Neonicotinoid insecticides and metabolites levels in neonatal first urine from southern China: Exploring links to preterm birth.

Neonicotinoids (NEOs) have indeed become the most widely used insecticides worldwide. Concerns have been raised about their potential impact on newborns due to maternal exposure and their unique neurotoxic mode of action. However, it is still poorly understood whether in utero exposure of pregnant women to environmental NEOs and their metabolites can cause carryover effects on vulnerable newborns and subsequent health consequences. In this study, we determined the concentrations of 13 NEOs and their metabolites in the first urine collected from 92 newborns, both preterm and full-term, in southern China during 2020 and 2021. NEOs and their metabolites were identified in 91 urine samples, with over 93% of samples containing a cocktail of these compounds, confirming their maternal-fetal transfer. N-desmethyl-acetamiprid, imidaclothiz, clothianidin and flonicamid were the most commonly detected analytes, with detection frequencies of 59-87% and medians of 0.024-0.291 ng/mL in the urine. The relative abundance of imidaclothiz was significantly higher in preterm newborns, those with head circumferences below 33 cm, birth lengths less than 47 cm, and weights below 2500 g (p < 0.05). When comparing newborns in the 2nd quartile of imidaclothiz concentrations with those in the 1st quartile, we observed a significant increase in the odds of preterm outcomes in the unadjusted model (odds ratio = 3.24, 95% confidence interval = 1.02-10.3). These results suggest that exposure to elevated concentrations of imidaclothiz may be associated with preterm birth.

Injectable silk fibroin peptide nanofiber hydrogel composite scaffolds for cartilage regeneration.

Transforming growth factor-ß1 (TGF-ß1) is essential for cartilage regeneration, but its susceptibility to enzymatic denaturation and high cost limit its application. Herein, we report Ac-LIANAKGFEFEFKFK-NH2 (LKP), a self-assembled peptide nanofiber hydrogel that can mimic the function of TGF-ß1. The LKP hydrogel is simple to synthesize, and in vitro experiments confirmed its good biocompatibility and cartilage-promoting ability. However, LKP hydrogels suffer from poor mechanical properties and are prone to fragmentation; therefore, we prepared a series of injectable hydrogel composite scaffolds (SF-GMA/LKP) by combining LKP with glycidyl methacrylate (GMA)-modified silk fibroin (SF). SF-GMA/LKP composite scaffolds instantaneously induced in-situ filling of cartilage defects and, at the same time, relied on the interaction between LKP and SF-GMA interaction to prolong the duration of action of LKP. The SF-GMA/LKP10 and SF-GMA/LKP20 composite scaffolds had the best effect on neocartilage and subchondral bone reconstruction. This composite hydrogel scaffold can be used for high-quality cartilage repair.

Preparation of Melatonin-Loaded Nanoparticles with Targeting and Sustained Release Function and Their Application in Osteoarthritis.

(1) The vicious cycle of innate immune response and reactive oxygen species (ROS) generation is an important pathological process of osteoarthritis (OA). Melatonin may be a new hope for the treatment of OA because of its antioxidant capacity. However, the mechanism of melatonin in the treatment of OA is still not completely clear, and the physiological characteristics of articular cartilage make melatonin unable to play a long-term role in OA. (2) The effects of melatonin on ROS and the innate immune response system in OA chondrocytes and the therapeutic effect in vivo were evaluated. Then, a melatonin-loaded nano-delivery system (MT@PLGA-COLBP) was prepared and characterized. Finally, the behavior of MT@PLGA-COLPB in cartilage and the therapeutic effect in OA mice were evaluated. (3) Melatonin can inhibit the activation of the innate immune system by inhibiting the TLR2/4-MyD88-NFκB signal pathway and scavenging ROS, thus improving cartilage matrix metabolism and delaying the progression of OA in vivo. MT@PLGA-COLBP can reach the interior of cartilage and complete the accumulation in OA knee joints. At the same time, it can reduce the number of intra-articular injections and improve the utilization rate of melatonin in vivo. (4) This work provides a new idea for the treatment of osteoarthritis, updates the mechanism of melatonin in the treatment of osteoarthritis, and highlights the application prospect of PLGA@MT-COLBP nanoparticles in preventing OA.

Design and Implement Strategy of Wireless Bite Force Device.

Abnormal bite force is an important risk factor for oral and maxillofacial disorders, which is a critical dilemma that dentists face every day without effective solutions. Therefore, it is of great clinical significance to develop a wireless bite force measurement device and explore quantitative measurement methods to help find effective strategies for improving occlusal diseases. This study designed the open window carrier of a bite force detection device through 3D printing technology, and then the stress sensors were integrated and embedded into a hollow structure. The sensor system mainly consisted of a pressure signal acquisition module, a main control module, and a server terminal. A machine learning algorithm will be leveraged for bite force data processing and parameter configuration in the future. This study implemented a sensor prototype system from scratch to fully evaluate each component of the intelligent device. The experimental results showed reasonable parameter metrics for the device carrier and demonstrated the feasibility of the proposed scheme for bite force measurement. An intelligent and wireless bite force device with a stress sensor system is a promising approach to occlusal disease diagnosis and treatment.

Apgar scores correlate with survival rate at discharge in extremely preterm infants with gestational age of 25-27 weeks.

Low Apgar score is associated with increased risk of death in preterm or full-term infants. However, the use of Apgar score to assess extremely preterm (EP) infants is controversial. In this study, we characterized the distribution of Apgar scores in EP infants with gestational age between 25 and 27 weeks, and investigated the association of Apgar score with survival rate at discharge by analyzing the clinical data of the EP infants discharged between January 2008 and December 2017 from 26 neonatal intensive care units in Guangdong Province, China. A total of 1567 infants with gestational age of 26.84±0.79 weeks and birth weight of 951±169 grams were involved in our study. The Apgar score increased with gestational age from 25 to 27 weeks and with time from birth from 1 to 10 min. The survival rate increased with a higher Apgar score, but no significant difference was found for 1-min Apgar score and the survival rate between infants with 25 or 26 weeks of gestation or 5-min Apgar score in infants with 25 weeks of gestation. The Apgar score is associated with survival of EP infants.

Mothers with hypertensive disorders of pregnancy increased risk of periventricular leukomalacia in extremely preterm or extremely low birth weight infants: A propensity score analysis.

Background: At present, the conclusions about the impact of hypertensive disorders of pregnancy (HDP) on the clinical outcomes of preterm infants are inconsistent. This study used the propensity score matching (PSM) analysis to evaluate the effect of HDP on clinical outcomes of extremely preterm or extremely low birth weight (EP/ELBW) infants. Methods: Retrospective analysis was performed on the EP/ELBW infants discharged from 26 tertiary neonatal intensive care units or died during hospitalization from 2008 to 2017, who were divided into HDP group and non-HDP group. The six covariates including sex, gestational age, birth weight, twin or multiple pregnancy, antenatal steroids administration, and conception method were matched through the PSM method at a ratio of 1:1. The survival rate at discharge and the major clinical complications were compared between the two groups. Results: After matching the six covariates, compared with the non-HDP group, there was no significant difference in the survival rate at discharge (64 vs. 63.2%, p > 0.05), the incidence of bronchopulmonary dysplasia (BPD) or moderate to severe BPD in the HDP group (58.3 vs. 54.9%, p > 0.05; 5.2 vs. 6.2%, p > 0.05). The incidence of periventricular leukomalacia (PVL) in the HDP group was significantly increased (5.7 vs. 1.9%, p < 0.05). Conclusions: HDP increased the risk of PVL in EP/ELBW infants, but had no significant effect on the survival rate at discharge, or the occurrence of other complications.

[Sex differences in clinical outcomes of extremely preterm infants/extremely low birth weight infants: a propensity score matching study]. / è¶ æ—©äº§å„¿/è¶ ä½Žå‡ºç”Ÿä½“é‡å„¿ä¸´åºŠç»“å±€çš„æ€§åˆ«å·®å¼‚ï¼šä¸€é¡¹å€¾å‘æ€§è¯„åˆ†åŒ¹é ç ”ç©¶.

OBJECTIVES: To study the effect of sex on the clinical outcome of extremely preterm infants (EPIs)/extremely low birth weight infants (ELBWIs) by propensity score matching. METHODS: A retrospective analysis was performed for the medical data of 731 EPIs or ELBWIs who were admitted from January 1, 2011 to December 31, 2020. These infants were divided into two groups: male and female. A propensity score matching analysis was performed at a ratio of 1:1. The matching variables included gestational age, birth weight, percentage of withdrawal from active treatment, percentage of small-for-gestational-age infant, percentage of use of pulmonary surfactant, percentage of 1-minute Apgar score ≤3, percentage of mechanical ventilation, duration of mechanical ventilation, percentage of antenatal use of inadequate glucocorticoids, and percentage of hypertensive disorders in pregnancy. The two groups were compared in the incidence rate of main complications during hospitalization and the rate of survival at discharge. RESULTS: Before matching, compared with the female group, the male group had significantly higher incidence rates of neonatal respiratory distress syndrome, bronchopulmonary dysplasia (BPD), severe intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, and patent ductus arteriosus (P<0.05), while after matching, the male group only had a significantly higher incidence rate of BPD than the female group (P<0.05). There was no significant difference in the rate of survival at discharge between the two groups before and after matching (P>0.05). CONCLUSIONS: Male EPIs/ELBWIs have a higher risk of BPD than female EPIs/ELBWIs, but male and female EPIs/ELBWIs tend to have similar outcomes.

Increased Risk for Respiratory Complications in Male Extremely Preterm Infants: A Propensity Score Matching Study.

Background: Many factors can affect the clinical outcome of extremely premature infants (EPIs), but the effect of sex is paradoxical. This study used propensity score matching to adjust baseline information to reassess the clinical outcome of EPIs based on sex. Methods: A retrospective analysis was performed on EPIs admitted in the Department of Neonatology of the Third Affiliated Hospital of Guangzhou Medical University from 2011 to 2020. A propensity score matching (PSM) analysis was used to adjust the confounding factors including gestational age, birth weight, 1-minute Apgar score ≤ 3, withholding or withdrawing life-sustaining treatment(WWLST), mechanical ventilation, duration of mechanical ventilation, the mother with advanced age (≥35 years old), complete-course antenatal steroid therapy and hypertensive disorders of pregnancy. The survival rate at discharge and the incidence of major complications were evaluated between the male and female groups. Results: A total of 439 EPIs were included, and 240 (54.7%) infants were males. After matching the nine confounding factors, 148 pairs of infants were finally enrolled. There was no significant difference in the survival rate at discharge, as well as the mortality of activating treatment or WWLST between the two groups (all P>0.05). However, the incidence of respiratory distress syndrome, bronchopulmonary dysplasia (BPD), and moderate to severe BPD in the male group was significantly increased (all P<0.01), especially at birth weight between 750 and 999 grams. Conclusions: The male EPIs have a higher risk of respiratory complications than females, particularly at 750 to 999 grams of birth weight.

Lateral epicondyle osteotomy approach vs. olecranon osteotomy approach: an anatomic study of cadavers.

BACKGROUND: Exposure of the articular surface is the key to successful open reduction and internal fixation treatment for coronal shear fractures of the distal humerus. The olecranon osteotomy approach has previously been described as one of the most effective exposure approaches. Nevertheless, this approach cannot expose the anterior trochlea, and it is impossible to reduce and fix the capitellum under direct vision. The purpose of this study was to compare the exposure of the articular surface of the distal humerus between the lateral epicondyle osteotomy approach (group L) and the olecranon osteotomy approach (group O). METHODS: Each approach was performed on 8 freshly frozen upper limbs of adult cadavers. After each approach was completed, a 0.5-mm Kirschner wire is inserted along the edge to mark the visible part of the articular surface. Then, the soft tissue of each elbow is removed, and a surface-scanning system is used to create a digital 3-dimensional model. The visible part of the articular surface obtained by each surgical approach was mapped and quantified using markers created by Kirschner wires. RESULTS: The lateral epicondyle osteotomy approach and the olecranon osteotomy approach exposed 0.8 ± 0.0 and 0.6 ± 0.0 of the distal humeral articular surface (P < .001), 1.0 ± 0.0 and 0.3 ± 0.1 of the capitellum (P < .001), 0.6 ± 0.0 and 0.7 ± 0.0 of the trochlea (P < .001), 0.7 ± 0.0 and 0.5 ± 0.1 of the anterior trochlea (P < .001), and 0.5 ± 0.0 and 1.0 ± 0.0 of the posterior trochlea, respectively (P < .001). CONCLUSION: Compared with the olecranon osteotomy approach, the lateral epicondyle osteotomy approach could more fully expose the total articular surface of the distal humerus, capitellum, and anterior trochlea, but the olecranon osteotomy approach could more fully expose the trochlea and posterior trochlea.

Apgar scores correlate with survival rate at discharge in extremely preterm infants with gestational age of 25-27 weeks

Low Apgar score is associated with increased risk of death in preterm or full-term infants. However, the use of Apgar score to assess extremely preterm (EP) infants is controversial. In this study, we characterized the distribution of Apgar scores in EP infants with gestational age between 25 and 27 weeks, and investigated the association of Apgar score with survival rate at discharge by analyzing the clinical data of the EP infants discharged between January 2008 and December 2017 from 26 neonatal intensive care units in Guangdong Province, China. A total of 1567 infants with gestational age of 26.84±0.79 weeks and birth weight of 951±169 grams were involved in our study. The Apgar score increased with gestational age from 25 to 27 weeks and with time from birth from 1 to 10 min. The survival rate increased with a higher Apgar score, but no significant difference was found for 1-min Apgar score and the survival rate between infants with 25 or 26 weeks of gestation or 5-min Apgar score in infants with 25 weeks of gestation. The Apgar score is associated with survival of EP infants.

Brain Delivery of Curcumin Through Low-Intensity Ultrasound-Induced Blood-Brain Barrier Opening via Lipid-PLGA Nanobubbles.

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder. Owing to the presence of blood-brain barrier (BBB), conventional pharmaceutical agents are difficult to the diseased nuclei and exert their action to inhibit or delay the progress of PD. Recent literatures have demonstrated that curcumin shows the great potential to treat PD. However, its applications are still difficult in vivo due to its poor druggability and low bioavailability through the BBB. METHODS: Melt-crystallization methods were used to improve the solubility of curcumin, and curcumin-loaded lipid-PLGA nanobubbles (Cur-NBs) were fabricated through encapsulating the curcumin into the cavity of lipid-PLGA nanobubbles. The bubble size, zeta potentials, ultrasound imaging capability and drug encapsulation efficiency of the Cur-NBs were characterized by a series of analytical methods. Low-intensity focused ultrasound (LIFU) combined with Cur-NB was used to open the BBB to facilitate curcumin delivery into the deep brain of PD mice, followed by behavioral evaluation for the treatment efficacy. RESULTS: The solubility of curcumin was improved by melt-crystallization methods, with 2627-fold higher than pure curcumin. The resulting Cur-NBs have a nanoscale size about 400 nm and show excellent contrast imaging performance. Curcumin drugs encapsulated into Cur-NBs could be effectively released when Cur-NBs were irradiated by LIFU at the optimized acoustic pressure, achieving 30% cumulative release rate within 6 h. Importantly, Cur-NBs combined with LIFU can open the BBB and locally deliver the curcumin into the deep-seated brain nuclei, significantly enhancing efficacy of curcumin in the Parkinson C57BL/6J mice model in comparison with only Cur-NBs and LIFU groups. CONCLUSION: In this work, we greatly improved the solubility of curcumin and developed Cur-NBs for brain delivery of curcumin against PD through combining with LIFU-mediating BBB. Cur-NBs provide a platform for these potential drugs which are difficult to cross the BBB to treat PD disease or other central nervous system (CNS) diseases.

Lateral epicondyle osteotomy approach for coronal shear fractures of the distal humerus: Report of three cases and review of the literature.

BACKGROUND: Coronal shear fractures of the distal humerus are rare injuries and are technically challenging to manage. Open reduction and internal fixation (ORIF) has become the preferred treatment because it provides anatomical reduction, stable internal fixation, and early motion, but the optimal surgical approach remains controversial. CASE SUMMARY: We report three cases of coronal shear fractures of the distal humerus treated successfully by ORIF via a novel surgical approach, in which lateral epicondyle osteotomy was performed based on the extended lateral approach. We named the novel surgical approach the lateral epicondyle osteotomy approach. All patients underwent surgical treatment and were discharged successfully. All patients had excellent functional results according to the Mayo elbow performance score. The average range of motion was 118° in flexion/extension and 172° in pronation/ supination. Only case 2 had a complication, which was implant prolapse. CONCLUSION: We demonstrated that the lateral epicondyle osteotomy approach in ORIF is effective and safe for coronal shear fractures of the distal humerus.

Sandwich Integration Technique for the Pressure Sensor Detection of Occlusal Force In Vitro.

Bite force measurement is an important parameter when checking the function and integrity of the masticatory system, whereas it is currently very difficult to measure bite force during functional movement. Hence, the purpose of this study is to explore the potential technique and device for the measurement and intervention of the continuous bite forces on functional and dynamic occlusal condition. A portable biosensor by sandwich technique was designed, and the validity, reliability, and sensitivity were determined by mechanical pressure loading tests; meanwhile, the pressure signal is acquired by, and transmitted to, voltage changes by the electrical measurements of the sensors. The result is that, when the mechanical stress detection device is thicker than 3.5 mm, it shows relatively ideal mechanical properties; however, when the thickness is less than 3.0 mm, there is a risk of cracking. Mechanical stress changing and voltage variation had a regularity and positive relationship in this study. The mechanical stress-measuring device made by medical and industrial cross has a good application prospect for the measurement of bite force during function.

Different concentrations of docosahexanoic acid supplement during lactation result in different outcomes in preterm Sprague-Dawley rats.

PROPOSE: In this study, we evaluated the effects of different concentrations of docosahexanoic acid (DHA) supplement on preterm Sprague-Dawley rat pups, and in parallel, measured the phosphorylation activity of the mTOR pathway in the hippocampal CA1 area. METHODS: Preterm Sprague-Dawley rat pups were randomly assigned to experimental groups which included; a sufficient DHA group (100 mg/kg/day); an enriched DHA group (300 mg/kg/day); an excess DHA group (800 mg/kg/day); and a deficient DHA group (normal saline gavage 0.1 ml/10 g). Body weight (g) was measured at days 1/7/14/21/28/42, respectively. Spatial learning and memory were also tested using the Morris water maze at week 6 (day 42). Finally, activation of the mTOR signaling pathway in hippocampal CA1 area were evaluated by western blotting. RESULTS: Postnatal sufficient/enriched docosahexanoic acid supplement ameliorated body weight restriction, spatial learning and memory restriction, and decreased phosphorylation of AKT, mTOR, P70S6K1, and 4EBP1 in hippocampal CA1 area. Furthermore, excess docosahexanoic acid supplement impeded weight gain and spatial learning and memory, perturbed serum unsaturated fatty acid, and downregulated phosphorylation of AKT, mTOR, P70S6K1, and 4EBP1 in hippocampal CA1 area. CONCLUSION: Postnatal sufficient/enriched DHA supplement ameliorated growth and spatial learning and memory impairment and upregulated the mTOR pathway in preterm pups, although excessive DHA supplement did not have any beneficial effects.

The association between surfactant protein B gene variation and bronchopulmonary dysplasia in Chinese premature newborns.

OBJECTIVE: This study aimed to correlate the pulmonary surfactant B (SP-B) gene variation with bronchopulmonary dysplasia (BPD) in ethnic Han, Chinese, premature newborns. METHOD: 47 newborns with BPD and 55 controls without BPD were included. Genomic DNA was extracted from cord or artery blood. Genotyping for the SP-B gene was performed by polymerase chain reaction or gene sequencing, and the clinical characteristics were also analyzed. RESULTS: Two types of SP-B gene variations in Exon 2 or Exon 5 were discovered, including V1 (Exon 2: c.[5A > C] + [5A > C] or c.[5A > C] + [=]) and V2 (Exon 5: c.[428C > T] + [428C > T] or c.[428C > T] + [=]). In the BPD group, there were 33 newborns with gene variations, of which type V1 and V2 accounted for 18 and 15 respectively. In the control group, there were 19 newborns with gene variations, of which type V1 and V2 accounted for 7 and 12 respectively. There was a significant difference between the two groups in type V1 variation (X2=8.956, P < 0.05), and V1 variation was more likely associated with BPD occurrence. Logistic regression analysis showed that gene variation, premature rupture of membranes, birth weight, and the duration of mechanical ventilation were associated with BPD development. Among them, gene variation and premature rupture of the membranes were risk factors for BPD development. CONCLUSIONS: The exon 2 or 5 of SP-B gene variations were associated with the BPD in Chinese premature newborns, and the type V1: Exon 2: c.[5A > C] + [5A > C] or c.[5A > C] + [=] was a risk factor for the development of BPD.

Postnatal high-protein diet improves learning and memory in premature rats via activation of mTOR signaling.

PURPOSE: The present study investigated whether a high-protein diet affects spatial learning and memory in premature rats via modulation of mammalian target of rapamycin (mTOR) signaling. METHODS: Pre- and full-term Sprague-Dawley pups were fed a normal (18% protein) or high-protein (30% protein) diet (HPD) for 6 or 8 weeks after weaning. Spatial learning and memory were tested in the Morris water maze at week 6 and 8. The activation of mTOR signaling pathway components was evaluated by western blotting. RESULTS: Spatial memory performance of premature rats consuming a normal and HPD was lower than that of full-term rats on the same diet at 6 weeks, and was associated with lower levels of ribosomal protein S6 kinase p70 subtype (p70S6K) and initiation factor 4E-binding protein 1 (4EBP1) phosphorylation in the hippocampus. Spatial memory was improved in 8-week-old premature rats on an HPD as compared to those on a normal diet. Premature rats on an HPD had p70S6K and 4EBP1 phosphorylation levels in the hippocampus that were comparable to those of full-term rats on an HPD. CONCLUSION: Long-term consumption of a protein-rich diet can restore the impairment in learning and memory in pre-term rats via upregulation of mTOR/p70S6K signaling.