testing. INTERVENTION: The dose of DEX for each subsequent patient was determined by the response of the previous patient with the biased coin design up-and-down sequential method with an interval of 0.25 µg∙kg-1. MEASUREMENTS: Children aged 1-3 years who received pulmonary function testing were involved in this dose-finding trial. Intranasal DEX started at a dose of 2 µg∙kg-1 on the first patient. The dose of DEX for each subsequent patient was determined by the response of the previous patient with the biased coin design up-and-down sequential method with an interval of 0.25 µg∙kg-1. The sedation was assessed by the Modified Observer Assessment of Alertness and Sedation (MOAA/S) scale, and recovery was assessed by the modified Aldrete recovery score. The ED95 was calculated using isotonic regression. Other variables, including the sedation onset time, examination time, wake-up time, blood pressure (BP), heart rate (HR), respiratory rate (RR), and oxyhaemoglobin desaturation (SpO2), were recorded. Adverse events such as hypotension, bradycardia, respiration depression, oxyhaemoglobin desaturation, regurgitation and vomiting were recorded. MAIN RESULTS: A total of 68 children were enrolled for the study; 62 children had successful sedation, and 6 had failed sedation. The ED95 of intranasal DEX was estimated to be 2.64 µg∙kg-1 [95% confidence interval (CI), 2.49-2.87 µg∙kg-1]. The sedation onset time for all patients was 15.0 (12.3-19.0) min. The sedation onset time of successful sedation patients was 15.0 (12.0-19.0) min, the sedation onset time of failed sedation patients was 16.0 (15.0-27.8) min, the examination time was 8 (7-10) min, and the wake-up time was 40 (35-43) min. There were no adverse events during the whole procedure. CONCLUSION: The ED95 of intranasal DEX sedation in children aged 1-3 years undergoing PFT was 2.64 µg∙kg-1.

Fifty Percent Effective Dose of Intranasal Dexmedetomidine Sedation for Transthoracic Echocardiography in Children With Cyanotic and Acyanotic Congenital Heart Disease.

OBJECTIVES: To determine the 50% and 95% effective dose of intranasal dexmedetomidine sedation for transthoracic echocardiography in children with cyanotic and acyanotic congenital heart disease. DESIGN: A prospective, nonrandomized study. SETTING: A tertiary care teaching hospital. PARTICIPANTS: Patients younger than 18 months with known or suspected congenital heart disease scheduled for transthoracic echocardiography with sedation. INTERVENTIONS: Patients were divided into a cyanotic group (blood oxygen saturation <85%) or an acyanotic group (blood oxygen saturation ≥85%). This study used Dixon's up-and-down method sequential allocation design. In both groups, the initial dose of intranasal dexmedetomidine was 2 µg/kg and the gradient of increase or decrease was 0.25 µg/kg. MEASUREMENTS AND MAIN RESULTS: The 50% effective dose (95% confidence interval) of intranasal dexmedetomidine sedation for transthoracic echocardiography was 3.2 (2.78-3.55) µg/kg and 1.9 (1.69-2.06) µg/kg in the cyanotic and acyanotic groups, respectively. None of the patients experienced significant adverse events. CONCLUSION: The 50% (95% confidence intervals) effective doses of intranasal dexmedetomidine sedation for transthoracic echocardiography were 3.2 (2.78-3.55) µg/kg and 1.9 (1.69-2.06) µg/kg in children with cyanotic and acyanotic congenital heart disease, respectively.

Automobile exhaust-derived PM2.5 induces blood-testis barrier damage through ROS-MAPK-Nrf2 pathway in sertoli cells of rats.

Particulate matter with an aerodynamic diameter of less than 2.5 µm (PM2.5) derived from automobile exhaust can lead to serious male spermatogenesis dysfunction, but its specific molecular mechanism is unclear. In this experiment, we focused on the blood-testis barriers (BTB) and explored the intracellular mechanisms underlying the fertility toxicity of PM2.5 originating from automobile exhaust in the primary cultured Sertoli cells(SCs) of rats. After PM2.5 exposure, excessive reactive oxygen species (ROS) and increased apoptosis of SCs were detected. The expression of the BTB related proteins including ZO-1, Occludin, N-cadherin and ß-catenin were significantly decreased and the spatial arrangement of F-actin was completely disordered through Immunofluorescence and Western blots tests. The phosphorylation of Jun N-terminal kinase (JNK), extracellular signal regulatory kinase (ERK), p38 mitogen-activated protein kinase (MAPK) were upregulated and nuclear factor (erythroid-derived 2) -like 2-related factor (Nrf2) was downregulated respectively. However, combined utilization of vitamin C and E were observed to prevent the increase of ROS generation, reduce celluar apoptosis, increase the expression of BTB related proteins, reconstructed the spatial arrangement of F-actin as well as improved the Nrf2 expression and attenuated the phosphorylation of the MAPK kinases and cleaved caspase-3 levels. Furthermore, ERK inhibitor (SCH772984), JNK inhibitor (SP600125) and p38 MAPK inhibitor (SB203580) obviously up-regulated BTB-related proteins expression as well as activated Nrf2 expression at varying degrees, indicating that ROS-MAPKs-Nrf2 is involved in the signaling pathway that leads to PM2.5-induced spermatogenesis dysfunction. These findings indicate that PM2.5 derived from automobile exhaust causes oxidative stress, which in turn causes cellular apoptosis of SCs and damage of the blood-testis barrier, resulting male spermatogenesis dysfunction, in which ROS-MAPK-Nrf-2 pathways may play a key role.

Determination of the 90% effective dose of intranasal dexmedetomidine for sedation during electroencephalography in children.

BACKGROUND: The intranasal route of dexmedetomidine (DEX) administration is becoming increasingly popular for providing adequate sedation during short examinations in infants and children. However, data on the 90% effective dose (ED90) of intranasal DEX are rare in children under 3 years old. METHODS: This is a double-blind trial using a biased coin design up-and-down sequential method (BCD-UDM). Fifty-three children aged under 3 years old requiring DEX for EEG were included in our study. The first patient received 2.5 µg kg-1 DEX, and the dose of DEX administered to the subsequent patient was determined by the response of the previous patient. The patient responses were recorded and analysed to calculate the ED90 by isotonic regression. The 95% confidence interval (CI) was estimated using a bootstrapping method. RESULTS: Fifty-three patients were included in our study, of which 45 patients were successfully sedated, and the 8 instances of failed sedation were rescued using sevoflurane inhalation, allowing the completion of the procedure. The 90% effective dose of DEX was calculated to be 3.28 µg kg-1 , and the 95% CI was 2.74 ~ 3.39 µg kg-1 . No significant adverse events occurred in any of the patients. CONCLUSION: The 90% effective dose of intranasal DEX sedation for EEG was 3.28 µg kg-1 in children under 3 years old.

Analysis of 17 948 pediatric patients undergoing procedural sedation with a combination of intranasal dexmedetomidine and ketamine.

BACKGROUND: Intranasal procedural sedation using dexmedetomidine is well described in the literature. The combination of intranasal dexmedetomidine and ketamine is a novel approach for which there are little data on the rate of successful sedation or adverse events. OBJECTIVES: The aim of this study is to evaluate the rate of successful sedation and adverse events of intranasal procedural sedation using a combination of dexmedetomidine and ketamine for diagnostic examination in children. METHODS: This was a retrospective study and data were collected after ethics approval. A total of 17 948 pediatric patients (7718 females, 10 230 males) in a tertiary hospital in China were evaluated. Patients received a combination of 2 µg kg-1 of dexmedetomidine and 1 mg kg-1 of ketamine intranasally for procedural sedation. The level of sedation and recovery was assessed by the Modified Observer Assessment of Alertness/Sedation scale and the Modified Aldrete Score. RESULTS: The rate of intranasal sedation success was 93% (16691/17948), intranasal sedation rescue was 1.8% (322/17948), and intranasal sedation failure was 5.2% (935/17948). Sedation success was defined as successful completed the diagnostic examination and obtained adequate diagnostic-quality images and reports. Intranasal sedation success, rescue and failure were respectively defined as sedation success with intranasal a single dose, additional bolus dose and the need for intravenous (IV) medications/inhalation agents. Median sedation time was 62 min (interquartile range: 55-70 min), median time for onset of sedation was 15 min (interquartile range: 15-20 min), and median sedation recovery time was 45 min (interquartile range: 38-53 min). Incidence of adverse events was low (0.58%; 105/17948), with major and minor adverse event being reported in 0.02% (4/17948) and 0.56% (101/17948) patients, respectively. Postoperative nausea and vomiting was the most common (0.3%; 53/17948) minor adverse event. CONCLUSION: Procedural sedation using a combination of intranasal dexmedetomidine and ketamine is associated with acceptable effectiveness and low rates of adverse events.

[Propofol combined with hypoxia induces cognitive dysfunction in immature rats via p38 pathway].

OBJECTIVE: To investigate the effects of propofol combined with hypoxia on cognitive function of immature rats and the possible role of p38 pathway and tau protein in mediating such effects. METHODS: Ninety 7-day-old (P7) SD rats were randomized for daily intraperitoneal injection of propofol (50 mg/kg) or lipid emulsion (5.0 mL/kg) for 7 consecutive days. After each injection, the rats were placed in a warm box (38 ℃) with an oxygen concentration of 18% (hypoxia), 21% (normal air), or 50% (oxygen) until full recovery of the righting reflex. Another 90 P7 rats were similarly grouped and received intraperitoneal injections of p-p38 blocker (15 mg/kg) 30 min before the same treaments. The phosphorylated tau protein, total tau protein and p-p38 content in the hippocampus were detected using Western blotting. The spatial learning and memory abilities of the rats were evaluated with Morris water maze test. RESULTS: Compared with lipid emulsion, propofol injection resulted in significantly increased levels of p-p38, phosphorylated tau and total tau proteins in rats with subsequent hypoxic or normal air treatment (P < 0.05), but propofol with oxygen and injections of the blocker before propofol did not cause significant changes in the proteins. Without subsequent oxygenation, the rats receiving injections of propofol, with and without prior blocker injection, all showed significantly prolonged latency time and reduced platform-crossing times and third quadrant residence time compared with the corresponding lipid emulsion groups (P < 0.05). With oxygen treatment, the rats in propofoland blocker-treated groups showed no significant difference in the performance in Morris water maze test from the corresponding lipid emulsion group. The results of Morris water maze test differed significantly between blocker-propofol group and propofol groups irrespective of exposures to different oxygen levels (P < 0.05), but not between the lipid emulsion and blocker group pairs with exposures to different oxygen levels. CONCLUSIONS: Propofol combined with hypoxia can affect the expression of tau protein through p38 pathway to impair the cognitive function of immature rats, in which oxygen plays a protective role.

Vitamin E and vitamin C attenuate Di-(2-ethylhexyl) phthalate-induced blood-testis barrier disruption by p38 MAPK in immature SD rats.

As an environmental endocrine disruptor, Di-(2-ethylhexyl) phthalate (DEHP) affects blood-testis barrier (BTB)-associated proteins expression, which compromises BTB integrity and causes infertility. Notably, DEHP-induced testicular toxicity is related to oxidative stress, but the specific mechanism remains unclear. Therefore, we sought to investigate this mechanism and determine whether vitamin C and vitamin E administration would attenuate the BTB impairment induced by DEHP in vivo and by Mono-(2-Ethylhexyl) Phthalate (MEHP) in vitro, respectively. HE staining and EM found that DEHP exposure led to spermatogenesis dysfunction and BTB disruption, respectively. The Western blot and immunofluorescence results showed that DEHP exposure caused BTB impairment through oxidative stress-mediated p38 mitogen-activated protein kinase (MAPK) signaling pathway. Furthermore, Vitamin E and vitamin C could alleviate the oxidative stress, block DEHP-induced spermatogenesis dysfunction and BTB disruption by inhibiting p38 MAPK signaling pathway. In summary, vitamin E and vitamin C are good candidates for the treatment of DEHP-induced male infertility.

Median effective dose of intranasal dexmedetomidine sedation for transthoracic echocardiography examination in postcardiac surgery and normal children: An up-and-down sequential allocation trial.

BACKGROUND: Dexmedetomidine (DEX) has been used for sedation in young infants and children undergoing transthoracic echocardiography (TTE). The median effective dose of intranasal DEX has not been described for postcardiac surgery children. Postcardiac surgery children could require more DEX to achieve satisfactory sedation for TTE examination than children suspected of congenital heart disease. OBJECTIVES: To study whether postcardiac surgery children need a larger dose of DEX for TTE than normal children. DESIGN: A double-blind sequential allocation trial with doses determined by the Dixon and Massey up-and-down method. SETTING: A tertiary care teaching hospital from 25 October to 30 November 2016. PATIENTS: Children under the age of 3 years requiring intranasal DEX for TTE. INTERVENTIONS: Children were allocated to a postcardiac surgery group (n = 20) or a normal group (n = 19). The first patient in both groups received intranasal DEX (2 µg kg): using the up-and-down method of Dixon and Massey, the next dose was dependent on the previous patient's response. MAIN OUTCOME MEASURES: Median effective dose was estimated from the up-and-down method of Dixon and Massey and probit regression. A second objective was to study haemodynamic stability and adverse events with these doses. RESULTS: The median effective dose (95% confidence interval) of intranasal DEX was higher in postcardiac surgery children than in normal children, 3.3 (2.72 to 3.78) µg kg versus 1.8 (1.71 to 2.04) (µg kg), respectively (P < 0.05). There were no significant differences in time to sedation, time to wake-up or TTE examination time between the two groups for successful sedation. Additionally, there were no significant adverse events. CONCLUSION: The median effective dose of intranasal DEX for TTE sedation in postcardiac surgery children was higher than in normal children. TRIAL REGISTRATION: chictr.org.cn identifier: ChiCTR-OOC-16009846.

[Effect of Di-(2-ethylhcxyl) phthalate exposure on blood-testis barrier integrity in rats].

OBJECTIVE: To investigate mechanism of di-(2-ethylhcxyl)phthalate (DEHP) exposure in causing blood-testis barrier (BTB) impairment in rats. METHODS: Two-months-old male SD rats were randomly divided into corn oil control group and DEHP (750 mg/kg) exposure group for daily intragastic treatment for 30 consecutive days. After the treatments the rats were examined for histomorphological changes of the testicle using HE staining and the expressions of the junction proteins N-cadherin ß-catenin, occludin and connexin43 of the BTB using Western blot. In the in vitro study, the vitality and ROS generation level in Sertoli cells exposed to different concentrations of DEHP were examined with MTT and ROS assay kits, respectively, and Nrf2 and p-p38 expressions were detected with Western blot. RESULTS: Compared with the control group, the rats with DEHP exposure showed structural damage of the seminiferous tubule and polarity loss of the spermatids. DEHP exposure caused significantly decreased expressions of occludin and connexin43 but increased expressions of N-cadherin and ß-catenin in the testicle tissues of the rats (P<0.05). The vitality of Sertoli cells was obviously decreased and ROS level increased significantly after exposure of the cells to increasing concentrations of DEHP, which also resulted in significantly up-regulated Nrf2 and p-p38 expressions (P<0.05). CONCLUSIONS: DEHP exposure causes increased oxidative stress in the Sertoli cells of the testis, activates p38 MAPK signaling pathway, and results eventually in impaired spermatogenesis in rats.

Median effective dose of intranasal dexmedetomidine sedation for transthoracic echocardiography in pediatric patients with noncyanotic congenital heart disease: An up-and-down sequential allocation trial.

BACKGROUND: Intranasal dexmedetomidine can provide adequate sedation during short procedures. However, previous literature investigating the single-dose use of intranasal dexmedetomidine for sedation during transthoracic echocardiography in younger children is scarce, and the effects of age on sedation with intranasal dexmedetomidine remain controversial. OBJECTIVE: This study was to determine the 50% effective dose and estimate the 95% effective dose of single-dose intranasal dexmedetomidine to induce sedation in pediatric patients with noncyanotic congenital heart disease, and also determine the effect of age on the dose required for sedation. METHODS: Patients were stratified into three age groups of 1-6 months, 7-12 months, and 13-36 months. Intranasal dexmedetomidine started at a dose of 2 µg kg-1 on the first patient. The dose of dexmedetomidine for each subsequent patient was determined by the previous patient's response using Dixon's up-and-down method with an interval of 0.25 µg kg-1 . Sedation scale and recovery were assessed by the Modified Observer Assessment of Alertness and Sedation Scale and Modified Aldrete Recovery Score. The 50% effective dose was determined by Dixon's up-and-down method. In addition, both 50% effective dose and 95% effective dose were obtained using a probit regression approach. Other variables included sedation onset time, echocardiography time, wake-up time, discharge time, heart rate, blood pressure, oxygen saturation, respiratory rate, and adverse events such as vomiting, regurgitation, and apnea. RESULTS: The study population was comprised of 70 patients. The 50% effective dose (95% confidence interval) and the 95% effective dose (95% confidence interval) of intranasal dexmedetomidine for sedation were 1.8 (1.58-2.00) µg kg-1 and 2.2 (1.92-5.62) µg kg-1 in patients aged 1-6 months, 1.8 (1.61-1.95) µg kg-1 and 2.1 (1.90-2.85) µg kg-1 in patients aged 7-12 months, 2.2 (1.92-2.37) µg kg-1 and 2.7 (2.34-6.88) µg kg-1 in patients aged 13-36 months, respectively. The 50% effective dose in age group 13-36 months was higher than those of age group 1-6 months (P = .042) and 7-12 months (P = .043). There were no differences in sedation onset time, echocardiography time, wake-up time, and discharge time between groups. None of the patients experienced oxyhemoglobin desaturation, hypotension, or bradycardia during the procedure. No significant adverse events occurred. CONCLUSION: Single-dose of intranasal dexmedetomidine was an effective agent for patients under the age of 3 years requiring sedation for transthoracic echocardiography. The 50% effective dose of intranasal dexmedetomidine for transthoracic echocardiography sedation in children aged 13-36 months was higher than in children <13 months.