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Infertility is not a fatal disease but it really produces infertility-related stress and affects individuals' quality of life to a great extent. This study aims to investigate the relations among infertility-related stress, negative emotions and quality of life in infertile outpatients, and suppose gender difference as well as Dark Triad, which contained three dark personality traits: Machiavellianism, narcissism, and psychopathy, would moderate the relations. 105 infertile outpatients age range 20-49 completed a cross-sectional questionnaire on the Fertility Quality of Life scale, the Fertility Problem Inventory, the Hospital Anxiety and Depression Scale a the Chinese version of Dirty Dozen. Results showed that negative emotions mediated the relations between infertility-related stress and quality of life. Dark Triad could not moderate the relations between infertility-related stress, negative emotions, and quality of life, but gender can moderate the associations between infertility-related stress and negative emotions. Specifically, the association between infertility-related stress and negative emotions was stronger in men than in women. Infertility-related stress has direct and indirect effects on infertile outpatients' quality of life. It is important to consider the important roles of emotions and gender difference between patients, and delivering targeted intervention programs., (© 2024. The Author(s).)

Pompano fishes have been widely farmed worldwide. As a representative commercial marine species of the Carangidae family, the golden pompano (Trachinotus blochii) has gained significant popularity in China and worldwide. However, because of rapid growth and high-density aquaculture, the golden pompano has become seriously threatened by various diseases. Cell lines are the most cost-effective resource for in vitro studies and are widely used for physiological and pathological research owing to their accessibility and convenience. In this study, we established a novel immortal cell line, GPF (Golden pompano fin cells). GPF has been passaged over 69 generations for 10 months. The morphology, adhesion and extension processes of GPF were evaluated using light and electron microscopy. GPF cells were passaged every 3 days with L-15 containing 20 % fetal bovine serum (FBS) at 1:3. The optimum conditions for GPF growth were 28 °C and a 20 % FBS concentration. DNA sequencing of 18S rRNA and mitochondrial 16S rRNA confirmed that GPF was derived from the golden pompano. Chromosomal analysis revealed that the number pattern of GPF was 48 chromosomes. Transfection experiments demonstrated that GPF could be utilized to express foreign genes. Furthermore, heavy metals (Cd, Cu, and Fe) exhibited dose-dependent cytotoxicity against GPF. After polyinosinic-polycytidylic acid (poly I:C) treatment, transcription of the retinoic acid-inducible gene I-like receptor (RLR) pathway genes, including mda5, mita, tbk1, irf3, and irf7 increased, inducing the expression of interferon (IFN) and anti-viral proteins in GPF cells. In addition, lipopolysaccharide (LPS) stimulation up-regulated the expression of inflammation-related factors, including myd88, irak1, nfκb, il1β, il6, and cxcl10 expression. To the best of our knowledge, this is the first study on the immune response signaling pathways of the golden pompano using an established fin cell line. In this study, we describe a preliminary investigation of the GPF cell line immune response to poly I:C and LPS, and provide a more rapid and efficient experimental material for research on marine fish immunology., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Ethnopharmacological Relevance: Qizhuyanggan Decoction (QZD), a traditional Chinese medicine formula, is frequently utilized in clinical practice for managing hepatic fibrosis. However, the specific target and mechanism of action of QZD for hepatic fibrosis treatment remain unknown., Aim of the Study: By combining network pharmacology, serum medicinal chemistry, and experimental validation methods, our study aimed to investigate the therapeutic effects of QZD on hepatic fibrosis, the anti-hepatic fibrosis active ingredients, and the possible mechanism of anti-hepatic fibrosis action., Materials and Methods: The study aimed to investigate the therapeutic effect of QZD on hepatic fibrosis induced by CCl 4 in SD rats, as well as its mechanism of action. The rats were anesthetized intraperitoneally using 3% pentobarbital and were executed after asphyxiation with high concentrations of carbon dioxide. Several techniques were employed to evaluate the efficacy of QZD, including ELISA, Western blot, HYP reagent assay, and various pathological examinations such as HE, Masson, Sirius Red staining, and immunohistochemistry (IHC). Additionally, serum biochemical assays were conducted to assess the effect of QZD on liver injury. Network pharmacology, UPLC, molecular docking, and molecular dynamics simulation were utilized to explore the mechanism of QZD in treating hepatic fibrosis. Finally, experimental validation was performed through ELISA, IHC, RT-qPCR, and Western blot analysis., Result: Liver histopathology showed that QZD reduced inflammation and inhibited collagen production, and QZD significantly reduced HA and LN content to treat hepatic fibrosis. Serum biochemical analysis showed that QZD improved liver injury. Network pharmacology combined with UPLC screened six active ingredients and obtained 87 targets for the intersection of active ingredients and diseases. The enrichment analysis results indicated that the PI3K/AKT pathway might be the mechanism of action of QZD in the treatment of hepatic fibrosis, and counteracting the inflammatory response might be one of the pathways of action of QZD. Molecular docking and molecular dynamics simulations showed that the active ingredient had good binding properties with PI3K, AKT, and mTOR proteins. Western blot, ELISA, PCR, and IHC results indicated that QZD may treat hepatic fibrosis by inhibiting the PI3K/AKT/mTOR pathway and suppressing M1 macrophage polarization, while also promoting M2 macrophage polarization., Conclusions: QZD may be effective in the treatment of hepatic fibrosis by inhibiting the PI3K/AKT/mTOR signaling pathway and M1 macrophage polarization, while promoting M2 macrophage polarization. This provides a strong basis for the clinical application of QZD., 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 © 2024. Published by Elsevier B.V.)

Elemene, derived from Curcuma wenyujin, one of the "8 famous genuine medicinal materials of Zhejiang province," exhibits remarkable antitumor activity. It has gained wide recognition in clinical practice for effectiveness on tumors. Dr. XIE Tian, introduced the innovative concept of "molecular compatibility theory" by combining Chinese medicine principles, specifically the "monarch, minister, assistant, and envoy" theory, with modern biomedical technology. This groundbreaking approach, along with a systematic analysis of Chinese medicine and modern biomedical knowledge, led to the development of elemene nanoliposome formulations. These novel formulations offer numerous advantages, including low toxicity, well-defined composition, synergistic effects on multiple targets, and excellent biocompatibility. Following the principles of the "molecular compatibility theory", further exploration of cancer treatment strategies and methods based on elemene was undertaken. This comprehensive review consolidates the current understanding of elemene's potential antitumor mechanisms, recent clinical investigations, advancements in drug delivery systems, and structural modifications. The ultimate goal of this review is to establish a solid theoretical foundation for researchers, empowering them to develop more effective antitumor drugs based on the principles of "molecular compatibility theory"., (© 2023. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Colorectal adenomas are an important precancerous lesion of colorectal adenoma with a high incidence. This study aims to explore new prognostic targets for colorectal adenomas through bioinformatics techniques., Materials and Methods: In this study, data from 29 colonic adenomas and 38 normal colonic mucosa in GSE37364 were analyzed to screen for differentially expressed genes (DEGs). Then, batch survival analysis, construction of risk model, mutation analysis, Cox regression analysis and expression analysis were performed on DEGs to determine the hub genes of this study. Finally, immune correlation analysis and cell experiments were carried out on the hub gene to explore its potential mechanism., Results: In our study, a total of 431 up-regulated and 809 down-regulated differentially expressed genes (DEGs) were identified. Among these, Unc-5 Netrin Receptor D (UNC5D) emerged as a pivotal gene associated with colorectal adenoma. Notably, UNC5D expression levels were found to be significantly higher in normal tissues compared to colorectal adenoma tissues. Furthermore, our analysis demonstrated that UNC5D showed promising diagnostic potential for patients with colon adenocarcinoma. In vitro experiments revealed that the overexpression of UNC5D had a profound impact on the behavior of colorectal tumor cells. Specifically, it led to a substantial reduction in the proliferation, motility, and invasion of these tumor cells. Additionally, UNC5D was shown to exert control over STAT1/STAT3 phosphorylation, which in turn regulated the expression of PD-L1 in response to interferon (IFN) stimulation. These findings highlight the significant role of UNC5D in modulating immune responses and the development of colorectal adenoma. UNC5D emerges as a potential diagnostic biomarker and an attractive immunotherapeutic target in the context of colorectal malignancies. These results call for further exploration of UNC5D-based strategies for the diagnosis and treatment of colorectal adenoma and adenocarcinoma., Conclusions: In addition to having the potential to be used as a diagnostic biomarker and an immunotherapeutic target in colorectal malignancies, UNC5D is necessary for the growth of colorectal adenomas. Additionally, UNC5D controlled STAT1/STAT3 phosphorylation to suppress the growth of colorectal cancers by regulating IFN-induced PD-L1 expression.

Angelicae Sinensis Radix is one of the main Chinese medicinal materials with both medicinal and edible values. It has the functions of tonifying and activating blood, regulating menstruation and relieving pain, and moistening intestines to relieve constipation. It is mainly produced in the southeastern Gansu province, and that produced in Minxian, Gansu is praised for the best quality. The chemical components of Angelicae Sinensis Radix mainly include volatile oils, organic acids, and polysaccharides, which have anti-inflammatory, pain-relieving, anti-tumor, anti-oxidation, immunomodulatory and other pharmacological effects. Therefore, this medicinal material is widely used in clinical practice. By reviewing the relevant literature, this study systematically introduced the research status about the chemical constituents and pharmacological effects of processed Angelicae Sinensis Radix products, aiming to provide a theoretical reference and support for the future research, development, and clinical application of related drugs.

Bronchopulmonary dysplasia (BPD) is the most common complication of prematurity involving both pre- and post-natal factors. A large, prospective, longitudinal cohort study was conducted to determine whether inflammation-related factors are associated with an increased risk of BPD in preterm infants who were born at a gestational age < 32 weeks, < 72 h after birth and respiratory score > 4. The study included infants from 25 participating hospitals in China between March 1, 2020 and March 31, 2022. The primary outcomes were BPD and severity of BPD at 36 weeks post-menstrual age. A total of 1362 preterm infants were enrolled in the study. After exclusion criteria, the remaining 1088 infants were included in this analysis, of whom, 588 (54.0%) infants were in the BPD group and 500 (46.0%) were in the non-BPD group. In the BPD III model, the following six factors were identified: birth weight (OR 0.175, 95% CI 0.060-0.512; p = 0.001), surfactant treatment (OR 8.052, 95% CI 2.658-24.399; p < 0.001), mean airway pressure (MAP) ≥ 12 cm H 2 O (OR 3.338, 95% CI 1.656-6.728; p = 0.001), late-onset sepsis (LOS) (OR 2.911, 95% CI 1.514-5.599; p = 0.001), ventilator-associated pneumonia (VAP) (OR 18.236, 95% CI 4.700-70.756; p < 0.001) and necrotizing enterocolitis (NEC) (OR 2.725, 95% CI 1.182-6.281; p = 0.019). Premature infants remained at high risk of BPD and with regional variation. We found that post-natal inflammation-related risk factors were associated with an increased risk of severe BPD, including LOS, VAP, NEC, MAP ≥ 12 cm H 2 O and use of surfactant., (© 2023. Springer Nature Limited.)

Objectives: To investigate the risk factors and prognosis of hypotension within 72 hours after birth in extremely preterm infants., Methods: A retrospective analysis was conducted on clinical data of extremely preterm infants admitted to the Children's Hospital of Zhejiang University School of Medicine from January 2019 to April 2022. Based on the presence of hypotension within 72 hours after birth, the eligible infants were divided into a hypotension group (41 cases) and a normotension group (82 cases). The clinical characteristics, echocardiographic parameters within 72 hours after birth, and early complications were compared between the two groups. Multivariate logistic regression analysis was used to explore the risk factors for hypotension within 72 hours after birth, and receiver operating characteristic curve analysis was performed to evaluate the predictive value of relevant indicators for the occurrence of hypotension within 72 hours after birth in the preterm infants., Results: The proportion of infants who required medication or surgical closure of patent ductus arteriosus (PDA), the proportions of infants with intraventricular hemorrhage ≥ grade III and severe pulmonary hemorrhage, and the mortality rate within 7 days in the hypotension group were significantly higher than those in the normotension group ( P <0.05). Multivariate logistic regression analysis showed that lower birth weight, larger PDA diameter, and hemodynamically significant PDA were risk factors for the occurrence of hypotension within 72 hours after birth in extremely preterm infants ( P <0.05). The receiver operating characteristic curve analysis showed that the combination of birth weight, PDA diameter, and hemodynamically significant PDA had an area under the curve of 0.873 (95% CI : 0.802-0.944, P <0.05) for predicting hypotension within 72 hours after birth, with a sensitivity of 73.2% and specificity of 91.5%., Conclusions: Hypotension within 72 hours after birth is closely related to birth weight and PDA, and increases the risk of early severe complications and mortality in extremely preterm infants.

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been widely used in the closure of ductus arteriosus in premature infants. We aimed to develop and validate an interpretable machine-learning model for predicting the efficacy of NSAIDs for closing hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants., Methods: We assessed 182 preterm infants ≤ 30 weeks of gestational age first treated with NSAIDs to close hsPDA. According to the treatment outcome, patients were divided into a "success" group and "failure" group. Variables for analysis were demographic features, clinical features, as well as laboratory and echocardiographic parameters within 72 h before medication use. We developed the machine-learning model using random forests. Model performance was assessed by the area under the receiver operating characteristic curve (AUC). Variable-importance and marginal-effect plots were constructed to explain the predictive model. The model was validated using an external cohort of two preterm infants who received ibuprofen (p.o.) to treat hsPDA., Results: Eighty-three cases (45.6%) were in the success group and 99 (54.4%) in the failure group. Infants in the success group were associated with maternal chorioamnionitis ( p  = 0.002), multiple births ( p  = 0.007), gestational age at birth ( p  = 0.020), use of indometacin ( p  = 0.007), use of inotropic agents ( p  < 0.001), noninvasive ventilation ( p  = 0.001), plasma albumin level ( p  < 0.001), PDA size ( p  = 0.038) and Vmax ( p  = 0.013). Multivariable binary logistic regression analysis showed that maternal chorioamnionitis, multiple births, use of indomethacin, use of inotropic agents, plasma albumin level, and PDA size were independent risk factors influencing the efficacy of NSAIDs ( p  < 0.05). The AUC of the random forest model was 0.792. The top-three features contributing most to the model in the variable-importance plot were the plasma albumin level and platelet count 72 h before treatment and 24-h urine volume before treatment. In the external cohort, treatment succeeded in one case and failed in the other. The probabilities of success and failure predicted by the random forest model were 60.2% and 48.4%, respectively., Conclusion: Based on clinical, laboratory, and echocardiographic features before first-time NSAIDs treatment, we constructed an interpretable machine-learning model, which has a certain reference value for predicting the closure of hsPDA in premature infants under 30 weeks of gestational age., 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., (© 2023 Liu, Zheng, Chen, Zhang, Li and Shi.)

Panax notoginseng contains triterpene saponins, flavonoids, amino acids, polysaccharides, volatile oil and other active components, which have the effects of promoting blood circulation, stopping bleeding, removing blood stasis, etc. This study summarized the herbal research, chemical constituents and main pharmacological activities of P. notoginseng, and based on the theory of Q-markers of traditional Chinese medicine, predicted and analyzed the Q-markers of P. notoginseng from the aspects of plant kinship, efficacy, drug properties, measurability of chemical components, etc. It was found that ginsenosides Rg&#95;1, Re, and Rb&#95;1 with specific content ratio, ginsenosides Rb&#95;2, Rb&#95;3, Rc, Rd, Rh&#95;2, and Rg&#95;3, notoginseng R&#95;1, dencichine and quercetin could be used as potential Q-markers of P. notoginseng, which facilitated the formulation of quality standards reflecting the efficacy of P. notoginseng.

The future of work has become a prominent topic for research and policy debate. However, the debate has focused entirely on paid work, even though people in industrialized countries on average spend comparable amounts of time on unpaid work. The objectives of this study are therefore (1) to expand the future of work debate to unpaid domestic work and (2) to critique the main methodology used in previous studies. To these ends, we conducted a forecasting exercise in which 65 AI experts from the UK and Japan estimated how automatable are 17 housework and care work tasks. Unlike previous studies, we applied a sociological approach that considers how experts' diverse backgrounds might shape their estimates. On average our experts predicted that 39 percent of the time spent on a domestic task will be automatable within ten years. Japanese male experts were notably pessimistic about the potentials of domestic automation, a result we interpret through gender disparities in the Japanese household. Our contributions are providing the first quantitative estimates concerning the future of unpaid work and demonstrating how such predictions are socially contingent, with implications to forecasting methodology., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lehdonvirta et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Perinatal Ureaplasma infection is associated with a variety of adverse outcomes and neonatal diseases. This meta-analysis is to evaluate current evidence evaluating the association between Ureaplasma and adverse pregnancy outcomes and bronchopulmonary dysplasia (BPD) in preterm infants., Methods: We searched for published articles on Ureaplasma, preterm and BPD in PubMed, the Cochrane Library, and Embase databases posted before August 28, 2021. In addition, the references of these articles were screened. A random/fixed-effect model was used to synthesize predefined outcomes., Results: A total of 19 cohort studies involving 11,990 pregnancy women met our inclusion criteria. Pregnancy Ureaplasma positive increased the risk of preterm birth [odds ratios (OR) 2.76, 95% confidence intervals (CI) 1.63-4.68], BPD (OR 2.39 95% CI 1.73-3.30), chorioamnionitis (OR 2.71, 95% CI 2.02-3.64) and premature rupture of membranes (PROM, OR 2.19, 95% CI 1.34-3.58)., Conclusions: Pregnancy Ureaplasma positive may increase the risk of developing preterm birth, chorioamnionitis, PROM and BPD in the preterm infant. The evidence base is, however, of low quality and well-designed studies are needed., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Omphalocele is a common congenital defect of the abdominal wall, management of giant omphalocele (GO) is particularly for pediatric surgeons and neonatologists worldwide. The current study aimed to review and summarize the clinical features and prognosis in neonates with GO complicated with pulmonary hypertension (PH), which is associated with increased mortality, while in hospital., Materials and Methods: Medical records of infants with GO between July 2015 and June 2020 were retrospectively analyzed. The patients enrolled were divided into PH and non-PH groups based on the presence or absence of PH, and patients with PH were divided into death and survival groups based on survival status. Clinical characteristics and outcomes were compared between groups, respectively. The risk factors for PH were analyzed by binary logistic regression., Results: In total, 67 neonates were identified as having GO and 24 (35.8%) were complicated with PH. Infants with PH were associated with intubation within 24 h after birth ( p = 0.038), pulmonary dysplasia ( p = 0.020), presence of patent ductus arteriosus (PDA; p = 0.028), a staged operation ( p = 0.002), longer mechanical ventilation days ( p < 0.001), oxygen requirement days ( p < 0.001), parenteral nutrition (PN) days ( p < 0.001), length of neonatal intensive care unit (NICU) or hospital stay ( p = 0.001 and 0.002, respectively), and mortality ( p = 0.001). The results of multivariable logistic regression analysis revealed that a staged operation was independently associated with PH. In addition, PH patients with lower birth weight, higher peak of pulmonary arterial systolic pressure, and refractory to pulmonary vasodilators (PVD) had increased mortality., Conclusion: Pulmonary hypertension is a serious complication and significantly increases the mortality and morbidities in infants with a GO. In addition, early and serial assessment of PH by echocardiography should be a routine screening scheme, especially in the neonatal omphalocele population who required a staged surgical repair. Clinicians should be aware that infants with PH who had low weight, severe and refractory PH have a higher risk of death., 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 Liu, Du, Ma, Chen and Shi.)

Objectives: To investigate the risk factors and short-term prognosis of early pulmonary hypertension (PH) in preterm infants. Methods: A retrospective case-control study was performed in preterm infants (gestational age <32 weeks) in the neonatal intensive care unit (NICU) of the Children's Hospital, Zhejiang University School of Medicine from January 2012 to December 2019. Eighty preterm infants with a diagnosis of PH between 3 and 14 days (early PH group) were matched in gestational age and sex with the controls (1∶2) of the same period in NICU. Perinatal clinical records, complications, echocardiography and early outcomes were collected. Characteristics and outcomes were compared between the two groups with t -test, nonparametric test or Chi-square test. Multivariate Logistic regression was used to analyze the predictive factors of early PH. Results: The gestational age of the early PH group and the control group were both (27.9±1.4) weeks, and 52 (65.0%) and 104 (65.0%) were males in each group, respectively. Univariate analysis showed that birth weights were lower in the early PH group than those in the control group (1 030 (850, 1 200) vs. 1 110 (1 000, 1 278) g, Z= -3.27, P= 0.001). The early PH group had higher rates of pregnancy-induced hypertension, prolonged rupture of membranes (PROM) >1 week, born by caesarean, small for gestational age (SGA), 1 and 5 min Apgar score ≤7 scores, neonatal respiratory distress syndrome (RDS) and hemodynamic significant patent ductus arteriosus (hsPDA) (12.5% (10/80) vs. 3.8% (6/160), 11.2% (9/80) vs. 3.8% (6/160), 48.8% (39/80) vs. 28.8% (46/160), 10.0% (8/80) vs. 1.9% (3/160), 70.8% (51/72) vs. 51.7% (74/143), 50.0% (36/72) vs. 20.3% (29/143), 88.8% (71/80) vs. 59.4% (95/160), 85.0% (68/80) vs. 22.5% (36/160), χ 2 = 6.56, 5.12, 3.31, 8.05, 7.17, 20.05, 21.58, 84.84, all P <0.05). Multivariate Logistic regression analysis showed that the independent predictive factors of early PH were PROM >1 week, SGA, 5 min Apgar score ≤7 scores, nenonatal RDS and hsPDA ( OR= 10.40, 18.61, 4.47, 4.13, 20.10, 95% CI 1.93-56.12, 2.82-122.76, 1.91-10.46, 1.50-11.39, 8.28-48.80, all P <0.05),respectively. Infants with early PH had higher incidence of bronchopulmonary dysplasia (BPD), BPD associated PH, severe intraventricular hemorrhage (IVH), extrauterine growth retardation (EUGR), laser treatment for retinopathy of prematurity (ROP) and mortality than the controls (all P< 0.05). The duration of invasive mechanical ventilation was also longer in the early PH group than that in the control group ( P< 0.05). Conclusions: Risk of early PH will be increased in preterm infants with PROM >1 week, SGA, 5 min Apgar score ≤7 scores, and comorbidities of nenonatal RDS and hsPDA. Early PH is associated with increased mortality, BPD, BPD associated PH, severe IVH, EUGR and laser treatment for ROP.

Vibrational properties associated with the intra- and intermolecular bonding of the crystalline Dibenz[a,h]anthracene at low temperatures are investigated by Raman scattering. A complete characterization of phonon spectra is given for this material. In the 120-150 K temperature region, several lattice modes show abrupt changes of splitting and the discontinuities in the temperature shift, but no emergence of new modes. Moreover, the intensity ratio of I 68 / 38 is greater than 1 below 130 K. Meanwhile, the aromatic C-C stretching modes exhibit anomalous behaviors in frequencies, widths, and intensities at about 130 K. These spectroscopic results demonstrate a disorder-order transition occurred at about 130 K. However, the modes, corresponding to C-H out-of-plane bending, C-H in-plane bending, and/or C-H rocking, have no significant change in the whole temperature range. It indicates that the transition mainly results from the change of the tilt angle between the molecules. Our work is of great significance to understand the internal vibrational properties of Dibenz[a,h]anthracene, and it also provides considerable supports for the further study of this material., 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 © 2022 Elsevier B.V. All rights reserved.)

Aim: Gut microbiota is of crucial importance to cardiac health. Astragaloside IV (AS-IV) is a main active ingredient of Huangqi, a traditional edible and medicinal herb that has been shown to have beneficial effects on cardiac fibrosis (CF). However, it is still uncertain whether the consumption of AS-IV alleviates cardiac fibrosis through the gut microbiota and its metabolites. Therefore, we assessed whether the anti-fibrosis effect of AS-IV is associated with changes in intestinal microbiota and fecal metabolites and if so, whether some specific gut microbes are conducive to the benefits of AS-IV., Methods: Male C57BL-6J mice were subcutaneously injected with isoprenaline (ISO) to induce cardiac fibrosis. AS-IV was administered to mice by gavage for 14 days. The effects of AS-IV on cardiac function, myocardial enzyme, cardiac weight index (CWI), and histopathology of ISO-induced CF mice were investigated. Moreover, 16S rRNA sequencing was used to establish gut-microbiota profiles. Fecal-metabolites profiles were established using the liquid chromatograph-mass spectrometry (LC-MS)., Results: AS-IV treatment prevented cardiac dysfunction, ameliorated myocardial damage, histopathological changes, and cardiac fibrosis induced by ISO. AS-IV consumption increased the richness of Akkermansia, Defluviitaleaceae&#95;UCG-011, and Rikenella. AS-IV also modulated gut metabolites in their feces. Among 141 altered gut metabolites, amino acid production was sharply changed. Furthermore, noticeable correlations were found between several specific gut microbes and altered fecal metabolites., Conclusions: An increase of Akkermansia, Defluviitaleaceae&#95;UCG-011, and Rikenella abundance, and modulation of amino acid metabolism, may contribute to the anti-fibrosis and cardiac protective effects of Astragaloside IV., 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 Du, Shi, Chen, Hu, Zuo, Xiong and Cao.)

Objectives: To study the effect of timing of surgical ligation of patent ductus arteriosus (PDA) on the prognosis of very low birth weight infants (VLBWI)., Methods: The medical data of VLBWI who underwent transthoracic ligation for PDA from June 2018 to May 2021 were reviewed retrospectively. The infants were divided into early ligation group (≤21 days of age) and late ligation group (>21 days of age) based on the age of ligation. The two groups were compared in terms of perioperative clinical features, complications, and mortality. The risk factors for early surgical ligation were analyzed., Results: A total of 72 VLBWI were enrolled, with 19 infants (26%) in the early ligation group and 53 infants (74%) in the late ligation group. There were significant differences in birth weight, gestational age, weight at operation, days of age at operation, rates of preoperative invasive and noninvasive mechanical ventilation, incidence rate of pulmonary hemorrhage, incidence rate of hypotension, preoperative PDA internal diameter (mm/kg), intraoperative PDA external diameter (mm/kg), incidence rate of post-ligation cardiac syndrome, and duration of postoperative invasive mechanical ventilation between the two groups ( P <0.05). A binary logistic regression analysis showed that pulmonary hemorrhage was an indication of early surgical ligation of PDA ( P <0.05). There were no significant differences in the incidence rates of post-operative complications and the mortality rate between the early ligation and late ligation groups., Conclusions: Early surgical ligation may be performed for VLBWI who are experiencing pulmonary hemorrhage and hemodynamically significant PDA confirmed by cardiac ultrasound after birth. However, post-ligation cardiac syndrome should attract enough attention. In addition, early surgical ligation of PDA does not increase the risk of surgery-related and long-term complications or death, indicating that it is a safe and feasible treatment option.

With growing flexibilization in the labour market, continuous and consistent career trajectories have become less the norm, and workers facing unemployment may need to look for employment opportunities outside the occupation they are trained in. But what are their employment chances? And what are the chances of returning to the occupation they were trained in after having worked in a different occupation? Despite much research on how employers evaluate job candidates with vertical skill mismatches (e.g. over-qualification and under-qualification) and unemployment, there is little research to investigate how employers view horizontal mismatch in comparison to unemployment, and whether a combination of both generates multiplicative negative effects. Using data gathered from an employer survey experiment in Switzerland and Greece, we find that in Switzerland both unemployment and horizontal mismatch significantly reduce employment chances, but the scarring effect of horizontal mismatch is much stronger. In contrast, in Greece horizontal mismatch significantly reduces employment chances but unemployment does not. Furthermore, we found that horizontal mismatch scarring is significantly stronger in Switzerland than in Greece. These findings suggest that the scarring effects of both unemployment and horizontal mismatch vary across contexts. Further analyses show that, rather than experiencing multiplicative scarring effects, unemployment does not add further disadvantages to mismatched candidates in either country, highlighting the importance of occupational specificity of skills in labour market matching. Overall, these findings facilitate a more nuanced understanding of demand-side labour market processes, highlighting the distinct interactive effects of unemployment and horizontal mismatch across national contexts., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: To study the features of catheter-related bloodstream infection (CRBSI) or central line-associated bloodstream infection (CLABSI) after peripherally inserted central catheterization (PICC) in neonates admitted to the neonatal intensive care unit (NICU) and the risk factors for CRBSI or CLABSI., Methods: A retrospective analysis was performed on the medical data of the neonates who were treated and required PICC in the NICU of the Children's Hospital, Zhejiang University School of Medicine from June 1, 2018 to May 1, 2020. The catheterization-related data were collected, including placement time, insertion site, removal time, and antimicrobial lock of PICC. The multivariate logistic regression model was used to investigate the risk factors for CRBSI or CLABSI in the neonates., Results: A total of 446 neonates were enrolled, with a mean gestational age of (30.8±4.0) weeks, a mean birth weight of (1 580±810) g, a median age of 9 days, and a median duration of PICC of 18 days. The incidence rates of CLABSI and CRBSI were 5.6 and 1.46 per 1 000 catheter days, respectively. Common pathogens for CLABSI caused by PICC included Staphylococcus epidermidis ( n =19) and Klebsiella pneumoniae ( n =11), and those for CRBSI caused by PICC included Klebsiella pneumoniae ( n =6). The risk of CLABSI caused by PICC increased significantly with prolonged durations of PICC and antibiotic use, and the PICC-related infection probability at head and neck was significantly lower than that in the upper and low limbs ( P <0.05), while the above conditions were more obvious in neonates with a birth weight of <1 500 g. The risk of CRBSI caused by PICC decreased with the increase in gestational age ( P <0.05)., Conclusions: CRBSI and CLABSI remain serious issues in NICU nosocomial infection. The identification of the risk factors for CRBSI and CLABSI provides a basis for improving the quality of clinical care and management.

Objectives: To study the value of bedside echocardiography in predicting persistent patency of the ductus arteriosus during the early postnatal period in very low birth weight (VLBW) infants., Methods: A retrospective analysis was performed for 51 VLBW infants who were admitted from March 2020 to June 2021, with an age of ≤3 days and a length of hospital stay of ≥14 days. According to the diameter of patent ductus arteriosus (PDA) on days 14 and 28 after birth, the infants were divided into three groups: large PDA group (PDA diameter ≥2 mm), small PDA group (PDA diameter <2 mm), and PDA closure group (PDA diameter =0 mm). The echocardiographic parameters measured at 72 hours after birth were compared among the three groups. The receiver operating characteristic (ROC) curve was used to evaluate the value of the echocardiographic parameters in predicting persistent patency of the ductus arteriosus (PDA≥2 mm) at the ages of 14 and 28 days., Results: On day 14 after birth, there were 17 infants in the large PDA group, 11 in the small PDA group, and 23 in the PDA closure group. On day 28 after birth, there were 14 infants in the large PDA group, 9 in the small PDA group, and 26 in the PDA closure group. There were significant differences in gestational age, birth weight, rate of pulmonary surfactant use, and incidence rate of hypotension among the three groups ( P <0.05). PDA diameter, end-diastolic velocity of the left pulmonary artery, left ventricular output, and left ventricular output/superior vena cava flow ratio measured at 72 hours after birth were associated with persistent patency of the ductus arteriosus at the ages of 14 and 28 days ( P <0.05), and the ratio of the left atrium to aorta diameter was associated with persistent patency of the ductus arteriosus at the age of 28 days ( P <0.05). The ROC curve analysis showed that the area under the curve that the PDA diameter measured at 72 hours after birth predicting the persistent patency of the ductus arteriosus at the ages of 14 and 28 days was the largest (0.841 and 0.927 respectively), followed by end-diastolic velocity of the left pulmonary artery, with the area under the curve of 0.793 and 0.833 respectively., Conclusions: The indicators obtained by beside echocardiography at 72 hours after birth, especially PDA diameter and end-diastolic velocity of the left pulmonary artery, can predict persistent patency of the ductus arteriosus at the ages of 14 and 28 days in VLBW infants, which provides a basis for the implementation of early targeted treatment strategy for PDA.

To investigate effect and mechanism of Ziqi Ruangan Decoction (ZQRGD) on hepatic fibrosis in rats. Rats were randomly assigned to blank group, model group, colchicine group, ZQRGD high-dose group, ZQRGD middle-dose group, and ZQRGD low-dose group. All groups except group A were intraperitoneally injected with 40% CCl4/olive oil for 8 weeks; group C was then given intragastric colchicine administration. Groups D, E, and F were intragastrically dosed with ZQRGD. Compared with the colchicine group, the superoxide dismutase (SOD) activity of each dose group of ZQRGD significantly increased. TNF-α and IL-6 concentration significantly decreased in each drug intervention group, while these significantly decreased in the high-dose and medium-dose ZQRGD groups. The expression of α-SMA and collagen I significantly decreased in the drug treatment group compared with the model group, as did the expression of PI3K, AKT, and mTOR. Ziqi Ruangan Decoction had a favorable anti-liver fibrosis effect and the mechanism is related to anti-oxidative stress, anti-inflammation, the inhibition of the PI3K/Akt/mTOR signaling pathway, and the inhibition of hepatic stellate cell activation.

Background: The outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread to become a global emergency since December 2019. Chinese herbal medicine plays an important role in the treatment of COVID-19. Chinese herbal medicine honeysuckle is an extremely used traditional edible and medicinal herb. Many trials suggest that honeysuckle has obtained a good curative effect for COVID-19; however, no systematic evaluation on the clinical efficacy of honeysuckle in the treatment of COVID-19 is reported. This study aimed to evaluate the efficacy and safety of Chinese herbal medicine honeysuckle in the treatment of COVID-19. Methods: Seven electronic databases (PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and China Biology Medicine) were searched to identify randomized controlled trials (RCTs) of honeysuckle for adult patients (aged ≥ 18 years) with COVID-19. The Cochrane Risk of Bias Tool was applied to assess the methodological quality of trials. Review Manager 5.3 software was used for data analysis. Results: Overall, nine RCTs involving 1,286 patients were enrolled. Our meta-analyses found that combination therapy of honeysuckle and conventional therapy was more effective than conventional therapy alone in lung computed tomography (CT) [relative risk (RR) = 1.24, 95% confidence interval (95%CI) (1.12, 1.37), P < 0.0001], clinical cure rate [RR = 1.21, 95%CI (1.12, 1.31), P < 0.00001], and rate of conversion to severe cases [RR = 0.50, 95%CI (0.33, 0.76), P = 0.001]. Besides, combination therapy can improve the symptom score of fever, cough reduction rate, symptom score of cough, and inflammatory biomarkers (white blood cell (WBC) count; C-reactive protein (CRP)) ( P < 0.05). Conclusion: Honeysuckle combined with conventional therapy may be beneficial for the treatment of COVID-19 in improving lung CT, clinical cure rate, clinical symptoms, and laboratory indicators and reducing the rate of conversion to severe cases. Besides, combination therapy did not increase adverse drug events. More high-quality RCTs are needed in the future., 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 © 2021 Du, Shi, Cao, Chen, Zuo and Hu.)

Objective: The aim of the present study was to evaluate the bioequivalence and safety of two types of daclatasvir hydrochloride tablets administered to healthy Chinese subjects under fasting and postprandial conditions., Materials and Methods: A total of 72 healthy Chinese subjects were randomly divided into two groups: the fasting group (n = 36) and the postprandial group (n = 36). A dose of 60 mg of both the test and reference preparations of the daclatasvir hydrochloride tablets was taken orally under fasting and postprandial conditions., Results: The main plasma pharmacokinetic parameters of the test and reference preparations in the fasting group were as follows: T 1/2 was 9.82 ± 1.00 and 9.67 ± 0.99 hours, respectively; t max was 1.00 hour in both; C max was 1,528.25 ± 428.80 and 1,504.25 ± 414.50 ng/mL -1 , respectively; AUC 0-t was 14,553.04 ± 4,013.26 and 14,391.97 ± 4,078.18 h/ng/mL -1 , respectively; the AUC 0-∞ was 14,660.80 ± 4,018.37 and 14,494.85 ± 4,095.57 ng/mL -1 , respectively. Meanwhile, the main plasma pharmacokinetic parameters of the test and reference preparations in the postprandial group were as follows: T 1/2 was 10.18 ± 1.38 and 10.18 ± 1.69 hours, respectively; t max was 2.00 and 1.75 hours, respectively; C max was 974.92 ± 248.50 and 981.44 ± 237.11 ng/mL -1 , respectively; AUC 0-t was 9,597.00 ± 3,094.28 and 9,982.83 ± 3,512.07 h/ng/mL -1 , respectively; AUC 0-∞ was 9,712.92 ± 3,130.43 and 10,113.97 ± 3,593.47 ng/mL -1 , respectively., Conclusion: Both types of daclatasvir hydrochloride tablets demonstrated good safety levels in healthy Chinese subjects under both fasting and postprandial conditions. Moreover, the two preparations were bioequivalent.

Background: Sorafenib is the first-line treatment for patients with advanced hepatocellular carcinoma (HCC). Y-box binding protein 1 (YB-1) is closely correlated with tumors and drug resistance. However, the relationship between YB-1 and sorafenib resistance and the underlying mechanism in HCC remain unknown., Aim: To explore the role and related mechanisms of YB-1 in mediating sorafenib resistance in HCC., Methods: The protein expression levels of YB-1 were assessed in human HCC tissues and adjacent nontumor tissues. Next, we constructed YB-1 overexpression and knockdown hepatocarcinoma cell lines with lentiviruses and stimulated these cell lines with different concentrations of sorafenib. Then, we detected the proliferation and apoptosis in these cells by terminal deoxynucleotidyl transferase dUTP nick end labeling, flow cytometry and Western blotting assays. We also constructed a xenograft tumor model to explore the effect of YB-1 on the efficacy of sorafenib in vivo . Moreover, we studied and verified the specific molecular mechanism of YB-1 mediating sorafenib resistance in hepatoma cells by digital gene expression sequencing (DGE-seq)., Results: YB-1 protein levels were found to be higher in HCC tissues than in corresponding nontumor tissues. YB-1 suppressed the effect of sorafenib on cell proliferation and apoptosis. Consistently, the efficacy of sorafenib in vivo was enhanced after YB-1 was knocked down. Furthermore, KEGG pathway enrichment analysis of DGE-seq demonstrated that the phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway was essential for the sorafenib resistance induced by YB-1. Subsequently, YB-1 interacted with two key proteins of the PI3K/Akt signaling pathway (Akt1 and PIK3R1) as shown by searching the BioGRID and HitPredict websites. Finally, YB-1 suppressed the inactivation of the PI3K/Akt signaling pathway induced by sorafenib, and the blockade of the PI3K/Akt signaling pathway by LY294002 mitigated YB-1-induced sorafenib resistance., Conclusion: Overall, we concluded that YB-1 augments sorafenib resistance through the PI3K/Akt signaling pathway in HCC and suggest that YB-1 is a key drug resistance-related gene, which is of great significance for the application of sorafenib in advanced-stage HCC., Competing Interests: Conflict-of-interest statement: The authors declare that there are no conflicts of interest in our study., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: Arteriovenous fistulas are a principal mainstay of long-term dialysis access for patients with end stage renal failure. However, the patency of arteriovenous fistulas is limited, often requiring percutaneous transluminal angioplasty as a salvage procedure. We report a case of percutaneous method of arteriovenous fistula salvage., Methods: A gentleman with brachiocephalic arteriovenous fistula created in 2015 was admitted under us for dialysis access issue. His fistula history was notable for recurrent and refractory venous outflow stenosis of the cephalic vein and the cephalic arch with multiple previous interventions. Ultrasound showed cephalic arch occlusion with high venous pressures. He underwent left brachicephalic fistula percutaneous bypass. We describe the percutaneous creation of a brachial-subclavian arteriovenous fistula via a bypass graft from a worsening brachial-cephalic fistula with cephalic arch occlusion that is not amendable to angioplasty., Results: Final angiogram showed smooth flow to central vein. He is 2 years post procedure, and his fistula remained patent with no interventions required., Conclusion: Percutaneously created jump bypass grafts can reliably produce sustained long-term patency.

Objective: To study the clinical effect of multi-oil fat emulsion for parenteral nutrition support in extremely low birth weight (ELBW) infants., Methods: A retrospective analysis was performed for 49 ELBW infants who were admitted from January 1, 2018 to July 30, 2020, with an age of ≤14 days on admission and a duration of parenteral nutrition of > 14 days. According to the type of lipid emulsion received, the ELBW infants were divided into two groups: soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOF) ( n =26) and medium-chain triglycerides/long-chain triglycerides (MCT/LCT) ( n =23). The two groups were compared in terms of clinical features, complications, nutrition support therapy, and outcome., Results: The 49 ELBW infants had a mean birth weight of (892±83) g and a mean gestational age of (28.2±2.3) weeks. There was no significant difference between the two groups in the incidence rates of hemodynamically significant patent ductus arteriosus, intraventricular hemorrhage, neonatal necrotizing enterocolitis, retinopathy of prematurity, bronchopulmonary dysplasia (BPD), grade Ⅲ BPD, sepsis, and pneumonia ( P > 0.05). There was also no significant difference in the duration of parenteral nutrition, the age of total enteral nutrition, and head circumference/body length/body weight at discharge between the two groups ( P > 0.05). Of all the infants, 22 (45%) had parenteral nutrition-associated cholestasis (PNAC), with 13 (50%) in the SMOF group and 9 (39%) in the MCT/LCT group but there was no significant difference in the incidence of PNAC between the two groups ( P > 0.05); however, the infants with PNAC in the SMOF group had significantly lower peak values of direct bilirubin and alanine aminotransferase than those in the MCT/LCT group ( P < 0.05)., Conclusions: The application of multi-oil fat emulsion in ELBW infants does not reduce the incidence rate of complications, but compared with MCT/LCT emulsion, SMOF can reduce the severity of PNAC in ELBW infants.

CaWRKY40 was previously found to be transcriptionally up-regulated by Ralstonia solanacearum inoculation (RSI) or heat stress (HS), but the underlying mechanism remains unknown. Herein, we report that a double-W box-element (DWE) in the promoter of CaWRKY40 is critical for these responses. The upstream W box unit WI of this composite element is crucial for preferential binding by CaWRKY40 and responsiveness to RSI or HS. DWE-driven CaWRKY40 can be transcriptionally and nonspecifically regulated by itself and by CaWRKY58 and CaWRKY27. The DWE was also found in the promoters of CaWRKY40 orthologs, including AtWRKY40, VvWRKY40, GmWRKY40, CplWRKY40, SaWRKY40, SpWRKY40, NtWRKY40, and NaWRKY40. DWE AtWRKY40 was analogous to DWE CaWRKY40 by responding to RSI or HS and AtWRKY40 expression. These data suggest that a conserved response of plants to pathogen infection or HS is probably mediated by binding of the DWE by WRKY40., (© 2020 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.)

Background: Post-discharge optimal growth and nutritional intake have beneficial effects for neurodevelopment in preterm very low birth weight infants (VLBWIs) with extrauterine growth retardation (EUGR). The present study aimed to compare the effects of a nutrient-dense formula (NDF) to a post-discharge formula (PDF) on post-discharge growth of preterm VLBWIs with EUGR., Methods: Forty-eight preterm VLBWIs with EUGR at discharge were randomised to receive NDF (100 kcal per 100 mL; 2.6 g protein per 100 mL) or PDF (74 kcal per 100 mL; 1.95 g protein per 100 mL) for 1-6 months until body weight reached the 50th percentile on growth charts with corrected age. Volume, nutrient intake, anthropometry and biochemistry data were collected., Results: Volume intake was lower in the NDF group than the PDF group during the first 2 months of feeding (P = 0.039 and 0.018, respectively).There were no significant differences in volume intake during months 2-6 of feeding. Energy, protein, carbohydrate and fat intake were higher in the NDF group during months 1-6 of feeding. There were no significant differences in weight, length, and head circumference Z-scores during months 1-6 between the two groups. The △length Z-score from discharge to month 6 was significantly higher in the NDF group than the PDF group (P = 0.043). No differences existed between the two groups with respect to biochemistry., Conclusions: After discharge, preterm VLBWIs with EUGR fed a NDF gain anthropometric parameter Z-scores similar to those for a PDF within 6 months of follow-up. A NDF leading to gain in length requires further follow-up., (© 2020 The British Dietetic Association Ltd.)

The outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV) has become a most challenging health emergency. Owing to rigorous quarantine and control measures taken in China, routine neonatal health surveillance and follow-up have become challenging. Without follow-up surveillance, some rapid and progressive newborn diseases, such as bilirubin encephalopathy, may be ignored. The characteristics of onset age of kernicterus suggest that monitoring of bilirubin level at home provides a useful way to alert hospital visits and to prevent the development of extremely hyperbilirubinemia. Therefore, we developed an online follow-up program for convenient monitoring of bilirubin level of newborns that is based on our practical experiences. The aim is to make our management strategies of neonatal jaundice tailored to the infection prevention and control during the COVID-19 epidemic.

Objective: To study the clinical features of neonatal enterovirus infection, especially severe enterovirus infection., Methods: A retrospective analysis was performed for the clinical data of 244 neonates with enterovirus infection. According to the severity of infection, they were divided into a common infection group with 231 neonates and a severe infection group with 13 neonates. Clinical features were compared between the two groups., Results: Of the 244 neonates, 207 (84.8%) developed the disease in May to October, with the highest number of patients in June to July. Compared with the common infection group, the severe infection group had a significantly lower gestational age at birth and a significantly higher proportion of preterm infants (P<0.05). Compared with the common infection group, the severe infection group had a significantly earlier onset time (P<0.05) and significantly higher incidence rates of skin petechiae and ecchymosis, respiratory symptoms, sepsis-like manifestations (poor appetite, crying less, and less movement), concomitant diseases (such as pneumonia, myocarditis, necrotic hepatitis, and coagulation disorder), thrombocytopenia, prolonged prothrombin time, elevated creatine kinase-MB, and elevated alanine aminotransferase (P<0.05). The severe infection group had a significantly higher mortality rate than the common infection group (P<0.05)., Conclusions: There are significant differences in onset time, common clinical manifestations, and concomitant diseases between the neonates with common and severe enterovirus infection. In the enterovirus epidemic season, if the neonates have rashes and/or sepsis-like manifestations such as poor appetite and less movement, especially if the laboratory tests suggest liver damage and coagulation dysfunction, it is necessary to pay particular attention to the possibility of severe enterovirus infection.

Objective: To compare the clinical diagnosis and outcomes of preterm infants with bronchopulmonary dysplasia (BPD) under two different diagnostic criteria. Methods: A retrospective study was performed in 157 preterm infants who were admitted to Neonatal Intensive Care Unit of the Children's Hospital, Zhejiang University School of Medicine from January 2015 to December 2018. Enrolled infants, with gestational age <32 weeks and survived >14 days, met the 2001 National Institute of Child Health and Human Development(NICHD) definition of moderate and severe BPD or died between 14 days of postnatal age and 36 weeks owing to persistent parenchymal lung disease and respiratory failure. The severities of BPD were revaluated according to the 2018 revised definition of BPD proposed by NICHD. Characteristics and outcomes of these infants were compared with the two different diagnostic criteria with t -test, nonparametric test or Chi-square test. Results: In the 157 enrolled infants (100 males), severities of BPD were classified as moderate in 62, severe in 84 and unclassifiable in 11 according to the 2001 NICHD criteria, while grade Ⅰ in 51, Ⅱ in 29, Ⅲ in 66 and ⅢA in 11 infants respectively according to the 2018 NICHD criteria. Duration of oxygen therapy, positive pressure ventilation and endotracheal intubation in grade Ⅱinfants of 2018 criteria were much longer than that in moderate infants of 2001 criteria (80 (65, 95) vs. 65 (59, 77) d, 52 (38, 58) vs. 30 (19, 48) d, 10 (2, 17) vs. 4 (0, 12) d, Z= -2.995, -3.750, -2.073, all P< 0.05). Mortality of moderate and severe infants in 2001 criteria was 10.3% (15/146), while mortality of BPD in 2018 criteria was 16.6% (26/157). Mortality of grade Ⅲ and ⅢA BPD in 2018 criteria was much higher than mortality of severe BPD in 2001 criteria (33.8% (26/77) vs. 17.9%(15/84), χ(2)=5.357, P< 0.05). Conclusion: Definition and classification of BPD based on 2001 NICHD criteria may cause missed or unclassified cases, resulting in the underestimation of the morbidity and mortality of infants with severe BPD.

Since December 2019, the outbreak of coronavirus disease (COVID-19) has become the most serious public health issue. As the special population with immature immune function, newborns with COVID-19 have been reported. Newborns with suspected or confirmed COVID-19 should be transferred to designated hospitals for isolation treatment. An emergency transfer response plan for newborns with COVID-19 has been worked out. This plan puts forward the indications for neonatal COVID-19 transfer, organization management, protection strategies for medical staff, work procedures, and disinfection methods for transfer equipment, in order to provide guidance and suggestions for the inter-hospital transfer of suspected or confirmed neonatal COVID-19.

Objective: To evaluate the efficacy and safety of Oryz-Aspergillus enzyme and pancreatin tablets (Combizym(®)) in the treatment of postprandial distress syndrome (PDS) in the elderly, compared with gastrointestinal motility drugs. Methods: A prospective randomized controlled trial was designed and registered in the China Clinical Trials Registry (ChiCTR-IPR-16008185). The elderly patients with PDS were randomly divided into three groups, including Mosapride group with Mosapride citrate tablets 5 mg 3 times per day for 2 weeks; Combizym(®) group with Combizym tablets 244 mg 3 times per day for 2 weeks; combined treatment group with both drugs and same doses for 2 weeks. The modified Nepean dyspepsia index (NDSI) score, discomfort intensity score and PDS score were calculated on patients before treatment, at the end of first and second week of treatment, as well as 4 weeks after treatment finished, respectively. Adverse effects were evaluated. Results: A total of 323 patients from 16 tertiary hospitals in China were enrolled in this study. Among them, 105 patients were in Mosapride group, 109 in Combizym(®) group and 109 in combined treatment group. There were 148 males (45.8%) and 175 females (54.2%) with median age 71.4±9.0 years (60-100 years). Baseline characteristics of three groups were comparable. After treatment, the NDSI scores in three groups all decreased significantly ( P< 0.001), while they were similar between groups ( P> 0.05). The discomfort intensity score and PDS score in three groups showed a significant reduction after treatment ( P< 0.001), especially in the combined treatment group. Compared with Mosapride group, the scores in Combizym(®) group decreased significantly after one or two weeks [discomfort intensity score: after one week, 4.0(2.5, 8.0) vs. 6.0(3.0, 10.0); after two weeks, 3.0(0.0, 5.0) vs. 4.0(2.0, 6.0); all P< 0.05. PDS score: after one week, 6.0(3.0, 9.0) vs. 7.0(3.5, 10.5); after two weeks, 3.0(0.0, 5.0) vs. 4.0(2.0, 7.0); all P< 0.05]. The efficacy rate in all patients after first week of treatment was over 15.0%. The efficacy rates after two weeks were 55.2%, 68.8% and 73.4% in Mosapride group, Combizym(®) group and combined treatment group, respectively. After two week treatment, the efficacy rates in Combizym(®) group ( P= 0.041) and combined group ( P= 0.006) were higher than that of Mosapride group. The recurrence rate of Mosapride group was 9.5%, which was significantly higher than that of Combizym(®) group (1.8%, P< 0.05) and combined treatment group (1.8%, P< 0.05). There were no serious adverse effects in the three groups. Conclusions: The efficacy of Oryz-Aspergillus enzyme and pancreatin tablets is comparable with that of Mosapride in elderly PDS patients, with fewer adverse effects and low recurrence rate. Combination regimen indicates better efficacy than that of Oryz-Aspergillus enzyme and pancreatin tablets or Mosapride alone.

Glutamatergic dysregulation has served as one common pathophysiology of major depressive disorder (MDD) and a promising target for treatment intervention. Previous studies implicate neurotransmission via metabotropic glutamate receptors (mGluRs) and Homer1 in stress-induced anhedonia, but the mechanisms have not been well elucidated. In the present study, we used two different animal models of depression, chronic social defeat stress (CSDS) and chronic restraint stress (CRS), to investigate the expression of Homer1 isoforms and functional interaction with mGluRs. We found that chronic stress selectively upregulated the expression of Homer1b/c in the hippocampus, whereas the level of Homer1a was unchanged. Additionally, there was a significant negative correlation between the levels of Homer1-mGluR5 signaling and depressive-like behaviors. Both application of paired-pulse low-frequency stimulation (PP-LFS) and the selective group 1 mGluRs agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) significantly enhanced mGluR-dependent long-term depression (LTD) at CA3-CA1 pyramidal cell synapses in slices from susceptible mice, whereas there was no change in NMDAR-dependent LTD induced by LFS. Furthermore, these effects were associated with the internalization of surface AMPARs in hippocampal pyramidal neurons, including reduced the expression of AMPARs and amplitude of AMPARs-mediated mEPSC. Finally, we found that chronic stress activated the KR-like ER kinase-eukaryotic initiation factor 2α (PERK-eIF2α) signaling pathway, subsequently phosphorylated cAMP response element binding protein (CREB) at the S129 and reduced the BDNF level, eventually leading to the impairment of synaptic transmission and depressive-like behaviors. Therefore, our study suggests that PERK-eIF2α acts as a critical target downstream of Homer1-mGluR5 complex to mediate chronic stress-induced depressive-like behaviors, and highlights them as a potential target for the treatment of mood disorder., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Four soil conditioners, SAMMNS, CCT01, Mineral, and Tebeigai were selected for this study. The effects of the four conditioners on soil pH, bulk density, organic matter, available nutrients, texture, microaggregates, Cd available in soil, and Cd content in brown rice were investigated using field-controlled cadmium tests conducted in cadmium-contaminated paddy fields in Pingxiang. The results showed that compared to the control, soil conditioners could increase pH, bulk density, and cation exchange capacity in soil. SAMMNS and CCT01 soil conditioners increased the amount of silt and clay, but that of sand decreased, whereas the Mineral and Tebeigai soil conditioners decreased silt and clay, and sand increased. In addition to the CCT01 soil conditioner, the application of soil conditioners increased large-scale agglomerates and reduced small-scale microaggregates. The effects of soil conditioners on soil physical and chemical properties promoted the conversion of Cd from contaminated soil from high activity to low activity, which reduced available Cd content in soil (5.21%-34.78%) and Cd content in brown rice (51.39%-68.06%). Correlation analysis showed that Cd content in brown rice was significantly positively correlated with available Cd and available phosphorus in soil, whereas it was negatively correlated with pH and bulk density in soil. Considering the effects of soil and brown rice on cadmium reduction and physicochemical properties, Tebeigai soil conditioner exhibited the best repair effects, followed by SENMES and Mineral soil conditioner.

Objective: MiRNAs have been verified to play a role in the development and progression of prostate cancer (PCa). However, the role of miR-492 in PCa has not been mentioned. We aim to detect the expression of miR-492 in PCa and explore its underlying mechanism., Patients and Methods: The relative expression of miR-492 in PCa tissue samples to normal prostate tissues was detected using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The level of miR-492 in PCa-derived cell lines compared with the normal prostate cell line was also measured. Cell counting kit-8 (CCK-8) and colony formation assays were employed to investigate the cell proliferation ability. Transwell assay and wound-healing assays were utilized to explore the cell invasion and migration abilities. Luciferase assay and Western blot were utilized to explore the underlying mechanism of miR-492 in PCa cells., Results: MiR-492 expressed significantly higher in PCa tissues than that in the normal tissues. Its expression level was also over-expressed in PCa cells compared with that in the normal cells. The up-regulation of miR-492 promoted the growth, invasion, and migration of the cells, while down-regulation had the opposite effects. SOCS2 was identified as a potential target for miR-492 in PCa. Silencing of SOCS2 could neutralize the inhibitory function of miR-492 inhibitor in PCa cells., Conclusions: This study demonstrated that miR-492 was over-expressed in PCa and exerted tumor-promoting function in PCa cells via repressing SOCS2 expression. This might provide a new sight for future accurate therapy for PCa.

Objective: To investigate the long-term prognosis of neonates with necrotizing enterocolitis (NEC)., Methods: A total of 83 preterm infants with NEC who survived and were discharged between December 2014 and September 2016 were enrolled and divided into surgery group (n=57) and non-surgery group (n=26). There were 0, 33 and 24 cases of stage I, II and III NEC respectively in the surgery group and 7, 19 and 0 cases respectively in the non-surgery group. The physical development and neurodevelopmental outcomes of the infants were followed up after discharge., Results: Of the 83 infants, the mean corrected age at the end of follow-up was 21±6 months. Of the 83 infants, 31 (37%) had subnormal body weight, and the surgery group had a higher rate of subnormal body weight than the non-surgery group (P<0.05). Twenty-two infants (27%) had subnormal body length and 14 children (17%) had subnormal head circumference among the 83 infants. Eighteen infants (22%) had motor developmental delay/developmental disorders, and the surgery group had a higher incidence rate of the disorders than the non-surgery group (28% vs 8%; P<0.05). Five infants (6%) were diagnosed with cerebral palsy, among whom 4 were in the surgery group and 1 was in the non-surgery group., Conclusions: Long-term physical development and neurodevelopmental outcomes may be adversely affected in neonates with NEC, in particular in those with severe conditions who need surgical treatment, suggesting that long-term follow-up should be performed for neonates with NEC.

Objective: To study the clinical features and prognosis of bronchopulmonary dysplasia (BPD) complicated by pulmonary hypertension (PH) in preterm infants., Methods: A retrospective analysis was performed on the clinical data of 191 preterm infants with BPD., Results: In the 191 preterm infants with BPD, 37 (19.4%), all with moderate or severe BPD, developed PH beyond 36 weeks' corrected age. The incidence rates of PH in infants with moderate and severe BPD were 5.7% (5/87) and 47.8% (32/67) respectively. Gestational age and birth weight were lower in infants with PH than in those without PH (P<0.01). Infants with PH had higher incidence rates of small for gestational age (SGA), severe BPD, surgical ligation of patent ductus arteriosus (PDA), neonatal respiratory distress syndrome, hemodynamically significant PDA, and pneumonia than those without PH (P<0.01). Durations of oxygen therapy, intubation, and positive pressure ventilation were longer in infants with PH than in those without PH (P<0.01). Infants with PH had higher incidence rates of retinopathy of prematurity and extrauterine growth retardation, a higher mortality, and a longer length of hospital stay compared with those without PH (P<0.01). In the 37 infants with PH (6 with mild PH, 14 with moderate PH, and 17 with severe PH), those with mild or moderate PH all survived; 15(88%) out of 17 infants with severe PH died., Conclusions: The incidence of PH is high in preterm infants with moderate or severe BPD. Regular screening of pulmonary artery pressure is recommended for infants with BPD. Infants with low gestational age and birth weight, SGA, and severe BPD are more likely to develop PH. Infants with BPD complicated by PH have relatively high incidence rates of complications, high mortality, and poor prognosis.

Background: CHARGE syndrome is an autosomal dominant malformation disorder caused by heterozygous loss of function mutations in the chromatin remodeler CHD7, which has been estimated to occur in 1:10,000 births worldwide. It is a genetic disorder closely resembles other pattern of anomalies. Genetic testing should be pointed out as a useful method for clinical diagnosis., Case Presentation: A female infant was the second child born to a 33-year-old, gravida 3, para 2 mother. The infant was born at 37 + 4 weeks of gestation with a birth weight of 2440 g (- 1.1 S.D.). Clinical examination showed atypical CHARGE syndrome, with choanal atresia, a heart defect, and sensorineural deafness. Genomic DNA was extracted from peripheral venous blood sample using molecular biological technique. We used the Illumina TruSigt One sequencing panel on the MiSeq next- generation sequencing (NGS) platform for mutation screening and found a novel frameshift mutation in chromodomain helicase DNA binding protein 7 (CHD7; c.4656dupT). This mutation results in a new reading frame ending in p.(Ile1553fs). At the first month of age, the patient had a posterior nostril plasty operation by nasal endoscope. At the second month of age, she had patent ductus arteriosus ligation surgery. At the 4th month of age, she was discharged from the hospital., Conclusions: Our findings further reveal that patients should not be rejected for CHD7 mutational analysis even if they do not fulfill CHARGE syndrome Verloes criteria.

Background: Invasive mechanical ventilation (IMV) is associated with the development of adverse pulmonary and non-pulmonary outcomes in very premature infants. Various modes of non-invasive respiratory support are increasingly being used to decrease the incidence of bronchopulmonary dysplasia. The aim of this trial is to compare the effect of non-invasive high-frequency oscillatory ventilation (NHFOV) and nasal continuous positive airway pressure (NCPAP) in preterm infants with respiratory distress syndrome (RDS) as a primary non-invasive ventilation support mode., Methods/design: In this multi-center randomized controlled trial, 300 preterm infants born at a gestational age of 26 6/7 to 33 6/7 weeks with a diagnosis of RDS will be randomized to NHFOV or NCPAP as a primary mode of non-invasive respiratory support. The study will be conducted in 18 tertiary neonatal intensive care units in China. The primary outcome is the need for IMV during the first 7 days after enrollment in preterm infants randomized to the two groups. The prespecified secondary outcomes include days of hospitalization, days on non-invasive respiratory support, days on IMV, days on supplemental oxygen, mortality, need for a surfactant, severe retinopathy of prematurity requiring laser treatment or surgery, patent ductus arteriosus needing ligation, bronchopulmonary dysplasia, abdominal distention, air leak syndromes, intraventricular hemorrhage (≥ grade 3), spontaneous intestinal perforation, necrotizing enterocolitis (≥II stage), and nasal trauma. Other secondary outcomes include Bayley Scales of Infant Development at 18-24 months of corrected age., Discussion: In recent decades, several observational studies have compared the effects of NHFOV and NCPAP in neonates as a rescue mode or during weaning from IMV. To our knowledge, this will be the first multi-center prospective, randomized controlled trial to evaluate NHFOV as a primary mode in preterm infants with RDS in China or any other part of the world. Our trial may help to establish guidelines for NHFOV in preterm infants with RDS to minimize the need for IMV, and to decrease the significant pulmonary and non-pulmonary morbidities associated with IMV., Trial Registration: ClinicalTrials.gov, NCT03099694 . Registered on 4 April 2017.

Objective: To study the clinical effect of probiotics in the treatment of non-alcoholic fatty liver disease (NAFLD). Methods: A total of 200 patients with NAFLD were randomly divided into 4 groups: control group (routine treatment group) and combined treatment group A, B and C. Each group had equal patients. The control group received orally polyene phosphatidylcholine capsules; whereas combined group A, B and C were given orally the live "combined Bifidobacterium Lactobacillus and Enterococcus powder" , "two live combined Bacillus subtilis and Enterococcus " , and the both probiotics respectively. The duration of treatment was 1 month. Laboratory parameters were evaluated before treatment and thirtieth day after treatment, including cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol(LDL-C), alanine aminotransferase(ALT), aspartate aminotransferase (AST), fasting blood glucose (FPG), serum high molecular weight adiponectin (HMW-APN) and serum TNFα. Meanwhile the faece sample was collected for routine test and bacterial culture. Liver ultrasound scan was done in all patients. Results: In terms of blood lipids and blood glucose, each group improved after treatment with significant differences ( P< 0.05) except for HDL-C. As for liver function, serum ALT and AST decreased after treatment in each group; especially in combined group C which were lower than those of control group [(33.7±7.6) U/L vs. (45.0±8.5) U/L; (22.0±1.6) U/L vs. (29.4±3.7) U/L; P< 0.05]. TNFα levels decreased after treatment in each group, in addition the values in combined group C was significantly lower than that of control group[(0.51±0.27) µg/L vs. (0.82±0.28) µg/L, P< 0.05]. Serum HMW-APN increased after treatment in each group, and the HMW-APN in combined C group was significantly higher than that of control group[(9.28±3.72) µg/L vs. (7.87±3.96)µg/L, P< 0.05]. (5) After treatment, all groups showed improvement of fatty liver by ultrasound, but the difference between groups was not statistically significant. (6) Compared with before treatment, fecal flora in combined groups was all reduced ( P< 0.01), but it was comparable before and after treatment in control group. Conclusions: Probiotics improve intestinal microecological system in NAFLD patients via inhibiting TNFα and enhancing adiponectin, possibly resulting in regulating blood glucose, lipid metabolism, and protecting liver injury from NAFLD.

Human epididymis protein 4 (HE4) was significantly up-regulated in colorectal cancer (CRC), while the potential relevance to radiation resistance of this phenomenon is still elusive. Relative expressions of target genes were quantified by real-time PCR. The protein level was determined by Western blot. The regulatory effect of miR-149 on WFDC2 (gene encoding HE4 protein) expression was analyzed by luciferase reporter assay. The response to radiation was evaluated by clonogenic assay in vitro and xenograft growth in vivo . WFDC2 was aberrantly up-regulated and miR-149 was down-regulated in CRC. MiR-149 repressed WFDC2 expression via directly targeting its 3'UTR region. The ectopic expression of miR-149 significantly sensitized CRC to radiation both in vitro and in vivo. Likewise, we further demonstrated that WFDC2-deficiency remarkably improved the radiation resistance in CRC. Simultaneously, WFDC2 rescue completely abolished the radiation sensitivity imposed by miR-149. Our data suggested that miR-149 sensitized CRC to radiation via directly inhibiting WFDC2/HE4, which would hold great promise for future therapeutic exploitations., Competing Interests: None.