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Background: Acral persistent papular mucinosis (APPM) is a rare idiopathic subtype of localized lichen myxedematosus. To date, there have been less than 41 APPM cases reported worldwide, however, almost all patients were older than 18 years of age. A 7-year-old child was first reported in this paper., Case Description: A 7-year-old boy was admitted to our hospital with a solitary skin-colored papule on the radial side of the middle segment of his right index finger. The patient wanted to know the exact diagnosis and remove it because the flexion movement of the middle segment had been affected. Thus, a surgery was performed. Histopathological examination of a biopsy specimen obtained from the papule on the radial side of the middle segment of his right index finger showed a focal and well-circumscribed deposit of mucin in the papillary and middermis. The deposit never extended deeply into the reticular dermis. Mucin spared a subepidermal area in the papillary dermis. Alcian blue stains can highlight the mucin. The papule was histologically diagnosed as an APPM and excised surgically. The wound gradually healed after the operation, and no obvious recurrence, scar or other discomfort was observed during follow-up so far., Conclusions: To the best of our knowledge, this is the rare case of a child APPM presenting as a solitary papule affecting the flexion movement of the middle segment. Since it is a rare disease, we report this case to contribute to future research on the diagnosis and pathogenesis of APPM., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-23-607/coif). The authors have no conflicts of interest to declare., (2024 Translational Pediatrics. All rights reserved.)

The trait-based unidimensional plant economics spectrum provides a valuable framework for understanding plant adaptation strategies to the environment. However, it is still uncertain whether there is a general multidimensionality of how variation of both leaf and fine root traits are influenced by environmental factors, and how these relate to microbial resource strategies. Here, we examined the coordination patterns of four pairs of similar leaf and fine root traits of herbaceous plants in an alpine meadow at the community-level, and their environmental driving patterns. We then assessed their correlation with microbial life-history strategies, as these exhibit analogous resource strategies with plants in terms of growth and resource utilization efficiency. Results exhibited an analogous multidimensionality of the economics spectrum for leaf and fine root traits: the first dimension, collaboration gradient, primarily represented a tradeoff between lifespan and resource foraging efficiency; the second dimension, conservation gradient, primarily represented a tradeoff between conservation and acquisition in resource uptake. Climate variables had a stronger impact on both dimensions for leaf and fine root traits than soil variables did; whereas, the primary drivers were more complex for fine root traits than for leaf traits. The collaboration gradient of leaf and fine root traits exhibited consistent relationships with soil microbial life-history strategies, both showed negative and positive correlation with bacterial and fungal strategies, respectively. Our findings suggest that both leaves and fine roots have general multidimensional strategies for adapting to new environments and provide a solid basis for further understanding the relationships between the adaptive strategies of plants and microbes., 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 Elsevier B.V. All rights reserved.)

Populus euphratica is an important tree species in the arid regions of Northwest China, which is sensitive to climate changes. Climate of the Northwest China is changing to be "warm and humid", but how it would affect the regional forest growth is not clear. In this study, the radial growth response of P. euphratica to major climatic factors and their temporal changes during 1984-2021 were analyzed by using dendrochronology method in the desert oasis ecotone of Cele in the southern Tarim basin. The results showed that tree-ring width index of P. euphratica had a significant negative correlation with temperature in September of the previous year, and in February and May of current year, had significant positive correlation with precipitation in September of previous year and March and May of current year, and had significant positive correlations with SPEI in February and May of current year. The relationships between tree-ring width index and combined month climatic factors were more obvious. The results of moving correlation analysis showed that the correlation between tree-ring width index and temperature in the growing season tended to be strengthened in recent years, while the correlation between tree-ring width index and precipitation, SPEI tended to be declined or remain stable. The variations of the relationships between tree-ring width index and combined month climatic factors were more obvious compared that with single month. Current regional climate is conducive to the growth and development, as well as the improvement of ecological shelter function of P. euphratica forest in the desert oasis ecotone of Cele.

Grazing and climate change both contribute to diversity loss and productivity fluctuations. Sensitive climate conditions and long-term grazing activities have a profound influence on community change, particularly in high-altitude mountain grassland ecosystems. However, knowledge about the role of long-term continuous grazing management on diversity, productivity and the regulation mechanisms in fragile grassland ecosystems is still rudimentary. We conducted a long-term grazing experiment on an alpine typical steppe in the Qilian Mountains to assess effects of grazing intensity on soil, diversity, productivity and the regulation mechanisms. Plants and soil were sampled along grazing gradients at different distances from the pasture entrance (0, 0.3, 0.6, 0.9, 1.2 and 1.5 km) under the non-growing (WP) and the growing season grazing pasture (SAP). The results revealed that community diversity and biomass did not change significantly on a time scale, while the concentration of soil organic carbon and total phosphorus increased significantly. Heavy grazing (0-0.3 km) decreased community diversity and biomass. Grazing increased soil chemical properties in heavy grazed areas of WP, while the opposite was recorded in SAP. Soil chemical properties explained the largest variances in community diversity and community biomass. The prediction model indicates that grazing in WP mainly affects community diversity through soil chemical properties, and promotes a positive correlation between community diversity and community biomass; in SAP, the direct effect of grazing gradients on community diversity and biomass is the main pathway, but not eliminating the single positive relationship between diversity and biomass, which means that diversity can still be used as a potential resource to promote productivity improvement. Therefore, we should focus on the regulation of soil chemical properties in WP, such as the health and quality of soil, strengthening its ability to store water, sequester carbon and increase nutrients; focus on the management of livestock in SAP, including providing fertilizer and sowing to increase diversity and production in heavily grazed regions and reducing grazing pressure through regional rotational grazing. Ultimately, we call for strengthening the stability and sustainability of ecosystems through targeted and active human intervention in ecologically sensitive areas to cope with future grazing pressures and climate disturbances., 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 © 2023 Elsevier Ltd. All rights reserved.)

Staphylococcus aureus (SA) is a major cause of sepsis, leading to acute lung injury (ALI) characterized by inflammation and oxidative stress. However, the role of the Nrf2/PHB2 pathway in SA-induced ALI (SA-ALI) remains unclear. In this study, serum samples were collected from SA-sepsis patients, and a SA-ALI mouse model was established by grouping WT and Nrf2 -/- mice after 6 h of intraperitoneal injection. A cell model simulating SA-ALI was developed using lipoteichoic acid (LTA) treatment. The results showed reduced serum Nrf2 levels in SA-sepsis patients, negatively correlated with the severity of ALI. In SA-ALI mice, downregulation of Nrf2 impaired mitochondrial function and exacerbated inflammation-induced ALI. Moreover, PHB2 translocation from mitochondria to the cytoplasm was observed in SA-ALI. The p-Nrf2/total-Nrf2 ratio increased in A549 cells with LTA concentration and treatment duration. Nrf2 overexpression in LTA-treated A549 cells elevated PHB2 content on the inner mitochondrial membrane, preserving genomic integrity, reducing oxidative stress, and inhibiting excessive mitochondrial division. Bioinformatic analysis and dual-luciferase reporter assay confirmed direct binding of Nrf2 to the PHB2 promoter, resulting in increased PHB2 expression. In conclusion, Nrf2 plays a role in alleviating SA-ALI by directly regulating PHB2 transcription and maintaining mitochondrial function in lung cells., Competing Interests: The authors have disclosed that they do not have any potential conflict of interest., (© 2023 The Authors. MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.)

Grassland health refers to the degree to which the integrity of soil and ecological processes is maintained, which primarily reflects the health status and productivity of grasslands. Evaluating the degree of grassland health is vital for the sustainable develop of grasslands. There are many methods for evaluating grassland health, with advantages and disadvantages for each one. However, there is still a lack of systematic literature offering an overview of methods of grassland health assessment and their applicability. We summarized 10 methods of grassland health assessment, including vigor-organization-resilience (VOR) index evaluation model, condition-vigor-organization-resilience (CVOR) index evaluation model, principal component analysis method, analytic hierarchy process, cluster analysis method, grey relational analysis, pressure-state-response evaluation model, fuzzy comprehensive evaluation method, comprehensive evaluation model of grassland health, and evaluation model using remote sensing technology. The advantages, disadvantages, and applicability of these methods were discussed, aiming to provide scientific basis for selecting more suitable methods of grassland health assessment for different scenarios in the future.

The population structure of Protosalanx chinensis is affected by a variety of factors, including water environment, intraspecific differentiation, interspecific competition and commercial fishing. To investigate the growth performance and the current status of resource utilization of P. chinensis in two important fish farming grounds (Dalong Lake and Amuta Lake) in Daqing, Northeast China, we collected 1513 P. chinensis samples from April to December 2018 for measurement and recording the basic biological characteristics. We estimated the parameters including population growth, mortality and exploitation using Von Bertalanffy growth formula, Beverton-Holt model, Pauly's empirical formula and length-based Bayesian biomass estimation method. The results showed that the asymptotic body lengths of Dalong Lake ( n =660) and Amuta Lake ( n =853) populations were 183.75 and 169.10 mm, respectively. The growth performance indices were both 4.85, and the body mass growth equations were W t =29.29×(1-e -2.1( t +0.07) ) 3.2977 and W t =28.72×(1-e -2.5( t +0.07) ) 3.4168 , respectively. The ages at inflection were 0.49 a and 0.43 a, and the condition factors were 5.30×10 -4 ±1.38×10 -4 and 4.00×10 -4 ±1.61×10 -4 . The exploitation rates were 0.60 and 0.61, and the relative catch per unit of supplementation were 0.069 and 0.075, respectively. The current differences in population resources between Dalong Lake and Amuta Lake in Daqing were mainly manifested in the parameters related to growth characteristics. The main reason for such differences was changes in the survival conditions of P. chinensis populations after the period of dietary transition induced by the density differences.

Extracellular vesicles (EVs) have emerged as a unique mediator of interorgan communications, playing important roles in the pathophysiologic process of various diseases, including diabetes and other metabolic diseases. Here, we reported that the EVs released by steatotic hepatocytes exerted a detrimental effect on pancreatic β cells, leading to β-cell apoptosis and dysfunction. The effect was profoundly attributable to an up-regulation of miR-126a-3p in the steatotic hepatocyte-derived EVs. Accordingly, overexpression of miR-126a-3p promoted, whereas inhibition of miR-126a-3p prevented β-cell apoptosis, through a mechanism related to its target gene, insulin receptor substrate-2. Moreover, inhibition of miR-126a-3p by its specific antagomir was able to partially reverse the loss of β-cell mass and ameliorate hyperglycaemia in diabetic mice. Thus, the findings reveal a novel pathogenic role of steatotic hepatocyte-derived EVs, which mechanistically links nonalcoholic fatty liver disease to the development of diabetes., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This study presents a general framework, namely, Sparse Spatiotemporal System Discovery (S3d), for discovering dynamical models given by Partial Differential Equations (PDEs) from spatiotemporal data. S3d is built on the recent development of sparse Bayesian learning, which enforces sparsity in the estimated PDEs. This approach enables a balance between model complexity and fitting error with theoretical guarantees. The proposed framework integrates Bayesian inference and a sparse priori distribution with the sparse regression method. It also introduces a principled iterative re-weighted algorithm to select dominant features in PDEs and solve for the sparse coefficients. We have demonstrated the discovery of the complex Ginzburg-Landau equation from a traveling-wave convection experiment, as well as several other PDEs, including the important cases of Navier-Stokes and sine-Gordon equations, from simulated data., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Transition metal phosphide (TMP) emerges as a promising electrocatalyst for overall water splitting (OWS). However, conventional TMP materials require exogenous metal ions to participate in coordination reactions, which usually suffer from active site blocking, pronounced intrinsic impedance, and inevitable catalyst shedding at high current density. Herein, a novel in-situ construction strategy has been developed to grow N-doped carbon (NC) enwrapped Co/CoP nanosheets directly onto Co foam (abbreviated as CoF) through a three-step transformation of Co to Co(OH) 2 to Co-Metal-Organic Framework (Co-MOF) to Co/CoP/NC. In the entire preparation process, Co metal is only provided by the CoF substrate without external metal sources. Such in-situ construction yields tight contact at the interface of the heterogeneous catalyst, leading to much-reduced impedance and boundary vacancy, while the porous nitrogen-doped carbon backbone further endows the catalyst with the exposure of massive active sites, promotes mass transfer, and possesses high electrical conductivity. The Co/CoP/NC/CoF requires overpotentials of only 64 mV/263 mV@10 mA cm -2 and 414 mV/481 mV@400 mA cm -2 for both HER/OER in 1.0 M KOH, respectively. Remarkably, it reveals excellent OWS catalytic activity with a cell voltage of 1.56 V@10 mA cm -2 and 1.88 V@200 mA cm -2 . This strategy of in-situ interface engineering transformation provides new ideas for direct device processing and construction of highly-efficient transition-metal-based OWS electrode materials., 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 © 2023 Elsevier Inc. All rights reserved.)

Objectives: Pulmonary fibrosis (PF) is a chronic and refractory interstitial lung disease with limited therapeutic options. 4-octyl itaconate (4-OI), a cell-permeable derivative of itaconate, has been shown to have anti-oxidative and anti-inflammatory properties. However, the effect and the underlying mechanism of 4-OI on PF are still unknown., Methods: WT or Nrf2 knockout (Nrf2 -/- ) mice were intratracheally injected with bleomycin (BLM) to establish PF model and then treated with 4-OI. The mechanism study was performed by using RAW264.7 cells, primary macrophages, and conditional medium-cultured MLE-12 cells., Results: 4-OI significantly alleviated BLM-induced PF and EMT process. Mechanism studies have found that 4-OI can not only directly inhibit EMT process, but also can reduce the production of TGF-β1 by restraining macrophage M2 polarization, which in turn inhibits EMT process. Moreover, the effect of 4-OI on PF and EMT depends on Nrf2., Conclusion: 4-OI ameliorates BLM-induced PF in an Nrf2-dependent manner, and its role in alleviating PF is partly due to the direct inhibition on EMT, and partly through indirect inhibition of M2-mediated EMT. These findings suggested that 4-OI has great clinical potential to develop as a new anti-fibrotic agent for PF therapy., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

A taxonomic study was carried out on strain BGMRC 0090 T , which was isolated from seawater. The isolate was a Gram-negative, aerobic, flagellated, rod-shaped bacterium with algicidal activity. Optimal growth was observed at 30 °C, pH 6.0 and with 2 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain BGMRC 0090 T belonged to the genus Parvularcula , with highest sequence similarity to Parvularcula lutaonensis CC-MMS-1 T (98.4 %). Average nucleotide identity, amino acid identity and digital DNA-DNA hybridization values between strain BGMRC 0090 T and five strains of the genus Parvularcula with publicly available genomes were below 84.0, 69.2 and 21.4 %, respectively. The genome of strain BGMRC 0090 T was 3.2 Mb with 64.8 mol% DNA G+C content and encoded 2905 predicted proteins, three rRNA, 42 tRNA and four ncRNA genes. Some algicidal biosynthesis-associated genes were detected in the genome. Strain BGMRC 0090 T contained Q-10 as the major quinone. The predominant fatty acids were identified as summed feature 8 (C 18 : 1 ω7 c /ω6 c ) and C 16 : 0 . Based on the polyphasic evidence presented in this paper, strain BGMRC 0090 T is concluded to represent a novel species of the genus Parvularcula , for which the name Parvularcula maris sp. nov. is proposed. The type strain is BGMRC 0090 T (= KCTC 92591 T =MCCC 1K08100 T ).

This research aimed to study the effect of Uremic Clearance Granules on chronic kidney disease in SD rats by using the methods of microbial functional genomics combined with metabolomics, and to preliminarily explore its mechanism. The SD rat model of chronic kidney disease was established by the adenine-induced method. After the model was successfully induced, the animals were randomly divided into a negative control group, a Uremic Clearance Granule treatment group, and a normal control group, with 8 rats in each group. After 4 weeks of administration, animal feces and serum were collected, and 16S rDNA sequencing technology was used to analyze the abundance, diversity, and function prediction of intestinal microorganisms. Liquid chromatography-mass spectrometry(LC-MS) technology was used to perform high-throughput sequencing to detect animal serum metabolites. The MetPA database was used to screen out potential biomarkers of chronic kidney disease in rats and conduct the enrichment analysis of metabolic pathways. Spearman's method was used to analyze the correlation between the two omics. The results showed that Uremic Clearance Granules effectively improved the body weight loss and renal function-related biochemical and appearance indicators in rats with chronic kidney disease. The results of 16S rDNA sequencing showed that Uremic Clearance Granules regulated the diversity and composition of the intestinal flora in rats with chronic kidney disease. The changes in the intestinal flora affected functional metabolic pathways such as amino acid biosynthesis and metabolism, lipid metabolism, and carbohydrate metabolism. The results of LC-MS showed that as compared with the negative control group, 15 metabolites were reversed in the Uremic Clearance Granule treatment group, among which 11 potential marker metabolites were significantly up-regulated and 4 potential marker metabolites were significantly down-regulated. Five amino acid metabolic pathways were mainly involved, which were significantly correlated with changes in the intestinal flora. Therefore, Uremic Clearance Granules can improve the renal function of rats with chronic kidney disease, and the mechanism may be related to its effect on the amino acid metabolism pathway by regulating the intestinal flora.

Objective: This study aims to identify potential prognostic and therapeutic biomarkers in papillary renal cell carcinoma (pRCC)., Methods: Two microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) were identified. The protein-protein interaction (PPI) networks and functional annotations of DEGs were established. Survival analysis was utilized to evaluate the prognostic significance of the DEGs and the association between the expression level of candidate biomarkers and various tumour-infiltrating immune cells was explored. The role of PTTG1 in tumour microenvironments (TME) was further explored using Single-cell RNA-seq and its prognostic and therapeutic significance was validated in Fudan University Shanghai Cancer Centre (FUSCC) cohort., Results: Eight genes, including BUB1B , CCNB1 , CCNB2 , MAD2L1 , TTK , CDC20 , PTTG1, and MCM were found to be negatively associated with patients' prognosis. The expression level of PTTG1 was found to be significantly associated with lymphocytes, immunomodulators, and chemokine in the TCGA cohort. Single-cell RNA-seq information indicated that PTTG1 was strongly associated with the proliferation of T cells. In the FUSCC cohort, the expression level of PTTG1 was also statistically significant for both progression-free survival (PFS) and overall survival (OS) prediction (HR = 2.683, p  < .001; HR = 2.673, p  = .001). And higher expression level of PTTG1 was significantly associated with immune checkpoint blockade (ICB) response in the FUSCC cohort ( χ 2 =3.99, p   <   .05)., Conclusions: Eight genes were identified as a prognostic biomarker and the expression level of PTTG1 was also found to serve as a potential predictor for ICB response in pRCC patients.Key messages:Eight genes, including BUB1B , CCNB1 , CCNB2 , MAD2L1 , TTK , CDC20 , PTTG1, and MCM were found to be negatively associated with pRCC patients' prognosis.Expression level of PTTG1 was significantly associated with tumour microenvironment including lymphocytes, immunomodulators, and chemokines.Higher expression level of PTTG1 was significantly associated with immune checkpoint blockade (ICB) response in FUSCC cohort.

Intrauterine growth restriction (IUGR), one of the major complications of pregnancy, is characterized by low birth weight and results in higher risks for long-term problems including developing metabolic and cardiovascular diseases. Short-chain fatty acids (SCFAs), especially propionate, have been reported to correct glucose and lipid disorders in metabolic diseases. We hypothesized that maternal propionate supplementation could prevent glucose and lipid metabolic disturbance in hypoxia-induced IUGR. Here, in our study, maternal hypoxia was induced from gestational day (GD) 11 to GD 17.5 to establish an IUGR mouse model. Maternal propionate treatment reversed reduced birth weight in male IUGR offspring. Hepatic transcriptomics demonstrated that SP treatment significantly lowered glucose and lipid metabolism-related genes ( Scd1 , G6pc , Pck1 and Fasl ) in IUGR offspring. KOG enrichment analysis showed that propionate-induced down-regulated differential expressed genes (DEGs) mainly belonged to lipid transport and metabolism. KEGG enrichment results showed that the down-regulated DEGs were mostly enriched in PPAR and FoxO signaling pathways. We also found that maternal oral administration of SP decreased serum lipid content, attenuated hepatic insulin resistance and liver lipid accumulation, reduced hepatic key gene expressions of gluconeogenesis and lipogenesis, increased energy expenditure and improved liver function in 11-week-old male IUGR offspring. These results indicate that maternal propionate supplementation increases birth weight and corrects hepatic glucose and lipid metabolic disturbance and energy expenditure in male mice born with IUGR, which may provide a basis for using propionate to treat IUGR disease.

Background: Managements for refractory proficient mismatch repair (pMMR) or microsatellite stable (MSS) metastatic colorectal cancer (mCRC) were still challenging and controversial. Our study sought to investigate the efficacy and safety of anti-programmed cell death protein 1 (anti-PD-1) antibodies plus regorafenib in refractory pMMR/MSS mCRC., Methods: We retrospectively analyzed the efficacy and safety of 103 pMMR/MSS mCRC patients treated with at least one dose of anti-PD-1 antibodies plus regorafenib (80 mg once daily for 21 days on/7 days off 28 days as a cycle) between July 2019 and June 2021 at the Hunan Cancer Hospital. All patients had previously received at least second-line treatment. The patients were evaluated by computed tomography every 2 or 3 treatment cycles until progression or being lost to follow-up. The primary end point was overall survival (OS)., Results: The median follow-up period was 5.30 (range, 0.50-22.50) months. The median OS (mOS) and medical progression-free survival (mPFS) were 8.40 and 2.50 months for the entire cohort, respectively. The mOS and mPFS were 16.07 and 3.10 months in patients who received >1 cycle of anti-PD-1 antibodies and regorafenib (n=55), which were significantly longer than 4.37 and 1.11 months in those received only 1 cycle (n=48) (both P<0.001, respectively). The Cox multivariate regression analysis demonstrated that the number of cycles of regorafenib plus PD-1 and previously undergone surgery were independent risk factors for OS, whereas Sintilimab was confirmed to have a significant better PFS compared to other anti-PD-1 antibodies. Of the 55 patients who were evaluated, 7 were diagnosed with a partial response (PR) and another 16 were diagnosed with stable disease (SD), but no patient showed a complete response (CR). Thus, the objective response rate (ORR) was 12.7% and the disease control rate was 41.8%. Treatment-related adverse events (TRAEs) of grade 3 or higher occurred in 13 (12.6%) patients., Conclusions: The combination of regorafenib plus anti-PD-1 antibodies has a manageable safety profile and may improve prognosis for pMMR/MSS mCRC patients, especially those who received >1 cycle. Compared to the other anti-PD-1 antibodies, sintilimab may be more efficacious; however, further prospective studies need to be conducted to confirm our findings., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-3690/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

The combined use of two or more different drugs can better promote nerve recovery and its prognosis for treatment of stroke. Salvianolate lyophilized injection (SLI) made from the aqueous extraction of salvia miltiorrhiza and Xueshuantong injection (lyophilized) (XST) made from the Panax Notoginseng extraction are two herbal standardized preparations that have been widely used in China for the treatment of ischemic stroke. In this study, we investigated the neuroprotective effects of XST combined with SLI in the recovery stage of middle cerebral artery occlusion / reperfusion (MCAO/R) injury rat. Wistar rats were subjects to MCAO/R, then were treated with SLI or XST alone, or with their combination (1X1S) via tail injection daily for 14 days. The pathological status of the brain was detected by neurological deficit scores, TTC, regional cerebral blood flow and Nissl staining. Golgi-Cox staining was used to assess dendritic, axonal and synaptic remodeling. The expression of MAP-2, β-Tubulin, PSD95, SYN, BDNF and VEGF were analyzed by western blotting and immunofluorescence. The results showed that administration of 1X1S not only significantly decreased neurological scores and infarct volumes, but also increased regional cerebral blood flow, strengthened dendritic and synaptic remodeling compared with XST, SLI used alone. And the mechanism of combined of 1X1S to exert neuroprotection may be associated with PI3K/ AKT/ mTOR and RhoA/ROCK2 pathways. Overall, these findings suggest that combination of XST and SLI promotes dendritic spine density and synaptic plasticity via upregulation of the PI3K/ AKT/ mTOR pathways and inhabitation the RhoA/ROCK2 signaling pathway in rat with MCAO/R, showing its multiple-action-multiple-target efficacy and suggest a potential new strategy for ischemia., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Hepatocellular carcinoma (HCC) is a cancer with extremely high mortality. Epithelial-mesenchymal transition (EMT) may play an important role in the occurrence, invasion and prognosis of HCC; however, its relationship with immunity in HCC has not yet been studied. Therefore, we investigated the diagnostic and prognostic values of EMT and explored its potential connections with tumorigenic immune infiltrates in HCC. We first proposed a quantitative metric of EMT activity, the EMT score. After applying this metric to 20 datasets from the Integrative Molecular Database of Hepatocellular Carcinoma, the Cancer Genome Atlas, and the Gene Expression Omnibus, we explored the ability of the EMT score to stratify across sample types. We then applied the EMT score for survival analysis and to differentiate patients with/without vascular invasion to test its prognostic value. We also collected and calculated data on the abundance of immune cells and immune cell markers in HCC and investigated their correlations with EMT scores. Finally, we synthesized and analyzed 20 datasets and constructed an EMT-gene-immune linkage network. The results showed higher EMT scores in HCC samples than in cirrhotic and normal livers. The cases with higher EMT scores also showed poorer performance in terms of prognostic factors such as vascular invasion and overall survival time. Our research demonstrated a broad correlation between EMT and the tumor immune microenvironment, and we uncovered multiple potential linkers associated with both EMT and immunity. Studying EMT has clinical relevance and high diagnostic and prognostic value for HCC., (© 2022 John Wiley & Sons Ltd.)

Objectives: Temozolomide (TMZ) resistance is a key factor that restricts the therapeutic effect of glioblastoma (GBM). YTH-domain family member 2 (YTHDF2) is highly expressed in GBM tissues, while the mechanism of YTHDF2 in TMZ resistance in GBM remains not fully elucidated., Methods: The YTHDF2 expression in TMZ-resistant tissues and cells was detected. Kaplan-Meier analysis was employed to evaluate the prognostic value of YTHDF2 in GBM. Effect of YTHDF2 in TMZ resistance in GBM was explored via corresponding experiments. RNA sequence, FISH in conjugation with fluorescent immunostaining, RNA immunoprecipitation, dual-luciferase reporter gene and immunofluorescence were applied to investigate the mechanism of YTHDF2 that boosted TMZ resistance in GBM., Results: YTHDF2 was up-regulated in TMZ-resistant tissues and cells, and patients with high expression of YTHDF2 showed lower survival rate than the patients with low expression of YTHDF2. The elevated YTHDF2 expression boosted TMZ resistance in GBM cells, and the decreased YTHDF2 expression enhanced TMZ sensitivity in TMZ-resistant GBM cells. Mechanically, YTHDF2 bound to the N6-methyladenosine (m 6 A) sites in the 3'UTR of EPHB3 and TNFAIP3 to decrease the mRNA stability. YTHDF2 activated the PI3K/Akt and NF-κB signals through inhibiting expression of EPHB3 and TNFAIP3, and the inhibition of the two pathways attenuated YTHDF2-mediated TMZ resistance., Conclusion: YTHDF2 enhanced TMZ resistance in GBM by activation of the PI3K/Akt and NF-κB signalling pathways via inhibition of EPHB3 and TNFAIP3., Competing Interests: All authors declare that they have no conflict of interest., (© 2022 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)

Tribbles homolog 3 (TRIB3), a pseudokinase that regulates multiple intracellular signaling pathways, has been reported to promote the growth of multiple tumors. However, its role in clear cell renal cell carcinoma (ccRCC) remains unelucidated. We evaluated the role of TRIB3 in ccRCC using publicly available data from The Cancer Genome Atlas and analyzed its relationship with the tumor microenvironment; moreover, we used gene knockout and overexpression techniques to detect the effects of TRIB3 on the biological behavior of ccRCC cells. RT-qPCR and western blotting were used to detect transfection efficiency, and the invasiveness of ccRCC cells was determined by Transwell migration assays. We found that TRIB3 overexpression was significantly associated with increased grade, stage, and distant metastasis, positively correlated with ccRCC invasiveness, and also an independent risk factor for overall survival (OS). In addition, 361 differentially expressed genes (DEGs) related to TRIB3 were identified. Functional enrichment analysis showed that DEGs were mainly enriched in humoral immune responses, collagen-containing extracellular matrix, and serine hydrolase activity. Immune landscape characterization revealed that TRIB3 expression was significantly and negatively associated with CD8 + T and hematopoietic stem cells, whereas it was positively associated with NK T and macrophage M1 cells. Single-cell sequencing showed that localization and binding targets of TRIB3 mainly involved monocytes/macrophages and CD4 + and CD8 + T cells. Overall, our study revealed that elevated TRIB3 expression represents a promising prognostic marker for ccRCC patients and may play a key role in tumor microenvironment modulation.

Cosmetic tattoos are difficult to remove, and their response to picosecond laser treatment has seldom been investigated. We compared the efficacy and adverse effects of picosecond versus Q-switched lasers for the removal of cosmetic tattoos. White, flesh-colored, and brown inks were irradiated using 532/1064 nm picosecond and Q-switched Nd:YAG lasers, and their absorption spectra before and after laser irradiation were analyzed. Nine rats were tattooed with all three inks. Each tattoo was divided into three sections and treated at 1064 nm with a picosecond laser or Q-switched laser, or left untreated, in four sessions at 1-month intervals. Skin biopsies were taken from treated and untreated sites. In vitro study showed the 1064 nm picosecond laser caused the least paradoxical color shift. In vivo study showed that all white tattoos achieved poor response scores, six flesh-colored tattoos achieved fair to good response scores, and seven brown tattoos achieved good to excellent response scores with the picosecond laser. The picosecond laser was superior to the Q-switched laser for removing flesh-colored tattoos (P < 0.05), but the effectiveness for white and brown tattoos was similar for both lasers. The degree of paradoxical darkening when removing the white and flesh-colored tattoos was significantly lower with the picosecond than that with the Q-switched laser (P < 0.01). Transmission electron microscopy showed that many tattoo ink particles had decreased in size after irradiations with both pulse durations. The 1064 nm picosecond Nd:YAG laser causes mild paradoxical darkening and might be more appropriate for removal of flesh-colored and brown cosmetic tattoos., (© 2021. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Ethyl ferulate (EF) is abundant in Rhizoma Chuanxiong and grains (e.g., rice and maize) and possesses antioxidative, antiapoptotic, antirheumatic, and anti-inflammatory properties. However, its effect on lipopolysaccharide (LPS)-induced acute lung injury (ALI) is still unknown. In the present study, we found that EF significantly alleviated LPS-induced pathological damage and neutrophil infiltration and inhibited the gene expression of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) in murine lung tissues. Moreover, EF reduced the gene expression of TNF-α, IL-1β, IL-6, and iNOS and decreased the production of NO in LPS-stimulated RAW264.7 cells and BMDMs. Mechanistic experiments revealed that EF prominently activated the AMPK/Nrf2 pathway and promoted Nrf2 nuclear translocation. AMPK inhibition (Compound C) and Nrf2 inhibition (ML385) abolished the beneficial effect of EF on the inflammatory response. Furthermore, the protective effect of EF on LPS-induced ALI was not observed in Nrf2 knockout mice. Taken together, the results of our study suggest that EF ameliorates LPS-induced ALI in an AMPK/Nrf2-dependent manner. These findings provide a foundation for developing EF as a new anti-inflammatory agent for LPS-induced ALI/ARDS therapy., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)

In grazing ecosystems, mature seeds fall directly to the soil to form the soil seed bank (SSB), or are ingested by grazing livestock to become part of the dung seed bank (DSB; i.e., seed circulation). Both the SSB and DSB form the basis for the natural regeneration of vegetation. However, little is known about the relationships between the SSB, DSB, and aboveground vegetation (AGV) community under different stocking rates (SRs). This study investigated the relationships between the SSB, seeds in Tan sheep ( Ovis aries ) dung, and AGV at different SRs (0, 2.7, 5.3, and 8.7 sheep ha -1 ) in a semiarid region of the Loess Plateau in China. We found that Tan sheep grazing increased the species richness heterogeneity of grassland vegetation, and negatively influenced the density of AGV. Under natural conditions, 17 species from soil-borne seeds and 10 species from Tan sheep dung germinated. There was low species similarity between the soil and DSBs and AGV. Sheep SR and the seed banks (soil and dung) were negatively correlated with AGV. Seeds are cycled from herbage to livestock to soil during cold season grazing; the seasonal nature of this seed dispersal is an adaptation to harsh, semiarid environments. Increased seed bank diversity under sheep grazing facilitates grassland regeneration on the Loess Plateau, similarly to other semiarid regions globally., Competing Interests: None., (© 2021 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Dehydrocostus lactone (DHL), a natural sesquiterpene lactone isolated from the traditional Chinese herbs Saussurea lappa and Inula helenium L., has important anti-inflammatory properties used for treating colitis, fibrosis, and Gram-negative bacteria-induced acute lung injury (ALI). However, the effects of DHL on Gram-positive bacteria-induced macrophage activation and ALI remains unclear. In this study, we found that DHL inhibited the phosphorylation of p38 MAPK, the degradation of IκBα, and the activation and nuclear translocation of NF-κB p65, but enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of Nrf2 and HO-1 in lipoteichoic acid (LTA)-stimulated RAW264.7 cells and primary bone-marrow-derived macrophages (BMDMs). Given the critical role of the p38 MAPK/NF-κB and AMPK/Nrf2 signaling pathways in the balance of M1/M2 macrophage polarization and inflammation, we speculated that DHL would also have an effect on macrophage polarization. Further studies verified that DHL promoted M2 macrophage polarization and reduced M1 polarization, then resulted in a decreased inflammatory response. An in vivo study also revealed that DHL exhibited anti-inflammatory effects and ameliorated methicillin-resistant Staphylococcus aureus (MRSA)-induced ALI. In addition, DHL treatment significantly inhibited the p38 MAPK/NF-κB pathway and activated AMPK/Nrf2 signaling, leading to accelerated switching of macrophages from M1 to M2 in the MRSA-induced murine ALI model. Collectively, these data demonstrated that DHL can promote macrophage polarization to an anti-inflammatory M2 phenotype via interfering in p38 MAPK/NF-κB signaling, as well as activating the AMPK/Nrf2 pathway in vitro and in vivo. Our results suggested that DHL might be a novel candidate for treating inflammatory diseases caused by Gram-positive bacteria.

Aberrations in long noncoding RNA (lncRNA) expression have been recognized in numerous human diseases. In the present study, the of role the long noncoding RNA HOX antisense intergenic RNA myeloid 1 variant (HOTAIRM1-1) in regulating the pathological progression of osteoarthritis (OA) was investigated. The aberrant expression of HOTAIRM1-1 in OA was demonstrated, but the molecular mechanisms require further analysis. The aim of the present study was to explore the function of miR-125b in modulating chondrocyte viability and apoptosis, and to address the functional association between HOTAIRM1-1 and miR-125b as potential targets. A miR-125b inhibitor was used, which laid the foundation for the following investigation. The study confirmed that HOTAIRM1-1 and miR-125b are inversely expressed in chondrocytes. The expression of HOTAIRM1-1 was downregulated and the expression of miR-125b was upregulated in tissues from patients with OA. HOTAIRM1-1 directly interacted with miR-125b in chondrocytes. HOTAIRM1-1 knockdown was associated with chondrocyte proliferation and extracellular matrix degradation. Furthermore, miR-125b reversed the effect of HOTAIRM1-1 on cell proliferation and apoptosis. In conclusion, the present study indicates that the loss of HOTAIRM1-1 function leads to aberrant increases in the proliferation and apoptosis of chondrocytes. miR-125b may be a potential downstream mechanism that regulates the function of HOTAIRM1-1, and this finding provides a therapeutic strategy for OA., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Liu et al.)

Objective: The present study aims to discuss the clinical characteristics, factors, and treatment methods affecting the prognosis in patients with severe radiation pneumonia (RP)., Methods: The radiotherapy status, clinical features, imaging characteristics, laboratory examination results, treatment methods, and prognoses of 34 patients with severe RP treated in our department between January 2011 and July 2017 were retrospectively analyzed. The severe RP grading was based on the Common Terminology Criteria for Adverse Events version 4.0; patients who scored Grade ≥3 were considered to have a severe case of RP., Results: The results of the present study showed that 22 patients had lung cancer, 6 had esophageal cancer, 5 had breast cancer, and 1 had colon cancer with lung metastasis. The total radiation dose was 37.5-66 Gy, and the overall average dose was 53 Gy; the average dose in the patients who died was 52.9 Gy. A total of 28 patients presented with a cough and sputum as the initial symptom, and 24 presented with wheezing as an accompanying symptom; of the 24 patients, 8 experienced fever, 2 experienced wheezing as the only symptom, 1 had chest pain, and 1 had chest tightness. In 26 patients, the changes were in the radiation field, and in 8 cases, the changes appeared both inside and outside the radiation field. After the use of glucocorticoid methylprednisolone, respiratory support, and anti-infection treatment, 18 patients were cured, 8 showed a condition improvement, and 8 died., Conclusion: The prognosis of severe RP was not significantly correlated with the administered radiation dose; however, lung cancer, a high Acute Physiology and Chronic Health Evaluation score, and delayed diagnosis were risk factors for patient death. However, a combination of antibiotic therapy, ventilator-assisted respiration, and steroid therapy could improve patient prognosis., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Li et al.)

Burrows provide burrowing animals with a place to hibernate, reproduce, and avoid predators and harsh weather conditions and thus have a vital impact on their survival. However, the general physical characteristics and ecological functions of Marmota himalayana burrows as well as whether there are differences in burrow traits under different terrains (e.g., sunny slopes, shady slopes, and flat areas) are not well understood. From July to August 2019 (warm season), we used unmanned aerial vehicles to fly at low altitudes and slow speeds to locate 131 M .  himalayana burrows (45 on shaded slopes, 51 on sunny slopes, and 35 on flat areas) in the northeastern Qinghai-Tibetan Plateau region. We then measured the physical characteristics (burrow density, entrance size, first tunnel length, volume, orientation, and plant characteristics near the burrow entrance) of these burrows on site. We found that terrain had a substantial influence on burrow density, orientation, and entrance size and on the angle of the burrow entrance; species richness had a substantial impact on path density and tunnel volume. The physical parameters of the M. himalayana burrows showed that they function to protect the marmots from natural enemies and bad weather, provide good drainage, and maintain a stable microclimate around the entrance. We discuss the ability of burrowing animals (e.g., M. himalayana ) to adapt to the external environment based on their burrow characteristics., Competing Interests: None declared., (© 2021 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Mitochondrial fusion/fission dynamics plays a fundamental role in neuroprotection; however, there is still a severe lack of therapeutic targets for this biological process. Here, we found that the naturally derived small molecule echinacoside (ECH) significantly promotes mitochondrial fusion progression. ECH selectively binds to the previously uncharacterized casein kinase 2 (CK2) α' subunit (CK2α') as a direct cellular target, and genetic knockdown of CK2α' abolishes ECH-mediated mitochondrial fusion. Mechanistically, ECH allosterically regulates CK2α' conformation to recruit basic transcription factor 3 (BTF3) to form a binary protein complex. Then, the CK2α'/BTF3 complex facilitates β-catenin nuclear translocation to activate TCF/LEF transcription factors and stimulate transcription of the mitochondrial fusion gene Mfn2. Strikingly, in a mouse middle cerebral artery occlusion (MCAO) model, ECH administration was found to significantly improve cerebral injuries and behavioral deficits by enhancing Mfn2 expression in wild-type but not CK2α' +/- mice. Taken together, our findings reveal, for the first time, that CK2 is essential for promoting mitochondrial fusion in a Wnt/β-catenin-dependent manner and suggest that pharmacologically targeting CK2 is a promising therapeutic strategy for ischemic stroke.

Male sterility refers to the phenomenon that stamens cannot grow normally and produce viable pollen grains in plants. Hybrid seed production by taking advantage of the trait of male sterility is an effective and quick strategy to increase crop yield. Up to date, the yield of rice (Oryza sativa L.), maize (Zea mays L.), wheat (Triticum aestivum L.) and other crops has been greatly increased based on hybrid vigor utilization. Soybean (Glycine max (L.) Merr.) is a self-pollination species, artificial emasculation is not only time-consuming, but also labor-intensive and economically impracticable. So far, large scale hybrid breeding has not been performed in soybean due to the shortage of male sterile lines suitable for hybrid production. Therefore, it is urgent to identify a stable male sterile system for the rapid utilization of heterosis in soybean. In this review, we summarize the progress on the discovery of soybean genic male sterility (GMS) mutants and GMS genes. Combining with the investigation of GMS genes in Arabidopsis, rice and maize, we provide important insights into the identification and potential utilization of GMS genes in soybean in the perspective of reverse genetics.

Few studies have comprehensively examined the effectiveness of simulation-based triage education on clinical reasoning of nursing students. This study evaluated the impact of a simulation-based triage exercise on nursing students' self-reported clinical reasoning ability. Three cohorts of third-year nursing students were divided into intervention group a (IG a, n = 62), intervention group b (IG b, n = 57), and a control group (CG, n = 53). Students in IG a and IG b participated in a simulation-based triage education consisting of 2 h of multiple patient triage simulations and an hour of structured debriefing. The CG participated in a traditional didactic triage course consisting of a 3-h lecture. Self-reported clinical reasoning ability in pre and post-triage education was measured by the Nurses Clinical Reasoning Scale. There was no significant difference in mean clinical reasoning ability scores between the three groups in pre-test (p > 0.05). Clinical reasoning ability scores in post-test among students in IG a and IG b were significantly higher than those in CG (p < 0.001). Nursing students exposed to a simulation-based triage education had more improvement in self-reported clinical reasoning ability as compared with students who participated in a lecture-based triage education program., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The aim of this paper was to investigate the effect of ethanol extract of Phellinus igniarius in lowering uric acid and changing the gut microbiome in hyperuricemia rats. A total of 36 SD rats were randomly divided into normal control group, model control group, positive drug control group, and high-dose, middle-dose and low-dose P. igniarius ethanol extract groups, with 6 rats in each group. Hyperuricemia rats were established by D-fructose combined with oteracil potassium(OAPS). One week later, the positive control group was given allopurinol 50 mg·kg~(-1) intragastrically, and P. igniarius ethanol extract groups were treated with 30, 60 and 90 mg·kg~(-1) drugs for 14 consecutive days. Body weight, blood glucose and serum uric acid(SUA) were monitored every week. After the model rats were administered with the ethanol extracts of P. igniarius by gavage for two weeks, the activities of creatinine, BUN, xanthine oxidase(XOD) and adenosine deaminase(ADA) were detected. The right kidney was taken to analyze the histological and morphological changes and the degree of damage to main organs of the extract of P. igniarius. The 16 S rDNA gene sequence technique was used to analyze the guts microbiota composition in feces. The results indicated that ethanol extract of P. igniarius could significantly lower the SUA level(P&lt;0.01), while inhibiting the activities of XOD and ADA(P&lt;0.05, P&lt;0.01). Histological examination showed that the allopurine group showed slight renal tubular dilation and inflammatory cell infiltration compared with the normal group, with no significant difference between the P. igniarius ethanol extract groups and the normal group. The 16 S sequencing results showed that the composition of gut microbiota has changed in each group. Therefore, ethanol extracts of P. igniarius may reduce the level of SUA in rats by inhibiting the activities of XOD and ADA, with a certain effect on the composition of gut microbiota.

Background: The aim was to compare the efficacy and safety of epsilon-aminocaproic acid (EACA) and tranexamic acid (TXA) in total hip arthroplasty (THA) and total knee arthroplasty (TKA)., Methods: Potential academic articles were identified from the Cochrane Library, Springer, PubMed, and ScienceDirect databases from inception to December 2019. Randomized controlled trials (RCTs) and non-RCTs involving EACA and TXA in THA or TKA were included. Pooled data were analyzed using RevMan 5.1., Results: Three RCTs and three non-RCTs met the inclusion criteria. The present meta-analysis reveals that EACA is associated with significantly more blood loss than TXA. No significant differences were identified in terms of blood transfusion rate, transfusion units, hemoglobin (Hb) level at discharge, operation time, length of hospital stay, deep venous thrombosis (DVT), or 30-day readmission., Conclusions: Compared with TXA, EACA led to more blood loss in patients undergoing THA or TKA. However, there was no significant difference in the blood transfusion rate, transfusion units, Hb level at discharge, operation time, length of hospital stay, DVT, or 30-day readmission between groups.

Objective: To explore whether acupuncture and moxibustion can prevent disease progression of advanced gastric cancer patients completing second-line chemotherapy and, if so, the related mechanism., Method: Progression-free survival (PFS) and overall survival (OS) were main outcome measures. The real-time quantitative PCR was used to detect the expression of genes including T-bet, IFN- γ , GATA3, and IL-4 in peripheral blood mononuclear cells (PBMCs). IL-4, IL-6, Ca199, CRP, and IFN- γ in plasma levels were checked., Results: 170 patients were randomly assigned in a 3 : 2 ratio to receive either acupuncture and moxibustion or sham acupuncture until progression. 135 patients were included in the primary analysis. Both PFS and OS in treatment group were proven to be better than control group. Acupuncture and moxibustion promoted typical Th1 cells drifting, as confirmed by increased T-bet/IFN- γ and decreased GATA3/IL-4 in mRNA levels from PBMCs, as well as upregulating IFN- γ and downregulating IL-4 in plasma levels. IL-6, Ca199, and CRP in plasma levels were also reduced by acupuncture and moxibustion., Conclusions: Acupuncture and moxibustion can prolong PFS and OS of advanced gastric cancer patients completing second-line chemotherapy by reversing Th1/Th2 shift and attenuating inflammatory responses., Competing Interests: All authors have no conflicts of interest with respect to the manuscript., (Copyright © 2020 Yong-jie Zhang et al.)

Objective: To study the differentially expressed mRNAs between MYCN-amplified neuroblastoma (NB) and non-amplified NB, to screen out the genes which can be used to predict the prognosis of MYCN-amplified NB, and to analyze their value in predicting prognosis., Methods: NB transcriptome data and the clinical data of children were obtained from the TARGET database. According to the presence or absence of MYCN amplification, the children were divided into two groups: MYCN amplification (n=33) and non-MYCN amplification (n=121). The expression of mRNAs was compared between the two groups to obtain differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analysis was performed to investigate the main functions of DEGs. The Cox proportional-hazards regression model analysis was used to investigate the genes influencing the prognosis of MYCN-amplified NB. The children were divided into a high-risk group (n=77) and a low-risk group (n=77) based on the median of risk score. A survival analysis was used to compare survival rate between the two groups. The receiver operating characteristic (ROC) curve was used to investigate the value of risk score in predicting the prognosis of children with MYCN-amplified NB., Results: A total of 582 DEGs were screened out, and they were involved in important biological functions such as ribosome composition, expression of cell adhesion molecules, and activity of membrane receptor protein. The multivariate Cox regression model analysis showed that FLVCR2, SCN7A, PRSS12, NTRK1, and XAGE1A genes had a marked influence on the prognosis of the children with NB in the MYCN amplification group (P<0.05). The survival analysis showed that the high-risk group had a significantly lower overall survival rate than the low-risk group (P<0.05). The ROC curve analysis showed that risk score had a certain value in predicting the prognosis of the children with NB in the MYCN amplification group (P<0.05), with an area under the ROC curve of 0.729, an optimal cut-off value of 1.316, a sensitivity of 53.2%, and a specificity of 84.4%., Conclusions: The mRNA expression of FLVCR2, SCN7A, PRSS12, NTRK1, and XAGE1A genes can be used as biomarkers to predict the prognosis of MYCN-amplified NB, which can help to refine clinical risk stratification.

The study explores the application of Tanreqing Injection into brain components in brain diseases. The components of Tanreqing Injection and its existing components in rat cerebrospinal fluid were qualitatively analyzed by liquid chromatography-mass spectrometry(LC-MS). The possible mechanism of action of Tanreqing Injection into brain on brain diseases was predicted by network pharmacological theory. In this study, 17 brain-entry components of Tanreqing Injection were founded, and 222 core targets were obtained from network pharmacological results. The biological processes include 31 items such as negative regulation of apoptotic process, MAPK cascade, Ras protein signal transduction, and 22 items such as PI3 K-Akt signal transduction, MAPK signal transduction and neurotrophic factor signal transduction. Nine brain diseases including stroke, migraine and meningioma were screened out by predicting the effect of Tanreqing Injection on brain components, which provide ideas and directions for further study of a certain encephalopathy and lay a theoretical foundation for further revealing its molecular mechanism.

The tumorigenic role and underlying mechanisms of lipid accumulation, commonly observed in many cancers, remain insufficiently understood. In this study, we identified an AMP-activated protein kinase (AMPK)-GATA-binding protein 3 (GATA3)-enoyl-CoA hydratase short-chain 1 (ECHS1) pathway that induces lipid accumulation and promotes cell proliferation in clear cell renal cell carcinoma (ccRCC). Decreased expression of ECHS1, which is responsible for inactivation of fatty acid (FA) oxidation and activation of de novo FA synthesis, positively associated with ccRCC progression and predicted poor patient survival. Mechanistically, ECHS1 downregulation induced FA and branched-chain amino acid (BCAA) accumulation, which inhibited AMPK-promoted expression of GATA3, a transcriptional activator of ECHS1. BCAA accumulation induced activation of mTORC1 and de novo FA synthesis, and promoted cell proliferation. Furthermore, GATA3 expression phenocopied ECHS1 in predicting ccRCC progression and patient survival. The AMPK-GATA3-ECHS1 pathway may offer new therapeutic approaches and prognostic assessment for ccRCC in the clinic. SIGNIFICANCE: These findings uncover molecular mechanisms underlying lipid accumulation in ccRCC, suggesting the AMPK-GATA3-ECHS1 pathway as a potential therapeutic target and prognostic biomarker., (©2019 American Association for Cancer Research.)

Zebrafish and human genomes are highly homologous; however, despite this genomic similarity, adult zebrafish can achieve neuronal proliferation, regeneration and functional restoration within 6-8 weeks after spinal cord injury, whereas humans cannot. To analyze differentially expressed zebrafish genes between axon-regenerated neurons and axon-non-regenerated neurons after spinal cord injury, and to explore the key genes and pathways of axonal regeneration after spinal cord injury, microarray GSE56842 was analyzed using the online tool, GEO2R, in the Gene Expression Omnibus database. Gene ontology and protein-protein interaction networks were used to analyze the identified differentially expressed genes. Finally, we screened for genes and pathways that may play a role in spinal cord injury repair in zebrafish and mammals. A total of 636 differentially expressed genes were obtained, including 255 up-regulated and 381 down-regulated differentially expressed genes in axon-regenerated neurons. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment results were also obtained. A protein-protein interaction network contained 480 node genes and 1976 node connections. We also obtained the 10 hub genes with the highest correlation and the two modules with the highest score. The results showed that spectrin may promote axonal regeneration after spinal cord injury in zebrafish. Transforming growth factor beta signaling may inhibit repair after spinal cord injury in zebrafish. Focal adhesion or tight junctions may play an important role in the migration and proliferation of some cells, such as Schwann cells or neural progenitor cells, after spinal cord injury in zebrafish. Bioinformatic analysis identified key candidate genes and pathways in axonal regeneration after spinal cord injury in zebrafish, providing targets for treatment of spinal cord injury in mammals., Competing Interests: None

Background: The influence of surgical delay on mortality and morbidity has been studied extensively among elderly hip fracture patients. However, most studies only focus on the timing of surgery when patients have already been hospitalized, without considering pre-admission waiting time. Therefore, the present study aims to explore the influence of admission delay on surgical outcomes., Methods: In this retrospective study, we recorded admission timing and interval from admission to surgery for included patient. Other covariates were also collected to control confounding. The primary outcome was 1-year mortality. The secondary outcomes were 1-month mortality, 3-month mortality, ICU admission and postoperative pneumonia. We mainly used multivariate logistic regression to determine the effect of admission timing on postoperative outcomes. An additional survival analysis was also performed to assess the impact of admission delay on survival status in the first year after operation., Results: The proportion of patients hospitalized on day 0, day 1, day 2 after injury was 25.4%, 54.7% and 66.3%, respectively. And 12.6% patients visited hospital one week later after injury. Mean time from admission to surgery was 5.2 days (standard deviation 2.8 days). Hospitalization at one week after injury was a risk factor for 1-year mortality (OR 1.762, 95% CI 1.026-3.379, P=0.041)., Conclusion: Admission delay of more than one week is significantly associated with higher 1-year mortality. As a supplement to the current guidelines which emphasizes early surgery after admission, we also advocate early admission once patients get injured., Competing Interests: Conflicts of interest: All authors declare no financial and personal relationships with other people or organizations., (Copyright: © 2020 World Journal of Emergency Medicine.)

Objective: To investigate and compare the influence of two numerical detrusor contractility parameters, the bladder contractility index (BCI) and the maximum Watts factor (WFmax), on transurethral resection of the prostate (TURP) outcome., Methods: A retrospective study was conducted on 236 patients who had undergone urodynamic assessment preoperatively and TURP for benign prostatic obstruction. They were evaluated by International Prostate Symptom Score (IPSS) and uroflowmetry preoperatively and 3 months postoperatively. Related criteria were established to determine the overall efficacy of TURP. Logistic regression analysis and receiver operating characteristic curves were made to investigate the influence of the BCI and WFmax on TURP efficacy., Results: Among the 236 patients, 195 treatments were effective and 41 ineffective. Multivariate analysis showed that both the BCI (OR 1.038) and the WFmax (OR 1.291) could influence TURP efficacy. For predicting TURP efficacy, the optimal cut-off values of the BCI and WFmax were 98.7 and 10.27 W/m2, respectively. The AUC, sensitivity and specificity of the BCI were 0.722, 78.5% and 61.0%; those of the WFmax were 0.761, 73.9% and 73.2%, with no significant difference (p > 0.05)., Conclusions: To some extent, the BCI and the WFmax can predict TURP efficacy equally well. A discrimination level of 10.27 W/m2 may be a threshold value for detrusor underactivity (DU); as regards the BCI, the current threshold value is appropriate to diagnose DU., (© 2019 S. Karger AG, Basel.)

Bladder urothelial carcinoma(BUC)is a common malignant tumor in the urinary system.Pt-based chemotherapy has long been a standard therapeutic method for resectable or metastatic BUC,but with poor outcomes.Immune checkpoint inhibitors specific to programmed death 1(PD-1)/programmed death-ligand 1(PD-L1)and cytotoxic T lymphocyte-associated protein 4(CTLA-4)pathways have shown significant antitumor activities,safety,and enduring reactivity in clinical trials,thus creating a new epoch for the treatment of advanced-stage BUC.This article reviews the relationships of BUC with PD-1/PD-L1 and CTLA-4 pathways,as demonstrated in clinical trials.In particular,the authors elucidate the clinical studies on the application of immune checkpoint inhibitors in different BUC stages and their optimal combining strategies,with an attempt to improve the clinical use of immune inhibitors for BUC treatment.

Background: Unsatisfactory analgesia would occur frequently during repeated cesarean section under epidural anesthesia. The aim of this study is to observe the effects of intravenous remifentanil on maternal comfort, maternal and neonatal safety during repeated cesarean section under epidural anesthesia., Methods: A total of 80 parturients undergoing repeated cesarean section were involved in the study. The patients were randomly divided into the intravenous remifentanil- assisted epidural group (group R) and epidural group (group E), respectively (n = 40). In group R, the remifentanil was continuously intravenously infused as an adjuvant to epidural anesthesia. In group E, 0.75% ropivacaine epidural or intravenous ketamine was administered as needed. Parturient baseline characteristics, vital signs, VAS scores, and comfort scores during surgery were recorded. Adverse effects were also recorded., Results: A total of 80 patients were enrolled in the current study and the final analyses included 39 patients in group R and 38 patients in group E. No differences in patients' baseline characteristics were found between the two groups (p > 0.05). Compared with group E, the comfort score was significantly higher in group R (9.1 ± 1.0 vs. 7.5 ± 1.3, p <  0.001), whereas the maximum VAS score was significantly lower in group R (1.8 ± 1.2 vs. 4.1 ± 1.0, p <  0.001). Maternal and neonatal adverse effects did not differ between the two groups during surgery (p > 0.05)., Conclusions: Continuous intravenous infusion of low-dose remifentanil can significantly improve the experience of parturients undergoing repeated cesarean section under epidural anesthesia, without noticeable maternal or neonatal adverse effects., Trial Registration: This study was pre-registered at http://www.chictr.org.cn/index.aspx (ChiCTR1800018423) on 17/09/2018.

Objective: To investigate the association between tumor PD-L1 expression and patient survival to determine whether PD-L1 represents an independent prognostic feature for patients with non-metastatic clear cell renal cell carcinoma (RCC). Patients and Methods: The tissue bank of the Fudan University Shanghai Cancer Center was queried to identity tissue samples of patients treated with radical nephrectomy, for non-metastatic sporadic clear cell RCC (ccRCC) between 2008 and 2015. Real-time polymerase chain reaction and immunohistochemistry staining was performed to detect the expression level of PD-L1 in paired cancer tissue and paracancerous tissue. Results: Three-hundred-and-thirty patients were enrolled in this study, with a mean age of 55.0 years at surgery and a mean tumor size of 5.2 cm. Two-hundred-and-forty-two (73.3%) and 88 (26.7%) patients showed a high and low expression of PD-L1 mRNA, respectively, while 254 patients had positive PD-L1 immunohistochemistry staining. Two-hundred-and-ninety-two patients had consistent results for mRNA and the PD-L1 protein based on these different detection methods. Patients with high PD-L1 expression were more likely to exhibit adverse pathologic features including an advanced T stage ( P = 0.002) and lymph node metastasis ( P = 0.044). The Kaplan-Meier curves of PFS and OS stratified by PD-L1 expression had a statistically significant difference. PD-L1 expression maintained a significant predictive role for PFS and OS in the multivariate cox model. Conclusions: Our data suggests that PD-L1 correlates with prognosis in RCC and targeting the PD-1/PD-L1 pathway should be considered in the treatment of RCC patients., (Copyright © 2019 Xiao, Xu, Zhang, Zhou, Zhang, Dai, Zhu, Shi, Shen, Zhu, Qu, Zhao and Ye.)

Liquid chromatography coupled with mass spectrometry has been used as metabolomics profiling tool to discover and identify the metabolites in metabolic diseases. Osteoporosis (OP) syndrome is a chronic metabolic disease characterized by bone mass reduction and changes in bone microstructure. Psoralea corylifolia Linn. seeds (PCS) have a therapeutic effect on osteoporosis, but their action mechanism and therapeutic target are still unclear. This study aims to explore the metabolic changes of the urine profile in glucocorticoid-induced OP model rats and the therapeutic effect of PCS. High-throughput metabolomics based on the liquid chromatography coupled with mass spectrometry quadrupole time-of-flight mass spectrometry and multivariate data analysis were used to analyze the urine metabolites. The results showed that has an obvious separation between model and control groups. OPLS-DA was used to further analyze and discover substances that contributed to the separation. 42 potential biomarkers and 12 related metabolic pathways were identified in combination with network databases. After the intervention of PCS, 24 biomarkers were significantly regulated, mainly with glycone, serine and threonine metabolism, glutathione metabolism and purine metabolism and other metabolic pathways are related and discovered. This study has proved that PCS has therapeutic effect against OP by regulating that metabolic pathways disturbed in the OP. It provided a basis for the research and future development of new drugs for OP treatment., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

A field experiment was conducted on Alhagi sparsifolia Shap. with a long-term clipping history (5-8 years) to investigate the adaptation strategy of A. sparsifolia to long-term clipping. The present study found that long-term clipping can reduce self-shading and increase the photosynthesis rate (Pn) in May. During the whole growth season, clipped plants can maintain a high Pn with less variation, which we denote as a 'stable photosynthesis strategy'. Although Pn in unclipped plants was higher than in the long-term clipping treatment in August, clipped plants accumulated more carbohydrates in shoots. The enhanced amount of carbohydrates could be correlated with the greater amount of lignin synthesis in stems. Therefore, long-term clipping induced the transition of A. sparsifolia from herbs to shrubs. After long-term clipping, plants allocated more resources to plant defence against stress, whereas the ratio of resources allocated to leaf growth decreased. Consequently, photosynthesis in long-term clipped plants decreased in August. In PSII, the energy used for both photochemical quenching and non-photochemical quenching decreased in the clipped plants during the early stage of the growth season. In addition, due to the lower stomatal conductance (gs), clipped plants retained more water in their leaves and suffered less water stress. Thus, clipped plants produced less reactive oxygen species (ROS), which in turn, delayed leaf senescence. Plants also exhibited over-compensatory growth after long-term clipping, but this phenomenon was not caused by the increase in specific leaf area (SLA). The stable photosynthesis strategy helped to extend the lifespan of plants in the growth season and improve their adaptation to light, temperature, and water stress.

Introduction and Hypothesis: Constipation is reported to be associated with urinary incontinence. However, the reported results have been inconsistent and contradictory. To evaluate the association between constipation and urinary incontinence in women, we performed a meta-analysis., Methods: A comprehensive search based on PubMed, EMBASE, and the Cochrane Library was performed up to July 2018 for eligible studies in relation to the influence of constipation on urinary incontinence in women. A random-effect model was used to calculate the pooled odds risk (OR) and corresponding 95% confidence interval (CI)., Results: A total of 16 observational studies with 35,629 participants and 6054 urinary incontinence patients were identified in the meta-analysis. Constipation was significantly associated with the risk of urinary incontinence in women (OR 2.46, 95% CI 1.79-3.38)., Conclusions: This meta-analysis suggests that constipation is significantly associated with urinary incontinence risk in women. However, further well-designed, large-scale prospective studies are needed to clarify the causality.

Inflammation and immunoreaction markers were correlated with the survival of patients in many tumors. However, there were no reports investigating the relationships between preoperative hematological markers and the prognosis of medulloblastoma (MB) patients based on the molecular subgroups (WNT, SHH, Group 3, and Group 4). A total 144 MB patients were enrolled in the study. The differences of preoperative hematological markers among molecular subgroups of MB were compared by One-way ANOVA method. Kaplan-Meier method was used to calculate the curves of progression free survival (PFS) and overall survival (OS). The comparison of survival rates in different groups were conducted by the Log-rank test. Multivariate analysis was used to evaluate independent prognostic factors. Increased preoperative NLR (neutrophil-to-lymphocyte ratio, PFS, P = 0.004, OS, P < 0.001) and PLR (platelet-to-lymphocyte ratio, PFS, P = 0.028, OS, P = 0.003) predicted poor prognosis in patients with MB, while preoperative MLR (monocyte-to-lymphocyte ratio), MPV (mean platelet volume), PDW (platelet distribution width), and AGR (albumin-to-globulin ratio) were revealed no predictive value on the prognosis of patients with MB. Furthermore, high preoperative NLR and PLR predicted unfavorable prognosis in childhood MB patients. However, preoperative NLR and PLR were not associated with the prognosis in adult MB patients. Multivariate analysis demonstrated preoperative NLR (PFS, P = 0.029, OS, P = 0.005) and PLR (PFS, P = 0.023, OS, P = 0.005) were the independent prognostic factors in MB patients. Emphatically, the levels of preoperative NLR and PLR in Group 3 MB were significantly higher than those in WNT MB. High preoperative NLR was associated with unfavorable OS in Group 3 (P = 0.032) and Group 4 (P = 0.027) tumors. Similarly, increased preoperative PLR predicted poor PFS (P = 0.012) and OS (P = 0.009) in Group 4 tumors. Preoperative NLR and PLR were the potential prognostic markers for MB patients. Preoperative NLR and PLR were significantly associated with the survival of Group 3 and Group 4 tumors.