Search

Lili Jiang,1 Yili Lu,1 Jiahui Jin,1 Lili Dong,1 Fengli Xu,1 Shuangshuang Chen,1 Zhanyue Wang,2 Guang Liang,2 Xiaoou Shan11Department of Pediatrics, The Second Affiliated Hospital, 2Chemical Biology Research Center at The School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of ChinaAbstract: Sepsis, which is caused by severe infection, is an important cause of mortality, but effective clinical treatment against sepsis is extremely limited. As the main component of the outer membrane of Gram-negative bacteria, lipopolysaccharide (LPS) plays a major role in inflammatory responses. Studies have shown beneficial pharmacological effects for Folium isatidis. The present study further illuminated the effects of n-butanol extract from Folium isatidis in LPS-induced septic shock and identified the main active chemical components. Our study showed that pretreatment with n-butanol extract from Folium isatidis not only significantly inhibited LPS-induced tumor necrosis factor-α and interleukin-6 production but also markedly and dose dependently enhanced the recruitment of MyD88, the phosphorylation of extracellular signal-regulated kinase, and the degradation of IκB-α. Additionally, the extract exhibited dramatic protective effects against lung injury and death in mice with septic shock. Eight main active compounds were identified, including organic acids, glycoside, indolinones, and flavonoids. These findings provide a perspective on the respiratory protection offered by n-butanol extract from Folium isatidis in LPS-induced sepsis and outline a novel therapeutic strategy for the treatment of sepsis.Keywords: Folium isatidis, sepsis, inflammatory cytokine

Objective:  This study aimed to investigate clinical features of inhaled nitric oxide (iNO) in preterm infants with a gestational age (GA) < 34 weeks in China., Study Design:  The clinical data of 434 preterm infants with GA < 34 weeks, treated with iNO in the neonatology departments of eight Class A tertiary hospitals in China over a 10-year period from January 2013 to December 2022, were included in this retrospective multicenter investigation. The infants were divided into three groups based on GA: 24 to 27 weeks (extremely preterm infants), 28 to 31 weeks (very preterm infants), and 32 to 33 weeks (moderate preterm infants). The use of iNO, perinatal data, incidence and mortality of indication for iNO treatment, therapeutic effects of iNO, incidence of short-term complications for iNO treatment, and mortality were compared among these three groups., Results:  Over the past 10 years, the proportion of iNO use was highest in extremely preterm infants each year. The lower the GA, the higher the iNO use rate: 4.20% for GA 24 to 27 weeks, 1.54% for GA 28 to 31 weeks, and 0.85% for GA 32 to 33 weeks. There was no significant difference in the therapeutic effect of iNO among the three groups. The incidence of neonatal pulmonary hemorrhage, neonatal shock, late-onset diseases, retinopathy of prematurity requiring intervention, intracranial hemorrhage (grade 3 or 4), periventricular leukomalacia, neonatal necrotizing enterocolitis (≥stage II), and moderate to severe bronchopulmonary dysplasia was highest in extremely preterm infants and increased with decreasing GA. Mortality was negatively correlated with GA and birth weight. The highest rate of iNO treatment in 24 to 27 weeks' preterm infants was due to hypoxic respiratory failure (HRF), whereas the highest rate of iNO treatment in 32 to 33 weeks' preterm infants was due to documented persistent pulmonary hypertension of the newborn (PPHN). The rates of iNO treatment due to HRF and documented PPHN were 54.3 and 60.6%, respectively, in extremely preterm infants, significantly higher than in very preterm and moderate preterm infants (all p  < 0.05). Within the same GA group, the proportion of preterm infants treated with iNO for HRF was lower than that for documented PPHN (all p  < 0.05), but there was no statistically significant difference in mortality between HRF and documented PPHN treated with iNO (all p  > 0.05)., Conclusion:  Among preterm infants with GA < 34 weeks, the rate of iNO usage was highest in extremely preterm infants. However, iNO failed to improve the clinical outcome of extremely preterm infants with refractory hypoxemia, and there was no significant difference in the therapeutic effect of iNO among preterm infants with different GAs., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: The level of the regulator of G-protein signaling 4-1 (RGS4-1) isoform, the longest RGS4 isoform, is significantly reduced in the dorsolateral prefrontal cortex (DLPFC) of people with schizophrenia. However, the mechanism behind this has not been clarified. The 3'untranslated regions (3'UTRs) are known to regulate the levels of their mRNA splice variants., Methods: We constructed recombinant pmir-GLO vectors with a truncated 3' regulatory region of the RGS4 gene (3R1, 3R2, 3R3, 3R4, 3R5, and 3R6). The dual-luciferase reporter assay was conducted to find functional regions in HEK-293, SK-N-SH, and U87cells and then predicted miRNA binding to these regions. We performed a dual-luciferase reporter assay and a Western blot analysis after transiently transfecting the predicted miRNAs., Results: The dual-luciferase reporter assay found that regions +401-+789, +789-+1152, and +1562-+1990 (with the last base of the termination codon being +1) might be functional regions. Hsa-miR-874-3p, associated with many psychiatric disorders, might target the +789-+1152 region in the 3'UTR of the RGS4 gene. In the dual-luciferase reporter assay, the hsa-miR-874-3p mimic, co-transfected with 3R1, down-regulated the relative fluorescence intensities. However, this was reversed when the hsa-miR-874-3p mimic was co-transfected with m3R1 (deletion of +853-+859). The hsa-miR-874-3p mimic significantly decreased the endogenous expression of the RGS4-1 isoform in HEK-293 cells., Conclusions: Hsa-miR-874-3p inhibits the expression of the RGS4-1 isoform by targeting +853-+859.

The aim of this study was to develop a real-time risk prediction model for extrauterine growth retardation (EUGR). A total of 2514 very preterm infants were allocated into a training set and an external validation set. The most appropriate independent variables were screened using univariate analysis and Lasso regression with tenfold cross-validation, while the prediction model was designed using binary multivariate logistic regression. A visualization of the risk variables was created using a nomogram, while the calibration plot and receiver operating characteristic (ROC) curves were used to calibrate the prediction model. Clinical efficacy was assessed using the decision curve analysis (DCA) curves. Eight optimal predictors that namely birth weight, small for gestation age (SGA), hypertensive disease complicating pregnancy (HDCP), gestational diabetes mellitus (GDM), multiple births, cumulative duration of fasting, growth velocity and postnatal corticosteroids were introduced into the logistic regression equation to construct the EUGR prediction model. The area under the ROC curve of the training set and the external verification set was 83.1% and 84.6%, respectively. The calibration curve indicate that the model fits well. The DCA curve shows that the risk threshold for clinical application is 0-95% in both set. Introducing Birth weight, SGA, HDCP, GDM, Multiple births, Cumulative duration of fasting, Growth velocity and Postnatal corticosteroids into the nomogram increased its usefulness for predicting EUGR risk in very preterm infants., (© 2024. The Author(s).)

Prohibitins (PHBs) are ubiquitously expressed conserved proteins in eukaryotes that are associated with apoptosis, cancer formation, aging, stress responses and cell proliferation. However, the function of the PHBs in immune regulation has largely not been determined. In the present study, we identified PHB2 in the red swamp crayfish Procambarus clarkii. PHB2 was found to be widely distributed in several tissues, and its expression was significantly upregulated by white spot syndrome virus (WSSV) challenge. PHB2 significantly reduced the amount of WSSV in crayfish and the mortality of WSSV-infected crayfish. Here, we observed that PHB2 promotes the nuclear translocation of STAT by binding to STAT. After blocking PHB2 or STAT with antibodies or interfering with PHB2 or STAT, the expression levels of the antiviral genes β-thymosin (PcThy-4) and crustin2 (Cru2) decreased. The gene sequence of PHB2 was analyzed and found to contain a nuclear introgression sequence (NIS). After in vivo injection of PHB2 with deletion of NIS (rΔNIS-PHB2), the nuclear translocation of STAT did not change significantly compared to that in the control group. These results suggest that PHB2 promoted the nuclear translocation of STAT through NIS and mediated the expression of antiviral proteins to inhibit WSSV infection., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Necrotizing enterocolitis (NEC) is a serious gastrointestinal disease, primarily affects preterm newborns and occurs after 7 days of life (late-onset NEC, LO-NEC). Unfortunately, over the past several decades, not much progress has been made in its treatment or prevention. This study aimed to analyze the risk factors for LO-NEC, and the impact of LO-NEC on short-term outcomes in very preterm infants (VPIs) with a focus on nutrition and different onset times., Method: Clinical data of VPIs were retrospectively collected from 28 hospitals in seven different regions of China from September 2019 to December 2020. A total of 2509 enrolled VPIs were divided into 2 groups: the LO-NEC group and non-LO-NEC group. The LO-NEC group was divided into 2 subgroups based on the onset time: LO-NEC occurring between 8 ~ 14d group and LO-NEC occurring after 14d group. Clinical characteristics, nutritional status, and the short-term clinical outcomes were analyzed and compared among these groups., Results: Compared with the non-LO-NEC group, the LO-NEC group had a higher proportion of anemia, blood transfusion, and invasive mechanical ventilation (IMV) treatments before NEC; the LO-NEC group infants had a longer fasting time, required longer duration to achieve the target total caloric intake (110 kcal/kg) and regain birthweight, and showed slower weight growth velocity; the cumulative dose of the medium-chain and long-chain triglyceride (MCT/LCT) emulsion intake in the first week after birth was higher and breastfeeding rate was lower. Additionally, similar results including a higher proportion of IMV, lower breastfeeding rate, more MCT/LCT emulsion intake, slower growth velocity were also found in the LO-NEC group occurring between 8 ~ 14d when compared to the LO-NEC group occurring after 14 d (all (P < 0.05). After adjustment for the confounding factors, high proportion of breastfeeding were identified as protective factors and long fasting time before NEC were identified as risk factors for LO-NEC; early feeding were identified as protective factors and low gestational age, grade III ~ IV neonatal respiratory distress syndrome (NRDS), high accumulation of the MCT/LCT emulsion in the first week were identified as risk factors for LO-NEC occurring between 8 ~ 14d. Logistic regression analysis showed that LO-NEC was a risk factor for late-onset sepsis, parenteral nutrition-associated cholestasis, metabolic bone disease of prematurity, and extrauterine growth retardation., Conclusion: Actively preventing premature birth, standardizing the treatment of grade III ~ IV NRDS, and optimizing enteral and parenteral nutrition strategies may help reduce the risk of LO-NEC, especially those occurring between 8 ~ 14d, which may further ameliorate the short-term clinical outcome of VPIs., Trial Registration: ChiCTR1900023418 (26/05/2019)., (© 2024. The Author(s).)

Background: Hyperglycemia in pregnancy (HGP) has generally been considered a risk factor associated with adverse outcomes in offspring, but its impact on the short-term outcomes of very preterm infants remains unclear., Methods: A secondary analysis was performed based on clinical data collected prospectively from 28 hospitals in seven regions of China from September 2019 to December 2020. According to maternal HGP, all infants were divided into the HGP group or the non-HGP group. A propensity score matching analysis was used to adjust for confounding factors, including gestational age, twin or multiple births, sex, antenatal steroid administration, delivery mode and hypertensive disorders of pregnancy. The main complications and the short-term growth status during hospitalization were evaluated in the HGP and non-HGP groups., Results: A total of 2,514 infants were eligible for analysis. After matching, there were 437 infants in the HGP group and 874 infants in the non-HGP group. There was no significant difference between the two groups in main complications including respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis, retinopathy of prematurity, patent ductus arteriosus, culture positive sepsis, intraventricular hemorrhage, periventricular leukomalacia, anemia, feeding intolerance, metabolic bone disease of prematurity, or parenteral nutrition-associated cholestasis. The incidences of extrauterine growth retardation and increased growth retardation for weight and head circumference in the non-HGP group were all higher than those in the HGP group after matching ( P  < 0.05)., Conclusions: HGP did not worsen the short-term outcomes of the surviving very preterm infants, as it did not lead to a higher risk of the main neonatal complications, and the infants' growth improved during hospitalization., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Li, Shen, Zhang, Mao, Liu, Chang, Ye, Qiu, Ma, Cheng, Wu, Chen, Chen, Xu, Mei, Wang, Xu, Ju, Tong, Lin and Wu.)

Waste oil-based drill cuttings contain dioxins and volatile organic compounds (VOCs), which have the potential to cause serious health effects in humans. Therefore, this paper took oil-based drill cuttings (OBDCs) as the research object and carried out the testing of VOCs and dioxins content by using GC-MS and HRGCS-HRMS and comprehensively evaluated the content, composition and distribution pattern of VOCs and dioxins and the risk to human health posed by the two pollutants in OBDCs. The results showed that the VOCs did not exceed the emission limits in ESPPI (GB 31571-2015), but it is vital to recognise that 1,2-dichloropropane has the potential to cause cancer risk, with soil and groundwater risk control values of 662.95 mg·kg -1 and 0.066 mg·kg -1 , respectively. Benzene, 1,2-dichloropropane and 8 other VOCs pose a non-carcinogenic risk to humans. The levels of polychlorinated dibenzofurans (PCDFs) exceeded those of polychlorinated dibenzo-p-dioxins (PCDDs), which accounted for 95.76 percent of the total PCDD/Fs, 2,3,4,7,8-P 5 CDF (56.00%), 2,3,7,8-T 4 CDF (9.20%), 1,2,3,6,7,8-H 6 CDF (8.80%) and 1,2,3,7,8-P5CDF (8.00%) were the main contributing monomers. The findings of the assessment on exposure risk indicate that there is a respiratory risk to oil-based drill cuttings dioxins for adults and children exceeded the World Health Organisation (WHO) acceptable daily intake (ADI) (1-4 pgTEQ/kg/d). Finally, three aspects of solid waste pre-treatment prior to incineration, the incineration process and post incineration were used to reduce the environmental and human health risks from dioxins., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To describe the current status and trends in the outcomes and care practices of extremely preterm infants at 22-25 weeks' gestation age from the Chinese Neonatal Network (CHNN) from 2019 to 2021. Methods: This cross-sectional study used data from the CHNN cohort of very preterm infants. All 963 extremely preterm infants with gestational age between 22-25 weeks who were admitted to neonatal intensive care units (NICU) of the CHNN from 2019 to 2021 were included. Infants admitted after 24 hours of life or transferred to non-CHNN hospitals were excluded. Perinatal care practices, survival rates, incidences of major morbidities, and NICU treatments were described according to different gestational age groups and admission years. Comparison among gestational age groups was conducted using χ 2 and Kruskal-Wallis tests. Trends by year were evaluated by Cochran-Armitage and Jonckheere-Terpstra tests for trend. Results: Of the 963 extremely preterm infants enrolled, 588 extremely preterm infants (61.1%) were male. The gestational age was 25.0 (24.4, 25.6) weeks, with 29 extremely preterm infants (3.0%), 88 extremely preterm infants (9.1%), 264 extremely preterm infants (27.4%), and 582 extremely preterm infants (60.4%) at 22, 23, 24, and 25 weeks of gestation age, respectively. The birth weight was 770 (680, 840) g. From 2019 to 2021, the number of extremely preterm infants increased each year (285, 312, and 366 extremely preterm infants, respectively). Antenatal steroids and magnesium sulfate were administered to 67.7% (615/908) and 51.1% (453/886) mothers of extremely preterm infants. In the delivery room, 20.8% (200/963) and 69.5% (669/963) extremely preterm infants received noninvasive positive end-expiratory pressure support and endotracheal intubation. Delayed cord clamping and cord milking were performed in 19.0% (149/784) and 30.4% (241/794) extremely preterm infants. From 2019 to 2021, there were significant increases in the usage of antenatal steroids, antenatal magnesium sulfate, and delivery room noninvasive positive-end expiratory pressure support (all P <0.05). Overall, 349 extremely preterm infants (36.2%) did not receive complete care, 392 extremely preterm infants (40.7%) received complete care and survived to discharge, and 222 extremely preterm infants (23.1%) received complete care but died in hospital. The survival rates for extremely preterm infants at 22, 23, 24 and 25 weeks of gestation age were 10.3% (3/29), 23.9% (21/88), 33.0% (87/264) and 48.3% (281/582), respectively. From 2019 to 2021, there were no statistically significant trends in complete care, survival, and mortality rates (all P >0.05). Only 11.5% (45/392) extremely preterm infants survived without major morbidities. Moderate to severe bronchopulmonary dysplasia (67.3% (264/392)) and severe retinopathy of prematurity (61.5% (241/392)) were the most common morbidities among survivors. The incidences of severe intraventricular hemorrhage or periventricular leukomalacia, necrotizing enterocolitis, and sepsis were 15.3% (60/392), 5.9% (23/392) and 19.1% (75/392), respectively. Overall, 83.7% (328/392) survivors received invasive ventilation during hospitalization, with a duration of 22 (10, 42) days. The hospital stay for survivors was 97 (86, 116) days. Conclusions: With the increasing number of extremely preterm infants at 22-25 weeks' gestation admitted to CHNN NICU, the survival rate remained low, especially the rate of survival without major morbidities. Further quality improvement initiatives are needed to facilitate the implementation of evidence-based care practices.

Waterlogging constrains crop yields in many regions around the world. Despite this, key drivers of crop sensitivity to waterlogging have received little attention. Here, we compare the ability of the SWAGMAN Destiny and CERES models in simulating soil aeration index, a variable contemporaneously used to compute three distinct waterlogging indices, denoted hereafter as WI Destiny , WI ASD1 , and WI ASD2 . We then account for effects of crop growth stage and soil temperature on waterlogging impact by introducing waterlogging severity indices, WI Growth , which accommodates growth stage tolerance, and WI Plus , which accounts for both soil temperature and growth stage. We evaluate these indices using data collected in pot experiments with genotypes "Yang mai 11" and "Zheng mai 7698" that were exposed to both single and double waterlogging events. We found that WI Plus exhibited the highest correlation with yield (-0.82 to -0.86) suggesting that waterlogging indices which integrate effects of temperature and growth stage may improve projections of yield penalty elicited by waterlogging. Importantly, WI Plus not only allows insight into physiological determinants, but also lends itself to remote computation through satellite imagery. As such, this index holds promise in scalable monitoring and forecasting of crop waterlogging., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xu, Hu, Wan, Harrison, Liu and Xiong.)

Background: To analyze the real-world growth pattern of very premature infants (VPI) with small for gestational age (SGA) after birth by using the ΔZ value of weight at discharge., Methods: The clinical data were collected from 28 hospitals in China from September 2019 to December 2020. They were divided into the EUGR(Extrauterine Growth Restriction) and the non-EUGR group according to the criterion of ΔZ value of weight at discharge < -1.28., Results: This study included 133 eligible VPI with SGA. Following the criterion of ΔZ value, the incidence of EUGR was 36.84% (49/133). The birth weight, the 5-min Apgar score, and the proportion of male infants in the EUGR group were lower (P < 0.05). The average invasive ventilation time, cumulative duration of the administration of antibiotics, blood transfusion time, blood transfusion ratio, and total days of hospitalization were significantly higher in the EUGR group (P < 0.05). In the EUGR group, several factors exhibited higher values (P < 0.05), including the initiation of enteral feeding, the volume of milk supplemented with human milk fortifier (HMF), the duration to achieve complete fortification, the cumulative duration of fasting, the duration to achieve full enteral feeding, the length of parenteral nutrition (PN), the number of days required to attain the desired total calorie intake and oral calorie intake, as well as the age at which birth weight was regained. The average weight growth velocity (GV) was significantly lower in the EUGR group (P < 0.001). The incidences of patent ductus arteriosus with hemodynamic changes (hsPDA), neonatal necrotizing enterocolitis (NEC) stage≥ 2, late-onset sepsis (LOS), and feeding intolerance (FI) in the EUGR group were higher (P < 0.05). Multivariate logistic regression analysis showed that birth weight, male, and GV were the protective factors, while a long time to achieve full-dose fortification, slow recovery of birth weight, and NEC stage ≥2 were the independent risk factors., Conclusion: SGA in VPI can reflect the occurrence of EUGR more accurately by using the ΔZ value of weight at discharge. Enhancing enteral nutrition support, achieving prompt and complete fortification of breast milk, promoting greater GV, reducing the duration of birth weight recovery, and minimizing the risk of NEC can contribute to a decreased occurrence of EUGR., Trial Registration: CHICTR, ChiCTR1900023418. Registered 26/05/2019, http://www.chictr.org.cn ., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Viruses have evolved various strategies to achieve early infection by initiating transcription of their own early genes via host transcription factors, such as NF-κb, STAT, and AP1. How the host copes with this immune escape has been a topic of interest. Tripartite motif (TRIM) family proteins with RING-type domains have E3 ubiquitin ligase activity and are known as host restriction factors. Trim has been reported to be associated with phagocytosis and is also believed to be involved in the activation of autophagy. Preventing the virus from entering the host cell may be the most economical way for the host to resist virus infection. The role of TRIM in the early stage of virus infection in host cells remains to be further interpreted. In the current study, a crayfish TRIM with a RING-type domain, designated as PcTrim, was significantly upregulated under white spot syndrome virus (WSSV) infection in the red swamp crayfish (Procambarus clarkii). Recombinant PcTrim significantly inhibited WSSV replication in crayfish. RNAi targeting PcTrim or blocking PcTrim with an antibody promoted WSSV replication in crayfish. Pulldown and co-IP assays showed that PcTrim can interact with the virus protein VP26. PcTrim restricts the expression level of dynamin, which is involved in the regulation of phagocytosis, by inhibiting AP1 entry into the nucleus. AP1-RNAi effectively reduced the expression levels of dynamin and inhibited host cell endocytosis of WSSV in vivo. Our study demonstrated that PcTrim might reduce early WSSV infection by binding to VP26 and then inhibiting AP1 activation, resulting in reduced endocytosis of WSSV in crayfish hemocytes. Video Abstract., (© 2023. The Author(s).)

Forensic DNA analysis of semen-vaginal fluid mixed stains is essential and necessary in sexual assault cases. Here, we used a magnetic bead conjugated acrosin binding protein (ACRBP) antibody to separate and enrich sperm cells from mixed stains. Previously, western blotting indicated that ACRBP was specifically expressed in sperm cells, but not in female blood and epithelial cells, while immunofluorescence data showed ACRBP was localized to the acrosome in sperm cells. In our study, sperm were separated from mixed samples at three sperm cell/female buccal epithelial cell ratios (10 3 :10 3 ; 10 3 :10 4 ; and 10 3 :10 5 ) using a magnetic bead conjugated ACRBP antibody. Subsequently, 23 autosomal short tandem repeat (STR) loci were amplified using the Huaxia™ Platinum PCR Amplification System and genotyped using capillary electrophoresis. The genotyping success rate for STR loci was 90% when the sperm to female buccal epithelial cell ratio was > 1:100 in mixed samples. Our results suggest that the magnetic bead conjugated ACRBP antibody is effective for isolating sperm cells in sexual assault cases., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: The management of enteral nutrition in very preterm infants (VPIs) is still controversial, and there is no consensus on the optimal time point after birth at which enteral nutrition can be started. The aim of this study was to investigate the effect of early initiation of enteral nutrition on the short-term clinical outcomes of VPIs., Methods: Data of infants (n = 2514) born before 32 wk of gestation were collected from 28 hospitals located in seven different regions of China. Based on whether enteral feeding was initiated within or after 24 h since birth, the infants were divided into an early initiation of enteral feeding (EIEF) group and a delayed initiation of enteral feeding (DIEF) group., Results: Compared with the DIEF group, the EIEF group was more likely to tolerate enteral nutrition and had less need for parenteral nutrition (all P < 0.05). The EIEF group was associated with lower incidence rates of feeding intolerance, extrauterine growth restriction (EUGR), and late-onset sepsis (LOS) (all P < 0.05). There was no significant difference in the incidence of necrotizing enterocolitis (NEC) (Bell stage ≥2) between the two groups (P = 0.118). The multivariate logistic regression analysis revealed that EIEF was a protective factor against EUGR (odds ratio [OR], 0.621; 95% confidence interval [CI], 0.544-0.735; P < 0.001), feeding intolerance (OR, 0.658; 95% CI, 0.554-0.782; P < 0.001), and LOS (OR, 0.706; 95% CI, 0.550-0.906; P = 0.006)., Conclusions: Early initiation of enteral feeding was associated with less frequency of feeding intolerance, EUGR, and LOS, and it may shorten the time to reach total enteral feeding without increasing the risk of NEC., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate local cerebral blood perfusion in preterm infants with bronchopulmonary dysplasia (BPD) based on cerebral blood flow (CBF) values of arterial spin labeling (ASL)., Methods: A prospective study was conducted on 90 preterm infants with a gestational age of <32 weeks and a birth weight of <1 500 g who were born in the Department of Obstetrics and admitted to the Department of Neonatology in the Third Affiliated Hospital of Zhengzhou University from August 2021 to June 2022. All of the infants underwent cranial MRI and ASL at the corrected gestational age of 35-40 weeks. According to the presence or absence of BPD, they were divided into a BPD group with 45 infants and a non-BPD group with 45 infants. The two groups were compared in terms of the CBF values of the same regions of interest (frontal lobe, temporal lobe, parietal lobe, occipital lobe, thalamus, and basal ganglia) on ASL image., Results: Compared with the non-BPD group, the BPD group had a significantly lower 1-minute Apgar score, a significantly longer duration of assisted ventilation, and a significantly higher incidence rate of fetal distress ( P <0.05). After control for the confounding factors such as corrected age and age at the time of cranial MRI by multiple linear regression analysis, compared with the non-BPD group, the BPD group still had higher CBF values of the frontal lobe, temporal lobe, parietal lobe, occipital lobe, basal ganglia, and thalamus at both sides ( P <0.05)., Conclusions: BPD can increase cerebral blood perfusion in preterm infants, which might be associated with hypoxia and a long duration of assisted ventilation in the early stage.

Sorafenib, a first-line drug for advanced hepatocellular carcinoma (HCC), shows a favorable anti-tumor effect while resistance is a barrier impeding patients from benefiting from it. Thus, more efforts are needed to lift this restriction. Herein, we first find that solute carrier family 27 member 5 (SLC27A5/FATP5), an enzyme involved in the metabolism of fatty acid and bile acid, is downregulated in sorafenib-resistant HCC. SLC27A5 deficiency facilitates the resistance towards sorafenib in HCC cells, which is mediated by suppressing ferroptosis. Further mechanism studies reveal that the loss of SLC27A5 enhances the glutathione reductase (GSR) expression in a nuclear factor erythroid 2-related factor 2 (NRF2)-dependent manner, which maintains glutathione (GSH) homeostasis and renders insensitive to sorafenib-induced ferroptosis. Notably, SLC27A5 negatively correlates with GSR, and genetic or pharmacological inhibition of GSR strengthens the efficacy of sorafenib through GSH depletion and the accumulation of lipid peroxide products in SLC27A5-knockout and sorafenib-resistant HCC cells. Based on our results, the combination of sorafenib and carmustine (BCNU), a selective inhibitor of GSR, remarkably hamper tumor growth by enhancing ferroptotic cell death in vivo. In conclusion, we describe that SLC27A5 serves as a suppressor in sorafenib resistance and promotes sorafenib-triggered ferroptosis via restraining the NRF2/GSR pathway in HCC, providing a potential therapeutic strategy for overcoming sorafenib resistance., (© 2023. The Author(s).)

Objective: To investigate the incidence and related factors of extrauterine growth retardation (EUGR) and "true EUGR" in very preterm infants (VPI) from different regions of China., Materials and Methods: Clinical data of VPI were prospectively collected from 28 hospitals in seven different regions of China from September 2019 to December 2020. The infants were divided into a small for gestational age (SGA) group or non-SGA group at birth, with non-SGA infants at 36 weeks of gestation or at discharge being further divided into a EUGR group or a non-EUGR group. Infants in the EUGR and non-SGA group were defined as "true EUGR." The general information of VPI, such as maternal complications during pregnancy, use of enteral nutrition and parenteral nutrition, and complications during hospitalization were compared between the groups., Results: Among the 2,514 VPI included in this study, 47.3, 41.5, and 33.3% of VPI were below the 10th percentile, and 22.6, 22.4, and 16.0% of VPI were below the 3rd percentile for weight, height, and head circumference at 36 weeks of gestation or at discharge, respectively, by the percentile on the 2013 Fenton curve. The incidences of EUGR and "true EUGR" evaluated by weight were 47.3 and 44.5%, respectively. Univariate analysis showed that there were statistically significant differences in the aspects of perinatal and nutritional characteristics, treatment, and complications between the groups. Multivariate analysis showed that in non-SGA infants, the cumulative caloric intake during the first week was a protective factor for "true EUGR," while days to reach total enteral nutrition, late initiation of human milk fortifier, and moderate to severe bronchopulmonary dysplasia were independent risk factors for "true EUGR.", Conclusion: More attention should be paid to the nutritional management of VPI to prevent "true EUGR." Cumulative caloric intake should be ensured and increased during the first week, total enteral nutrition should be achieved as early as possible, human milk fortifier should be added early, and moderate to severe bronchopulmonary dysplasia should be prevented. These strategies are very important for reducing the incidence of "true EUGR" in VPI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shen, Wu, Mao, Liu, Chang, Zhang, Zheng, Ye, Qiu, Ma, Cheng, Wu, Chen, Chen, Xu, Mei, Wang, Xu, Ju, Chen, Tong and Lin.)

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The Spike protein that mediates coronavirus entry into host cells is a major target for COVID-19 vaccines and antibody therapeutics. However, multiple variants of SARS-CoV-2 have emerged, which may potentially compromise vaccine effectiveness. Using a pseudovirus-based assay, we evaluated SARS-CoV-2 cell entry mediated by the viral Spike B.1.617 and B.1.1.7 variants. We also compared the neutralization ability of monoclonal antibodies from convalescent sera and neutralizing antibodies (NAbs) elicited by CoronaVac (inactivated vaccine) and ZF2001 (RBD-subunit vaccine) against B.1.617 and B.1.1.7 variants. Our results showed that, compared to D614G and B.1.1.7 variants, B.1.617 shows enhanced viral entry and membrane fusion, as well as more resistant to antibody neutralization. These findings have important implications for understanding viral infectivity and for immunization policy against SARS-CoV-2 variants., (© 2021 Chongqing Medical University. Production and hosting by Elsevier B.V.)

Objective: Nutritional deficiency soon after birth is a risk factor of chronic lung disease (bronchopulmonary dysplasia, BPD). Afflicted infants are further prone to inadequate growth during hospitalization (extrauterine growth restriction, EUGR). This multi-center retrospective study investigated risk factors of EUGR, specifically in very preterm infants with BPD., Method: Data of infants with BPD who were born less than 32 weeks gestation (n = 1010) were collected from 7 regions of China. All infants were non-small for gestational age at birth. Infants were characterized as EUGR or non-EUGR at 36 weeks gestation or discharge, or stratified by gestational age or birthweight. Logistic regression analysis was applied., Results: In 65.5% of the population, the BPD was mild. Infants with severe BPD (8.3%) had the highest rate of EUGR (72.6%, P < 0.001). Groups stratified by gestational age did not differ in rates of EUGR, but the birthweight of the EUGR group was significantly lower than that of the non-EUGR (P < 0.001). Birthweights of < 1000, 1000-1499, and ≥ 1500 g showed EUGR rates of 65.9%, 43.4%, and 23.8%, respectively (P < 0.001). Overall, the independent risk factors of EUGR were: moderate-to-severe BPD, gestational hypertension, cesarean section, cumulative fasting time, time required to achieve 110 kcal/kg/d, and hemodynamically significant patent ductus arteriosus (hsPDA)., Conclusion: In very preterm infants with BPD, the lower the birthweight or the more severe the BPD, the greater the risk of EUGR. In those with hsPDA, or moderate-to-severe BPD, it is especially important to prevent EUGR through perinatal management, enteral nutrition, and nutritional strategies., (© 2022. The Author(s).)

Objectives: To establish a nomogram model for predicting the risk of death of very preterm infants during hospitalization., Methods: A retrospective analysis was performed on the medical data of 1 714 very preterm infants who were admitted to the Department of Neonatology, the Third Affiliated Hospital of Zhengzhou University, from January 2015 to December 2019. These infants were randomly divided into a training cohort (1 179 infants) and a validation cohort (535 infants) at a ratio of 7∶3. The logistic regression analysis was used to screen out independent predictive factors and establish a nomogram model, and the feasibility of the nomogram model was assessed by the validation set. The area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA) were used to assess the discriminatory ability, accuracy, and clinical applicability of the model., Results: Among the 1 714 very preterm infants, 260 died and 1 454 survived during hospitalization. By the multivariate logistic regression analysis of the training set, 8 variables including gestational age <28 weeks, birth weight <1 000 g, severe asphyxia, severe intraventricular hemorrhage (IVH), grade III-IV respiratory distress syndrome (RDS), and sepsis, cesarean section, and use of prenatal glucocorticoids were selected and a nomogram model for predicting the risk of death during hospitalization was established. In the training cohort, the nomogram model had an AUC of 0.790 (95% CI : 0.751-0.828) in predicting the death of very preterm infants during hospitalization, while in the validation cohort, it had an AUC of 0.808 (95% CI : 0.754-0.861). The Hosmer-Lemeshow goodness-of-fit test showed a good fit ( P >0.05). DCA results showed a high net benefit of clinical intervention in very preterm infants when the threshold probability was 10%-60% for the training cohort and 10%-70% for the validation cohort., Conclusions: A nomogram model for predicting the risk of death during hospitalization has been established and validated in very preterm infants, which can help clinicians predict the probability of death during hospitalization in these infants.

Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious disease caused by PRRS virus (PRRSV), characterized by sow reproductive failure and respiratory symptoms in pigs of all ages. PRRSV mainly causes severe lung damage by invading alveolar macrophages. Visfatin is closely related to acute lung injury, immune response and inflammation along with virus invasion to the host. Therefore, the current study was performed to clarify the relationship between visfatin and PRRSV infection. We used ternary piglets to construct a piglet model to explore the expression of visfatin and tight junction protein in lung injury induced by PRRSV infection, and then further studied the inhibition effect of visfatin on PRRSV replication by PRRSV infection of Marc-145 cells. Our results indicated that both PRRSV attenuated and virulent infections could damage the lung tissues, which could not only lead to severe inflammatory reaction (such as increased expression of TNF-α, TGF-β, IL-8 and IL-10) in lung tissues of piglets, but also brought about the sharp decrease of ZO-1 and Tricellulin expressions resulting in impaired alveolar epithelial barrier. Meanwhile, we found significantly up-regulated expression of visfatin in lungs and serum of pigs after PRRSV infection that were related to both the degree of lung injury and the virulence of PRRSV strain. Moreover, visfatin might inhibit the PRRSV infection to Marc-145 cells in time dependent fashion. Hence, the current investigation provides the novel information about the effect of visfatin and PRRSV co-culture on Marc-145 cells and the effect of visfatin on PRRSV proliferation at different time points., (Copyright © 2022. Published by Elsevier Ltd.)

Objectives: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China., Methods: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group ( n =1 189) and non-EUGR ( n =1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined., Results: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR ( P <0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR ( P <0.05)., Conclusions: It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.

Background: Schizophrenia is a complex brain disorder, the pathogenesis of which remains unclear. Regulator of G-protein signaling 4 is regarded as a candidate gene for schizophrenia risk. The association between the regulator of G-protein signaling 4 gene and the risk of schizophrenia is complicated and controversial, thus, an updated meta-analysis is needed., Methods: A search strategy using Medical Subject Headings was developed in English (PubMed, SZGene) and Chinese (CNKI, Wanfang, and Weipu) databases. Inclusion and exclusion criteria were used to screen for eligible studies. Parameters, such as P value of Hardy-Weinberg equilibrium, odds ratios, 95% confidence intervals, P values of association, heterogeneity (Ph), and publication bias, were analyzed by the Stata software using a random effects model. Subgroup analyses were performed to detect heterogeneity., Results: There were 15 articles regarding rs10917670 (8046 cases and 8837 controls), 16 regarding rs951436 (8990 cases and 10,568 controls), 15 regarding rs951439 (7995 cases and 8646 controls), 15 regarding rs2661319 (8320 cases and 9440 controls), and 4 regarding rs10759 (2752 cases and 2866 controls). The frequencies of rs10917670 and rs951439 were not significantly different between the case and control groups (P > .05). As shown by the East Asian and hospital-based subgroup analyses, the genotype TT of rs951436 might be related to the risk of schizophrenia. The genotypes CC + CT of rs2661319 and CC + CA of rs10759 were statistically different between the 2 groups, and the East Asian population contributed to these differences., Conclusion: The genotypes CC + CT of rs2661319 and CC + CA of rs10759 might be associated with the risk of schizophrenia., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: To construct risk prediction models for bronchopulmonary dysplasia (BPD) in preterm infants on postnatal days 3, 7, and 14., Methods: A retrospective analysis was performed on the medical data of 414 preterm infants, with a gestational age of <32 weeks and a birth weight (BW) of <1 500 g, who were admitted to the neonatal intensive care unit from July 2019 to April 2021. According to the diagnostic criteria for BPD revised in 2018, they were divided into a BPD group with 98 infants and a non-BPD group with 316 infants. The two groups were compared in terms of general status, laboratory examination results, treatment, and complications. The logistic regression model was used to identify the variables associated with BPD. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of models., Results: The logistic regression analysis showed that BW, asphyxia, grade III-IV respiratory distress syndrome (RDS), acute chorioamnionitis, interstitial pneumonia, fraction of inspired oxygen (FiO 2 ), and respiratory support mode were the main risk factors for BPD ( P <0.05). The prediction models on postnatal days 7 and 14 were established as logit (P 7 ) =-2.049-0.004×BW (g) +0.686×asphyxia (no=0, yes=1) +1.842×grade III-IV RDS (no=0, yes=1) +0.906×acute chorioamnionitis (no=0, yes=1) +0.506×interstitial pneumonia (no=0, yes=1) +0.116×FiO 2 (%) +0.816×respiratory support mode (no=0, nasal tube=1, nasal continuous positive airway pressure=2, conventional mechanical ventilation=3, high-frequency mechanical ventilation=4) and logit (P 14 ) =-1.200-0.004×BW (g) +0.723×asphyxia+2.081×grade III-IV RDS+0.799×acute chorioamnionitis+0.601×interstitial pneumonia+0.074×FiO 2 (%) +0.800×respiratory support mode, with an area under the ROC curve (AUC) of 0.876 and 0.880, respectively, which was significantly larger than the AUC of the prediction model on postnatal day 3 ( P <0.05)., Conclusions: BW, asphyxia, grade III-IV RDS, acute chorioamnionitis, interstitial pneumonia, FiO 2 , and respiratory support mode are the main risk factors for BPD and can be used to construct risk prediction models. The prediction models on postnatal days 7 and 14 can effectively predict BPD.

Residual levels and temporal-spatial distribution characteristics of polycyclic aromatic hydrocarbons (PAHs) in dustfall were studied at the seasonal scale between June 2010 and May 2011 in the fifth largest shallow lake in China. PAHs flux of atmospheric deposition and the impact on the PAHs in the lake water column were estimated. The major sources of PAHs were identified by multiple methods. We found that (1) the seasonal residual levels of 16 priority controlled PAHs (PAH 16 ) were spring (8.89 ± 3.93 μg g -1 ) > summer (6.68 ± 4.31 μg g -1 ) > winter (6.06 ± 2.95 μg g -1 ) > autumn (3.55 ± 2.21 μg g -1 ). (2) Significant positive correlations were found between the PAH levels in the dustfall and the suspended particle material (SPM) content, as well as between the deposition flux and the PAH content in the water in all four seasons. (3) Vehicle emissions, coal combustion, biomass combustion, and coke ovens were the four major sources in Lake Chaohu, accounting for 12.7%, 40.9%, 14.5%, and 31.9% of the total PAHs, respectively. (4) Compared to long-distance trajectories, short-distance trajectories played a more important role in the external sources of atmospheric PAHs in the region of Lake Chaohu., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To study the correlation of fractional anisotropy (FA) on magnetic resonance diffusion tensor imaging with Neonatal Behavioral Neurological Assessment (NBNA) score in preterm infants, and to study the role of FA in evaluating white matter development from the perspective of imaging., Methods: A prospective study was performed for 98 preterm infants who were admitted to the Neonatal Intensive Care Unit of the Third Affiliated Hospital of Zhengzhou University within 24 hours after birth from October 2016 to January 2020. According to the results of NBNA, they were divided into an abnormal group with 51 infants (NBNA score <37) and a normal group with 47 infants (NBNA score ≥37). The FA values of 10 regions of interest were collected and compared between the two groups. The correlations of FA value and umbilical arterial blood gas pH value with the NBNA score were analyzed., Results: Compared with the normal group, the abnormal group had significantly lower FA value of the posterior limb of the internal capsule and umbilical arterial blood pH ( P <0.05). The FA value of the posterior limb of the internal capsule and umbilical arterial blood pH were positively correlated with the NBNA score ( r =0.584 and 0.604 respectively, P <0.001), and the FA value of the posterior limb of the internal capsule was positively correlated with umbilical arterial blood pH ( r =0.426, P <0.05)., Conclusions: The FA value of the posterior limb of the internal capsule can quantitatively reflect white matter development in preterm infants and is correlated with the NBNA score. The combination of the two indices can help to evaluate white matter development in preterm infants more accurately and objectively. Citation .

Except for a few stick insects that are economically valuable, most species be considered to be forest pests, so it is extremely important to obtain plant host-use information of more stick insects. In this paper, the plant hosts of three species of stick insects were recorded for the first time. We also discovered these stick insects can feed upon the flowers or leaves of plants. Lopaphus unidentatus (Chen & He, 1995) (Phasmida: Lonchodidae) attacked Hypericum choisianum Wall. ex N. Robson, 1973 (Hypericaceae), Leurophasma dolichocercum Bi, 1995 (Phasmida: Aschiphasmatidae) attacked Antenoron filiforme (Thunb.) Roberty & Vautier, 1964 (Polygonaceae) and Megalophasma granulatum Bi, 1995 (Phasmida: Lonchodidae) attacked Debregeasia orientalis C. J. Chen, 1991 (Urticaceae). Finally, we were lucky enough to also obtain photographs of them mating and feeding.

Visfatin is a multifunctional protein involved in inflammatory immune stress. The aim of current study was to explore the role of visfatin in lipopolysaccharide (LPS)-induced intestinal mucosal inflammation and to confirm its cellular effect in inflammatory immune response through silencing of Toll-like receptors (TLRs). We divided Kunming mice into three groups: Saline group, LPS group, and LPS + visfatin group and performed hematoxylin and eosin staining, immunohistochemistry, quantitative polymerase chain reaction, Western blot, enzyme linked immunosorbent assay and RNA-seq analysis. Pretreatment of visfatin improves LPS-stimulated reduction of tight junction protein 1 (ZO-1) and secretory immunoglobulin A, inhibits overexpression of Claudin-1 and vascular endothelial growth factor, and reduces intestinal mucosal damage and inflammation. RNA-seq analysis of cellular transcriptomes indicated that visfatin is involved in down-regulation of mRNA level of TLR4 as well as attenuation of protein levels of TLR8 and nucleotide-binding oligomerization domain-containing protein 2, revealing that visfatin could reduce intestinal mucosal inflammation through TLR signaling pathway in mice ileum. In RAW264.7 cells, the genes silencing of Toll/IL-1R family, such as TLR4, TLR2, and IL-1R1, was accompanied by decreased expressions of inflammatory factors (TNF-α, IL-1β, IL-6 and MCP-1) along with lower cellular visfatin levels. Hence, visfatin maintains the intestinal mucosal barrier structure and attenuates the intestinal mucosal inflammation through the TLR signaling pathway. Likewise, the Toll/IL-1R family regulates the release of visfatin, which can participate in the inflammatory reaction through the regulation of inflammatory factors.

Objective: To investigate the birth condition of preterm infants and the causes of preterm birth in Henan Province, China, and to provide a basis for the prevention and treatment of preterm birth., Methods: An epidemiological investigation was conducted for live-birth preterm infants who were born in 53 hospitals in 17 cities of Henan Province from January 1, 2019 to December 31, 2019 to investigate the incidence rate of preterm birth, the distribution of gestational age and birth weight, the use of antenatal glucocorticoids, and the causes of preterm birth., Results: The incidence rate of preterm birth was 5.84% (12 406/212 438) in the 53 hospitals. The proportions of preterm infants with gestational ages of < 28 weeks, 28 - < 32 weeks, 32 - < 34 weeks, and 34 - < 37 weeks were 1.58% (196/12 406), 11.46% (1 422/12 406), 15.18% (1 883/12 406), and 71.78% (8 905/12 406) respectively. The proportions of preterm infants with birth weights of < 1 000 g, 1 000- < 1 500 g, 1 500- < 2 500 g, 2 500- < 4 000 g, and ≥ 4 000 g were 1.95% (240/12 313), 8.54% (1 051/12 313), 49.53% (6 099/12 313), 39.59% (4 875/12 313), and 0.39% (48/12 313) respectively. The infants born by natural labor accounted for 28.76% (3 568/12 406), and those born by cesarean section accounted for 70.38% (8 731/12 406). The rate of use of antenatal glucocorticoids was 52.52% (6 293/11 983) for preterm infants and 68.69% (2 319/3 376) for the preterm infants with a gestational age of < 34 weeks. Iatrogenic preterm labor was the leading cause of preterm birth[40.06% (4 915/12 270)], followed by spontaneous preterm birth[30.16% (3 701/12 270)] and preterm birth due to premature rupture of membranes[29.78% (3 654/12 270)]. The top three causes of iatrogenic preterm birth were hypertensive disorders of pregnancy[47.12% (2 316/4 915)], fetal intrauterine distress[22.85% (1 123/4 915)], and placenta previa/placental abruption[18.07% (888/4 915)]., Conclusions: There is a relatively low incidence rate of preterm birth in Henan Province, and late preterm infants account for a relatively high proportion. Iatrogenic preterm birth is the main cause of preterm birth in Henan Province, and hypertensive disorders of pregnancy and fetal intrauterine distress are the main causes of iatrogenic preterm birth.

In order to obtain the porcine recombinant visfatin protein with high expression and low endotoxin content, the current study aims to express and verify the biological activity of the purified porcine recombinant visfatin protein. Firstly, four different expression strains were successfully constructed. Then they were simultaneously induced at 37 °C for 4 h and 16 °C for 16 h. The results showed that Visfatin-pET28a-Transetta was the best strain with high protein expression and purity at 16 °C induction for 16 h. After that, endotoxin was reduced from the recombinant visfatin until the residual endotoxin was less than one endotoxin units per milliliter (EU/mL). Finally, the purified porcine recombinant visfatin protein was incubated with RAW264.7 cells. The results of cell counting kit-8 (CCK-8) showed the survival rate of the cells first increased and then decreased with the increase in visfatin concentration. When the concentration of visfatin was 700 ng/mL, the survival rate of the cells was the highest. Thereafter, control (PBS), Visfatin and Visfatin + PolymyxinB (Ploy.B) groups were incubated with the RAW264.7 cells for 6 h. Real-time quantitative polymerase chain reaction (RT-qPCR) and Enzyme Linked Immuno-Sorbent Assay (ELISA) results showed that, as compared to the control group, the expressions of interleukin (IL)-1β, tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1 in Visfatin group were significantly increased (P < 0.05). However, there was no significant difference between the Visfatin and Visfatin + Poly.B groups, indicating that porcine recombinant visfatin protein promoted the inflammatory activity of RAW264.7 cells while the residual endotoxin did not play a role, suggesting biological activity of porcine recombinant visfatin protein., (Copyright © 2020. Published by Elsevier Inc.)

Background: As the survival rate of premature infants increases, the incidence of bronchopulmonary dysplasia (BPD), a chronic complication of premature infants, is also higher than before. The pathogenesis of BPD is complicated, and immune imbalance and inflammatory response may play important roles in it., Objective: To investigate the correlation between lymphocyte subsets in peripheral blood, especially γδ-T cells, and BPD of preterm infants., Materials and Method: The study was carried out with the peripheral blood of premature infants (GA < 32 weeks, BW < 1500 g), which were collected at 24 h or 3-4 weeks after birth. The infants were divided into non-BPD groups and BPD groups that were classified as mild or moderate and severe in preterm infants based on the magnitude of respiratory support at 28 days age and 36 weeks postmenstrual age. The γδ-T, CD3+, CD4+, CD8+ and total lymphocyte subsets in peripheral blood were detected by flow cytometry., Results: The percentages of T lymphocyte subsets in peripheral blood were not different between BPD and non-BPD within 24 h after birth. And no significant difference was found in T lymphocyte subsets among neonates with BPD of different severities. However, the infants who developed BPD had a significant increase in γδ-T cells compared to non-BPD ones within 3-4 weeks after birth., Conclusions: It seems that γδ-T cells in peripheral blood are correlated with BPD. However, the causality of BPD and various lymphocytes remains unclear, which need to be further studied., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Background: The abnormal expression Dopamine D1 receptor (DRD1) gives rise to the dysfunction of dopaminergic neurotransmitter and may be associated with the occurrence of schizophrenia. MicroRNAs (miRNAs) can regulate the DRD1 expression by binding 3'UTR and be involved in the post-transcriptional regulation. Methods: We first constructed the pmirGLO-recombined vectors of series of DRD1 gene 3'UTR-truncated fragments and performed the luciferase receptor assay to screen the underlying 3'UTR sequence targeted by miRNAs. Then, we predicted the potential miRNAs binding the target sequence and confirmed their effects using luciferase receptor assay after transfection of the miRNA mimics/inhibitors. We also examined the effects of the miRNA on the endogenous DRD1 expression. Results: We found that the DRD1 3'UTR ranging from -12 to +1135 bp was essential for the post-transcriptional regulation of miRNAs. The deletion of -12 to +154 bp fragment significantly increased the luciferase expression but not the mRNA expression. The miRNA-15a, miRNA-15b and miRNA 16 affected DRD1 expression in HEK293, U87, SK-N-SH and SH-SY5Y cell lines. Conclusion: The miRNA-15a, miRNA-15b and miRNA-16 inhibit the human dopamine D1 receptor expression by targeting 3'UTR -12 to +154 bp.Highlights DRD1 3'UTR ranging from -12 to +1135 bp was essential for the post-transcriptional regulation of miRNAs.The deletion of -12 to +154 bp fragment significantly increased the luciferase expression but not the mRNA expression.The miRNA-15a, miRNA-15b and miRNA 16 affected DRD1 expression in different cell lines, respectively.

Aims: To investigate whether combination of acetazolamide and cisplatin can enhance the chemosensitivity of human head and neck squamous cell carcinoma (HNSCC) cell line TU868., Methods: MTT assay was performed to determine the effect of acetazolamide, cisplatin and their combination on the proliferation of TU868 cells. Then the effect of these 2 drugs on the expression of proliferation-related and apoptosis-related proteins was detected by Western blot. Moreover, the effect of acetazolamide and cisplatin on the expression of aquaporin-1 was detected by RT-qPCR. Loss-of-function assays was performed to assess whether the effect of acetazolamide and cisplatin on TU868 cells was mediated by aquaporin-1. The effect of acetazolamide and cisplatin on tumor cell growth was confirmed in mice by testing the tumor growth size., Results: Acetazolamide and cisplatin treatment displayed synergistic effects on the inhibition of TU868 cell growth compared with the drugs used alone. Moreover, the acetazolamide/cisplatin combination could decrease the level of PCNA but increase the level of p53; decrease the ratio of Bcl-2/Bax and increase the expression of caspase-3 compared with the single drug treated group. Moreover, we found that the combination also significantly inhibits aquaporin-1 expression. Loss-of-function assays suggested that the anti-tumor effect of these 2 drugs was achieved via affecting aquaporin-1. Consistent with the in vitro assays, combined treatment with acetazolamide and cisplatin significantly inhibits the tumor growth in mice compared with the single drug treated group., Conclusion: These results demonstrated that combined treatment with acetazolamide and cisplatin could synergistically inhibit the malignant development of HNSCC cells., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Schizophrenia is a serious neurodevelopmental disorder. Genetics is an important factor leading to schizophrenia, but its exact role is still unclear. Many studies have focused on neurotransmitters and regulators that participate in the processes mediated by these neurotransmitters. Alcohol dehydrogenase may not only catalyze the oxidation of retinol and ethanol but also be involved in a variety of neurotransmitter metabolic pathways. Therefore, our study investigated whether ADH7 gene variations in the Chinese Han population were associated with schizophrenia. Genomic DNA was extracted from a cohort of 275 schizophrenic patients (136 men and 139 women) and 313 healthy controls (160 men and 153 women) from the Northern Han Chinese population. The Hardy-Weinberg equilibrium test and linkage disequilibrium analysis were performed. Differences in genotypes, alleles, and haplotypes between the schizophrenic and control groups were determined using the chi-square test and correlation analysis. The distribution of the CC + TT genotype of rs284787 was statistically different between the case and control groups (p = 0.026, OR = 1.448); however, the difference disappeared after Bonferroni correction. Linkage analysis indicated that rs739147, rs284787, rs3805329, rs894369, rs3805331, and rs284786 were closely linked in one block. The haplotype analysis found no association between the composed haplotypes and the occurrence of schizophrenia. Our study showed that the ADH7 gene was not associated with the risk of schizophrenia. Additional studies with larger cohorts of different ethnicities are needed to validate our findings.

Neonicotinoid insecticides (NNIs) are the most widely used insecticides in China and worldwide. Continuous use of NNIs can lead to their accumulation in soil, causing potential ecological risks due to their relatively long half-life. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to investigate the residual levels of nine neonicotinoids in greenhouse soils in Shouguang, East China, at different soil depths and with different crops (tomato and cucumber) after varying periods of cultivation. Seven neonicotinoids were detected in the soils of the tomato greenhouses and six were detected in the soils of the cucumber greenhouses, with total concentrations ranging from 0.731 to 11.383 μg kg -1 and 0.363 to 19.224 μg kg -1 , respectively. In all samples, the neonicotinoid residues in the soils cultivated for 8-9 years were lower than in those cultivated for 2 years and 14-17 years. In the tomato greenhouse soils, the residual levels of NNIs were highest in the topsoil, with progressively lower concentrations found with depth. Under cucumber cultivation, the NNI residue levels were also highest in the topsoil but there was little difference between the middle and lower soil layers. Total organic carbon (TOC) decreased with soil depth while pH showed the opposite trend, showing a significant negative correlation in both types of soils (tomato soils ρ = -0.900, p = .001; cucumber soils ρ = -0.883, p = .002). Furthermore, TOC was significantly positively correlated, and pH was negatively correlated, with total NNI concentrations in both types of soils (TOC: tomato soils ρ = 0.800, p = .010; cucumber soils ρ = 0.881, p = .004; pH: tomato soils ρ = -0.850, p = .004; cucumber soils ρ = -0.643, p = .086). The results of an ecological risk analysis showed that acetamiprid represents a particularly high toxicity risk in these soils. Based on our analysis, NNI residues in the soils of tomato greenhouses and their associated ecological risks deserve more attention than those of cucumber greenhouse soils., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To assess white matter development in preterm infants with bronchopulmonary dysplasia (BPD) using fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values of diffusion tensor imaging (DTI)., Methods: Ninety-six infants with a gestational age of ≤32 weeks and a birth weight of <1 500 g who were admitted to the neonatal intensive care unit within 24 hours after birth from August 2016 to April 2019 and underwent head MRI and DTI before discharge were enrolled. According to the discharge diagnosis, they were divided into BPD group with 48 infants and non-BPD group with 48 infants. The two groups were compared in terms of FA and ADC values of the same regions of interest on DTI image., Results: There were no significant differences in the incidence rates of periventricular/intraventricular hemorrhage, periventricular leukomalacia, and punctate white matter lesions between the two groups (P>0.05). Compared with the non-BPD group, the BPD group had significantly lower FA values and significantly higher ADC values of the posterior limb of the internal capsule, the splenium of the corpus callosum, the occipital white matter, the cerebellum, and the cerebral peduncle (P<0.05). Compared with the non-BPD group, the BPD group had a significantly higher frequency of apnea, a significantly higher proportion of infants with pneumonia or mechanical ventilation, and a significantly longer duration of assisted ventilation (P<0.05)., Conclusions: BPD may has potential adverse effects to white matter development in preterm infants, leading to delayed white matter development. Therefore, it is necessary to pay attention to the neurological function of these infants.

Objective: To study the occurrence of serious adverse events (SAEs) related to chemotherapy with CCCG-ALL-2015 regimen in children with acute lymphoblastic leukemia (ALL) and the risk factors for death after the SAEs., Methods: A retrospective analysis was performed on the medical data of 734 children with ALL. They were treated with CCCG-ALL-2015 regimen from January 2015 to June 2019. The occurrence of SAEs during the treatment was investigated. The children with SAEs were divided into a death group with 25 children and a survival group with 31 children. A multivariate logistic regression analysis was used to analyze the risk factors for death after the SAEs., Results: Among the 734 children with ALL, 56 (7.6%) experienced SAEs (66 cases) after chemotherapy, among which 41 cases occurred in the stage of remission induction therapy. Of all 66 cases of SAEs, 46 (70%) were infection-related SAEs, including 25 cases of septic shock (38%), 20 cases of severe pneumonia (30%), and 1 case of severe chickenpox (2%), and 87% of the children with infection-related SAEs had neutrophil deficiency. The most common infection sites were blood and the lungs. The most common pathogens were Gram-negative bacteria, viruses, fungi, and Gram-positive bacteria. There were 16 cases (24%) of hemorrhage-related SAEs, with 11 cases of gastrointestinal bleeding (17%), 4 cases of pulmonary bleeding (6%), and 1 case of intracranial bleeding (2%). Of all 734 children with ALL, 66 (9.0%) died, among whom 25 died due to SAEs. The treatment-related mortality rate was 3.4%, and infection (72%) and bleeding (24%) were the main causes of death. Severe pneumonia was an independent risk factor for treatment-related death in ALL children (OR=4.087, 95%CI: 1.161-14.384, P=0.028)., Conclusions: SAEs often occur in the stage of remission induction therapy, and infection-related SAEs are more common in ALL children accepting chemotherapy with CCCG-ALL-2015 regimen. The development of severe pneumonia suggests an increased risk for death in these children.

In the largest developing country, China, plastic has become a serious environmental issue because of its overuse and non-treatment. In fact, plasticizers, such as phthalate esters (PAEs), are more toxic than plastic, and their global awareness is rising. To determine the response of sensitive PAE congeners to the anthropogenic activities in a typical lake ecosystem of China, in the present study, 12 PAEs in the water and the suspended particulate matter (SPM) phases of 46 lakes in China were measured. The concentrations of all the Σ 12 PAEs in water and SPM phases ranged from 3.647 to 65.618 μg/L and 0.175 to 10.921 μg/L, respectively. Di-n-butyl phthalate (DnBP) was the predominant PAEs in the water phase, whereas diisobutyl phthalate (DIBP), DnBP, and bis(2-ethylhexyl) phthalate (DEHP) were the dominating PAEs in the SPM phase. Forty-six lakes were divided into four groups based on the anthropogenic activity intensities. The PAEs in both the water and SPM phases had increasing tendency along the human activity gradient. DIBP appears to be a sensitive PAE indicator that could distinguish the lake regions with different human industrial and agricultural activities. Dimethyl phthalate (DMP) and diethyl phthalate (DEP) are intensely affected by industrial development. DnBP and DEHP were positively correlated with agricultural activities, including the use of films and pesticides. It is suggested to control the addition and usage of PAEs in agricultural activities and improve their removal rates in industrial wastewater to reduce the PAE pollution in the water bodies in the environment management of China., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Epidemiological studies have shown that genetic factors are among the causes of schizophrenia. Galanin receptor 1 is an inhibitory receptor of galanin that is widely distributed in the central nervous system. This study mainly explored the relationship between polymorphisms of the 5' region of the GALR1 gene and schizophrenia in the northern Chinese Han population., Methods: A 1545 bp fragment of the 5' regulatory region of the GALR1 gene was amplified and sequenced in 289 schizophrenia patients and 347 healthy controls., Results: Among the haplotypes composed of the 16 detected SNPs, the haplotype H3 was identified as conferring a risk of schizophrenia ( p =0.011, OR=1.430, 95% CI=1.084-1.886). In addition, the haplotypes H4 and H7 were both protective against schizophrenia ( p =0.024, OR=0.526, 95% CI=0.298-0.927; p =0.037, OR=0.197, 95% CI=0.044-0.885, respectively). In the subgroup analysis by sex, it was found that seven SNP alleles (rs72978691, rs11662010, rs11151014, rs11151015, rs13306374, rs5373, rs13306375) conferred a risk of schizophrenia in females ( p <0.05), while allele G of rs7242919 ( p =0.007) was protective against schizophrenia in females. Moreover, the rs72978691 AA+AC genotype ( p =0.006, OR=1.874, 95% CI=1.196-2.937, power=0.780), rs7242919 CC+CG genotype ( p =0.002, OR=2.027, 95% CI=1.292-3.180, power=0.861), rs11151014 GG+GT genotype ( p =0.008, OR=1.834, 95% CI=1.168-2.879, power=0.735), rs11151015 GG+AG genotype ( p =0.002, OR=2.013, 95% CI =1.291-3.137, power=0.843), rs13306374 CC+AC genotype ( p =0.006, OR=1.881, 95% CI=1.198-2.953, power=0.788), and rs13306375 GG+AG genotype ( p =0.006, OR=1.868, 95% CI=1.194-2.921, power=0.770) increased the risk of schizophrenia in females. The haplotype FH2 consisting of rs72978691, rs11662010, rs7242919, rs11151014, rs11151015, rs13306374, rs5373, and rs13306375 may also be associated with the risk of schizophrenia in females ( p =0.024)., Conclusion: This study identified an association between polymorphisms in the 5' region of the GALR1 gene and schizophrenia, especially in females., Competing Interests: The authors declare no conflicts of interest., (© 2020 Li et al.)

The feasibility of coordinated use of water-based drilling cuttings (WDC), fly ash, and phosphogypsum (PG) as raw materials for the preparation of WDC non-autoclaved aerated concrete (WNAAC) was evaluated by laboratory experiment. The results showed that the pozzolanic reaction of the multi-component cementitious system containing 40% (in mass) of WDC is significantly promoted. Newly formed C-S-H gel and ettringite with the uniform distribution of fibrous and flake-like shape occur, presenting a denser and interlock microstructure. In addition, after cured by steam at 80 °C for 24 h, the mechanical property and unit weight of the WNAAC prepared with 40% WDC fully meet the B06, A3.5 grade of China state standard (GB/T11968-2006). Environmental performance tests confirm that the WNAAC prepared with 40% WDC does not create any secondary contamination.

Objective: Schizophrenia is a severe neurodevelopmental disorder with a complex genetic and environmental etiology. The gene encoding EF-hand domain-containing protein D2 ( EFHD2 ) may be a genetic risk locus for schizophrenia., Methods: We genotyped four EFHD2 single-nucleotide polymorphisms (281 schizophrenia cases [SCZ], 321 controls) from northern Chinese Han individuals using Sanger sequencing and polymerase chain reaction-restriction fragment length polymorphism analysis. Differences existed in genotype, allele, and haplotype frequency distributions between SCZ and control groups., Results: The rs2473357 genotype and allele frequency distributions differed between SCZ and controls; however, this difference disappeared after Bonferroni correction. Differences in rs2473357 genotype and allele frequency distributions between SCZ and controls were more pronounced in men than in women. The G allele increased schizophrenia risk (odds ratio = 1.807, 95% confidence interval = 1.164-2.803). Among six haplotypes (G-, A-, G-insC, A-C, G-C, and G-T), the G- haplotype frequency distribution differed between SCZ and controls in women; the A-C and G-C haplotype frequency distributions differed between SCZ and controls in men., Conclusions: EFHD2 may be involved in schizophrenia. Sex differences in EFHD2 genotype and allele frequency distributions existed among schizophrenia patients. Further research is needed to determine the role of EFHD2 in schizophrenia.

Microsorum pteropus has been proven to be a potential novel aquatic Cd hyperaccumulator. In this study, Non-invasive Micro-test Technology (NMT) was used to observe the ion fluxes of different M. pteropus tissues under Cd exposure. M. pteropus can hyperaccumulate more than 1000 mg/kg Cd in roots and leaves and approximately 600 mg/kg Cd in stems after seven days of exposure to 500 μM Cd, showing that this plant have a great capacity for Cd enrichment and resistance. The NMT test found H + fluxes increased in all tissues after Cd exposure, with the largest increases being observed in stems, followed by the leaves and roots. Cd 2+ fluxes showed different accumulation levels in different tissues, with low-level Cd exposure leading to influxes into roots and leaves, and high-level Cd exposure resulting in effluxes from roots. No significant influxes or effluxes were observed in leaves under high-level Cd exposure, or in stems under low- and high-levels of Cd exposure. However, transient high-level Cd exposure showed long-term Cd 2+ influxes into roots and short-term Cd 2+ effluxes out of stems and leaves. The roots of M. pteropus had greater regulation mechanisms for Cd enrichment and resistance, with influxes occurring following low-level exposure and effluxes occurring from high-level exposure. When exposed to Cd, M. pteropus stems showed less transportation and absorption. Low-level Cd exposure resulted in individual leaves directly absorbing Cd from hydroponic solutions. Different Cd enrichment and resistance mechanisms were exhibited by different M. pteropus tissues., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Abnormal RGS4 gene expression may cause neurotransmitter disorders, resulting in schizophrenia. The association between RGS4 and the risk of schizophrenia is controversial, and there has been little research on the SNPs in the promoter region of RGS4 ., Purpose: The present study was performed to detect the association between SNPs in the promoter region of the RGS4 gene and the risk of schizophrenia., Materials and Methods: In this study, the 1757-bp fragment (-1119-+600, TSS+1) of RGS4 was amplified and sequenced in 198 schizophrenia patients and 264 healthy controls of the northern Chinese Han population. Allele, genotype and haplotype frequencies were analyzed by chi-square test., Results: Four SNPs were detected in the region. LD analysis determined that rs7515900 was linked to rs10917671 (D' = 1, r 2 = 1). Therefore, the data for rs10917671 were eliminated from further analysis. Genotype TT of rs12041948 ( P = 0.009, OR = 1.829, and 95% CI = 0.038-0.766) was significantly different between the two groups in the northern Chinese Han population. In males, genotype GG of rs6678136 ( P = 0.009, OR = 2.292, and 95% CI = 1.256-4.18) and CC of rs7515900 ( P = 0.003, OR = 2.523, and 95% CI = 1.332-4.778) were significantly different., Conclusion: The results of this study suggested that genotype TT of rs12041948 in the pooled male and female samples and GG of rs6678136 and CC of rs7515900 in the male samples could be risk factors for schizophrenia. The present study is the first to detect an association between SNPs in the promoter region of the RGS4 gene and the risk of schizophrenia in the northern Chinese Han population. Functional studies are required to confirm these findings., Competing Interests: The authors declare no conflicts of interest in this work., (© 2020 Xu et al.)